Differential DNA methylation marks and gene comethylation of COPD in African-Americans with COPD exacerbations.

PubMed

Busch, Robert; Qiu, Weiliang; Lasky-Su, Jessica; Morrow, Jarrett; Criner, Gerard; DeMeo, Dawn

2016-11-05

Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide. Identifying COPD-associated DNA methylation marks in African-Americans may contribute to our understanding of racial disparities in COPD susceptibility. We determined differentially methylated genes and co-methylation network modules associated with COPD in African-Americans recruited during exacerbations of COPD and smoking controls from the Pennsylvania Study of Chronic Obstructive Pulmonary Exacerbations (PA-SCOPE) cohort. We assessed DNA methylation from whole blood samples in 362 African-American smokers in the PA-SCOPE cohort using the Illumina Infinium HumanMethylation27 BeadChip Array. Final analysis included 19302 CpG probes annotated to the nearest gene transcript after quality control. We tested methylation associations with COPD case-control status using mixed linear models. Weighted gene comethylation networks were constructed using weighted gene coexpression network analysis (WGCNA) and network modules were analyzed for association with COPD. There were five differentially methylated CpG probes significantly associated with COPD among African-Americans at an FDR less than 5 %, and seven additional probes that approached significance at an FDR less than 10 %. The top ranked gene association was MAML1, which has been shown to affect NOTCH-dependent angiogenesis in murine lung. Network modeling yielded the "yellow" and "blue" comethylation modules which were significantly associated with COPD (p-value 4 × 10 -10 and 4 × 10 -9 , respectively). The yellow module was enriched for gene sets related to inflammatory pathways known to be relevant to COPD. The blue module contained the top ranked genes in the concurrent differential methylation analysis (FXYD1/LGI4, gene significance p-value 1.2 × 10 -26 ; MAML1, p-value 2.0 × 10 -26 ; CD72, p-value 2.1 × 10 -25 ; and LPO, p-value 7.2 × 10 -25 ), and was significantly associated with lung development processes in Gene Ontology gene-set enrichment analysis. We identified 12 differentially methylated CpG sites associated with COPD that mapped to biologically plausible genes. Network module comethylation patterns have identified candidate genes that may be contributing to racial differences in COPD susceptibility and severity. COPD-associated comethylation modules contained genes previously associated with lung disease and inflammation and recapitulated known COPD-associated genes. The genes implicated by differential methylation and WGCNA analysis may provide mechanistic targets contributing to COPD susceptibility, exacerbations, and outcomes among African-Americans. Trial Registration: NCT00774176 , Registry: ClinicalTrials.gov, URL: www.clinicaltrials.gov , Date of Enrollment of First Participant: June 2004, Date Registered: 04 January 2008 (retrospectively registered).

Epidemiology, radiology, and genetics of nicotine dependence in COPD.

PubMed

Kim, Deog Kyeom; Hersh, Craig P; Washko, George R; Hokanson, John E; Lynch, David A; Newell, John D; Murphy, James R; Crapo, James D; Silverman, Edwin K

2011-01-13

Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers. Current smokers with COPD (GOLD stage ≥ 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes. Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p < .0001) as well as in COPD cases (ρ = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers. Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.

Bipartite Community Structure of eQTLs.

PubMed

Platig, John; Castaldi, Peter J; DeMeo, Dawn; Quackenbush, John

2016-09-01

Genome Wide Association Studies (GWAS) and expression quantitative trait locus (eQTL) analyses have identified genetic associations with a wide range of human phenotypes. However, many of these variants have weak effects and understanding their combined effect remains a challenge. One hypothesis is that multiple SNPs interact in complex networks to influence functional processes that ultimately lead to complex phenotypes, including disease states. Here we present CONDOR, a method that represents both cis- and trans-acting SNPs and the genes with which they are associated as a bipartite graph and then uses the modular structure of that graph to place SNPs into a functional context. In applying CONDOR to eQTLs in chronic obstructive pulmonary disease (COPD), we found the global network "hub" SNPs were devoid of disease associations through GWAS. However, the network was organized into 52 communities of SNPs and genes, many of which were enriched for genes in specific functional classes. We identified local hubs within each community ("core SNPs") and these were enriched for GWAS SNPs for COPD and many other diseases. These results speak to our intuition: rather than single SNPs influencing single genes, we see groups of SNPs associated with the expression of families of functionally related genes and that disease SNPs are associated with the perturbation of those functions. These methods are not limited in their application to COPD and can be used in the analysis of a wide variety of disease processes and other phenotypic traits.

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

PubMed Central

Kim, Deog Kyeom; Cho, Michael H.; Hersh, Craig P.; Lomas, David A.; Miller, Bruce E.; Kong, Xiangyang; Bakke, Per; Gulsvik, Amund; Agustí, Alvar; Wouters, Emiel; Celli, Bartolome; Coxson, Harvey; Vestbo, Jørgen; MacNee, William; Yates, Julie C.; Rennard, Stephen; Litonjua, Augusto; Qiu, Weiliang; Beaty, Terri H.; Crapo, James D.; Riley, John H.; Tal-Singer, Ruth

2012-01-01

Rationale: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. Objectives: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P < 1 × 10−8), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Measurements and Main Results: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P = 0.009–0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P = 0.001–0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID:23144326

Family History Is a Risk Factor for COPD

PubMed Central

Hokanson, John E.; Lynch, David A.; Washko, George R.; Make, Barry J.; Crapo, James D.; Silverman, Edwin K.

2011-01-01

Background: Studies have shown that family history is a risk factor for COPD, but have not accounted for family history of smoking. Therefore, we sought to identify the effects of family history of smoking and family history of COPD on COPD susceptibility. Methods: We compared 821 patients with COPD to 776 control smokers from the Genetic Epidemiology of COPD (COPDGene) Study. Questionnaires captured parental histories of smoking and COPD, as well as childhood environmental tobacco smoke (ETS) exposure. Socioeconomic status was defined by educational achievement. Results: Parental history of smoking (85.5% case patients, 82.9% control subjects) was more common than parental history of COPD (43.0% case patients, 30.8% control subjects). In a logistic regression model, parental history of COPD (OR, 1.73; P < .0001) and educational level (OR, 0.48 for some college vs no college; P < .0001) were significant predictors of COPD, but parental history of smoking and childhood ETS exposure were not significant. The population-attributable risk from COPD family history was 18.6%. Patients with COPD with a parental history had more severe disease, with lower lung function, worse quality of life, and more frequent exacerbations. There were nonsignificant trends for more severe emphysema and airway disease on quantitative chest CT scans. Conclusions: Family history of COPD is a strong risk factor for COPD, independent of family history of smoking, personal lifetime smoking, or childhood ETS exposure. Although further studies are required to identify genetic variants that influence COPD susceptibility, clinicians should question all smokers, especially those with known or suspected COPD, regarding COPD family history. PMID:21310839

Genetic Epidemiology of Cigarette Smoke–Induced Lung Disease

PubMed Central

2012-01-01

Chronic obstructive pulmonary disease (COPD) and lung cancer represent two diseases that share a strong risk factor in smoking, and COPD increases risk of lung cancer even after adjusting for the effects of smoking. These diseases not only occur jointly within an individual but also there is evidence of shared occurrence within families. Understanding the genetic contributions to these diseases, both individually and jointly, is needed to identify the highest risk group for screening and targeted prevention, as well as aiding in the development of targeted treatments. The chromosomal regions that have been identified as being associated either jointly or independently with lung cancer, COPD, nicotine addiction, and lung function are presented. Studies jointly measuring genetic variation in lung cancer and COPD have been limited by the lack of detailed COPD diagnosis and severity data in lung cancer populations, the lack of lung cancer–specific phenotypes (histology and tumor markers) in COPD populations, and the lack of inclusion of minorities. African Americans, who smoke fewer cigarettes per day and have different linkage disequilibrium and disease patterns than whites, and Asians, also with different patterns of exposure to lung carcinogens and linkage patterns, will provide invaluable information to better understand shared and independent genetic contributions to lung cancer and COPD to more fully define the highest risk group of individuals who will most benefit from screening and to develop molecular signatures to aid in targeted treatment and prevention efforts. PMID:22550237

Evaluation of Genetic Diversity of Candida spp. and Klebsiella spp. Isolated from the Denture Plaque of COPD Patients.

PubMed

Przybyłowska, D; Piskorska, K; Gołaś, M; Sikora, M; Swoboda-Kopeć, E; Kostrzewa-Janicka, J; Mierzwińska-Nastalska, E

2017-01-01

Yeast-like fungi and gram-negative bacilli are the most frequent potential pathogens of the respiratory tract isolated from the denture plaque of patients with chronic obstructive pulmonary disease (COPD). Dominant species among yeast-like fungi are Candida albicans and Candida tropicalis. Significant frequency is also exhibited by Klebsiella pneumoniae and Klebsiella oxytoca. The purpose of this study was to analyze genetic diversity of the strains of C. albicans, C. tropicalis, and Klebsiella spp. present in patients in stable phases of COPD. The analysis was conducted by the random amplified polymorphic DNA (RAPD) method on clinical strains isolated from patients with COPD and control patients in overall good health. Forty one strains of Candida albicans, 12 of Candida tropicalis, as well as 9 strains of K. pneumoniae and 7 of K. oxytoca were scrutinized. The dominant species in clinical material from COPD patients was Candida albicans with a substantial degree of variations of genetic profiles. On the basis of affinity analysis, 19 genetic types were identified within this strain. An analysis of the banding patterns among C. tropicalis strains indicated the existence of 6 genetic types. A considerable diversity of genetic profiles among Klebsiella spp. also was established. The genotype diversity of Klebsiella spp. strains may indicate the endogenic character of the majority of infections, regardless of the therapy applied for the underlying condition.

PTEN IDENTIFIED AS IMPORTANT RISK FACTOR OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

PubMed Central

Hosgood, H Dean; Menashe, Idan; He, Xingzhou; Chanock, Stephen; Lan, Qing

2009-01-01

Common genetic variation may play an important role in altering chronic obstructive pulmonary disease (COPD) risk. In Xuanwei, China, the COPD rate is more than twice the Chinese national average, and COPD is strongly associated with in-home coal use. To identify genetic variation that may be associated with COPD in a population with substantial in-home coal smoke exposures, we evaluated 1,261 single nucleotide polymorphisms (SNPs) in 380 candidate genes potentially relevant for cancer and other human diseases in a population-based case-control study in Xuanwei (53 cases; 107 controls). PTEN was the most significantly associated gene with COPD in a minP analysis using 20,000 permutations (P = 0.00005). SNP-based analyses found that homozygote variant carriers of PTEN rs701848 (ORTT = 0.12, 95%CI = 0.03 - 0.47) had a significant decreased risk of COPD. PTEN, or phosphatase and tensin homolog, is an important regulator of cell cycle progression and cellular survival via the AKT signaling pathway. Our exploratory analysis suggests that genetic variation in PTEN may be an important risk factor of COPD in Xuanwei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuanwei and other populations with coal smoke exposures. PMID:19625176

Common Genetic Variants Associated with Resting Oxygenation in Chronic Obstructive Pulmonary Disease

PubMed Central

Cho, Michael H.; Sørheim, Inga-Cecilie; Lutz, Sharon M.; Castaldi, Peter J.; Lomas, David A.; Coxson, Harvey O.; Edwards, Lisa D.; MacNee, William; Vestbo, Jørgen; Yates, Julie C.; Agusti, Alvar; Calverley, Peter M. A.; Celli, Bartolome; Crim, Courtney; Rennard, Stephen I.; Wouters, Emiel F. M.; Bakke, Per; Tal-Singer, Ruth; Miller, Bruce E.; Gulsvik, Amund; Casaburi, Richard; Wells, J. Michael; Regan, Elizabeth A.; Make, Barry J.; Hokanson, John E.; Lange, Christoph; Crapo, James D.; Beaty, Terri H.; Silverman, Edwin K.; Hersh, Craig P.

2014-01-01

Hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD) that correlates with disease prognosis. Identifying genetic variants associated with oxygenation may provide clues for deciphering the heterogeneity in prognosis among patients with COPD. However, previous genetic studies have been restricted to investigating COPD candidate genes for association with hypoxemia. To report results from the first genome-wide association study (GWAS) of resting oxygen saturation (as measured by pulse oximetry [Spo2]) in subjects with COPD, we performed a GWAS of Spo2 in two large, well characterized COPD populations: COPDGene, including both the non-Hispanic white (NHW) and African American (AA) groups, and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We identified several suggestive loci (P < 1 × 10−5) associated with Spo2 in COPDGene in the NHW (n = 2810) and ECLIPSE (n = 1758) groups, and two loci on chromosomes 14 and 15 in the AA group (n = 820) from COPDGene achieving a level of genome-wide significance (P < 5 × 10−8). The chromosome 14 single-nucleotide polymorphism, rs6576132, located in an intergenic region, was nominally replicated (P < 0.05) in the NHW group from COPDGene. The chromosome 15 single-nucleotide polymorphisms were rare in subjects of European ancestry, so the results could not be replicated. The chromosome 15 region contains several genes, including TICRR and KIF7, and is proximal to RHCG (Rh family C glyocoprotein gene). We have identified two loci associated with resting oxygen saturation in AA subjects with COPD, and several suggestive regions in subjects of European descent with COPD. Our study highlights the importance of investigating the genetics of complex traits in different racial groups. PMID:24825563

Common genetic variants associated with resting oxygenation in chronic obstructive pulmonary disease.

PubMed

McDonald, Merry-Lynn N; Cho, Michael H; Sørheim, Inga-Cecilie; Lutz, Sharon M; Castaldi, Peter J; Lomas, David A; Coxson, Harvey O; Edwards, Lisa D; MacNee, William; Vestbo, Jørgen; Yates, Julie C; Agusti, Alvar; Calverley, Peter M A; Celli, Bartolome; Crim, Courtney; Rennard, Stephen I; Wouters, Emiel F M; Bakke, Per; Tal-Singer, Ruth; Miller, Bruce E; Gulsvik, Amund; Casaburi, Richard; Wells, J Michael; Regan, Elizabeth A; Make, Barry J; Hokanson, John E; Lange, Christoph; Crapo, James D; Beaty, Terri H; Silverman, Edwin K; Hersh, Craig P

2014-11-01

Hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD) that correlates with disease prognosis. Identifying genetic variants associated with oxygenation may provide clues for deciphering the heterogeneity in prognosis among patients with COPD. However, previous genetic studies have been restricted to investigating COPD candidate genes for association with hypoxemia. To report results from the first genome-wide association study (GWAS) of resting oxygen saturation (as measured by pulse oximetry [Spo2]) in subjects with COPD, we performed a GWAS of Spo2 in two large, well characterized COPD populations: COPDGene, including both the non-Hispanic white (NHW) and African American (AA) groups, and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We identified several suggestive loci (P < 1 × 10(-5)) associated with Spo2 in COPDGene in the NHW (n = 2810) and ECLIPSE (n = 1758) groups, and two loci on chromosomes 14 and 15 in the AA group (n = 820) from COPDGene achieving a level of genome-wide significance (P < 5 × 10(-8)). The chromosome 14 single-nucleotide polymorphism, rs6576132, located in an intergenic region, was nominally replicated (P < 0.05) in the NHW group from COPDGene. The chromosome 15 single-nucleotide polymorphisms were rare in subjects of European ancestry, so the results could not be replicated. The chromosome 15 region contains several genes, including TICRR and KIF7, and is proximal to RHCG (Rh family C glyocoprotein gene). We have identified two loci associated with resting oxygen saturation in AA subjects with COPD, and several suggestive regions in subjects of European descent with COPD. Our study highlights the importance of investigating the genetics of complex traits in different racial groups.

Genetic regulation of gene expression in the lung identifies CST3 and CD22 as potential causal genes for airflow obstruction.

PubMed

Lamontagne, Maxime; Timens, Wim; Hao, Ke; Bossé, Yohan; Laviolette, Michel; Steiling, Katrina; Campbell, Joshua D; Couture, Christian; Conti, Massimo; Sherwood, Karen; Hogg, James C; Brandsma, Corry-Anke; van den Berge, Maarten; Sandford, Andrew; Lam, Stephen; Lenburg, Marc E; Spira, Avrum; Paré, Peter D; Nickle, David; Sin, Don D; Postma, Dirkje S

2014-11-01

COPD is a complex chronic disease with poorly understood pathogenesis. Integrative genomic approaches have the potential to elucidate the biological networks underlying COPD and lung function. We recently combined genome-wide genotyping and gene expression in 1111 human lung specimens to map expression quantitative trait loci (eQTL). To determine causal associations between COPD and lung function-associated single nucleotide polymorphisms (SNPs) and lung tissue gene expression changes in our lung eQTL dataset. We evaluated causality between SNPs and gene expression for three COPD phenotypes: FEV(1)% predicted, FEV(1)/FVC and COPD as a categorical variable. Different models were assessed in the three cohorts independently and in a meta-analysis. SNPs associated with a COPD phenotype and gene expression were subjected to causal pathway modelling and manual curation. In silico analyses evaluated functional enrichment of biological pathways among newly identified causal genes. Biologically relevant causal genes were validated in two separate gene expression datasets of lung tissues and bronchial airway brushings. High reliability causal relations were found in SNP-mRNA-phenotype triplets for FEV(1)% predicted (n=169) and FEV(1)/FVC (n=80). Several genes of potential biological relevance for COPD were revealed. eQTL-SNPs upregulating cystatin C (CST3) and CD22 were associated with worse lung function. Signalling pathways enriched with causal genes included xenobiotic metabolism, apoptosis, protease-antiprotease and oxidant-antioxidant balance. By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified CST3 and CD22 as potential causal genes for airflow obstruction. This study also augmented the understanding of previously described COPD pathways. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Suppressed Expression of T-Box Transcription Factors is Involved in Senescence in Chronic Obstructive Pulmonary Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acquaah-Mensah, George; Malhotra, Deepti; Vulimiri, Madhulika

2012-06-19

Chronic obstructive pulmonary disease (COPD) is a major global health problem. The etiology of COPD has been associated with apoptosis, oxidative stress, and inflammation. However, understanding of the molecular interactions that modulate COPD pathogenesis remains only partly resolved. We conducted an exploratory study on COPD etiology to identify the key molecular participants. We used information-theoretic algorithms including Context Likelihood of Relatedness (CLR), Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE), and Inferelator. We captured direct functional associations among genes, given a compendium of gene expression profiles of human lung epithelial cells. A set of genes differentially expressed in COPD,more » as reported in a previous study were superposed with the resulting transcriptional regulatory networks. After factoring in the properties of the networks, an established COPD susceptibility locus and domain-domain interactions involving protein products of genes in the generated networks, several molecular candidates were predicted to be involved in the etiology of COPD. These include COL4A3, CFLAR, GULP1, PDCD1, CASP10, PAX3, BOK, HSPD1, PITX2, and PML. Furthermore, T-box (TBX) genes and cyclin-dependent kinase inhibitor 2A (CDKN2A), which are in a direct transcriptional regulatory relationship, emerged as preeminent participants in the etiology of COPD by means of senescence. Contrary to observations in neoplasms, our study reveals that the expression of genes and proteins in the lung samples from patients with COPD indicate an increased tendency towards cellular senescence. The expression of the anti-senescence mediators TBX transcription factors, chromatin modifiers histone deacetylases, and sirtuins was suppressed; while the expression of TBX-regulated cellular senescence markers such as CDKN2A, CDKN1A, and CAV1 was elevated in the peripheral lung tissue samples from patients with COPD. The critical balance between senescence and anti-senescence factors is disrupted towards senescence in COPD lungs.« less

Enhancement of COPD biological networks using a web-based collaboration interface

PubMed Central

Boue, Stephanie; Fields, Brett; Hoeng, Julia; Park, Jennifer; Peitsch, Manuel C.; Schlage, Walter K.; Talikka, Marja; Binenbaum, Ilona; Bondarenko, Vladimir; Bulgakov, Oleg V.; Cherkasova, Vera; Diaz-Diaz, Norberto; Fedorova, Larisa; Guryanova, Svetlana; Guzova, Julia; Igorevna Koroleva, Galina; Kozhemyakina, Elena; Kumar, Rahul; Lavid, Noa; Lu, Qingxian; Menon, Swapna; Ouliel, Yael; Peterson, Samantha C.; Prokhorov, Alexander; Sanders, Edward; Schrier, Sarah; Schwaitzer Neta, Golan; Shvydchenko, Irina; Tallam, Aravind; Villa-Fombuena, Gema; Wu, John; Yudkevich, Ilya; Zelikman, Mariya

2015-01-01

The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks. PMID:25767696

Enhancement of COPD biological networks using a web-based collaboration interface.

PubMed

Boue, Stephanie; Fields, Brett; Hoeng, Julia; Park, Jennifer; Peitsch, Manuel C; Schlage, Walter K; Talikka, Marja; Binenbaum, Ilona; Bondarenko, Vladimir; Bulgakov, Oleg V; Cherkasova, Vera; Diaz-Diaz, Norberto; Fedorova, Larisa; Guryanova, Svetlana; Guzova, Julia; Igorevna Koroleva, Galina; Kozhemyakina, Elena; Kumar, Rahul; Lavid, Noa; Lu, Qingxian; Menon, Swapna; Ouliel, Yael; Peterson, Samantha C; Prokhorov, Alexander; Sanders, Edward; Schrier, Sarah; Schwaitzer Neta, Golan; Shvydchenko, Irina; Tallam, Aravind; Villa-Fombuena, Gema; Wu, John; Yudkevich, Ilya; Zelikman, Mariya

2015-01-01

The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks.

Genetics of Sputum Gene Expression in Chronic Obstructive Pulmonary Disease

PubMed Central

Qiu, Weiliang; Cho, Michael H.; Riley, John H.; Anderson, Wayne H.; Singh, Dave; Bakke, Per; Gulsvik, Amund; Litonjua, Augusto A.; Lomas, David A.; Crapo, James D.; Beaty, Terri H.; Celli, Bartolome R.; Rennard, Stephen; Tal-Singer, Ruth; Fox, Steven M.; Silverman, Edwin K.; Hersh, Craig P.

2011-01-01

Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus. PMID:21949713

Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease.

PubMed

Bade, Geetanjali; Khan, Meraj Alam; Srivastava, Akhilesh Kumar; Khare, Parul; Solaiappan, Krishna Kumar; Guleria, Randeep; Palaniyar, Nades; Talwar, Anjana

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process.

Association of lung function genes with chronic obstructive pulmonary disease.

PubMed

Kim, Woo Jin; Lim, Myoung Nam; Hong, Yoonki; Silverman, Edwin K; Lee, Ji-Hyun; Jung, Bock Hyun; Ra, Seung Won; Choi, Hye Sook; Jung, Young Ju; Park, Yong Bum; Park, Myung Jae; Lee, Sei Won; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang Do

2014-08-01

Spirometric measurements of pulmonary function are important in diagnosing and determining the severity of chronic obstructive pulmonary disease (COPD). We performed this study to determine whether candidate genes identified in genome-wide association studies of spirometric measurements were associated with COPD and if they interacted with smoking intensity. The current analysis included 1,000 COPD subjects and 1,000 controls recruited from 24 hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide association studies of spirometric measurements in the Korean population cohorts, were genotyped. Genetic association tests were performed, adjusting for age, sex, and smoking intensity, using models including a SNP-by-smoking interaction term. PID1 and FAM13A were significantly associated with COPD susceptibility. There were also significant interactions between SNPs in ACN9 and FAM13A and smoking pack-years, and an association of ACN9 with COPD in the lowest smoking tertile. The risk allele of FAM13A was associated with increased expression of FAM13A in the lung. We have validated associations of FAM13A and PID1 with COPD. ACN9 showed significant interaction with smoking and is a potential candidate gene for COPD. Significant associations of genetic variants of FAM13A with gene expression levels suggest that the associated loci may act as genetic regulatory elements for FAM13A gene expression.

Genetic mannose binding lectin deficiency is associated with airway microbiota diversity and reduced exacerbation frequency in COPD.

PubMed

Dicker, Alison J; Crichton, Megan L; Cassidy, Andrew J; Brady, Gill; Hapca, Adrian; Tavendale, Roger; Einarsson, Gisli G; Furrie, Elizabeth; Elborn, J Stuart; Schembri, Stuart; Marshall, Sara E; Palmer, Colin N A; Chalmers, James D

2018-06-01

In cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear. Preclinical data suggest MBL interferes with phagocytosis of Haemophilus influenzae , a key COPD pathogen. We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD. Patients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality. A nested subcohort of 141 patients, followed for up to 6 months, was studied to test if MBL deficiency was associated with altered sputum microbiota, through 16S rRNA PCR and sequencing, or airway inflammation during stable and exacerbated COPD. Patients with MBL deficiency with COPD were significantly less likely to have severe exacerbations (incidence rate ratio (IRR) 0.66, 95% CI 0.48 to 0.90, p=0.009), or to have moderate or severe exacerbations (IRR 0.77, 95% CI 0.60 to 0.99, p=0.047). MBL deficiency did not affect rate of FEV 1 decline or mortality. In the subcohort, patients with MBL deficiency had a more diverse lung microbiota (p=0.008), and were less likely to be colonised with Haemophilus spp. There were lower levels of airway inflammation in patients with MBL deficiency. Patients with MBL deficient genotype with COPD have a lower risk of exacerbations and a more diverse lung microbiota. This is the first study to identify a genetic association with the lung microbiota in COPD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease.

PubMed

Lee, Jin Hwa; McDonald, Merry-Lynn N; Cho, Michael H; Wan, Emily S; Castaldi, Peter J; Hunninghake, Gary M; Marchetti, Nathaniel; Lynch, David A; Crapo, James D; Lomas, David A; Coxson, Harvey O; Bakke, Per S; Silverman, Edwin K; Hersh, Craig P

2014-08-20

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD. We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.7 and FEV1 < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis. Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10-8). In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

Genetic polymorphism of matrix metalloproteinase family and chronic obstructive pulmonary disease susceptibility: a meta-analysis.

PubMed

Zhou, Hongbin; Wu, Yinfang; Jin, Yan; Zhou, Jiesen; Zhang, Chao; Che, Luanqing; Jing, Jiyong; Chen, Zhihua; Li, Wen; Shen, Huahao

2013-10-02

Matrix metalloproteinase (MMP) family is considered to be associated with chronic obstructive pulmonary disease (COPD) pathogenesis, however, no consistent results have been provided by previous studies. In this report, we performed Meta analysis to investigate the association between four kinds of MMP single nucleotide polymorphisms (SNP, MMP1 -1607 1G/2G, MMP3 -1171 5A/6A, MMP9 -1562 C/T, MMP12 -82 A/G) and COPD risk from 21 studies including 4184 cases and 5716 controls. Both overall and subgroup association between SNP and COPD susceptibility were tested. There was no evident association between MMP polymorphisms and COPD susceptibility in general population. On the other hand, subgroup analysis suggested that MMP9 -1562 C/T polymorphism was related to COPD, as we found that C allele carriers were at lower risk in some subgroups stratified by lung function, age and genotype identification method, compared with TT homozygotes. Our results indicated the genotype TT might be one genetic risk factor of severe COPD.

Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management.

PubMed

Roca, Josep; Vargas, Claudia; Cano, Isaac; Selivanov, Vitaly; Barreiro, Esther; Maier, Dieter; Falciani, Francesco; Wagner, Peter; Cascante, Marta; Garcia-Aymerich, Judith; Kalko, Susana; De Mas, Igor; Tegnér, Jesper; Escarrabill, Joan; Agustí, Alvar; Gomez-Cabrero, David

2014-11-28

Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics. To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena. (1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering. The results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.

Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort.

PubMed

Divo, Miguel J; Celli, Bartolome R; Poblador-Plou, Beatriz; Calderón-Larrañaga, Amaia; de-Torres, Juan Pablo; Gimeno-Feliu, Luis A; Bertó, Juan; Zulueta, Javier J; Casanova, Ciro; Pinto-Plata, Victor M; Cabrera-Lopez, Carlos; Polverino, Francesca; Carmona Píréz, Jonás; Prados-Torres, Alexandra; Marin, Jose M

2018-01-01

Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network's density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age.

Development of a program for tele-rehabilitation of COPD patients across sectors: co-innovation in a network

PubMed Central

Dinesen, Birthe; Seeman, Janne; Gustafsson, Jeppe

2011-01-01

Introduction The aim of the Telekat project is to prevent re-admissions of patients with chronic obstructive pulmonary disease (COPD) by developing a preventive program of tele-rehabilitation across sectors for COPD patients. The development of the program is based on a co-innovation process between COPD patients, relatives, healthcare professionals and representatives from private firms and universities. This paper discusses the obstacles that arise in the co-innovation process of developing an integrated technique for tele-rehabilitation of COPD patients. Theory Network and innovation theory. Methods The case study was applied. A triangulation of data collection techniques was used: documents, observations (123 hours), qualitative interviews (n=32) and action research. Findings Obstacles were identified in the network context; these obstacles included the mindset of the healthcare professionals, inter-professionals relations, views of technology as a tool and competing visions for the goals of tele-rehabilitation. Conclusion We have identified obstacles that emerge in the co-innovation process when developing a programme for tele-rehabilitation of COPD patients in an inter-organizational context. Action research has been carried out and can have helped to facilitate the co-innovation process. PMID:21637709

Exploring the interaction among EPHX1, GSTP1, SERPINE2, and TGFB1 contributing to the quantitative traits of chronic obstructive pulmonary disease in Chinese Han population.

PubMed

An, Li; Lin, Yingxiang; Yang, Ting; Hua, Lin

2016-05-18

Currently, the majority of genetic association studies on chronic obstructive pulmonary disease (COPD) risk focused on identifying the individual effects of single nucleotide polymorphisms (SNPs) as well as their interaction effects on the disease. However, conventional genetic studies often use binary disease status as the primary phenotype, but for COPD, many quantitative traits have the potential correlation with the disease status and closely reflect pathological changes. Here, we genotyped 44 SNPs from four genes (EPHX1, GSTP1, SERPINE2, and TGFB1) in 310 patients and 203 controls which belonged to the Chinese Han population to test the two-way and three-way genetic interactions with COPD-related quantitative traits using recently developed generalized multifactor dimensionality reduction (GMDR) and quantitative multifactor dimensionality reduction (QMDR) algorithms. Based on the 310 patients and the whole samples of 513 subjects, the best gene-gene interactions models were detected for four lung-function-related quantitative traits. For the forced expiratory volume in 1 s (FEV1), the best interaction was seen from EPHX1, SERPINE2, and GSTP1. For FEV1%pre, the forced vital capacity (FVC), and FEV1/FVC, the best interactions were seen from SERPINE2 and TGFB1. The results of this study provide further evidence for the genotype combinations at risk of developing COPD in Chinese Han population and improve the understanding on the genetic etiology of COPD and COPD-related quantitative traits.

Association of multiple genetic variants with chronic obstructive pulmonary disease susceptibility in Hainan region.

PubMed

Ding, Yipeng; Niu, Huan; Zhou, Long; Zhou, Wenjing; Chen, Jiannan; Xie, Shiliang; Geng, Tingting; Ouyang, Yanhong; He, Ping; Sun, Pei; Feng, Tian; Jin, Tianbo

2017-11-01

Recent genome-wide association studies have shown associations between variants in loci (4q28.1, 6p21.32, 6p21.1, 6q16.1, 10q22.1 and 10q22.3) and chronic obstructive pulmonary disease (COPD) or smoking behaviors. The objective of this study was to look for associations between 16 single nucleotide polymorphisms (SNP) at these six loci and COPD susceptibility in Hainan region. A case-control cohort was composed of 200 COPD cases and 401 controls that were genotyped and analyzed statistically. Odds ratios (OR) and 95% confidence intervals (CIs) were computed by chi-square (χ 2 ) test and genetic models by unconditional logistic regression. After Hardy-Weinberg equilibrium (HWE) P value screening, we excluded the SNP rs12220777 with P < 0.001. By χ 2 test only rs9296092 which located on 6p21.32 was provided the strongest evidence of an increasing risk of COPD with an OR of 3.28 (95% CI = 1.03 - 2.32; P = 0.003) between cases and controls. By genetic models analysis, we not only found rs9296092 increased COPD risk, but also found in the over-dominant model the genotype 'C/T' (OR = 0.55; 95% CI = 0.33 - 0.93; P = 0.023) of rs950063 was proved to be associated with decreased COPD risk. This study is the first to provide evidence of importance of rs9296092 and rs950063 for risk of COPD in Hainan Province. Further studies are needed to characterize the functional sequences that cause COPD. © 2015 John Wiley & Sons Ltd.

Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling

PubMed Central

Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future. PMID:27669518

COPD360social Online Community: A Social Media Review.

PubMed

Stellefson, Michael; Paige, Samantha R; Alber, Julia M; Stewart, Margaret

2018-06-01

People living with chronic obstructive pulmonary disease (COPD) commonly report feelings of loneliness and social isolation due to lack of support from family, friends, and health care providers. COPD360social is an interactive and disease-specific online community and social network dedicated to connecting people living with COPD to evidence-based resources. Through free access to collaborative forums, members can explore, engage, and discuss an array of disease-related topics, such as symptom management. This social media review provides an overview of COPD360social, specifically its features that practitioners can leverage to facilitate patient-provider communication, knowledge translation, and community building. The potential of COPD360social for chronic disease self-management is maximized through community recognition programming and interactive friend-finding tools that encourage members to share their own stories through blogs and multimedia (e.g., images, videos). The platform also fosters collaborative knowledge dissemination and helping relationships among patients, family members, friends, and health care providers. Successful implementation of COPD360social has dramatically expanded patient education and self-management support resources for people affected by COPD. Practitioners should refer patients and their families to online social networks such as COPD360social to increase knowledge and awareness of evidence-based chronic disease management practices.

THE ROLE OF GENETIC SUSCEPTIBILITY IN EXPERIMENTAL INDUCTION CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND PARTICULATE MATTER (PM) HEALTH EFFECTS.

EPA Science Inventory

Human COPD represents the 4th common cause of mortality worldwide and is characterized by presence of chronic bronchitis/inflammation and emphysema. The primary cause is cigarette smoking, as nearly all COPD patients are smokers. However, only about 10% of smokers develop this di...

Increased Severity and Mortality of CAP in COPD: Results from the German Competence Network, CAPNETZ

PubMed Central

Braeken, Dionne C.W.; Franssen, Frits M.E.; Schütte, Hartwig; Pletz, Mathias W.; Bals, Robert; Martus, Peter; Rohde, Gernot G.U.

2015-01-01

Background:Mortality of community acquired pneumonia (CAP) remains high despite significant research efforts. Knowledge about comorbidities including chronic obstructive pulmonary disease (COPD) might help to improve management and ultimately, survival. The impact of COPD on CAP severity and mortality remains a point of discussion. Objectives:Assess the prevalence and clinical characteristics of COPD in the observational German Competence Network for CAP, CAPNETZ, and to study the impact of COPD on CAP severity and mortality. Methods:1307 consecutive patients with CAP (57.0% males, age 59.0±18.5), classified as CAP-only (n=1043; 78.0%) and CAP-COPD (n=264; 20.2%) were followed up for 180 days. Associations between CAP, COPD and mortality were evaluated by univariate/multivariate and Kaplan-Meier survival analyses. Results:CAP-COPD patients were older, more often males, current/former smokers, with higher confusion-urea-respiratory rate-blood pressure, (CURB) scores. Length of hospital stay, urea, glucose and leucocytes plasma levels, and arterial carbon dioxide tension (PaCO2) were significantly increased in CAP-COPD. Thirty, 90- and 180-day mortality rates were significantly increased in CAP-COPD (p=0.046, odds ratio [OR]=2.48, 95% confidence interval [CI] 1.015-6.037; p=0.003, OR=2.80, 95%CI 1.430-5.468; p=0.001, OR=2.57, 95%CI 1.462-4.498; respectively). Intensive care unit (ICU)-admission and age, but not COPD, were identified as independent predictors of short- and long-term mortality. Conclusion:Severity as well as mortality was significantly higher in COPD patients with CAP. To improve CAP management with the aim to decrease its still-too-high mortality, underlying comorbidities, particularly COPD, need to be assessed. PMID:28848837

Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases.

PubMed

Liu, Gang; Cooley, Marion A; Jarnicki, Andrew G; Hsu, Alan C-Y; Nair, Prema M; Haw, Tatt Jhong; Fricker, Michael; Gellatly, Shaan L; Kim, Richard Y; Inman, Mark D; Tjin, Gavin; Wark, Peter A B; Walker, Marjorie M; Horvat, Jay C; Oliver, Brian G; Argraves, W Scott; Knight, Darryl A; Burgess, Janette K; Hansbro, Philip M

2016-06-16

Airway and/or lung remodeling, involving exaggerated extracellular matrix (ECM) protein deposition, is a critical feature common to pulmonary diseases including chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Fibulin-1 (Fbln1), an important ECM protein involved in matrix organization, may be involved in the pathogenesis of these diseases. We found that Fbln1 was increased in COPD patients and in cigarette smoke-induced (CS-induced) experimental COPD in mice. Genetic or therapeutic inhibition of Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-α, IL-33, and CXCL1) in experimental COPD. Fbln1c -/- mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases.

Genetic Association Analysis of Functional Impairment in Chronic Obstructive Pulmonary Disease

PubMed Central

Hersh, Craig P.; DeMeo, Dawn L.; Lazarus, Ross; Celedón, Juan C.; Raby, Benjamin A.; Benditt, Joshua O.; Criner, Gerard; Make, Barry; Martinez, Fernando J.; Scanlon, Paul D.; Sciurba, Frank C.; Utz, James P.; Reilly, John J.; Silverman, Edwin K.

2006-01-01

Rationale: Patients with severe chronic obstructive pulmonary disease (COPD) may have varying levels of disability despite similar levels of lung function. This variation may reflect different COPD subtypes, which may have different genetic predispositions. Objectives: To identify genetic associations for COPD-related phenotypes, including measures of exercise capacity, pulmonary function, and respiratory symptoms. Methods: In 304 subjects from the National Emphysema Treatment Trial, we genotyped 80 markers in 22 positional and/or biologically plausible candidate genes. Regression models were used to test for association, using a test–replication approach to guard against false-positive results. For significant associations, effect estimates were recalculated using the entire cohort. Positive associations with dyspnea were confirmed in families from the Boston Early-Onset COPD Study. Results: The test–replication approach identified four genes—microsomal epoxide hydrolase (EPHX1), latent transforming growth factor-β binding protein-4 (LTBP4), surfactant protein B (SFTPB), and transforming growth factor-β1 (TGFB1)—that were associated with COPD-related phenotypes. In all subjects, single-nucleotide polymorphisms (SNPs) in EPHX1 (p ⩽ 0.03) and in LTBP4 (p ⩽ 0.03) were associated with maximal output on cardiopulmonary exercise testing. Markers in LTBP4 (p ⩽ 0.05) and SFTPB (p = 0.005) were associated with 6-min walk test distance. SNPs in EPHX1 were associated with carbon monoxide diffusing capacity (p ⩽ 0.04). Three SNPs in TGFB1 were associated with dyspnea (p ⩽ 0.002), one of which replicated in the family study (p = 0.02). Conclusions: Polymorphisms in several genes seem to be associated with COPD-related traits other than FEV1. These associations may identify genes in pathways important for COPD pathogenesis. PMID:16456143

Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences-Comorbidities Network Study.

PubMed

Houben-Wilke, Sarah; Jörres, Rudolf A; Bals, Robert; Franssen, Frits M E; Gläser, Sven; Holle, Rolf; Karch, Annika; Koch, Armin; Magnussen, Helgo; Obst, Anne; Schulz, Holger; Spruit, Martijn A; Wacker, Margarethe E; Welte, Tobias; Wouters, Emiel F M; Vogelmeier, Claus; Watz, Henrik

2017-01-15

Knowledge about the prevalence of objectively assessed peripheral artery disease (PAD) and its clinical relevance in patients with chronic obstructive pulmonary disease (COPD) is scarce. We aimed to: (1) assess the prevalence of PAD in COPD compared with distinct control groups; and (2) study the association between PAD and functional capacity as well as health status. The ankle-brachial index was used to diagnose PAD (ankle-brachial index ≤ 0.9). The 6-minute-walk distance, health status (St. George's Respiratory Questionnaire), COPD Assessment Test, and EuroQol-5-Dimensions were assessed in patients enrolled in the German COPD and Systemic Consequences-Comorbidities Network cohort study. Control groups were derived from the Study of Health in Pomerania. A total of 2,088 patients with COPD (61.1% male; mean [SD] age, 65.3 [8.2] years, GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV: 9.4, 42.5, 37.5, and 10.5%, respectively) were included, of which 184 patients (8.8%; GOLD stage I-IV: 5.1, 7.4, 11.1, and 9.5%, respectively, vs. 5.9% in patients with GOLD stage 0 in the COPD and Systemic Consequences-Comorbidities Network) had PAD. In the Study of Health in Pomerania, PAD ranged from 1.8 to 4.2%. Patients with COPD with PAD had a significantly shorter 6-minute-walk distance (356 [108] vs. 422 [103] m, P < 0.001) and worse health status (St. George's Respiratory Questionnaire: 49.7 [20.1] vs. 42.7 [20.0] points, P < 0.001; COPD Assessment Test: 19.6 [7.4] vs. 17.9 [7.4] points, P = 0.004; EuroQol-5-Dimensions visual analog scale: 51.2 [19.0] vs. 57.2 [19.6], P < 0.001). Differences remained significant after correction for several confounders. In a large cohort of patients with COPD, 8.8% were diagnosed with PAD, which is higher than the prevalence in control subjects without COPD. PAD was associated with a clinically relevant reduction in functional capacity and health status.

The association of genetic polymorphisms of hypoxia inducible factor-1 alpha and vascular endothelial growth factor with increased risk of chronic obstructive pulmonary disease: A case-control study.

PubMed

Yu, Zhen-Gang; Wang, Bing-Zhe; Cheng, Zhao-Zhong

2017-09-01

Accumulated data over the years have suggested that hypoxia inducible factor-1 alpha (HIF-1α) and its downstream vascular endothelial growth factor (VEGF) gene may be linked with chronic obstructive pulmonary disease (COPD). This study aims to investigate the association of HIF-1α and VEGF genetic polymorphisms and their correlated risks with COPD. COPD patients (case group) and healthy individuals (control group) were recruited. DNA was extracted to detect HIF-1α and VEGF genetic polymorphisms. Basal lung volume and forced expiratory capacity in 1st second (FEV1)/forced vital capacity (FVC) and FEV 1 /predicted value (pred)% were calculated. Genotype and allele distributions in HIF-1α and VEGF genes were analyzed. Kaplan-Meier curves and logistic regression model were used for analysis of survival and COPD risk factors. Haplotypes for HIF-1α rs11549465 and rs11549467 were analyzed. FEV 1 /FVC and FEV1/pred% in the case group were lower than the control group. Frequencies of HIF-1α rs11549465 CT + TT genotype and T allele, and rs11549467 GA + AA genotype and A allele were higher in the case group than the control group. Patients with rs11549465 CT + TT had higher COPD risk than those with the CC genotype. Patients with rs11549467 GA + AA showed higher COPD risk and lower FEV 1 /FVC and FEV 1 /pred% than those with the GG genotype. Patients with HIF-1α TA haplotype showed higher COPD risk than those with the CG haplotype. Survival rate of patients with HIF-1α rs11549467 GG genotype was higher than those with the GA + AA genotype. HIF-1α rs11549467 polymorphism may be associated with COPD risk. Copyright © 2017. Published by Elsevier Taiwan.

COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity.

PubMed

Mannino, David M

2002-05-01

COPD continues to cause a heavy health and economic burden both in the United States and around the world. Some of the risk factors for COPD are well-known and include smoking, occupational exposures, air pollution, airway hyperresponsiveness, asthma, and certain genetic variations, although many questions, such as why < 20% of smokers develop significant airway obstruction, remain. Precise definitions of COPD vary and are frequently dependent on an accurate diagnosis of the problem by a physician. These differences in the definition of COPD can have large effects on the estimates of COPD in the population. Furthermore, evidence that COPD represents several different disease processes with potentially different interventions continues to emerge. In most of the world, COPD prevalence and mortality are still increasing and likely will continue to rise in response to increases in smoking, particularly by women and adolescents. Resources aimed at smoking cessation and prevention, COPD education and early detection, and better treatment will be of the most benefit in our continuing efforts against this important cause of morbidity and mortality.

Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility.

PubMed

Bruse, Shannon; Moreau, Michael; Bromberg, Yana; Jang, Jun-Ho; Wang, Nan; Ha, Hongseok; Picchi, Maria; Lin, Yong; Langley, Raymond J; Qualls, Clifford; Klensney-Tait, Julia; Zabner, Joseph; Leng, Shuguang; Mao, Jenny; Belinsky, Steven A; Xing, Jinchuan; Nyunoya, Toru

2016-01-07

Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15-20 % smokers manifest COPD, suggesting a role for genetic predisposition. Although genome-wide association studies have identified common genetic variants that are associated with susceptibility to COPD, effect sizes of the identified variants are modest, as is the total heritability accounted for by these variants. In this study, an extreme phenotype exome sequencing study was combined with in vitro modeling to identify COPD candidate genes. We performed whole exome sequencing of 62 highly susceptible smokers and 30 exceptionally resistant smokers to identify rare variants that may contribute to disease risk or resistance to COPD. This was a cross-sectional case-control study without therapeutic intervention or longitudinal follow-up information. We identified candidate genes based on rare variant analyses and evaluated exonic variants to pinpoint individual genes whose function was computationally established to be significantly different between susceptible and resistant smokers. Top scoring candidate genes from these analyses were further filtered by requiring that each gene be expressed in human bronchial epithelial cells (HBECs). A total of 81 candidate genes were thus selected for in vitro functional testing in cigarette smoke extract (CSE)-exposed HBECs. Using small interfering RNA (siRNA)-mediated gene silencing experiments, we showed that silencing of several candidate genes augmented CSE-induced cytotoxicity in vitro. Our integrative analysis through both genetic and functional approaches identified two candidate genes (TACC2 and MYO1E) that augment cigarette smoke (CS)-induced cytotoxicity and, potentially, COPD susceptibility.

Exome Array Analysis Identifies a Common Variant in IL27 Associated with Chronic Obstructive Pulmonary Disease

PubMed Central

Parker, Margaret M.; Chen, Han; Lao, Taotao; Hardin, Megan; Qiao, Dandi; Hawrylkiewicz, Iwona; Sliwinski, Pawel; Yim, Jae-Joon; Kim, Woo Jin; Kim, Deog Kyeom; Castaldi, Peter J.; Hersh, Craig P.; Morrow, Jarrett; Celli, Bartolome R.; Pinto-Plata, Victor M.; Criner, Gerald J.; Marchetti, Nathaniel; Bueno, Raphael; Agustí, Alvar; Make, Barry J.; Crapo, James D.; Calverley, Peter M.; Donner, Claudio F.; Lomas, David A.; Wouters, Emiel F. M.; Vestbo, Jorgen; Paré, Peter D.; Levy, Robert D.; Rennard, Stephen I.; Zhou, Xiaobo; Laird, Nan M.; Lin, Xihong; Beaty, Terri H.; Silverman, Edwin K.

2016-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) susceptibility is in part related to genetic variants. Most genetic studies have been focused on genome-wide common variants without a specific focus on coding variants, but common and rare coding variants may also affect COPD susceptibility. Objectives: To identify coding variants associated with COPD. Methods: We tested nonsynonymous, splice, and stop variants derived from the Illumina HumanExome array for association with COPD in five study populations enriched for COPD. We evaluated single variants with a minor allele frequency greater than 0.5% using logistic regression. Results were combined using a fixed effects meta-analysis. We replicated novel single-variant associations in three additional COPD cohorts. Measurements and Main Results: We included 6,004 control subjects and 6,161 COPD cases across five cohorts for analysis. Our top result was rs16969968 (P = 1.7 × 10−14) in CHRNA5, a locus previously associated with COPD susceptibility and nicotine dependence. Additional top results were found in AGER, MMP3, and SERPINA1. A nonsynonymous variant, rs181206, in IL27 (P = 4.7 × 10−6) was just below the level of exome-wide significance but attained exome-wide significance (P = 5.7 × 10−8) when combined with results from other cohorts. Gene expression datasets revealed an association of rs181206 and the surrounding locus with expression of multiple genes; several were differentially expressed in COPD lung tissue, including TUFM. Conclusions: In an exome array analysis of COPD, we identified nonsynonymous variants at previously described loci and a novel exome-wide significant variant in IL27. This variant is at a locus previously described in genome-wide associations with diabetes, inflammatory bowel disease, and obesity and appears to affect genes potentially related to COPD pathogenesis. PMID:26771213

A Genome-Wide Linkage Study for Chronic Obstructive Pulmonary Disease in a Dutch Genetic Isolate Identifies Novel Rare Candidate Variants.

PubMed

Nedeljkovic, Ivana; Terzikhan, Natalie; Vonk, Judith M; van der Plaat, Diana A; Lahousse, Lies; van Diemen, Cleo C; Hobbs, Brian D; Qiao, Dandi; Cho, Michael H; Brusselle, Guy G; Postma, Dirkje S; Boezen, H M; van Duijn, Cornelia M; Amin, Najaf

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a complex and heritable disease, associated with multiple genetic variants. Specific familial types of COPD may be explained by rare variants, which have not been widely studied. We aimed to discover rare genetic variants underlying COPD through a genome-wide linkage scan. Affected-only analysis was performed using the 6K Illumina Linkage IV Panel in 142 cases clustered in 27 families from a genetic isolate, the Erasmus Rucphen Family (ERF) study. Potential causal variants were identified by searching for shared rare variants in the exome-sequence data of the affected members of the families contributing most to the linkage peak. The identified rare variants were then tested for association with COPD in a large meta-analysis of several cohorts. Significant evidence for linkage was observed on chromosomes 15q14-15q25 [logarithm of the odds (LOD) score = 5.52], 11p15.4-11q14.1 (LOD = 3.71) and 5q14.3-5q33.2 (LOD = 3.49). In the chromosome 15 peak, that harbors the known COPD locus for nicotinic receptors, and in the chromosome 5 peak we could not identify shared variants. In the chromosome 11 locus, we identified four rare (minor allele frequency (MAF) <0.02), predicted pathogenic, missense variants. These were shared among the affected family members. The identified variants localize to genes including neuroblast differentiation-associated protein ( AHNAK ), previously associated with blood biomarkers in COPD, phospholipase C Beta 3 ( PLCB3 ), shown to increase airway hyper-responsiveness, solute carrier family 22-A11 ( SLC22A11 ), involved in amino acid metabolism and ion transport, and metallothionein-like protein 5 ( MTL5 ), involved in nicotinate and nicotinamide metabolism. Association of SLC22A11 and MTL5 variants were confirmed in the meta-analysis of 9,888 cases and 27,060 controls. In conclusion, we have identified novel rare variants in plausible genes related to COPD. Further studies utilizing large sample whole-genome sequencing should further confirm the associations at chromosome 11 and investigate the chromosome 15 and 5 linked regions.

Increased Transcript Complexity in Genes Associated with Chronic Obstructive Pulmonary Disease

PubMed Central

Lackey, Lela; McArthur, Evonne; Laederach, Alain

2015-01-01

Genome-wide association studies aim to correlate genotype with phenotype. Many common diseases including Type II diabetes, Alzheimer’s, Parkinson’s and Chronic Obstructive Pulmonary Disease (COPD) are complex genetic traits with hundreds of different loci that are associated with varied disease risk. Identifying common features in the genes associated with each disease remains a challenge. Furthermore, the role of post-transcriptional regulation, and in particular alternative splicing, is still poorly understood in most multigenic diseases. We therefore compiled comprehensive lists of genes associated with Type II diabetes, Alzheimer’s, Parkinson’s and COPD in an attempt to identify common features of their corresponding mRNA transcripts within each gene set. The SERPINA1 gene is a well-recognized genetic risk factor of COPD and it produces 11 transcript variants, which is exceptional for a human gene. This led us to hypothesize that other genes associated with COPD, and complex disorders in general, are highly transcriptionally diverse. We found that COPD-associated genes have a statistically significant enrichment in transcript complexity stemming from a disproportionately high level of alternative splicing, however, Type II Diabetes, Alzheimer’s and Parkinson’s disease genes were not significantly enriched. We also identified a subset of transcriptionally complex COPD-associated genes (~40%) that are differentially expressed between mild, moderate and severe COPD. Although the genes associated with other lung diseases are not extensively documented, we found preliminary data that idiopathic pulmonary disease genes, but not cystic fibrosis modulators, are also more transcriptionally complex. Interestingly, complex COPD transcripts are more often the product of alternative acceptor site usage. To verify the biological importance of these alternative transcripts, we used RNA-sequencing analyses to determine that COPD-associated genes are frequently expressed in lung and liver tissues and are regulated in a tissue-specific manner. Additionally, many complex COPD-associated genes are spliced differently between COPD and non-COPD patients. Our analysis therefore suggests that post-transcriptional regulation, particularly alternative splicing, is an important feature specific to COPD disease etiology that warrants further investigation. PMID:26480348

Association between RTEL1 gene polymorphisms and COPD susceptibility in a Chinese Han population.

PubMed

Ding, Yipeng; Xu, Heping; Yao, Jinjian; Xu, Dongchuan; He, Ping; Yi, Shengyang; Li, Quanni; Liu, Yuanshui; Wu, Cibing; Tian, Zhongjie

2017-01-01

We investigated the association between single-nucleotide polymorphisms in regulation of telomere elongation helicase 1 ( RTEL1 ), which has been associated with telomere length in several brain cancers and age-related diseases, and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese Han population. In a case-control study that included 279 COPD cases and 290 healthy controls, five single-nucleotide polymorphisms in RTEL1 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. In the genotype model analysis, we determined that rs4809324 polymorphism had a decreased effect on the risk of COPD (CC versus TT: OR =0.28; 95% CI =0.10-0.82; P =0.02). In the genetic model analysis, we found that the "C/C" genotype of rs4809324 was associated with a decreased risk of COPD based on the codominant model (OR =0.33; 95% CI =0.13-0.86; P =0.022) and recessive model (OR =0.32; 95% CI =0.12-0.80; P =0.009). Our data shed new light on the association between genetic polymorphisms of RTEL1 and COPD susceptibility in the Chinese Han population.

Inflammation, chronic obstructive pulmonary disease and aging.

PubMed

Provinciali, Mauro; Cardelli, Maurizio; Marchegiani, Francesca

2011-12-01

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal persistent inflammatory response to noxious environmental stimuli, particularly cigarette smoke. The determinants of the dysregulated immune responses, which play a role both in the onset and continuation of COPD, are largely unknown. We examined several molecular mechanisms regulating the inflammatory pathway, such as cytokine polymorphisms, miRNA expression, and DNA methylation in COPD and aging, with the aim to provide evidence supporting the view that aging of the immune system may predispose to COPD. The incidence of COPD increases with age. The pathogenesis of the disease is linked to a chronic inflammation and involves the recruitment and regulation of innate and adaptive immune cells. A chronic systemic inflammation characterizes aging and has been correlated with many diseases, most of them age-related. COPD and aging are associated with significant dysregulation of the immune system that leads to a chronic inflammatory response. The similar molecular mechanisms and the common genetic signature shared by COPD and aging suggest that immunosenescence may contribute to the development of COPD.

Personalized medicine and chronic obstructive pulmonary disease.

PubMed

Wouters, E F M; Wouters, B B R A F; Augustin, I M L; Franssen, F M E

2017-05-01

The current review summarizes ongoing developments in personalized medicine and precision medicine in chronic obstructive pulmonary disease (COPD). Our current approach is far away of personalized management algorithms as current recommendations for COPD are largely based on a reductionist disease description, operationally defined by results of spirometry. Besides precision medicine developments, a personalized medicine approach in COPD is described based on a holistic approach of the patient and considering illness as the consequence of dynamic interactions within and between multiple interacting and self-adjusting systems. Pulmonary rehabilitation is described as a model of personalized medicine. Largely based on current understanding of inflammatory processes in COPD, targeted interventions in COPD are reviewed. Augmentation therapy for α-1-antitrypsine deficiency is described as model of precision medicine in COPD based in profound understanding of the related genetic endotype. Future developments of precision medicine in COPD require identification of relevant endotypes combined with proper identification of phenotypes involved in the complex and heterogeneous manifestations of COPD.

Genetic influences on right ventricular systolic pressure (RVSP) in chronic obstructive pulmonary disease (COPD).

PubMed

Shaw, Janet G; Dent, Annette G; Passmore, Linda H; Burstow, Darryl J; Bowman, Rayleen V; Zimmerman, Paul V; Fong, Kwun M; Yang, Ian A

2012-06-13

Pulmonary hypertension (PH) is a complication of chronic obstructive pulmonary disease (COPD). This study examined genetic variations in mediators of vascular remodelling and their association with PH in patients with COPD. In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia. In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia. 580 COPD patients were recruited, 341 patients had a transthoracic echocardiogram, with RVSP measurable in 278 patients (mean age 69  years, mean FEV1 50% predicted, mean RVSP 44  mmHg, median history of 50 pack-years). Of the 7 tested SNPs, the NOS3-VNTR polymorphism was significantly associated with RVSP in a dose-dependent fashion for the risk allele: mean RVSP for a/a and a/b genotypes were 52.0 and 46.6  mmHg respectively, compared to 43.2  mmHg for b/b genotypes (P = 0.032). No associations were found between RVSP and other polymorphisms. ACE II or ID genotypes were associated with a lower FEV1% predicted than the ACE DD genotype (P = 0.028). The NOS3-298 TT genotype was associated with lower KCO % predicted than the NOS3-298 GG or GT genotype (P = 0.031). The NOS3-VNTR polymorphism was associated with RVSP in patients with COPD, supporting its involvement in the pathogenesis of PH in COPD. ACE and NOS3 genotypes were associated with COPD disease severity, but not with the presence of PH. Further study of these genes could lead to the development of prognostic and screening tools for PH in COPD.

Alpha-1-antitrypsin deficiency in Madeira (Portugal): the highest prevalence in the world.

PubMed

Spínola, Carla; Bruges-Armas, Jácome; Pereira, Conceição; Brehm, António; Spínola, Hélder

2009-10-01

Alpha-1-antitrypsin (AAT) deficiency is a common genetic disease which affects both lung and liver. Early diagnosis can help asymptomatic patients to adjust their lifestyle choices in order to reduce the risk of Chronic Obstructive Pulmonary Disease (COPD). The determination of this genetic deficiency prevalence in Madeira Island (Portugal) population is important to clarify susceptibility and define the relevance of performing genetic tests for AAT on individuals at risk for COPD. Two hundred samples of unrelated individuals from Madeira Island were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using Polymerase Chain Reaction-Mediated Site-Directed Mutagenesis. Our results show one of the highest frequencies for both mutations when compared to any already studied population in the world. In fact, PI*S mutation has the highest prevalence (18%), and PI*Z mutation (2.5%) was the third highest worldwide. The frequency of AAT deficiency genotypes in Madeira (PI*ZZ, PI*SS, and PI*SZ) is estimated to be the highest in the world: 41 per 1000. This high prevalence of AAT deficiency on Madeira Island reveals an increased genetic susceptibility to COPD and suggests a routine genetic testing for individuals at risk.

A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

PubMed

Turan, Nil; Kalko, Susana; Stincone, Anna; Clarke, Kim; Sabah, Ayesha; Howlett, Katherine; Curnow, S John; Rodriguez, Diego A; Cascante, Marta; O'Neill, Laura; Egginton, Stuart; Roca, Josep; Falciani, Francesco

2011-09-01

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

Early-Onset Chronic Obstructive Pulmonary Disease Is Associated with Female Sex, Maternal Factors, and African American Race in the COPDGene Study

PubMed Central

Foreman, Marilyn G.; Zhang, Lening; Murphy, James; Hansel, Nadia N.; Make, Barry; Hokanson, John E.; Washko, George; Regan, Elizabeth A.; Crapo, James D.; Silverman, Edwin K.

2011-01-01

Rationale: The characterization of young adults who develop late-onset diseases may augment the detection of novel genes and promote new pathogenic insights. Methods: We analyzed data from 2,500 individuals of African and European ancestry in the COPDGene Study. Subjects with severe, early-onset chronic obstructive pulmonary disease (COPD) (n = 70, age < 55 yr, FEV1 < 50% predicted) were compared with older subjects with COPD (n = 306, age > 64 yr, FEV1 < 50% predicted). Measurements and Main Results: Subjects with severe, early-onset COPD were predominantly females (66%), P = 0.0004. Proportionally, early-onset COPD was seen in 42% (25 of 59) of African Americans versus 14% (45 of 317) of non-Hispanic whites, P < 0.0001. Other risk factors included current smoking (56 vs. 17%, P < 0.0001) and self-report of asthma (39 vs. 25%, P = 0.008). Maternal smoking (70 vs. 44%, P = 0.0001) and maternal COPD (23 vs. 12%, P = 0.03) were reported more commonly in subjects with early-onset COPD. Multivariable regression analysis found association with African American race, odds ratio (OR), 7.5 (95% confidence interval [CI], 2.3–24; P = 0.0007); maternal COPD, OR, 4.7 (95% CI, 1.3–17; P = 0.02); female sex, OR, 3.1 (95% CI, 1.1–8.7; P = 0.03); and each pack-year of smoking, OR, 0.98 (95% CI, 0.96–1.0; P = 0.03). Conclusions: These observations support the hypothesis that severe, early-onset COPD is prevalent in females and is influenced by maternal factors. Future genetic studies should evaluate (1) gene-by-sex interactions to address sex-specific genetic contributions and (2) gene-by-race interactions. PMID:21562134

Association between RTEL1 gene polymorphisms and COPD susceptibility in a Chinese Han population

PubMed Central

Ding, Yipeng; Xu, Heping; Yao, Jinjian; Xu, Dongchuan; He, Ping; Yi, Shengyang; Li, Quanni; Liu, Yuanshui; Wu, Cibing; Tian, Zhongjie

2017-01-01

Objective We investigated the association between single-nucleotide polymorphisms in regulation of telomere elongation helicase 1 (RTEL1), which has been associated with telomere length in several brain cancers and age-related diseases, and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese Han population. Methods In a case–control study that included 279 COPD cases and 290 healthy controls, five single-nucleotide polymorphisms in RTEL1 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. Results In the genotype model analysis, we determined that rs4809324 polymorphism had a decreased effect on the risk of COPD (CC versus TT: OR =0.28; 95% CI =0.10–0.82; P=0.02). In the genetic model analysis, we found that the “C/C” genotype of rs4809324 was associated with a decreased risk of COPD based on the codominant model (OR =0.33; 95% CI =0.13–0.86; P=0.022) and recessive model (OR =0.32; 95% CI =0.12–0.80; P=0.009). Conclusion Our data shed new light on the association between genetic polymorphisms of RTEL1 and COPD susceptibility in the Chinese Han population. PMID:28360516

Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort

PubMed Central

Celli, Bartolome R.; Poblador-Plou, Beatriz; Calderón-Larrañaga, Amaia; de-Torres, Juan Pablo; Gimeno-Feliu, Luis A.; Bertó, Juan; Casanova, Ciro; Pinto-Plata, Victor M.; Cabrera-Lopez, Carlos; Polverino, Francesca; Marin, Jose M.

2018-01-01

Background Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. Methods and findings We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers’ subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network’s density for the COPD group aged 56–65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. Conclusion Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age. PMID:29470502

Role of the inflammasome in chronic obstructive pulmonary disease (COPD).

PubMed

Colarusso, Chiara; Terlizzi, Michela; Molino, Antonio; Pinto, Aldo; Sorrentino, Rosalinda

2017-10-10

Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), a pulmonary disorder characterized by chronic bronchitis, chronic airway obstruction, emphysema, associated to progressive and irreversible decline of lung function. Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. So far, scientific evidence has focused on nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome, a specialized inflammatory signaling platform that governs the maturation and secretion of IL-1-like cytokines through the regulation of caspase-1-dependent proteolytic processing. Some studies revealed that it is involved during airway inflammation typical of COPD. Based on the influence of cigarette smoke in various respiratory diseases, including COPD, in this view we report its effects in inflammatory and immune responses in COPD mouse models and in human subjects affected by COPD. In sharp contrast to what reported on experimental and clinical studies, randomized clinical trials show that indirect inflammasome inhibitors did not have any beneficial effect in moderate to severe COPD patients.

Familial transmission of chronic obstructive pulmonary disease in adoptees: a Swedish nationwide family study

PubMed Central

Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina

2015-01-01

Objectives Familial clustering of chronic obstructive pulmonary disease (COPD) is well established, but the familial risk of COPD has not been determined among adoptees. The aim was to determine whether the familial transmission of COPD is related to disease in biological and/or adoptive parents. Design Historic cohort study. Participants 80 214 (50% females). Methods The Swedish Multi-Generation Register was used to follow all Swedish-born adoptees born in 1932–2004 (n=80 214) between 1 January 1964 and 31 December 2010 for COPD (n=1978). The risk of COPD was estimated in adoptees with at least one biological parent with COPD but no adoptive parent with COPD (n=162) compared with adoptees without a biological or adoptive parent with COPD. The risk of COPD was also determined in adoptees with at least one adoptive parent but no biological parent with COPD (n=110), and in adoptees with both affected biological and adoptive parents (n=162). Primary outcome measure COPD in adoptees. Results Adoptees with COPD in at least one biological parent but no adoptive parent were more likely to have COPD than adoptees without a biological or adoptive parent with COPD (standardised incidence ratio, SIR=1.98 (95% CI 1.69 to 2.31)). The familial SIR for adoptees with both a biological parent and an adoptive parent with COPD was 1.68 (95% CI 1.39 to 2.00). Adoptees with at least one adoptive parent with COPD but no biological parent with COPD were not at an increased risk of COPD (SIR=1.12 (95% CI 0.92 to 1.35)). Conclusions The findings of the study show that the familial transmission of COPD is associated with COPD in biological but not adoptive parents, suggesting that genetic or early life factors are important in the familial transmission of COPD. PMID:25869691

Familial transmission of chronic obstructive pulmonary disease in adoptees: a Swedish nationwide family study.

PubMed

Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina

2015-04-13

Familial clustering of chronic obstructive pulmonary disease (COPD) is well established, but the familial risk of COPD has not been determined among adoptees. The aim was to determine whether the familial transmission of COPD is related to disease in biological and/or adoptive parents. Historic cohort study. 80,214 (50% females). The Swedish Multi-Generation Register was used to follow all Swedish-born adoptees born in 1932-2004 (n=80,214) between 1 January 1964 and 31 December 2010 for COPD (n=1978). The risk of COPD was estimated in adoptees with at least one biological parent with COPD but no adoptive parent with COPD (n=162) compared with adoptees without a biological or adoptive parent with COPD. The risk of COPD was also determined in adoptees with at least one adoptive parent but no biological parent with COPD (n=110), and in adoptees with both affected biological and adoptive parents (n=162). COPD in adoptees. Adoptees with COPD in at least one biological parent but no adoptive parent were more likely to have COPD than adoptees without a biological or adoptive parent with COPD (standardised incidence ratio, SIR=1.98 (95% CI 1.69 to 2.31)). The familial SIR for adoptees with both a biological parent and an adoptive parent with COPD was 1.68 (95% CI 1.39 to 2.00). Adoptees with at least one adoptive parent with COPD but no biological parent with COPD were not at an increased risk of COPD (SIR=1.12 (95% CI 0.92 to 1.35)). The findings of the study show that the familial transmission of COPD is associated with COPD in biological but not adoptive parents, suggesting that genetic or early life factors are important in the familial transmission of COPD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Identification of proteomic signatures associated with lung cancer and COPD.

PubMed

Pastor, M D; Nogal, A; Molina-Pinelo, S; Meléndez, R; Salinas, A; González De la Peña, M; Martín-Juan, J; Corral, J; García-Carbonero, R; Carnero, A; Paz-Ares, L

2013-08-26

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. The aim of this study was to identify distinct proteomic profiles able to discriminate these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC without COPD, and control with neither COPD nor LC. Proteins were separated into spots by bidimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 40 proteins were differentially expressed in the LC and/or COPD groups as compared with the control group. Distinct protein profiles were identified and validated for each pathological entity (LC and COPD). The main networks involved were related to inflammatory signalling, free radical scavenging and oxidative stress response, and glycolysis and gluconeogenesis pathways. The most relevant signalling link between LC and COPD was through the NF-κB pathway. In conclusion, the protein profiles identified contribute to elucidate the underlying pathogenic pathways of both diseases, and provide new tools of potential use as biomarkers for the early diagnosis of LC. Sequence coverage. The protein sequence coverage (95%) was estimated for specific proteins by the percentage of matching amino acids from the identified peptides having confidence greater than or equal to 95% divided by the total number of amino acids in the sequence. Ingenuity Pathways Analysis. Mapping of our proteins onto biological pathways and disease networks demonstrated that 22 proteins were linked to inflammatory signalling (p-value: 1.35 10(-08)-1.42 10(-02)), 15 proteins were associated with free radical scavenging and oxidative stress response (p-value: 4.93 10(-11)-1.27 10(-02)), and 9 proteins were related with glycolysis and gluconeogenesis pathways (p-value: 7.39 10(-09)-1.58 10(-02)). Copyright © 2013 Elsevier B.V. All rights reserved.

Study Design and Interim Outcomes of Guangzhou Institute of Respiratory Disease COPD Biobank.

PubMed

Lu, Wenju; Zheng, Zeguang; Chen, Xindong; Tan, Hui; Wang, Jian; Zhang, Zili; Zheng, Jinping; Chen, Rongchang; Zhang, Chenting; Xu, Xiaoming; Chen, Yuqin; Yang, Quan; Xiong, Mingmei; Guo, Meihua; Zhou, Qipeng; Tang, Chun; Wang, Yingfeng; Ye, Jinmei; Li, Defu; Shu, Jiaze; Tan, Shu; Xu, Chuyi; Wang, Yan; Lai, Ning; Yang, Kai; Lu, Jiachun; Ran, Pixin; Zhong, Nanshan

2016-01-01

GIRD COPD Biobank is a multicenter observational study blood-based database with local characteristics, in order to investigate the causes, risk factors, pathogenesis, prevalence patterns and trends of COPD and promote new pathogenic insights in China. We enrolled 855 clinically COPD patients and 660 controls with normal lung function. Extensive data collection has been undertaken with questionnaires, clinical measurements, and collection and storage of blood specimens, following Standard Operating Procedures (SOP). All surveys had similar quality controls, supervisions, and training of the investigator team. Since September 2010, a total of 1515 subjects (1116 [73.7%] males; 855 [56.4%] diagnosed with COPD) were enrolled. Analyses of the design and interim results of the GIRD COPD Biobank Study identified patients with COPD were older, lower educational level, a longer history of pack-year smoking, less in kitchen fan usage, X-ray exposure, and history of disease (P < 0.01 for all); Most of the COPD subjects belonged to moderately severe or worse, stratified according to Global Lung Function Initiative (GLI); COPD patients had relatively more co-morbidities than controls; Environmental hazard exposures might be the main contributors to the reported respiratory symptoms; Cold air, haze, and influenza acted the top three factors to induce respiratory symptoms in both COPD cases and controls. The GIRD COPD Biobank Study has the potential to provide substantial novel insights into the genetics, biomarkers, environmental and lifestyle aspects of COPD. It is expected to provide new insights for pathogenesis and the long-term progression of COPD.

Lobar Emphysema Distribution Is Associated With 5-Year Radiological Disease Progression.

PubMed

Boueiz, Adel; Chang, Yale; Cho, Michael H; Washko, George R; San José Estépar, Raul; Bowler, Russell P; Crapo, James D; DeMeo, Dawn L; Dy, Jennifer G; Silverman, Edwin K; Castaldi, Peter J

2018-01-01

Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Genetic association between human chitinases and lung function in COPD.

PubMed

Aminuddin, F; Akhabir, L; Stefanowicz, D; Paré, P D; Connett, J E; Anthonisen, N R; Fahy, J V; Seibold, M A; Burchard, E G; Eng, C; Gulsvik, A; Bakke, P; Cho, M H; Litonjua, A; Lomas, D A; Anderson, W H; Beaty, T H; Crapo, J D; Silverman, E K; Sandford, A J

2012-07-01

Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.

Uric acid, lung function, physical capacity and exacerbation frequency in patients with COPD: a multi-dimensional approach.

PubMed

Kahnert, Kathrin; Alter, Peter; Welte, Tobias; Huber, Rudolf M; Behr, Jürgen; Biertz, Frank; Watz, Henrik; Bals, Robert; Vogelmeier, Claus F; Jörres, Rudolf A

2018-06-04

Recent investigations showed single associations between uric acid levels, functional parameters, exacerbations and mortality in COPD patients. The aim of this study was to describe the role of uric acid within the network of multiple relationships between function, exacerbation and comorbidities. We used baseline data from the German COPD cohort COSYCONET which were evaluated by standard multiple regression analyses as well as path analysis to quantify the network of relations between parameters, particularly uric acid. Data from 1966 patients were analyzed. Uric acid was significantly associated with reduced FEV 1 , reduced 6-MWD, higher burden of exacerbations (GOLD criteria) and cardiovascular comorbidities, in addition to risk factors such as BMI and packyears. These associations remained significant after taking into account their multiple interdependences. Compared to uric acid levels the diagnosis of hyperuricemia and its medication played a minor role. Within the limits of a cross-sectional approach, our results strongly suggest that uric acid is a biomarker of high impact in COPD and plays a genuine role for relevant outcomes such as physical capacity and exacerbations. These findings suggest that more attention should be paid to uric acid in the evaluation of COPD disease status.

A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease

PubMed Central

Turan, Nil; Kalko, Susana; Stincone, Anna; Clarke, Kim; Sabah, Ayesha; Howlett, Katherine; Curnow, S. John; Rodriguez, Diego A.; Cascante, Marta; O'Neill, Laura; Egginton, Stuart; Roca, Josep; Falciani, Francesco

2011-01-01

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients. PMID:21909251

Genome-Wide Association Analysis of Body Mass in Chronic Obstructive Pulmonary Disease

PubMed Central

Wan, Emily S.; Cho, Michael H.; Boutaoui, Nadia; Klanderman, Barbara J.; Sylvia, Jody S.; Ziniti, John P.; Won, Sungho; Lange, Christoph; Pillai, Sreekumar G.; Anderson, Wayne H.; Kong, Xiangyang; Lomas, David A.; Bakke, Per S.; Gulsvik, Amund; Regan, Elizabeth A.; Murphy, James R.; Make, Barry J.; Crapo, James D.; Wouters, Emiel F.; Celli, Bartolome R.; Silverman, Edwin K.; DeMeo, Dawn L.

2011-01-01

Cachexia, whether assessed by body mass index (BMI) or fat-free mass index (FFMI), affects a significant proportion of patients with chronic obstructive pulmonary disease (COPD), and is an independent risk factor for increased mortality, increased emphysema, and more severe airflow obstruction. The variable development of cachexia among patients with COPD suggests a role for genetic susceptibility. The objective of the present study was to determine genetic susceptibility loci involved in the development of low BMI and FFMI in subjects with COPD. A genome-wide association study (GWAS) of BMI was conducted in three independent cohorts of European descent with Global Initiative for Chronic Obstructive Lung Disease stage II or higher COPD: Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-Points (ECLIPSE; n = 1,734); Norway-Bergen cohort (n = 851); and a subset of subjects from the National Emphysema Treatment Trial (NETT; n = 365). A genome-wide association of FFMI was conducted in two of the cohorts (ECLIPSE and Norway). In the combined analyses, a significant association was found between rs8050136, located in the first intron of the fat mass and obesity–associated (FTO) gene, and BMI (P = 4.97 × 10−7) and FFMI (P = 1.19 × 10−7). We replicated the association in a fourth, independent cohort consisting of 502 subjects with COPD from COPDGene (P = 6 × 10−3). Within the largest contributing cohort of our analysis, lung function, as assessed by forced expiratory volume at 1 second, varied significantly by FTO genotype. Our analysis suggests a potential role for the FTO locus in the determination of anthropomorphic measures associated with COPD. PMID:21037115

Genetic polymorphisms of matrix metalloproteinases and protein levels in chronic obstructive pulmonary disease in a Mexican population.

PubMed

Hernández-Montoya, Jazmín; Pérez-Ramos, Julia; Montaño, Martha; Ramírez-Venegas, Alejandra; Sansores, Raúl H; Pérez-Rubio, Gloria; Velázquez-Uncal, Mónica; Camarena, Angel; Ramos, Carlos; Falfán-Valencia, Ramcés

2015-01-01

To evaluate association of single nucleotide polymorphisms (SNPs) in the MMP1, MMP2, MMP9 and MMP12 genes and serum MMP-2 and MMP-9 levels in smoking chronic obstructive pulmonary disease (COPD) patients. Genotyping using real-time PCR in 330 smokers with COPD (COPD), 658 smokers without COPD (SNC) and 150 nonsmokers (NCNS), the analysis of samples used was χ(2) test. Using ELISA, the proteins were evaluated. Multiple comparisons were made by ANOVA. rs243864 (OR: 7.44; 95% CI: 3.62-15.26) and rs11646643 (OR: 1.58; 95% CI: 1.07-2.34) of the MMP-2 gene and rs3918253 (OR: 1.72; 95% CI: 1.08-2.71) of the MMP-9 gene, were associated with the risk of COPD. Serum MMP-2 level in the COPD group was lower compared with SNC (p < 0.05). Serum MMP-9 level was elevated in the COPD group compared with SNC (p < 0.05). Polymorphisms in MMP2 and MMP9 but not in MMP1 and MMP12 are associated with the risk of COPD in the Mexican mestizo population.

Candidate genes for COPD in two large data sets.

PubMed

Bakke, P S; Zhu, G; Gulsvik, A; Kong, X; Agusti, A G N; Calverley, P M A; Donner, C F; Levy, R D; Make, B J; Paré, P D; Rennard, S I; Vestbo, J; Wouters, E F M; Anderson, W; Lomas, D A; Silverman, E K; Pillai, S G

2011-02-01

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV₁) % predicted and FEV₁/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV₁ % predicted and FEV₁/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

Role of the inflammasome in chronic obstructive pulmonary disease (COPD)

PubMed Central

Colarusso, Chiara; Terlizzi, Michela; Molino, Antonio; Pinto, Aldo; Sorrentino, Rosalinda

2017-01-01

Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), a pulmonary disorder characterized by chronic bronchitis, chronic airway obstruction, emphysema, associated to progressive and irreversible decline of lung function. Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. So far, scientific evidence has focused on nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome, a specialized inflammatory signaling platform that governs the maturation and secretion of IL-1-like cytokines through the regulation of caspase-1-dependent proteolytic processing. Some studies revealed that it is involved during airway inflammation typical of COPD. Based on the influence of cigarette smoke in various respiratory diseases, including COPD, in this view we report its effects in inflammatory and immune responses in COPD mouse models and in human subjects affected by COPD. In sharp contrast to what reported on experimental and clinical studies, randomized clinical trials show that indirect inflammasome inhibitors did not have any beneficial effect in moderate to severe COPD patients. PMID:29137224

Profiles of chronic obstructive lung disease: characteristics of stable chronic obstructive lung disease in different parts of Asia.

PubMed

Bhome, Arvind B; Brashier, Bill

2014-03-01

This review discusses the recent Asian chronic obstructive lung disease (COPD) studies that characterize stable COPD, to understand its peculiarities. Asian research has improved our understanding of COPD. Household air pollution (HAP) is as important as smoking. Smoking in Asia is varied, and noncigarette smoking exposure remains under-investigated. Prevalence studies are often questionnaire based. Spirometry-based prevalence needs study. Burden of obstructive lung disease studies are getting published. Female COPD in Asia is predominantly HAP induced. The patients are underweight, milder 'Global Initiative for Obstructive Lung Disease- class' and have compromised health-related quality of life often with depression and anxiety, but other comorbidities do occur and are getting defined.Nonsmokers' COPD is often associated with small airway thickening, less emphysema, but considerable morbidity. Asian COPD may have an eosinophilic component, but its significance is unknown. There is genetic predisposition among some Asians to COPD, and among some patients to lung cancer. The emerging pandemic of lifestyle diseases demands that metabolic and cardiovascular comorbidities in COPD need investigation. COPD in Asia is increasing and burdensome. It is affecting both sexes; is caused by HAP as much as smoking; causes poor quality of life and intense psychological burden; and is associated with unique patho-physiology, which will require research and action.

Genetic variant in the 3'-untranslated region of VEGFR1 gene influences chronic obstructive pulmonary disease and lung cancer development in Chinese population.

PubMed

Wang, Hui; Yang, Lei; Deng, Jieqiong; Wang, Bo; Yang, Xiaorong; Yang, Rongrong; Cheng, Mei; Fang, Wenxiang; Qiu, Fuman; Zhang, Xin; Ji, Weidong; Ran, Pixin; Zhou, Yifeng; Lu, Jiachun

2014-09-01

Lung inflammation and epithelial to mesenchymal transition (EMT) are two pathogenic features for the two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. VEGFR1 (or FLT1) plays a certain role in promoting tumour growth, inflammation and EMT. To simultaneously test the association between the single nucleotide polymorphisms (SNPs) in VEGFR1 and risk of COPD and lung cancer would reveal genetic mechanisms shared by these two diseases and joint aetiology. We conducted a two-population hospital-based case-control study. Three potential functional SNPs (rs664393, rs7326277 and rs9554314) were genotyped in southern Chinese and validated in eastern Chinese to explore their associations with COPD risk in 1511 COPD patients and 1677 normal lung function controls, and with lung cancer risk in 1559 lung cancer cases and 1679 cancer-free controls. We also detected the function of the promising SNP. Individuals carrying the rs7326277C (CT+CC) variant genotypes of VEGFR1 had a significant decrease in risk of both COPD (OR = 0.78; 95% CI = 0.68-0.90) and lung cancer (OR = 0.79; 95% CI = 0.64-0.98), compared with those carrying the rs7326277TT genotype. Functional assays further showed that the rs7326277C genotypes had lower transcriptional activity and caused decreased VEGFR expression, compared with the rs7326277TT genotype. However, no significant association was observed for the other two SNPs (rs664393 and rs9554314) and either COPD or lung cancer risk. Our data suggested that the rs7326277C variant of VEGFR1 could reduce both COPD and lung cancer risk by lowering VEGFR1 mRNA expression; the SNP might be a common susceptible locus for both COPD and lung cancer. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Context Relevant Prediction Model for COPD Domain Using Bayesian Belief Network

PubMed Central

Saleh, Lokman; Ajami, Hicham; Mili, Hafedh

2017-01-01

In the last three decades, researchers have examined extensively how context-aware systems can assist people, specifically those suffering from incurable diseases, to help them cope with their medical illness. Over the years, a huge number of studies on Chronic Obstructive Pulmonary Disease (COPD) have been published. However, how to derive relevant attributes and early detection of COPD exacerbations remains a challenge. In this research work, we will use an efficient algorithm to select relevant attributes where there is no proper approach in this domain. Such algorithm predicts exacerbations with high accuracy by adding discretization process, and organizes the pertinent attributes in priority order based on their impact to facilitate the emergency medical treatment. In this paper, we propose an extension of our existing Helper Context-Aware Engine System (HCES) for COPD. This project uses Bayesian network algorithm to depict the dependency between the COPD symptoms (attributes) in order to overcome the insufficiency and the independency hypothesis of naïve Bayesian. In addition, the dependency in Bayesian network is realized using TAN algorithm rather than consulting pneumologists. All these combined algorithms (discretization, selection, dependency, and the ordering of the relevant attributes) constitute an effective prediction model, comparing to effective ones. Moreover, an investigation and comparison of different scenarios of these algorithms are also done to verify which sequence of steps of prediction model gives more accurate results. Finally, we designed and validated a computer-aided support application to integrate different steps of this model. The findings of our system HCES has shown promising results using Area Under Receiver Operating Characteristic (AUC = 81.5%). PMID:28644419

Efficacy and safety profile of xanthines in COPD: a network meta-analysis.

PubMed

Cazzola, Mario; Calzetta, Luigino; Barnes, Peter J; Criner, Gerard J; Martinez, Fernando J; Papi, Alberto; Gabriella Matera, Maria

2018-06-30

Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD. Copyright ©ERS 2018.

Genes and chronic obstructive pulmonary disease.

PubMed

Foreman, Marilyn G; Campos, Michael; Celedón, Juan C

2012-07-01

Although much remains to be done, recent advances and the advent of new methodologies are promising and should yield increased understanding of the genetic and epigenetic mechanisms influencing the pathogenesis of COPD, both related and unrelated to severe AAT deficiency. Such understanding should ultimately be translated into novel approaches to prevent, diagnose, and treat COPD. Copyright © 2012 Elsevier Inc. All rights reserved.

PHENOTYPIC AND GENETIC HETEROGENEITY AMONG SUBJECTS WITH MILD AIRFLOW OBSTRUCTION IN COPDGENE

PubMed Central

Lee, Jin Hwa; Cho, Michael H.; McDonald, Merry-Lynn N.; Hersh, Craig P.; Castaldi, Peter J.; Crapo, James D.; Wan, Emily S.; Dy, Jennifer G.; Chang, Yale; Regan, Elizabeth A.; Hardin, Megan; DeMeo, Dawn L.; Silverman, Edwin K.

2014-01-01

Background Chronic obstructive pulmonary disease (COPD) is characterized by marked phenotypic heterogeneity. Most previous studies have focused on COPD subjects with FEV1 < 80% predicted. We investigated the clinical and genetic heterogeneity in subjects with mild airflow limitation in spirometry grade 1 defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD 1). Methods Data from current and former smokers participating in the COPDGene Study (NCT00608764) were analyzed. K-means clustering was performed to explore subtypes within 794 GOLD 1 subjects. For all subjects with GOLD 1 and with each cluster, a genome-wide association study and candidate gene testing were performed using smokers with normal lung function as a control group. Combinations of COPD genome-wide significant single nucleotide polymorphisms (SNPs) were tested for association with FEV1 (% predicted) in GOLD 1 and in a combined group of GOLD1 and smoking control subjects. Results K-means clustering of GOLD 1 subjects identified putative “near-normal”, “airway-predominant”, “emphysema-predominant” and “lowest FEV1 % predicted” subtypes. In non-Hispanic whites, the only SNP nominally associated with GOLD 1 status relative to smoking controls was rs7671167 (FAM13A) in logistic regression models with adjustment for age, sex, pack-years of smoking, and genetic ancestry. The emphysema-predominant GOLD 1 cluster was nominally associated with rs7671167 (FAM13A) and rs161976 (BICD1). The lowest FEV1 % predicted cluster was nominally associated with rs1980057 (HHIP) and rs1051730 (CHRNA3). Combinations of COPD genome-wide significant SNPs were associated with FEV1 (% predicted) in a combined group of GOLD 1 and smoking control subjects. Conclusions Our results indicate that GOLD 1 subjects show substantial clinical heterogeneity, which is at least partially related to genetic heterogeneity. PMID:25154699

Phenotypic and genetic heterogeneity among subjects with mild airflow obstruction in COPDGene.

PubMed

Lee, Jin Hwa; Cho, Michael H; McDonald, Merry-Lynn N; Hersh, Craig P; Castaldi, Peter J; Crapo, James D; Wan, Emily S; Dy, Jennifer G; Chang, Yale; Regan, Elizabeth A; Hardin, Megan; DeMeo, Dawn L; Silverman, Edwin K

2014-10-01

Chronic obstructive pulmonary disease (COPD) is characterized by marked phenotypic heterogeneity. Most previous studies have focused on COPD subjects with FEV1 < 80% predicted. We investigated the clinical and genetic heterogeneity in subjects with mild airflow limitation in spirometry grade 1 defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD 1). Data from current and former smokers participating in the COPDGene Study (NCT00608764) were analyzed. K-means clustering was performed to explore subtypes within 794 GOLD 1 subjects. For all subjects with GOLD 1 and with each cluster, a genome-wide association study and candidate gene testing were performed using smokers with normal lung function as a control group. Combinations of COPD genome-wide significant single nucleotide polymorphisms (SNPs) were tested for association with FEV1 (% predicted) in GOLD 1 and in a combined group of GOLD 1 and smoking control subjects. K-means clustering of GOLD 1 subjects identified putative "near-normal", "airway-predominant", "emphysema-predominant" and "lowest FEV1% predicted" subtypes. In non-Hispanic whites, the only SNP nominally associated with GOLD 1 status relative to smoking controls was rs7671167 (FAM13A) in logistic regression models with adjustment for age, sex, pack-years of smoking, and genetic ancestry. The emphysema-predominant GOLD 1 cluster was nominally associated with rs7671167 (FAM13A) and rs161976 (BICD1). The lowest FEV1% predicted cluster was nominally associated with rs1980057 (HHIP) and rs1051730 (CHRNA3). Combinations of COPD genome-wide significant SNPs were associated with FEV1 (% predicted) in a combined group of GOLD 1 and smoking control subjects. Our results indicate that GOLD 1 subjects show substantial clinical heterogeneity, which is at least partially related to genetic heterogeneity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

PubMed Central

Cloonan, Suzanne M.; Glass, Kimberly; Laucho-Contreras, Maria E.; Bhashyam, Abhiram R.; Cervo, Morgan; Pabón, Maria A.; Konrad, Csaba; Polverino, Francesca; Siempos, Ilias I.; Perez, Elizabeth; Mizumura, Kenji; Ghosh, Manik C.; Parameswaran, Harikrishnan; Williams, Niamh C.; Rooney, Kristen T.; Chen, Zhi-Hua; Goldklang, Monica P.; Yuan, Guo-Cheng; Moore, Stephen C.; Demeo, Dawn L.; Rouault, Tracey A.; D’Armiento, Jeanine M.; Schon, Eric A.; Manfredi, Giovanni; Quackenbush, John; Mahmood, Ashfaq; Silverman, Edwin K.; Owen, Caroline A.; Choi, Augustine M.K.

2015-01-01

Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. PMID:26752519

The Challenges of Precision Medicine in COPD.

PubMed

Cazzola, Mario; Calzetta, Luigino; Rogliani, Paola; Matera, Maria Gabriella

2017-08-01

Pheno-/endotyping chronic obstructive pulmonary disease (COPD) is really important because it provides patients with precise and personalized medicine. The central concept of precision medicine is to take individual variability into account when making management decisions. Precision medicine should ensure that patients get the right treatment at the right dose at the right time, with minimum harmful consequences and maximum efficacy. Ideally, we should search for genetic and molecular biomarker-based profiles. Given the clinical complexity of COPD, it seems likely that a panel of several biomarkers will be required to characterize pathogenetic factors and their course over time. The need for biomarkers to guide the clinical care of individuals with COPD and to enhance the possibilities of success in drug development is clear and urgent, but biomarker development is tremendously challenging and expensive, and translation of research efforts to date has been largely ineffective. Furthermore, the development of personalized treatments will require a much more detailed understanding of the clinical and biological heterogeneity of COPD. Therefore, we are still far from being able to apply precision medicine in COPD and the treatable traits and FEV 1 -free approaches are attempts to precision medicine in COPD that must be considered still quite unsophisticated.

Molecular mechanisms underlying variations in lung function: a systems genetics analysis

PubMed Central

Obeidat, Ma’en; Hao, Ke; Bossé, Yohan; Nickle, David C; Nie, Yunlong; Postma, Dirkje S; Laviolette, Michel; Sandford, Andrew J; Daley, Denise D; Hogg, James C; Elliott, W Mark; Fishbane, Nick; Timens, Wim; Hysi, Pirro G; Kaprio, Jaakko; Wilson, James F; Hui, Jennie; Rawal, Rajesh; Schulz, Holger; Stubbe, Beate; Hayward, Caroline; Polasek, Ozren; Järvelin, Marjo-Riitta; Zhao, Jing Hua; Jarvis, Deborah; Kähönen, Mika; Franceschini, Nora; North, Kari E; Loth, Daan W; Brusselle, Guy G; Smith, Albert Vernon; Gudnason, Vilmundur; Bartz, Traci M; Wilk, Jemma B; O’Connor, George T; Cassano, Patricia A; Tang, Wenbo; Wain, Louise V; Artigas, María Soler; Gharib, Sina A; Strachan, David P; Sin, Don D; Tobin, Martin D; London, Stephanie J; Hall, Ian P; Paré, Peter D

2016-01-01

Summary Background Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC) in the general population. The lung expression quantitative trait loci (eQTLs) study mapped the genetic architecture of gene expression in lung tissue from 1111 individuals. We used a systems genetics approach to identify single nucleotide polymorphisms (SNPs) associated with lung function that act as eQTLs and change the level of expression of their target genes in lung tissue; termed eSNPs. Methods The SpiroMeta-CHARGE GWAS results were integrated with lung eQTLs to map eSNPs and the genes and pathways underlying the associations in lung tissue. For comparison, a similar analysis was done in peripheral blood. The lung mRNA expression levels of the eSNP-regulated genes were tested for associations with lung function measures in 727 individuals. Additional analyses identified the pleiotropic effects of eSNPs from the published GWAS catalogue, and mapped enrichment in regulatory regions from the ENCODE project. Finally, the Connectivity Map database was used to identify potential therapeutics in silico that could reverse the COPD lung tissue gene signature. Findings SNPs associated with lung function measures were more likely to be eQTLs and vice versa. The integration mapped the specific genes underlying the GWAS signals in lung tissue. The eSNP-regulated genes were enriched for developmental and inflammatory pathways; by comparison, SNPs associated with lung function that were eQTLs in blood, but not in lung, were only involved in inflammatory pathways. Lung function eSNPs were enriched for regulatory elements and were over-represented among genes showing differential expression during fetal lung development. An mRNA gene expression signature for COPD was identified in lung tissue and compared with the Connectivity Map. This in-silico drug repurposing approach suggested several compounds that reverse the COPD gene expression signature, including a nicotine receptor antagonist. These findings represent novel therapeutic pathways for COPD. Interpretation The system genetics approach identified lung tissue genes driving the variation in lung function and susceptibility to COPD. The identification of these genes and the pathways in which they are enriched is essential to understand the pathophysiology of airway obstruction and to identify novel therapeutic targets and biomarkers for COPD, including drugs that reverse the COPD gene signature in silico. Funding The research reported in this article was not specifically funded by any agency. See Acknowledgments for a full list of funders of the lung eQTL study and the Spiro-Meta CHARGE GWAS. PMID:26404118

Method for evaluating multiple mediators: mediating effects of smoking and COPD on the association between the CHRNA5-A3 variant and lung cancer risk.

PubMed

Wang, Jian; Spitz, Margaret R; Amos, Christopher I; Wu, Xifeng; Wetter, David W; Cinciripini, Paul M; Shete, Sanjay

2012-01-01

A mediation model explores the direct and indirect effects between an independent variable and a dependent variable by including other variables (or mediators). Mediation analysis has recently been used to dissect the direct and indirect effects of genetic variants on complex diseases using case-control studies. However, bias could arise in the estimations of the genetic variant-mediator association because the presence or absence of the mediator in the study samples is not sampled following the principles of case-control study design. In this case, the mediation analysis using data from case-control studies might lead to biased estimates of coefficients and indirect effects. In this article, we investigated a multiple-mediation model involving a three-path mediating effect through two mediators using case-control study data. We propose an approach to correct bias in coefficients and provide accurate estimates of the specific indirect effects. Our approach can also be used when the original case-control study is frequency matched on one of the mediators. We employed bootstrapping to assess the significance of indirect effects. We conducted simulation studies to investigate the performance of the proposed approach, and showed that it provides more accurate estimates of the indirect effects as well as the percent mediated than standard regressions. We then applied this approach to study the mediating effects of both smoking and chronic obstructive pulmonary disease (COPD) on the association between the CHRNA5-A3 gene locus and lung cancer risk using data from a lung cancer case-control study. The results showed that the genetic variant influences lung cancer risk indirectly through all three different pathways. The percent of genetic association mediated was 18.3% through smoking alone, 30.2% through COPD alone, and 20.6% through the path including both smoking and COPD, and the total genetic variant-lung cancer association explained by the two mediators was 69.1%.

[Are there specific characteristics of COPD in women?].

PubMed

Raherison, C; Biron, E; Nocent-Ejnaini, C; Taillé, C; Tillie-Leblond, I; Prudhomme, A

2010-06-01

Chronic Obstructive Pulmonary Disease (COPD) is a disorder resulting from an interaction between a genetic predisposition, still poorly understood, and the impact of environmental factors including tobacco smoke or professional or domestic air contaminants. The prevalence of COPD in the world concerns women as much as men, but it remains under diagnosed among women smokers. The mortality data show an increase in mortality among women compared to men. It thus seems that COPD in women presents more often a particular phenotype, characterized more by bronchial attacks than by emphysema, and by more marked functional effects on the quality of life. Anxiety and depression seem more marked with further repercussions on the quality of life. The effectiveness of treatment may be different, in particular with regard to nicotine weaning and respiratory rehabilitation. In the evaluation of chronic diseases in women little is known about COPD. Further studies, focusing specifically on these differences, are needed in order to improve the diagnosis and management of COPD in women. Copyright 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.

[Comorbidities of COPD].

PubMed

Brinchault, G; Diot, P; Dixmier, A; Goupil, F; Guillais, P; Gut-Gobert, C; Leroyer, C; Marchand-Adam, S; Meurice, J-C; Morel, H; Person, C; Cavaillès, A

2015-12-01

COPD is a slowly progressive chronic respiratory disease causing an irreversible decrease in air flow. The main cause is smoking, which provokes inflammatory phenomena in the respiratory tract. COPD is a serious public health issue, causing high morbidity, mortality and disability. Related comorbidities are linked to ageing, common risk factors and genetic predispositions. A combination of comorbidities increases healthcare costs. For instance, patients with more than two comorbidities represent a quarter of all COPD sufferers but account for half the related health costs. Our review describes different comorbidities and their impact on the COPD prognosis. The comorbidities include: cardiovascular diseases, osteoporosis, denutrition, obesity, ageing, anemia, sleeping disorders, diabetes, metabolic syndrome, anxiety-depression and lung cancer. The prognosis worsens with one or more comorbidities. Clinicians are faced with the challenge of finding practical and appropriate ways of treating these comorbidities, and there is increasing interest in developing a global, multidisciplinary approach to management. Managing this chronic disease should be based on a holistic, patient-centred approach and smoking cessation remains the key factor in the care of COPD patients. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Association of tumor necrosis factor-alpha-863C/A gene polymorphism with chronic obstructive pulmonary disease.

PubMed

Chen, Yung-Che; Liu, Shih-Feng; Chin, Chien-Hung; Wu, Chao-Chien; Chen, Chung-Jen; Chang, Hsueh-Wen; Wang, Yi-Hsi; Chung, Yu-Hsiu; Chao, Tung-Ying; Lin, Meng-Chih

2010-08-01

The aim of this study was to investigate genetic effects on the pathogenesis of chronic obstructive pulmonary disease (COPD). The study was conducted as a prospective case-control study in a medical center in southern Taiwan. The patient group consisted of 145 male patients with smoking-related COPD and a control group of 139 resistant smokers from July 2004 to September 2009. We compared allele and genotype frequencies of three tag single nucleotide polymorphisms (SNP) of the TNF-alpha gene promoter region at -308, -863, and -1031 in all subjects. We also analyzed the influence of each genetic variant on pulmonary function parameters, body mass index (BMI), serum TNF-alpha levels, and outcomes among heavy smokers with or without COPD. COPD patients had a significantly lower A allele frequency (9.7 vs. 15.1%, OR = 0.6, p = 0.048, false discovery rate q = 0.144) and a significantly lower A carrier genotype frequency (19.3 vs. 30.2%, OR = 0.52, p = 0.042, q = 0.135) than resistant smokers. The -863 CA genotype was associated with a better FEV(1)/FVC ratio (79 vs. 71.5%, p = 0.034), and higher BMI (24.9 vs. 23.6 kg/m(2), p = 0.048). In addition, COPD patients with the -1031 C carrier genotype had higher serum TNF-alpha levels (20.9 vs. 16.2 pg/ml, p = 0.01). BMI (hazard ratio = 0.84, 95% CI = 0.74-0.96, p = 0.008) was the only independent predictor for mortality. The TNF-alpha -863 A allele may confer a degree of resistance to the susceptibility to and muscle wasting of COPD among heavy smokers.

The prevalence of PI*S and PI*Z SERPINA1 alleles in healthy individuals and COPD patients in Saudi Arabia: A case-control study.

PubMed

Al-Jameil, Noura; Hassan, Amina A; Hassanato, Rana; Isac, Sree R; Otaiby, Maram Al; Al-Shareef, Fadwa; Al-Maarik, Basmah; Ajeyan, Iman Al; Al-Bahloul, Khloud; Ghani, Samina; Al-Torbak, Dana

2017-10-01

Alpha-1 antitrypsin (AAT) is an acute phase protein produced in hepatocytes. Its deficiency affects the lungs and liver. A case-control study was carried out to determine the prevalence of 2 common deficiency alleles, PI*S and PI*Z, for alpha-1 antitrypsin deficiency (AATD) in both healthy and chronic obstructive pulmmonary disease (COPD)-affected Saudi populations and to clarify the importance of genetic tests in the screening of people at risk for COPD.One thousand blood samples from healthy individuals and 1000 from COPD-affected Saudi individuals were genotyped for the above-mentioned alleles, using real-time polymerase chain reaction (PCR), with the exclusion of any other nationalities. Data were analyzed by determining the allele and genotype frequencies through gene counting and its confidence intervals. The allele frequencies, derived by the Hardy-Weinberg equilibrium method, were analyzed by Pearson Chi-squared tests. The confidence intervals for genotype frequencies were calculated using exploratory software for confidence intervals.Of the 1000 COPD patients included in our study, the prevalence of PI*S and PI*Z was 21.8% and 7.7%, respectively, while within the 1000 normal samples, these alleles occurred in 8.9% of patients for PI*S and 1.6% for PI*Z. The AAT deficiency genotype frequencies (PI*ZZ, PI*SS, and PI*SZ) were 6.5 per 1000 and 87 per 1000 for normal and COPD-affected Saudi individuals.Our results indicated a high prevalence of AATD alleles in the normal Saudi population and an association between AAT deficiency and pulmonary disease development. Additionally, our research confirms the importance of genetic screening to achieve early and accurate diagnosis of AATD.

Chronic obstructive pulmonary disease among lung cancer-free smokers: The importance of healthy controls.

PubMed

Karpman, Michelle D; Eldridge, Ronald; Follis, Jack L; Etzel, Carol J; Shete, Sanjay; El-Zein, Randa A

2018-01-01

The prevalence of chronic obstructive pulmonary disease (COPD) in smokers enrolled as "healthy" controls in studies is 10-50%. The COPD status of ideal smoker populations for lung cancer case-control studies should be checked via spirometry; however, this is often not feasible, because no medical indications exist for asymptomatic smokers to undergo spirometry prior to study enrollment. Therefore, there is an unmet need for robust, cost effective assays for identifying undiagnosed lung disease among asymptomatic smokers. Such assays would help excluding unhealthy smokers from lung cancer case-control studies. We used the cytokinesis-blocked micronucleus (CBMN) assay (a measure of genetic instability) to identify undiagnosed lung disease among asymptomatic smokers. We used a convenience population from an on-going lung cancer case-control study including smokers with lung cancer (n = 454), smoker controls (n = 797), and a self-reported COPD (n = 200) contingent within the smoker controls. Significant differences for all CBMN endpoints were observed when comparing lung cancer to All controls (which included COPD) and Healthy controls (with no COPD). The risk ratio (RR) was increased in the COPD group vs. Healthy controls for nuclear buds (RR 1.28, 95% confidence interval 1.01-1.62), and marginally increased for micronuclei (RR 1.06, 0.98-1.89) and nucleoplasmic bridges (RR 1.07, 0.97-1.15). These findings highlight the importance of using truly healthy controls in studies geared toward assessment of lung cancer risk. Using genetic instability biomarkers would facilitate the identification of smokers susceptible to tobacco smoke carcinogens and therefore predisposed to either disease. Copyright © 2017 The Japanese Respiratory Society. All rights reserved.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol.

PubMed

Strange, Charlie; Senior, Robert M; Sciurba, Frank; O'Neal, Scott; Morris, Alison; Wisniewski, Stephen R; Bowler, Russell; Hochheiser, Harry S; Becich, Michael J; Zhang, Yingze; Leader, Joseph K; Methé, Barbara A; Kaminski, Naftali; Sandhaus, Robert A

2015-10-01

Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis α1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define chronic obstructive pulmonary disease (COPD) phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; and blood microRNA and blood mononuclear cell RNA and DNA profiling. We will rely on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off alpha-1 antitrypsin augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from the Subpopulations and Intermediate Outcome Measures in COPD Study who match on FEV1 and age will be compared. In the primary analysis, we will determine if the PiZZ individuals on augmentation therapy have a difference in lower respiratory tract microbes identified compared with matched PiZZ individuals who are not on augmentation therapy. By characterizing the microbiome in alpha-1 antitrypsin deficiency (AATD), we hope to define new phenotypes of COPD that explain some of the diversity of clinical presentations. As a unique genetic cause of COPD, AATD may inform typical COPD pathogenesis, and better understanding of it may illuminate the complex interplay between environment and genetics. Although the biologic approaches are hypothesis generating, the results may lead to development of novel biomarkers, better understanding of COPD phenotypes, and development of novel diagnostic and therapeutic trials in AATD and COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01832220).

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol

PubMed Central

Senior, Robert M.; Sciurba, Frank; O’Neal, Scott; Morris, Alison; Wisniewski, Stephen R.; Bowler, Russell; Hochheiser, Harry S.; Becich, Michael J.; Zhang, Yingze; Leader, Joseph K.; Methé, Barbara A.; Kaminski, Naftali; Sandhaus, Robert A.

2015-01-01

Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis α1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define chronic obstructive pulmonary disease (COPD) phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; and blood microRNA and blood mononuclear cell RNA and DNA profiling. We will rely on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off alpha-1 antitrypsin augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from the Subpopulations and Intermediate Outcome Measures in COPD Study who match on FEV1 and age will be compared. In the primary analysis, we will determine if the PiZZ individuals on augmentation therapy have a difference in lower respiratory tract microbes identified compared with matched PiZZ individuals who are not on augmentation therapy. By characterizing the microbiome in alpha-1 antitrypsin deficiency (AATD), we hope to define new phenotypes of COPD that explain some of the diversity of clinical presentations. As a unique genetic cause of COPD, AATD may inform typical COPD pathogenesis, and better understanding of it may illuminate the complex interplay between environment and genetics. Although the biologic approaches are hypothesis generating, the results may lead to development of novel biomarkers, better understanding of COPD phenotypes, and development of novel diagnostic and therapeutic trials in AATD and COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01832220) PMID:26153726

Operating a sustainable disease management program for chronic obstructive pulmonary disease.

PubMed

Endicott, Linda; Corsello, Phillip; Prinzi, Michele; Tinkelman, David G; Schwartz, Abby

2003-01-01

Chronic obstructive pulmonary disease (COPD) is one of our nation's most rapidly growing chronic health conditions. It is estimated that over 16 million individuals are diagnosed with COPD (Friedman & Hilleman, 2001). In addition, another 16 million are misdiagnosed as asthma or not diagnosed at all. COPD is a condition that affects the working-age as well as the elderly. Despite the high mortality rate, COPD is a treatable and modifiable condition. Disease management programs (DMPs) for asthma are a common initiative within many health insurance plans and integrated delivery networks. Similar initiatives are not as common for COPD. This article will highlight the National Jewish Medical and Research Center's COPD DMP interventions and outcomes. To outline interventions and operational strategies critical in developing and operating a sustainable and effective disease management program for COPD. Disease Management is an effective model for managing individuals with COPD. Applying a case management model that includes (1) risk-identification and stratification; (2) education and empowerment regarding self-monitoring and management; (3) lifestyle modification; (4) communication and collaboration amongst patients, healthcare providers, and case managers to enhance the treatment plan; (5) providing after-hours support; and (6) monitoring care outcomes is crucial. Applying these interventions in a credible manner will improve the quality of life and quality of care delivered to individuals with mild, moderate, severe, and very severe COPD. Additionally, these interventions can significantly reduce utilization events.

Chronic obstructive pulmonary disease

PubMed Central

Vijayan, V.K.

2013-01-01

The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio <0.70. COPD is characterized by an accelerated decline in FEV1. Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines recommend influenza and pneumococcal vaccinations. PMID:23563369

Flavonoids and Reduction of Cardiovascular Disease (CVD) in Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Russo, Patrizia; Prinzi, Giulia; Lamonaca, Palma; Cardaci, Vittorio; Fini, Massimo

2018-05-13

Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CV) often coexist. COPD and CVD are complex diseases characterized by a strict interaction between environment and genetic. The mechanisms linking these two diseases are complex, multifactorial and not entirely understood, influencing the therapeutic approach. COPD is characterized by several comorbidities, it is hypothesizable that treatment of cardiovascular co-morbidities may reduce morbidity and mortality. Flavonoids are an important class of plant low molecular weight secondary metabolites (SMs). Convincing data from laboratory, epidemiological, and human clinical studies point to an important effects on CVD risk prevention. This review aims to provide up-to-date information on the ability of Flavonoids to reduce the CVD risk. Current studies support the potential of Flavonoids to prevent the risk of CVD. Well-designed clinical studies are suggested to evaluate advantages and limits of Flavonoids for managing CVD comorbidity in COPD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Association Between Plasminogen Activator Inhibitor-1-675 4G/5G Insertion/Deletion Polymorphism and Chronic Obstructive Pulmonary Disease.

PubMed

Essa, Enas S; El Wahsh, Rabab A

2016-12-01

Molecular pathology of chronic obstructive pulmonary disease (COPD) is still being investigated to discover relationships with disease pathogenesis. Evidence of plasminogen activator inhibitor-1 (PAI-1) overexpression in the sputum and the blood of COPD patients is growing. We aimed to investigate the potential relation between PAI-1 promoter 4G/5G insertion/deletion polymorphism and COPD development. In a case-control study, we genotyped 117 COPD patients and 160 control subjects for PAI-1 promoter 4G/5G polymorphism by an allele-specific polymerase chain reaction analysis. All subjects were male smokers. In the co-dominant model, there was a significant difference in the distribution of 5G/5G, 4G/5G and 4G/4G genotypes between COPD patients and controls (p = 0.002). In the recessive model, carriers of 4G/4G genotype were significantly higher in COPD patients than controls (p = 0.01). Carriers of 4G/4G genotype were at higher risk to develop COPD than those carrying 5G/5G or 4G/5G genotypes (crude odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.19-3.73, adjusted OR = 2.5, 95% CI = 1.22-3.99). In conclusion, PAI-1 4G/5G genetic variations are associated with COPD development in males.

Non-emphysematous chronic obstructive pulmonary disease is associated with diabetes mellitus.

PubMed

Hersh, Craig P; Make, Barry J; Lynch, David A; Barr, R Graham; Bowler, Russell P; Calverley, Peter M A; Castaldi, Peter J; Cho, Michael H; Coxson, Harvey O; DeMeo, Dawn L; Foreman, Marilyn G; Han, MeiLan K; Harshfield, Benjamin J; Hokanson, John E; Lutz, Sharon; Ramsdell, Joe W; Regan, Elizabeth A; Rennard, Stephen I; Schroeder, Joyce D; Sciurba, Frank C; Steiner, Robert M; Tal-Singer, Ruth; van Beek, Edwin; Silverman, Edwin K; Crapo, James D

2014-10-24

Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients. Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%). Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized. Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St. George's Respiratory Questionnaire score 43 vs 31, p < 0.0001). Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use. The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study. Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes. COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa. Clinicaltrials.gov identifiers: COPDGene NCT00608764, ECLIPSE NCT00292552.

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

PubMed

Klar, Joakim; Blomstrand, Peter; Brunmark, Charlott; Badhai, Jitendra; Håkansson, Hanna Falk; Brange, Charlotte Sollie; Bergendal, Birgitta; Dahl, Niklas

2011-10-01

Genetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal. The hypothesis behind this study was that constitutive FGF10 insufficiency may lead to pulmonary disorder. Therefore investigation of the pulmonary functions of patients heterozygous for loss of function mutations in the FGF10 gene was performed. The spirometric measures of lung function from patients and non-carrier siblings were compared and both groups were related to matched reference data for normal human lung function. The patients show a significant decrease in lung function parameters when compared to control values. The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted) and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1. Patients with FGF10 haploinsufficiency have lung function parameters indicating COPD. A modest response to Terbutalin confirms an irreversible obstructive lung disease. These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD.

Genome-Wide Association Study of the Genetic Determinants of Emphysema Distribution.

PubMed

Boueiz, Adel; Lutz, Sharon M; Cho, Michael H; Hersh, Craig P; Bowler, Russell P; Washko, George R; Halper-Stromberg, Eitan; Bakke, Per; Gulsvik, Amund; Laird, Nan M; Beaty, Terri H; Coxson, Harvey O; Crapo, James D; Silverman, Edwin K; Castaldi, Peter J; DeMeo, Dawn L

2017-03-15

Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe-predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. To identify the genetic influences of emphysema distribution in non-alpha-1 antitrypsin-deficient smokers. A total of 11,532 subjects with complete genotype and computed tomography densitometry data in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]; non-Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), and GenKOLS (Genetics of Chronic Obstructive Lung Disease) studies were analyzed. Two computed tomography scan emphysema distribution measures (difference between upper-third and lower-third emphysema; ratio of upper-third to lower-third emphysema) were tested for genetic associations in all study subjects. Separate analyses in each study population were followed by a fixed effect metaanalysis. Single-nucleotide polymorphism-, gene-, and pathway-based approaches were used. In silico functional evaluation was also performed. We identified five loci associated with emphysema distribution at genome-wide significance. These loci included two previously reported associations with COPD susceptibility (4q31 near HHIP and 15q25 near CHRNA5) and three new associations near SOWAHB, TRAPPC9, and KIAA1462. Gene set analysis and in silico functional evaluation revealed pathways and cell types that may potentially contribute to the pathogenesis of emphysema distribution. This multicohort genome-wide association study identified new genomic loci associated with differential emphysematous destruction throughout the lungs. These findings may point to new biologic pathways on which to expand diagnostic and therapeutic approaches in chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease.

PubMed

Fernandez Fernandez, Elena; de Santi, Chiara; De Rose, Virginia; Greene, Catherine M

2018-05-11

Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. Areas covered: Although the pathogenesis and pathophysiology of CF and COPD differ, they do share key phenotypic features and because of these similarities there is great interest in exploring common mechanisms and/or factors affected by CFTR mutations and environmental insults involved in COPD. Various molecular, cellular and clinical studies have confirmed that CFTR protein dysfunction is common in both the CF and COPD airways. This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert Commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.

MMP12, lung function, and COPD in high-risk populations.

PubMed

Hunninghake, Gary M; Cho, Michael H; Tesfaigzi, Yohannes; Soto-Quiros, Manuel E; Avila, Lydiana; Lasky-Su, Jessica; Stidley, Chris; Melén, Erik; Söderhäll, Cilla; Hallberg, Jenny; Kull, Inger; Kere, Juha; Svartengren, Magnus; Pershagen, Göran; Wickman, Magnus; Lange, Christoph; Demeo, Dawn L; Hersh, Craig P; Klanderman, Barbara J; Raby, Benjamin A; Sparrow, David; Shapiro, Steven D; Silverman, Edwin K; Litonjua, Augusto A; Weiss, Scott T; Celedón, Juan C

2009-12-31

Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups. We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV(1)]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV(1) and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD. The minor allele (G) of a functional variant in the promoter region of MMP12 (rs2276109 [-82A-->G]) was positively associated with FEV(1) in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2x10(-6)). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P=0.02) and with a reduced risk of COPD in a cohort of smokers (odds ratio, 0.63; 95% CI, 0.45 to 0.88; P=0.005) and among participants in a family-based study of early-onset COPD (P=0.006). The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers. 2009 Massachusetts Medical Society

Prediction of acute respiratory disease in current and former smokers with and without COPD.

PubMed

Bowler, Russell P; Kim, Victor; Regan, Elizabeth; Williams, André A A; Santorico, Stephanie A; Make, Barry J; Lynch, David A; Hokanson, John E; Washko, George R; Bercz, Peter; Soler, Xavier; Marchetti, Nathaniel; Criner, Gerard J; Ramsdell, Joe; Han, MeiLan K; Demeo, Dawn; Anzueto, Antonio; Comellas, Alejandro; Crapo, James D; Dransfield, Mark; Wells, J Michael; Hersh, Craig P; MacIntyre, Neil; Martinez, Fernando; Nath, Hrudaya P; Niewoehner, Dennis; Sciurba, Frank; Sharafkhaneh, Amir; Silverman, Edwin K; van Beek, Edwin J R; Wilson, Carla; Wendt, Christine; Wise, Robert A

2014-10-01

The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD

PubMed Central

Kim, Victor; Regan, Elizabeth; Williams, André A. A.; Santorico, Stephanie A.; Make, Barry J.; Lynch, David A.; Hokanson, John E.; Washko, George R.; Bercz, Peter; Soler, Xavier; Marchetti, Nathaniel; Criner, Gerard J.; Ramsdell, Joe; Han, MeiLan K.; Demeo, Dawn; Anzueto, Antonio; Comellas, Alejandro; Crapo, James D.; Dransfield, Mark; Wells, J. Michael; Hersh, Craig P.; MacIntyre, Neil; Martinez, Fernando; Nath, Hrudaya P.; Niewoehner, Dennis; Sciurba, Frank; Sharafkhaneh, Amir; Silverman, Edwin K.; van Beek, Edwin J. R.; Wilson, Carla; Wendt, Christine; Wise, Robert A.; Curtis, Jeffrey; Kazerooni, Ella; Hanania, Nicola; Alapat, Philip; Bandi, Venkata; Guntupalli, Kalpalatha; Guy, Elizabeth; Lunn, William; Mallampalli, Antara; Trinh, Charles; Atik, Mustafa; DeMeo, Dawn; Hersh, Craig; Jacobson, Francine; Graham Barr, R.; Thomashow, Byron; Austin, John; MacIntyre, Neil; Washington, Lacey; Page McAdams, H.; Rosiello, Richard; Bresnahan, Timothy; McEvoy, Charlene; Tashjian, Joseph; Wise, Robert; Hansel, Nadia; Brown, Robert; Casaburi, Richard; Porszasz, Janos; Fischer, Hans; Budoff, Matt; Sharafkhaneh, Amir; Niewoehner, Dennis; Allen, Tadashi; Rice, Kathryn; Foreman, Marilyn; Westney, Gloria; Berkowitz, Eugene; Bowler, Russell; Friedlander, Adam; Meoni, Eleonora; Criner, Gerard; Kim, Victor; Marchetti, Nathaniel; Satti, Aditi; James Mamary, A.; Steiner, Robert; Dass, Chandra; Bailey, William; Dransfield, Mark; Gerald, Lynn; Nath, Hrudaya; Ramsdell, Joe; Ferguson, Paul; Friedman, Paul; McLennan, Geoffrey; van Beek, Edwin JR; Martinez, Fernando; Han, MeiLan; Thompson, Deborah; Kazerooni, Ella; Wendt, Christine; Allen, Tadashi; Sciurba, Frank; Weissfeld, Joel; Fuhrman, Carl; Bon, Jessica; Anzueto, Antonio; Adams, Sandra; Orozco, Carlos; Santiago Restrepo, C.; Mumbower, Amy; Crapo, James; Silverman, Edwin; Make, Barry; Regan, Elizabeth; Samet, Jonathan; Willis, Amy; Stinson, Douglas; Beaty, Terri; Klanderman, Barbara; Laird, Nan; Lange, Christoph; Ionita, Iuliana; Santorico, Stephanie; Silverman, Edwin; Lynch, David; Schroeder, Joyce; Newell, John; Reilly, John; Coxson, Harvey; Judy, Philip; Hoffman, Eric; San Jose Estepar, Raul; Washko, George; Leek, Rebecca; Zach, Jordan; Kluiber, Alex; Rodionova, Anastasia; Mann, Tanya; Crapo, Robert; Jensen, Robert; Farzadegan, Homayoon; Murphy, James; Everett, Douglas; Wilson, Carla; Hokanson, John

2014-01-01

BACKGROUND: The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS: Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS: At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George’s Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS: Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD. PMID:24945159

Association of five genetic variants with chronic obstructive pulmonary disease susceptibility and spirometric phenotypes in a Chinese Han population.

PubMed

Yang, Jing; Zhou, Haixia; Liang, Binmiao; Xiao, Jun; Su, Zhiguang; Chen, Hong; Ma, Chunlan; Li, Dengxue; Feng, Yulin; Ou, Xuemei

2014-02-01

Recent genome-wide association studies have shown associations between variants at five loci (TNS1, GSTCD, HTR4, AGER and THSD4) and chronic obstructive pulmonary disease (COPD) or lung function. However, their association with COPD has not been proven in Chinese Han population, nor have COPD-related phenotypes been studied. The objective of this study was to look for associations between five single nucleotide polymorphisms (SNP) in these novel candidate genes and COPD susceptibility or lung function in a Chinese Han population. Allele and genotype data on 680 COPD patients and 687 healthy controls for sentinel SNP in these five loci were investigated. Allele frequencies and genotype distributions were compared between cases and controls, and odds ratios were calculated. Potential relationships between these SNP and COPD-related lung function were assessed. No significant associations were found between any of the SNP and COPD in cases and controls. The SNP (rs3995090) in HTR4 was associated with COPD (adjusted P = 0.022) in never-smokers, and the SNP (rs2070600) in AGER was associated with forced expiratory volume in 1 s (FEV1 %) predicted (β = -0.066, adjusted P = 0.016) and FEV1 /forced vital capacity (β = -0.071, adjusted P = 0.009) in all subjects. The variant at HTR4 was associated with COPD in never-smokers, and the SNP in AGER was associated with pulmonary function in a Chinese Han population. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD.

PubMed

Yoo, Seungyeul; Takikawa, Sachiko; Geraghty, Patrick; Argmann, Carmen; Campbell, Joshua; Lin, Luan; Huang, Tao; Tu, Zhidong; Foronjy, Robert F; Feronjy, Robert; Spira, Avrum; Schadt, Eric E; Powell, Charles A; Zhu, Jun

2015-01-01

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic, epigenetic, and environmental factors are known to contribute to COPD risk and disease progression. Therefore we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profile and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system development. We confirmed that EPAS1 protein levels are lower in human COPD lung tissue compared to non-disease controls and that Epas1 gene expression is reduced in mice chronically exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes, and genes associated with emphysema severity. Our first integrative analysis of genome-wide DNA methylation and gene expression profiles illustrates that not only does DNA methylation play a 'causal' role in the molecular pathophysiology of COPD, but it can be leveraged to directly identify novel key mediators of this pathophysiology.

Assessment of automated analysis of portable oximetry as a screening test for moderate-to-severe sleep apnea in patients with chronic obstructive pulmonary disease

PubMed Central

Andrés-Blanco, Ana M.; Álvarez, Daniel; Crespo, Andrea; Arroyo, C. Ainhoa; Cerezo-Hernández, Ana; Gutiérrez-Tobal, Gonzalo C.; Hornero, Roberto

2017-01-01

Background The coexistence of obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) leads to increased morbidity and mortality. The development of home-based screening tests is essential to expedite diagnosis. Nevertheless, there is still very limited evidence on the effectiveness of portable monitoring to diagnose OSAS in patients with pulmonary comorbidities. Objective To assess the influence of suffering from COPD in the performance of an oximetry-based screening test for moderate-to-severe OSAS, both in the hospital and at home. Methods A total of 407 patients showing moderate-to-high clinical suspicion of OSAS were involved in the study. All subjects underwent (i) supervised portable oximetry simultaneously to in-hospital polysomnography (PSG) and (ii) unsupervised portable oximetry at home. A regression-based multilayer perceptron (MLP) artificial neural network (ANN) was trained to estimate the apnea-hypopnea index (AHI) from portable oximetry recordings. Two independent validation datasets were analyzed: COPD versus non-COPD. Results The portable oximetry-based MLP ANN reached similar intra-class correlation coefficient (ICC) values between the estimated AHI and the actual AHI for the non-COPD and the COPD groups either in the hospital (non-COPD: 0.937, 0.909–0.956 CI95%; COPD: 0.936, 0.899–0.960 CI95%) and at home (non-COPD: 0.731, 0.631–0.808 CI95%; COPD: 0.788, 0.678–0.864 CI95%). Regarding the area under the receiver operating characteristics curve (AUC), no statistically significant differences (p >0.01) between COPD and non-COPD groups were found in both settings, particularly for severe OSAS (AHI ≥30 events/h): 0.97 (0.92–0.99 CI95%) non-COPD vs. 0.98 (0.92–1.0 CI95%) COPD in the hospital, and 0.87 (0.79–0.92 CI95%) non-COPD vs. 0.86 (0.75–0.93 CI95%) COPD at home. Conclusion The agreement and the diagnostic performance of the estimated AHI from automated analysis of portable oximetry were similar regardless of the presence of COPD both in-lab and at-home. Particularly, portable oximetry could be used as an abbreviated screening test for moderate-to-severe OSAS in patients with COPD. PMID:29176802

Assessment of automated analysis of portable oximetry as a screening test for moderate-to-severe sleep apnea in patients with chronic obstructive pulmonary disease.

PubMed

Andrés-Blanco, Ana M; Álvarez, Daniel; Crespo, Andrea; Arroyo, C Ainhoa; Cerezo-Hernández, Ana; Gutiérrez-Tobal, Gonzalo C; Hornero, Roberto; Del Campo, Félix

2017-01-01

The coexistence of obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) leads to increased morbidity and mortality. The development of home-based screening tests is essential to expedite diagnosis. Nevertheless, there is still very limited evidence on the effectiveness of portable monitoring to diagnose OSAS in patients with pulmonary comorbidities. To assess the influence of suffering from COPD in the performance of an oximetry-based screening test for moderate-to-severe OSAS, both in the hospital and at home. A total of 407 patients showing moderate-to-high clinical suspicion of OSAS were involved in the study. All subjects underwent (i) supervised portable oximetry simultaneously to in-hospital polysomnography (PSG) and (ii) unsupervised portable oximetry at home. A regression-based multilayer perceptron (MLP) artificial neural network (ANN) was trained to estimate the apnea-hypopnea index (AHI) from portable oximetry recordings. Two independent validation datasets were analyzed: COPD versus non-COPD. The portable oximetry-based MLP ANN reached similar intra-class correlation coefficient (ICC) values between the estimated AHI and the actual AHI for the non-COPD and the COPD groups either in the hospital (non-COPD: 0.937, 0.909-0.956 CI95%; COPD: 0.936, 0.899-0.960 CI95%) and at home (non-COPD: 0.731, 0.631-0.808 CI95%; COPD: 0.788, 0.678-0.864 CI95%). Regarding the area under the receiver operating characteristics curve (AUC), no statistically significant differences (p >0.01) between COPD and non-COPD groups were found in both settings, particularly for severe OSAS (AHI ≥30 events/h): 0.97 (0.92-0.99 CI95%) non-COPD vs. 0.98 (0.92-1.0 CI95%) COPD in the hospital, and 0.87 (0.79-0.92 CI95%) non-COPD vs. 0.86 (0.75-0.93 CI95%) COPD at home. The agreement and the diagnostic performance of the estimated AHI from automated analysis of portable oximetry were similar regardless of the presence of COPD both in-lab and at-home. Particularly, portable oximetry could be used as an abbreviated screening test for moderate-to-severe OSAS in patients with COPD.

Entropy change of biological dynamics in COPD.

PubMed

Jin, Yu; Chen, Chang; Cao, Zhixin; Sun, Baoqing; Lo, Iek Long; Liu, Tzu-Ming; Zheng, Jun; Sun, Shixue; Shi, Yan; Zhang, Xiaohua Douglas

2017-01-01

In this century, the rapid development of large data storage technologies, mobile network technology, and portable medical devices makes it possible to measure, record, store, and track analysis of large amount of data in human physiological signals. Entropy is a key metric for quantifying the irregularity contained in physiological signals. In this review, we focus on how entropy changes in various physiological signals in COPD. Our review concludes that the entropy change relies on the types of physiological signals under investigation. For major physiological signals related to respiratory diseases, such as airflow, heart rate variability, and gait variability, the entropy of a patient with COPD is lower than that of a healthy person. However, in case of hormone secretion and respiratory sound, the entropy of a patient is higher than that of a healthy person. For mechanomyogram signal, the entropy increases with the increased severity of COPD. This result should give valuable guidance for the use of entropy for physiological signals measured by wearable medical device as well as for further research on entropy in COPD.

Gene expression analysis uncovers novel Hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells

PubMed Central

Zhou, Xiaobo; Qiu, Weiliang; Sathirapongsasuti, J. Fah.; Cho, Michael H.; Mancini, John D.; Lao, Taotao; Thibault, Derek M.; Litonjua, Gus; Bakke, Per S.; Gulsvik, Amund; Lomas, David A.; Beaty, Terri H.; Hersh, Craig P.; Anderson, Christopher; Geigenmuller, Ute; Raby, Benjamin A.; Rennard, Stephen I.; Perrella, Mark A.; Choi, Augustine M.K.; Quackenbush, John; Silverman, Edwin K.

2013-01-01

Hedgehog Interacting Protein (HHIP) was implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS). However, it remains unclear how HHIP contributes to COPD pathogenesis. To identify genes regulated by HHIP, we performed gene expression microarray analysis in a human bronchial epithelial cell line (Beas-2B) stably infected with HHIP shRNAs. HHIP silencing led to differential expression of 296 genes; enrichment for variants nominally associated with COPD was found. Eighteen of the differentially expressed genes were validated by real-time PCR in Beas-2B cells. Seven of 11 validated genes tested in human COPD and control lung tissues demonstrated significant gene expression differences. Functional annotation indicated enrichment for extracellular matrix and cell growth genes. Network modeling demonstrated that the extracellular matrix and cell proliferation genes influenced by HHIP tended to be interconnected. Thus, we identified potential HHIP targets in human bronchial epithelial cells that may contribute to COPD pathogenesis. PMID:23459001

Association between the length of the MUC8-minisatellite 5 region and susceptibility to chronic obstructive pulmonary disease (COPD).

PubMed

Lee, Se-Ra; Kim, Won-Tae; Kim, Tae Nam; Nam, Jong Kil; Kim, Woo Jin; Leem, Sun-Hee

2018-01-01

In asthma and chronic obstructive pulmonary disease (COPD), mucins display disease-related alterations caused by airway mucus obstruction. MUC5AC, MUC5B and MUC8 are known as the major secretory mucins in human airway epithelial cells. Analysis of mucin genes has identified the presence of several features with a variable number of tandem repeats (VNTR; minisatellites) in the central region of each mucin. In our previous study, six minisatellites in the region of the MUC8 gene were identified, and the MUC8-MS5 minisatellite showed the highest heterozygosity among them. In this study, we evaluated the relationship between MUC8-MS5 and susceptibility to asthma and COPD. A case-control study was performed with 229 controls, 123 COPD cases and 77 asthma cases. A significant association (OR 3.96) between short alleles (2/2 repeats) and the occurrence of COPD was observed [95% confidence interval (CI) 1.32-11.88; p = 0.008]. Hence, the increased frequency of 2/2 homo-short alleles were also found in asthma cases (3.11; CI 0.88-11.05; p = 0.066), though this association was not statistically significant. These results revealed a genetic association between MUC8 and COPD, and that the specific short minisatellite alleles (2/2) of MUC8-MS5 may be a risk factor for COPD.

Prevalence, determinants and clinical correlates of vitamin D deficiency in patients with Chronic Obstructive Pulmonary Disease in London, UK.

PubMed

Jolliffe, David A; James, Wai Yee; Hooper, Richard L; Barnes, Neil C; Greiller, Claire L; Islam, Kamrul; Bhowmik, Angshu; Timms, Peter M; Rajakulasingam, Raj K; Choudhury, Aklak B; Simcock, David E; Hyppönen, Elina; Walton, Robert T; Corrigan, Christopher J; Griffiths, Christopher J; Martineau, Adrian R

2018-01-01

Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD), yet a comprehensive analysis of environmental and genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with this condition is lacking. We conducted a multi-centre cross-sectional study in 278 COPD patients aged 41-92 years in London, UK. Details of potential environmental determinants of vitamin D status and COPD symptom control and severity were collected by questionnaire, and blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction. All participants performed spirometry and underwent measurement of weight and height. Quadriceps muscle strength (QS) was measured in 134 participants, and sputum induction with enumeration of lower airway eosinophil and neutrophil counts was performed for 44 participants. Thirty-seven single nucleotide polymorphisms (SNP) in 11 genes in the vitamin D pathway (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, CYP27A1, CYP3A4, LRP2, CUBN, RXRA, and VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration and to determine whether vitamin D status or genetic factors independently associated with % predicted forced expiratory volume in one second (FEV 1 ), % predicted forced vital capacity (FVC), the ratio of FEV 1 to FVC (FEV 1 :FVC), daily inhaled corticosteroid (ICS) dose, respiratory quality of life (QoL), QS, and the percentage of eosinophils and neutrophils in induced sputum. Mean serum 25(OH)D concentration was 45.4nmol/L (SD 25.3); 171/278 (61.5%) participants were vitamin D deficient (serum 25[OH]D concentration <50nmol/L). Lower vitamin D status was independently associated with higher body mass index (P=0.001), lower socio-economic position (P=0.037), lack of vitamin D supplement consumption (P<0.001), sampling in Winter or Spring (P for trend=0.006) and lack of a recent sunny holiday (P=0.002). Vitamin D deficiency associated with reduced % predicted FEV 1 (P for trend=0.060) and % predicted FVC (P for trend=0.003), but it did not associate with FEV 1 :FVC, ICS dose, QoL, QS, or the percentage of eosinophils or neutrophils in induced sputum. After correction for multiple comparisons testing, genetic variation in the vitamin D pathway was not found to associate with serum 25(OH)D concentration or clinical correlates of COPD severity. Vitamin D deficiency was common in this group of COPD patients in the UK, and it associated independently with reduced % predicted FEV1 and FVC. However, genetic variation in the vitamin D pathway was not associated with vitamin D status or severity of COPD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic obstructive pulmonary disease in women: exploring gender differences.

PubMed

Varkey, Anita B

2004-03-01

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality throughout the world. This major public health threat is ranked twelfth as a worldwide burden of disease and is projected to rank fifth by the year 2020 as a cause of lost quantity and quality of life. The impact of this disease in women is significantly understudied but the evidence that does exist reveals potentially substantial gender differences in the susceptibility to, severity of, and response to management of COPD. The best known risk factor for the development of COPD is tobacco smoking. While smoking rates in women have largely stabilized in developed countries, the rates are continuing to climb in developing countries. While it is not clear whether women are more susceptible to the toxic effects of cigarette smoke than men, it is known that the incidence and prevalence of COPD will continue to climb as more women smoke. Other known risk factors for the development of COPD include air pollution, infections, occupational exposures, and genetic factors. Air pollution, particularly fine particulate indoor air pollution from biomass fuels disproportionately affects women. Infections such as human immunodeficiency virus (HIV) and tuberculosis (TB) disproportionately affect vulnerable populations such as poor women and occupational exposures to various dusts and toxins are often gender specific. Genetic factors are still being explored but there seems a preponderance of women who are affected by early-onset and non-smoking related COPD. Women with COPD also seem to be underdiagnosed by physicians and may have different responses to medical treatment, smoking cessation interventions, and pulmonary rehabilitation programs. Chronic obstructive pulmonary disease in women is an understudied subject but is gaining attention as a significant public health threat. In developed countries, efforts at preventing the initiation of tobacco smoking and targeting smoking cessation programs in women are needed. In developing countries, efforts to promote cleaner fuels, improved stoves, better home ventilation, reduce toxic dust and fume exposures, combat infectious diseases such as TB and HIV, and improve nutrition are all ways in which the lung health of women can be improved.

Cigarette smoke–induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD

PubMed Central

Dove, Rosamund E.; Leong-Smith, Pheneatia; Roos-Engstrand, Ester; Pourazar, Jamshid; Shah, Mittal; Behndig, Annelie F.; Mudway, Ian S.; Blomberg, Anders

2015-01-01

Background Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke. Methods Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13). Results Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers. Conclusions We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke–induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression. PMID:26557249

Integrative Analysis of DNA Methylation and Gene Expression Data Identifies EPAS1 as a Key Regulator of COPD

PubMed Central

Yoo, Seungyeul; Takikawa, Sachiko; Geraghty, Patrick; Argmann, Carmen; Campbell, Joshua; Lin, Luan; Huang, Tao; Tu, Zhidong; Feronjy, Robert; Spira, Avrum; Schadt, Eric E.; Powell, Charles A.; Zhu, Jun

2015-01-01

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic, epigenetic, and environmental factors are known to contribute to COPD risk and disease progression. Therefore we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profile and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system development. We confirmed that EPAS1 protein levels are lower in human COPD lung tissue compared to non-disease controls and that Epas1 gene expression is reduced in mice chronically exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes, and genes associated with emphysema severity. Our first integrative analysis of genome-wide DNA methylation and gene expression profiles illustrates that not only does DNA methylation play a ‘causal’ role in the molecular pathophysiology of COPD, but it can be leveraged to directly identify novel key mediators of this pathophysiology. PMID:25569234

Impact of I/D polymorphism of ACE gene on risk of development and course of chronic obstructive pulmonary disease.

PubMed

Mlak, Radosław; Homa-Mlak, Iwona; Powrózek, Tomasz; Mackiewicz, Barbara; Michnar, Marek; Krawczyk, Paweł; Dziedzic, Marcin; Rubinsztajn, Renata; Chazan, Ryszarda; Milanowski, Janusz; Małecka-Massalska, Teresa

2016-04-01

Chronic obstructive pulmonary disease (COPD) affects more than 10% of the world's population over 40 years of age. The main exogenous risk factor is cigarette smoking; however, only 20% of smokers develop COPD, indicating that some other factors, e.g. genetic, may play an important role in the disease pathogenesis. Recent research indicates that ACE (angiotensin-converting enzyme) may be a susceptibility gene for asthma or COPD. The aim of our study was to determine the influence of I/D (insertion/deletion) polymorphism of the ACE gene (AluYa5, rs4646994) on the risk and course of COPD. We investigated ACE I/D polymorphism in 206 COPD and 165 healthy Caucasian subjects. In the generalized linear model (GLZ) analysis of the influence of selected factors on presence of COPD we found a significant independent effect for male sex (repeatedly increases the risk of COPD, OR = 7.7, p = 0.049), as well as smoking or lower body mass index, but only in combination with older age (OR = 0.96, p = 0.003 and OR = 1.005, p = 0.04 respectively). Interestingly, analysis of factors which may influence the risk of a higher number of exacerbations demonstrated that occurrence of DD genotype, but only in men, is associated with a lower risk (OR = 0.7, p = 0.03) of this complication. We suggest that ACE may not be a susceptibility gene for the origin of COPD but a disease-modifying gene. Since the impact of I/D polymorphism of the ACE gene on COPD risk is moderate or negligible, other molecular changes, that will help predict the development of this disease, should still be sought.

Comorbidities of COPD Have a Major Impact on Clinical Outcomes, Particularly in African Americans

PubMed Central

Putcha, Nirupama; Han, Meilan K.; Martinez, Carlos H.; Foreman, Marilyn G.; Anzueto, Antonio R.; Casaburi, Richard; Cho, Michael H.; Hanania, Nicola A.; Hersh, Craig P.; Kinney, Gregory L.; Make, Barry J.; Steiner, Robert M.; Lutz, Sharon M.; Thomashow, Byron M.; Williams, Andre A.; Bhatt, Surya P.; Beaty, Terri H.; Bowler, Russell P.; Ramsdell, Joe W.; Curtis, Jeffrey L.; Everett, Douglas; Hokanson, John E.; Lynch, David A.; Sutherland, E. Rand; Silverman, Edwin K.; Crapo, James D.; Wise, Robert A.; Regan, Elizabeth A.; Hansel, Nadia N.

2014-01-01

Background: COPD patients have a great burden of comorbidity. However, it is not well established whether this is due to shared risk factors such as smoking, if the comorbidities impact patients’ exercise capacity and quality of life, or whether there are racial disparities in their impact on COPD. Methods: We analyzed data from 10,192 current and ex-smokers with (cases) and without COPD (controls) from the Genetic Epidemiology of COPD (COPDGene®) study cohort to establish risk for COPD comorbidities adjusted for pertinent covariates. In adjusted models, we examined comorbidity prevalence and impact in African-Americans (AA) and non-Hispanic whites (NHW). Results: Comorbidities are more common in individuals with COPD compared to those with normal spirometry (controls), and the risk persists after adjustments for covariates including pack-years smoked. After adjustment for confounders, 8 conditions were independently associated with worse exercise capacity, quality of life and dyspnea. There were racial disparities in the impact of comorbidities on exercise capacity, dyspnea and quality of life, with the presence of osteoarthritis and gastroesophageal reflux disease having a greater negative impact on all three outcomes in AAs than NHWs (p<0.05 for all interaction terms). Conclusions: Individuals with COPD have a higher risk for comorbidities than controls, an important finding shown for the first time comprehensively after accounting for confounders. Individual comorbidities are associated with worse exercise capacity, quality of life, and dyspnea, in AAs compared with NHWs. Note: The abstract of a previous version of this work was presented at the American Thoracic Society Conference in Philadelphia, PA on May 21, 2013. PMID:25695106

Evaluating Comparative Effectiveness Research Priorities for Care Coordination in Chronic Obstructive Pulmonary Disease: A Community-Based eDelphi Study

PubMed Central

Alber, Julia; Paige, Samantha; Castro, Daniela; Singh, Briana

2015-01-01

Background Despite research supporting the use of care coordination in chronic obstructive pulmonary disease (COPD), there is relatively little known about the comparative effectiveness of different strategies used to organize care for patients. To investigate the most important COPD care coordination strategies, community-based stakeholder input is needed, especially from medically underserved populations. Web-based platforms are electronic tools now being used to bring together individuals from underrepresented populations to share input and obtain clarification on comparative effectiveness research (CER) ideas, questions, and hypotheses. Objective Use low computer-literate, collaborative survey technology to evaluate stakeholder priorities for CER in COPD care coordination. Methods A mixed-method, concurrent triangulation design was used to collect survey data from a virtual advisory board of community-based stakeholders including medically underserved patients with COPD, informal caregivers, clinicians, and research scientists. The eDelphi method was used to conduct 3 iterative rounds of Web-based surveys. In the first 2 survey rounds, panelists viewed a series of “mini research prospectus” YouTube video presentations and rated their level of agreement with the importance of 10 COPD care coordination topics using 7-point Likert scales. In the final third-round survey, panelists ranked (1=most important, 8=least important) and commented on 8 remaining topics that panelists favored most throughout the first 2 survey rounds. Following the third-round survey, panelists were asked to provide feedback on the potential impact of a Web-based stakeholder engagement network dedicated to improving CER in COPD. Results Thirty-seven panelists rated the following care coordination topics as most important (lower means indicate greater importance): (1) measurement of quality of care (mean 2.73, SD 1.95); (2) management of COPD with other chronic health issues (mean 2.92, SD 1.67); (3) pulmonary rehabilitation as a model for care (mean 3.72; SD 1.93); (4) quality of care coordination (mean 4.12, SD 2.41); and (5) comprehensive COPD patient education (mean 4.27, SD 2.38). Stakeholder comments on the relative importance of these care coordination topics primarily addressed the importance of comparing strategies for COPD symptom management and evaluating new methods for patient-provider communication. Approximately one half of the virtual panel assembled indicated that a Web-based stakeholder engagement network could enable more online community meetings (n=19/37, 51%) and facilitate more opportunities to suggest, comment on, and vote for new CER ideas in COPD (n=18/37, 49%). Conclusions Members of this unique virtual advisory board engaged in a structured Web-based communication process that identified the most important community-specific COPD care coordination research topics and questions. Findings from this study support the need for more CER that evaluates quality of care measures used to assess the delivery of treatments and interventions among medically underserved patients with COPD. PMID:26268741

IL-22 Defect During Streptococcus pneumoniae Infection Triggers Exacerbation of Chronic Obstructive Pulmonary Disease.

PubMed

Pichavant, Muriel; Sharan, Riti; Le Rouzic, Olivier; Olivier, Cécile; Hennegrave, Florence; Rémy, Gaëlle; Pérez-Cruz, Magdiel; Koné, Bachirou; Gosset, Pierre; Just, Nicolas; Gosset, Philippe

2015-11-01

Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.

MMP12, Lung Function, and COPD in High-Risk Populations

PubMed Central

Hunninghake, Gary M.; Cho, Michael H.; Tesfaigzi, Yohannes; Soto-Quiros, Manuel E.; Avila, Lydiana; Lasky-Su, Jessica; Stidley, Chris; Melén, Erik; Söderhäll, Cilla; Hallberg, Jenny; Kull, Inger; Kere, Juha; Svartengren, Magnus; Pershagen, Göran; Wickman, Magnus; Lange, Christoph; Demeo, Dawn L.; Hersh, Craig P.; Klanderman, Barbara J.; Raby, Benjamin A.; Sparrow, David; Shapiro, Steven D.; Silverman, Edwin K.; Litonjua, Augusto A.; Weiss, Scott T.; Celedón, Juan C.

2010-01-01

BACKGROUND Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease (COPD), particularly in high-risk groups. METHODS We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV1]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV1 and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD. RESULTS The minor allele (G) of a functional variant in the promoter region of MMP12 (rs2276109 [−82A→G]) was positively associated with FEV1 in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2×10−6). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P = 0.02) and with a reduced risk of COPD in a cohort of smokers (odds ratio, 0.63; 95% CI, 0.45 to 0.88; P = 0.005) and among participants in a family-based study of early-onset COPD (P = 0.006). CONCLUSIONS The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers. PMID:20018959

Functional polymorphisms in NFκB1/IκBα predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.

PubMed

Huang, Dongsheng; Yang, Lei; Liu, Yehua; Zhou, Yumin; Guo, Yuan; Pan, Mingan; Wang, Yunnan; Tan, Yigang; Zhong, Haibo; Hu, Min; Lu, Wenju; Ji, Weidong; Wang, Jian; Ran, Pixin; Zhong, Nanshan; Zhou, Yifeng; Lu, Jiachun

2013-04-01

Lung inflammation is the major pathogenetic feature for both chronic obstructive pulmonary disease (COPD) and lung cancer. The nuclear factor-kappa B (NFκB) and its inhibitor (IκB) play crucial roles in inflammatory. Here, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in NFκB/IκB confer consistent risks for COPD and lung cancer. Four putative functional SNPs (NFκB1: -94del>insATTG; NFκB2: -2966G>A; IκBα: -826C>T, 2758G>A) were analyzed in southern and validated in eastern Chineses to test their associations with COPD risk in 1,511 COPD patients and 1,677 normal lung function controls, as well as lung cancer risk in 1,559 lung cancer cases and 1,679 cancer-free controls. We found that the -94ins ATTG variants (ins/del + ins/ins) in NFκB1 conferred an increased risk of COPD (OR 1.27, 95% CI 1.06-1.52) and promoted COPD progression by accelerating annual FEV1 decline (P = 0.015). The 2758AA variant in IκBα had an increased risk of lung cancer (OR 1.53, 95% CI 1.30-1.80) by decreasing IκBα expression due to the modulation of microRNA hsa-miR-449a but not hsa-miR-34b. Furthermore, both adverse genotypes exerted effect on increasing lung cancer risk in individuals with pre-existing COPD, while the -94del>insATTG did not in those without pre-existing COPD. However, no significant association with COPD or lung cancer was observed for -2966G>A and -826C>T. Our data suggested a common susceptible mechanism of inflammation in lung induced by genetic variants in NFκB1 (-94del>ins ATTG) or IκBα (2758G>A) to predict risk of COPD or lung cancer.

Entropy change of biological dynamics in COPD

PubMed Central

Cao, Zhixin; Sun, Baoqing; Lo, Iek Long; Liu, Tzu-Ming; Zheng, Jun; Sun, Shixue; Shi, Yan; Zhang, Xiaohua Douglas

2017-01-01

In this century, the rapid development of large data storage technologies, mobile network technology, and portable medical devices makes it possible to measure, record, store, and track analysis of large amount of data in human physiological signals. Entropy is a key metric for quantifying the irregularity contained in physiological signals. In this review, we focus on how entropy changes in various physiological signals in COPD. Our review concludes that the entropy change relies on the types of physiological signals under investigation. For major physiological signals related to respiratory diseases, such as airflow, heart rate variability, and gait variability, the entropy of a patient with COPD is lower than that of a healthy person. However, in case of hormone secretion and respiratory sound, the entropy of a patient is higher than that of a healthy person. For mechanomyogram signal, the entropy increases with the increased severity of COPD. This result should give valuable guidance for the use of entropy for physiological signals measured by wearable medical device as well as for further research on entropy in COPD. PMID:29066881

Genome-Wide Association Study of the Genetic Determinants of Emphysema Distribution

PubMed Central

Boueiz, Adel; Lutz, Sharon M.; Cho, Michael H.; Hersh, Craig P.; Bowler, Russell P.; Washko, George R.; Halper-Stromberg, Eitan; Bakke, Per; Gulsvik, Amund; Laird, Nan M.; Beaty, Terri H.; Coxson, Harvey O.; Crapo, James D.; Silverman, Edwin K.; Castaldi, Peter J.

2017-01-01

Rationale: Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe–predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. Objectives: To identify the genetic influences of emphysema distribution in non–alpha-1 antitrypsin–deficient smokers. Methods: A total of 11,532 subjects with complete genotype and computed tomography densitometry data in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]; non-Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), and GenKOLS (Genetics of Chronic Obstructive Lung Disease) studies were analyzed. Two computed tomography scan emphysema distribution measures (difference between upper-third and lower-third emphysema; ratio of upper-third to lower-third emphysema) were tested for genetic associations in all study subjects. Separate analyses in each study population were followed by a fixed effect metaanalysis. Single-nucleotide polymorphism–, gene-, and pathway-based approaches were used. In silico functional evaluation was also performed. Measurements and Main Results: We identified five loci associated with emphysema distribution at genome-wide significance. These loci included two previously reported associations with COPD susceptibility (4q31 near HHIP and 15q25 near CHRNA5) and three new associations near SOWAHB, TRAPPC9, and KIAA1462. Gene set analysis and in silico functional evaluation revealed pathways and cell types that may potentially contribute to the pathogenesis of emphysema distribution. Conclusions: This multicohort genome-wide association study identified new genomic loci associated with differential emphysematous destruction throughout the lungs. These findings may point to new biologic pathways on which to expand diagnostic and therapeutic approaches in chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764). PMID:27669027

Global scientific collaboration in COPD research.

PubMed

Su, Yanbing; Long, Chao; Yu, Qi; Zhang, Juan; Wu, Daisy; Duan, Zhiguang

2017-01-01

This study aimed to investigate the multiple collaboration types, quantitatively evaluate the publication trends and review the performance of institutions or countries (regions) across the world in COPD research. Scientometric methods and social network analysis were used to survey the development of publication trends and understand current collaboration in the field of COPD research based on the Web of Science publications during the past 18 years. The number of publications developed through different collaboration types has increased. Growth trends indicate that the percentage of papers authored through multinational and domestic multi-institutional collaboration (DMIC) have also increased. However, the percentage of intra-institutional collaboration and single-authored (SA) studies has reduced. The papers that produced the highest academic impact result from international collaboration. The second highest academic impact papers are produced by DMIC. Out of the three, the papers that are produced by SA studies have the least amount of impact upon the scientific community. A handful of internationally renowned institutions not only take the leading role in the development of the research within their country (region) but also play a crucial role in international research collaboration in COPD. Both the amount of papers produced and the amount of cooperation that occurs in each study are disproportionally distributed between high-income countries (regions) and low-income countries (regions). Growing attention has been generated toward research on COPD from more and more different academic domains. Despite the rapid development in COPD research, collaboration in the field of COPD research still has room to grow, especially between different institutions or countries (regions), which would promote the progress of global COPD research.

Classification of Exacerbation Frequency in the COPDGene Cohort Using Deep Learning with Deep Belief Networks.

PubMed

Ying, Jun; Dutta, Joyita; Guo, Ning; Hu, Chenhui; Zhou, Dan; Sitek, Arkadiusz; Li, Quanzheng

2016-12-21

This study aims to develop an automatic classifier based on deep learning for exacerbation frequency in patients with chronic obstructive pulmonary disease (COPD). A threelayer deep belief network (DBN) with two hidden layers and one visible layer was employed to develop classification models and the models' robustness to exacerbation was analyzed. Subjects from the COPDGene cohort were labeled with exacerbation frequency, defined as the number of exacerbation events per year. 10,300 subjects with 361 features each were included in the analysis. After feature selection and parameter optimization, the proposed classification method achieved an accuracy of 91.99%, using a 10-fold cross validation experiment. The analysis of DBN weights showed that there was a good visual spatial relationship between the underlying critical features of different layers. Our findings show that the most sensitive features obtained from the DBN weights are consistent with the consensus showed by clinical rules and standards for COPD diagnostics. We thus demonstrate that DBN is a competitive tool for exacerbation risk assessment for patients suffering from COPD.

Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Ecological Study in the Basque Country, Spain (2000-2011).

PubMed

Tamayo-Uria, Ibon; Altzibar, Jone M; Mughini-Gras, Lapo; Dorronsoro, Miren

2016-12-01

Chronic obstructive pulmonary disease (COPD) is a prevalent condition in adults aged ≥40 years characterized by progressive airflow limitation associated with chronic inflammatory response to noxious particles in the airways and lungs. Smoking, genetics, air pollution, nutrition and other factors may influence COPD development. Most hospitalizations and deaths for COPD are caused by its acute exacerbations, which greatly affect the health and quality of life of COPD patients and pose a high burden on health services. The aims of this project were to identify trends, geographic patterns and risk factors for COPD exacerbations, as revealed by hospitalizations and deaths, in the Basque Country, Spain, over a period of 12 years (2000-2011). Hospitalization and mortality rates for COPD were 262 and 18 per 100,000 population, respectively, with clusters around the biggest cities. Hospital mortality was 7.4%. Most hospitalized patients were male (77.4%) and accounted for 72.1% of hospital mortality. Hospitalizations decreased during the study period, except for 50-64 year-old women, peaking significantly. Using a multivariate modeling approach it was shown that hospitalizations were positively correlated with increased atmospheric concentrations of NO 2 , CO, PM 10 , and SO 2 , and increased influenza incidence, but were negatively associated with increased temperatures and atmospheric O 3 concentration. COPD exacerbations decreased in the Basque Country during 2000-2011, but not among 50-64-year-old women, reflecting the high smoking prevalence among Spanish women during the 1970-1990s. The main metropolitan areas were those with the highest risk for COPD exacerbations, calling attention to the role of heavy car traffic. Influenza virus, cold temperatures, and increased atmospheric NO 2 , CO, PM 10 , and SO 2 (but decreased O 3 ) concentrations were identified as potential contributors to the burden of COPD exacerbations in the community. These findings are important for both the understanding of the disease process and in providing potential targets for COPD-reducing initiatives and new avenues for research.

Evaluation of whether the ACE gene I/D polymorphism constitutes a risk factor for chronic obstructive pulmonary disease in the Turkish population.

PubMed

Ayada, C; Toru, U; Genç, O; Yerlikaya, A; Sahin, S; Turgut, S; Turgut, G

2014-12-12

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction that occurs as a result of the normal inflammatory process to protect against harmful irritants and chemicals. Another physiological regulatory process, the renin angiotensin system (RAS), plays an important role in the pathology of many diseases. Angiotensin converting enzyme (ACE) is a key enzyme of RAS. We investigated the frequency of the ACE gene I/D polymorphism in patients with COPD in Turkey. This study was performed on 47 unrelated patients with COPD and 64 healthy subjects. DNA samples were isolated from peripheral blood, and ACE DNA was amplified by polymerase chain reaction. The frequencies of ACE genotypes were 27.7, 55.3, and 17% for DD, ID, and II in the COPD group, respectively, and 43.8, 43.8, and 12.4% in the control group. There was no statistically significant difference between groups (X(2) = 3.078; df = 2; P = 0.220). The distributions of ACE gene D alleles were 38.2% (N = 52) in the COPD group and 61.8% (N = 84) in the control group; and those of I alleles were 48.8% (N = 42) in the COPD group and 51.2% (N = 44) in the control group. There was no statistically significant difference between groups for allele frequency (X(2) = 2.419; df = 2; P = 0.120). We believe these results can be useful for large-scale population genetic research considering the frequency of the ACE gene variation in COPD patients in the Turkish population.

Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.

PubMed

Saccone, Nancy L; Culverhouse, Robert C; Schwantes-An, Tae-Hwi; Cannon, Dale S; Chen, Xiangning; Cichon, Sven; Giegling, Ina; Han, Shizhong; Han, Younghun; Keskitalo-Vuokko, Kaisu; Kong, Xiangyang; Landi, Maria Teresa; Ma, Jennie Z; Short, Susan E; Stephens, Sarah H; Stevens, Victoria L; Sun, Lingwei; Wang, Yufei; Wenzlaff, Angela S; Aggen, Steven H; Breslau, Naomi; Broderick, Peter; Chatterjee, Nilanjan; Chen, Jingchun; Heath, Andrew C; Heliövaara, Markku; Hoft, Nicole R; Hunter, David J; Jensen, Majken K; Martin, Nicholas G; Montgomery, Grant W; Niu, Tianhua; Payne, Thomas J; Peltonen, Leena; Pergadia, Michele L; Rice, John P; Sherva, Richard; Spitz, Margaret R; Sun, Juzhong; Wang, Jen C; Weiss, Robert B; Wheeler, William; Witt, Stephanie H; Yang, Bao-Zhu; Caporaso, Neil E; Ehringer, Marissa A; Eisen, Tim; Gapstur, Susan M; Gelernter, Joel; Houlston, Richard; Kaprio, Jaakko; Kendler, Kenneth S; Kraft, Peter; Leppert, Mark F; Li, Ming D; Madden, Pamela A F; Nöthen, Markus M; Pillai, Sreekumar; Rietschel, Marcella; Rujescu, Dan; Schwartz, Ann; Amos, Christopher I; Bierut, Laura J

2010-08-05

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10(-35) and <10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.

Association Between ADRB2 Genetic Polymorphisms and the Risk of Chronic Obstructive Pulmonary Disease: A Case-Control Study in a Chinese Population.

PubMed

Zhao, Hui; Wu, Xuan; Dong, Chun-Ling; Wang, Bi-Ying; Zhao, Jiao; Cao, Xian-E

2017-08-01

This study was designed to investigate the association between single nucleotide polymorphisms (SNPs) of the β2-adrenergic receptor (ADRB2) gene and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese population. From January 2010 to October 2014, 261 COPD patients were selected as the case group and 239 healthy subjects were selected as the control group. Pulmonary function tests were performed to detect forced vital capacity (FVC), 1-s forced expiratory volume (FEV 1 ), and FEV 1 /FVC (%). rs1042711, rs1042714, and rs1042718 were selected as tagSNPs of the ADRB2 gene from the HapMap database in accordance with previous studies. The ADRB2 genotypes were established by real-time polymerase chain reaction assays using TaqMan-labeled probes. The relationships between the ADRB2 polymorphisms and COPD risk were estimated using logistic regression analyses. The frequency of the genotypes and alleles of rs1042711 in ADRB2 showed a significant difference between the COPD and control groups (p < 0.05); compared with the CC genotype, the non-CC genotypes showed an increased COPD risk (p = 0.002). Compared with the CC haplotype, the TG haplotype increased COPD risk, while the CG haplotype reduced COPD risk for normal individuals. Compared with the CC genotype, the TT genotype showed significantly lower FEV 1 and FEV 1 /FVC (p = 0.022, p = 0.0191, respectively). Both the TC and TG haplotypes showed lower FEV 1 and FEV 1 /FVC in comparison with the CC haplotype (both p < 0.05). The results of logistic regression analysis showed that rs1042711 of ADRB2 and smoking history were associated with COPD risk (both p < 0.05). It is indicated that the TT genotype of rs1042711 and smoking pack years are both risk factors for COPD.

Large-scale external validation and comparison of prognostic models: an application to chronic obstructive pulmonary disease.

PubMed

Guerra, Beniamino; Haile, Sarah R; Lamprecht, Bernd; Ramírez, Ana S; Martinez-Camblor, Pablo; Kaiser, Bernhard; Alfageme, Inmaculada; Almagro, Pere; Casanova, Ciro; Esteban-González, Cristóbal; Soler-Cataluña, Juan J; de-Torres, Juan P; Miravitlles, Marc; Celli, Bartolome R; Marin, Jose M; Ter Riet, Gerben; Sobradillo, Patricia; Lange, Peter; Garcia-Aymerich, Judith; Antó, Josep M; Turner, Alice M; Han, Meilan K; Langhammer, Arnulf; Leivseth, Linda; Bakke, Per; Johannessen, Ane; Oga, Toru; Cosio, Borja; Ancochea-Bermúdez, Julio; Echazarreta, Andres; Roche, Nicolas; Burgel, Pierre-Régis; Sin, Don D; Soriano, Joan B; Puhan, Milo A

2018-03-02

External validations and comparisons of prognostic models or scores are a prerequisite for their use in routine clinical care but are lacking in most medical fields including chronic obstructive pulmonary disease (COPD). Our aim was to externally validate and concurrently compare prognostic scores for 3-year all-cause mortality in mostly multimorbid patients with COPD. We relied on 24 cohort studies of the COPD Cohorts Collaborative International Assessment consortium, corresponding to primary, secondary, and tertiary care in Europe, the Americas, and Japan. These studies include globally 15,762 patients with COPD (1871 deaths and 42,203 person years of follow-up). We used network meta-analysis adapted to multiple score comparison (MSC), following a frequentist two-stage approach; thus, we were able to compare all scores in a single analytical framework accounting for correlations among scores within cohorts. We assessed transitivity, heterogeneity, and inconsistency and provided a performance ranking of the prognostic scores. Depending on data availability, between two and nine prognostic scores could be calculated for each cohort. The BODE score (body mass index, airflow obstruction, dyspnea, and exercise capacity) had a median area under the curve (AUC) of 0.679 [1st quartile-3rd quartile = 0.655-0.733] across cohorts. The ADO score (age, dyspnea, and airflow obstruction) showed the best performance for predicting mortality (difference AUC ADO - AUC BODE = 0.015 [95% confidence interval (CI) = -0.002 to 0.032]; p = 0.08) followed by the updated BODE (AUC BODE updated - AUC BODE = 0.008 [95% CI = -0.005 to +0.022]; p = 0.23). The assumption of transitivity was not violated. Heterogeneity across direct comparisons was small, and we did not identify any local or global inconsistency. Our analyses showed best discriminatory performance for the ADO and updated BODE scores in patients with COPD. A limitation to be addressed in future studies is the extension of MSC network meta-analysis to measures of calibration. MSC network meta-analysis can be applied to prognostic scores in any medical field to identify the best scores, possibly paving the way for stratified medicine, public health, and research.

Global scientific collaboration in COPD research

PubMed Central

Su, Yanbing; Long, Chao; Yu, Qi; Zhang, Juan; Wu, Daisy; Duan, Zhiguang

2017-01-01

Purpose This study aimed to investigate the multiple collaboration types, quantitatively evaluate the publication trends and review the performance of institutions or countries (regions) across the world in COPD research. Materials and methods Scientometric methods and social network analysis were used to survey the development of publication trends and understand current collaboration in the field of COPD research based on the Web of Science publications during the past 18 years. Results The number of publications developed through different collaboration types has increased. Growth trends indicate that the percentage of papers authored through multinational and domestic multi-institutional collaboration (DMIC) have also increased. However, the percentage of intra-institutional collaboration and single-authored (SA) studies has reduced. The papers that produced the highest academic impact result from international collaboration. The second highest academic impact papers are produced by DMIC. Out of the three, the papers that are produced by SA studies have the least amount of impact upon the scientific community. A handful of internationally renowned institutions not only take the leading role in the development of the research within their country (region) but also play a crucial role in international research collaboration in COPD. Both the amount of papers produced and the amount of cooperation that occurs in each study are disproportionally distributed between high-income countries (regions) and low-income countries (regions). Growing attention has been generated toward research on COPD from more and more different academic domains. Conclusion Despite the rapid development in COPD research, collaboration in the field of COPD research still has room to grow, especially between different institutions or countries (regions), which would promote the progress of global COPD research. PMID:28123294

Lung Cancer and Chronic Obstructive Pulmonary Disease: Needs and Opportunities for Integrated Research

PubMed Central

Szabo, Eva; Croxton, Thomas L.; Shapiro, Steven D.; Dubinett, Steven M.

2009-01-01

Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality in the United States and worldwide. They share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by the incidence of these diseases in only a fraction of smokers. The presence of COPD increases the risk of lung cancer up to 4.5-fold. To investigate commonalities in disease mechanisms and perspectives for disease chemoprevention, the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) held a workshop. The participants identified four research objectives: 1) clarify common epidemiological characteristics of lung cancer and COPD; 2) identify shared genetic and epigenetic risk factors; 3) identify and validate biomarkers, molecular signatures, and imaging-derived measurements of each disease; and 4) determine common and disparate pathogenetic mechanisms. These objectives should be reached via four research approaches: 1) identify, publicize, and enable the evaluation and analysis of existing datasets and repositories of biospecimens; 2) obtain phenotypic and outcome data and biospecimens from large studies of subjects with and/or at risk for COPD and lung cancer; 3) develop and use animal and other preclinical models to investigate pathogenetic links between the diseases; and 4) conduct early-phase clinical trials of potential chemopreventive agents. To foster much needed research interactions, two final recommendations were made by the participants: 1) incorporate baseline phenotyping and outcome measures for both diseases in future longitudinal studies of each disease and 2) expand collaborative efforts between the NCI and NHLBI. PMID:19351920

WISARD: workbench for integrated superfast association studies for related datasets.

PubMed

Lee, Sungyoung; Choi, Sungkyoung; Qiao, Dandi; Cho, Michael; Silverman, Edwin K; Park, Taesung; Won, Sungho

2018-04-20

A Mendelian transmission produces phenotypic and genetic relatedness between family members, giving family-based analytical methods an important role in genetic epidemiological studies-from heritability estimations to genetic association analyses. With the advance in genotyping technologies, whole-genome sequence data can be utilized for genetic epidemiological studies, and family-based samples may become more useful for detecting de novo mutations. However, genetic analyses employing family-based samples usually suffer from the complexity of the computational/statistical algorithms, and certain types of family designs, such as incorporating data from extended families, have rarely been used. We present a Workbench for Integrated Superfast Association studies for Related Data (WISARD) programmed in C/C++. WISARD enables the fast and a comprehensive analysis of SNP-chip and next-generation sequencing data on extended families, with applications from designing genetic studies to summarizing analysis results. In addition, WISARD can automatically be run in a fully multithreaded manner, and the integration of R software for visualization makes it more accessible to non-experts. Comparison with existing toolsets showed that WISARD is computationally suitable for integrated analysis of related subjects, and demonstrated that WISARD outperforms existing toolsets. WISARD has also been successfully utilized to analyze the large-scale massive sequencing dataset of chronic obstructive pulmonary disease data (COPD), and we identified multiple genes associated with COPD, which demonstrates its practical value.

Dyspnea-Related Cues Engage the Prefrontal Cortex

PubMed Central

Herigstad, Mari; Hayen, Anja; Evans, Eleanor; Hardinge, Frances M.; Davies, Robert J.; Wiech, Katja

2015-01-01

BACKGROUND: Dyspnea is the major source of disability in COPD. In COPD, environmental cues (eg, the prospect of having to climb stairs) become associated with dyspnea and may trigger dyspnea even before physical activity commences. We hypothesized that brain activation relating to such cues would be different between patients with COPD and healthy control subjects, reflecting greater engagement of emotional mechanisms in patients. METHODS: Using functional MRI (FMRI), we investigated brain responses to dyspnea-related word cues in 41 patients with COPD and 40 healthy age-matched control subjects. We combined these findings with scores on self-report questionnaires, thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enabled identification of brain networks responsible for pain processing despite absence of a physical challenge. RESULTS: Patients with COPD demonstrated activation in the medial prefrontal cortex and anterior cingulate cortex, which correlated with the visual analog scale (VAS) response to word cues. This activity independently correlated with patient responses on questionnaires of depression, fatigue, and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex, and precuneus correlated with the VAS dyspnea scale but not with the questionnaires. CONCLUSIONS: The findings suggest that engagement of the emotional circuitry of the brain is important for interpretation of dyspnea-related cues in COPD and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and the findings suggest that such mechanisms may be relevant in COPD. PMID:26134891

Association between vitamin D receptor polymorphisms and osteoporosis in patients with COPD

PubMed Central

Kim, Sei Won; Lee, Jong Min; Ha, Jick Hwan; Kang, Hyeon Hui; Rhee, Chin Kook; Kim, Jin Woo; Moon, Hwa Sik; Baek, Ki Hyun; Lee, Sang Haak

2015-01-01

Background Patients with COPD are at an increased risk of osteoporosis. Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD. In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD. Patients and methods In total, 200 patients with COPD were included in this study. The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples. BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry. Other clinical parameters were also evaluated. Haplotype and multivariate analyses were also performed. Results Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis. Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD. Haplotypes GCT and GAT were related to osteoporosis. Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20–6.48, P=0.018) compared with carriers in the dominant model. Conclusion Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD. Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD. PMID:26379431

76 FR 37132 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... clearly unwarranted invasion of personal privacy. Name of Committee: National Heart, Lung, and Blood..., Special Emphasis Panel. Studies to Identify Genetic Determinants of COPD. Date: July 20, 2011. Time: 2 to...

A Chronic Obstructive Pulmonary Disease Susceptibility Gene, FAM13A, Regulates Protein Stability of β-Catenin.

PubMed

Jiang, Zhiqiang; Lao, Taotao; Qiu, Weiliang; Polverino, Francesca; Gupta, Kushagra; Guo, Feng; Mancini, John D; Naing, Zun Zar Chi; Cho, Michael H; Castaldi, Peter J; Sun, Yang; Yu, Jane; Laucho-Contreras, Maria E; Kobzik, Lester; Raby, Benjamin A; Choi, Augustine M K; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

2016-07-15

A genetic locus within the FAM13A gene has been consistently associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies. However, the mechanisms by which FAM13A contributes to COPD susceptibility are unknown. To determine the biologic function of FAM13A in human COPD and murine COPD models and discover the molecular mechanism by which FAM13A influences COPD susceptibility. Fam13a null mice (Fam13a(-/-)) were generated and exposed to cigarette smoke. The lung inflammatory response and airspace size were assessed in Fam13a(-/-) and Fam13a(+/+) littermate control mice. Cellular localization of FAM13A protein and mRNA levels of FAM13A in COPD lungs were assessed using immunofluorescence, Western blotting, and reverse transcriptase-polymerase chain reaction, respectively. Immunoprecipitation followed by mass spectrometry identified cellular proteins that interact with FAM13A to reveal insights on FAM13A's function. In murine and human lungs, FAM13A is expressed in airway and alveolar type II epithelial cells and macrophages. Fam13a null mice (Fam13a(-/-)) were resistant to chronic cigarette smoke-induced emphysema compared with Fam13a(+/+) mice. In vitro, FAM13A interacts with protein phosphatase 2A and recruits protein phosphatase 2A with glycogen synthase kinase 3β and β-catenin, inducing β-catenin degradation. Fam13a(-/-) mice were also resistant to elastase-induced emphysema, and this resistance was reversed by coadministration of a β-catenin inhibitor, suggesting that FAM13A could increase the susceptibility of mice to emphysema development by inhibiting β-catenin signaling. Moreover, human COPD lungs had decreased protein levels of β-catenin and increased protein levels of FAM13A. We show that FAM13A may influence COPD susceptibility by promoting β-catenin degradation.

[The evaluation of asthma and COPD awareness in Turkey (GARD Turkey Project-National Control Program of Chronic Airway Diseases)].

PubMed

Yıldız, Füsun; Bingöl Karakoç, Gülbin; Ersu Hamutçu, Refika; Yardım, Nazan; Ekıncı, Banu; Yorgancıoğlu, Arzu

2013-01-01

Although chronic respiratory disorders are important causes of morbidity and mortality, health care workers, patients and caretakers are not well informed about these disorders. Therefore these problems are underdiagnosed and undertreated; also preventive measures are not widely taken. Our aim was to evaluate the knowledge of asthma and chronic obstructive pulmonary disease (COPD) in Turkey. This study was designed and performed as a Global Alliance Against Respiratory Disorders (GARD) project. People greater than 15 years of age who lived in cities with a population of 200 or greater were eligible for the study. A questionnaire including demographic data and questions regarding asthma and COPD was used for the evalution of the participants. 12.000 people were selected (6000 in rural and 6000 in urban areas); 8527 people were reached. 8342 people who completed the questionnaire were included to the study. There were 4182 (50.1%) female and 4160 (%49.9) male subjects. 49.6% of the subjcets knew that COPD is a lung disease, 51.1% indicated that smoking is the most important risk factor for COPD and 48% identified quitting smoking as the most important preventive measure. Every other person had baseline knowledge on COPD. However only 25.2% knew that there are treatment options for COPD. 80% of subjects said astma can be seen in all age groups. 51.1% knew asthma is a genetic disease and 58% said it is not an infectious disease. However when whether asthma medications caused drug dependency only 27% answered as "No" while 55.2% said "They do not know". Awareness of COPD and asthma seem to be infsufficient among Turkish people. Since these disorders are important causes of morbidity and mortality and have high impact on work and economic loss, it is important to increase knowledge among public.

Combining systems pharmacology, transcriptomics, proteomics, and metabolomics to dissect the therapeutic mechanism of Chinese herbal Bufei Jianpi formula for application to COPD

PubMed Central

Zhao, Peng; Yang, Liping; Li, Jiansheng; Li, Ya; Tian, Yange; Li, Suyun

2016-01-01

Bufei Jianpi formula (BJF) has long been used as a therapeutic agent in the treatment of COPD. Systems pharmacology identified 145 active compounds and 175 potential targets of BJF in a previous study. Additionally, BJF was previously shown to effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production, in vivo. However, the system-level mechanism of BJF for the treatment of COPD is still unclear. The aim of this study was to gain insight into its system-level mechanisms by integrating transcriptomics, proteomics, and metabolomics together with systems pharmacology datasets. Using molecular function, pathway, and network analyses, the genes and proteins regulated in COPD rats and BJF-treated rats could be mainly attributed to oxidoreductase activity, antioxidant activity, focal adhesion, tight junction, or adherens junction. Furthermore, a comprehensive analysis of systems pharmacology, transcript, protein, and metabolite datasets is performed. The results showed that a number of genes, proteins, metabolites regulated in BJF-treated rats and potential target proteins of BJF were involved in lipid metabolism, cell junction, oxidative stress, and inflammatory response, which might be the system-level therapeutic mechanism of BJF treatment. PMID:27042044

Genetic Ablation of the Aryl Hydrocarbon Receptor Causes Cigarette Smoke-induced Mitochondrial Dysfunction and Apoptosis*

PubMed Central

Rico de Souza, Angela; Zago, Michela; Pollock, Stephen J.; Sime, Patricia J.; Phipps, Richard P.; Baglole, Carolyn J.

2011-01-01

Cigarette smoke is the primary risk factor for chronic obstructive pulmonary disease (COPD). Alterations in the balance between apoptosis and proliferation are involved in the etiology of COPD. Fibroblasts and epithelial cells are sensitive to the oxidative properties of cigarette smoke, and whose loss may precipitate the development of COPD. Fibroblasts express the aryl hydrocarbon receptor (AhR), a transcription factor that attenuates pulmonary inflammation and may also regulate apoptosis. We hypothesized the AhR would prevent apoptosis caused by cigarette smoke. Using genetically deleted in vitro AhR expression models and an established method of cigarette smoke exposure, we report that AhR expression regulates fibroblasts proliferation and prevents morphological features of apoptosis, including membrane blebbing and chromatin condensation caused by cigarette smoke extract (CSE). Absence of AhR expression results in cleavage of PARP, lamin, and caspase-3. Mitochondrial dysfunction, including cytochrome c release, was associated with loss of AhR expression, indicating activation of the intrinsic apoptotic cascade. Heightened sensitivity of AhR-deficient fibroblasts was not the result of alterations in GSH, Nrf2, or HO-1 expression. Instead, AhR−/− cells had significantly less MnSOD and CuZn-SOD expression, enzymes that protects against oxidative stress. The ability of the AhR to suppress apoptosis was not restricted to fibroblasts, as siRNA-mediated knockdown of the AhR in lung epithelial cells also increased sensitivity to smoke-induced apoptosis. Collectively, these results suggest that cigarette smoke induced loss of lung structural support (i.e. fibroblasts, epithelial cells) caused by aberrations in AhR expression may explain why some smokers develop lung diseases such as COPD. PMID:21984831

Genetic Polymorphism of Angiotensin-Converting Enzyme and Chronic Obstructive Pulmonary Disease Risk: An Updated Meta-Analysis

PubMed Central

Kang, Sang Wook; Kim, Su Kang; Jung, Hee-Jae; Kim, Kwan-Il; Kim, Jinju

2016-01-01

The relationship between polymorphism of the angiotensin I converting enzyme (ACE) gene and chronic obstructive pulmonary disease (COPD) has been examined in many previous studies. However, their results were controversial. Therefore, we performed a meta-analysis to evaluate the relationship between the ACE gene and the risk of COPD. Fourteen case-control studies were included in this meta-analysis. The pooled p value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association. The meta-analysis was performed using comprehensive meta-analysis software. Our meta-analysis results revealed that ACE polymorphisms were not related to the risk of COPD (p > 0.05 in each model). In further analyses based on ethnicity, we observed an association between insertion/deletion polymorphism of the ACE gene and risk of COPD in the Asian population (codominant 2, OR = 3.126, 95% CI = 1.919–5.093, p < 0.001; recessive, OR = 3.326, 95% CI = 2.190–5.050, p < 0.001) but not in the Caucasian population (p > 0.05 in each model). In conclusion, the present meta-analysis indicated that the insertion/deletion polymorphism of the ACE gene may be associated with susceptibility to COPD in the Asian population but not in the Caucasian population. However, the results of the present meta-analysis need to be confirmed in a larger sample. PMID:27830153

Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on the human lung microbiome

PubMed Central

Schloter-Hai, Brigitte; Kublik, Susanne; Granitsiotis, Michael S.; Boschetto, Piera; Stendardo, Mariarita; Barta, Imre; Dome, Balazs; Deleuze, Jean-François; Boland, Anne; Müller-Quernheim, Joachim; Prasse, Antje; Welte, Tobias; Hohlfeld, Jens; Subramanian, Deepak; Parr, David; Gut, Ivo Glynne; Greulich, Timm; Koczulla, Andreas Rembert; Nowinski, Adam; Gorecka, Dorota; Singh, Dave; Gupta, Sumit; Brightling, Christopher E.; Hoffmann, Harald; Frankenberger, Marion; Hofer, Thomas P.; Burggraf, Dorothe; Heiss-Neumann, Marion; Ziegler-Heitbrock, Loems; Schloter, Michael; zu Castell, Wolfgang

2017-01-01

Background Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. Methods Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons. Results We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype. Conclusion Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system. PMID:28704452

Steroid Resistant CD8+CD28null NKT-Like Pro-inflammatory Cytotoxic Cells in Chronic Obstructive Pulmonary Disease.

PubMed

Hodge, Greg; Hodge, Sandra

2016-01-01

Corticosteroid resistance is a major barrier to effective treatment in chronic obstructive pulmonary disease (COPD), and failure to suppress systemic inflammation in these patients may result in increased comorbidity. Although much of the research to date has focused on the role of macrophages and neutrophils involved in inflammation in the airways in COPD, recent evidence suggests that CD8 + T cells may be central regulators of the inflammatory network in this disease. CD8 + cytotoxic pro-inflammatory T cells have been shown to be increased in the peripheral blood and airways in patients with COPD, whereas smokers that have not progressed to COPD only show an increase in the lungs. Although the mechanisms underlying steroid resistance in these lymphocytes is largely unknown, new research has identified a role for cytotoxic pro-inflammatory CD8 + T-cells and CD8 + natural killer T-like (NKT-like) cells. Increased numbers of these cells and their significant loss of the co-stimulatory molecule CD28 have been shown in COPD, consistent with findings in the elderly and in clinical conditions involving chronic activation of the immune system. In COPD, these senescent cells expressed increased levels of the cytotoxic mediators, perforin and granzyme b, and the pro-inflammatory cytokines, IFNγ and TNFα. They also demonstrated increased cytotoxicity toward lung epithelial cells and importantly were resistant to immunosuppression by corticosteroids compared with their CD28 + counterparts. Further research has shown these cells evade the immunosuppressive effects of steroids via multiple mechanisms. This mini review will focus on cytotoxic pro-inflammatory CD8 + CD28 null NKT-like cells involved in COPD and novel approaches to reverse steroid resistance in these cells.

Steroid Resistant CD8+CD28null NKT-Like Pro-inflammatory Cytotoxic Cells in Chronic Obstructive Pulmonary Disease

PubMed Central

Hodge, Greg; Hodge, Sandra

2016-01-01

Corticosteroid resistance is a major barrier to effective treatment in chronic obstructive pulmonary disease (COPD), and failure to suppress systemic inflammation in these patients may result in increased comorbidity. Although much of the research to date has focused on the role of macrophages and neutrophils involved in inflammation in the airways in COPD, recent evidence suggests that CD8+ T cells may be central regulators of the inflammatory network in this disease. CD8+ cytotoxic pro-inflammatory T cells have been shown to be increased in the peripheral blood and airways in patients with COPD, whereas smokers that have not progressed to COPD only show an increase in the lungs. Although the mechanisms underlying steroid resistance in these lymphocytes is largely unknown, new research has identified a role for cytotoxic pro-inflammatory CD8+ T-cells and CD8+ natural killer T-like (NKT-like) cells. Increased numbers of these cells and their significant loss of the co-stimulatory molecule CD28 have been shown in COPD, consistent with findings in the elderly and in clinical conditions involving chronic activation of the immune system. In COPD, these senescent cells expressed increased levels of the cytotoxic mediators, perforin and granzyme b, and the pro-inflammatory cytokines, IFNγ and TNFα. They also demonstrated increased cytotoxicity toward lung epithelial cells and importantly were resistant to immunosuppression by corticosteroids compared with their CD28+ counterparts. Further research has shown these cells evade the immunosuppressive effects of steroids via multiple mechanisms. This mini review will focus on cytotoxic pro-inflammatory CD8+CD28null NKT-like cells involved in COPD and novel approaches to reverse steroid resistance in these cells. PMID:28066427

Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on the human lung microbiome.

PubMed

Engel, Marion; Endesfelder, David; Schloter-Hai, Brigitte; Kublik, Susanne; Granitsiotis, Michael S; Boschetto, Piera; Stendardo, Mariarita; Barta, Imre; Dome, Balazs; Deleuze, Jean-François; Boland, Anne; Müller-Quernheim, Joachim; Prasse, Antje; Welte, Tobias; Hohlfeld, Jens; Subramanian, Deepak; Parr, David; Gut, Ivo Glynne; Greulich, Timm; Koczulla, Andreas Rembert; Nowinski, Adam; Gorecka, Dorota; Singh, Dave; Gupta, Sumit; Brightling, Christopher E; Hoffmann, Harald; Frankenberger, Marion; Hofer, Thomas P; Burggraf, Dorothe; Heiss-Neumann, Marion; Ziegler-Heitbrock, Loems; Schloter, Michael; Zu Castell, Wolfgang

2017-01-01

Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons. We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype. Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system.

THE SPONTANEOUSLY HYPERTENSIVE RAT: AN EXPERIMENTAL MODEL OF SULFUR DIOXIDE-INDUCED AIRWAYS DISEASE

EPA Science Inventory

Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation and mucus hypersecretion; features that capture bronchitis, emphysema and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisp...

A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease.

PubMed

Hardin, M; Cho, M H; McDonald, M-L; Wan, E; Lomas, D A; Coxson, H O; MacNee, W; Vestbo, J; Yates, J C; Agusti, A; Calverley, P M A; Celli, B; Crim, C; Rennard, S; Wouters, E; Bakke, P; Bhatt, S P; Kim, V; Ramsdell, J; Regan, E A; Make, B J; Hokanson, J E; Crapo, J D; Beaty, T H; Hersh, C P

2016-08-01

Short-acting β2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled β2-agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 (P=2.02 × 10(-7)) and KCNJ2 (P=1.79 × 10(-7)) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1 × 10(-9)). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.65.

Determinants of airflow obstruction in severe alpha‐1‐antitrypsin deficiency

PubMed Central

DeMeo, Dawn L; Sandhaus, Robert A; Barker, Alan F; Brantly, Mark L; Eden, Edward; McElvaney, N Gerard; Rennard, Stephen; Burchard, Esteban; Stocks, James M; Stoller, James K; Strange, Charlie; Turino, Gerard M; Campbell, Edward J; Silverman, Edwin K

2007-01-01

Background Severe α1‐antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency. Methods The AAT Genetic Modifier Study is a multicentre family‐based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33–80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV1) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV1 <50% predicted). Results In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV1 percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV1 values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non‐index cases (p<0.01). Men had lower pre‐ and post‐bronchodilator FEV1 percentage predicted than women (p<0.0001); the lowest FEV1 values were observed in men reporting a history of childhood asthma (26.9%). This trend for more severe obstruction in men remained when index and non‐index groups were examined separately, with men representing the majority of non‐index individuals with airflow obstruction (71%). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non‐index men but not women. Conclusion In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment. PMID:17389752

Occupational chronic obstructive pulmonary disease: a systematic literature review.

PubMed

Omland, Oyvind; Würtz, Else Toft; Aasen, Tor Brøvig; Blanc, Paul; Brisman, Jonas Brisman; Miller, Martin Reginald; Pedersen, Ole Find; Schlünssen, Vivi; Sigsgaard, Torben; Ulrik, Charlotte Suppli; Viskum, Sven

2014-01-01

Occupational-attributable chronic obstructive pulmonary disease (COPD) presents a substantial health challenge. Focusing on spirometric criteria for airflow obstruction, this review of occupational COPD includes both population-wide and industry-specific exposures. We used PubMed and Embase to identify relevant original epidemiological peer-reviewed articles, supplemented with citations identified from references in key review articles. This yielded 4528 citations. Articles were excluded for lack of lung function measurement, insufficient occupational exposure classification, lack of either external or internal referents, non-accounting of age or smoking effect, or major analytic inadequacies preventing interpretation of findings. A structured data extraction sheet was used for the remaining 147 articles. Final inclusion was based on a positive qualitative Scottish Intercollegiate Guidelines Network (SIGN) score (≥2+) for study quality, yielding 25 population-wide and 34 industry/occupation-specific studies, 15 on inorganic and 19 on organic dust exposure, respectively. There was a consistent and predominantly significant association between occupational exposures and COPD in 22 of 25 population-based studies, 12 of 15 studies with an inorganic/mineral dust exposure, and 17 of 19 studies on organic exposure, even though the studies varied in design, populations, and the use of measures of exposure and outcome. A nearly uniform pattern of a dose-response relationship between various exposures and COPD was found, adding to the evidence that occupational exposures from vapors, gas, dust, and fumes are risk factors for COPD. There is strong and consistent evidence to support a causal association between multiple categories of occupational exposure and COPD, both within and across industry groups.

Features of a Mobile Support App for Patients With Chronic Obstructive Pulmonary Disease: Literature Review and Current Applications

PubMed Central

Philip, Nada; Kayyali, Reem; Nabhani-Gebara, Shereen; Pierscionek, Barbara; Vaes, Anouk W; Spruit, Martijn A; Kaimakamis, Evangelos

2017-01-01

Background Chronic obstructive pulmonary disease (COPD) is a serious long-term lung disease in which the airflow from the lungs is progressively reduced. By 2030, COPD will become the third cause of mortality and seventh cause of morbidity worldwide. With advances in technology and mobile communications, significant progress in the mobile health (mHealth) sector has been recently observed. Mobile phones with app capabilities (smartphones) are now considered as potential media for the self-management of certain types of diseases such as asthma, cancer, COPD, or cardiovascular diseases. While many mobile apps for patients with COPD are currently found on the market, there is little published material on the effectiveness of most of them, their features, and their adoption in health care settings. Objectives The aim of this study was to search the literature for current systems related to COPD and identify any missing links and studies that were carried out to evaluate the effectiveness of COPD mobile apps. In addition, we reviewed existing mHealth apps from different stores in order to identify features that can be considered in the initial design of a COPD support tool to improve health care services and patient outcomes. Methods In total, 206 articles related to COPD management systems were identified from different databases. Irrelevant materials and duplicates were excluded. Of those, 38 articles were reviewed to extract important features. We identified 214 apps from online stores. Following exclusion of irrelevant apps, 48 were selected and 20 of them were downloaded to review some of their common features. Results Our review found that out of the 20 apps downloaded, 13 (65%, 13/20) had an education section, 5 (25%, 5/20) consisted of medication and guidelines, 6 (30%, 6/20) included a calendar or diary and other features such as reminders or symptom tracking. There was little published material on the effectiveness of the identified COPD apps. Features such as (1) a social networking tool; (2) personalized education; (3) feedback; (4) e-coaching; and (5) psychological motivation to enhance behavioral change were found to be missing in many of the downloaded apps. Conclusions This paper summarizes the features of a COPD patient-support mobile app that can be taken into consideration for the initial design of an integrated care system to encourage the self-management of their condition at home. PMID:28219878

Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease.

PubMed

Brehm, John M; Hagiwara, Koichi; Tesfaigzi, Yohannes; Bruse, Shannon; Mariani, Thomas J; Bhattacharya, Soumyaroop; Boutaoui, Nadia; Ziniti, John P; Soto-Quiros, Manuel E; Avila, Lydiana; Cho, Michael H; Himes, Blanca; Litonjua, Augusto A; Jacobson, Francine; Bakke, Per; Gulsvik, Amund; Anderson, Wayne H; Lomas, David A; Forno, Erick; Datta, Soma; Silverman, Edwin K; Celedón, Juan C

2011-12-01

Traditional genome-wide association studies (GWASs) of large cohorts of subjects with chronic obstructive pulmonary disease (COPD) have successfully identified novel candidate genes, but several other plausible loci do not meet strict criteria for genome-wide significance after correction for multiple testing. The authors hypothesise that by applying unbiased weights derived from unique populations we can identify additional COPD susceptibility loci. Methods The authors performed a homozygosity haplotype analysis on a group of subjects with and without COPD to identify regions of conserved homozygosity haplotype (RCHHs). Weights were constructed based on the frequency of these RCHHs in case versus controls, and used to adjust the p values from a large collaborative GWAS of COPD. The authors identified 2318 RCHHs, of which 576 were significantly (p<0.05) over-represented in cases. After applying the weights constructed from these regions to a collaborative GWAS of COPD, the authors identified two single nucleotide polymorphisms (SNPs) in a novel gene (fibroblast growth factor-7 (FGF7)) that gained genome-wide significance by the false discovery rate method. In a follow-up analysis, both SNPs (rs12591300 and rs4480740) were significantly associated with COPD in an independent population (combined p values of 7.9E-7 and 2.8E-6, respectively). In another independent population, increased lung tissue FGF7 expression was associated with worse measures of lung function. Weights constructed from a homozygosity haplotype analysis of an isolated population successfully identify novel genetic associations from a GWAS on a separate population. This method can be used to identify promising candidate genes that fail to meet strict correction for multiple testing.

Associations of IL6 polymorphisms with lung function decline and COPD

PubMed Central

He, Jian-Qing; Foreman, Marilyn G.; Shumansky, Karey; Zhang, Xuekui; Akhabir, Loubna; Sin, Don D; Man, S F Paul; DeMeo, Dawn L.; Litonjua, Augusto A.; Silverman, Edwin K.; Connett, John E; Anthonisen, Nicholas R; Wise, Robert A; Paré, Peter D; Sandford, Andrew J

2010-01-01

Background Interleukin-6 (IL6) is a pleiotropic pro-inflammatory and immunomodulatory cytokine which likely plays an important role in the pathogenesis of COPD. There is a functional single nucleotide polymorphism (SNP), −174G/C, in the promoter region of IL6. We hypothesized that IL6 SNPs influence susceptibility for impaired lung function and COPD in smokers. Methods Seven and 5 SNPs in IL6 were genotyped in two nested case-control samples derived from the Lung Health Study (LHS) based on phenotypes of rate of decline of forced expiratory volume in one second (FEV1) over 5 years and baseline FEV1 at the beginning of the LHS. Serum IL6 concentrations were measured for all subjects. A partially overlapping panel of 9 IL6 SNPs was genotyped in 389 COPD cases from the National Emphysema Treatment Trial (NETT) and 420 controls from the Normative Aging Study (NAS). Results In the LHS, three IL6 SNPs were associated with FEV1 decline (0.023 ≤ P ≤ 0.041 in additive models). Among them the IL6_−174C allele was associated with rapid decline of lung function. The association was more significant in a genotype-based analysis (P = 0.006). In the NETT-NAS study, IL6_−174G/C and four other IL6 SNPs, all of which are in linkage disequilibrium with IL6_−174G/C, were associated with susceptibility to COPD (0.01 ≤ P ≤ 0.04 in additive genetic models). Conclusion Our results suggest that the IL6_−174G/C SNP is associated with rapid decline of FEV1 and susceptibility to COPD in smokers. PMID:19359268

Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease.

PubMed

Yun, Jeong H; Lamb, Andrew; Chase, Robert; Singh, Dave; Parker, Margaret M; Saferali, Aabida; Vestbo, Jørgen; Tal-Singer, Ruth; Castaldi, Peter J; Silverman, Edwin K; Hersh, Craig P

2018-06-01

Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n = 1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n = 1,895). A subset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300 cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300 cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300 cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. Patients with moderate-to-severe COPD and blood eosinophil counts of 300 cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review.

PubMed

Edgar, Ross G; Patel, Mitesh; Bayliss, Susan; Crossley, Diana; Sapey, Elizabeth; Turner, Alice M

2017-01-01

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition predisposing individuals to chronic obstructive pulmonary disease (COPD). The treatment is generally extrapolated from COPD unrelated to AATD; however, most COPD trials exclude AATD patients; thus, this study sought to systematically review AATD-specific literature to assist evidence-based patient management. Standard review methodology was used with meta-analysis and narrative synthesis (PROSPERO-CRD42015019354). Eligible studies were those of any treatment used in severe AATD. Randomized controlled trials (RCTs) were the primary focus; however, case series and uncontrolled studies were eligible. All studies had ≥10 participants receiving treatment or usual care, with baseline and follow-up data (>3 months). Risk of bias was assessed appropriately according to study methodology. In all, 7,296 studies were retrieved from searches; 52 trials with 5,632 participants met the inclusion criteria, of which 26 studies involved alpha-1 antitrypsin augmentation and 17 concerned surgical treatments (largely transplantation). Studies were grouped into four management themes: COPD medical, COPD surgical, AATD specific, and other treatments. Computed tomography (CT) density, forced expiratory volume in 1 s, diffusing capacity of the lungs for carbon monoxide, health status, and exacerbation rates were frequently used as outcomes. Meta-analyses were only possible for RCTs of intravenous augmentation, which slowed progression of emphysema measured by CT density change, 0.79 g/L/year versus placebo ( P =0.002), and associated with a small increase in exacerbations 0.29/year ( P =0.02). Mortality following lung transplant was comparable between AATD- and non-AATD-related COPD. Surgical reduction of lung volume demonstrated inferior outcomes compared with non-AATD-related emphysema. Intravenous augmentation remains the only disease-specific therapy in AATD and there is evidence that this slows decline in emphysema determined by CT density. There is paucity of data around other treatments in AATD. Treatments for usual COPD may not be as efficacious in AATD, and further studies may be required for this disease group.

Age-Related Differences in Health-Related Quality of Life in COPD: An Analysis of the COPDGene and SPIROMICS Cohorts.

PubMed

Martinez, Carlos H; Diaz, Alejandro A; Parulekar, Amit D; Rennard, Stephen I; Kanner, Richard E; Hansel, Nadia N; Couper, David; Holm, Kristen E; Hoth, Karin F; Curtis, Jeffrey L; Martinez, Fernando J; Hanania, Nicola A; Regan, Elizabeth A; Paine, Robert; Cigolle, Christine T; Han, MeiLan K

2016-04-01

Younger persons with COPD report worse health-related quality of life (HRQL) than do older individuals. The factors explaining these differences remain unclear. The objective of this article was to explore factors associated with age-related differences in HRQL in COPD. Cross-sectional analysis of participants with COPD, any Global Initiative for Chronic Obstructive Lung Disease grade of airflow limitation, and ≥ 50 years old in two cohorts: the Genetic Epidemiology of COPD (COPDGene) study and the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). We compared St. George's Respiratory Questionnaire (SGRQ) scores by age group: middle-aged (age, 50-64) vs older (age, 65-80) adults. We used multivariate linear modeling to test associations of age with HRQL, adjusting for demographic and clinical characteristics and comorbidities. Among 4,097 participants in the COPDGene study (2,170 middle-aged and 1,927 older adults) SGRQ total scores were higher (worse) among middle-aged (mean difference, -4.2 points; 95% CI, -5.7 to -2.6; P < .001) than older adults. Age had a statistically significant interaction with dyspnea (P < .001). Greater dyspnea severity (modified Medical Research Council ≥ 2, compared with 0-1) had a stronger association with SGRQ score among middle-aged (β, 24.6; 95% CI, 23.2-25.9) than older-adult (β, 21.0; 95% CI, 19.6-22.3) participants. In analyses using SGRQ as outcome in 1,522 participants in SPIROMICS (598 middle-aged and 924 older adults), we found similar associations, confirming that for the same severity of dyspnea there is a stronger association with HRQL among younger individuals. Age-related differences in HRQL may be explained by a higher impact of dyspnea among younger subjects with COPD. ClinicalTrials.gov; No.: NCT00608764 and No.: NCT01969344; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Angiotensinogen gene M235T and angiotensin II-type 1 receptor gene A/C1166 polymorphisms in chronic obtructive pulmonary disease

PubMed Central

Ayada, Ceylan; Toru, Ümran; Genç, Osman; Şahin, Server; Turgut, Sebahat; Turgut, Günfer

2015-01-01

Chronic obstructive pulmonary disease (COPD) occurs irreversibly and is characterized by progressive airflow obstruction. Renin angiotensin system (RAS) has many different key enzymes and receptors that have a role for different systemic processes. We aimed to determine genotype and allele frequencies of angiotensinogen (AGT) M235T and angiotensin II-type 1 receptor (AT1-R) A/C1166 polymorphisms in patients with COPD. This study was performed on 56 unrelated COPD patients and 29 healthy subjects. DNA samples for each individual were isolated from peripheral blood by phenol/chloroform method, analyzed by polymerase chain reaction and enzymatic digestion methodologies. The distribution for each of AGT genotypes were 23.2% for MM (13), 75.0% for MT (42) and 1.8% for TT (1) in the COPD group; 37.9% for MM (11), 34.5% for MT (10) and 27.6% for TT (8) in the control group. The distribution of AGT genotypes was found significantly different between groups (X2 = 18.604; df = 2; P = 0.000). The frequencies for each of the AT1-R genotypes were found as 53.6% for AA (30), 42.9% for AC (24), 3.6% for CC (2) in the COPD group; 55.2% for AA (16), 41.4% for AC (12) and 3.4% for CC (1) in the control group. The distribution of AT1-R genotypes did not change significantly between groups. Allele frequencies of interested genes were not significantly different between groups. We suggest that AGT polymorphism may play a role for the development of COPD. We believe these data can be served for large scale population genetics research, considering the frequency of AGT and AT1-R genes and alleles in COPD patients in the Turkish population. PMID:26064378

Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases

PubMed Central

Stankovic, Marija; Divac-Rankov, Aleksandra; Petrovic-Stanojevic, Natasa; Mitic-Milikic, Marija; Nagorni-Obradovic, Ljudmila; Radojkovic, Dragica

2012-01-01

Aim: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. Methods: The study included the adults with chronic obstructive pulmonary disease (COPD) (n=348), asthma (n=71), and bronchiectasis (n=35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. Results: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1:5519, 1:38, and 1:5519). Conclusion: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population. PMID:22971141

Risk Factors for Venous Thromboembolism in Chronic Obstructive Pulmonary Disease

PubMed Central

Kim, Victor; Goel, Nishant; Gangar, Jinal; Zhao, Huaqing; Ciccolella, David E.; Silverman, Edwin K.; Crapo, James D.; Criner, Gerard J.

2014-01-01

Background: COPD patients are at increased risk for venous thromboembolism (VTE). VTE however remains under-diagnosed in this population and the clinical profile of VTE in COPD is unclear. Methods: Global initiative for chronic Obstructive Lung Disease (GOLD) stages II-IV participants in the COPD Genetic Epidemiology (COPDGene) study were divided into 2 groups: VTE+, those who reported a history of VTE by questionnaire, and VTE-, those who did not. We compared variables in these 2 groups with either t-test or chi-squared test for continuous and categorical variables, respectively. We performed a univariate logistic regression for VTE, and then a multivariate logistic regression using the significant predictors of interest in the univariate analysis to ascertain the determinants of VTE. Results: The VTE+ group was older, more likely to be Caucasian, had a higher body mass index (BMI), smoking history, used oxygen, had a lower 6-minute walk distance, worse quality of life scores, and more dyspnea and respiratory exacerbations than the VTE- group. Lung function was not different between groups. A greater percentage of the VTE+ group described multiple medical comorbidities. On multivariate analysis, BMI, 6-minute walk distance, pneumothorax, peripheral vascular disease, and congestive heart failure significantly increased the odds for VTE by history. Conclusions: BMI, exercise capacity, and medical comorbidities were significantly associated with VTE in moderate to severe COPD. Clinicians should suspect VTE in patients who present with dyspnea and should consider possibilities other than infection as causes of COPD exacerbation. PMID:25844397

The impact of dual bronchodilation on cardiovascular serious adverse events and mortality in COPD: a quantitative synthesis

PubMed Central

Rogliani, Paola; Matera, Maria Gabriella; Ora, Josuel; Cazzola, Mario; Calzetta, Luigino

2017-01-01

Objective Long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are burdened by the potential risk of inducing cardiovascular serious adverse events (SAEs) in COPD patients. Since the risk of combining a LABA with a LAMA could be greater, we have carried out a quantitative synthesis to investigate the cardiovascular safety profile of LABA/LAMA fixed-dose combinations (FDCs). Methods A pair-wise and network meta-analysis was performed by using the data of the repository database ClinicalTrials.gov concerning the impact of approved LABA/LAMA FDCs versus monocomponents and/or placebo on cardiovascular SAEs in COPD. Results Overall, LABA/LAMA FDCs did not significantly (P>0.05) modulate the risk of cardiovascular SAEs versus monocomponents. However, the network meta-analysis indicated that aclidinium/formoterol 400/12 µg and tiotropium/olodaterol 5/5 µg were the safest FDCs, followed by umeclidinium/vilanterol 62.5/25 µg which was as safe as placebo, whereas glycopyrronium/formoterol 14.9/9.6, glycopyrronium/indacaterol 15.6/27.5 µg, and glycopyrronium/indacaterol 50/110 µg were the least safe FDCs. No impact on mortality was detected for each specific FDC. Conclusion This meta-analysis indicates that LABA/LAMA FDC therapy is characterized by an excellent cardiovascular safety profile in COPD patients. However, the findings of this quantitative synthesis have been obtained from populations that participated in randomized clinical trials, and were devoid of major cardiovascular diseases. Thus, post-marketing surveillance and observational studies may help to better define the real impact of specific FDCs with regard to the cardiovascular risk. PMID:29255354

Understanding influences on the uptake of pulmonary rehabilitation in the East of England: an Inclusive Design/mixed-methods study protocol

PubMed Central

Dickerson, Terry; Early, Frances; Fuld, Jonathan; Clarkson, P John

2018-01-01

Introduction 1.2 million people in the UK have chronic obstructive pulmonary disease (COPD) that causes breathlessness, difficulty with daily activities, infections and hospitalisation. Pulmonary rehabilitation (PR), a programme of supervised exercise and education, is recommended for patients with COPD. However, only 1 in 10 of those who need it receive PR. Also, the UK National COPD Audit Programme concluded that the COPD treatment might not be accessible to people with disabilities. This paper applies an Inclusive Design approach to community-based PR service provisions. It aims to inform improvements to the PR service by identifying barriers to the uptake of PR in the COPD care journey in relation to patients’ capabilities that can affect their access to PR. Methods and analysis The protocol includes four steps. Step 1 will involve interviews with healthcare professionals and patients to gather insight into their experiences and produce a hierarchical task analysis of the COPD care journeys. Step 2 will estimate the service exclusion: the demand of every task on patients’ capabilities will be rated by predefined scales, and the proportion of the population excluded from the service will be estimated by an exclusion calculator. Step 3 will identify the challenges of the PR service; a framework analysis will guide the data analysis of the interviews and care journey. Step 4 will propose recommendations to help patients manage their COPD care informed by the challenges identified in step 3 and refine recommendations through interviews and focus groups. Ethics and dissemination The Cambridge Central Research Ethics Committee gave the study protocol a positive ethical opinion (17/EE/0136). Study results will be disseminated through peer-reviewed journals, conferences and the British Lung Foundation networks. They will also be fed into a Research for Patient Benefit project on increasing the referral and uptake of PR. PMID:29691248

Real-Time Environmental Sensors to Improve Health in the Sensing City

NASA Astrophysics Data System (ADS)

Marek, L.; Campbell, M.; Epton, M.; Storer, M.; Kingham, S.

2016-06-01

The opportunity of an emerging smart city in post-disaster Christchurch has been explored as a way to improve the quality of life of people suffering Chronic Obstructive Pulmonary Disease (COPD), which is a progressive disease that affects respiratory function. It affects 1 in 15 New Zealanders and is the 4th largest cause of death, with significant costs to the health system. While, cigarette smoking is the leading cause of COPD, long-term exposure to other lung irritants, such as air pollution, chemical fumes, or dust can also cause and exacerbate it. Currently, we do know little what happens to the patients with COPD after they leave a doctor's care. By learning more about patients' movements in space and time, we can better understand the impacts of both the environment and personal mobility on the disease. This research is studying patients with COPD by using GPS-enabled smartphones, combined with the data about their spatiotemporal movements and information about their actual usage of medication in near real-time. We measure environmental data in the city, including air pollution, humidity and temperature and how this may subsequently be associated with COPD symptoms. In addition to the existing air quality monitoring network, to improve the spatial scale of our analysis, we deployed a series of low-cost Internet of Things (IoT) air quality sensors as well. The study demonstrates how health devices, smartphones and IoT sensors are becoming a part of a new health data ecosystem and how their usage could provide information about high-risk health hotspots, which, in the longer term, could lead to improvement in the quality of life for patients with COPD.

Features of a Mobile Support App for Patients With Chronic Obstructive Pulmonary Disease: Literature Review and Current Applications.

PubMed

Sobnath, Drishty D; Philip, Nada; Kayyali, Reem; Nabhani-Gebara, Shereen; Pierscionek, Barbara; Vaes, Anouk W; Spruit, Martijn A; Kaimakamis, Evangelos

2017-02-20

Chronic obstructive pulmonary disease (COPD) is a serious long-term lung disease in which the airflow from the lungs is progressively reduced. By 2030, COPD will become the third cause of mortality and seventh cause of morbidity worldwide. With advances in technology and mobile communications, significant progress in the mobile health (mHealth) sector has been recently observed. Mobile phones with app capabilities (smartphones) are now considered as potential media for the self-management of certain types of diseases such as asthma, cancer, COPD, or cardiovascular diseases. While many mobile apps for patients with COPD are currently found on the market, there is little published material on the effectiveness of most of them, their features, and their adoption in health care settings. The aim of this study was to search the literature for current systems related to COPD and identify any missing links and studies that were carried out to evaluate the effectiveness of COPD mobile apps. In addition, we reviewed existing mHealth apps from different stores in order to identify features that can be considered in the initial design of a COPD support tool to improve health care services and patient outcomes. In total, 206 articles related to COPD management systems were identified from different databases. Irrelevant materials and duplicates were excluded. Of those, 38 articles were reviewed to extract important features. We identified 214 apps from online stores. Following exclusion of irrelevant apps, 48 were selected and 20 of them were downloaded to review some of their common features. Our review found that out of the 20 apps downloaded, 13 (65%, 13/20) had an education section, 5 (25%, 5/20) consisted of medication and guidelines, 6 (30%, 6/20) included a calendar or diary and other features such as reminders or symptom tracking. There was little published material on the effectiveness of the identified COPD apps. Features such as (1) a social networking tool; (2) personalized education; (3) feedback; (4) e-coaching; and (5) psychological motivation to enhance behavioral change were found to be missing in many of the downloaded apps. This paper summarizes the features of a COPD patient-support mobile app that can be taken into consideration for the initial design of an integrated care system to encourage the self-management of their condition at home. ©Drishty D Sobnath, Nada Philip, Reem Kayyali, Shereen Nabhani-Gebara, Barbara Pierscionek, Anouk W Vaes, Martijn A Spruit, Evangelos Kaimakamis. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 20.02.2017.

Respiratory motor training and neuromuscular plasticity in patients with chronic obstructive pulmonary disease: A pilot study.

PubMed

Ovechkin, Alexander V; Sayenko, Dimitry G; Ovechkina, Elena N; Aslan, Sevda C; Pitts, Teresa; Folz, Rodney J

2016-07-15

The objective of this study was to examine the feasibility of a full-scale investigation of the neurophysiological mechanisms of COPD-induced respiratory neuromuscular control deficits. Characterization of respiratory single- and multi-muscle activation patterns using surface electromyography (sEMG) were assessed along with functional measures at baseline and following 21±2 (mean±SD) sessions of respiratory motor training (RMT) performed during a one-month period in four patients with GOLD stage II or III COPD. Pre-training, the individuals with COPD showed significantly increased (p<0.05) overall respiratory muscle activity and disorganized multi-muscle activation patterns in association with lowered spirometrical measures and decreased fast- and slow-twitch fiber activity as compared to healthy controls (N=4). Following RMT, functional and respiratory sEMG activation outcomes during quite breathing and forced expiratory efforts were improved suggesting that functional improvements, induced by task-specific RMT, are evidence respiratory neuromuscular networks re-organization. Published by Elsevier B.V.

Early Detection of Peak Demand Days of Chronic Respiratory Diseases Emergency Department Visits Using Artificial Neural Networks.

PubMed

Khatri, Krishan L; Tamil, Lakshman S

2018-01-01

Chronic respiratory diseases, mainly asthma and chronic obstructive pulmonary disease (COPD), affect the lives of people by limiting their activities in various aspects. Overcrowding of hospital emergency departments (EDs) due to respiratory diseases in certain weather and environmental pollution conditions results in the degradation of quality of medical care, and even limits its availability. A useful tool for ED managers would be to forecast peak demand days so that they can take steps to improve the availability of medical care. In this paper, we developed an artificial neural network based classifier using multilayer perceptron with back propagation algorithm that predicts peak event (peak demand days) of patients with respiratory diseases, mainly asthma and COPD visiting EDs in Dallas County of Texas in the United States. The precision and recall for peak event class were 77.1% and 78.0%, respectively, and those for nonpeak events were 83.9% and 83.2%, respectively. The overall accuracy of the system is 81.0%.

Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene.

PubMed

Wan, Emily S; Castaldi, Peter J; Cho, Michael H; Hokanson, John E; Regan, Elizabeth A; Make, Barry J; Beaty, Terri H; Han, MeiLan K; Curtis, Jeffrey L; Curran-Everett, Douglas; Lynch, David A; DeMeo, Dawn L; Crapo, James D; Silverman, Edwin K

2014-08-06

Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported. Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering. The prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter's syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative "COPD-subtype", "Restrictive-subtype", and a highly symptomatic "Metabolic-subtype". PRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted. Clinicaltrials.gov Identifier: NCT000608764.

Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter Syndrome

PubMed Central

Wan, Emily S.; Qiu, Weiliang; Morrow, Jarrett; Beaty, Terri H.; Hetmanski, Jacqueline; Make, Barry J.; Lomas, David A.; Silverman, Edwin K.; DeMeo, Dawn L.

2015-01-01

Klinefelter syndrome (KS) (47 XXY) is a common sex-chromosome aneuploidy with an estimated prevalence of 1 in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary X chromosome; systematic investigations of the epigenome have been limited. We obtained genome-wide DNA methylation data from peripheral blood using the Illumina HumanMethylation450K platform in 5 KS (47 XXY), 102 male (46 XY), and 113 female (46 XX) control subjects participating in the chronic obstructive pulmonary disease (COPD) Gene Study. Empirical Bayes-mediated models were used to test for differential methylation by KS status. CpG sites with a false-discovery rate <0.05 from the first-generation HumanMethylation27K platform were further examined in an independent replication cohort of 2 KS subjects, 590 male, and 495 female controls drawn from the International COPD Genetics Network (ICGN). Differential methylation at sites throughout the genome were identified, including 86 CpG sites that were differentially methylated in KS subjects relative to both male and female controls. CpG sites annotated to the HEN1 methyltransferase homolog 1 (HENMT1), calcyclin-binding protein (CACYBP), and GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) genes were among the “KS-specific” loci that were replicated in ICGN. We therefore conclude that site-specific differential methylation exists throughout the genome in KS. The functional impact and clinical relevance of these differentially methylated loci should be explored in future studies. PMID:25988574

[Evaluation of therapy efficiency in patients with combined course of copd and osteoarthritis].

PubMed

Хайменова, Галина С; Шилкина, Людмила Н; Бабанина, Марина Ю; Волченко, Григорий В; Ткаченко, Максим В; Ждан, Вячеслав Н

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a disease that is characterized by chronic airflow limitation, a variety of pathological changes in the lungs, significant extrapulmonary manifestations, and severe comorbidities which may further aggravate the course of COPD [GOLD, 2013]. Intensity of systemic manifestations increases with the progression of obstruction, therefore the abovementioned symptoms are often overlooked and become apparent in the later stages of the disease. Systemic manifestations impair the quality of life, lead to early disability and significantly contribute to mortality in patients with COPD. Diseases of cardiovascular and musculoskeletal systems are the most serious and socially significant systemic manifestations of chronic obstructive pulmonary disease. Currently, there is no doubt that the activation of non-specific and specific immune responses in patients with COPD is associated with the influence of a number of universal mediators, among which a special place belongs to the cytokine network that controls implementation processes of the immune and inflammatory reactivity. The aim of our work was to increase the effectiveness of treatment in patients with chronic obstructive pulmonary disease in combination with osteoarthritis based on the study of clinical course, assessment of patient's life quality and substantiation of pharmacological correction. The work was conducted on the basis of Poltava Regional Clinical Hospital named after N.V. Sklifosovskiy. The study was carried out at Research Institute for Genetics and Immunological Grounds of Pathology and Pharmacogenetics of Higher State Educational Establishment of Ukraine "Ukrainian Medical Stomatological Academy" (HSEEU "UMUMCA"). The study involved 40 patients with an average age of 54.4 ± 3.1 years with acute exacerbation of COPD (clinical group B-C - GOLD II-III), in combination with OA. The duration of COPD was 16.2 ± 2.1 years. Among patients there were 28 (70%) men and 12 (30%) women. All patients were smokers; the smoking period was 32.4 ± 2.9 pack-years. OA in the phase of unstable remission was verified in all patients, large joints were involved - knee, shoulder, and ankle. Depending on the chosen option of treatment, patients were divided into two representative groups - I and II. Patients of group I received only standard treatment for COPD in accordance with existing protocols, and in group II fenspiride hydrochloride 80 mg 2 times a day was added to the basic therapy for 12 days. Full examination of patients was carried out at admission and after 3 months from the date of admission. According to the study, on addition of fenspiride to basic therapy in patients with constellation of COPD and OA, the regression of disease (reduction in cough) was observed by 2.9 ± 0.4 days earlier, dyspnea by 2.3 ± 0.33 than in the comparison group (p < 0.05), quality of life improved, and exercise tolerance increased. FEV1 in patients of group I after 3 months amounted to 62.6 ± 4.2%, in group II - 68.1 ± 4.9%, recurrence of airflow obstruction in both groups increased: in group I - by 4.2 ± 1.1%, in group II - by 5.6 ± 1.5%. Adding fenspiride hydrochloride to the treatment significantly improved the life quality of patients with COPD combined with OA at all scales of SF-36 questionnaire, reflecting the patient's physical condition, namely, physical activity, the role of physical problems in vital functions, the intensity of pain, overall health status, vitality. After 3 months of follow-up, in patients with comorbidity influenced by fenspiride hydrochloride against the background of traditional pathogenic therapy, the indicators of VAS significantly decreased by 1.9 times (3.18 ± 0.24 cm versus 6.01 ± 0.59 cm, p <0, 05), Lequesne index - by 2.0 times (9.42 ± 1.81 points against 19.17 ± 4.15 points, p <0.05) and WOM AC by 1.6 times (38.7 ± 3.7 points against 63.8 ± 8.3 points, p <0.05), respectively. In patients of group II, a more pronounced positive dynamics of reducing inflammatory activity, confirmed by the decrease in TNF-α content by 1.9 times (61.8 ± 5.9 pg / ml versus 131.5 ± 6.9 pg / ml, p <0.001) was observed. The hospitalization period of patients in group I was 14.3 ± 0.4 days, in group II it was less and amounted to 12.9 ± 0.5 days. Supplementary application of fenspiride hydrochloride in the treatment of COPD patients in combination with OA improves the outcomes of patients' treatment, quality of life and prolongation of remission, indicating a decrease in the severity of systemic inflammation.

Association of SERPINE2 With Asthma

PubMed Central

Klanderman, Barbara; Ziniti, John; Senter-Sylvia, Jody; Soto-Quiros, Manuel E.; Avila, Lydiana; Celedón, Juan C.; Lange, Christoph; Mariani, Thomas J.; Lasky-Su, Jessica; Hersh, Craig P.; Raby, Benjamin A.; Silverman, Edwin K.; Weiss, Scott T.; DeMeo, Dawn L.

2011-01-01

Background: The “Dutch hypothesis” suggests that asthma and COPD have common genetic determinants. The serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 (SERPINE2) gene previously has been associated with COPD. We sought to determine whether SERPINE2 is associated with asthma and asthma-related phenotypes. Methods: We measured the association of 39 SERPINE2 single-nucleotide polymorphisms (SNPs) with asthma-related phenotypes in 655 parent-child trios from the Childhood Asthma Management Program (CAMP), and we measured the association of 19 SERPINE2 SNPs with asthma in a case-control design of 359 CAMP probands and 846 population control subjects. We attempted to replicate primary asthma-related phenotype findings in one independent population and primary asthma affection status findings in two independent populations. We compared association results with CAMP proband expression quantitative trait loci. Results: Nine of 39 SNPs had P < .05 for at least one phenotype in CAMP, and two of these replicated in an independent population of 426 people with childhood asthma. Six of 19 SNPs had P < .05 for association with asthma in CAMP/Illumina. None of these replicated in two independent populations. The expression quantitative trait loci revealed that five SNPs associated with asthma in CAMP/Illumina and one SNP associated with FEV1 in CAMP are strongly correlated with SERPINE2 expression levels. Comparison of results to previous COPD studies identified five SNPs associated with both asthma- and COPD-related phenotypes. Conclusions: Our results weakly support SERPINE2 as a Dutch hypothesis candidate gene through nominally significant associations with asthma and related traits. Further study of SERPINE2 is necessary to verify its involvement in asthma and COPD. PMID:21436250

Development and Validation of a Predictive Model to Identify Individuals Likely to Have Undiagnosed Chronic Obstructive Pulmonary Disease Using an Administrative Claims Database.

PubMed

Moretz, Chad; Zhou, Yunping; Dhamane, Amol D; Burslem, Kate; Saverno, Kim; Jain, Gagan; Devercelli, Giovanna; Kaila, Shuchita; Ellis, Jeffrey J; Hernandez, Gemzel; Renda, Andrew

2015-12-01

Despite the importance of early detection, delayed diagnosis of chronic obstructive pulmonary disease (COPD) is relatively common. Approximately 12 million people in the United States have undiagnosed COPD. Diagnosis of COPD is essential for the timely implementation of interventions, such as smoking cessation programs, drug therapies, and pulmonary rehabilitation, which are aimed at improving outcomes and slowing disease progression. To develop and validate a predictive model to identify patients likely to have undiagnosed COPD using administrative claims data. A predictive model was developed and validated utilizing a retro-spective cohort of patients with and without a COPD diagnosis (cases and controls), aged 40-89, with a minimum of 24 months of continuous health plan enrollment (Medicare Advantage Prescription Drug [MAPD] and commercial plans), and identified between January 1, 2009, and December 31, 2012, using Humana's claims database. Stratified random sampling based on plan type (commercial or MAPD) and index year was performed to ensure that cases and controls had a similar distribution of these variables. Cases and controls were compared to identify demographic, clinical, and health care resource utilization (HCRU) characteristics associated with a COPD diagnosis. Stepwise logistic regression (SLR), neural networking, and decision trees were used to develop a series of models. The models were trained, validated, and tested on randomly partitioned subsets of the sample (Training, Validation, and Test data subsets). Measures used to evaluate and compare the models included area under the curve (AUC); index of the receiver operating characteristics (ROC) curve; sensitivity, specificity, positive predictive value (PPV); and negative predictive value (NPV). The optimal model was selected based on AUC index on the Test data subset. A total of 50,880 cases and 50,880 controls were included, with MAPD patients comprising 92% of the study population. Compared with controls, cases had a statistically significantly higher comorbidity burden and HCRU (including hospitalizations, emergency room visits, and medical procedures). The optimal predictive model was generated using SLR, which included 34 variables that were statistically significantly associated with a COPD diagnosis. After adjusting for covariates, anticholinergic bronchodilators (OR = 3.336) and tobacco cessation counseling (OR = 2.871) were found to have a large influence on the model. The final predictive model had an AUC of 0.754, sensitivity of 60%, specificity of 78%, PPV of 73%, and an NPV of 66%. This claims-based predictive model provides an acceptable level of accuracy in identifying patients likely to have undiagnosed COPD in a large national health plan. Identification of patients with undiagnosed COPD may enable timely management and lead to improved health outcomes and reduced COPD-related health care expenditures.

Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease.

PubMed

Yu, Lianchun; De Mazancourt, Marine; Hess, Agathe; Ashadi, Fakhrul R; Klein, Isabelle; Mal, Hervé; Courbage, Maurice; Mangin, Laurence

2016-08-01

Breathing involves a complex interplay between the brainstem automatic network and cortical voluntary command. How these brain regions communicate at rest or during inspiratory loading is unknown. This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. Hum Brain Mapp 37:2736-2754, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Cost effectiveness of pharmacological maintenance treatment for chronic obstructive pulmonary disease: a review of the evidence and methodological issues.

PubMed

Rutten-van Mölken, Maureen P M H; Goossens, Lucas M A

2012-04-01

Over 200 million people have chronic obstructive pulmonary disease (COPD) worldwide. The number of disease-year equivalents and deaths attributable to COPD are high. Guidelines for the pharmacological treatment of the disease recommend an individualized step-up approach in which treatment is intensified when results are unsatisfactory. Our objective was to present a systematic review of the cost effectiveness of pharmacological maintenance treatment for COPD and to discuss the methodological strengths and weaknesses of the studies. A systematic literature search for economic evaluations of drug therapy in COPD was performed in MEDLINE, EMBASE, the Economic Evaluation Database of the UK NHS (NHS-EED) and the European Network of Health Economic Evaluation Databases (EURONHEED). Full economic evaluations presenting both costs and health outcomes were included. A total of 40 studies were included in the review. Of these, 16 were linked to a clinical trial, 14 used Markov models, eight were based on observational data and two used a different approach. The few studies on combining short-acting bronchodilators were consistent in finding net cost savings compared with monotherapy. Studies comparing inhaled corticosteroids (ICS) with placebo or no maintenance treatment reported inconsistent results. Studies comparing fluticasone with salmeterol consistently found salmeterol to be more cost effective. The cost-effectiveness studies of tiotropium versus placebo, ipratropium or salmeterol pointed towards a reduction in total COPD-related healthcare costs for tiotropium in many but not all studies. All of these studies reported additional health benefits of tiotropium. The cost-effectiveness studies of the combination of inhaled long-acting β₂-agonists and ICS all report additional health benefits at an increase in total COPD-related costs in most studies. The cost-per-QALY estimates of this combination treatment vary widely and are very sensitive to the assumptions on mortality benefit and time horizon. The currently available economic evaluations indicate differences in cost effectiveness between COPD maintenance therapies, but for a more meaningful comparison of results it is important to improve the consistency with respect to study methodology and choice of comparator.

Understanding influences on the uptake of pulmonary rehabilitation in the East of England: an Inclusive Design/mixed-methods study protocol.

PubMed

Liu, Yuanyuan; Dickerson, Terry; Early, Frances; Fuld, Jonathan; Clarkson, P John

2018-04-24

1.2 million people in the UK have chronic obstructive pulmonary disease (COPD) that causes breathlessness, difficulty with daily activities, infections and hospitalisation. Pulmonary rehabilitation (PR), a programme of supervised exercise and education, is recommended for patients with COPD. However, only 1 in 10 of those who need it receive PR. Also, the UK National COPD Audit Programme concluded that the COPD treatment might not be accessible to people with disabilities. This paper applies an Inclusive Design approach to community-based PR service provisions. It aims to inform improvements to the PR service by identifying barriers to the uptake of PR in the COPD care journey in relation to patients' capabilities that can affect their access to PR. The protocol includes four steps. Step 1 will involve interviews with healthcare professionals and patients to gather insight into their experiences and produce a hierarchical task analysis of the COPD care journeys. Step 2 will estimate the service exclusion: the demand of every task on patients' capabilities will be rated by predefined scales, and the proportion of the population excluded from the service will be estimated by an exclusion calculator. Step 3 will identify the challenges of the PR service; a framework analysis will guide the data analysis of the interviews and care journey. Step 4 will propose recommendations to help patients manage their COPD care informed by the challenges identified in step 3 and refine recommendations through interviews and focus groups. The Cambridge Central Research Ethics Committee gave the study protocol a positive ethical opinion (17/EE/0136). Study results will be disseminated through peer-reviewed journals, conferences and the British Lung Foundation networks. They will also be fed into a Research for Patient Benefit project on increasing the referral and uptake of PR. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Life Impact and Treatment Preferences of Individuals with Asthma and Chronic Obstructive Pulmonary Disease: Results from Qualitative Interviews and Focus Groups.

PubMed

Svedsater, Henrik; Roberts, June; Patel, Chloe; Macey, Jake; Hilton, Emma; Bradshaw, Lisa

2017-06-01

The impact of asthma and chronic obstructive pulmonary disease (COPD) on individuals' lives may be substantial, yet clinical practice often focuses only on symptoms. We aimed to better understand the perspective of asthma or COPD patients and to identify condition-related burden, life impact, priorities, unmet needs, and treatment goals. Individuals aged at least 18 years with asthma or COPD were identified by a recruitment panel via clinical referrals, support groups, consumer networks, and a patient database. Interviews were carried out individually (by telephone) or in focus groups (with no more than five participants per group). A semi-structured interview guide was used with prespecified topics, informed by a literature review, that were considered impactful in asthma or COPD (symptoms and daily-life impact, satisfaction with current treatment, important aspects of treatment, adherence, and ideal treatment). Overall, 72 people participated in focus groups/individual interviews (asthma n = 18/n = 21; COPD n = 15/n = 18). "Shortness of breath" was the most frequently reported symptom; however, participants discussed the life impact of their condition more than symptoms alone. Reported physical impacts included the inability to sleep and socialize, while emotional impacts included "embarrassment, stigma, and/or self-consciousness", "fear and/or panic", and "sadness, anxiety, and/or depression". Coping mechanisms for normal activities included continuing at reduced pace and avoidance. Treatment preferences centered on resolving impacts; improved sleep, "speed of action", and "length of relief" were the most frequently reported ideal treatment factors. Patients with asthma or COPD experience substantial quality of life limitations and tend to focus on these in their expressions of concern, rather than symptoms per se. Life impacts of these conditions may have implications beyond those commonly appreciated in routine practice; these considerations will be applied to a future discrete choice experiment survey. GSK funded study (H0-15-15502/204821).

Genetic polymorphisms of surfactant protein D rs2243639, Interleukin (IL)-1β rs16944 and IL-1RN rs2234663 in chronic obstructive pulmonary disease, healthy smokers, and non-smokers.

PubMed

Issac, Marianne Samir M; Ashur, Wafaa; Mousa, Heba

2014-06-01

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of this study was to investigate the association between surfactant protein D (SFTPD) rs2243639, interleukin (IL)-1β rs16944 and IL-1 receptor antagonist (IL-1RN) rs2234663 gene polymorphisms and COPD susceptibility, as well as examining the association between the various IL-1RN/IL-1β haplotypes and pulmonary function tests (PFT). Secondly, we aimed to examine the influence of SFTPD rs2243639 polymorphism on serum surfactant protein D (SP-D) level. A total of 114 subjects were recruited in this study and divided into three groups: 63 COPD patients, 25 asymptomatic smokers, and 26 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for the detection of SFTPD rs2243639 and IL-1β rs16944 polymorphisms. Detection of variable numbers of an 86-bp tandem repeat (VNTR) of IL-1RN was done using PCR. Serum SP-D level was measured using enzyme linked-immunosorbent assay. PFTs were measured by spirometry. Carriers of the SFTPD AG and AA polymorphic genotypes constituted 71.4 % of COPD patients versus 48 % in asymptomatic smokers, with a statistically significant difference between the two groups (p = 0.049). Smokers who were carriers of the polymorphic SFTPD rs2243639 A allele (AG and AA genotypes) have a 2.708 times risk of developing COPD when compared with wild-type GG genotype carriers [odds ratio (OR) 2.708 (95 % CI 1.041-7.047)]. Forced expiratory flow (FEF) 25-75 % predicted was higher in IL-1RN*1/*1 when compared with *1/*2 (p = 0.013). FEF25-75 % predicted in carriers of haplotype IL-1RN *1/IL-1β T (49.21 ± 10.26) was statistically significantly higher than in carriers of IL-1RN *2/IL-1β T (39.67 ± 12.64) [p = 0.005]. Forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) in carriers of haplotype IL-1RN *1/IL-1β T (64.09 ± 6.39) was statistically significantly higher than in carriers of IL-1RN *2/IL-1βT (59.44 ± 7.71) [p = 0.048]. There was no association between SFTPD rs2243639 genotypes and serum SP-D level. Smokers who are carriers of the SFTPD AG and AA polymorphic genotypes may be at a higher risk of developing COPD when compared with wild-type GG genotype carriers. IL-1RN rs2234663/IL-1β rs16944 haplotypes influence FEF25-75 % predicted and FEV1/FVC. SFTPD rs2243639 polymorphism did not influence serum SP-D levels in our group of recruited subjects.

The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.

PubMed

Gai, Liping; Liu, Hui; Cui, Jing-Hui; Yu, Weijian; Ding, Xiao-Dong

2017-03-20

The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis. Copyright © 2016. Published by Elsevier B.V.

Chronic obstructive pulmonary disease history assessment in Spain: a multidimensional chronic obstructive pulmonary disease evaluation. Study methods and organization.

PubMed

López-Campos, José Luis; Peces-Barba, Germán; Soler-Cataluña, Juan José; Soriano, Joan B; de Lucas Ramos, Pilar; de-Torres, Juan P; Marín, José M; Casanova, Ciro

2012-12-01

This present paper describes the method and the organization of the study known as the COPD History Assessment In SpaiN (CHAIN), whose main objective is to evaluate the long-term natural history of a chronic obstructive pulmonary disease (COPD) patient cohort from a multidimensional standpoint and to identify clinical phenotypes, in comparison with another non-COPD control cohort. CHAIN is a multicenter, observational study of prospective cohorts carried out at 36 Spanish hospitals. Both cohorts will be followed-up during a 5-year study period with complete office visits every 12 months and telephone interviews every 6 months in order to evaluate exacerbations and the vital state of the subjects. The recruitment period for cases was between 15 January 2010 and 31 March 2012. At each annual visit, information will be collected on: (i) clinical aspects (socio-economic situation, anthropometric data, comorbidities, smoking, respiratory symptoms, exacerbations, quality of life, anxiety-depression scale, daily life activities, treatments); (ii) respiratory function (spirometry, blood gases, hyperinflation, diffusion, respiratory pressures); (iii) BODE index (main study variable); (iv) peripheral muscle function, and (v) blood work-up (including IgE and cardiovascular risk factors). In addition, a serum bank will be created for the future determination of biomarkers. The data of the patients are anonymized in a database with a hierarchical access control in order to guarantee secure information access. The CHAIN study will provide information about the progression of COPD and it will establish a network of researchers for future projects related with COPD. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

Improving care for advanced COPD through practice change: Experiences of participation in a Canadian spread collaborative

PubMed Central

Verma, Jennifer Y; Amar, Claudia; Sibbald, Shannon

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of death, morbidity, and health-care spending. The Halifax, Nova Scotia-based INSPIRED COPD Outreach Program™ has proved highly beneficial for patients and the health-care system. With direct investment of <$1-million CAD, a pan-Canadian quality improvement collaborative (QIC) supported the spread of INSPIRED to 19 teams in the 10 Canadian provinces contingent upon participation in evaluation. The collaborative evaluation followed a mixed-methods summative approach relying on collated quantitative data, team documents, and surveys sent to core members of the 19 teams. Survey questions included a series of multiple-choice responses, Likert scale ratings, and open-ended questions. The qualitative evaluation entailed key informant interviews and focus groups undertaken between February and April 2016 post-collaborative. Teams reported that the year-long QIC helped bring focus to a needed, though often overlooked area of improvement, facilitating innovation spread. They report examples of new work practices as well as unanticipated cultural change (given the short QIC time frame). Most teams gained new skills in quality improvement (QI) and evidence-based medicine, showing progress in their ability to measure and implement COPD care improvements. Teams felt networking with other teams across the country toward a common solution as well as learning from a team of clinical innovators and evidence-based innovation were critical to their success. Factors affecting sustainability included local leadership support, involvement of frontline clinicians, and sharing milestones to motivate continued QI. The INSPIRED QIC enabled teams across Canada to adapt and implement a new COPD care model for high users of health-care with rapid improvements to work practices, cultural change, and skill sets, and at relatively low cost. PMID:28612657

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

PubMed

Sun, Wei; Kechris, Katerina; Jacobson, Sean; Drummond, M Bradley; Hawkins, Gregory A; Yang, Jenny; Chen, Ting-Huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R Graham; Basta, Patricia V; Bleecker, Eugene R; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H; Comellas, Alejandro; Crapo, James D; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A; Couper, David J; Curtis, Jeffrey L; Doerschuk, Claire M; Freeman, Christine M; Gouskova, Natalia A; Han, MeiLan K; Hanania, Nicola A; Hansel, Nadia N; Hersh, Craig P; Hoffman, Eric A; Kaner, Robert J; Kanner, Richard E; Kleerup, Eric C; Lutz, Sharon; Martinez, Fernando J; Meyers, Deborah A; Peters, Stephen P; Regan, Elizabeth A; Rennard, Stephen I; Scholand, Mary Beth; Silverman, Edwin K; Woodruff, Prescott G; O'Neal, Wanda K; Bowler, Russell P

2016-08-01

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10-10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group.

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

PubMed Central

Drummond, M. Bradley; Hawkins, Gregory A.; Yang, Jenny; Chen, Ting-huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R. Graham; Bleecker, Eugene R.; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H.; Comellas, Alejandro; Crapo, James D.; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A.; Couper, David J.; Doerschuk, Claire M.; Freeman, Christine M.; Gouskova, Natalia A.; Han, MeiLan K.; Hanania, Nicola A.; Hansel, Nadia N.; Hersh, Craig P.; Hoffman, Eric A.; Kaner, Robert J.; Kanner, Richard E.; Kleerup, Eric C.; Lutz, Sharon; Martinez, Fernando J.; Meyers, Deborah A.; Peters, Stephen P.; Regan, Elizabeth A.; Rennard, Stephen I.; Scholand, Mary Beth; Silverman, Edwin K.; Woodruff, Prescott G.; O’Neal, Wanda K.; Bowler, Russell P.

2016-01-01

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group. PMID:27532455

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1

PubMed Central

Won, Sungho; Mattheisen, Manuel; Castaldi, Peter J.; Cho, Michael H.; Rutten, Erica; Hardin, Megan; Yip, Wai‐Ki; Rennard, Stephen I.; Lomas, David A.; Wouters, Emiel F.M.; Agusti, Alvar; Casaburi, Richard; Lange, Christoph P.; O'Connor, George; Hersh, Craig P.; Silverman, Edwin K.

2017-01-01

Abstract Background There have been a number of candidate gene association studies of cancer cachexia‐related traits, but no genome‐wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. Methods A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single‐nucleotide polymorphisms (SNPs). Results Two SNPs reached a level of genome‐wide significance (P < 5 × 10−8) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10−8); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10−8). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (β meta‐analyis = 0.10, P meta‐analyis = 9.3 × 10−10). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. Conclusions In sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases. PMID:28044437

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1.

PubMed

McDonald, Merry-Lynn Noelle; Won, Sungho; Mattheisen, Manuel; Castaldi, Peter J; Cho, Michael H; Rutten, Erica; Hardin, Megan; Yip, Wai-Ki; Rennard, Stephen I; Lomas, David A; Wouters, Emiel F M; Agusti, Alvar; Casaburi, Richard; Lange, Christoph P; O'Connor, George; Hersh, Craig P; Silverman, Edwin K

2017-06-01

There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162). Four GWAS of ΔBMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single-nucleotide polymorphisms (SNPs). Two SNPs reached a level of genome-wide significance (P < 5 × 10 -8 ) with ΔBMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (β = 0.13, P = 4.3 × 10 -8 ); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (β = 0.10, P = 1.9 × 10 -8 ). The DOCK1 SNP association replicated in the ΔBMI GWAS among COPD cases (β meta-analyis  = 0.10, P meta-analyis  = 9.3 × 10 -10 ). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. In sum, one statistically significant common variant in the DOCK1 gene was associated with ΔBMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ΔBMI in complex diseases. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Evaluation of a Therapeutic Interchange from Fluticasone/Salmeterol to Mometasone/Formoterol in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Yip, Elaine; Karimi, Sahar; Pien, Linda T

2016-04-01

Combination treatment with an inhaled corticosteroid and long-acting beta2-agonist is among the many treatment options for chronic obstructive pulmonary disease (COPD) that has been shown to improve clinical outcomes. While mometasone/formoterol does not currently have an FDA-approved indication for COPD, evidence from 2 phase 3 trials demonstrated that mometasone/formoterol can improve lung function and was well tolerated in patients with moderate-to-very severe COPD. Based on these data, a therapeutic interchange was implemented in the Kaiser Permanente Mid-Atlantic States region to convert patients with a COPD diagnosis from fluticasone/salmeterol to mometasone/formoterol. To evaluate the impact of a therapeutic interchange from fluticasone/salmeterol to mometasone/formoterol on health outcomes in patients with COPD in a large ambulatory and managed care setting. The investigators retrospectively reviewed the electronic medical records of patients with a COPD diagnosis who had a prescription for fluticasone/salmeterol converted to mometasone/formoterol between March 6, 2011, to March 6, 2013. Kaiser Permanente's Pharmacy and Therapeutics Committee provided recommended equivalent doses for conversion from fluticasone/salmeterol to mometasone/formoterol. Nonetheless, the final approval for the change in medication and selection of the dose was left to each physician's clinical judgment. Patients were excluded if they were (a) prescribed fluticasone/salmeterol 100/50 mcg, which has no equivalent mometasone/formoterol dose; (b) less than aged 18 years; or (c) prescribed fluticasone/salmeterol for a duration of less than 6 months preconversion to mometasone/formoterol. In addition, patients who left the Kaiser Permanente network or became deceased during the study period of interest were excluded. After the application of the inclusion and exclusion criteria, 521 patients were included in the data analysis. The primary endpoint was the determination of the difference in the occurrence of COPD exacerbations 6 months pre- and postconversion from fluticasone/salmeterol to mometasone/formoterol. COPD exacerbations were defined by the diagnosis or documentation of a COPD exacerbation during any hospitalizations, urgent care (UC)/emergency department (ED) visits, or clinic encounters. Secondary outcomes included the determination of the difference in the occurrence of intensive care unit admissions, hospitalizations, UC/ED visits, and clinic encounters for COPD exacerbations 6 months pre- and postconversion; number of patients who required modification in therapy; and any reasons for mometasone/for-moterol discontinuation postconversion. Patients served as their own controls to compare any differences in outcomes while taking mometasone/formoterol versus fluticasone/salmeterol. Within our patient population, 34.2% (n = 178) of patients experienced at least 1 COPD exacerbation while prescribed fluticasone/salmeterol compared with 28.6% (n = 149) of patients while prescribed mometasone/formoterol (P = 0.030). Mometasone/formoterol therapy did not demonstrate any statistically significant differences in the secondary outcomes (P < 0.050). A later subgroup analysis of the primary outcome revealed that factors associated with a statistically significant decrease in the occurrence of COPD exacerbations were male sex (P = 0.023), comorbid asthma (P = 0.026), and conversion from fluticasone/salmeterol to a more potent dose of mometasone/formoterol (P = 0.014). There was a statistically significant decrease in the proportion of patients who experienced COPD exacerbations postconversion from fluticasone/salmeterol to mometasone/formoterol. This study is an example of a real-world therapeutic interchange that provides additional data to support the use of mometasone/formoterol for its unlabeled COPD indication. No outside funding supported this study. The authors report no financial or other conflicts of interest related to the subject of this article. All authors contributed to study design and manuscript revision. Yip collected and analyzed data and prepared the manuscript.

Examining the Effects of Age on Health Outcomes of Chronic Obstructive Pulmonary Disease: Results From the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate Endpoints Cohorts.

PubMed

Parulekar, Amit D; Martinez, Carlos; Tsai, Chu-Lin; Locantore, Nicholas; Atik, Mustafa; Yohannes, Abebaw M; Kao, Christina C; Al-Azzawi, Hassan; Mohsin, Ali; Wise, Robert A; Foreman, Marilyn G; Demeo, Dawn L; Regan, Elizabeth A; Make, Barry J; Boriek, Aladin M; Wiener, Laura E; Hanania, Nicola A

2017-12-01

The prevalence of chronic obstructive pulmonary disease (COPD) and its associated comorbidities increase with age. However, little is understood about differences in the disease in patients over 65 years of age compared with younger patients. To determine disease characteristics of COPD and its impact in older patients compared with younger patients. We examined baseline characteristics of patients with COPD (global obstructive lung disease stage II-IV) in 2 large cohorts: Genetic Epidemiology of COPD Study (COPDGene) and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared demographics, indices of disease severity, prevalence of comorbidities, exacerbation frequency, and quality of life scores in patients ≥65 years of age vs patients <65 years of age. We also tested for associations of age with disease characteristics and health outcomes. In the COPDGene cohort, older patients (n = 1663) had more severe disease as measured by forced expiratory volume in 1 second (1.22 vs 1.52 L, P < .001), use of long-term oxygen therapy (35% vs 22%, P < .001), 6-minute walk distance (355 vs 375 m, P < .001), and radiographic evidence of emphysema (14% vs 8%, P < .001) and air trapping (47% vs 36%, P < .001) and were more likely to have comorbidities compared with younger patients (n = 2027). Similarly, in the ECLIPSE cohort, older patients (n = 1030) had lower forced expiratory volume in 1 second (1.22 vs 1.34 L, P < .001), greater use of long-term oxygen therapy (7% vs 5%, P = .02), shorter 6- minute walk distance (360 vs 389 m, P < .001), and more radiographic evidence of emphysema (17% vs 14%, P = .009) than younger patients (n = 1131). In adjusted analyses of both cohorts, older age was associated with decreased frequency of exacerbations [odds ratio = 0.52, 95% confidence interval (CI) = 0.43-0.64 in COPDGene, odds ratio = 0.79, 95% CI = 0.64-0.99 in ECLIPSE] and a better quality of life (lower St. Georges respiratory questionnaire score) (β = -8.7, 95% CI = -10.0 to -7.4 in COPDGene, β = -4.4, 95% CI = -6.1 to -3.2 in ECLIPSE). Despite greater severity of illness, older patients with COPD had better quality of life and reported fewer exacerbations than younger patients. Although this observation needs to be explored further, it may be related to the fact that older patients change their expectations and learn to adapt to their disease. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Systematic Review and Quality Appraisal of Cost-Effectiveness Analyses of Pharmacologic Maintenance Treatment for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Recommendations.

PubMed

van der Schans, Simon; Goossens, Lucas M A; Boland, Melinde R S; Kocks, Janwillem W H; Postma, Maarten J; van Boven, Job F M; Rutten-van Mölken, Maureen P M H

2017-01-01

Worldwide, chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung disease with considerable clinical and socioeconomic impact. Pharmacologic maintenance drugs (such as bronchodilators and inhaled corticosteroids) play an important role in the treatment of COPD. The cost effectiveness of these treatments has been frequently assessed, but studies to date have largely neglected the impact of treatment sequence and the exact stage of disease in which the drugs are used in real life. We aimed to systematically review recently published articles that reported the cost effectiveness of COPD maintenance treatments, with a focus on key findings, quality and methodological issues. We performed a systematic literature search in Embase, PubMed, the UK NHS Economic Evaluation Database (NHS-EED) and EURONHEED (European Network of Health Economics Evaluation Databases) and included all relevant articles published between 2011 and 2015 in either Dutch, English or German. Main study characteristics, methods and outcomes were extracted and critically assessed. The Quality of Health Economic Studies (QHES) instrument was used as basis for quality assessment, but additional items were also addressed. The search identified 18 recent pharmacoeconomic analyses of COPD maintenance treatments. Papers reported the cost effectiveness of long-acting muscarinic antagonist (LAMA) monotherapy (n = 6), phosphodiesterase (PDE)-4 inhibitors (n = 4), long-acting beta agonist/inhaled corticosteroid (LABA/ICS) combinations (n = 4), LABA monotherapy (n = 2) and LABA/LAMA combinations (n = 2). All but two studies were funded by the manufacturer, and all studies indicated favourable cost effectiveness; however, the number of quality-adjusted life-years (QALYs) gained was small. Less than half of the studies reported a COPD-specific outcome in addition to a generic outcome (mostly QALYs). Exacerbation and mortality rates were found to be the main drivers of cost effectiveness. According to the QHES, the quality of the studies was generally sufficient, but additional assessment revealed that most studies poorly represented the cost effectiveness of real-life medication use. The majority of studies showed that pharmacologic COPD maintenance treatment is cost effective, but most studies poorly reflected real-life drug use. Consistent and COPD-specific methodology is recommended.

Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study.

PubMed

van Geffen, Wouter H; Bruins, Marcel; Kerstjens, Huib A M

2016-06-16

Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose (e-nose) could fit this profile but has never been tested in this setting before. In a single-center registered trial (NTR 4601) patients admitted with AECOPD were tested with the Aeonose(®) electronic nose, and a diagnosis of viral or bacterial infection was obtained by bacterial culture on sputa and viral PCR on nose swabs. A neural network with leave-10%-out cross-validation was used to assess the e-nose data. Forty three patients were included. In the bacterial infection model, 22 positive cases were tested versus the negatives; and similarly 18 positive cases were tested in the viral infection model. The Aeonose was able to distinguish between COPD-subjects suffering from a viral infection and COPD patients without infection, showing an area under the curve (AUC) of 0.74. Similarly, for bacterial infections, an AUC of 0.72 was obtained. The Aeonose e-nose yields promising results in 'smelling' the presence or absence of a viral or bacterial respiratory infection during an acute exacerbation of COPD. Validation of these results using a new and large cohort is required before introduction into clinical practice.

The Chronic Bronchitic Phenotype of COPD

PubMed Central

Han, MeiLan K.; Vance, Gwendolyn B.; Make, Barry J.; Newell, John D.; Hokanson, John E.; Hersh, Craig P.; Stinson, Douglas; Silverman, Edwin K.; Criner, Gerard J.

2011-01-01

Background: Chronic bronchitis (CB) in patients with COPD is associated with an accelerated lung function decline and an increased risk of respiratory infections. Despite its clinical significance, the chronic bronchitic phenotype in COPD remains poorly defined. Methods: We analyzed data from subjects enrolled in the Genetic Epidemiology of COPD (COPDGene) Study. A total of 1,061 subjects with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II to IV were divided into two groups: CB (CB+) if subjects noted chronic cough and phlegm production for ≥ 3 mo/y for 2 consecutive years, and no CB (CB−) if they did not. Results: There were 290 and 771 subjects in the CB+ and CB− groups, respectively. Despite similar lung function, the CB+ group was younger (62.8 ± 8.4 vs 64.6 ± 8.4 years, P = .002), smoked more (57 ± 30 vs 52 ± 25 pack-years, P = .006), and had more current smokers (48% vs 27%, P < .0001). A greater percentage of the CB+ group reported nasal and ocular symptoms, wheezing, and nocturnal awakenings secondary to cough and dyspnea. History of exacerbations was higher in the CB+ group (1.21 ± 1.62 vs 0.63 ± 1.12 per patient, P < .027), and more patients in the CB+ group reported a history of severe exacerbations (26.6% vs 20.0%, P = .024). There was no difference in percent emphysema or percent gas trapping, but the CB+ group had a higher mean percent segmental airway wall area (63.2% ± 2.9% vs 62.6% ± 3.1%, P = .013). Conclusions: CB in patients with COPD is associated with worse respiratory symptoms and higher risk of exacerbations. This group may need more directed therapy targeting chronic mucus production and smoking cessation not only to improve symptoms but also to reduce risk, improve quality of life, and improve outcomes. Trial registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov PMID:21474571

Association between glutathione S-transferase P1 Ile (105) Val gene polymorphism and chronic obstructive pulmonary disease: A meta-analysis based on seventeen case-control studies.

PubMed

Yang, Lingjing; Li, Xixia; Tong, Xiang; Fan, Hong

2015-12-01

Previous studies have shown that glutathione S-transferase P1 (GSTP1) was associated with chronic obstructive pulmonary disease (COPD). However, the association between GSTP1 Ile (105) Val gene polymorphism and COPD remains controversial. To drive a more precise estimation, we performed a meta-analysis based on published case-control studies. An electronic search of PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated (CNKI) Database for papers on GSTP1 Ile (105) Val gene polymorphism and COPD risk was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive mode. Statistical heterogeneity, test of publication bias and sensitivity analysis was performed. The software STATA (Version 13.0) was used data analysis. Overall, seventeen studies with 1892 cases and 2012 controls were included in this meta-analysis. The GSTP1 Ile (105) Val polymorphism showed pooled odds ratios for the homozygote comparison (OR = 1.501, 95%CI [0.862, 2.614]), heterozygote comparison (OR = 0.924, 95%CI [0.733, 1.165]), dominant model (OR = 1.003, 95%CI [0.756, 1.331]), recessive model (OR = 1.510, 95%CI [0.934, 2.439]), and an additive model (OR = 1.072, 95%CI [0.822, 1.398]). In conclusion, the current meta-analysis, based on the most updated information, showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in any genetic models. The results of subgroup analysis also showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in Asian population and Caucasian population. Further studies involving large populations and careful control with age, sex, ethnicity, and cigarette smoking are greatly needed.

The relationship between different diet quality indices and severity of airflow obstruction among COPD patients

PubMed Central

Yazdanpanah, Leila; Paknahad, Zamzam; Moosavi, Ali Javad; Maracy, Mohammad Reza; Zaker, Mohammad Masoud

2016-01-01

Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide. Smoking is the number one cause of COPD; however, genetic, environmental and dietary factors contribute to the etiology of this disease. In this study, we assessed the association between three diet quality indices -the Healthy Eating Index-2005 (HEI-2005), the Healthy Eating Index-2010 (HEI-2010), and Mediterranean Diet Score (MED)- and the severity of disease in COPD patients. Methods: This cross-sectional study was performed at Rasul-e-Akram Hospital in Tehran on 121 COPD patients with the mean age of (SD) of 66.1(10.9) years. A pulmonary specialist diagnosed all participants based on a spirometry test. They were categorized into four groups (1, 2, 3, 4 stages of disease). Three diet quality indices, spirometry test and determination of disease severity were performed for all the participants. ANCOVA and Kruskal-Wallis test were used to assess the relationship between dietary quality indices and severity of the disease. The relationship between HEI-2010, HEI-2005, MED score, their components and lung function was assessed using a multiple linear regression analysis. All analyses were done using SPSS 18. Results: Reduction of the Healthy Eating Index-2010 and MED score were observed along with the increase in disease severity, but they were not significant. The relationship between the three diet quality indices and lung function showed a significant association between MED score and Forced expiratory volume in one second (FEV1), The Forced Vital Capacity (FVC) (β=2.9, 95% CI (1.1, 4.8), p=0.002), (β=2.8, 95% CI (0.9, 4.8), p=0.007), respectively. Conclusion: Mediterranean dietary pattern and obtaining a better score on HEI-2010 diet were associated with a better lung function test. PMID:27493924

Association between glutathione S-transferase P1 Ile (105) Val gene polymorphism and chronic obstructive pulmonary disease: A meta-analysis based on seventeen case–control studies

PubMed Central

Yang, Lingjing; Li, Xixia; Tong, Xiang; Fan, Hong

2015-01-01

Introduction Previous studies have shown that glutathione S-transferase P1 (GSTP1) was associated with chronic obstructive pulmonary disease (COPD). However, the association between GSTP1 Ile (105) Val gene polymorphism and COPD remains controversial. To drive a more precise estimation, we performed a meta-analysis based on published case–control studies. Methods An electronic search of PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated (CNKI) Database for papers on GSTP1 Ile (105) Val gene polymorphism and COPD risk was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive mode. Statistical heterogeneity, test of publication bias and sensitivity analysis was performed. The software STATA (Version 13.0) was used data analysis. Results Overall, seventeen studies with 1892 cases and 2012 controls were included in this meta-analysis. The GSTP1 Ile (105) Val polymorphism showed pooled odds ratios for the homozygote comparison (OR = 1.501, 95%CI [0.862, 2.614]), heterozygote comparison (OR = 0.924, 95%CI [0.733, 1.165]), dominant model (OR = 1.003, 95%CI [0.756, 1.331]), recessive model (OR = 1.510, 95%CI [0.934, 2.439]), and an additive model (OR = 1.072, 95%CI [0.822, 1.398]). Conclusions In conclusion, the current meta-analysis, based on the most updated information, showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in any genetic models. The results of subgroup analysis also showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in Asian population and Caucasian population. Further studies involving large populations and careful control with age, sex, ethnicity, and cigarette smoking are greatly needed. PMID:26504746

α1-Antitrypsin Protease Inhibitor MZ Heterozygosity Is Associated With Airflow Obstruction in Two Large Cohorts

PubMed Central

Sørheim, Inga-Cecilie; Bakke, Per; Gulsvik, Amund; Pillai, Sreekumar G.; Johannessen, Ane; Gaarder, Per I.; Campbell, Edward J.; Agustí, Alvar; Calverley, Peter M. A.; Donner, Claudio F.; Make, Barry J.; Rennard, Stephen I.; Vestbo, Jørgen; Wouters, Emiel F. M.; Paré, Peter D.; Levy, Robert D.; Coxson, Harvey O.; Lomas, David A.; Hersh, Craig P.

2010-01-01

Background: Severe α1-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1-antitrypsin, but whether they have an increased risk of COPD is uncertain. Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. Results: PI MZ was associated with a 3.5% lower FEV1/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV1/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals. PMID:20595457

Different pattern of viral infections and clinical outcomes in patient with acute exacerbation of chronic obstructive pulmonary disease and chronic obstructive pulmonary disease with pneumonia.

PubMed

Kim, Ho-Cheol; Choi, Sang-Ho; Huh, Jin-Won; Sung, Heungsup; Hong, Sang Bum; Lim, Chae-Man; Koh, Younsuck

2016-12-01

Respiratory viruses are well-known causes of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and also important pathogens for concomitant pneumonia in COPD (CP-COPD). However, the differences in a viral infection pattern and clinical impacts of respiratory viruses between the two groups have not been well investigated. The clinical and microbiological data from COPD patients admitted with AE-COPD (n = 281) or CP-COPD (n = 284) between January 2010 and December 2012 were reviewed. After excluding 88 patients (40 with AE-COPD and 48 with CP-COPD) who did not undergo a multiplex RT-PCR test for respiratory viruses, the demographic characteristics, identified viruses, and clinical outcomes of the AE-COPD and CP-COPD groups were compared. Respiratory viruses were identified in 41.9% of AE-COPD group and 33.5% of the CP-COPD groups. The most common virus was influenza virus in the AE-COPD group (33.7%) versus human coronavirus (24.1%) in the CP-COPD group. Influenza virus was significantly more common in the AE-ACOPD group than in the CP-COPD group (P < 0.01). In-hospital mortality of AE-COPD and CP-COPD were 1.2% and 12.3%, respectively (P < 0.01). Among CP-COPD patients, in-hospital mortality of patients with only viral infection group, only bacterial infection group, and viral-bacterial co-infection were 2.6%, 25.8%, and 17.5%, respectively (P = 0.01). Respiratory viruses were commonly identified in both AE-COPD and CP-COPD, influenza virus and human coronavirus were the most common viruses identified in AE-COPD and CP-COPD patients, respectively. The mortality rates of only viral infection group was significantly lower than only bacterial infection or viral-bacterial co-infection group in CP-COPD patients. J. Med. Virol. 88:2092-2099, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Exercises

MedlinePlus

... COPD) COPD Overview COPD Lifestyle Management COPD: Exercises COPD: Exercises Make an Appointment Refer a Patient Ask ... program is another very important step in managing COPD. It is common for people with lung disease ...

Investigation of Hydrogen Sulfide Exposure and Lung Function, Asthma and Chronic Obstructive Pulmonary Disease in a Geothermal Area of New Zealand

PubMed Central

Bates, Michael N.; Crane, Julian; Balmes, John R.; Garrett, Nick

2015-01-01

Background Results have been conflicting whether long-term ambient hydrogen sulfide (H2S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world’s largest population exposed to ambient H2S—from geothermal sources. Objectives We investigated associations of H2S with lung function, COPD and asthma in this population. Methods 1,204 of 1,639 study participants, aged 18–65 years during 2008–2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H2S monitoring networks across Rotorua. Four metrics for H2S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H2S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV1/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV1 response to bronchodilator) with H2S exposure quartiles. Results None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H2S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H2S exposures were beneficially associated with lung function parameters. Conclusions The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H2S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung function associated with recent ambient H2S exposures require confirmation in other studies. PMID:25822819

Investigation of hydrogen sulfide exposure and lung function, asthma and chronic obstructive pulmonary disease in a geothermal area of New Zealand.

PubMed

Bates, Michael N; Crane, Julian; Balmes, John R; Garrett, Nick

2015-01-01

Results have been conflicting whether long-term ambient hydrogen sulfide (H2S) affects lung function or is a risk factor for asthma or chronic obstructive pulmonary disease (COPD). Rotorua city, New Zealand, has the world's largest population exposed to ambient H2S-from geothermal sources. We investigated associations of H2S with lung function, COPD and asthma in this population. 1,204 of 1,639 study participants, aged 18-65 years during 2008-2010, provided satisfactory spirometry results. Residences, workplaces and schools over the last 30 years were geocoded. Exposures were estimated from data collected by summer and winter H2S monitoring networks across Rotorua. Four metrics for H2S exposure, representing both current and long-term (last 30 years) exposure, and also time-weighted average and peak exposures, were calculated. Departures from expected values for pre-bronchodilator lung function, calculated from prediction equations, were outcomes for linear regression models using quartiles of the H2S exposure metrics. Separate models examined participants with and without evidence of asthma or COPD, and never- and ever-smokers. Logistic regression was used to investigate associations of COPD (a post-bronchodilator FEV1/FVC < 70% of expected) and asthma (doctor-diagnosed or by FEV1 response to bronchodilator) with H2S exposure quartiles. None of the exposure metrics produced evidence of lung function decrement. The logistic regression analysis showed no evidence that long-term H2S exposure at Rotorua levels was associated with either increased COPD or asthma risk. Some results suggested that recent ambient H2S exposures were beneficially associated with lung function parameters. The study found no evidence of reductions in lung function, or increased risk of COPD or asthma, from recent or long-term H2S exposure at the relatively high ambient concentrations found in Rotorua. Suggestions of improved lung function associated with recent ambient H2S exposures require confirmation in other studies.

miR-638 regulates gene expression networks associated with emphysematous lung destruction

PubMed Central

2013-01-01

Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by varying degrees of emphysematous lung destruction and small airway disease, each with distinct effects on clinical outcomes. There is little known about how microRNAs contribute specifically to the emphysema phenotype. We examined how genome-wide microRNA expression is altered with regional emphysema severity and how these microRNAs regulate disease-associated gene expression networks. Methods We profiled microRNAs in different regions of the lung with varying degrees of emphysema from 6 smokers with COPD and 2 controls (8 regions × 8 lungs = 64 samples). Regional emphysema severity was quantified by mean linear intercept. Whole genome microRNA and gene expression data were integrated in the same samples to build co-expression networks. Candidate microRNAs were perturbed in human lung fibroblasts in order to validate these networks. Results The expression levels of 63 microRNAs (P < 0.05) were altered with regional emphysema. A subset, including miR-638, miR-30c, and miR-181d, had expression levels that were associated with those of their predicted mRNA targets. Genes correlated with these microRNAs were enriched in pathways associated with emphysema pathophysiology (for example, oxidative stress and accelerated aging). Inhibition of miR-638 expression in lung fibroblasts led to modulation of these same emphysema-related pathways. Gene targets of miR-638 in these pathways were amongst those negatively correlated with miR-638 expression in emphysema. Conclusions Our findings demonstrate that microRNAs are altered with regional emphysema severity and modulate disease-associated gene expression networks. Furthermore, miR-638 may regulate gene expression pathways related to the oxidative stress response and aging in emphysematous lung tissue and lung fibroblasts. PMID:24380442

Gender differences in chronic obstructive pulmonary diseases: a narrative review.

PubMed

Nicolini, Antonello; Barbagelata, Elena; Tagliabue, Elena; Colombo, Daniela; Monacelli, Fiammetta; Braido, Fulvio

2018-06-01

Chronic obstructive pulmonary disease (COPD) is generally considered to be prevalent in males. However, smoking is rising in women in developing and developed countries, while exposure to biomass fuel for domestic purposes is a recognized risk factor among females. Females developing more severe COPD patterns due to tobacco exposure than men maybe due to a genetic predisposition, a greater dose-dependent effect of smoke related to smaller airways caliber and an increased oxidative stress with augmented TGF-beta1 signaling. Gender hormones also seem to be involved in tobacco-smoke metabolism and in lung and pulmonary development. while menopause is associated with accelerated alveolar loss and decline of lung function pulmonary function. The time to diagnosis differs between the sexes since a lower rate of spirometry is performed in women. Also comorbidities differ between genders: osteoporosis, inflammatory bowel diseases, reflux, hypertension, rheumatoid arthritis, and mental diseases are more common in women. Women pay more attention to breathlessness, maybe due to higher emotional response and anxiety. These elements could lead to higher hospitalization rates in women. The aim of this review is to provide the available evidence with the aim of inviting healthcare professionals to evaluate gender differences in patients with COPD, key point for optimizing the care plan.

COPD - control drugs

MedlinePlus

Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - ...

Early Detection of Chronic Obstructive Pulmonary Disease in Primary Care.

PubMed

Kobayashi, Seiichi; Hanagama, Masakazu; Yanai, Masaru

2017-12-01

Objective To evaluate the effectiveness of an early detection program for chronic obstructive pulmonary disease (COPD) in a primary care setting in Japan. Methods Participants of ≥40 years of age who regularly visited a general practitioner's clinic due to chronic disease were asked to complete a COPD screening questionnaire (COPD Population Screener; COPD-PS) and undergo simplified spirometry using a handheld spirometric device. Patients who showed possible COPD were referred to a respiratory specialist and underwent a detailed examination that included spirometry and chest radiography. Results A total of 111 patients with possible COPD were referred for close examination. Among these patients, 27 patients were newly diagnosed with COPD. The patients with COPD were older, had lower BMI values, and had a longer smoking history in comparison to non-COPD patients. COPD patients also had more comorbid conditions. A diagnosis of COPD was significantly associated with a high COPD-PS score (p<0.001) and the detection of possible airflow limitation evaluated by the handheld spirometric device (p<0.01). An ROC curve analysis demonstrated that 5 points was the best COPD-PS cut-off value for the diagnosis of COPD. The combination of both tools showed 40.7% of sensitivity and 96.4% of specificity. Conclusion The use of the COPD-PS plus a handheld spirometric device could facilitate the early detection of undiagnosed COPD in primary care.

Cellular assessment of muscle in COPD: case studies of two males.

PubMed

Green, Howard J; Bombardier, Eric; Burnett, Margaret E; D'Arsigny, Christine L; Iqbal, Sobia; Webb, Katherine A; Ouyang, Jing; O'Donnell, Denis E

2009-12-29

The objective of this paper is to provide an overview of the recent developments in muscle physiology and biochemistry in general, and with respect to chronic obstructive pulmonary disease (COPD) specifically. As a way of illustration, we have presented data on the remodeling that occurs in vastus lateralis in two patients with COPD (COPD #1, forced expiratory volume in one second/forced vital capacity [FEV(1)/FVC] = 63%; COPD #2, FEV(1)/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV(1)/FVC = 111 +/- 2.2%, n = 4). Type I fibers percentages were lower in both COPD #1 (16.7) and COPD #2 (24.9) compared to CON (57.3 +/- 5.2). Cross sectional area of the type I fibers of the patients ranged between 65%-68% of CON and for the type II subtypes (IIA, IIAX, IIX) between 74% and 89% (COPD #1) and 17%-32% (COPD #2). A lower number of capillary contacts were observed for all fiber types in COPD #1 but not COPD #2. Lower concentrations of adenosine triphosphate (ATP) (24%-26%) and phosphocreatine (18%-20%), but not lactate occurred in COPD. In contrast to COPD #1, who displayed normal glucose transporter content, GLUT1 and GLUT4 were only 71% and 54%, respectively of CON in COPD #2. Lower monocarboxylate contents were found for MCT1 in both COPD #1 (63%) and COPD #2 (41%) and for MCT4 (78%) in COPD #1. Maximal oxidative enzyme activities (V(max)) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, V(max) ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in V(max) of the Na(+)-K(+)-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while V(max) of the Ca(2+)-ATPase was near normal in COPD #1 (84% CON). It is concluded that disturbances can occur in muscle to a wide range of excitation, contraction and metabolic processes in COPD.

Incidence and relative risk for developing cancer among patients with COPD: a nationwide cohort study in Taiwan

PubMed Central

Ho, Chung-Han; Chen, Yi-Chen; Wang, Jhi-Joung; Liao, Kuang-Ming

2017-01-01

Objectives This observational study aimed to examine the incidence of malignant diseases, including specific cancer types, after the diagnosis of chronic obstructive pulmonary disease (COPD) in Taiwanese patients. Setting Taiwan's National Health Insurance Research Database. Participants The definition of a patient with COPD was a patient with a discharge diagnosis of COPD or at least 3 ambulatory visits for COPD. The index date was the date of the first COPD diagnosis. Patients with a history of malignancy disorders before the index date were excluded. After matching age and gender, 13 289 patients with COPD and 26 578 control participants without COPD were retrieved and analysed. They were followed from the index date to malignancy diagnosis, death or the end of study follow-up (31 December 2011), whichever came first. Primary outcome measures Patients were diagnosed with cancer (n=1681, 4.2%; 973 (7.3%) for patients with COPD and 728 (2.7%) for patients without COPD). The risk of 7 major cancer types, including lung, liver, colorectal, breast, prostate, stomach and oesophagus, between patients with COPD and patients without COPD was also estimated. Results The mean age of all study participants was 57.9±13.5 years. The average length of follow-up to cancer incidence was 3.9 years for patients with COPD and 5.0 years for patients without COPD (p<0.01). Patients with COPD were diagnosed with cancer (n=973, 73%) at a significantly higher rate than patients without COPD (n=708, 2.7%; p<0.01). The HR for developing cancer in patients with COPD was 2.8 (95% CI 2.6 to 3.1) compared with patients without COPD after adjusting for age, sex and comorbidities. The most common cancers in patients with COPD include lung, liver, colorectal, breast, prostate and stomach cancers. Conclusions The risk of developing cancer is higher in patients with COPD compared with patients without COPD. Cancer screening is warranted in patients with COPD. PMID:28279996

Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management.

PubMed

Woodruff, Prescott G; Agusti, Alvar; Roche, Nicolas; Singh, Dave; Martinez, Fernando J

2015-05-02

Chronic obstructive pulmonary disease (COPD) is a common, complex, and heterogeneous disorder that is responsible for substantial and growing morbidity, mortality, and health-care expense worldwide. Of imperative importance to decipher the complexity of COPD is to identify groups of patients with similar clinical characteristics, prognosis, or therapeutic needs, the so-called clinical phenotypes. This strategy is logical for research but might be of little clinical value because clinical phenotypes can overlap in the same patient and the same clinical phenotype could result from different biological mechanisms. With the goal to match assessment with treatment choices, the latest iteration of guidelines from the Global Initiative for Chronic Obstructive Lung Disease reorganised treatment objectives into two categories: to improve symptoms (ie, dyspnoea and health status) and to decrease future risk (as predicted by forced expiratory volume in 1 s level and exacerbations history). This change thus moves treatment closer to individualised medicine with available bronchodilators and anti-inflammatory drugs. Yet, future treatment options are likely to include targeting endotypes that represent subtypes of patients defined by a distinct pathophysiological mechanism. Specific biomarkers of these endotypes would be particularly useful in clinical practice, especially in patients in which clinical phenotype alone is insufficient to identify the underlying endotype. A few series of potential COPD endotypes and biomarkers have been suggested. Empirical knowledge will be gained from proof-of-concept trials in COPD with emerging drugs that target specific inflammatory pathways. In every instance, specific endotype and biomarker efforts will probably be needed for the success of these trials, because the pathways are likely to be operative in only a subset of patients. Network analysis of human diseases offers the possibility to improve understanding of disease pathobiological complexity and to help with the development of new treatment alternatives and, importantly, a reclassification of complex diseases. All these developments should pave the way towards personalised treatment of patients with COPD in the clinic. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study of Pre-disposing Factors of Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Antibiotic Prescribing Pattern with Reference to Antibiotic Sensitivity Test.

PubMed

Shrestha, R; Shrestha, B; Shakya Shrestha, S; Pant, A; Prajapati, B; Karmacharya, B M

2015-01-01

Background Chronic Obstructive Pulmonary Disease (COPD) affects about 329 million people worldwide, which is nearly 5% of the entire global population. In the context of Nepal, COPD accounts for 43% of the non-communicable disease burden and 2.56% of hospitalizations. Various pre-disposing factors like bacterial, viral, fungal, smoking, occupational exposures and genetic factors have been proposed to precipitate COPD and its exacerbation though, the definitive pre-disposing factors and factors related to acute exacerbation have not been determined in the context of Nepal. Objective To find out the pre-disposing factors and the related causative agents for COPD. Method A cross sectional study was conducted in a tertiary care hospital. Patients of all age group who were diagnosed as COPD and admitted in the hospital were included in this study. Patients were interviewed using structured questionnaire. The sociodemographic data including personal and medical history were recorded from those participants. In addition, sputum from those patients was sent for culture to investigate the possible responsible pathogens as well as its antibiotic sensitivity pattern. Result A total of 150 patients having Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) who have admitted from either emergency or out-patient department of the hospital were included in this study. Among the total number of patients, more than half of them were female (n=82). In addition, analysis of occupations shows that most of them were either farmer (36.0%) or housewife (30.7%). In total studied patients (n=150), most of them were using traditional firewood (83%) for cooking purpose and majority of patients (91%) were smokers. Most of the sputum samples show growth of gram-positive cocci (26.7%) and gram negative bacilli (27.5%). Considering the overall sensitivity pattern, the higher sensitivity was recorded for Co-trimoxazole and Ciprofloxacin while higher rate of resistance was noted for Penicillin group of drugs. The most widely used antibiotics were found to be Cephalosporin group of drugs (68%). Conclusion The present study revealed that the case of COPD is more in female and the commonest pre-disposing factor is found to be smoke/firewood. Cephalosporin group of drugs is the most commonly prescribed drug.

The effect of adipose derived stromal cells on oxidative stress level, lung emphysema and white blood cells of guinea pigs model of chronic obstructive pulmonary disease

PubMed Central

2014-01-01

Background Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic disease and a major cause of death and disability. The present study aimed to elucidate pharmacological effects of adipose derived stromal cells (ASCs) on pathological and biochemical factors in a guinea pig model of COPD. Guinea pigs were randomized into 5 groups including: Control, COPD, COPD + intratracheal delivery of PBS as a vehicle (COPD-PBS), COPD + intratracheal delivery of ASCs (COPD-ITASC) and COPD + intravenous injection of ASCs (COPD-IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months. Cell therapy was performed immediately after the end of animal exposure to cigarette smoke and 14 days after that, white blood cells, oxidative stress indices and pathological changes of the lung were measured. Results Compared with control group, emphysema was clearly observed in the COPD and COPD-PBS groups (p < 0.001). Lung histopathologic changes of COPD-ITASC and COPD-IVASC groups showed non-significant improvement compared to COPD-PBS group. The COPD-ITASC group showed a significant increase in total WBC compared to COPD-PBS group but there was not a significant increase in this regard in COPD-IVASC group. The differential WBC showed no significant change in number of different types of leukocytes. The serum level of malondialdehyde (MDA) significantly decreased but thiol groups of broncho-alveolar lavage fluid (BALF) increased in both cell treated groups (p < 0.05 for all cases). Weight of animals decreased during smoke exposure and improved after PBS or cell therapy. However, no significant change was observed between the groups receiving PBS and the ones receiving ASCs. Conclusion Cell therapy with ASCs can help in reducing oxidative damage during smoking which may collectively hold promise in attenuation of the severity of COPD although the lung structural changes couldn’t be ameliorated with these pharmacological therapeutic methods. PMID:24495506

The effect of adipose derived stromal cells on oxidative stress level, lung emphysema and white blood cells of guinea pigs model of chronic obstructive pulmonary disease.

PubMed

Ghorbani, Ahmad; Feizpour, Azadeh; Hashemzahi, Milad; Gholami, Lila; Hosseini, Mahmoud; Soukhtanloo, Mohammad; Vafaee Bagheri, Farzaneh; Khodaei, Esmaeil; Mohammadian Roshan, Nema; Boskabady, Mohammad Hossein

2014-02-04

Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic disease and a major cause of death and disability. The present study aimed to elucidate pharmacological effects of adipose derived stromal cells (ASCs) on pathological and biochemical factors in a guinea pig model of COPD. Guinea pigs were randomized into 5 groups including: Control, COPD, COPD + intratracheal delivery of PBS as a vehicle (COPD-PBS), COPD + intratracheal delivery of ASCs (COPD-ITASC) and COPD + intravenous injection of ASCs (COPD-IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months. Cell therapy was performed immediately after the end of animal exposure to cigarette smoke and 14 days after that, white blood cells, oxidative stress indices and pathological changes of the lung were measured. Compared with control group, emphysema was clearly observed in the COPD and COPD-PBS groups (p < 0.001). Lung histopathologic changes of COPD-ITASC and COPD-IVASC groups showed non-significant improvement compared to COPD-PBS group. The COPD-ITASC group showed a significant increase in total WBC compared to COPD-PBS group but there was not a significant increase in this regard in COPD-IVASC group. The differential WBC showed no significant change in number of different types of leukocytes. The serum level of malondialdehyde (MDA) significantly decreased but thiol groups of broncho-alveolar lavage fluid (BALF) increased in both cell treated groups (p < 0.05 for all cases). Weight of animals decreased during smoke exposure and improved after PBS or cell therapy. However, no significant change was observed between the groups receiving PBS and the ones receiving ASCs. Cell therapy with ASCs can help in reducing oxidative damage during smoking which may collectively hold promise in attenuation of the severity of COPD although the lung structural changes couldn't be ameliorated with these pharmacological therapeutic methods.

The Mevalonate Pathway and Innate Immune Hyper-Responsiveness in the Pathogenesis of COPD and Lung Cancer: Potential for Chemoprevention.

PubMed

Young, Robert P; Hopkins, Raewyn J

2017-01-01

Current evidence suggests that persisting and/or exaggerated inflammation in the lungs initiated by smoking, and up-regulated through genetic susceptibility, may result in lung remodelling and impaired repair. The mevalonate pathway, through its modifying effects on innate immune responsiveness, may be involved in these processes providing a plausible pathogenic link between the development of chronic obstructive pulmonary disease (COPD) and lung cancer. The mevalonate pathway, mediates these effects through important intra-cellular signalling molecules called guanine phosphate transferases (GTPases) such as Rho-A. Smoke exposure activates cell surface proteins which, through the mediating influence of GTPases, then modify the activation of NFkB and its downstream effects on genes underlying innate immunity, neutrophilic inflammation and carcinogenesis. The mevalonate pathway is readily and substantially modified by inhibition of the enzyme 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMGCo-A) reductase. This enzyme controls the rate limiting step of the mevalonate pathway and is subject to inhibition by statin drugs and small chain fatty acids derived from high dietary fibre intake. Thus inhibiting the mevelonate pathway, and dampening the innate immune response to smoking, may play a critical role in modifying pulmonary inflammation and lung remodelling. Such an action might slow the progression of COPD and reduce the tendency to the development of lung cancer. This review examines the pre-clinical and clinical data suggesting that HMGCoA-reductase inhibition and it's modification of the mevalonate pathway, may have a chemo-preventive effect on lung cancer, particularly in patients with COPD where pulmonary inflammation is increased and the risk of lung cancer is greatest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transcriptomic Analysis of Lung Tissue from Cigarette Smoke-Induced Emphysema Murine Models and Human Chronic Obstructive Pulmonary Disease Show Shared and Distinct Pathways.

PubMed

Yun, Jeong H; Morrow, Jarrett; Owen, Caroline A; Qiu, Weiliang; Glass, Kimberly; Lao, Taotao; Jiang, Zhiqiang; Perrella, Mark A; Silverman, Edwin K; Zhou, Xiaobo; Hersh, Craig P

2017-07-01

Although cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD), the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6 and NZW/LacJ) and two genetic models with mutations in COPD genome-wide association study genes (HHIP and FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene expression patterns that correlate with severity of emphysema in murine and human lungs. Xenobiotic metabolism and nuclear erythroid 2-related factor 2-mediated oxidative stress response were commonly regulated molecular response patterns in C57BL/6, Hhip +/- , and Fam13a -/- murine strains exposed chronically to CS. The CS-resistant Fam13a -/- mouse and NZW/LacJ strain revealed gene expression response pattern differences. The Fam13a -/- strain diverged in gene expression compared with C57BL/6 control only after CS exposure. However, the NZW/LacJ strain had a unique baseline expression pattern, enriched for nuclear erythroid 2-related factor 2-mediated oxidative stress response and xenobiotic metabolism, and converged to a gene expression pattern similar to the more susceptible wild-type C57BL/6 after CS exposure. These results suggest that distinct molecular pathways may account for resistance to emphysema. Surprisingly, there were few genes commonly modulated in mice and humans. Our study suggests that gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS.

Associations between DSM-IV mental disorders and subsequent COPD diagnosis.

PubMed

Rapsey, Charlene M; Lim, Carmen C W; Al-Hamzawi, Ali; Alonso, Jordi; Bruffaerts, Ronny; Caldas-de-Almeida, J M; Florescu, Silvia; de Girolamo, Giovanni; Hu, Chiyi; Kessler, Ronald C; Kovess-Masfety, Viviane; Levinson, Daphna; Medina-Mora, María Elena; Murphy, Sam; Ono, Yutaka; Piazza, Maria; Posada-Villa, Jose; ten Have, Margreet; Wojtyniak, Bogdan; Scott, Kate M

2015-11-01

COPD and mental disorder comorbidity is commonly reported, although findings are limited by substantive weaknesses. Moreover, few studies investigate mental disorder as a risk for COPD onset. This research aims to investigate associations between current (12-month) DSM-IV mental disorders and COPD, associations between temporally prior mental disorders and subsequent COPD diagnosis, and cumulative effect of multiple mental disorders. Data were collected using population surveys of 19 countries (n=52,095). COPD diagnosis was assessed by self-report of physician's diagnosis. The World Mental Health-Composite International Diagnostic Interview (WMH-CIDI) was used to retrospectively assess lifetime prevalence and age at onset of 16 DSM-IV disorders. Adjusting for age, gender, smoking, education, and country, survival analysis estimated associations between first onset of mental disorder and subsequent COPD diagnosis. COPD and several mental disorders were concurrently associated across the 12-month period (ORs 1.5-3.8). When examining associations between temporally prior disorders and COPD, all but two mental disorders were associated with COPD diagnosis (ORs 1.7-3.5). After comorbidity adjustment, depression, generalized anxiety disorder, and alcohol abuse were significantly associated with COPD (ORs 1.6-1.8). There was a substantive cumulative risk of COPD diagnosis following multiple mental disorders experienced over the lifetime. Mental disorder prevalence is higher in those with COPD than those without COPD. Over time, mental disorders are associated with subsequent diagnosis of COPD; further, the risk is cumulative for multiple diagnoses. Attention should be given to the role of mental disorders in the pathogenesis of COPD using prospective study designs. Copyright © 2015 Elsevier Inc. All rights reserved.

Associations between DSM-IV mental disorders and subsequent COPD diagnosis

PubMed Central

Rapsey, Charlene M.; Lim, Carmen C.W.; Al-Hamzawi, Ali; Alonso, Jordi; Bruffaerts, Ronny; Caldas-de-Almeida, J.M.; Florescu, Silvia; de Girolamo, Giovanni; Hu, Chiyi; Kessler, Ronald C.; Kovess-Masfety, Viviane; Levinson, Daphna; Elena Medina-Mora, María; Murphy, Sam; Ono, Yutaka; Piazza, Maria; Posada-Villa, Jose; ten Have, Margreet; Wojtyniak, Bogdan; Scott, Kate M.

2016-01-01

Objectives COPD and mental disorder comorbidity is commonly reported, although findings are limited by substantive weaknesses. Moreover, few studies investigate mental disorder as a risk for COPD onset. This research aims to investigate associations between current (12-month) DSM-IV mental disorders and COPD, associations between temporally prior mental disorders and subsequent COPD diagnosis, and cumulative effect of multiple mental disorders. Methods Data were collected using population surveys of 19 countries (n = 52,095). COPD diagnosis was assessed by self-report of physician's diagnosis. The World Mental Health-Composite International Diagnostic Interview (WMH-CIDI) was used to retrospectively assess lifetime prevalence and age at onset of 16 DSM-IV disorders. Adjusting for age, gender, smoking, education, and country, survival analysis estimated associations between first onset of mental disorder and subsequent COPD diagnosis. Results COPD and several mental disorders were concurrently associated across the 12-month period (ORs 1.5–3.8). When examining associations between temporally prior disorders and COPD, all but two mental disorders were associated with COPD diagnosis (ORs 1.7–3.5). After comorbidity adjustment, depression, generalized anxiety disorder, and alcohol abuse were significantly associated with COPD (ORs 1.6–1.8). There was a substantive cumulative risk of COPD diagnosis following multiple mental disorders experienced over the lifetime. Conclusions: Mental disorder prevalence is higher in those with COPD than those without COPD. Over time, mental disorders are associated with subsequent diagnosis of COPD; further, the risk is cumulative for multiple diagnoses. Attention should be given to the role of mental disorders in the pathogenesis of COPD using prospective study designs. PMID:26526305

Evidence of eosinophil extracellular trap cell death in COPD: does it represent the trigger that switches on the disease?

PubMed Central

Uribe Echevarría, Loli; Leimgruber, Carolina; García González, Jorge; Nevado, Alberto; Álvarez, Ruth; García, Luciana N; Quintar, Amado A; Maldonado, Cristina A

2017-01-01

In spite of the numerous studies on chronic obstructive pulmonary disease (COPD), the cellular and molecular basis of the disease’s development remain unclear. Neutrophils and eosinophils are known to be key players in COPD. Recently, neutrophil extracellular trap cell death (NETosis), a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD. However, there is limited knowledge about eosinophil extracellular trap cell death (EETosis) and its role in the pathogenesis of COPD. The aim of this study was to evaluate EETosis in stable COPD. Induced sputum obtained from healthy smokers and low exacerbation risk COPD A or B group patients or high exacerbation risk COPD C or D group patients were included. Samples were examined using electron microscopy and immunofluorescence. Healthy smokers (n=10) and COPD A (n=19) group exhibited neutrophilic or paucigranulocytic phenotypes, with NETosis being absent in these patients. In contrast, COPD B (n=29), with eosinophilic or mixed phenotypes, showed EETosis and incipient NETosis. COPD C (n=18) and COPD D groups (n=13) were differentiated from low exacerbation rate-COPD group by the abundant cellular debris, with COPD C group having an eosinophilic pattern and numerous cells undergoing EETosis. A hallmark of this group was the abundant released membranes that often appeared phagocytosed by neutrophils, which coincidentally exhibited early NETosis changes. The COPD D group included patients with a neutrophilic or mixed pattern, with abundant neutrophil extracellular trap-derived material. This study is the first to demonstrate EETosis at different stages of stable COPD. The results suggest a role for eosinophils in COPD pathophysiology, especially at the beginning and during the persistence of the disease, regardless of whether the patient quit smoking, with EETosis debris probably triggering uncontrolled NETosis. The main target of these findings should be young smokers with the potential to develop COPD. PMID:28352169

COPD and stroke: are systemic inflammation and oxidative stress the missing links?

PubMed Central

Austin, Victoria; Crack, Peter J.; Bozinovski, Steven; Miller, Alyson A.

2016-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. PMID:27215677

Is Chronic Obstructive Pulmonary Disease Caused by Wood Smoke a Different Phenotype or a Different Entity?

PubMed

Torres-Duque, Carlos A; García-Rodriguez, María Carmen; González-García, Mauricio

2016-08-01

Around 40% of the world's population continue using solid fuel, including wood, for cooking or heating their homes. Chronic exposure to wood smoke is a risk factor for developing chronic obstructive pulmonary disease (COPD). In some regions of the world, this can be a more important cause of COPD than exposure to tobacco smoke from cigarettes. Significant differences between COPD associated with wood smoke (W-COPD) and that caused by smoking (S-COPD) have led some authors to suggest that W-COPD should be considered a new COPD phenotype. We present a review of the differences between W-COPD and S-COPD. On the premise that wood smoke and tobacco smoke are not the same and the physiopathological mechanisms they induce may differ, we have analyzed whether W-COPD can be considered as another COPD phenotype or a distinct nosological entity. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Worse Prognosis for Stage IA Lung Cancer Patients with Smoking History and More Severe Chronic Obstructive Pulmonary Disease.

PubMed

Yoshida, Yukihiro; Kage, Hidenori; Murakawa, Tomohiro; Sato, Yasunori; Ota, Satoshi; Fukayama, Masashi; Nakajima, Jun

2015-01-01

This retrospective study examined whether the severity of chronic obstructive lung disease (COPD) affects surgical outcomes. The subjects were 243 consecutive patients who underwent lobectomy for clinical stage IA lung cancer from 1999 to 2008 in our hospital. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system was used to classify the severity of COPD in smokers. Among the 149 smokers, 62 were diagnosed with COPD (25 as GOLD 1, 33 as GOLD 2, and 4 as GOLD 3). In univariate analysis, postoperative pulmonary complications were associated with male sex and more severe COPD. The frequencies were 17.1% in non-COPD, 24.0% in GOLD 1-COPD, and 46.0% in GOLD 2/3-COPD smokers (p = 0.0006). In univariate analysis, older age, smoking history, higher smoking pack-years and more severe COPD were associated with poor relapse-free survival. Relapse-free survival at five years was 80.7%, 66.9%, and 61.3% in non-COPD, GOLD 1-COPD, and GOLD 2/3-COPD smokers, respectively (p = 0.0005). Multivariate analyses showed that only GOLD 2/3-COPD was associated with postoperative pulmonary complications and relapse-free survival. Inhaled bronchodilators were prescribed preoperatively to 24.3% of the GOLD 2/3-COPD group. Smokers with GOLD 2/3-COPD are at high risk for pulmonary complications and have an unfavorable long-term prognosis.

Could symptoms and risk factors diagnose COPD? Development of a Diagnosis Score for COPD

PubMed Central

Salameh, Pascale; Khayat, Georges; Waked, Mirna

2012-01-01

Background: Diagnosing chronic obstructive pulmonary disease (COPD) without spirometry is still a challenge. Our objective in this study was to develop a scale for diagnosis of COPD. Methods: Data were taken from a cross-sectional epidemiological study. After reducing chronic respiratory symptoms, a logistic regression was used to select risk factors for and symptoms of COPD. The rounded coefficients generated a Diagnosis Score for COPD (DS-COPD), which was dichotomized and differentiated between COPD and other individuals with respiratory symptoms. Results: We constructed a tool for COPD diagnosis with good properties, comprising 12 items. The area under the curve was 0.849; the positive predictive value was 76% if the DS-COPD was >20 and the negative predictive value was 97% if the DS-COPD was <10. A DS-COPD of 10–19 represented a zone mostly suggestive of no COPD (77%). The score was also inversely correlated with forced expiratory volume in 1 second/forced vital capacity. Conclusion: In this study, a tool for diagnosis of COPD was constructed with good properties for use in the epidemiological setting, mainly in cases of low or high scoring. It would be of particular interest in the primary care setting, where spirometry may not be available. Prospective studies and application in clinical settings would be necessary to validate this scale further. PMID:23071403

Genetic variation in antioxidant enzymes, cigarette smoking, and longitudinal change in lung function.

PubMed

Tang, Wenbo; Bentley, Amy R; Kritchevsky, Stephen B; Harris, Tamara B; Newman, Anne B; Bauer, Douglas C; Meibohm, Bernd; Cassano, Patricia A

2013-10-01

Antioxidant enzymes play an important role in the defense against oxidative stress in the lung and in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sequence variation in genes encoding antioxidant enzymes may alter susceptibility to COPD by affecting longitudinal change in lung function in adults. We genotyped 384 sequence variants in 56 candidate genes in 1281 African American and 1794 European American elderly adults in the Health, Aging, and Body Composition study. Single-marker associations and gene-by-smoking interactions with rate of change in FEV₁ and FEV₁/FVC were evaluated using linear mixed-effects models, stratified by race/ethnicity. In European Americans, rs17883901 in GCLC was statistically significantly associated with rate of change in FEV₁/FVC; the recessive genotype (TT) was associated with a 0.9% per year steeper decline (P = 4.50 × 10(-5)). Statistically significant gene-by-smoking interactions were observed for variants in two genes in European Americans: the minor allele of rs2297765 in mGST3 attenuated the accelerated decline in FEV₁/FVC in smokers by 0.45% per year (P = 1.13 × 10(-4)); for participants with greater baseline smoking pack-years, the minor allele of rs2073192 in IDH3B was associated with an accelerated decline in FEV₁/FVC (P = 2.10 × 10(-4)). For both genes, nominally significant interactions (P < 0.01) were observed at the gene level in African Americans (P = 0.007 and 4.60 × 10(-4), respectively). Nominally significant evidence of association was observed for variants in SOD3 and GLRX2 in multiple analyses. This study identifies two novel genes associated with longitudinal lung function phenotypes in both African and European Americans and confirms a prior finding for GCLC. These findings suggest novel mechanisms and molecular targets for future research and advance the understanding of genetic determinants of lung function and COPD risk. Copyright © 2013 Elsevier Inc. All rights reserved.

White donor, younger donor and double lung transplant are associated with better survival in sarcoidosis patients.

PubMed

Salamo, Oriana; Roghaee, Shiva; Schweitzer, Michael D; Mantero, Alejandro; Shafazand, Shirin; Campos, Michael; Mirsaeidi, Mehdi

2018-05-03

Sarcoidosis commonly affects the lung. Lung transplantation (LT) is required when there is a severe and refractory involvement. We compared post-transplant survival rates of sarcoidosis patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). We also explored whether the race and age of the donor, and double lung transplant have any effect on the survival in the post transplant setting. We analyzed 9,727 adult patients with sarcoidosis, COPD, and IPF who underwent LT worldwide between 2005-2015 based on United Network for Organ Sharing (UNOS) database. Survival rates were compared with Kaplan-Meier, and risk factors were investigated by Cox-regression analysis. 469 (5%) were transplanted because of sarcoidosis, 3,688 (38%) for COPD and 5,570 (57%) for IPF. Unadjusted survival analysis showed a better post-transplant survival rate for patients with sarcoidosis (p < 0.001, Log-rank test). In Cox-regression analysis, double lung transplant and white race of the lung donor showed to have a significant survival advantage. Since double lung transplant, those who are younger and have lower Lung Allocation Score (LAS) at the time of transplant have a survival advantage, we suggest double lung transplant as the procedure of choice, especially in younger sarcoidosis subjects and with lower LAS scores.

Efficacy and mechanisms of behavioral therapy components for insomnia coexisting with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial.

PubMed

Kapella, Mary C; Herdegen, James J; Laghi, Franco; Steffen, Alana D; Carley, David W

2016-05-23

Difficulty falling asleep, staying asleep or poor-quality sleep (insomnia) is common in people with chronic obstructive pulmonary disease (COPD). Insomnia is related to greater mortality and morbidity, with four times the risk of mortality for sleep times below 300 min. However, insomnia medications are used with caution in COPD due to their potential adverse effects. While cognitive behavioral therapy for insomnia (CBT-I) is effective for people with primary insomnia and people with other chronic illnesses, the efficacy and mechanisms of action of such a therapy are yet unclear in people with both insomnia and COPD. The purpose of this study is to rigorously test the efficacy of two components of insomnia therapy - CBT-I and COPD education (COPD-ED) - in people with coexisting insomnia and COPD, and to identify mechanisms responsible for therapy outcomes. The rationale for the proposed study is that once the efficacy and mechanisms of CBT-I and COPD-ED are known, new and innovative approaches for insomnia coexisting with COPD can be developed to non-pharmacologically minimize insomnia and fatigue, thereby leading to longer, higher-quality and more productive lives for people with COPD, and reduced societal cost due to the effects of insomnia. We are conducting a randomized, controlled, parallel-group (N = 35 each group) comparison of CBT-I, COPD-ED and non-COPD, non-sleep health education Attention Control (AC) using a highly efficient four-group design. Arm 1 comprises 6 weekly sessions of CBT-I + AC; Arm 2 = 6 weekly sessions of COPD-ED + AC; Arm 3 = 6 weekly sessions of CBT-I + COPD-ED; and Arm 4 = 6 weekly sessions of AC. This design will allow completion of the following specific aims: (1) to determine the efficacy of individual treatment components, CBT-I and COPD-ED, on insomnia and fatigue, (2) to define the mechanistic contributors to the outcomes after CBT-I and COPD-ED. The research is innovative because it represents a new and substantive departure from the usual insomnia therapy, namely by testing traditional CBT-I with education to enhance outcomes. The work proposed in aims 1 and 2 will provide systematic evidence of the efficacy and mechanisms of components of a novel approach to insomnia comorbid with COPD. Such results are highly likely to provide new approaches for preventive and therapeutic interventions for insomnia and fatigue in COPD. ClinicalTrials.gov Identifier: NCT01973647 . Registered on 22 October 2013.

Differences in Adjustment between Individuals with Alpha-1 Antitrypsin Deficiency (AATD) Associated COPD and Non-AATD COPD

PubMed Central

Holm, Kristen E.; Borson, Soo; Sandhaus, Robert A.; Ford, Dee W.; Strange, Charlie; Bowler, Russell P.; Make, Barry J.; Wamboldt, Frederick S.

2013-01-01

Smokers who have severe alpha-1 antitrypsin deficiency (AATD) are at risk for developing COPD earlier in life than smokers without AATD, and are likely to experience challenges adjusting to their illness because they are in a highly productive life stage when they are diagnosed with COPD. This study examined whether individuals with AATD-associated COPD differ from individuals with non-AATD COPD with regard to depression, anxiety, dyspnea, and health-related quality of life (HRQL). Cross-sectional data were collected via self-report questionnaires completed by 480 individuals with non-AATD COPD and 578 individuals with AATD-associated COPD under protocols with IRB approval. Multiple linear regression models were used to test whether individuals with non-AATD COPD differed from individuals with AATD-associated COPD with regard to depression, anxiety, dyspnea, and HRQL. All models adjusted for demographic and health characteristics. Individuals with AATD-associated COPD did not report more symptoms of depression or anxiety; however, they did report more dyspnea (B = 0.31, 95% CI = 0.16 to 0.47, p < 0.001) and impairment in HRQL (B = 4.75, 95% CI = 2.10 to 7.41, p < 0.001) than other individuals with COPD. Individuals with AATD-associated COPD were more likely to be a member of a couple (rather than single) and had a higher level of education when compared to individuals with non-AATD COPD. Resources available to persons with AATD-associated COPD, such as being in a serious relationship and having higher education, may offset the effect of age when considering symptoms of depression and anxiety in patients with COPD. PMID:23547634

Differences in adjustment between individuals with alpha-1 antitrypsin deficiency (AATD)-associated COPD and non-AATD COPD.

PubMed

Holm, Kristen E; Borson, Soo; Sandhaus, Robert A; Ford, Dee W; Strange, Charlie; Bowler, Russell P; Make, Barry J; Wamboldt, Frederick S

2013-04-01

Smokers who have severe alpha-1 antitrypsin deficiency (AATD) are at risk for developing COPD earlier in life than smokers without AATD, and are likely to experience challenges adjusting to their illness because they are in a highly productive life stage when they are diagnosed with COPD. This study examined whether individuals with AATD-associated COPD differ from individuals with non-AATD COPD with regard to depression, anxiety, dyspnea, and health-related quality of life (HRQL). Cross-sectional data were collected via self-report questionnaires completed by 480 individuals with non-AATD COPD and 578 individuals with AATD-associated COPD under protocols with IRB approval. Multiple linear regression models were used to test whether individuals with non-AATD COPD differed from individuals with AATD-associated COPD with regard to depression, anxiety, dyspnea, and HRQL. All models adjusted for demographic and health characteristics. Individuals with AATD-associated COPD did not report more symptoms of depression or anxiety; however, they did report more dyspnea (B = 0.31, 95% CI = 0.16 to 0.47, p < 0.001) and impairment in HRQL (B = 4.75, 95% CI = 2.10 to 7.41, p < 0.001) than other individuals with COPD. Individuals with AATD-associated COPD were more likely to be a member of a couple (rather than single) and had a higher level of education when compared to individuals with non-AATD COPD. Resources available to persons with AATD-associated COPD, such as being in a serious relationship and having higher education, may offset the effect of age when considering symptoms of depression and anxiety in patients with COPD.

Clinical characteristics of patients with chronic obstructive pulmonary disease overlapped with bronchial asthma.

PubMed

Liang, Jing-Bo; Liu, Li-Jin; Fang, Qiu-Hong

2017-05-01

The clinical characteristics of patients with chronic obstructive pulmonary disease overlapped with bronchial asthma (COPD-BA) have not been discussed thoroughly. To reveal the clinical features of patients with COPD-BA, to evaluate the risk factors of COPD-BA, and to provide suggestions for COPD individualized therapy. A retrospective observational study was performed. A total of 182 patients with COPD (90 with COPD-BA and 92 with pure COPD) were recruited in the study. Information on the following items was collected: demographics, clinical manifestations, complications, laboratory findings, other histories, and inpatient treatments during exacerbation. A total of 182 patients were diagnosed with COPD, with 90 (49.45%) being classified as having COPD-BA. Patients with COPD-BA were more likely to be female (P = .004) and experienced more severe respiratory exacerbations (P = .04) despite being younger (P = .008). Those patients at onset of recurrent cough and sputum production were younger (P = .001). Significantly, a positive asthmatic family history (P = .03) was observed. Patients with COPD-BA usually had higher level of total serum IgE (although no differences were observed), had higher positive rates of the serum specific IgE (P = .004), and were more like to have an allergic history (P = .003). Allergic factor was the risk factor of COPD-BA (odds ratio, 4.477). During hospitalization, patients with COPD-BA tended to be treated with systemic corticosteroids (P = .008). Patients with COPD-BA were characterized by persistent airflow limitation with unique clinical features. Allergic factor was associated with the presence of asthmatic characteristics in patients with COPD. When hospitalized for exacerbation, the individualized therapy for COPD-BA might include the use of corticosteroids systemically. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Resource use during the last 6 months of life among COPD patients: a population level study.

PubMed

Faes, Kristof; Cohen, Joachim; Annemans, Lieven

2018-06-11

Chronic obstructive pulmonary disease (COPD) patients often have several comorbidities, such as cardiovascular diseases (CVD) or lung cancer (LC), which might influence resource use in the final months of life. However, no previous studies documented resource use in end-of-life COPD patients at a population level, thereby differentiating whether COPD patients die of their COPD, CVD or LC. To describe end-of-life resource use in people diagnosed with COPD and compare this resource use between those dying of COPD, CVD and LC. We performed a full-population retrospective analysis of all Belgian decedents. Those who died of COPD were selected based on the primary cause of death. Those who died with COPD but with CVD or LC as primary cause of death were identified based on a validated algorithm expanded with COPD as intermediate or associated. Resource use among 13.086 patients dying of or with COPD was studied. Those who died of COPD received less opioids, sedatives and morphine; used less palliative care services; and received more invasive and non-invasive ventilation as compared to the other 2 groups. Those who died of LC had more specialist contacts, hospital admissions and medical imaging as compared to those who died of COPD or CVD. Those who died of CVD used less palliative care services when compared to those who died of LC and had a comparable use of hospital, ICU, home care, opioids, sedatives and morphine as those who died of COPD. The presence of lung cancer and cardiovascular diseases influences resource use in COPD patients at life's end. We recommend that future research on end-of-life care in COPD systematically accounts for specific comorbidities. Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Forecasting Hospitalization and Emergency Department Visit Rates for Chronic Obstructive Pulmonary Disease. A Time-Series Analysis.

PubMed

Gershon, Andrea; Thiruchelvam, Deva; Moineddin, Rahim; Zhao, Xiu Yan; Hwee, Jeremiah; To, Teresa

2017-06-01

Knowing trends in and forecasting hospitalization and emergency department visit rates for chronic obstructive pulmonary disease (COPD) can enable health care providers, hospitals, and health care decision makers to plan for the future. We conducted a time-series analysis using health care administrative data from the Province of Ontario, Canada, to determine previous trends in acute care hospitalization and emergency department visit rates for COPD and then to forecast future rates. Individuals aged 35 years and older with physician-diagnosed COPD were identified using four universal government health administrative databases and a validated case definition. Monthly COPD hospitalization and emergency department visit rates per 1,000 people with COPD were determined from 2003 to 2014 and then forecasted to 2024 using autoregressive integrated moving average models. Between 2003 and 2014, COPD prevalence increased from 8.9 to 11.1%. During that time, there were 274,951 hospitalizations and 290,482 emergency department visits for COPD. After accounting for seasonality, we found that monthly COPD hospitalization and emergency department visit rates per 1,000 individuals with COPD remained stable. COPD prevalence was forecasted to increase to 12.7% (95% confidence interval [CI], 11.4-14.1) by 2024, whereas monthly COPD hospitalization and emergency department visit rates per 1,000 people with COPD were forecasted to remain stable at 2.7 (95% CI, 1.6-4.4) and 3.7 (95% CI, 2.3-5.6), respectively. Forecasted age- and sex-stratified rates were also stable. COPD hospital and emergency department visit rates per 1,000 people with COPD have been stable for more than a decade and are projected to remain stable in the near future. Given increasing COPD prevalence, this means notably more COPD health service use in the future.

Prevalence of asthma with airflow limitation, COPD, and COPD with variable airflow limitation in older subjects in a general Japanese population: the Hisayama Study.

PubMed

Matsumoto, Koichiro; Seki, Nanae; Fukuyama, Satoru; Moriwaki, Atsushi; Kan-o, Keiko; Matsunaga, Yuko; Noda, Naotaka; Yoshida, Makoto; Koto, Hiroshi; Takata, Shohei; Nakanishi, Yoichi; Kiyohara, Yutaka; Inoue, Hiromasa

2015-01-01

Elucidating the prevalence of asthma and chronic obstructive pulmonary disease (COPD) is important for designing a public health strategy. Recent studies have discriminated a phenotype of COPD with variable airflow limitation (COPD-VAL) associated with asthma-COPD overlap syndrome. Its prevalence remains uncertain. The age and occupational distributions in the town of Hisayama and in Japan are nearly identical. Each disease's prevalence was estimated for the town's residents. In 2008, town residents (≥ 40 years) were solicited to participate in a health checkup. Individuals with abnormal spirometry (forced expiratory volume in 1s/forced vital capacity [FEV1/FVC]<70% and/or %FVC<80%) were recommended for further evaluations. Two pulmonologists in a blinded fashion reviewed their medical records, including bronchodilator reversibility. Individuals with airflow limitation were classified as having asthma, COPD, COPD-VAL, or other diseases. The prevalence of each disease was then estimated. A total of 2100 residents (43.4% of residents in the age group) completed spirometry. In 455 residents with abnormal spirometry, 190 residents had further evaluations, and the medical records of 174 residents were reviewed. The prevalence of asthma with airflow limitation, COPD, and COPD-VAL, were 2.0%, 8.4%, and 0.9%, respectively. The prevalence of COPD and COPD-VAL were higher in men and smokers than in women and never-smokers. The prevalence of COPD, but not COPD-VAL or asthma, increased with age. The prevalence of asthma with airflow limitation, COPD, and COPD-VAL were estimated in a population of residents (≥ 40 years) in Hisayama. Copyright © 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Lung function and blood markers of nutritional status in non-COPD aging men with smoking history: a cross-sectional study.

PubMed

Shiozawa, Nobuyoshi; Hayashimoto, Kanae; Suzuki, Etsuji; Kikuchi, Hiroshi; Takata, Shingo; Ashida, Kozo; Watanabe, Masutaka; Hosaki, Yasuhiro; Mitsunobu, Fumihiro

2010-08-09

Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men. This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV(1)/FVC), and 17 with COPD (COPD group). After adjustment for potential confounders, lower FEV(1)/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group. In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.

Osteoporosis in Chronic Obstructive Pulmonary Disease

PubMed Central

Sarkar, Malay; Bhardwaj, Rajeev; Madabhavi, Irappa; Khatana, Jasmin

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related chronic inflammatory pulmonary disease associated with significant morbidity and mortality worldwide. COPD is associated with various comorbidities found in all stages of COPD. The comorbidities have significant impact in terms of morbidity, mortality, and economic burden in COPD. Management of comorbidities should be incorporated into the comprehensive management of COPD as this will also have an effect on the outcome in COPD patients. Various comorbidities reported in COPD include cardiovascular disease, skeletal muscle dysfunction, anemia, metabolic syndrome, and osteoporosis. Osteoporosis is a significant comorbidity in COPD patients. Various risk factors, such as tobacco smoking, systemic inflammation, vitamin D deficiency, and the use of oral or inhaled corticosteroids (ICSs) are responsible for its occurrence in patients with COPD. This review will focus on the prevalence, pathogenesis, risk factors, diagnosis, and treatment of osteoporosis in COPD patients. PMID:25788838

Understanding COPD-overlap syndromes.

PubMed

Poh, Tuang Yeow; Mac Aogáin, Micheál; Chan, Adrian Kwok Wai; Yii, Anthony Chau Ang; Yong, Valerie Fei Lee; Tiew, Pei Yee; Koh, Mariko Siyue; Chotirmall, Sanjay Haresh

2017-04-01

Chronic obstructive pulmonary disease accounts for a large burden of lung disease. It can 'overlap' with other respiratory diseases including bronchiectasis, fibrosis and obstructive sleep apnea (OSA). While COPD alone confers morbidity and mortality, common features with contrasting clinical outcomes can occur in COPD 'overlap syndromes'. Areas covered: Given the large degree of heterogeneity in COPD, individual variation to treatment is adopted based on its observed phenotype, which in turn overlaps with features of other respiratory disease states such as asthma. This is coined asthma-COPD overlap syndrome ('ACOS'). Other examples of such overlapping clinical states include bronchiectasis-COPD ('BCOS'), fibrosis-COPD ('FCOS') and OSA-COPD ('OCOS'). The objective of this review is to highlight similarities and differences between the COPD-overlap syndromes in terms of risk factors, pathophysiology, diagnosis and potential treatment differences. Expert commentary: As a consequence of COPD overlap syndromes, a transition from the traditional 'one size fits all' treatment approach is necessary. Greater treatment stratification according to clinical phenotype using a precision medicine approach is now required. In this light, it is important to recognize and differentiate COPD overlap syndromes as distinct disease states compared to individual diseases such as asthma, COPD, fibrosis or bronchiectasis.

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

PubMed

Braido, F; Scichilone, N; Lavorini, F; Usmani, O S; Dubuske, L; Boulet, L P; Mosges, R; Nunes, C; Sanchez-Borges, M; Ansotegui, I J; Ebisawa, M; Levi-Schaffer, F; Rosenwasser, L J; Bousquet, J; Zuberbier, T; Canonica, G Walter; Cruz, A; Yanez, A; Yorgancioglu, A; Deleanu, D; Rodrigo, G; Berstein, J; Ohta, K; Vichyanond, P; Pawankar, R; Gonzalez-Diaz, S N; Nakajima, S; Slavyanskaya, T; Fink-Wagner, A; Loyola, C Baez; Ryan, D; Passalacqua, G; Celedon, J; Ivancevich, J C; Dobashi, K; Zernotti, M; Akdis, M; Benjaponpitak, S; Bonini, S; Burks, W; Caraballo, L; El-Sayed, Z Awad; Fineman, S; Greenberger, P; Hossny, E; Ortega-Martell, J A; Saito, H; Tang, M; Zhang, L

2016-01-01

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA 2 LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD.

PubMed

Davidsen, Peter K; Herbert, John M; Antczak, Philipp; Clarke, Kim; Ferrer, Elisabet; Peinado, Victor I; Gonzalez, Constancio; Roca, Josep; Egginton, Stuart; Barberá, Joan A; Falciani, Francesco

2014-01-01

A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting. We have used a systems biology approach to compare the transcriptional profile of hindlimb skeletal muscles from a Guinea pig rodent model exposed to CS and/or chronic hypoxia to COPD patients with muscle wasting. We show that guinea pigs exposed to long-term CS accurately reflect most of the transcriptional changes observed in dysfunctional limb muscle of severe COPD patients when compared to matched controls. Using network inference, we could then show that the expression profile in whole lung of genes encoding for soluble inflammatory mediators is informative of the molecular state of skeletal muscles in the guinea pig smoking model. Finally, we show that CXCL10 and CXCL9, two of the candidate systemic cytokines identified using this pre-clinical model, are indeed detected at significantly higher levels in serum of COPD patients, and that their serum protein level is inversely correlated with the expression of aerobic energy metabolism genes in skeletal muscle. We conclude that CXCL10 and CXCL9 are promising candidate inflammatory signals linked to the regulation of central metabolism genes in skeletal muscles. On a methodological level, our work also shows that a system level analysis of animal models of diseases can be very effective to generate clinically relevant hypothesis.

Pulmonary Rehabilitation in Ontario: A Cross-Sectional Survey

PubMed Central

Bowen, James M; Campbell, Kaitryn; Sutherland, Simone; Bartlett, Ann; Brooks, Dina; Qureshi, Riaz; Goldstein, Roger; Gershon, Andrea S; Prevost, Shelley; Samis, Lorelei; Kaplan, Alan G; Hopkins, Robert B; MacDougald, Craig; Nunes, Erica; O'Reilly, Daria J; Goeree, Ron

2015-01-01

Background Pulmonary rehabilitation (PR) is a comprehensive intervention of exercise training, education, and behaviour change to improve the physical and psychological condition of people with chronic respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and to promote long-term adherence to health-enhancing behaviours. Although PR is considered the standard of care for patients with COPD who remain symptomatic despite bronchodilator therapies, current evidence suggests that only 1.15% of COPD patients across Canada have access to PR facilities for care. Objectives The objectives of this study were to identify the number of health care facilities across Ontario providing PR services for patients with COPD, describe the scope of those services, and determine the province's current capacity to provide PR services relative to need, for the province as a whole and by local health integration network (LHIN). Methods The Pulmonary Rehabilitation Programs in Ontario (PRO) Survey was a province-wide, descriptive, cross-sectional survey of health care facilities (hospitals, family health teams, and community health centres). It was distributed to 409 facilities to collect information on various aspects of PR services in the province. Results Between April 2013 and February 2014, 187 facilities responded to the survey (46% response rate). Most responding centres (144) did not offer PR services, and only 43 were full PR sites providing a comprehensive program. Hospital-based programs made up the majority of sites offering full PR services (67%), followed by programs based at family health teams (19%) and community health centres (14%). More than 90% of PR programs are outpatient-based. The average wait time for outpatient PR was 6.9 weeks, and 58% of programs provide services 5 days per week. More than 80% of patients attending PR complete the full program. Across all program types, the total estimated provincial capacity for PR outpatient care is 4,524 patients per year, or 0.66% to 1.78% of patients with COPD, depending on the estimated prevalence of disease. Limitations These results are representative of 12 of the 14 LHINs in Ontario due to low response rates in facilities in 2 LHINs. Conclusions Although some increase in capacity has occurred since a similar survey in 2005, PR resources in Ontario are insufficient to support the delivery of care to people with COPD in accordance with clinical practice guideline recommendations. PMID:26366242

[A cross-sectional survey of familial aggregation of chronic obstructive pulmonary disease: in seven provinces/cities in China].

PubMed

Zhou, Yumin; Wang, Chen; Yao, Wanzhen; Chen, Ping; Kang, Jian; Huang, Shaoguang; Chen, Baoyuan; Wang, Changzheng; Ni, Diantao; Wang, Xiaoping; Wang, Dali; Liu, Shengming; Lyu, Jiachun; Zheng, Jinping; Zhong, Nanshan; Ran, Pixin

2014-05-01

To investigate the familial aggregation in chronic obstructive pulmonary disease (COPD). Based on a cross-sectional survey in seven provinces/cities in China (Beijing, Shanghai, Guangdong, Liaoning, Tianjin, Chongqing and Shaanxi) from 2002 to 2004, the familial aggregation of COPD was investigated with multi-stage cluster random sampling method.One urban and one rural area were selected as samples from each of seven provinces/cities. All residents equal or older than 40 years old received questionnaires and pulmonary function tests. Questionnaires included risk factors of COPD, respiratory symptoms, quality of life, diagnosis and prevention conditions of COPD. Bronchodilator tests, physical examination, X-ray and electrocardiograph (ECG) were conducted in those subjects.In pulmonary function tests, the ratio of the first second forced expiratory volume (FEV1) /forced vital capacity (FVC) less than 70% fulfill the diagnostic criteria of COPD.If any of siblings and parents had chronic bronchitis, emphysema, asthma or COPD, it should be considered as a positive family history of COPD-related disease.Otherwise, it was negative. FEV1 was lower in the subjects with a family history of COPD-related diseases than in those without [(2.24 ± 0.70) L vs (2.28 ± 0.73) L]. The prevalence of COPD in the population with history of COPD-related diseases was 12.1% (540/4 481), which was significantly higher than that without [7.2% (1 128/15 764), χ(2) = 110.599, P < 0.001]. After adjusted for potential confounder, the population with a family history of COPD-related diseases still had much higher incidence of COPD [OR = 2.18 (95%CI 1.94-2.46)]. Furthermore, the population having two or more first-degree relatives with COPD-related diseases, exhibited the highest likelihood of COPD [OR = 2.48 (95%CI 2.00-3.08)]. The population having only one first-degree relative with COPD-related diseases showed an increased risk of COPD with an OR = 2.10 (95%CI 1.84-2.40) compared with those without any one. Those whose father, mother or siblings had COPD-related diseases were similarly likely to have COPD, with an OR of 1.54 (95%CI 1.32-1.80), 1.83 (95%CI 1.56-2.15) and 1.81 (95%CI 1.48-2.23), respectively. There is a familial aggregation in COPD. The more relatives have COPD-related diseases in the family, the greater risk of COPD the subject will have.

COPD and stroke: are systemic inflammation and oxidative stress the missing links?

PubMed

Austin, Victoria; Crack, Peter J; Bozinovski, Steven; Miller, Alyson A; Vlahos, Ross

2016-07-01

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. © 2016 The Author(s).

Characterization of throat microbial flora in smokers with or without COPD

PubMed Central

Diao, Wenqi; Shen, Ning; Du, Yipeng; Qian, Ke; He, Bei

2017-01-01

The study aimed to determine the relationship between throat microbiome and COPD. Sixty-five Chinese males (n=20, smokers without COPD; n=45 smokers with COPD) were included. Nonmetric multidimensional scaling indicated differences of microbiome between COPD and controls, but no difference was observed between COPD patients with differing degrees of lung function or disease severity. Rarefaction analyses suggested that operational taxonomic units (OTUs, species-level) richness decreased in COPD. The dominant taxa between COPD and controls were similar, but the proportions of taxonomic distribution were different. The dominant phyla were Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria. The dominant genera were Haemophilus, Leptotrichia, Porphyromonas, Fusobacterium, Veillonella, Streptococcus, Neisseria and Prevotella. Two dominant OTUs, otu3 (Veillonella_dispar) and otu4 (Streptococcus_unclassified), were identified. Otu3 and its father-level taxa, which were negatively correlated with predicted percent of forced expiratory volume in a second (FEV1%pred), were increased in COPD. By contrast, otu4 and its father-level taxa, which were positively correlated with FEV1%pred, were decreased in COPD. Otu4 also showed a slight potential as a COPD biomarker. To conclude, the throat microbiome was different between smokers with or without COPD, which is similar to findings from the lower respiratory tract. This study may strengthen our understanding of the relationship between microbiomes of different airway sites and COPD. PMID:28740374

Chronic obstructive pulmonary disease and body mass index in five Latin America cities: the PLATINO study.

PubMed

Montes de Oca, Maria; Tálamo, Carlos; Perez-Padilla, Rogelio; Jardim, José Roberto B; Muiño, Adriana; Lopez, Maria Victorina; Valdivia, Gonzalo; Pertuzé, Julio; Moreno, Dolores; Halbert, Ronald J; Menezes, Ana Maria B

2008-05-01

The body mass index (BMI) is a prognostic factor for chronic obstructive pulmonary disease (COPD). Despite its importance, little information is available regarding BMI alteration in COPD from a population-based study. We examined characteristics by BMI categories in the total and COPD populations in five Latin-American cities, and explored the factors influencing BMI in COPD. COPD was defined as a postbronchodilator forced expiratory volume in the first second/forced vital capacity (FEV(1)/FVC) <0.70. BMI was categorized as underweight (< 20 kg/m(2)), normal weight (20-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (> or = 30.0 kg/m(2)). Interviews were completed in 5571 subjects from 6711 eligible individuals, and spirometry was performed in 5314 subjects. There were 759 subjects with COPD and 4555 without COPD. Compared with the non-COPD group, there was a higher proportion of COPD subjects in the underweight and normal weight categories, and a lower proportion in the obese category. Over one-half COPD subjects had BMI over 25 kg/m(2). No differences in BMI strata among countries were found in COPD subjects. Factors associated with lower BMI in males with COPD were aging, current smoking, and global initiative for chronic obstructive lung disease (GOLD) stages III-IV, whereas wheeze and residing in Santiago and Montevideo were associated with higher BMI. In females with COPD, current smoking, lower education, and GOLD stages II-IV were associated with lower BMI, while dyspnea and wheeze were associated with higher BMI. BMI alterations are common in COPD with no significant differences among countries. Current smoking, age, GOLD stages, education level, residing in Santiago and Montevideo, dyspnea and wheeze were independently associated with BMI in COPD.

Impaired Hemorheology in Exacerbations of COPD

PubMed Central

Can, Ilknur; Kilic-Erkek, Ozgen; Altinisik, Goksel; Bor-Kucukatay, Melek

2017-01-01

Background Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation. Cardiovascular-related comorbidities are established to contribute to morbidity and mortality especially during exacerbations. The aim of the current study was to determine alterations in hemorheology (erythrocyte aggregation, deformability) in newly diagnosed COPD patients and their response to medical treatment and to compare with values of COPD patients with exacerbations. Materials and Methods The study comprised 13 COPD patients, 12 controls, and 16 COPD patients with exacerbations. The severity of COPD was determined according to Global Initiative for Chronic Obstructive Lung Disease guidelines. Red blood cell (RBC) deformability and aggregation were measured by an ektacytometer. Results RBC deformability of COPD patients with exacerbations was decreased compared to the other groups. Erythrocyte aggregation and plasma fibrinogen of COPD patients determined during exacerbations were higher than control. Conclusion Decreased RBC deformability and increased aggregation associated with exacerbations of COPD may serve as unfavorable mechanisms to worsen oxygenation and thus clinical symptoms of the patient. Treatment modalities that modify rheological parameters might be beneficial. PMID:29089816

An integrated programme after pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: effect on emotional and functional dimensions of quality of life.

PubMed

Moullec, G; Ninot, G

2010-02-01

To assess whether a maintenance integrated health care programme is effective in improving functional and emotional dimensions of quality of life in patients with chronic obstructive pulmonary disease (COPD) after a first pulmonary rehabilitation. Prospective controlled trial. Three rehabilitation centres and three patient self-help associations within a health care network in France. Forty patients with moderate to severe COPD. After a first four-week inpatient pulmonary rehabilitation programme, patients took part in a maintenance integrated health care programme or usual care for 12 months. The primary outcomes were the change in functional and emotional dimensions of quality of life measured by the St George's Respiratory Questionnaire (SGRQ), the brief World Health Organization Quality of Life questionnaire (Brief-WHOQOL) and six specific questions using a 10-cm visual analogue scale. Secondary outcomes were change in exercise tolerance measured by six-minute walking test and cycle exercise. At one year, the maintenance intervention (n = 11) produced improvements in functional and emotional dimensions scores of quality of life and exercise tolerance. Patients in the usual aftercare group (n = 16) exhibited maintenance of functional dimension scores of quality of life, but a clinically relevant decline in emotional scores of quality of life and in six-minute walking distance one year after the pulmonary rehabilitation. Patient self-help association seems to be an innovative and efficient organizational structure to support patients with COPD after pulmonary rehabilitation in real-life settings. A distinction between emotional and functional dimensions of quality of life may improve the design and evaluation of integrated health care programmes in patients with COPD.

Disease Staging and Prognosis in Smokers Using Deep Learning in Chest Computed Tomography.

PubMed

González, Germán; Ash, Samuel Y; Vegas-Sánchez-Ferrero, Gonzalo; Onieva Onieva, Jorge; Rahaghi, Farbod N; Ross, James C; Díaz, Alejandro; San José Estépar, Raúl; Washko, George R

2018-01-15

Deep learning is a powerful tool that may allow for improved outcome prediction. To determine if deep learning, specifically convolutional neural network (CNN) analysis, could detect and stage chronic obstructive pulmonary disease (COPD) and predict acute respiratory disease (ARD) events and mortality in smokers. A CNN was trained using computed tomography scans from 7,983 COPDGene participants and evaluated using 1,000 nonoverlapping COPDGene participants and 1,672 ECLIPSE participants. Logistic regression (C statistic and the Hosmer-Lemeshow test) was used to assess COPD diagnosis and ARD prediction. Cox regression (C index and the Greenwood-Nam-D'Agnostino test) was used to assess mortality. In COPDGene, the C statistic for the detection of COPD was 0.856. A total of 51.1% of participants in COPDGene were accurately staged and 74.95% were within one stage. In ECLIPSE, 29.4% were accurately staged and 74.6% were within one stage. In COPDGene and ECLIPSE, the C statistics for ARD events were 0.64 and 0.55, respectively, and the Hosmer-Lemeshow P values were 0.502 and 0.380, respectively, suggesting no evidence of poor calibration. In COPDGene and ECLIPSE, CNN predicted mortality with fair discrimination (C indices, 0.72 and 0.60, respectively), and without evidence of poor calibration (Greenwood-Nam-D'Agnostino P values, 0.307 and 0.331, respectively). A deep-learning approach that uses only computed tomography imaging data can identify those smokers who have COPD and predict who are most likely to have ARD events and those with the highest mortality. At a population level CNN analysis may be a powerful tool for risk assessment.

Risk of death and readmission of hospital-admitted COPD exacerbations: European COPD Audit.

PubMed

Hartl, Sylvia; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Castro-Acosta, Ady; Studnicka, Michael; Kaiser, Bernhard; Roberts, C Michael

2016-01-01

Studies report high in-hospital and post-discharge mortality of chronic obstructive pulmonary disease (COPD) exacerbations varying depending upon patient characteristics, hospital resources and treatment standards. This study aimed to investigate the patient, resource and organisational factors associated with in-hospital and 90-day post-discharge mortality and readmission of COPD exacerbations within the European COPD Audit. The audit collected data of COPD exacerbation admissions from 13 European countries.On admission, only 49.7% of COPD patients had spirometry results available and only 81.6% had blood gases taken. Using logistic regression analysis, the risk associated with in-hospital and post-discharge mortality was higher age, presence of acidotic respiratory failure, subsequent need for ventilatory support and presence of comorbidity. In addition, the 90-day risk of COPD readmission was associated with previous admissions. Only the number of respiratory specialists per 1000 beds, a variable related to hospital resources, decreased the risk of post-discharge mortality.The European COPD Audit identifies risk factors associated with in-hospital and post-discharge mortality and COPD readmission. Addressing the deficiencies in acute COPD care such as making spirometry available and measuring blood gases and providing noninvasive ventilation more regularly would provide opportunities to improve COPD outcomes. Copyright ©ERS 2016.

Chronic obstructive pulmonary disease and malnutrition in developing countries.

PubMed

Sehgal, Inderpaul S; Dhooria, Sahajal; Agarwal, Ritesh

2017-03-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disorder characterized by progressive, poorly reversible airflow limitation. In addition to its pulmonary manifestations, COPD is also associated with several systemic expressions including anemia, osteoporosis, coronary artery disease, and malnutrition. In COPD, malnutrition is a consequence of reduced nutritional intake and muscle loss, further compounded by systemic inflammation. In the developing world, malnutrition is a significant problem by itself, even without any systemic illness. It is likely that the occurrence and consequence of malnutrition in COPD may be even more profound in developing countries. In this review, we discuss the relationship between malnutrition and COPD and their overall impact in the developing world. COPD is highly prevalent in developing countries with an estimated 15-43 million patients suffering from COPD. The pooled prevalence of malnutrition in COPD was found to be 47.6% [95% confidence interval (CI), 23.5-71.5%] with the prevalence being higher in acute exacerbations of COPD compared to stable COPD. There is a need for generating good quality evidence from the developing world regarding the prevalence of malnutrition in COPD, the role of nutritional supplementation and its impact on exercise capacity, and overall health-related quality of life in patients with COPD.

Impact of chronic obstructive pulmonary diseases on left ventricular diastolic function in hospitalized elderly patients.

PubMed

Huang, Ying-Shuo; Feng, Ying-Chao; Zhang, Jian; Bai, Li; Huang, Wei; Li, Min; Sun, Ying

2015-01-01

To evaluate the impact of chronic obstructive pulmonary disease (COPD) on left ventricular (LV) diastolic function in hospitalized elderly patients. This was a case-control observational study of 148 consecutive hospitalized elderly patients (≥65 years old): 73 subjects without COPD as controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1 and 2, while severe and very severe COPD was defined as stages 3 and 4, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Clinical characteristics and echocardiographic parameters were analyzed and compared. Compared with the control group, patients with COPD had a higher frequency of LV diastolic dysfunction and heart failure with preserved ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the COPD group (all P<0.05). COPD patients showed more abnormalities in diastolic function (E/e': 11.51±2.50 vs 10.42±3.25, P=0.047), but no differences in systolic function and right ventricular function (all P>0.05). Patients with severe/very severe COPD showed no differences in LV diastolic function compared to patients with mild/moderate COPD (P>0.05), but serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05). Results suggest that early-stage COPD may have an impact on the LV diastolic function. Severe COPD mainly affected right ventricular function. In hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken into account together with right ventricular function.

Chronic obstructive airway disease among patients hospitalized with acute heart failure; clinical characteristics, precipitating factors, management and outcome: Observational report from the Middle East.

PubMed

Khafaji, Hadi A R; Sulaiman, Kadhim; Singh, Rajvir; Alhabib, Khalid F; Asaad, Nidal; Alsheikh-Ali, Alawi; Al-Jarallah, Mohammed; Bulbanat, Bassam; Almahmeed, Wael; Ridha, Mustafa; Bazargani, Nooshin; Amin, Haitham; Al-Motarreb, Ahmed; Faleh, Husam Al; Elasfar, Abdelfatah; Panduranga, Prashanth; Suwaidi, Jassim Al

2015-12-01

The purpose of this study was to report the prevalence, clinical characteristics, contributing factors, management and outcome of patients with chronic obstructive pulmonary disease (COPD) among patients hospitalized with heart failure (HF). Data were derived from Gulf Care (Gulf acute heart failure registry), a prospective multicenter study of 5005 consecutive patients hospitalized with acute heart failure during February to November 2012 in seven Middle Eastern countries. Data were described and compared for demographics, management and outcomes. The prevalence of COPD among HF patients was 10%. COPD patients were older, more likely to be female and to have diabetes, hypertension, chronic kidney disease and sleep apnea (P = 0.001 for all) when compared to non-COPD patients. Contributing factors for hospitalization were systemic infection and atrial arrhythmias in COPD patients compared to acute coronary syndrome, uncontrolled hypertension and anemia in the non-COPD patients. Left-ventricular ejection fraction was higher in COPD patients; while BNP levels were comparable between the two groups. Non-invasive ventilation was used more frequently among COPD patients compared to non-COPD patients (P = 0.001). On multivariate logistic regression analysis, COPD was not associated with increased risk in-hospital and one-year death among acute heart failure (AHF) population and β blockers treatment appear to have neutral mortality effect in COPD patients with HF. COPD have distinct cardiovascular risk profile and precipitating factors for hospitalization with HF when compared to non-COPD patients. COPD history had no impact on the short-term and one-year mortality.

Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both.

PubMed

Olloquequi, Jordi; Jaime, Sergio; Parra, Viviana; Cornejo-Córdova, Elizabeth; Valdivia, Gonzalo; Agustí, Àlvar; Silva O, Rafael

2018-01-18

Exposure to noxious gases and particles contained in both tobacco smoking (TS) and biomass smoke (BS) are well recognized environmental risk factors for chronic obstructive pulmonary disease (COPD). COPD is characterized by an abnormal inflammatory response, both in the pulmonary and systemic compartments. The differential effects of TS, BS or their combined exposure have not been well characterized yet. This study sought to compare the lung function characteristics and systemic inflammatory response in COPD patients exposed to TS, BS or their combination. Sociodemographic, clinical and lung functional parameters were compared across 49 COPD patients with a history of smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and 52 healthy controls (HC) who have never been exposed neither to TS or BS. Blood cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE) levels were quantified in all four groups. TS + BS COPD patients exhibited significantly lower oxygen saturation than the rest of groups (p < 0.01). Spirometry and diffusing capacity were significantly higher in BS than in TS or TS + BS patients. CRP levels were significantly higher in TS COPD patients than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients with a history of smoking (TS and TS + BS) when compared to control subjects (p < 0.01). Finally, COPD patients with BS exposure (BS and BS + TS groups) showed higher IgE levels than TS and HC (p < 0.05). There are significant physiological and inflammatory differences between COPD patients with TS, BS and TS + BS exposures. The latter had worse blood oxygenation, whereas the raised levels of IgE in BS exposed patients suggests a differential Th2 systemic inflammatory pattern triggered by this pollutant.

Lung cancer and chronic obstructive pulmonary disease: From a clinical perspective

PubMed Central

Dai, Jie; Yang, Ping; Cox, Angela; Jiang, Gening

2017-01-01

Chronic obstructive pulmonary disease (COPD) and lung cancer are devastating pulmonary diseases that commonly coexist and present a number of clinical challenges. COPD confers a higher risk for lung cancer development, but available chemopreventive measures remain rudimentary. Current studies have shown a marked benefit of cancer screening in the COPD population, although challenges remain, including the common underdiagnosis of COPD. COPD-associated lung cancer presents distinct clinical features. Treatment for lung cancer coexisting with COPD is challenging as COPD may increase postoperative morbidities and decrease survival. In this review, we outline current progress in the understanding of the clinical association between COPD and lung cancer, and suggest possible cancer prevention strategies in this patient population. PMID:28061470

Risk of fall in patients with COPD.

PubMed

Hakamy, Ali; Bolton, Charlotte E; Gibson, Jack E; McKeever, Tricia M

2018-03-21

A matched cohort study was conducted to determine the incidence of falls in patients following a diagnosis of COPD using a UK primary care database. 44 400 patients with COPD and 175 545 non-COPD subjects were identified. The incidence rate of fall per 1000 person-years in patients with COPD was higher (44.9; 95% CI 44.1 to 45.8) compared with non-COPD subjects (24.1; 95% CI 23.8 to 24.5) (P<0.0001). Patients with COPD were 55% more likely to have an incident record of fall than non-COPD subjects (adjusted HR, 1.55; 95% CI 1.50 to 1.59). The greater falls risk in patients with COPD needs consideration and modifiable factors addressed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chronic obstructive pulmonary disease and sleep related disorders.

PubMed

Tsai, Sheila C

2017-03-01

Sleep related disorders are common and under-recognized in the chronic obstructive pulmonary disease (COPD) population. COPD symptoms can disrupt sleep. Similarly, sleep disorders can affect COPD. This review highlights the common sleep disorders seen in COPD patients, their impact, and potential management. Treatment of sleep disorders may improve quality of life in COPD patients. Optimizing inhaler therapy improves sleep quality. Increased inflammatory markers are noted in patients with the overlap syndrome of COPD and obstructive sleep apnea versus COPD alone. There are potential benefits of noninvasive positive pressure ventilation therapy for overlap syndrome patients with hypercapnia. Nocturnal supplemental oxygen may be beneficial in certain COPD subtypes. Nonbenzodiazepine hypnotic therapy for insomnia has shown benefit without associated respiratory failure or worsening respiratory symptoms. Melatonin may provide mild hypnotic and antioxidant benefits. This article discusses the impact of sleep disorders on COPD patients and the potential benefits of managing sleep disorders on respiratory disease control and quality of life.

Difference in serum magnesium level among patients with stable chronic obstructive pulmonary disease (COPD) and exacerbated COPD

NASA Astrophysics Data System (ADS)

Sanowara, R.; Keliat, E. N.; Abidin, A.

2018-03-01

Stable COPD is marked with various degrees of inflammation throughout large and small airways also in the alveoli which cause mucus hypersecretion, narrowing of the airway, and alveoli damage. Exacerbation is an episode of elevated inflammation. The relation between inflammation response and magnesium has been observed with the increase of proinflammation cytokines in magnesium deficiency. A cross-sectional study of 34 patients who came to RSUP H. Adam Malik (17 stable COPD patients and 17 acute exacerbated COPD patients) was conducted to examine serum magnesium level and spirometry in stable condition. Mean serum magnesium level for stable COPD patients group was 2.09 ± 0.11 mEq/L. It was higher than in the exacerbated COPD patients group 1.69 ± 0.27 mEq/L. Mann–Whitney statistical analysis showed a significant difference in magnesium level between stable COPD and exacerbated COPD groups (p<0.05).

Deposition of insoluble elastin by pulmonary fibroblasts from patients with COPD is increased by treatment with versican siRNA.

PubMed

Wu, Lian; Zhang, Jing; Qu, Jie Ming; Bai, Chun-Xue; Merrilees, Mervyn J

2017-01-01

A reduced content of alveolar elastic fibers is a key feature of COPD lung. Despite continued elastogenic potential by alveolar fibroblasts in the lung affected by COPD, repair of elastic fibers does not take place, which is due to increased levels of the chondroitin sulfate proteoglycan versican that inhibits the assembly of tropoelastin into fibers. In this study, primary pulmonary fibroblast cell lines from COPD and non-COPD patients were treated with a small interfering RNA (siRNA) against versican to determine if knockdown of versican could restore the deposition of insoluble elastin. Versican siRNA treatment reduced versican expression and secretion by pulmonary fibroblasts from both COPD and non-COPD patients ( P <0.01) and significantly increased deposition of insoluble elastin in the COPD cell cultures ( P <0.05). The treatment, however, did not significantly affect production of soluble elastin (tropoelastin) in either the COPD or non-COPD cell cultures, supporting a role for versican in inhibiting assembly but not synthesis of tropoelastin. These results suggest that removal or knockdown of versican may be a possible therapeutic strategy for increasing deposition of insoluble elastin and stimulating repair of elastic fibers in COPD lung.

FEV1 decline in patients with chronic obstructive pulmonary disease associated with biomass exposure.

PubMed

Ramírez-Venegas, Alejandra; Sansores, Raul H; Quintana-Carrillo, Roger H; Velázquez-Uncal, Monica; Hernandez-Zenteno, Rafael J; Sánchez-Romero, Candelaria; Velazquez-Montero, Alejandra; Flores-Trujillo, Fernando

2014-11-01

Biomass exposure is an important risk factor for chronic obstructive pulmonary disease (COPD). However, the time-course behavior of FEV1 in subjects exposed to biomass is unknown. We undertook this study to determine the FEV1 rate decline in subjects exposed to biomass. Pulmonary function was assessed every year in a Mexican cohort of patients with COPD associated with biomass or tobacco during a 15-year follow-up period. The mean rate of decline was significantly lower for the biomass exposure COPD group (BE-COPD) than for the tobacco smoke COPD group (TS-COPD) (23 vs. 42 ml, respectively; P < 0.01). Of the TS-COPD group, 11% were rapid decliners, whereas only one rapid decliner was found in the BE-COPD group; 69 and 21% of smokers versus 17 and 83% of the BE-COPD group were slow decliners and sustainers, respectively. A higher FEV1 both as % predicted and milliliters was a predictive factor for decline for BE-COPD and TS-COPD, whereas reversibility to bronchodilator was a predictive factor for both groups when adjusted by FEV1% predicted and only for the TS-COPD group when adjusted by milliliters. In the biomass exposure COPD group the rate of FEV1 decline is slower and shows a more homogeneous rate of decline over time in comparison with smokers. The rapid rate of FEV1 decline is a rare feature of biomass-induced airflow limitation.

COPD: Unique to Older Adults

MedlinePlus

... relaxed state Psychotherapy – individual, family, or group counseling Cardiovascular disease and COPD People with COPD tend to develop cardiovascular diseases at a higher rate than those without COPD. ...

Determinants of underdiagnosis of COPD in national and international surveys.

PubMed

Lamprecht, Bernd; Soriano, Joan B; Studnicka, Michael; Kaiser, Bernhard; Vanfleteren, Lowie E; Gnatiuc, Louisa; Burney, Peter; Miravitlles, Marc; García-Rio, Francisco; Akbari, Kaveh; Ancochea, Julio; Menezes, Ana M; Perez-Padilla, Rogelio; Montes de Oca, Maria; Torres-Duque, Carlos A; Caballero, Andres; González-García, Mauricio; Buist, Sonia

2015-10-01

COPD ranks within the top three causes of mortality in the global burden of disease, yet it remains largely underdiagnosed. We assessed the underdiagnosis of COPD and its determinants in national and international surveys of general populations. We analyzed representative samples of adults aged ≥ 40 years randomly selected from well-defined administrative areas worldwide (44 sites from 27 countries). Postbronchodilator FEV1/FVC < lower limit of normal (LLN) was used to define chronic airflow limitation consistent with COPD. Undiagnosed COPD was considered when participants had postbronchodilator FEV1/FVC < LLN but were not given a diagnosis of COPD. Among 30,874 participants with a mean age of 56 years, 55.8% were women, and 22.9% were current smokers. Population prevalence of (spirometrically defined) COPD ranged from 3.6% in Barranquilla, Colombia, to 19.0% in Cape Town, South Africa. Only 26.4% reported a previous lung function test, and only 5.0% reported a previous diagnosis of COPD, whereas 9.7% had a postbronchodilator FEV1/FVC < LLN. Overall, 81.4% of (spirometrically defined) COPD cases were undiagnosed, with the highest rate in Ile-Ife, Nigeria (98.3%) and the lowest rate in Lexington, Kentucky (50.0%). In multivariate analysis, a greater probability of underdiagnosis of COPD was associated with male sex, younger age, never and current smoking, lower education, no previous spirometry, and less severe airflow limitation. Even with substantial heterogeneity in COPD prevalence, COPD underdiagnosis is universally high. Because effective management strategies are available for COPD, spirometry can help in the diagnosis of COPD at a stage when treatment will lead to better outcomes and improved quality of life.

Continuing to Confront COPD International Patient Survey: Economic Impact of COPD in 12 Countries.

PubMed

Foo, Jason; Landis, Sarah H; Maskell, Joe; Oh, Yeon-Mok; van der Molen, Thys; Han, MeiLan K; Mannino, David M; Ichinose, Masakazu; Punekar, Yogesh

2016-01-01

The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries. Using data from this survey we evaluated the economic impact of COPD. This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications. Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale. Combined direct and indirect costs estimated the total societal costs per patient. The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs. The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%. Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities. The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities. Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs.

Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma.

PubMed

Menezes, Ana Maria B; Montes de Oca, Maria; Pérez-Padilla, Rogelio; Nadeau, Gilbert; Wehrmeister, Fernando César; Lopez-Varela, Maria Victorina; Muiño, Adriana; Jardim, José Roberto B; Valdivia, Gonzalo; Tálamo, Carlos

2014-02-01

Several COPD phenotypes have been described; the COPD-asthma overlap is one of the most recognized. The aim of this study was to evaluate the prevalence of three subgroups (asthma, COPD, and COPD-asthma overlap) in the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) study population, to describe their main characteristics, and to determine the association of the COPD-asthma overlap group with exacerbations, hospitalizations, limitations due to physical health, and perception of general health status (GHS). The PLATINO study is a multicenter population-based survey carried out in five Latin American cities. Outcomes were self-reported exacerbations (defined by deterioration of breathing symptoms that affected usual daily activities or caused missed work), hospitalizations due to exacerbations, physical health limitations, and patients' perception of their GHS obtained by questionnaire. Subjects were classified in three specific groups: COPD--a postbronchodilator (post-BD) FEV₁/FVC ratio of < 0.70; asthma--presence of wheezing in the last year and a minimum post-BD increase in FEV₁ or FVC of 12% and 200 mL; and overlap COPD-asthma--the combination of the two. Out of 5,044 subjects, 767 were classified as having COPD (12%), asthma (1.7%), and COPD-asthma overlap (1.8%). Subjects with COPD-asthma overlap had more respiratory symptoms, had worse lung function, used more respiratory medication, had more hospitalization and exacerbations, and had worse GHS. After adjusting for confounders, the COPD-asthma overlap was associated with higher risks for exacerbations (prevalence ratio [PR], 2.11; 95% CI, 1.08-4.12), hospitalizations (PR, 4.11; 95% CI, 1.45-11.67), and worse GHS (PR, 1.47; 95% CI, 1.18-1.85) compared with those with COPD. The coexisting COPD-asthma phenotype is possibly associated with increased disease severity.

Inflammatory biomarkers and radiologic measurements in never-smokers with COPD: A cross-sectional study from the CODA cohort

PubMed Central

Lee, Hyun; Hong, Yoonki; Lim, Myoung Nam; Bak, So Hyeon; Kim, Min-Ji; Kim, Kyunga; Kim, Woo Jin; Park, Hye Yun

2017-01-01

Various biomarkers have emerged as potential surrogates to represent various subgroups of chronic obstructive pulmonary disease (COPD), which manifest with different phenotypes. However, the biomarkers representing never-smokers with COPD have not yet been well elucidated. The aim of this study was to evaluate the associations of certain serum and radiological biomarkers with the presence of COPD in never-smokers. To explore the associations of serum and radiological biomarkers with the presence of COPD in never-smokers, we conducted a cross-sectional patient cohort study composed of never-smokers from the COPD in Dusty Areas (CODA) cohort, consisting of subjects living in dusty areas near cement plants in South Korea. Of the 131 never-smokers in the cohort, 77 (58.8%) had COPD. There were no significant differences in the number of subjects with high levels of inflammatory biomarkers (>90th percentile of never-smokers without COPD), including white blood cell count, total bilirubin, interleukin (IL)-6, IL-8, and C-reactive protein, or radiologic measurements (including emphysema index and mean wall area percentage) between never-smokers with COPD and those without COPD. However, the number of subjects with high uric acid was significantly higher in never-smokers with COPD than never-smokers without COPD (31.2% (24/77) vs. 11.1% (6/54); p = 0.013). In addition, multivariate analysis revealed that high uric acid was significantly associated with the presence of COPD in never-smokers (adjusted relative risk: 1.63; 95% confidence interval: 1.21, 2.18; p = 0.001). Our study suggests that high serum levels of uric acid might be a potential biomarker for assessing the presence of COPD in never-smokers. PMID:29117798

Cost analysis of chronic obstructive pulmonary disease in a tertiary care setting in Taiwan.

PubMed

Chiang, Chi-Huei

2008-09-01

The prevalence of COPD in the Western Pacific is increasing. The present study determined the total direct health-care costs for the management of COPD patients with differing degrees of disease severity. The study also aimed to find the key cost drivers in the management of COPD. COPD patients were recruited from a tertiary care hospital during April 2002 and March 2003. One-year costs were identified by applying cost data to medical information obtained by review of medical records. Costs included those for medications, oxygen therapy, laboratory and diagnostic tests, clinic visits, emergency room visits and hospital stays. There were 160 patients recruited. Patients were categorized by COPD severity: moderate A COPD (50

Heat and moisture exchangers in mechanically ventilated intensive care unit patients: a plea for an independent assessment of their performance.

PubMed

Thiéry, Guillaume; Boyer, Alexandre; Pigné, Etienne; Salah, Amar; De Lassence, Arnaud; Dreyfuss, Didier; Ricard, Jean-Damien

2003-03-01

To determine whether use of a hygroscopic and hydrophobic heat and moisture exchanger (HME) for 7 days without change affects its efficiency in long-term, mechanically ventilated, chronic obstructive pulmonary disease (COPD) patients. Prospective, randomized, controlled clinical study comparing two combined HMEs. Medical intensive care unit at a university teaching hospital. Long-term, mechanically ventilated, COPD patients compared with non-COPD patients. In the first part of the study, COPD patients were studied with the Hygroster HME changed once a week. For the second part, the Hygroster was assessed in non-COPD patients and compared with the Hygrobac HME used in COPD and non-COPD patients for 1 wk without change. Devices could be changed if hygrometric measurements indicated insufficient humidity delivery. Daily measurements were recorded for inspired gas temperature and relative and absolute humidity. Ventilatory variables, clinical indicators of efficient humidification, were also recorded. No tracheal tube occlusion occurred. However, contrary to the manufacturer advertisement, the Hygroster experienced surprisingly low values for absolute humidity in both COPD and non-COPD patients. Such events did not occur with the Hygrobac. Absolute humidity with the Hygroster was constantly and significantly lower during the 7-day study period than with the Hygrobac. Absolute humidity measured in COPD patients was identical to that measured in the rest of the study population with both HMEs. Manufacturer specifications and bedside measurements of absolute humidity differed considerably for the Hygroster, which in certain instances did not achieve efficient humidification in both COPD and non-COPD patients. This did not occur with the Hygrobac, which performed well throughout the 7-day period in both COPD and non-COPD patients. Our results speak for independent and evaluation of HMEs.

Metabolic syndrome and Chronic Obstructive Pulmonary Disease (COPD): The interplay among smoking, insulin resistance and vitamin D.

PubMed

Piazzolla, Giuseppina; Castrovilli, Anna; Liotino, Vito; Vulpi, Maria Rosaria; Fanelli, Margherita; Mazzocca, Antonio; Candigliota, Mafalda; Berardi, Elsa; Resta, Onofrio; Sabbà, Carlo; Tortorella, Cosimo

2017-01-01

A close relationship between Metabolic Syndrome (MetS) and Chronic Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of this link remains unclear. Current epidemiological data refer exclusively to the MetS prevalence among patients with COPD and data about the prevalence of COPD in MetS patients are still unavailable. To analyse and compare risk factors, clinical and metabolic characteristics, as well as the main respiratory function parameters, among patients affected by MetS, COPD or both diseases. We recruited 59 outpatients with MetS and 76 outpatients with COPD. After medical history collection, physical examination, blood sampling for routine analysis, spirometric evaluation, they were subdivided into MetS (n = 46), MetS+COPD (n = 60), COPD (n = 29). A MetS diagnosis was assigned to 62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology Department, while the COPD prevalence in MetS patients enrolled in the Internal Medicine Metabolic Disorders Outpatients Clinic was 22%. More than 60% of subjects enrolled in each Department were unaware that they suffered from an additional disease. MetS+COPD patients exhibited significantly higher C-peptide levels. We also found a positive relation between C-peptide and pack-years in all subjects and a negative correlation between C-peptide and vitamin D only in current smokers. Finally, a negative association emerged between smoking and vitamin D. We have estimated, for the first time, the COPD prevalence in MetS and suggest a potential role of smoking in inducing insulin resistance. Moreover, a direct effect of smoking on vitamin D levels is proposed as a novel mechanism, which may account for both insulin resistance and COPD development.

Total management of chronic obstructive pulmonary disease (COPD) as an independent risk factor for cardiovascular disease.

PubMed

Onishi, Katsuya

2017-08-01

Patients with cardiovascular disease (CVD) often have multiple comorbid conditions that may interact with each other, confound the choice of treatments, and reduce mortality. Chronic obstructive pulmonary disease (COPD) is one of the most important comorbidities of CVD, which causes serious consequences in patients with ischemic heart disease, stroke, arrhythmia, and heart failure. COPD shares common risk factors such as tobacco smoking and aging with CVD, is associated with less physical activity, and produces systemic inflammation and oxidative stress. Overall, patients with COPD have a 2-3-fold increased risk of CVD as compared to age-matched controls when adjusted for tobacco smoking. Chronic heart failure (HF) is a frequent and important comorbidity which has a significant impact on prognosis in COPD, and vice versa. HF overlaps in symptoms and signs and has a common comorbidity with COPD, so that diagnosis of COPD is difficult in patients with HF. The combination of HF and COPD presents many therapeutic challenges including beta-blockers (BBs) and beta-agonists. Inhaled long-acting bronchodilators including beta2-agonists and anticholinergics for COPD would not worsen HF. Diuretics are relatively safe, and angiotensin-converting enzyme inhibitors are preferred to treat HF accompanied with COPD. BBs are only relatively contraindicated in asthma, but not in COPD. Low doses of cardioselective BBs should be aggressively initiated in clinically stable patients with HF accompanied with COPD combined with close monitoring for signs of airway obstruction and gradually up-titrated to the maximum tolerated dose. Encouraging appropriate and aggressive treatment for both HF and COPD should be recommended to improve quality of life and mortality in HF patients with COPD. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Prevalence of COPD in Spain: impact of undiagnosed COPD on quality of life and daily life activities.

PubMed

Miravitlles, M; Soriano, J B; García-Río, F; Muñoz, L; Duran-Tauleria, E; Sanchez, G; Sobradillo, V; Ancochea, J

2009-10-01

This study aimed to determine the prevalence of chronic obstructive pulmonary disease (COPD) in Spain and identify the level of undiagnosed disease and its impact on health-related quality of life (HRQL) and activities of daily living (ADL). A population-based sample of 4274 adults aged 40-80 years was surveyed. They were invited to answer a questionnaire and undergo prebrochodilator and postbronchodilator spirometry. COPD was defined as a postbronchodilator FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio of <0.70. For 3802 participants with good-quality postbronchodilator spirometry, the overall prevalence of COPD was 10.2% (95% CI 9.2% to 11.1%) and was higher in men (15.1%) than in women (5.6%). The prevalence of COPD stage II or higher was 4.4% (95%CI; 3.8%-5.1%). The prevalence of COPD increased with age and with cigarette smoking and was higher in those with a low educational level. A previous diagnosis of COPD was reported by only 27% of those with COPD. Diagnosed patients had more severe disease, higher cumulative tobacco consumption and more severely impaired HRQL compared with undiagnosed subjects. However, even patients with undiagnosed COPD stage I+ already showed impairment in HRQL and in some aspects of ADL compared with participants without COPD. The prevalence of COPD in individuals between 40 and 80 years of age in Spain is 10.2% and increases with age, tobacco consumption and lower educational levels. The rate of diagnosised COPD is very high and undiagnosed individuals with COPD already have a significant impairment in HRQL and ADL.

Impact of chronic obstructive pulmonary diseases on left ventricular diastolic function in hospitalized elderly patients

PubMed Central

Huang, Ying-Shuo; Feng, Ying-Chao; Zhang, Jian; Bai, Li; Huang, Wei; Li, Min; Sun, Ying

2015-01-01

Objective To evaluate the impact of chronic obstructive pulmonary disease (COPD) on left ventricular (LV) diastolic function in hospitalized elderly patients. Methods This was a case–control observational study of 148 consecutive hospitalized elderly patients (≥65 years old): 73 subjects without COPD as controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1 and 2, while severe and very severe COPD was defined as stages 3 and 4, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Clinical characteristics and echocardiographic parameters were analyzed and compared. Results Compared with the control group, patients with COPD had a higher frequency of LV diastolic dysfunction and heart failure with preserved ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the COPD group (all P<0.05). COPD patients showed more abnormalities in diastolic function (E/e′: 11.51±2.50 vs 10.42±3.25, P=0.047), but no differences in systolic function and right ventricular function (all P>0.05). Patients with severe/very severe COPD showed no differences in LV diastolic function compared to patients with mild/moderate COPD (P>0.05), but serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05). Conclusion Results suggest that early-stage COPD may have an impact on the LV diastolic function. Severe COPD mainly affected right ventricular function. In hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken into account together with right ventricular function. PMID:25565790

Managing comorbidities in COPD

PubMed Central

Hillas, Georgios; Perlikos, Fotis; Tsiligianni, Ioanna; Tzanakis, Nikolaos

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities. COPD exacerbations and comorbidities contribute to the overall severity in individual patients. Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age. Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations. However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide. This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale. Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases. All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases. In this review, we focus on the major comorbidities that affect COPD patients. We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs. We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. PMID:25609943

B cells in chronic obstructive pulmonary disease: moving to center stage

PubMed Central

Polverino, Francesca; Seys, Leen J. M.; Bracke, Ken R.

2016-01-01

Chronic inflammatory responses in the lungs contribute to the development and progression of chronic obstructive pulmonary disease (COPD). Although research studies focused initially on the contributions of the innate immune system to the pathogenesis of COPD, more recent studies have implicated adaptive immune responses in COPD. In particular, studies have demonstrated increases in B cell counts and increases in the number and size of B cell-rich lymphoid follicles in COPD lungs that correlate directly with COPD severity. There are also increases in lung levels of mediators that promote B cell maturation, activation, and survival in COPD patients. B cell products such as autoantibodies directed against lung cells, components of cells, and extracellular matrix proteins are also present in COPD lungs. These autoantibodies may contribute to lung inflammation and injury in COPD patients, in part, by forming immune complexes that activate complement components. Studies of B cell-deficient mice and human COPD patients have linked B cells most strongly to the emphysema phenotype. However, B cells have protective activities during acute exacerbations of COPD by promoting adaptive immune responses that contribute to host defense against pathogens. This review outlines the evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD and the mechanisms involved. It also reviews the potential and limitations of B cells as therapeutic targets to slow the progression of human COPD. PMID:27542809

Co-morbidities of COPD in primary care: frequency, relation to COPD, and treatment consequences.

PubMed

van der Molen, Thys

2010-12-01

In the Western world, chronic obstructive pulmonary disease (COPD) is predominantly caused by long-term smoking, which results in pulmonary inflammation that is often associated with systemic inflammation. A number of co-morbid conditions, such as cardiovascular disease, muscle wasting, type 2 diabetes and asthma, may coexist with COPD; these and other co-morbidities not directly related to COPD are major causes of excess morbidity and mortality. This review sets out to explore the most frequent co-morbidities in COPD and their implications for treatment. Review of the literature on co-morbidities of COPD. Co-morbidities are frequent, but often remain undiagnosed in the COPD patient. In order to provide the best possible care for people with COPD, the physician should be aware of all potential co-morbidities that may arise, and the critical role that effective management of these co-morbidities can play in improving patient outcomes. Increased awareness of the potential co-morbidities of COPD, although potentially adding to the general practitioner's work burden, may provide insights into this difficult disease state and possibly improve each individual's prospects for effective management.

Reconsidering sex-based stereotypes of COPD.

PubMed

Ohar, Jill; Fromer, Leonard; Donohue, James F

2011-12-01

Chronic obstructive pulmonary disease (COPD) has historically been considered a disease of older, white, male smokers, as illustrated in Frank Netter's classic images of the 'pink puffer' and 'blue bloater'. However, women may be more susceptible to COPD than men, and the disease course may be reflective of that increased susceptibility. From a review of epidemiological data of COPD, we found differences in the way men and women present with COPD symptoms, a bias in the way COPD symptoms are treated in men and women, and differences in susceptibility to airway obstruction based on age, sex, and smoking history. These data show that classic stereotypes of COPD - including male predominance - should be abandoned, and that there are not two but multiple COPD phenotypes, which are characterised by differences between women and men in susceptibility, symptoms, and disease progression. These differences impact on physician perception. Although further research into this concept is needed, the differences we found should prompt, in the short term, changes in the way (and in whom) COPD is evaluated, diagnosed, and treated; in the long term, these differences should prompt research into the prognosis of COPD based on sex differences.

Epidemiology and clinical impact of major comorbidities in patients with COPD

PubMed Central

Smith, Miranda Caroline; Wrobel, Jeremy P

2014-01-01

Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival. There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes. Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD. Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication. The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities. Unfortunately, comorbidities are often under-recognized and under-treated. This review focuses on the epidemiology of ten major comorbidities in patients with COPD. Further, we emphasize the clinical impact upon prognosis and management considerations. This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. PMID:25210449

ROLE OF GENETIC SUSCEPTIBILITY TO LATENT ADENOVIRAL INFECTION AND DECREASED LUNG FUNCTION

PubMed Central

Kasuga, Ikuma; Hogg, James C.; Paré, Peter D.; Hayashi, Shizu; Sedgwick, Edward G.; Ruan, Jian; Wallace, Alison M.; He, Jian-Qing; Zhang, Xiaozhu; Sandford, Andrew J.

2009-01-01

Background Latent adenoviral infection may amplify cigarette smoke-induced lung inflammation and therefore play an important role in the development of chronic obstructive pulmonary disease (COPD). Adenoviruses can evade the human immune response via their 19-kDa protein (19K) which delays the expression of class I human leukocyte antigen (HLA) proteins. The 19K protein shows higher affinity to HLA-B7 and A2 compared with HLA-A1 and A3. The receptor for adenovirus (CXADR) and integrin β5 (ITGB5) are host factors which might affect adenovirus infection. Therefore, we investigated the contribution of HLA, CXADR, and ITGB5 genetic variants to the presence of the E1A gene and to level of lung function. Methods Study subjects were assayed for HLA-B7, A1, A2 and A3 by PCR-based assays using allele-specific primers. Polymorphisms of the CXADR and ITGB5 genes were genotyped by PCR-based restriction fragment length polymorphism assays. Detection of adenoviral E1A gene was performed by a real-time PCR TaqMan assay. Results E1A positive individuals have a lower FEV1 compared with E1A negative individuals. However, there was no significant difference in E1A positivity rate between the high (HLA-B7 and A2) and low (HLA-A1 and A3) 19K affinity groups. There was also no significant difference in FEV1 level between each affinity group. There was no significant difference in E1A positivity rate or lung function among the CXADR and ITGB5 genotypes. Conclusions Genetic variants in HLA, CXADR and ITGB5 do not influence latent adenoviral infections and are not associated with COPD. PMID:19502044

Chronic Obstructive Pulmonary Disease, Cognitive Impairment, and Development of Disability: The Health and Retirement Study

PubMed Central

Richardson, Caroline R.; Han, MeiLan K.; Cigolle, Christine T.

2014-01-01

Rationale: The relationship between chronic obstructive pulmonary disease (COPD) and cognitive impairment in leading to disability has not been characterized. Objectives: We aimed to investigate the prevalence and cumulative incidence of disability among adults with and without COPD and the association of COPD and cognitive impairment with disability. Methods: We analyzed 2006–2008 waves of the Health and Retirement Study, a nationally representative longitudinal health survey. COPD was self-reported. Prevalent disability was defined as baseline dependency in one or more activities of daily living (ADLs) and incident disability as one or more additional ADL dependencies. We used a validated performance-based measure of cognition to identify dementia and mild cognitive impairment. Covariates included seven chronic diseases, four geriatric syndromes, and sociodemographics. We used logistic regression to test associations between COPD, cognitive status, and prevalent/incident disability. Measurements and Main Results: Of 17,535 participants at least 53 years of age in wave 2006 (representing 77.7 million Americans), 9.5% reported COPD and 13.5% mild cognitive impairment; 17.5% of those with COPD had mild cognitive impairment. Prevalent disability for COPD was 12.8% (5.2% for no-COPD, P < 0.001). An additional 9.2% with COPD developed incident disability at 2 years (4.0% for no-COPD, P < 0.001). In adjusted models, COPD was associated with baseline (odds ratio, 2.0) and incident disability (odds ratio, 2.1; adjusted for baseline disability). Cognitive impairment had an additive effect to COPD. The COPD–disability association, prevalent/incident, was of similar or greater magnitude than that of other chronic diseases (e.g., stroke, diabetes). The associations were maintained in sensitivity analyses using alternative definitions of disability (dependency in two or more ADLs, dependency in instrumental ADLs), and in analysis excluding respondents with dementia. Conclusions: Both COPD and mild cognitive impairment increase the risk of disability. The risk conferred by COPD is significant and similar or higher than other chronic diseases. PMID:25285360

Disease burden of COPD in China: a systematic review

PubMed Central

Zhu, Bifan; Wang, Yanfang; Ming, Jian; Chen, Wen; Zhang, Luying

2018-01-01

Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease. The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease. The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10. Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China. The prevalence rate of COPD was higher among men (7.76%) than women (4.07%). The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%). The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%. The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%. Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD. COPD ranked among the top three leading causes of death in China. The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income. The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions. The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression. The COPD burden in China was high in terms of economic burden and QoL. In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. PMID:29731623

Unmet needs of patients with chronic obstructive pulmonary disease (COPD): a qualitative study on patients and doctors.

PubMed

Wong, Stalia S L; Abdullah, Nurdiana; Abdullah, Adina; Liew, Su-May; Ching, Siew-Mooi; Khoo, Ee-Ming; Jiwa, Moyez; Chia, Yook-Chin

2014-04-16

Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease with repeated exacerbations resulting in gradual debilitation. The quality of life has been shown to be poor in patients with COPD despite efforts to improve self-management. However, the evidence on the benefit of self-management in COPD is conflicting. Whether this could be due to other unmet needs of patients have not been investigated. Therefore, we aimed to explore unmet needs of patients from both patients and doctors managing COPD. We conducted a qualitative study with doctors and patients in Malaysia. We used convenience sampling to recruit patients until data saturation. Eighteen patients and eighteen doctors consented and were interviewed using a semi-structured interview guide. The interviews were audio-recorded, transcribed verbatim and checked by the interviewers. Data were analysed using a thematic approach. The themes were similar for both the patients and doctors. Three main themes emerged: knowledge and awareness of COPD, psychosocial and physical impact of COPD and the utility of self-management. Knowledge about COPD was generally poor. Patients were not familiar with the term chronic obstructive pulmonary disease or COPD. The word 'asthma' was used synonymously with COPD by both patients and doctors. Most patients experienced difficulties in their psychosocial and physical functions such as breathlessness, fear and helplessness. Most patients were not confident in self-managing their illness and prefer a more passive role with doctors directing their care. In conclusion, our study showed that knowledge of COPD is generally poor. There was mislabelling of COPD as asthma by both patients and physicians. This could have resulted in the lack of understanding of treatment options, outcomes, and prognosis of COPD. The misconception that cough due to COPD was contagious, and breathlessness that resulted from COPD, had important physical and psychosocial impact, and could lead to social isolation. Most patients and physicians did not favour self-management approaches, suggesting innovations based on self-management may be of limited benefit.

The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD.

PubMed

Leung, Janice M; Tiew, Pei Yee; Mac Aogáin, Micheál; Budden, Kurtis F; Yong, Valerie Fei Lee; Thomas, Sangeeta S; Pethe, Kevin; Hansbro, Philip M; Chotirmall, Sanjay H

2017-05-01

COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe-COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe-host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD. © 2017 Asian Pacific Society of Respirology.

Patterns and management of chronic obstructive pulmonary disease in urban and rural China: a community-based survey of 25 000 adults across 10 regions.

PubMed

Kurmi, Om P; Davis, Kourtney J; Hubert Lam, Kin Bong; Guo, Yu; Vaucher, Julien; Bennett, Derrick; Wang, Jenny; Bian, Zheng; Du, Huaidong; Li, Liming; Clarke, Robert; Chen, Zhengming

2018-01-01

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, with COPD deaths in China accounting for one-third of all such deaths. However, there is limited available evidence on the management of COPD in China. A random sample of 25 011 participants in the China Kadoorie Biobank, aged 38-87 years, from 10 regions in China was surveyed in 2013-2014. Data were collected using interviewer-administered questionnaires on the diagnosis ('doctor-diagnosed' or 'symptoms-based') and management of COPD (including use of medication and other healthcare resources), awareness of diagnosis and severity of symptoms in COPD cases. Overall, 6.3% of the study population were identified as COPD cases (doctor-diagnosed cases: 4.8% and symptom-based cases: 2.4%). The proportion having COPD was higher in men than in women (7.9% vs 5.3%) and varied by about threefold (3.7%-10.0%) across the 10 regions. Among those with COPD, 54% sought medical advice during the last 12 months, but <10% reported having received treatment for COPD. The rates of hospitalisation for COPD, use of oxygen therapy at home and influenza or pneumococcal vaccinations in the previous year were 15%, 3% and 4%, respectively. Of those with COPD, half had moderate or severe respiratory symptoms, and over 80% had limited understanding of their disease and need for treatment. Despite a high prevalence of COPD in China and its substantial impact on activities of daily living, knowledge about COPD and its management were limited.

A discriminant function model as an alternative method to spirometry for COPD screening in primary care settings in China.

PubMed

Cui, Jiangyu; Zhou, Yumin; Tian, Jia; Wang, Xinwang; Zheng, Jingping; Zhong, Nanshan; Ran, Pixin

2012-12-01

COPD is often underdiagnosed in a primary care setting where the spirometry is unavailable. This study was aimed to develop a simple, economical and applicable model for COPD screening in those settings. First we established a discriminant function model based on Bayes' Rule by stepwise discriminant analysis, using the data from 243 COPD patients and 112 non-COPD subjects from our COPD survey in urban and rural communities and local primary care settings in Guangdong Province, China. We then used this model to discriminate COPD in additional 150 subjects (50 non-COPD and 100 COPD ones) who had been recruited by the same methods as used to have established the model. All participants completed pre- and post-bronchodilator spirometry and questionnaires. COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria. The sensitivity and specificity of the discriminant function model was assessed. THE ESTABLISHED DISCRIMINANT FUNCTION MODEL INCLUDED NINE VARIABLES: age, gender, smoking index, body mass index, occupational exposure, living environment, wheezing, cough and dyspnoea. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, accuracy and error rate of the function model to discriminate COPD were 89.00%, 82.00%, 4.94, 0.13, 86.66% and 13.34%, respectively. The accuracy and Kappa value of the function model to predict COPD stages were 70% and 0.61 (95% CI, 0.50 to 0.71). This discriminant function model may be used for COPD screening in primary care settings in China as an alternative option instead of spirometry.

Using cluster analysis to identify phenotypes and validation of mortality in men with COPD.

PubMed

Chen, Chiung-Zuei; Wang, Liang-Yi; Ou, Chih-Ying; Lee, Cheng-Hung; Lin, Chien-Chung; Hsiue, Tzuen-Ren

2014-12-01

Cluster analysis has been proposed to examine phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). The aim of this study was to use cluster analysis to define COPD phenotypes and validate them by assessing their relationship with mortality. Male subjects with COPD were recruited to identify and validate COPD phenotypes. Seven variables were assessed for their relevance to COPD, age, FEV(1) % predicted, BMI, history of severe exacerbations, mMRC, SpO(2), and Charlson index. COPD groups were identified by cluster analysis and validated prospectively against mortality during a 4-year follow-up. Analysis of 332 COPD subjects identified five clusters from cluster A to cluster E. Assessment of the predictive validity of these clusters of COPD showed that cluster E patients had higher all cause mortality (HR 18.3, p < 0.0001), and respiratory cause mortality (HR 21.5, p < 0.0001) than those in the other four groups. Cluster E patients also had higher all cause mortality (HR 14.3, p = 0.0002) and respiratory cause mortality (HR 10.1, p = 0.0013) than patients in cluster D alone. COPD patient with severe airflow limitation, many symptoms, and a history of frequent severe exacerbations was a novel and distinct clinical phenotype predicting mortality in men with COPD.

16S rDNA analysis of periodontal plaque in chronic obstructive pulmonary disease and periodontitis patients.

PubMed

Wu, Xingwen; Chen, Jiazhen; Xu, Meng; Zhu, Danting; Wang, Xuyang; Chen, Yulin; Wu, Jing; Cui, Chenghao; Zhang, Wenhong; Yu, Liying

2017-01-01

This study investigated if chronic obstructive pulmonary disease (COPD) is correlated with periodontitis via periodontal microbiota and if certain bacteria affect periodontitis as well as COPD. Moreover, the study investigated whether suffering from COPD is associated with a decrease in the richness and diversity of periodontal microbiota. Subgingival plaque was obtained from 105 patients. Bacterial DNA was isolated from 55 COPD and 50 non-COPD participants (either with or without periodontitis). 16S rRNA gene metagenomic sequencing was used to characterize the microbiota and to determine taxonomic classification. In the non-periodontitis patients, suffering from COPD resulted in a decrease in bacteria richness and diversity in the periodontal microenvironment. An increase in the genera Dysgonomonas , Desulfobulbus , and Catonella and in four species ( Porphyromonas endodontalis , Dysgonomonas wimpennyi , Catonella morbi , and Prevotella intermedia ) in both COPD and periodontitis patients suggests that an increase in these periodontitis-associated microbiota may be related to COPD. Three genera ( Johnsonella , Campylobacter , and Oribacterium ) were associated with COPD but not with periodontitis. The decrease in the genera Arcanobacterium , Oribacterium , and Streptomyces in COPD patients implies that these genera may be health-associated genera, and the decrease in these genera may be related to disease. These data support the hypothesis that COPD is correlated with periodontitis via these significantly changed specific bacteria.

Clinical characteristics, treatment patterns, and socio-economic burden of COPD in Bulgaria.

PubMed

Kamusheva, Maria; Dimitrova, Maria; van Boven, Job F M; Postma, Maarten J; van der Molen, Thys; Kocks, Janwillem W H; Mitov, Konstantin; Doneva, Miglena; Petrova, Daniela; Georgiev, Ognyan; Petkova, Valentina; Petrova, Guenka

2017-05-01

While the impact of COPD in Western-Europe is known, data from Eastern-Europe is scarce. This study aimed to evaluate clinical characteristics, treatment patterns, and the socio-economic burden of COPD in Eastern-Europe, taking Bulgaria as a reference case. A representative sample of Bulgarian patients with COPD was randomly chosen by pulmonologists, based on the following inclusion criteria: COPD diagnosis with at least 1 year of living with COPD, ≥40 years of age, and use of COPD medication. Patient characteristics, treatment, quality-of-life, healthcare resource use, and costs were systematically assessed. A total of 426 COPD patients were enrolled. Approximately 69% were male, 40% had occupational risk factors, 45% had severe and 11% had very severe COPD. Mean CAT scores were 13.80 (GOLD A), 21.80 (GOLD B), 17.35 (GOLD C), and 26.70 (GOLD D). Annual per-patient costs of healthcare utilization were €579. Yearly pharmacotherapy costs were €693. Indirect costs (reduced and lost work productivity) outnumbered direct costs three times. Bulgaria has relatively high percentages of (very) severe COPD patients, resulting in considerable socio-economic burden. High smoking rates, occupational risk factors, air pollution, and a differential health system may be related to this finding. Eastern-European COPD strategies should focus on prevention, risk-factor awareness, and early detection.

COPD predicts mortality in HF: the Norwegian Heart Failure Registry.

PubMed

De Blois, Jonathan; Simard, Serge; Atar, Dan; Agewall, Stefan

2010-03-01

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (HF) are common clinical conditions that share tobacco as a risk factor. Our aim was to evaluate the prognostic impact of COPD on HF patients. The Norwegian Heart Failure Registry was used. The study included 4132 HF patients (COPD, n = 699) from 22 hospitals (mean follow-up, 13.3 months). COPD patients were older, more often smokers and diabetics, less often on beta-blockers and had a higher heart rate. They were more often in New York Heart Association (NYHA) Class III or IV (COPD, 63%; no COPD, 51%), although left ventricular ejection fraction (LVEF) distribution was similar. COPD independently predicted death (adjusted hazard ratio [HR], 1.188; 95% CI: 1.015 to 1.391; P = 0.03) along with age, creatinine, NYHA Class III/IV (HR, 1.464; 95% CI: 1.286 to 1.667) and diabetes. beta-blockers at baseline were associated with improved survival in patients with LVEF < or =40% independently of COPD. COPD is associated with a poorer survival in HF patients. COPD patients are overrated in terms of NYHA class in comparison with patients with similar LVEF. Nonetheless, NYHA class remains the strongest predictor of death in these patients. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Chronic obstructive lung disease and posttraumatic stress disorder: current perspectives

PubMed Central

Abrams, Thad E; Blevins, Amy; Weg, Mark W Vander

2015-01-01

Background Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD) and psychiatric conditions, with the most robust evidence base demonstrating an impact of comorbid anxiety and depression on COPD-related outcomes. In recent years, research has sought to determine if there is a co-occurrence between COPD and posttraumatic stress disorder (PTSD) as well as for associations between PTSD and COPD-related outcomes. To date, there have been no published reviews summarizing this emerging literature. Objectives The primary objective of this review was to determine if there is adequate evidence to support a co-occurrence between PTSD and COPD. Secondary objectives were to: 1) determine if there are important clinical considerations regarding the impact of PTSD on COPD management, and 2) identify targeted areas for further research. Methods A structured review was performed using a systematic search strategy limited to studies in English, addressing adults, and to articles that examined: 1) the co-occurrence of COPD and PTSD and 2) the impact of PTSD on COPD-related outcomes. To be included, articles must have addressed some type of nonreversible obstructive lung pathology. Results A total of 598 articles were identified for initial review. Upon applying the inclusion and exclusion criteria, n=19 articles or abstracts addressed our stated objectives. Overall, there is inconclusive evidence to support the co-occurrence between PTSD and COPD. Studies finding a significant co-occurrence generally had inferior methods of identifying COPD; in contrast, studies that utilized more robust COPD measures (such as a physician exam) generally failed to find a relationship. Among studies that examined the impact of PTSD on COPD-related outcomes, there was more consistent evidence that PTSD affects the perception of respiratory symptom burden and management. In addition, methods for measuring an important confounder (smoking) were generally lacking. Conclusion There is inconclusive evidence to support the co-occurrence of COPD and PTSD. There was stronger evidence implicating PTSD as an important comorbidity impacting COPD management. Further research is needed to: 1) determine whether or not COPD and PTSD are likely to be comorbid, and 2) further elucidate the mechanisms connecting PTSD and COPD-related outcomes. PMID:26508851

Chronic obstructive lung disease and posttraumatic stress disorder: current perspectives.

PubMed

Abrams, Thad E; Blevins, Amy; Weg, Mark W Vander

2015-01-01

Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD) and psychiatric conditions, with the most robust evidence base demonstrating an impact of comorbid anxiety and depression on COPD-related outcomes. In recent years, research has sought to determine if there is a co-occurrence between COPD and posttraumatic stress disorder (PTSD) as well as for associations between PTSD and COPD-related outcomes. To date, there have been no published reviews summarizing this emerging literature. The primary objective of this review was to determine if there is adequate evidence to support a co-occurrence between PTSD and COPD. Secondary objectives were to: 1) determine if there are important clinical considerations regarding the impact of PTSD on COPD management, and 2) identify targeted areas for further research. A structured review was performed using a systematic search strategy limited to studies in English, addressing adults, and to articles that examined: 1) the co-occurrence of COPD and PTSD and 2) the impact of PTSD on COPD-related outcomes. To be included, articles must have addressed some type of nonreversible obstructive lung pathology. A total of 598 articles were identified for initial review. Upon applying the inclusion and exclusion criteria, n=19 articles or abstracts addressed our stated objectives. Overall, there is inconclusive evidence to support the co-occurrence between PTSD and COPD. Studies finding a significant co-occurrence generally had inferior methods of identifying COPD; in contrast, studies that utilized more robust COPD measures (such as a physician exam) generally failed to find a relationship. Among studies that examined the impact of PTSD on COPD-related outcomes, there was more consistent evidence that PTSD affects the perception of respiratory symptom burden and management. In addition, methods for measuring an important confounder (smoking) were generally lacking. There is inconclusive evidence to support the co-occurrence of COPD and PTSD. There was stronger evidence implicating PTSD as an important comorbidity impacting COPD management. Further research is needed to: 1) determine whether or not COPD and PTSD are likely to be comorbid, and 2) further elucidate the mechanisms connecting PTSD and COPD-related outcomes.

From patient care to research: a validation study examining the factors contributing to data quality in a primary care electronic medical record database.

PubMed

Coleman, Nathan; Halas, Gayle; Peeler, William; Casaclang, Natalie; Williamson, Tyler; Katz, Alan

2015-02-05

Electronic Medical Records (EMRs) are increasingly used in the provision of primary care and have been compiled into databases which can be utilized for surveillance, research and informing practice. The primary purpose of these records is for the provision of individual patient care; validation and examination of underlying limitations is crucial for use for research and data quality improvement. This study examines and describes the validity of chronic disease case definition algorithms and factors affecting data quality in a primary care EMR database. A retrospective chart audit of an age stratified random sample was used to validate and examine diagnostic algorithms applied to EMR data from the Manitoba Primary Care Research Network (MaPCReN), part of the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). The presence of diabetes, hypertension, depression, osteoarthritis and chronic obstructive pulmonary disease (COPD) was determined by review of the medical record and compared to algorithm identified cases to identify discrepancies and describe the underlying contributing factors. The algorithm for diabetes had high sensitivity, specificity and positive predictive value (PPV) with all scores being over 90%. Specificities of the algorithms were greater than 90% for all conditions except for hypertension at 79.2%. The largest deficits in algorithm performance included poor PPV for COPD at 36.7% and limited sensitivity for COPD, depression and osteoarthritis at 72.0%, 73.3% and 63.2% respectively. Main sources of discrepancy included missing coding, alternative coding, inappropriate diagnosis detection based on medications used for alternate indications, inappropriate exclusion due to comorbidity and loss of data. Comparison to medical chart review shows that at MaPCReN the CPCSSN case finding algorithms are valid with a few limitations. This study provides the basis for the validated data to be utilized for research and informs users of its limitations. Analysis of underlying discrepancies provides the ability to improve algorithm performance and facilitate improved data quality.

Chronic obstructive pulmonary disease, hospital visits, and comorbidities: National Survey of Residential Care Facilities, 2010.

PubMed

Wheaton, Anne G; Ford, Earl S; Cunningham, Timothy J; Croft, Janet B

2015-04-01

To characterize the prevalence of chronic obstructive pulmonary disease (COPD) among residential care facility (RCF) residents in the United States, and to compare patterns of hospital visits and comorbidities with residents without COPD. Resident data from the 2010 National Survey of Residential Care Facilities were analyzed. Medical history and information on past-year hospital visits for 8,089 adult residents were obtained from interviews with RCF staff. COPD prevalence was 12.4%. Compared with residents without COPD, emergency department visits or overnight hospital stays in the previous year were more prevalent (p < .05) among residents with COPD. Less than 3% of residents with COPD had no comorbidities. Arthritis, depression, congestive heart failure (CHF), diabetes, coronary heart disease, and asthma were more common (p < .05) among residents with COPD than those without COPD, but Alzheimer's disease was less common. COPD is associated with more emergency department visits, hospital stays, and comorbidities among RCF residents. © The Author(s) 2014.

[Importance for surveillance on chronic obstructive pulmonary disease among Chinese adults].

PubMed

Fang, L W; Wang, L H

2018-05-10

The first national surveillance of COPD in mainland China was carried out in 2014, with the nationally representative data obtained. The national surveillance was significantly important for the monitoring of prevalence, risk factors, and changing trend of COPD among Chinese adults aged ≥ 40. The surveillance was also important in the development of national COPD prevention and control policy, the evaluation of prevention and control progress, the establishment of COPD comprehensive surveillance system, and the building of a professional COPD monitoring and prevention team. In this editorial, we briefly introduced the method and content of COPD surveillance, and reported the rate of spirometry examination and COPD awareness among adults aged ≥40 in China. We also analyzed the rate of main risk factors for COPD, such as tobacco smoking, occupational exposure to dust or chemical and indoor exposure to biomass or coal, and the distribution of high-risk population. This study provided fundamental data for the prevention and control of COPD in China.

The 2nd National COPD Readmissions Summit and Beyond: From Theory to Implementation.

PubMed

Willard, Kristen S; Sullivan, Jamie B; Thomashow, Byron M; Jones, Catherine S; Fromer, Leonard; Yawn, Barbara P; Amin, Alpesh; Rommes, Jean M; Rotert, Rhonda

2016-10-06

Chronic obstructive pulmonary disease (COPD) hospitalizations and readmissions adversely impact the health and quality of life of COPD patients. Under the Hospital Readmissions Reduction Program, the Centers for Medicare & Medicaid Services reduce payments to those hospitals exceeding expected rates of COPD readmissions within 30 days of hospital discharge. It was within this climate that the COPD Foundation held its 2 nd COPD Readmissions Summit in March 2015. Experts in attendance: (1) categorized challenges to optimal COPD care, ( 2) analyzed the state of care delivery and readmissions reduction strategies and (3) identified the best available evidence-based approaches to improving care delivery across the continuum, including early diagnosis via spirometry, ongoing device, oxygen and medication reconciliation, treatment that addresses comorbidities and preventive care, robust patient education, prompt post-acute follow up, home health services and pulmonary rehabilitation. Results of this collaborative event formed the basis for PRAXIS, the COPD Foundation's initiative to improve COPD care across the health continuum and to reduce readmissions.

Scabies increased the risk and severity of COPD: a nationwide population-based study

PubMed Central

Chen, Jung-Yueh; Liu, Jui-Ming; Chang, Fung-Wei; Chang, Hung; Cheng, Kuan-Chen; Yeh, Chia-Lun; Wei, Yu-Feng; Hsu, Ren-Jun

2016-01-01

Background Scabies is a common parasitic infectious disease, and COPD is a major pulmonary disease. However, there have been no previous studies that have investigated the relationship between scabies and COPD. Materials and methods This nationwide population-based study included a total of 3,568 patients with scabies as the study group and 14,255 patients as a control group. We followed up patients in both groups for a 5-year period to identify any new diagnoses of COPD. We then followed them up for an additional 2-year period to determine the severity of any newly diagnosed cases of COPD as indicated by acute respiratory events. Cox proportional hazard regression analyses were performed to calculate the hazard ratio (HR) of COPD during the 5-year follow-up period and COPD complication during the additional 2-year follow-up period. Results Of the 17,823 patients in the study, 2,765 (15.5%) were newly diagnosed with COPD during the 5-year follow-up period; 904 (32.7%) were from the scabies group; and 1,861 (67.3%) were from the control group. Compared to the patients without scabies, the adjusted HR (aHR) for COPD for the subjects with scabies was 1.72 (95% CI: 1.59–1.87) during the 5-year follow-up period. For those newly diagnosed with COPD, the aHR for COPD with acute exacerbation was 1.85 (95% CI: 1.67–2.06), the aHR for COPD with pneumonia was 3.29 (95% CI: 2.77–3.92), the aHR for COPD with acute respiratory failure was 4.00 (95% CI: 3.08–5.19), and the aHR for COPD with cardiopulmonary arrest was 3.95 (95% CI: 2.25–6.95) during the additional 2-year follow-up period. Conclusion The results of this study indicate a 72% increased risk for COPD among patients with scabies. The results also reveal an increased risk of severe COPD complications such as acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation among patients with scabies. This useful information may help physicians in treating scabies and remaining alert to the potential development of COPD and its severe complications. PMID:27672322

Asthma and COPD: Differences and Similarities

MedlinePlus

... and COPD: differences and similarities Share | Asthma and COPD: Differences and Similarities This article has been reviewed ... or you could have Chronic Obstructive Pulmonary Disease (COPD) , such as emphysema or chronic bronchitis. Because asthma ...

What Causes COPD?

MedlinePlus

... please turn JavaScript on. Feature: The Challenge of COPD What Causes COPD? Past Issues / Fall 2014 Table of Contents Long- ... and the airways usually is the cause of COPD. In the United States, the most common irritant ...

COPD: Learn More, Breathe Better

MedlinePlus

... Health Information for the Public » Educational Campaigns & Programs » COPD (Chronic Obstructive Pulmonary Disease) Join the conversation: Doctors ... Diesases explain what you need to know about COPD. Get the Facts COPD is on the rise— ...

An Epidemiological Overview of Chronic Obstructive Pulmonary Disease: What Can Real-Life Data Tell Us about Disease Management?

PubMed

Soriano, Joan B

2017-03-15

Chronic obstructive pulmonary disease (COPD) is a common condition, associated with increasing age and smoking exposure. COPD is a leading cause of morbidity, mortality and health care expenditure worldwide; yet, only 10-15% of all cases are identified medically. Alpha-1-antitrypsin deficiency (AATD) is responsible for about 1% of COPD cases but is also largely under-recognised, leading to diagnostic delay and missed treatment opportunities in patients who remain undetected. New evidence has recently highlighted the extent of overlap between COPD and bronchiectasis and the implications of comorbidity on clinical course and mortality. COPD with comorbid bronchiectasis deserves to be given research priority. This article overviews the epidemiology of COPD and examines the implications of overlap between COPD and AATD and between COPD and bronchiectasis.

Recognition, diagnosis, and treatment of cognitive and psychiatric disorders in patients with COPD

PubMed Central

Ouellette, Daniel R; Lavoie, Kim L

2017-01-01

COPD is highly prevalent and associated with substantial morbidity and mortality. Clinicians have long been aware that patients with COPD have problems with cognition and are susceptible to mood (depression) and anxiety disorders. With the increasing awareness of COPD as a multisystem disorder, many studies have evaluated the prevalence of neuropsychiatric conditions in patients with COPD. This review presents evidence regarding the prevalence of neuropsychiatric conditions (cognitive disorders/impairment, depression/anxiety) in COPD, their risk factors, and their impact on relevant outcomes. It also discusses both assessment and treatment of neuropsychiatric conditions and makes recommendations for improved screening and treatment. The findings suggest that clinicians caring for patients with COPD must become familiar with diagnosing these comorbid conditions and that future treatment has the potential to impact these patients and thereby improve COPD outcomes. PMID:28243081

Impact of Chronic Obstructive Pulmonary Disease on Long-Term Outcome in Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

PubMed

Zhang, Ming; Cheng, Yun-Jiu; Zheng, Wei-Ping; Liu, Guang-Hui; Chen, Huai-Sheng; Ning, Yu; Zhao, Xin; Su, Li-Xiao; Liu, Li-Juan

2016-01-01

Objective . The aim of this study was to investigate the association between COPD and major adverse cardiovascular and cerebral events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). Methods . 2,362 patients who underwent PCI were included in this study. Subjects were divided into 2 groups: with COPD ( n = 233) and without COPD ( n = 2,129). Cox proportional hazards models were analyzed to determine the effect of COPD on the incidence of MACCE. Results . The patients with COPD were older ( P < 0.0001) and were more likely to be current smokers ( P = 0.02) and have had hypertension ( P = 0.02) and diabetes mellitus ( P = 0.01). Prevalence of serious cardiovascular comorbidity was higher in the patients with COPD, including a history of MI ( P = 0.02) and HF ( P < 0.0001). Compared with non-COPD group, the COPD group showed a higher risk of all-cause death (hazard ratio (HR): 2.45, P < 0.0001), cardiac death (HR: 2.53, P = 0.0002), MI (HR: 1.387, P = 0.027), and HF (HR: 2.25, P < 0.0001). Conclusions . Patients with CAD and concomitant COPD are associated with a higher incidence of MACCE (all-cause death, cardiac death, MI, and HF) compared to patients without COPD. The patients with a history of COPD have higher in-hospital and long-term mortality rates than those without COPD after PCI.

Prevalence and Determinants of Chronic Obstructive Pulmonary Disease (COPD) in Bangladesh.

PubMed

Alam, Dewan S; Chowdhury, Muhammad Ah; Siddiquee, Ali T; Ahmed, Shyfuddin; Clemens, John D

2015-01-01

There is a paucity of population-based data on COPD prevalence and its determinants in Bangladesh. To measure COPD prevalence and socioeconomic and lifestyle determinants among ≥40 years Bangladeshi adults. In a cross-sectional study, we measured lung function of 3744 randomly selected adults ≥40 years from rural and urban areas in Bangladesh, using a handheld spirometer. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second (FEV1) to Forced Vital Capacity (FVC) < 0.7. In addition, COPD was also assessed by the lower limit of normal (LLN) threshold defined as lower fifth percentile for the predicted FEV1/FVC. The prevalence of COPD was 13.5% by GOLD criteria and 10.3% by LLN criteria. Prevalence of COPD was higher among rural than urban residents and in males than females. More than half of the COPD cases were stage II COPD by both criteria. Milder cases (Stages I and II) were over estimated by the GOLD fixed criteria, but more severe cases (Stages III and IV) were similarly classified. In multiple logistic regression analysis, older age, male sex, illiteracy, underweight, history of smoking (both current and former), history of asthma and solid fuel use were significant predictors of COPD. COPD is a highly prevalent and grossly underdiagnosed public health problem in Bangladeshi adults aged 40 years or older. Illiteracy, smoking and biomass fuel burning are modifiable determinants of COPD.

The association between periodontal disease and chronic obstructive pulmonary disease: a case control study.

PubMed

Öztekin, Görkem; Baser, Ulku; Kucukcoskun, Meric; Tanrikulu-Kucuk, Sevda; Ademoglu, Evin; Isik, Gulden; Ozkan, Gulcihan; Yalcin, Funda; Kiyan, Esen

2014-08-01

Although there are studies evaluating the effects of periodontal health on chronic obstructive pulmonary disease (COPD), the effects of COPD - a systemic disease, on periodontal tissue is unknown. The aim of this study is to evaluate the effects of COPD on periodontal tissues by comparing COPD patients and controls. Fifty-two COPD patients and 38 non-COPD controls were included in this case-control study. Number of teeth, plaque index (PI), gingival index (GI), bleeding on probing, clinical attachment level and probing depth were included in the periodontal examination. In addition to clinical evaluations, gingival crevicular fluid (GCF) levels of high-sensitive C-reactive protein (hs-CRP), interleukin-1 beta (IL-lb) and prostaglandin-E2 (PGE2), and serum hs-CRP levels were measured in COPD patients and the controls. The number of teeth was significantly lower while PI and GI were significantly higher in COPD patients when compared to the controls. As well as serum hs-CRP levels, the GCF levels of hs-CRP, IL-1b and PGE2 were significantly higher in COPD patients than the controls. Our results demonstrated that COPD may be associated with periodontal disease as manifested by lower number of teeth and higher levels of inflammatory mediators especially CRP in GCF. This finding may be a reflection of systemic effects of COPD on periodontal tissues. Poor oral health behavior of COPD patients have to be considered in larger size group studies in the future.

CFTR gene variant IVS8-5T in disseminated bronchiectasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pignatti, P.F.; Bombieri, C.; Benetazzo, M.

1996-04-01

Obstructive pulmonary disease includes asthma, chronic obstructive pulmonary disease (COPD; i.e., pulmonary emphysema and chronic bronchitis), bronchiectasis, and cystic fibrosis (CF). It represents a leading cause of death in developed countries. Both familial clustering of non-CF obstructive pulmonary disease and familial aggregation of impaired lung function have been described. This suggests that genetic factors contribute to non-CF obstructive pulmonary disease, even if it is difficult to determine the relative contribution of environmental factors. 11 refs., 1 tab.

Undernutrition in patients with COPD and its treatment.

PubMed

Itoh, Masayuki; Tsuji, Takao; Nemoto, Kenji; Nakamura, Hiroyuki; Aoshiba, Kazutetsu

2013-04-18

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung and whole body caused mainly by tobacco smoking. Patients with advanced COPD are in a state of undernutrition, referred to as pulmonary cachexia; the exercise performance and quality of life (QOL) of these patients are deteriorated, the vital prognosis is unfavorable, and the medico-economic burden posed by poorly nourished COPD patients is high. The mainstays of COPD treatment are pharmacotherapy, mainly with bronchodilators, and non-pharmacotherapeutic approaches such as respiratory rehabilitation and nutrition counseling. Nutritional supplement therapy, consisting primarily of high calorie intake, has been demonstrated to be effective for maintaining and improving the muscle strength and exercise tolerance in poorly nourished COPD patients. The efficacy of intake of various nutrients, besides a high calorie intake, for amelioration of the disease state of COPD has also been reported. The roles of adipokines in the pathophysiology of COPD have begun to receive attention recently, and not only their regulatory effects on appetite and nutritional status, but also their influence on systemic inflammation have been increasingly clarified. We review the papers on COPD and nutrition and discuss the role of nutritional supplement therapy in the treatment of COPD.

Impaired Tumor-infiltrating T Cells in Patients with COPD Impacts Lung Cancer Response to PD-1 Blockade.

PubMed

Biton, Jérôme; Ouakrim, Hanane; Dechartres, Agnès; Alifano, Marco; Mansuet-Lupo, Audrey; Si, Han; Halpin, Rebecca; Creasy, Todd; Bantsimba-Malanda, Claudie; Arrondeau, Jennifer; Goldwasser, François; Boudou-Rouquette, Pascaline; Fournel, Ludovic; Roche, Nicolas; Burgel, Pierre-Régis; Goc, Jeremy; Devi-Marulkar, Priyanka; Germain, Claire; Dieu-Nosjean, Marie-Caroline; Cremer, Isabelle; Herbst, Ronald; Damotte, Diane

2018-03-08

Patients with chronic obstructive pulmonary disease (COPD) have a higher prevalence of lung cancer. The chronic inflammation associated with COPD probably promotes the earliest stages of carcinogenesis. However, once tumors have progressed to malignancy, the impact of COPD on the tumor immune microenvironment remains poorly defined, and its effects on immune-checkpoint blockers' efficacy are still unknown. To study the impact of COPD on the immune contexture of non-small cell lung cancer (NSCLC). We performed in depth immune profiling of lung tumors by immunohistochemistry and we determined its impact on patients' survival (n=435). Tumor-infiltrating T lymphocyte (TILs) exhaustion by flow cytometry (n=50) was also investigated. The effectiveness of an anti-PD-1 treatment (nivolumab) was evaluated in 39 advanced-stage NSCLC patients. All data were analyzed according to patients' COPD status. Measurments and Main Results: Remarkably, COPD severity is positively correlated with the coexpression of PD-1/TIM-3 by CD8 T cells. In agreement, we observed a loss of CD8 T cell-associated favorable clinical outcome in COPD+ patients. Interestingly, a negative prognostic value of PD-L1 expression by tumor cells was observed only in highly CD8 T cell-infiltrated tumors of COPD+ patients. Finally, data obtained on 39 advanced-stage NSCLC patients treated by an anti-PD-1 antibody showed longer progression free survival in COPD+ patients, and also that the association between the severity of smoking and the response to nivolumab was preferentially observed in COPD+ patients. COPD is associated with an increased sensitivity of CD8 TILs to immune escape mechanisms developed by tumors, thus suggesting a higher sensitivity to PD-1 blockade in patients with COPD.

Risk of community-acquired pneumonia in chronic obstructive pulmonary disease stratified by smoking status: a population-based cohort study in the United Kingdom.

PubMed

Braeken, Dionne Cw; Rohde, Gernot Gu; Franssen, Frits Me; Driessen, Johanna Hm; van Staa, Tjeerd P; Souverein, Patrick C; Wouters, Emiel Fm; de Vries, Frank

2017-01-01

Smoking increases the risk of community-acquired pneumonia (CAP) and is associated with the development of COPD. Until now, it is unclear whether CAP in COPD is due to smoking-related effects, or due to COPD pathophysiology itself. To evaluate the association between COPD and CAP by smoking status. In total, 62,621 COPD and 191,654 control subjects, matched by year of birth, gender and primary care practice, were extracted from the Clinical Practice Research Datalink (2005-2014). Incidence rates (IRs) were estimated by dividing the total number of CAP cases by the cumulative person-time at risk. Time-varying Cox proportional hazard models were used to estimate the hazard ratios (HRs) for CAP in COPD patients versus controls. HRs of CAP by smoking status were calculated by stratified analyses in COPD patients versus controls and within both subgroups with never smoking as reference. IRs of CAP in COPD patients (32.00/1,000 person-years) and controls (6.75/1,000 person-years) increased with age and female gender. The risk of CAP in COPD patients was higher than in controls (HR 4.51, 95% CI: 4.27-4.77). Current smoking COPD patients had comparable CAP risk (HR 0.92, 95% CI: 0.82-1.02) as never smoking COPD patients (reference), whereas current smoking controls had a higher risk (HR 1.23, 95% CI: 1.13-1.34) compared to never smoking controls. COPD patients have a fourfold increased risk to develop CAP, independent of smoking status. Identification of factors related with the increased risk of CAP in COPD is warranted, in order to improve the management of patients at risk.

Impact of chronic ischemic heart disease on the health care costs of COPD patients - An analysis of German claims data.

PubMed

Schwarzkopf, Larissa; Wacker, Margarethe; Ertl, Julia; Hapfelmeier, Jana; Larisch, Katharina; Leidl, Reiner

2016-09-01

Chronic Obstructive Pulmonary Disease (COPD) has a substantial impact on health care systems worldwide. Particularly, cardiovascular diseases such as ischemic heart disease (IHD) are frequent in individuals with COPD, but the economic consequences of combined COPD and IHD are by large unknown. Therefore, our study has the objective to investigate excess costs of IHD in COPD patients. Out of German Statutory Health Insurance claims data we identified 26,318 COPD patients with and 10,287 COPD patients without IHD based on ICD-10 codes (COPD J44; IHD I2[0,1,2,5]) of the year 2011 and matched 9986 of them in a 1:1 ratio based on age and gender. Then, we investigated health care service expenditures in 2012 via Generalized Linear Models. Moreover, we evaluated a potential non-linear association between health care expenditures and age in a gender-stratified Generalized Additive Model. The prevalence of IHD in individuals with COPD increases with rising age up to a share of 50%. COPD patients with IHD cause adjusted mean annual per capita health care service expenditures of ca. €7400 compared with ca. €5800 in COPD patients without IHD. Moreover, excess costs of IHD have an inverse u-shape, peaking in the early (men) respectively late seventies (women). IHD in COPD patients is associated with excess costs of ca. € 1,500, with the exact amount varying age- and gender-dependently. Subgroups with high excess costs indicate medical need that calls for efficient care strategies, considering COPD and IHD together particularly between 70 and 80 years of age. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiovascular Disease is Associated with COPD Severity and Reduced Functional Status and Quality of Life

PubMed Central

Black-Shinn, Jennifer L.; Kinney, Gregory L.; Wise, Anastasia L.; Regan, Elizabeth A.; Make, Barry; Krantz, Mori J.; Barr, R. Graham; Murphy, James R.; Lynch, David; Silverman, Edwin K.; Crapo, James D.; Hokanson, John E.

2015-01-01

Introduction Smoking is a major risk factor for both cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). More individuals with COPD die from CVD than respiratory causes and the risk of developing CVD appears to be independent of smoking burden. Although CVD is a common comorbid condition within COPD, the nature of its relationships to COPD affection status and severity, and functional status is not well understood. Methods The first 2,500 members of the COPDGene cohort were evaluated. Subjects were current and former smokers with a minimum 10 pack year history of cigarette smoking. COPD was defined by spirometry as an FEV1/FVC < lower limit of normal (LLN) with further identification of severity by FEV1 percent of predicted (GOLD stages 2, 3, and 4) for the main analysis. The presence of physician-diagnosed self-reported CVD was determined from a medical history questionnaire administered by a trained staff member. Results A total of 384 (15%) had pre-existing CVD. Self-reported CVD was independently related to COPD (Odds Ratio=1.61, 95% CI=1.18–2.20, p=0.01) after adjustment for covariates with CHF having the greatest association with COPD. Within subjects with COPD, pre-existing self-reported CVD placed subjects at greater risk of hospitalization due to exacerbation, higher BODE index, and greater St. George’s questionnaire score. The presence of self-reported CVD was associated with a shorter six-minute walk distance in those with COPD (p<0.05). Conclusions Self-reported CVD was independently related to COPD with presence of both self-reported CVD and COPD associated with a markedly reduced functional status and reduced quality of life. Identification of CVD in those with COPD is an important consideration in determining functional status. PMID:24831864

Exploring the impact of chronic obstructive pulmonary disease (COPD) on diabetes control in diabetes patients: a prospective observational study in general practice.

PubMed

Luijks, Hilde D; de Grauw, Wim J C; Bor, Jacobus H J; van Weel, Chris; Lagro-Janssen, Antoine L M; Biermans, Marion C J; Schermer, Tjard R

2015-04-23

Little is known about the association between COPD and diabetes control parameters. To explore the association between comorbid COPD and longitudinal glycaemic control (HbA1C) and systolic blood pressure (SBP) in a primary care cohort of diabetes patients. This is a prospective cohort study of type 2 diabetes patients in the Netherlands. In a mixed model analysis, we tested differences in the 5-year longitudinal development of HbA1C and SBP according to COPD comorbidity (present/absent). We corrected for relevant covariates. In subgroup effect analyses, we tested whether potential differences between diabetes patients with/without COPD were modified by age, sex, socio-economic status (SES) and body mass index (BMI). We analysed 610 diabetes patients. A total of 63 patients (10.3%) had comorbid COPD. The presence of COPD was not significantly associated with the longitudinal development of HbA1C (P=0.54) or SBP (P=0.33), but subgroup effect analyses showed significant effect modification by SES (P<0.01) and BMI (P=0.03) on SBP. Diabetes patients without COPD had a flat SBP trend over time, with higher values in patients with a high BMI. For diabetes patients with COPD, SBP gradually increased over time in the middle- and high-SES groups, and it decreased over time in those in the low-SES group. The longitudinal development of HbA1C was not significantly associated with comorbid COPD in diabetes patients. The course of SBP in diabetes patients with COPD is significantly associated with SES (not BMI) in contrast to those without COPD. Comorbid COPD was associated with longitudinal diabetes control parameters, but it has complex interactions with other patient characteristics. Further research is needed.

Responsiveness of blood and sputum inflammatory cells in Japanese COPD patients, non-COPD smoking controls, and non-COPD nonsmoking controls

PubMed Central

Kawayama, Tomotaka; Kinoshita, Takashi; Matsunaga, Kazuko; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm; Hoshino, Tomoaki

2016-01-01

Purpose To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC). Patients and methods This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation. Results In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α). Conclusion This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation. PMID:26929615

Efficient screening for COPD using three steps: a cross-sectional study in Mexico City.

PubMed

Franco-Marina, Francisco; Fernandez-Plata, Rosario; Torre-Bouscoulet, Luis; García-Sancho, Cecilia; Sanchez-Gallen, Elisa; Martinez, David; Perez-Padilla, Rogelio

2014-05-20

Underdiagnosis of chronic obstructive pulmonary disease (COPD) in primary care can be improved by a more efficient screening strategy. To evaluate a three-step method of screening for COPD consisting of an initial short questionnaire followed by measurement of forced expiratory volume in 1s/forced expiratory volume in 6s (FEV1/FEV6) using an inexpensive pocket spirometer in those with high risk, and diagnostic quality spirometry in those with a low FEV1/FEV6. We analysed two related Mexico City cross-sectional samples. The 2003 Mexico City PLATINO survey (n=542) was used to develop a short questionnaire to determine the risk of COPD and a 2010 survey (n=737) additionally used a pocket spirometer. The discriminatory power of the two instruments was assessed with receiver operator characteristic (ROC) curves using three COPD definitions. The developed COPD scale included two variables from a simple questionnaire and, in ROC analysis, an area under the curve (AUC) between 0.64 and 0.77 was found to detect COPD. The pocket spirometer had an AUC between 0.85 and 0.88 to detect COPD. Using the COPD scale as a first screening step excluded 35-48% of the total population from further testing at the cost of not detecting 8-18% of those with COPD. Using the pocket spirometer and sending those with a FEV1/FEV6<0.80 for diagnostic quality spirometry is very efficient, and substantially improved the positive predictive value at the cost of not detecting one-third of COPD cases. A three-step screening strategy for COPD substantially reduces the need for spirometry testing when only a COPD scale is used for screening.

Exhaled Breath Temperature as a Novel Marker of Future Development of COPD: Results of a Follow-Up Study in Smokers.

PubMed

Labor, Marina; Vrbica, Žarko; Gudelj, Ivan; Labor, Slavica; Jurić, Iva; Plavec, Davor

2016-12-01

Although only less than one-third of smokers develop COPD, early marker(s) of COPD development are lacking. The aim of this research was to assess the ability of an average equilibrium exhaled breath temperature (EBT) in identifying susceptibility to cigarette smoke so as to predict COPD development in smokers at risk. The study was a part of a multicenter prospective cohort study in current smokers (N = 140, both sexes, 40-65 years, ≥20 pack-years) with no prior diagnosis of COPD. Diagnostic workup includes history, physical, quality of life, hematology and highly sensitive CRP, EBT before and after smoking a cigarette, lung function with bronchodilator test, and 6-minute walk test. Patients without a diagnosis of COPD and in GOLD 1 stage at initial assessment were reassessed after 2 years. COPD was additionally diagnosed based on lower level of normal (LLN) lung function criteria. Utility of EBT for disease progression was analyzed using receiver operator curve (ROC) and logistic regression analyses. Change in EBT after smoking a cigarette at initial visit (ΔEBT) was significantly predictive for disease progression (newly diagnosed COPD; newly diagnosed COPD + severity progression) after 2 years (p < 0.05 for both). ΔEBT had an AUC of 0.859 (p = 0.011) with sensitivity of 66.7% and specificity of 98.1% for newly diagnosed COPD using LLN criteria. We conclude that EBT shows potential for predicting the future development of COPD in current smokers. This was best seen using LLN to diagnose COPD, adding further evidence to question the use of GOLD criteria for diagnosing COPD.

Tumor necrosis factor receptor 2 as a possible marker of COPD in smokers and ex-smokers

PubMed Central

Caram, Laura Miranda de Oliveira; Ferrari, R; Nogueira, DL; Oliveira, MRM; Francisqueti, FV; Tanni, SE; Corrêa, CR; Godoy, I

2017-01-01

Introduction Oxidative stress and systemic inflammation are higher in smokers and patients with COPD; however, markers that may help differentiate between smokers and patients with COPD have not yet been identified. We hypothesized that tumor necrosis factor-alpha receptor (TNFR) and soluble form of the receptor for advanced glycation end products (sRAGE) can be indicators of COPD in asymptomatic patients. Patients and methods We evaluated 32 smokers (smoking history >10 pack-years), 32 patients with mild/moderate COPD (smokers and ex-smokers), and 32 never smokers. Concentrations of C-reactive protein (CRP), interleukin (IL)-6, TNFR1 and TNFR2, advanced glycation end products (AGEs), and the sRAGE were measured in serum. Results There were higher CRP and AGEs concentrations in smokers and in patients with COPD (P<0.001 and P=0.01, respectively) compared to controls, without statistical difference between smokers and patients with COPD. Concentrations of sRAGE, IL-6, and TNFR1 did not differ between study groups. TNFR2 was significantly higher in patients with COPD than in smokers (P=0.004) and controls (P=0.004), and the presence of COPD (P=0.02) and CRP (P=0.001) showed a positive association with TNFR2. Positive associations for smoking (P=0.04), CRP (P=0.03), and IL-6 (P=0.03) with AGEs were also found. The interaction variable (smoking × COPD) showed a positive association with IL-6. Conclusion Our data suggest that TNFR2 may be a possible marker of COPD in asymptomatic smokers and ex-smokers. Although smokers and patients with early COPD presented other increased systemic inflammation markers (eg, CRP) and oxidative stress (measured by AGEs), they did not differentiate smokers from COPD. PMID:28744116

Serum Heat Shock Protein Levels and the Relationship of Heat Shock Proteins with Various Parameters in Chronic Obstructive Pulmonary Disease Patients

PubMed Central

Ünver, Ramazan; Deveci, Figen; Kırkıl, Gamze; Telo, Selda; Kaman, Dilara; Kuluöztürk, Mutlu

2016-01-01

OBJECTIVES Chronic Obstructive Pulmonary Disease (COPD) is accompanied by increased cellular stress and inflammation. Most of the Heat Shock Proteins (HSPs) have strong cytoprotective effects. The role of HSPs in COPD pathogenesis has not determined completely. We investigated the serum level of HSPs in COPD patients, smokers without COPD and healthy non-smoking controls. Also, we evaluated the relationship of HSPs with various parameters (inflammatory, oxidative, functional status, quality of life) in COPD patients. MATERIAL AND METHODS The levels of stress protein (HSP27, HSP70, HSP60, HSP90, CyPA), interleukin-6, C-reactive protein and malondialdehyde were measured in 16 healthy non-smoker, 14 smokers without COPD and 50 patients with stable COPD. Pulmonary function tests (PFT) and arterial blood gases parameters were measured. Health Related Quality of Life was evaluated and exercise capacity was measured with 6 minute walking test. RESULTS Only HSP27 levels was significantly higher in COPD patients when compared with both healthy non-smoker and smokers without COPD (for both, p< 0.001). There was a weak-moderate negative correlation between serum levels of HSP27 and PFT parameters and between HSP27 levels and PaO2. Serum levels of HSP27 showed a weak-moderate positive correlation with symptom, activity and total scores. Subjects evaluated only smokers without COPD and patients with COPD; HSP27 had an area under the curve (AUC) in the receiver operating characteristic (ROC) curve of 0.819 (0.702–0.935; 95% CI; p= 0.000). CONCLUSION Increased serum levels of HSP27 was found in COPD patients and our results showed sensitivity and specificity of serum HSP27 as diagnostic markers for COPD. PMID:29404146

Serum Heat Shock Protein Levels and the Relationship of Heat Shock Proteins with Various Parameters in Chronic Obstructive Pulmonary Disease Patients.

PubMed

Ünver, Ramazan; Deveci, Figen; Kırkıl, Gamze; Telo, Selda; Kaman, Dilara; Kuluöztürk, Mutlu

2016-10-01

Chronic Obstructive Pulmonary Disease (COPD) is accompanied by increased cellular stress and inflammation. Most of the Heat Shock Proteins (HSPs) have strong cytoprotective effects. The role of HSPs in COPD pathogenesis has not determined completely. We investigated the serum level of HSPs in COPD patients, smokers without COPD and healthy non-smoking controls. Also, we evaluated the relationship of HSPs with various parameters (inflammatory, oxidative, functional status, quality of life) in COPD patients. The levels of stress protein (HSP27, HSP70, HSP60, HSP90, CyPA), interleukin-6, C-reactive protein and malondialdehyde were measured in 16 healthy non-smoker, 14 smokers without COPD and 50 patients with stable COPD. Pulmonary function tests (PFT) and arterial blood gases parameters were measured. Health Related Quality of Life was evaluated and exercise capacity was measured with 6 minute walking test. Only HSP27 levels was significantly higher in COPD patients when compared with both healthy non-smoker and smokers without COPD (for both, p< 0.001). There was a weak-moderate negative correlation between serum levels of HSP27 and PFT parameters and between HSP27 levels and PaO 2 . Serum levels of HSP27 showed a weak-moderate positive correlation with symptom, activity and total scores. Subjects evaluated only smokers without COPD and patients with COPD; HSP27 had an area under the curve (AUC) in the receiver operating characteristic (ROC) curve of 0.819 (0.702-0.935; 95% CI; p= 0.000). Increased serum levels of HSP27 was found in COPD patients and our results showed sensitivity and specificity of serum HSP27 as diagnostic markers for COPD.

Responsiveness of blood and sputum inflammatory cells in Japanese COPD patients, non-COPD smoking controls, and non-COPD nonsmoking controls.

PubMed

Kawayama, Tomotaka; Kinoshita, Takashi; Matsunaga, Kazuko; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm; Hoshino, Tomoaki

2016-01-01

To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC). This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation. In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α). This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation.

Tomographic and functional findings in severe COPD: comparison between the wood smoke-related and smoking-related disease *

PubMed Central

González-García, Mauricio; Gomez, Dario Maldonado; Torres-Duque, Carlos A.; Barrero, Margarita; Villegas, Claudia Jaramillo; Pérez, Juan Manuel; Varon, Humberto

2013-01-01

OBJECTIVE: Wood smoke exposure is a risk factor for COPD. For a given degree of airway obstruction, the reduction in DLCO is smaller in individuals with wood smoke-related COPD than in those with smoking-related COPD, suggesting that there is less emphysema in the former. The objective of this study was to compare HRCT findings between women with wood smoke-related COPD and women with smoking-related COPD. METHODS: Twenty-two women with severe COPD (FEV1/FVC ratio < 70% and FEV1 < 50%) were divided into two groups: those with wood smoke-related COPD (n = 12) and those with smoking-related COPD (n = 10). The two groups were compared regarding emphysema scores and airway involvement (as determined by HRCT); and functional abnormalities-spirometry results, DLCO, alveolar volume (VA), the DLCO/VA ratio, lung volumes, and specific airway resistance (sRaw). RESULTS: There were no significant differences between the two groups in terms of FEV1, sRaw, or lung hyperinflation. Decreases in DLCO and in the DLCO/VA ratio were greater in the smoking-related COPD group subjects, who also had higher emphysema scores, in comparison with the wood smoke-related COPD group subjects. In the wood smoke-related COPD group, HRCT scans showed no significant emphysema, the main findings being peribronchial thickening, bronchial dilation, and subsegmental atelectasis. CONCLUSIONS: Female patients with severe wood smoke-related COPD do not appear to develop emphysema, although they do show severe airway involvement. The reduction in DLCO and VA, with a normal DLCO/VA ratio, is probably due to severe bronchial obstruction and incomplete mixing of inspired gas during the determination of single-breath DLCO. PMID:23670499

Time pressured deprioritization of COPD in primary care: a qualitative study.

PubMed

Sandelowsky, Hanna; Hylander, Ingrid; Krakau, Ingvar; Modin, Sonja; Ställberg, Björn; Nager, Anna

2016-01-01

To identify factors that hinder discussions regarding chronic obstructive pulmonary disease (COPD) between primary care physicians (PCPs) and their patients in Sweden. Primary health care centres (PHCCs) in Stockholm, Sweden. A total of 59 PCPs. Semi-structured individual and focus-group interviews between 2012 and 2014. Data were analysed inspired by grounded theory methods (GTM). Time-pressured patient-doctor consultations lead to deprioritization of COPD. During unscheduled visits, deprioritization resulted from focusing only on acute health concerns, while during routine care visits, COPD was deprioritized in multi-morbid patients. The reasons PCPs gave for deprioritizing COPD are: "Not becoming aware of COPD", "Not becoming concerned due to clinical features", "Insufficient local routines for COPD care", "Negative personal attitudes and views about COPD", "Managing diagnoses one at a time", and "Perceiving a patient's motivation as low''. De-prioritization of COPD was discovered during PCP consultations and several factors were identified associated with time constraints and multi-morbidity. A holistic consultation approach is suggested, plus extended consultation time for multi-morbid patients, and better documentation and local routines. Under-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care. A patient-doctor consultation offers a key opportunity to identify and provide COPD care. Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation. Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation. Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.

Influence of heart failure on resting lung volumes in patients with COPD

PubMed Central

de Souza, Aline Soares; Sperandio, Priscila Abreu; Mazzuco, Adriana; Alencar, Maria Clara; Arbex, Flávio Ferlin; de Oliveira, Mayron Faria; O'Donnell, Denis Eunan; Neder, José Alberto

2016-01-01

ABSTRACT Objective: To evaluate the influence of chronic heart failure (CHF) on resting lung volumes in patients with COPD, i.e., inspiratory fraction-inspiratory capacity (IC)/TLC-and relative inspiratory reserve-[1 − (end-inspiratory lung volume/TLC)]. Methods: This was a prospective study involving 56 patients with COPD-24 (23 males/1 female) with COPD+CHF and 32 (28 males/4 females) with COPD only-who, after careful clinical stabilization, underwent spirometry (with forced and slow maneuvers) and whole-body plethysmography. Results: Although FEV1, as well as the FEV1/FVC and FEV1/slow vital capacity ratios, were higher in the COPD+CHF group than in the COPD group, all major "static" volumes-RV, functional residual capacity (FRC), and TLC-were lower in the former group (p < 0.05). There was a greater reduction in FRC than in RV, resulting in the expiratory reserve volume being lower in the COPD+CHF group than in the COPD group. There were relatively proportional reductions in FRC and TLC in the two groups; therefore, IC was also comparable. Consequently, the inspiratory fraction was higher in the COPD+CHF group than in the COPD group (0.42 ± 0.10 vs. 0.36 ± 0.10; p < 0.05). Although the tidal volume/IC ratio was higher in the COPD+CHF group, the relative inspiratory reserve was remarkably similar between the two groups (0.35 ± 0.09 vs. 0.44 ± 0.14; p < 0.05). Conclusions: Despite the restrictive effects of CHF, patients with COPD+CHF have relatively higher inspiratory limits (a greater inspiratory fraction). However, those patients use only a part of those limits, probably in order to avoid critical reductions in inspiratory reserve and increases in elastic recoil. PMID:27832235

The COPD Helplessness Index

PubMed Central

Katz, Patricia P.; Yelin, Edward H.; Iribarren, Carlos; Knight, Sara J.; Blanc, Paul D.; Eisner, Mark D.

2010-01-01

Background: Psychologic factors affect how patients with COPD respond to attempts to improve their self-management skills. Learned helplessness may be one such factor, but there is no validated measure of helplessness in COPD. Methods: We administered a new COPD Helplessness Index (CHI) to 1,202 patients with COPD. Concurrent validity was assessed through association of the CHI with established psychosocial measures and COPD severity. The association of helplessness with incident COPD exacerbations was then examined by following subjects over a median 2.1 years, defining COPD exacerbations as COPD-related hospitalizations or ED visits. Results: The CHI demonstrated internal consistency (Cronbach α = 0.75); factor analysis was consistent with the CHI representing a single construct. Greater CHI-measured helplessness correlated with greater COPD severity assessed by the BODE (Body-mass, Obstruction, Dyspnea, Exercise) Index (r = 0.34; P < .001). Higher CHI scores were associated with worse generic (Short Form-12, Physical Component Summary Score) and respiratory-specific (Airways Questionnaire 20) health-related quality of life, greater depressive symptoms, and higher anxiety (all P < .001). Controlling for sociodemographics and smoking status, helplessness was prospectively associated with incident COPD exacerbations (hazard ratio = 1.31; P < .001). After also controlling for the BODE Index, helplessness remained predictive of COPD exacerbations among subjects with BODE Index ≤ median (hazard ratio = 1.35; P = .01), but not among subjects with higher BODE Index values (hazard ratio = 0.93; P = .34). Conclusions: The CHI is an internally consistent and valid measure, concurrently associated with health status and predictively associated with COPD exacerbations. The CHI may prove a useful tool in analyzing differential clinical responses mediated by patient-centered attributes. PMID:19837823

Impaired Left Ventricular Filling in COPD and Emphysema: Is It the Heart or the Lungs?

PubMed Central

Smith, Benjamin M.; Prince, Martin R.; Hoffman, Eric A.; Bluemke, David A.; Liu, Chia-Ying; Rabinowitz, Dan; Hueper, Katja; Parikh, Megha A.; Gomes, Antoinette S.; Michos, Erin D.; Lima, João A. C.; Barr, R. Graham

2013-01-01

Background: COPD and heart failure with preserved ejection fraction overlap clinically, and impaired left ventricular (LV) filling is commonly reported in COPD. The mechanism underlying these observations is uncertain, but may include upstream pulmonary dysfunction causing low LV preload or intrinsic LV dysfunction causing high LV preload. The objective of this study is to determine if COPD and emphysema are associated with reduced pulmonary vein dimensions suggestive of low LV preload. Methods: The population-based Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers aged 50 to 79 years who were free of clinical cardiovascular disease. COPD was defined by spirometry. Percent emphysema was defined as regions < −910 Hounsfield units on full-lung CT scan. Ostial pulmonary vein cross-sectional area was measured by contrast-enhanced cardiac magnetic resonance and expressed as the sum of all pulmonary vein areas. Linear regression was used to adjust for age, sex, race/ethnicity, body size, and smoking. Results: Among 165 participants, the mean (± SD) total pulmonary vein area was 558 ± 159 mm2 in patients with COPD and 623 ± 145 mm2 in control subjects. Total pulmonary vein area was smaller in patients with COPD (−57 mm2; 95% CI, −106 to −7 mm2; P = .03) and inversely associated with percent emphysema (P < .001) in fully adjusted models. Significant decrements in total pulmonary vein area were observed among participants with COPD alone, COPD with emphysema on CT scan, and emphysema without spirometrically defined COPD. Conclusions: Pulmonary vein dimensions were reduced in COPD and emphysema. These findings support a mechanism of upstream pulmonary causes of underfilling of the LV in COPD and in patients with emphysema on CT scan. PMID:23764937

Th-2 signature in chronic airway diseases: towards the extinction of asthma-COPD overlap syndrome?

PubMed

Cosío, Borja G; Pérez de Llano, Luis; Lopez Viña, Antolin; Torrego, Alfons; Lopez-Campos, Jose Luis; Soriano, Joan B; Martinez Moragon, Eva; Izquierdo, Jose Luis; Bobolea, Irina; Callejas, Javier; Plaza, Vicente; Miravitlles, Marc; Soler-Catalunya, Juan Jose

2017-05-01

We aimed to describe the differences and similarities between patients with chronic obstructive airway disease classified on the basis of classical diagnostic labels (asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap (ACOS)) or according to the underlying inflammatory pattern (Th-2 signature, either Th-2-high or Th-2-low).We performed a cross-sectional study of patients aged ≥40 years and with a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio ≤0.7 with a previous diagnosis of asthma (non-smoking asthmatics (NSA)), COPD or ACOS, the latter including both smoking asthmatics (SA) and patients with eosinophilic COPD (COPD-e). Clinical, functional and inflammatory parameters (blood eosinophil count, IgE and exhaled nitric oxide fraction ( F eNO )) were compared between groups. Th-2 signature was defined by a blood eosinophil count ≥300 cells·μL -1 and/or a sputum eosinophil count ≥3%.Overall, 292 patients were included in the study: 89 with COPD, 94 NSA and 109 with ACOS (44 SA and 65 with COPD-e). No differences in symptoms or exacerbation rate were found between the three groups. With regards the underlying inflammatory pattern, 94 patients (32.2%) were characterised as Th-2-high and 198 (67.8%) as Th-2-low. The Th-2 signature was found in 49% of NSA, 3.3% of patients with COPD, 30% of SA and 49.3% of patients with COPD-e. This classification yielded significant differences in demographic, functional and inflammatory characteristics.We conclude that a classification based upon the inflammatory profile, irrespective of the taxonomy, provides a more clear distinction of patients with chronic obstructive airway disease. Copyright ©ERS 2017.

History of pneumonia is a strong risk factor for chronic obstructive pulmonary disease (COPD) exacerbation in South Korea: the Epidemiologic review and Prospective Observation of COPD and Health in Korea (EPOCH) study.

PubMed

Hwang, Yong Il; Lee, Sang Haak; Yoo, Jee Hong; Jung, Bock Hyun; Yoo, Kwang Ha; Na, Moon Jun; Lee, Jong Deog; Park, Myung Jae; Jung, Chi Young; Shim, Jae Jeong; Kim, Kyung Chan; Kim, Yeon Jae; Choi, Hye Sook; Choi, Ik Su; Lee, Choon-Taek; Lee, Sang Do; Kim, Do Jin; Uh, Soo-Taek; Lee, Ho Sung; Kim, Young Sam; Lee, Kwan Ho; Ra, Seung Won; Kim, Hak Ryul; Choi, Soo Jeon; Park, In Won; Park, Yong Bum; Park, So Young; Lee, Jaehee; Jung, Ki-Suck

2015-12-01

In South Korea, chronic obstructive pulmonary disease (COPD) is one of the ten leading causes of death. COPD exacerbations are significantly associated with mortality in COPD patients. This study was conducted to investigate the epidemiology of COPD in South Korea, specifically the clinical characteristics of South Korean COPD patients, the COPD exacerbation rate and the risk factors associated with COPD exacerbations. This study covers a 2-year interval. One year was data collected retrospectively and the second year was prospectively obtained data. A total of 1,114 subjects were enrolled in the study. These subjects were observed for a period of 1 year from the enrollment, and a total of 920 subjects completed the study. A total of 1,357 COPD exacerbations occurred in 711 subjects (63.8%) out of the total of 1,114 subjects during the study period of 2 years. Multivariate logistic regression results showed that if patients had had a pneumonia before the retrospective year of analysis, they had a 18 times greater chance of having an exacerbation during the prospective year when other variables were controlled. Also, the subjects who had a history of two or more exacerbations during the retrospective year were approximately 6 times more likely to experience the COPD exacerbation compared to those who did not. This study examined the demographic and clinical characteristics of South Korean COPD patients and found that a history of pneumonia and two or more occurrences of exacerbation within 1 year was significantly associated with a higher rate of COPD exacerbation.

Tumor necrosis factor receptor 2 as a possible marker of COPD in smokers and ex-smokers.

PubMed

Caram, Laura Miranda de Oliveira; Ferrari, R; Nogueira, D L; Oliveira, Mrm; Francisqueti, F V; Tanni, S E; Corrêa, C R; Godoy, I

2017-01-01

Oxidative stress and systemic inflammation are higher in smokers and patients with COPD; however, markers that may help differentiate between smokers and patients with COPD have not yet been identified. We hypothesized that tumor necrosis factor-alpha receptor (TNFR) and soluble form of the receptor for advanced glycation end products (sRAGE) can be indicators of COPD in asymptomatic patients. We evaluated 32 smokers (smoking history >10 pack-years), 32 patients with mild/moderate COPD (smokers and ex-smokers), and 32 never smokers. Concentrations of C-reactive protein (CRP), interleukin (IL)-6, TNFR1 and TNFR2, advanced glycation end products (AGEs), and the sRAGE were measured in serum. There were higher CRP and AGEs concentrations in smokers and in patients with COPD ( P <0.001 and P =0.01, respectively) compared to controls, without statistical difference between smokers and patients with COPD. Concentrations of sRAGE, IL-6, and TNFR1 did not differ between study groups. TNFR2 was significantly higher in patients with COPD than in smokers ( P =0.004) and controls ( P =0.004), and the presence of COPD ( P =0.02) and CRP ( P =0.001) showed a positive association with TNFR2. Positive associations for smoking ( P =0.04), CRP ( P =0.03), and IL-6 ( P =0.03) with AGEs were also found. The interaction variable (smoking × COPD) showed a positive association with IL-6. Our data suggest that TNFR2 may be a possible marker of COPD in asymptomatic smokers and ex-smokers. Although smokers and patients with early COPD presented other increased systemic inflammation markers (eg, CRP) and oxidative stress (measured by AGEs), they did not differentiate smokers from COPD.

Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD): follow-up interviews on patient-centred outcomes.

PubMed

Doward, Lynda; Svedsater, Henrik; Whalley, Diane; Crawford, Rebecca; Leather, David; Lay-Flurrie, James; Bosanquet, Nick

2017-12-15

This study investigated patient perceptions, experiences and management of COPD throughout the SLS COPD study. Follow-up interviews were conducted with 400 patients who completed SLS COPD; a mixed-methods approach was used to collect quantitative and qualitative information. Structured interviews using closed-ended questions were conducted with 360 patients, detailing aspects of background/lifestyle information and COPD. Extended interviews containing open-ended questions on perceptions of COPD and quality of life (QoL) in addition to the closed-ended questions were completed by 40 further patients. Participants also completed the Adherence Starts with Knowledge-12 (ASK-12) and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Quantitative data were analysed descriptively; qualitative data were analysed using qualitative description. The participants (n = 400) were reasonably representative of the SLS COPD population; mean age was 66.2 years. Breathlessness was the most commonly recalled symptom of/associated with COPD (88.5% of patients) and was the symptom that changed the most (improved, 26.8%/worsened, 20.9%) throughout the study. Participants' daily functioning and activities were most affected by symptoms of/associated with COPD, followed by relationships and psychological issues. 66.5% of participants experienced exacerbations, 60.5% of whom reported self-management as their first treatment strategy (taking antibiotics, resting and/or corticosteroids). Qualitative analysis revealed COPD symptoms, breathlessness in particular, to have a significant impact on mobility and in turn QoL. In conclusion, breathlessness was cited in these interviews as the COPD symptom with the greatest impact on participants' daily functioning, activities and self-care. The findings provided significant additional knowledge to the SLS COPD study findings.

Lightweight magnesium nanocomposites: electrical conductivity of liquid magnesium doped by CoPd nanoparticles

NASA Astrophysics Data System (ADS)

Yakymovych, Andriy; Slabon, Adam; Plevachuk, Yuriy; Sklyarchuk, Vasyl; Sokoliuk, Bohdan

2018-04-01

The effect of monodisperse bimetallic CoPd NP admixtures on the electrical conductivity of liquid magnesium was studied. Temperature dependence of the electrical conductivity of liquid Mg98(CoPd)2, Mg96(CoPd)4, and Mg92(CoPd)8 alloys was measured in a wide temperature range above the melting point by a four-point method. It was shown that the addition of even small amount of CoPd nanoparticles to liquid Mg has a significant effect on the electrical properties of the melts obtained.

[Effects of COPD on cognitive functions: a case control study].

PubMed

Sarınç Ulaşlı, Sevinç; Oruç, Serdar; Günay, Ersin; Aktaş, Orçun; Akar, Olcay; Koyuncu, Tülay; Ünlü, Mehmet

2013-01-01

Assessment of disease severity, effects of disease on health status and future events should be considered to direct treatment strategies in chronic obstructive pulmonary disease (COPD) management. Although extrapulmonary effects of COPD are well known, effects of COPD on cognitive functions have not been evaluated sufficiently. therefore we aimed to determine cognitive functions of copd patients in the present study. 112 COPD patients with moderate, severe and very severe irreversible airway obstruction and 44 age matched healthy subjects without COPD and systemic diseases as control group were enrolled to the study. Mini mental state examination (MMSE) was performed to evaluate cognitive functions. MMSE results were compared between patient and control groups. Moreover relationship between exacerbation frequency and cognitive functions was evaluated. Total 156 subjects as 112 COPD patients and 44 healthy subjects were included to the study. Mean age of COPD patients was 65.03 ± 7.63 years, and mean age of control group was 63.63 ± 8.96 years (p= 0.364). Mean score of MMSE in COPD patients was 23.8 ± 4.39, and mean score of MMSE in control group was 26.7 ± 2.88. We determined a significant difference in terms of MMSE scores betweeen patient and control group (p< 0.0001). MMSE scores and FEV1 values were significantly different among patients with moderate, sevre and very severe airflow obstruction (p= 0.001; p< 0.0001 respectively). We found a significant negative correlation between MMSE results and exacerbation frequency during last year (p= 0.003; r= -0.239). Lower MMSE scores of COPD patients than subjects in control group indicates the impairment of cognitive functions in COPD patients. Moreover a negative relationship between MMSE scores with exacerbation frequency during last year suggests that prevention from exacerbation can decrease cognitive impairment in COPD patients. We believe that assessment of cognitive functions and preventive strategies should be considered in COPD management.

Association of chronic obstructive pulmonary disease and hemorrhoids

PubMed Central

Lin, Lih-Hwa; Siu, Justin Ji-Yuen; Liao, Po-Chi; Chiang, Jen-Huai; Chou, Pei-Chi; Chen, Huey-Yi; Ho, Tsung-Jung; Tsai, Ming-Yen; Chen, Yung-Hsiang; Chen, Wen-Chi

2017-01-01

Abstract According to traditional Chinese medicine (TCM) theory, a specific physiological and pathological relationship exists between the lungs and the large intestine. The aim of this study is to delineate the association of chronic obstructive pulmonary disease (COPD) and hemorrhoids in order to verify the “interior–exterior” relationship between the lungs and the large intestine. A retrospective cohort study is conceived from the National Health Insurance Research Database, Taiwan. The 2 samples (COPD cohort and non-COPD cohort) were selected from the 2000 to 2003 beneficiaries of the NHI, representing patients age 20 and older in Taiwan, with the follow-up ending on December 31, 2011. The COPD cohort (n = 51,506) includes every patient newly diagnosed as having Chronic Obstructive Pulmonary Disease (COPD, ICD-9-CM: 490–492, 494, 496), who have made at least 2 confirmed visits to the hospital/clinic. The non-COPD cohort (n = 103,012) includes patients without COPD and is selected via a 1:2 (COPD: non-COPD) matching by age group (per 5 years), gender, and index date (diagnosis date of COPD for the COPD cohort). Compared with non-COPD cohorts, patients with COPD have a higher likelihood of having hemorrhoids and the age-, gender- and comorbidies-adjusted hazard ratio (HR) for hemorrhoids is 1.56 (95% confidence intervals [CI]:1.50–1.62). The adjusted HR of hemorrhoids for females is 0.79 (95% CI: 0.77–0.83), which is significantly less than that for males. The elderly groups, 40 to 59 years and aged 60 or above, have higher adjusted HRs than younger age groups (20–39 years), 1.19 (95% CI: 1.14–1.26), and 1.18 (95% CI: 1.12–1.24), respectively. Patients with COPD may have a higher likelihood to have hemorrhoids in this retrospective cohort study. This study verifies the fundamental theorem of TCM that there is a definite pathogenic association between the lungs and large intestine. PMID:28272246

Association of chronic obstructive pulmonary disease and hemorrhoids: A nationwide cohort study.

PubMed

Lin, Lih-Hwa; Siu, Justin Ji-Yuen; Liao, Po-Chi; Chiang, Jen-Huai; Chou, Pei-Chi; Chen, Huey-Yi; Ho, Tsung-Jung; Tsai, Ming-Yen; Chen, Yung-Hsiang; Chen, Wen-Chi

2017-03-01

According to traditional Chinese medicine (TCM) theory, a specific physiological and pathological relationship exists between the lungs and the large intestine. The aim of this study is to delineate the association of chronic obstructive pulmonary disease (COPD) and hemorrhoids in order to verify the "interior-exterior" relationship between the lungs and the large intestine. A retrospective cohort study is conceived from the National Health Insurance Research Database, Taiwan. The 2 samples (COPD cohort and non-COPD cohort) were selected from the 2000 to 2003 beneficiaries of the NHI, representing patients age 20 and older in Taiwan, with the follow-up ending on December 31, 2011. The COPD cohort (n = 51,506) includes every patient newly diagnosed as having Chronic Obstructive Pulmonary Disease (COPD, ICD-9-CM: 490-492, 494, 496), who have made at least 2 confirmed visits to the hospital/clinic. The non-COPD cohort (n = 103,012) includes patients without COPD and is selected via a 1:2 (COPD: non-COPD) matching by age group (per 5 years), gender, and index date (diagnosis date of COPD for the COPD cohort). Compared with non-COPD cohorts, patients with COPD have a higher likelihood of having hemorrhoids and the age-, gender- and comorbidies-adjusted hazard ratio (HR) for hemorrhoids is 1.56 (95% confidence intervals [CI]:1.50-1.62). The adjusted HR of hemorrhoids for females is 0.79 (95% CI: 0.77-0.83), which is significantly less than that for males. The elderly groups, 40 to 59 years and aged 60 or above, have higher adjusted HRs than younger age groups (20-39 years), 1.19 (95% CI: 1.14-1.26), and 1.18 (95% CI: 1.12-1.24), respectively. Patients with COPD may have a higher likelihood to have hemorrhoids in this retrospective cohort study. This study verifies the fundamental theorem of TCM that there is a definite pathogenic association between the lungs and large intestine.

Detection of adenovirus and respiratory syncytial virus in patients with chronic obstructive pulmonary disease: Exacerbation versus stable condition.

PubMed

Kokturk, Nurdan; Bozdayi, Gulendam; Yilmaz, Senay; Doğan, Bora; Gulbahar, Ozlem; Rota, Seyyal; Tatlicioglu, Turkan

2015-08-01

Latent infection with adenovirus and respiratory syncytial virus (RSV) is associated with chronic obstructive pulmonary disease (COPD). The role of respiratory viral infections are emerging in COPD exacerbations. The present study aimed to investigate the prevalence of adenovirus and RSV serotypes A and B in individuals with acute exacerbations of COPD (COPD-AE) and stable COPD. Twenty seven patients with COPD-AE were evaluated using a prospective longitudinal study design. Induced sputum, sera and nasal smears were sampled from patients experiencing COPD-AE and those in a stable condition. Adenoplex® multiplex polymerase chain reaction (PCR) kits and Invitek RTP® DNA/RNA Virus Mini kits were used for PCR assays of adenovirus and RSV, respectively. Eighteen patients who experienced a COPD-AE were also evaluated while in a stable condition. The results showed that three sputum samples were positive for adenovirus in patients experiencing an exacerbation, while one was positive among the patients in a stable condition. RSV serotype A was detected in 17/27 (63%) patients with COPD-AE and 10/18 (55.6%) patients in a stable condition. RSV serotype B was not detected. Patients with COPD-AE, who were positive for RSV serotype A exhibited higher serum fibrinogen levels than those who were negative (438.60 ± 126.08 mg/dl compared with 287.60 ± 85.91 mg/dl; P=0.004). Eight/ten patients who were positive for RSV serotype A while in a stable condition, were also positive during COPD-AE. The results of the present study suggested that RSV infection may be prevalent in patients with COPD-AE and in those in a stable condition. Therefore, chronic RSV infection may occur in COPD. The detection and prevention of RSV may be useful in the management of COPD.

Bronchial hyperresponsiveness in women with chronic obstructive pulmonary disease related to wood smoke

PubMed Central

González-García, Mauricio; Torres-Duque, Carlos A; Bustos, Adriana; Jaramillo, Claudia; Maldonado, Darío

2012-01-01

Purpose Chronic obstructive pulmonary disease (COPD) related to wood smoke exposure is characterized by important inflammation of the central and peripheral airways without significant emphysema. The objective of this study is to describe the bronchial hyperresponsiveness (BHR) level in women with COPD related to wood smoke exposure and to compare it with the BHR in women with COPD related to tobacco smoking. Materials and methods Two groups of women with stable COPD were studied: (1) wood smoke exposed (WS-COPD); and (2) tobacco smoke exposed (TS-COPD). A methacholine challenge test (MCT) was performed in all patients according to American Thoracic Society criteria. BHR levels were compared using the methacholine concentration, which caused a 20% fall in the FEV1 (PC20). Results Thirty-one patients, 19 with WS-COPD and 12 with TS-COPD, were included. There were no significant differences between the groups in baseline FVC, FEV1, IC, FEF25–75, and FEF25–75/FVC. All 31 patients had a positive MCT (PC20 < 16 mg/mL) and the fall in the FEV1 and IC was similar in both groups. The severity of BHR was significantly higher in the WS-COPD patients (PC20: 0.39 mg/mL) than in the TS-COPD patients (PC20: 1.24 mg/mL) (P = 0.028). The presence of cough, phlegm, and dyspnea during the test were similar in both groups. Conclusion We found moderate to severe BHR in women with WS-COPD, which was more severe than in the TS-COPD women with similar age and airflow obstruction. This paper suggests that the structural and inflammatory changes induced by the chronic exposure to wood smoke, described in other studies, can explain the differences with TS-COPD patients. Future studies may clarify our understanding of the impact of BHR on COPD physiopathology, phenotypes, and treatment strategies. PMID:22791990

Hand grip strength and chronic obstructive pulmonary disease in Korea: an analysis in KNHANES VI.

PubMed

Lee, Su Hwan; Kim, Soo Jung; Han, Yeji; Ryu, Yon Ju; Lee, Jin Hwa; Chang, Jung Hyun

2017-01-01

Muscle mass is known to be associated with mortality in elderly adults. Because hand grip strength (HGS) is known as a simple assessment tool for muscular strength, many researchers have studied the association between HGS and disease. However, empirical evidence for the relationship between chronic obstructive pulmonary disease (COPD) and HGS is still controversial. The aim of this study was to evaluate the association between COPD and HGS, using Korean population data. This was a population-based cross-sectional study. Data were obtained from the sixth Korean National Health and Nutrition Examination Survey, which was conducted from 2013 to 2015. To reduce the effects of HGS-related factors and potential confounding factors, propensity score matching was used to match subjects with and without COPD. Among 14,930 subjects, 832 were enrolled in each group (non-COPD and COPD) after propensity score matching. COPD subjects did not have lower HGS than non-COPD subjects (non-COPD vs COPD, male, 38.0±7.0 vs 38.9±7.0 kg, P =0.044, female, 23.8±4.6 vs 24.2±4.9 kg, P =0.342). Lung function was classified by Global Initiative for Chronic Obstructive Lung Disease stages and was not significantly associated with HGS. For male COPD subjects, there was a significant correlation between HGS and the EuroQol Five-Dimension Questionnaire (EQ5D) utility score index, which is an indicator of quality of life that adjusts for age and body mass index ( r =0.201, P <0.001). The correlation was absent for female subjects ( r =0.098, P =0.170). COPD subjects did not have lower HGS than non-COPD subjects. HGS did not associate with lung function. However, the HGS of male COPD subjects was positively associated with EQ5D utility score index, an indicator of quality of life. HGS may be helpful as an additional method to the evaluation of quality of life in male COPD patients.

The prevalence of COPD co-morbidities in Serbia: results of a national survey

PubMed Central

Nagorni-Obradovic, Ljudmila M; Vukovic, Dejana S

2014-01-01

Background: Research studies have found different prevalence rates for co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Aims: The aim of our study was to investigate the prevalence of co-morbidities as well as functional limitations in subjects with COPD. Methods: The study was based on a nationally representative sample of the population of Serbia. Information on the health of the population was obtained from interviews and anthropometric measurements. In this study we analysed a total of 10,013 respondents aged 40 years or older. There were 653 subjects with COPD and 9,360 respondents without COPD. Results: Out of the 10,013 respondents, 5,377 were aged 40–59 years and 4,636 were 60 years or older. The prevalence of COPD was 5.0% in respondents aged 40–59 years and 8.3% in those aged 60 years or older; the total prevalence was 6.5%. The most prevalent co-morbidities among respondents with COPD were hypertension (54.5%) and dyslipidaemia (26.5%). The prevalence of all analysed co-morbidities was higher in respondents with COPD and the difference was highly statistically significant, except for stroke and malignancies, for which the difference was significant. Analysis showed that respondents with COPD had a higher prevalence of all analysed clinical factors (dizziness, obesity, anaemia and frailty) and functional impairments (mobility and hearing and visual impairment) compared with respondents without COPD. For those aged 40–59 years the difference was highest for mobility difficulty (four times higher prevalence in COPD patients) and anaemia (three times higher in COPD patients). Conclusion: Our analysis showed that the most prevalent co-morbidities in COPD were hypertension, dyslipidaemia, chronic renal disease and anxiety/depression. The finding suggests that health professionals should actively assess co-morbidities in patients with COPD. PMID:24921714

Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink.

PubMed

Landis, Sarah; Suruki, Robert; Maskell, Joe; Bonar, Kerina; Hilton, Emma; Compton, Chris

2018-03-20

Blood eosinophil count may be a useful biomarker for predicting response to inhaled corticosteroids and exacerbation risk in chronic obstructive pulmonary disease (COPD) patients. The optimal cut point for categorizing blood eosinophil counts in these contexts remains unclear. We aimed to determine the distribution of blood eosinophil count in COPD patients and matched non-COPD controls, and to describe demographic and clinical characteristics at different cut points. We identified COPD patients within the UK Clinical Practice Research Database aged ≥40 years with a FEV 1 /FVC <0.7, and ≥1 blood eosinophil count recorded during stable disease between January 1, 2010 and December 31, 2012. COPD patients were matched on age, sex, and smoking status to non-COPD controls. Using all blood eosinophil counts recorded during a 12-month period, COPD patients were categorized as "always above," "fluctuating above and below," and "never above" cut points of 100, 150, and 300 cells/μL. The geometric mean blood eosinophil count was statistically significantly higher in COPD patients versus matched controls (196.6 cells/µL vs. 182.1 cells/µL; mean difference 8%, 95% CI: 6.8, 9.2), and in COPD patients with versus without a history of asthma (205.0 cells/µL vs. 192.2 cells/µL; mean difference 6.7%, 95%, CI: 4.9, 8.5). About half of COPD patients had all blood eosinophil counts above 150 cells/μL; this persistent higher eosinophil phenotype was associated with being male, higher body mass index, and history of asthma. In conclusion, COPD patients demonstrated higher blood eosinophil count than non-COPD controls, although there was substantial overlap in the distributions. COPD patients with a history of asthma had significantly higher blood eosinophil count versus those without.

Incidence of pulmonary embolism during COPD exacerbation*, **

PubMed Central

Akpinar, Evrim Eylem; Hoşgün, Derya; Akpýnar, Serdar; Ataç, Gökçe Kaan; Doğanay, Beyza; Gülhan, Meral

2014-01-01

OBJECTIVE: Because pulmonary embolism (PE) and COPD exacerbation have similar presentations and symptoms, PE can be overlooked in COPD patients. Our objective was to determine the prevalence of PE during COPD exacerbation and to describe the clinical aspects in COPD patients diagnosed with PE. METHODS: This was a prospective study conducted at a university hospital in the city of Ankara, Turkey. We included all COPD patients who were hospitalized due to acute exacerbation of COPD between May of 2011 and May of 2013. All patients underwent clinical risk assessment, arterial blood gas analysis, chest CT angiography, and Doppler ultrasonography of the lower extremities. In addition, we measured D-dimer levels and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. RESULTS: We included 172 patients with COPD. The prevalence of PE was 29.1%. The patients with pleuritic chest pain, lower limb asymmetry, and high NT-pro-BNP levels were more likely to develop PE, as were those who were obese or immobile. Obesity and lower limb asymmetry were independent predictors of PE during COPD exacerbation (OR = 4.97; 95% CI, 1.775-13.931 and OR = 2.329; 95% CI, 1.127-7.105, respectively). CONCLUSIONS: The prevalence of PE in patients with COPD exacerbation was higher than expected. The association between PE and COPD exacerbation should be considered, especially in patients who are immobile or obese. PMID:24626268

16S rDNA analysis of periodontal plaque in chronic obstructive pulmonary disease and periodontitis patients

PubMed Central

Wu, Xingwen; Chen, Jiazhen; Xu, Meng; Zhu, Danting; Wang, Xuyang; Chen, Yulin; Wu, Jing; Cui, Chenghao; Zhang, Wenhong; Yu, Liying

2017-01-01

ABSTRACT This study investigated if chronic obstructive pulmonary disease (COPD) is correlated with periodontitis via periodontal microbiota and if certain bacteria affect periodontitis as well as COPD. Moreover, the study investigated whether suffering from COPD is associated with a decrease in the richness and diversity of periodontal microbiota. Subgingival plaque was obtained from 105 patients. Bacterial DNA was isolated from 55 COPD and 50 non-COPD participants (either with or without periodontitis). 16S rRNA gene metagenomic sequencing was used to characterize the microbiota and to determine taxonomic classification. In the non-periodontitis patients, suffering from COPD resulted in a decrease in bacteria richness and diversity in the periodontal microenvironment. An increase in the genera Dysgonomonas, Desulfobulbus, and Catonella and in four species (Porphyromonas endodontalis, Dysgonomonas wimpennyi, Catonella morbi, and Prevotella intermedia) in both COPD and periodontitis patients suggests that an increase in these periodontitis-associated microbiota may be related to COPD. Three genera (Johnsonella, Campylobacter, and Oribacterium) were associated with COPD but not with periodontitis. The decrease in the genera Arcanobacterium, Oribacterium, and Streptomyces in COPD patients implies that these genera may be health-associated genera, and the decrease in these genera may be related to disease. These data support the hypothesis that COPD is correlated with periodontitis via these significantly changed specific bacteria. PMID:28748030

Validation of the Spanish Version of the COPD-Q Questionnaire on COPD Knowledge.

PubMed

Puente-Maestu, Luis; Chancafe-Morgan, Jorge; Calle, Myriam; Rodríguez-Hermosa, Juan L; Malo de Molina, Rosa; Ortega-González, Ángel; Fuster, Antonia; Márquez-Martín, Eduardo; Marcos, Pedro J; Ramírez, Laura; Ray, Shaunta'; Franks, Andrea

2016-01-01

Although recognition of the importance of educating chronic obstructive pulmonary disease (COPD) patients has grown in recent years, their understanding of this disease is not being measured due to a lack of specific instruments. The aim of this study was to validate the COPD-Q questionnaire, a 13-item instrument for determining COPD knowledge. The COPD-Q was translated and backtranslated, and subsequently submitted to logic and content validation by a group of COPD experts and 8 COPD patients. Reliability was studied in an independent group of 59 patients with severe COPD seen in the pulmonology ward or clinics of 6 hospitals in Spain (Andalusia, Baleares, Castilla-La Mancha, Galicia and Madrid). This sample was also used for other internal and external validations. The mean age of the group was approximately 70 years and their health awareness was low-to-medium. The number of correct answers was 8.3 (standard deviation: 1.9), median 8, range 3-13. Floor and ceiling effects were 0% and 1.5%, respectively. Internal consistency of the questionnaire was good (Cronbach's alpha=0.85) and reliability was also high, with a kappa coefficient >0.6 for all items and an intraclass correlation efficient of 0.84 for the total score. The 13-item COPD-Q is a valid, applicable and reliable instrument for determining patients' knowledge of COPD. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Prevalence of. cap alpha. /sub 1/-antitrypsin heterozygotes (Pi MZ) in patients with obstructive pulmonary disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shigeoka, J.W.; Hall, W.J.; Hyde, R.W.

1976-01-01

An increased incidence of intermediate deficiency of serum ..cap alpha../sub 1/-antitrypsin resulting from Pi phenotype MZ has been reported in patients with chronic obstructive pulmonary disease (COPD) by some laboratories but not confirmed by others. Prevalence of Pi MZ was determined in patients with COPD among 502 subjects referred to a pulmonary function testing laboratory in a region with low concentrations of air pollutants. Control prevalences were obtained from 930 randomly selected subjects in the same community as well as from patients without COPD referred to the laboratory. Depending on criteria used to define COPD, 155 to 306 subjects hadmore » COPD. Pi MZ prevalence in subjects with COPD varied from 1.5 to 4 times the prevalence in the community control group and in the patients without COPD. This difference approached significance or was significant. Because Pi MZ was present in only 3.5 to 4.5% of patients with COPD, Pi MZ is not a major factor in the etiology of COPD in this community. The higher incidence of Pi MZ in patients with COPD reported by other investigators may be explained by small sample size, bias in selection of study or control population groups, or the development of COPD from interaction between Pi MZ and air pollutants or other factors not present in this community.« less

The chronic bronchitis phenotype in subjects with and without COPD: the PLATINO study.

PubMed

de Oca, Maria Montes; Halbert, Ronald J; Lopez, Maria Victorina; Perez-Padilla, Rogelio; Tálamo, Carlos; Moreno, Dolores; Muiño, Adrianna; Jardim, José Roberto B; Valdivia, Gonzalo; Pertuzé, Julio; Menezes, Ana Maria B

2012-07-01

Little information exists regarding the epidemiology of the chronic bronchitis phenotype in unselected chronic obstructive pulmonary disease (COPD) populations. We examined the prevalence of the chronic bronchitis phenotype in COPD and non-COPD subjects from the PLATINO study, and investigated how it is associated with important outcomes. Post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70 was used to define COPD. Chronic bronchitis was defined as phlegm on most days, at least 3 months per year for ≥ 2 yrs. We also analysed another definition: cough and phlegm on most days, at least 3 months per year for ≥ 2 yrs. Spirometry was performed in 5,314 subjects (759 with and 4,554 without COPD). The proportion of subjects with and without COPD with chronic bronchitis defined as phlegm on most days, at least 3 months per year for ≥ 2 yrs was 14.4 and 6.2%, respectively. Using the other definition the prevalence was lower: 7.4% with and 2.5% without COPD. Among subjects with COPD, those with chronic bronchitis had worse lung function and general health status, and had more respiratory symptoms, physical activity limitation and exacerbations. Our study helps to understand the prevalence of the chronic bronchitis phenotype in an unselected COPD population at a particular time-point and suggests that chronic bronchitis in COPD is possibly associated with worse outcomes.

Domain-specific cognitive impairment in patients with COPD and control subjects

PubMed Central

Cleutjens, Fiona AHM; Franssen, Frits ME; Spruit, Martijn A; Vanfleteren, Lowie EGW; Gijsen, Candy; Dijkstra, Jeanette B; Ponds, Rudolf WHM; Wouters, Emiel FM; Janssen, Daisy JA

2017-01-01

Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P<0.001), planning (17.8% vs 1.1%; P<0.001), and cognitive flexibility (43.3% vs 12.2%; P<0.001). General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls. PMID:28031706

Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.

PubMed

Guiedem, Elise; Ikomey, George Mondinde; Nkenfou, Céline; Walter, Pefura-Yone Eric; Mesembe, Martha; Chegou, Novel Njweipi; Jacobs, Graeme Brendon; Okomo Assoumou, Marie Claire

2018-03-27

The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 10 6 /ml and 2.48 × 10 6 /ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.

Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

PubMed Central

Broekman, Winifred; Khedoe, Padmini P S J; Schepers, Koen; Roelofs, Helene; Stolk, Jan; Hiemstra, Pieter S

2018-01-01

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research. PMID:29653970

[Chronic obstructive pulmonary disease (COPD) and the interior environment].

PubMed

Khayath, N; Qi, S; de Blay, F

2016-10-01

In COPD, the risk attributable to smoking is very variable according to published studies. A significant number shows that the risk of COPD in non-smokers is far from negligible. The links between COPD and pollution of the interior environment vary between developed and developing countries. In developing countries, numerous studies have shown a link between COPD and exposure to substances derived from the combustion of biomass fuels, particularly in women where the exposure is the greatest. Nevertheless, a cause and effect relationship has not always been demonstrated. In developed countries, there is no evidence of a role of exposure to domestic interior pollution in the genesis of COPD and interior pollutants such as NO 2  and particulates seem only to aggravate already existing COPD. Further studies are necessary to evaluate their role in COPD and explore the underlying mechanisms. Irritative phenomena could be involved. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012–2013

PubMed Central

Landis, Sarah H; Muellerova, Hana; Mannino, David M; Menezes, Ana M; Han, MeiLan K; van der Molen, Thys; Ichinose, Masakazu; Aisanov, Zaurbek; Oh, Yeon-Mok; Davis, Kourtney J

2014-01-01

Purpose The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999–2000. Materials and methods Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples. Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments. Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale. Results Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey. COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%–9%. In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%–14%) than among women (range 5%–11%). A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries. Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment. Conclusion This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey. A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. PMID:24944511

Smoke, Biomass Exposure, and COPD Risk in the Primary Care Setting: The PUMA Study.

PubMed

Montes de Oca, Maria; Zabert, Gustavo; Moreno, Dolores; Laucho-Contreras, Maria E; Lopez Varela, Maria Victorina; Surmont, Filip

2017-08-01

The evidence indicates that risk factors other than smoking are important in the development of COPD. It has been postulated that less traditional risk factors (eg, exposure to coal and/or biomass smoke) may interact with smoking to further increase COPD risk. This analysis evaluated the effect of exposure to biomass and smoking on COPD risk in a primary care setting in Latin America. Subjects attending routine primary care visits, ≥40 y old, who were current or former smokers or were exposed to biomass smoke, completed a questionnaire and performed spirometry. COPD was defined as post-bronchodilator FEV 1 /FVC < 0.70 and the lower limit of normal. Smoking was defined by pack-years (≤ 20, 20-30, or > 30), and biomass exposure was defined as an exposure to coal or wood (for heating, cooking, or both) for ≥ 10 y. One thousand seven hundred forty-three individuals completed the questionnaire, and 1,540 performed spirometry. Irrespective of COPD definition, approximately 40% of COPD subjects reported exposure to biomass versus 30% of those without COPD. A higher proportion of COPD subjects (post-bronchodilator FEV 1 /FVC < 0.70) than those without COPD smoked > 30 pack-years (66% vs 39%); similar results were found with the lower limit of normal definition. Analysis of exposure to biomass > 10 y plus smoking > 20 pack-years (reference was no exposure) found that tobacco smoking (crude odds ratio [OR] 4.50, 95% CI 2.73-7.41; adjusted OR 3.30, 95% CI 1.93-5.63) and biomass exposure (crude OR 3.66, 95% CI 2.00-6.73; adjusted OR 2.28, 95% CI 1.18-4.41) were risk factors for COPD, with smoking a possible confounder for the association between biomass and COPD (post-bronchodilator FEV 1 /FVC < 0.70); similar results were found with the lower limit of normal definition. Subjects with COPD from primary care had a higher exposure to biomass and smoking compared with non-COPD subjects. Smoking and biomass are both risk factors for COPD, but they do not appear to have an additive effect. Copyright © 2017 by Daedalus Enterprises.

Pulmonary arterial stiffening in COPD and its implications for right ventricular remodelling.

PubMed

Weir-McCall, Jonathan R; Liu-Shiu-Cheong, Patrick Sk; Struthers, Allan D; Lipworth, Brian J; Houston, J Graeme

2018-02-27

Pulmonary pulse wave velocity (PWV) allows the non-invasive measurement of pulmonary arterial stiffening, but has not previously been assessed in COPD. The aim of the current study was to assess PWV in COPD and its association with right ventricular (RV) remodelling. Fifty-eight participants with COPD underwent pulmonary function tests, 6-min walk test and cardiac MRI, while 21 healthy controls (HCs) underwent cardiac MRI. Thirty-two COPD patients underwent a follow-up MRI to assess for longitudinal changes in RV metrics. Cardiac MRI was used to quantify RV mass, volumes and PWV. Differences in continuous variables between the COPD and HC groups was tested using an independent t-test, and associations between PWV and right ventricular parameters was examined using Pearson's correlation coefficient. Those with COPD had reduced pulsatility (COPD (mean±SD):24.88±8.84% vs. HC:30.55±11.28%, p=0.021), pulmonary acceleration time (COPD:104.0±22.9ms vs. HC: 128.1±32.2ms, p<0.001), higher PWV (COPD:2.62±1.29ms -1 vs. HC:1.78±0.72ms -1 , p=0.001), lower RV end diastolic volume (COPD:53.6±11.1ml vs. HC:59.9±13.0ml, p=0.037) and RV stroke volume (COPD:31.9±6.9ml/m 2 vs. HC:37.1±6.2ml/m 2 , p=0.003) with no difference in mass (p=0.53). PWV was not associated with right ventricular parameters. While pulmonary vascular remodelling is present in COPD, cardiac remodelling favours reduced filling rather than increased afterload. Treatment of obstructive lung disease may have greater effect on cardiac function than treatment of pulmonary vascular disease in most COPD patients KEY POINTS: • Pulmonary pulse wave velocity (PWV) is elevated in COPD. • Pulmonary PWV is not associated with right ventricular remodelling. • Right ventricular remodelling is more in keeping with that of reduced filling.

Global Mapping of the Yeast Genetic Interaction Network

NASA Astrophysics Data System (ADS)

Tong, Amy Hin Yan; Lesage, Guillaume; Bader, Gary D.; Ding, Huiming; Xu, Hong; Xin, Xiaofeng; Young, James; Berriz, Gabriel F.; Brost, Renee L.; Chang, Michael; Chen, YiQun; Cheng, Xin; Chua, Gordon; Friesen, Helena; Goldberg, Debra S.; Haynes, Jennifer; Humphries, Christine; He, Grace; Hussein, Shamiza; Ke, Lizhu; Krogan, Nevan; Li, Zhijian; Levinson, Joshua N.; Lu, Hong; Ménard, Patrice; Munyana, Christella; Parsons, Ainslie B.; Ryan, Owen; Tonikian, Raffi; Roberts, Tania; Sdicu, Anne-Marie; Shapiro, Jesse; Sheikh, Bilal; Suter, Bernhard; Wong, Sharyl L.; Zhang, Lan V.; Zhu, Hongwei; Burd, Christopher G.; Munro, Sean; Sander, Chris; Rine, Jasper; Greenblatt, Jack; Peter, Matthias; Bretscher, Anthony; Bell, Graham; Roth, Frederick P.; Brown, Grant W.; Andrews, Brenda; Bussey, Howard; Boone, Charles

2004-02-01

A genetic interaction network containing ~1000 genes and ~4000 interactions was mapped by crossing mutations in 132 different query genes into a set of ~4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.

COPD in Never Smokers

PubMed Central

McBurnie, Mary Ann; Vollmer, William M.; Gudmundsson, Gunnar; Welte, Tobias; Nizankowska-Mogilnicka, Ewa; Studnicka, Michael; Bateman, Eric; Anto, Josep M.; Burney, Peter; Mannino, David M.; Buist, Sonia A.

2011-01-01

Background: Never smokers comprise a substantial proportion of patients with COPD. Their characteristics and possible risk factors in this population are not yet well defined. Methods: We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study. Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines. In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio. Results: Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD. Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD. This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio. Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations. Conclusion: This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD. Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. PMID:20884729

Prevalence and Risk Factors of Respiratory Viral Infections in Exacerbations of Chronic Obstructive Pulmonary Disease.

PubMed

Kwak, Hyun Jung; Park, Dong Won; Kim, Jee Eun; Park, Min Kyung; Koo, Gun Woo; Park, Tai Sun; Moon, Ji-Yong; Kim, Tae Hyung; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Kim, Sang-Heon

2016-10-01

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections. Furthermore, we tried to examine if COPD exacerbations caused by viral infections have more severe clinical outcomes in comparison with those with non-viral causes. We enrolled the patients with acute exacerbations of COPD who were hospitalized in a university hospital, over a 2-year period. Nasopharyngeal swabs were taken and viruses were identified by multiplex polymerase chain reaction. A total of 278 episodes of COPD exacerbations were recorded in 213 patients with COPD (number of females = 73). Among the COPD exacerbations, viral infection was detected in 78 episodes (28.1%) from 67 subjects. The most common virus was rhinovirus (38.8%), followed by respiratory syncytial virus, coronavirus, influenza A, parainfluenza, adenovirus and metapneumovirus. In multivariate regression analysis adjusting for sex, age, BMI, lung function and history of exacerbations, female subjects were found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 2.58, 95%CI 1.25-5.31, P = 0.010). The severity of COPD exacerbations were not different between positive and negative viral detections. In conclusion, the prevalence of viral infection was 28.1% in the hospitalized patients with COPD exacerbations. Moreover, female subjects are at significantly higher risk for viral infections in COPD exacerbations.

Validation of a structured questionnaire for COPD and prevalence of COPD in rural area of Mysore: A pilot study.

PubMed

Mahesh, P A; Jayaraj, B S; Prahlad, S T; Chaya, S K; Prabhakar, A K; Agarwal, A N; Jindal, S K

2009-07-01

The prevalence of chronic obstructive pulmonary disease (COPD) is increasing in India and there is a need to study the prevalence of COPD, particularly in the rural areas, which may be most affected due to their lifestyle. FIRST STAGE: Validation of the questionnaire-105 consecutive patients underwent administration of the structured questionnaire and spirometry was used as a gold standard for the diagnosis of COPD. Second stage: Adults above 40 years (n = 900) in two villages of Mysore district were administered with the validated questionnaire, Knowledge and Attitude questionnaire and Fagerstorm questionnaire, to assess nicotine dependency. The questionnaire was found to have a sensitivity of 62.5% and specificity of 87.6% to diagnose COPD. Of the total 900 adults surveyed (Males: 453, Females: 447), the total prevalence of COPD was 7.1%. Males had a higher prevalence (11.1%) compared to females (4.5%). The prevalence of smoking was very high among men at 71.9% and all the women were nonsmokers. The prevalence of COPD was 14.7% in smokers, 19.3% had mild to moderate nicotine dependency and 12.8% were highly dependent. Of the women exposed to regular biomass fuels, the prevalence of COPD was 3.9%, which increased to 4.8% on addition of regular passive smoking. In smoking, male gender and age were significantly associated with COPD (P < 0.05). The structured questionnaire is a useful tool for the screening of COPD in field studies. Smoking and biomass fuel exposure are important risk factors for COPD.

Early detection of COPD: a case finding study in general practice.

PubMed

Vandevoorde, Jan; Verbanck, Sylvia; Gijssels, Lieve; Schuermans, Daniel; Devroey, Dirk; De Backer, Joan; Kartounian, Jan; Vincken, Walter

2007-03-01

To estimate the prevalence of undiagnosed chronic obstructive pulmonary disease (COPD) in a population of general practice patients at risk for developing COPD. A further aim was to evaluate the presence of respiratory symptoms as a predictor for the diagnosis of COPD. This study was conducted by eight general practitioners (GP) in six semi-rural general practices. During two consecutive months all patients attending their GP were included if they met the following criteria: current smokers between 40 and 70 yr of age, and a smoking history of at least 15 pack-years. A questionnaire regarding smoking history, respiratory symptoms, exposure to dust or chemical fumes, and history of respiratory diseases was completed for all patients. Subjects without known COPD were invited for spirometric testing. Off the 146 general practice patients included, 17.1% already had an established COPD diagnosis. Screening by spirometry revealed a 46.6% prevalence of COPD. Underdiagnosis of COPD was more frequent in the younger age categories (40-49 Yr; 50-59 Yr). Objective wheezing was the only sign that was significantly more frequent in COPD patients than in non-COPD patients (P<0.001). Patients with previously known COPD were significantly older, and complained more of chronic cough and fatigue than newly detected patients. Almost half of a general practice population of current smokers between 40 and 70 years of age, with a smoking history of at least 15 pack-years, was diagnosed with COPD, and roughly two thirds of these were newly detected as a result of the case finding programme.

Impact of chronic obstructive pulmonary disease on clinical course after an episode of acute heart failure. EAHFE-COPD study.

PubMed

Jacob, Javier; Tost, Josep; Miró, Òscar; Herrero, Pablo; Martín-Sánchez, Francisco Javier; Llorens, Pere

2017-01-15

To study if the coexistence of chronic obstructive pulmonary disease (COPD) in patients diagnosed with acute heart failure (AHF) at the emergency department (ED) has an impact on short- and long-term outcomes. The EAHFE-COPD study included patients who attended in 34 Spanish EDs for AHF. We compared patients with AHF plus COPD with patients with AHF in whom COPD was neither diagnosed nor excluded by functional respiratory tests (FRT). Outcome analysis included all-cause mortality, prolonged hospitalization, and ED revisit. Crude results were adjusted by differences between patients with and without COPD. We included 8099 patients with AHF, 2069 having COPD (25.6%; AHF-COPD-known). Compared with AHF-COPD-unknown, AHF-COPD-known differed in 20 variables. After adjusting for differences between the two groups, AHF-COPD-known patients showed no significant differences in 30-day mortality (OR=0.89; 95% CI=0.71-1.11), prolonged hospitalization in general wards (OR=1.04; 95% CI=0.89-1.22) or SSU (OR=1.38; 95% CI=0.97-1.97), and 1-year mortality (HR: 1.02; 95% CI=0.89-1.17), but showed a higher 30-day revisit rate (OR=1.32; 95% CI=1.13-1.54). In patients attending the ED for AHF, the coexistence of COPD is only associated with an increased risk of short-term ED revisit, but not prolonged hospitalization and short- or long-term mortality. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

COPD - managing stress and your mood

MedlinePlus

Chronic obstructive pulmonary disease - emotions; Stress - COPD; Depression - COPD ... Having COPD can affect your mood and emotions for several reasons: You cannot do all the things you used to do. You may need to do things much slower than you ...

Breathtaking: Managing a COPD Diagnosis | NIH MedlinePlus the Magazine

MedlinePlus

... Managing a COPD Diagnosis Photo: iStock Chronic obstructive pulmonary disease (COPD) is a serious lung disease that makes it hard to breathe. It’s also known as emphysema or chronic bronchitis. In people who have COPD, ...

Prospective impact of illness uncertainty on outcomes in chronic lung disease.

PubMed

Hoth, Karin F; Wamboldt, Frederick S; Strand, Matthew; Ford, Dee W; Sandhaus, Robert A; Strange, Charlie; Bekelman, David B; Holm, Kristen E

2013-11-01

To determine which aspect of illness uncertainty (i.e., ambiguity or complexity) has a stronger association with psychological and clinical outcomes over a 2-year period among individuals with a genetic subtype of chronic obstructive pulmonary disease (COPD). Ambiguity reflects uncertainty about physical cues and symptoms, and complexity reflects uncertainty about treatment and the medical system. Four-hundred and 7 individuals with alpha-1 antitrypsin deficiency-associated COPD completed questionnaires at baseline, 1- and 2-year follow-up. Uncertainty was measured using the Mishel Uncertainty in Illness Scale. Outcomes were measured using the Hospital Anxiety and Depression Scale, St. George's Respiratory Questionnaire, and MMRC Dyspnea Scale. Ambiguity and complexity were examined as predictors of depressive symptoms, anxiety, quality of life, and breathlessness using linear mixed models adjusting for demographic and health characteristics. Ambiguity was associated with more depressive symptoms (b = 0.09, SE = 0.02, p < .001) and anxiety (b = 0.13, SE = 0.02, p < .001), worse quality of life (b = 0.57, SE = 0.10, p < .001), and more breathlessness (b = 0.02, SE = 0.006, p < .001). Complexity did not have an independent effect on any outcome. Interactions between ambiguity and time since diagnosis were not statistically significant. Ambiguity was prospectively associated with worse mood, quality of life, and breathlessness. Thus, ambiguity should be targeted in psychosocial interventions. Time since diagnosis did not affect the association between ambiguity and outcomes, suggesting that the impact of ambiguity is equally strong throughout the course of COPD.

The Impact of Age on Outcomes in Chronic Obstructive Pulmonary Disease Differs by Relationship Status

PubMed Central

Holm, Kristen E.; Plaufcan, Melissa R.; Ford, Dee W.; Sandhaus, Robert A.; Strand, Matthew; Strange, Charlie; Wamboldt, Frederick S.

2013-01-01

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that can lead to early-onset chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the impact of age on psychological and clinical outcomes among individuals with AATD-associated COPD. 468 individuals with AATD-associated COPD (age 32 to 84 at baseline) completed questionnaires at baseline, 1- and 2-year follow-up. Age was examined as a predictor of depression, anxiety, health-related quality of life, and breathlessness at all three time points using linear mixed models. Age was associated with anxiety (b = −0.09, SE = 0.02, p < 0.001) and health-related quality of life (b = −0.29, SE = 0.09, p < 0.001). Age also had a statistically significant interaction with relationship status when predicting depression, health-related quality of life, and breathlessness. Among individuals who were single, younger age was associated with more symptoms of depression (b = −0.08, SE = 0.03, p < 0.01), worse health-related quality of life (b = −0.61, SE = 0.16, p < 0.001), and more breathlessness (b = −0.023, SE = 0.009, p < 0.01) throughout the two-year study. Age was not associated with these three outcomes among individuals who were married/part of an unmarried couple. Results suggest that individuals who develop a chronic illness at a young age, particularly those who are single, may be more likely to have worse psychological and clinical outcomes. PMID:23645147

Attacking the Multi-tiered Proteolytic Pathology of COPD: New Insights from Basic and Translational Studies

PubMed Central

Djekic, Uros V; Gaggar, Amit; Weathington, Nathaniel M

2015-01-01

Protease activity in inflammation is complex. Proteases released by cells in response to infection, cytokines, or environmental triggers like cigarette smoking cause breakdown of the extracellular matrix (ECM). In chronic inflammatory diseases like chronic obstructive pulmonary disease (COPD), current findings indicate that pathology and morbidity are driven by dysregulation of protease activity, either through hyperactivity of proteases or deficiency or dysfunction their antiprotease regulators. Animal studies demonstrate the accuracy of this hypothesis through genetic and pharmacologic tools. New work shows that ECM destruction generates peptide fragments active on leukocytes via neutrophil or macrophage chemotaxis towards collagen and elastin derived peptides respectively. Such fragments now have been isolated and characterized in vivo in each case. Collectively, this describes a biochemical circuit in which protease activity leads to activation of local immunocytes, which in turn release cytokines and more proteases, leading to further leukocyte infiltration and cyclical disease progression that is chronic. This circuit concept is well known, and is intrinsic to the protease-antiprotease hypothesis; recently analytic techniques have become sensitive enough to establish fundamental mechanisms of this hypothesis, and basic and clinical data now implicate protease activity and peptide signaling as pathologically significant pharmacologic targets. This review discusses targeting protease activity for chronic inflammatory disease with special attention to COPD, covering important basic and clinical findings in the field; novel therapeutic strategies in animal or human studies; and a perspective on the successes and failures of agents with a focus on clinical potential in human disease. PMID:19026684

Airway epithelial cell PPARγ modulates cigarette smoke-induced chemokine expression and emphysema susceptibility in mice.

PubMed

Solleti, Siva Kumar; Simon, Dawn M; Srisuma, Sorachai; Arikan, Meltem C; Bhattacharya, Soumyaroop; Rangasamy, Tirumalai; Bijli, Kaiser M; Rahman, Arshad; Crossno, Joseph T; Shapiro, Steven D; Mariani, Thomas J

2015-08-01

Chronic obstructive pulmonary disease (COPD) is a highly prevalent, chronic inflammatory lung disease with limited existing therapeutic options. While modulation of peroxisome proliferator-activating receptor (PPAR)-γ activity can modify inflammatory responses in several models of lung injury, the relevance of the PPARG pathway in COPD pathogenesis has not been previously explored. Mice lacking Pparg specifically in airway epithelial cells displayed increased susceptibility to chronic cigarette smoke (CS)-induced emphysema, with excessive macrophage accumulation associated with increased expression of chemokines, Ccl5, Cxcl10, and Cxcl15. Conversely, treatment of mice with a pharmacological PPARγ activator attenuated Cxcl10 and Cxcl15 expression and macrophage accumulation in response to CS. In vitro, CS increased lung epithelial cell chemokine expression in a PPARγ activation-dependent fashion. The ability of PPARγ to regulate CS-induced chemokine expression in vitro was not specifically associated with peroxisome proliferator response element (PPRE)-mediated transactivation activity but was correlated with PPARγ-mediated transrepression of NF-κB activity. Pharmacological or genetic activation of PPARγ activity abrogated CS-dependent induction of NF-κB activity. Regulation of NF-κB activity involved direct PPARγ-NF-κB interaction and PPARγ-mediated effects on IKK activation, IκBα degradation, and nuclear translocation of p65. Our data indicate that PPARG represents a disease-relevant pathophysiological and pharmacological target in COPD. Its activation state likely contributes to NF-κB-dependent, CS-induced chemokine-mediated regulation of inflammatory cell accumulation.

Prognostic Significance of Large Airway Dimensions on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

PubMed

Oelsner, Elizabeth C; Smith, Benjamin M; Hoffman, Eric A; Kalhan, Ravi; Donohue, Kathleen M; Kaufman, Joel D; Nguyen, Jennifer N; Manichaikul, Ani W; Rotter, Jerome I; Michos, Erin D; Jacobs, David R; Burke, Gregory L; Folsom, Aaron R; Schwartz, Joseph E; Watson, Karol; Barr, R Graham

2018-06-01

Large airway dimensions on computed tomography (CT) have been associated with lung function, symptoms, and exacerbations in chronic obstructive pulmonary disease (COPD), as well as with symptoms in smokers with preserved spirometry. Their prognostic significance in persons without lung disease remains undefined. To examine associations between large airway dimensions on CT and respiratory outcomes in a population-based cohort of adults without prevalent lung disease. The Multi-Ethnic Study of Atherosclerosis recruited participants ages 45-84 years without cardiovascular disease in 2000-2002; we excluded participants with prevalent chronic lower respiratory disease (CLRD). Spirometry was measured in 2004-2006 and 2010-2012. CLRD hospitalizations and deaths were classified by validated criteria through 2014. The average wall thickness for a hypothetical airway of 10-mm lumen perimeter on CT (Pi10) was calculated using measures of airway wall thickness and lumen diameter. Models were adjusted for age, sex, principal components of ancestry, body mass index, smoking, pack-years, scanner, percent emphysema, genetic risk score, and initial forced expiratory volume in 1 second (FEV 1 ) percent predicted. Greater Pi10 was associated with 9% faster FEV 1 decline (95% confidence interval [CI], 2 to 15%; P = 0.012) and increased incident COPD (odds ratio, 2.22; 95% CI, 1.43-3.45; P = 0.0004) per standard deviation among 1,830 participants. Over 78,147 person-years, higher Pi10 was associated with a 57% higher risk of first CLRD hospitalization or mortality (P = 0.0496) per standard deviation. Of Pi10's component measures, both greater airway wall thickness and narrower lumen predicted incident COPD and CLRD clinical events. In adults without CLRD, large airway dimensions on CT were prospectively associated with accelerated lung function decline and increased risks of COPD and CLRD hospitalization and mortality.

Lung cancer in patients with chronic obstructive pulmonary disease. Development and validation of the COPD Lung Cancer Screening Score.

PubMed

de-Torres, Juan P; Wilson, David O; Sanchez-Salcedo, Pablo; Weissfeld, Joel L; Berto, Juan; Campo, Arantzazu; Alcaide, Ana B; García-Granero, Marta; Celli, Bartolome R; Zulueta, Javier J

2015-02-01

Patients with chronic obstructive pulmonary disease (COPD) are at high risk for lung cancer (LC) and represent a potential target to improve the diagnostic yield of screening programs. To develop a predictive score for LC risk for patients with COPD. The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) and the Pittsburgh Lung Screening Study (PLuSS) databases were analyzed. Only patients with COPD on spirometry were included. By logistic regression we determined which factors were independently associated with LC in PLuSS and developed a COPD LC screening score (COPD-LUCSS) to be validated in P-IELCAP. By regression analysis, age greater than 60, body mass index less than 25 kg/m(2), pack-years history greater than 60, and emphysema presence were independently associated with LC diagnosis and integrated into the COPD-LUCSS, which ranges from 0 to 10 points. Two COPD-LUCSS risk categories were proposed: low risk (scores 0-6) and high risk (scores 7-10). In comparison with low-risk patients, in both cohorts LC risk increased 3.5-fold in the high-risk category. The COPD-LUCSS is a good predictor of LC risk in patients with COPD participating in LC screening programs. Validation in two different populations adds strength to the findings.

Short-term Evaluation of a Comprehensive Education Program Including Inhaler Training and Disease Management on Chronic Obstructive Pulmonary Disease.

PubMed

Yoo, Kwang Ha; Chung, Wou Young; Park, Joo Hun; Hwang, Sung Chul; Kim, Tae Eun; Oh, Min Jung; Kang, Dae Ryong; Rhee, Chin Kook; Yoon, Hyoung Kyu; Kim, Tae Hyung; Kim, Deog Kyeom; Park, Yong Bum; Kim, Sang Ha; Yum, Ho Kee

2017-10-01

Proper education regarding inhaler usage and optimal management of chronic obstructive pulmonary disease (COPD) is essential for effectively treating patients with COPD. This study was conducted to evaluate the effects of a comprehensive education program including inhaler training and COPD management. We enlisted 127 patients with COPD on an outpatient basis at 43 private clinics in Korea. The patients were educated on inhaler usage and disease management for three visits across 2 weeks. Physicians and patients were administered a COPD assessment test (CAT) and questionnaires about the correct usage of inhalers and management of COPD before commencement of this program and after their third visit. The outcomes of 127 COPD patients were analyzed. CAT scores (19.6±12.5 vs. 15.1±12.3) improved significantly after this program (p<0.05). Patients with improved CAT scores of 4 points or more had a better understanding of COPD management and the correct technique for using inhalers than those who did not have improved CAT scores (p<0.05). A comprehensive education program including inhaler training and COPD management at a primary care setting improved CAT scores and led to patients' better understanding of COPD management. Copyright©2017. The Korean Academy of Tuberculosis and Respiratory Diseases

A study on quantifying COPD severity by combining pulmonary function tests and CT image analysis

NASA Astrophysics Data System (ADS)

Nimura, Yukitaka; Kitasaka, Takayuki; Honma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Mori, Kensaku

2011-03-01

This paper describes a novel method that can evaluate chronic obstructive pulmonary disease (COPD) severity by combining measurements of pulmonary function tests and measurements obtained from CT image analysis. There is no cure for COPD. However, with regular medical care and consistent patient compliance with treatments and lifestyle changes, the symptoms of COPD can be minimized and progression of the disease can be slowed. Therefore, many diagnosis methods based on CT image analysis have been proposed for quantifying COPD. Most of diagnosis methods for COPD extract the lesions as low-attenuation areas (LAA) by thresholding and evaluate the COPD severity by calculating the LAA in the lung (LAA%). However, COPD is usually the result of a combination of two conditions, emphysema and chronic obstructive bronchitis. Therefore, the previous methods based on only LAA% do not work well. The proposed method utilizes both of information including the measurements of pulmonary function tests and the results of the chest CT image analysis to evaluate the COPD severity. In this paper, we utilize a multi-class AdaBoost to combine both of information and classify the COPD severity into five stages automatically. The experimental results revealed that the accuracy rate of the proposed method was 88.9% (resubstitution scheme) and 64.4% (leave-one-out scheme).

COPD control: Can a consensus be found?

PubMed

Guimarães, M; Bugalho, A; Oliveira, A S; Moita, J; Marques, A

2016-01-01

There are currently no reliable instruments for assessing the onset and progression of chronic obstructive pulmonary disease (COPD) or predicting its prognosis. Currently, a comprehensive assessment of COPD including several objective and subjective parameters is recommended. However, the lack of biomarkers precludes a correct assessment of COPD severity, which consequently hampers adequate therapeutic approaches and COPD control. In the absence of a definition of "well-controlled disease", a consensus regarding COPD control will be difficult to reach. However, COPD patient assessment should be multidimensional, and anchored in five points: control of symptoms, decline of pulmonary function, levels of physical activity, exacerbations, and Quality of Life. Several non-pharmacological and pharmacological measures are currently available to achieve disease control. Smoking cessation, vaccination, exercise training programs and pulmonary rehabilitation are recognized as important non-pharmacological measures but bronchodilators are the pivotal therapy in the control of COPD. This paper discusses several objective and subjective parameters that may bridge the gap between disease assessment and disease control. The authors conclude that, at present, it is not possible to reach a consensus regarding COPD control, essentially due to the lack of objective instruments to measure it. Some recommendations are set forth, but true COPD control awaits further objective assessments. Copyright © 2016. Published by Elsevier España, S.L.U.

COPD and exercise: does it make a difference?

PubMed Central

Burtin, Chris; De Boever, Patrick; Langer, Daniël; Vogiatzis, Ioannis; Wouters, Emiel F.M.; Franssen, Frits M.E.

2016-01-01

Key points Physiological changes are observed following a structured exercise training programme in patients with COPD, without changes in resting lung function. Exercise training is the cornerstone of a comprehensive pulmonary rehabilitation programme in patients with COPD. Most comorbidities in patients referred for pulmonary rehabilitation remain undiagnosed and untreated. After careful screening, it is safe for COPD patients with comorbidities to obtain significant and clinically relevant improvements in functional exercise capacity and health status after an exercise-based pulmonary rehabilitation programme. Educational aims To inform readers of the positive effects of exercise-based pulmonary rehabilitation in patients with COPD, even with comorbid conditions. To inform readers of the importance of physical activity in patients with COPD. Exercise training is widely regarded as the cornerstone of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). Indeed, exercise training has been identified as the best available means of improving muscle function and exercise tolerance in patients with COPD. So, exercise training truly makes a difference in the life of patients with COPD. In this review, an overview is provided on the history of exercise training (as standalone intervention or as part of a comprehensive pulmonary rehabilitation programme), exercise training in comorbid patients with COPD, and the impact of physical activity counselling in a clean air environment. PMID:27408645

An Update on the Global Initiative for Chronic Obstructive Lung Disease 2017 Guidelines With a Focus on Classification and Management of Stable COPD.

PubMed

Burkes, Robert M; Donohue, James F

2018-06-01

The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines offer important changes to the assessment and management of stable COPD of importance to practitioners, respiratory therapists, pharmacists, and nurses who care for patients with COPD. Therapies are now chosen based on the burden of symptoms and the history of COPD exacerbations, and inhaler regimens are modifiable based on continual clinical reassessment. Although identifying the degree of airway obstruction remains important for informing the clinical status of the patient with COPD, FEV 1 is no longer used to direct the therapeutic approach. Therapies and modes of inhaled medication delivery for each GOLD grouping have been modified and reflect the need for reevaluation of patient symptoms and COPD exacerbation history as an indicator to add or withdraw therapies. As the knowledge of this important disease continues to expand, exacerbation and symptom prevention in patients with stable COPD will remain as an important target of COPD therapies and research. Novel drug combinations and delivery devices are sure to positively affect the practitioner's approach to patients with stable COPD. The new 2017 GOLD guidelines represent a step toward personalized care of the patient with COPD. Copyright © 2018 by Daedalus Enterprises.

Trends in Readmission Rates, Hospital Charges, and Mortality for Patients With Chronic Obstructive Pulmonary Disease (COPD) in Florida From 2009 to 2014.

PubMed

Jiang, Xinyi; Xiao, Hong; Segal, Richard; Mobley, William Cary; Park, Haesuk

2018-04-01

Chronic obstructive pulmonary disease (COPD) is a leading and costly cause of readmissions to the hospital, with one of the highest rates reported in Florida. From 2009 to 2014, strategies such as readmission reduction programs, as well as updated guidelines for COPD management, were instituted to reduce readmission rates for patients with COPD. Thus, the question has been raised whether COPD-related 30-day hospital readmission rates in Florida have decreased and whether COPD-related readmission costs during this period have changed. In addition, we examined trends in length of stay, hospital charges, and in-hospital mortality associated with COPD, as well as identified patient-level risk factors associated with 30-day readmissions. A retrospective analysis of adult patients (≥18 years of age) with COPD was conducted by using the Healthcare Cost and Utilization Project Florida State Inpatient Database, 2009 to 2014. Weighted least squares regression was used to assess trends in the COPD readmission rate on a yearly basis, as well as other outcomes of interest. A multivariable logistic regression was used to identify patient characteristics that were associated with 30-day COPD readmissions. Overall, 268,084 adults were identified as having COPD. Between 2009 and 2014, more than half of patients aged 65-84 years, most were white, 55% were female, and 73% had Medicare. The unadjusted rate for COPD-related 30-day readmissions did not change (8.04% to 7.85%; P = 0.434). However, the mean total charge for 30-day COPD-related readmissions was significantly higher in 2014 ($40,611) compared with that in 2009 ($36,714) (P = 0.011). The overall unadjusted in-hospital mortality of COPD-related hospitalizations significantly decreased from 1.83% in 2009 to 1.34% in 2014 (P < 0.001). In a multivariable logistic regression model, patients with COPD were 2% less likely to be readmitted to the hospital for each additional year (odds ratio [OR], 0.98 [95% confidence interval (CI), 0.97-0.99]). Factors associated with significantly higher odds of COPD-related readmission were: older age (45 ≤ age ≤ 64 years; OR, 1.91 [95% CI, 1.70-2.14]), being male (OR, 1.14 [95% CI, 1.10-1.17]), and being a Medicaid beneficiary (OR, 1.28 [95% CI, 1.21-1.35]). Although the adjusted odds of COPD readmissions slightly decreased, as did the length of stay and all-cause in-patient mortality, the financial burden increased substantially. Future strategies to further reduce readmissions of patients with COPD and curb financial burden in Florida are needed. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Commensurate distances and similar motifs in genetic congruence and protein interaction networks in yeast

PubMed Central

Ye, Ping; Peyser, Brian D; Spencer, Forrest A; Bader, Joel S

2005-01-01

Background In a genetic interaction, the phenotype of a double mutant differs from the combined phenotypes of the underlying single mutants. When the single mutants have no growth defect, but the double mutant is lethal or exhibits slow growth, the interaction is termed synthetic lethality or synthetic fitness. These genetic interactions reveal gene redundancy and compensating pathways. Recently available large-scale data sets of genetic interactions and protein interactions in Saccharomyces cerevisiae provide a unique opportunity to elucidate the topological structure of biological pathways and how genes function in these pathways. Results We have defined congruent genes as pairs of genes with similar sets of genetic interaction partners and constructed a genetic congruence network by linking congruent genes. By comparing path lengths in three types of networks (genetic interaction, genetic congruence, and protein interaction), we discovered that high genetic congruence not only exhibits correlation with direct protein interaction linkage but also exhibits commensurate distance with the protein interaction network. However, consistent distances were not observed between genetic and protein interaction networks. We also demonstrated that congruence and protein networks are enriched with motifs that indicate network transitivity, while the genetic network has both transitive (triangle) and intransitive (square) types of motifs. These results suggest that robustness of yeast cells to gene deletions is due in part to two complementary pathways (square motif) or three complementary pathways, any two of which are required for viability (triangle motif). Conclusion Genetic congruence is superior to genetic interaction in prediction of protein interactions and function associations. Genetically interacting pairs usually belong to parallel compensatory pathways, which can generate transitive motifs (any two of three pathways needed) or intransitive motifs (either of two pathways needed). PMID:16283923

Subjects with COPD and productive cough have an increased risk for exacerbations and death.

PubMed

Lindberg, Anne; Sawalha, Sami; Hedman, Linnea; Larsson, Lars-Gunnar; Lundbäck, Bo; Rönmark, Eva

2015-01-01

Chronic bronchitis is related to worse general health status, exacerbations and mortality among subjects with COPD. Also less longstanding cough and phlegm may be related to worse prognosis in COPD but this has rarely been evaluated in population-based studies. To evaluate the relationship between productive cough, exacerbations and mortality among subjects with and without COPD. All subjects with COPD (n = 993) were identified together with sex- and age matched reference subjects without obstructive lung function impairment from four population-based cohorts in 2002-04. Baseline spirometry and structured interview including data on exacerbations last 12 months were used in this study (n = 1986) together with mortality data collected until February 2012. Productive cough was more common in COPD than non-COPD (42.8 vs. 23.5%, p < 0.001), more common in men than women, but associated to exacerbations in both sexes. COPD-subjects with productive cough had the highest risk for exacerbations in both sexes and they had a significantly increased risk for death (HR 1.48, 95% CI 1.13-1.94) also when adjusted for sex, age, BMI, smoking habits and heart disease. Productive cough was common and increased the risk for exacerbations in both sexes, in both COPD and non-COPD. COPD-subjects with productive cough had the highest risk for exacerbations and a significantly higher risk for death also after adjustment for common risk factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chronic obstructive pulmonary disease associated with increased risk of bipolar disorder.

PubMed

Su, Vincent Yi-Fong; Hu, Li-Yu; Yeh, Chiu-Mei; Chiang, Huey-Ling; Shen, Cheng-Che; Chou, Kun-Ta; Chen, Tzeng-Ji; Lu, Ti; Tzeng, Cheng-Hwai; Liu, Chia-Jen

2017-05-01

Epidemiological studies have identified a trend in the development of depressive and anxiety disorders following a diagnosis of chronic obstructive pulmonary disease (COPD). However, the relationship between COPD and subsequent bipolar disorder remains unclear. From January 1, 2000, we identified adult patients with COPD from the Taiwan National Health Insurance Research Database. A nationwide population-based study was conducted; 46,778 COPD patients and 46,778 age-, sex-, and comorbidity-matched subjects between 2000 and 2011 were enrolled. The two cohorts were followed up till December 31, 2011 and observed for occurrence of bipolar disorder. We observed the COPD and comparison cohorts for 263,020 and 267,895 person-years, respectively, from 2000 to 2011. The incidence rate for bipolar disorder was 1.6/1000 person-years in the COPD cohort and 1.2/1000 person-years in the comparison cohort ( p < 0.001). After multivariate adjustment, the hazard ratio (HR) for subsequent bipolar disorder among the COPD patients was 1.42 (95% confidence interval [CI], 1.22-1.64; p < 0.001). In the COPD patients, short-acting beta-agonists (SABAs) was associated with a significantly increased risk of bipolar disorder development (HR = 1.83, 95% CI = 1.25-2.69, p = 0.002). Other COPD medications were not associated with the risk of bipolar disorder development. The study results indicate that COPD may be an independent risk factor for the development of bipolar disorder. The regular use of SABAs might increase the risk of bipolar disorder in COPD patients.

Organizational structure for chronic heart failure and chronic obstructive pulmonary disease.

PubMed

Rinne, Seppo T; Liu, Chuan-Fen; Wong, Edwin S; Hebert, Paul L; Heidenreich, Paul; Bastian, Lori A; Au, David H

2016-03-01

In contrast to chronic heart failure (CHF), measures of quality of care for chronic obstructive pulmonary disease (COPD) are poor. Our objective was to examine differences in organizational structure available to support quality of care for patients with CHF and COPD. We performed 2 nationwide surveys exploring organizational structure for the management of CHF and COPD. We surveyed the chief of medicine and the chief of cardiology and pulmonary medicine at 120 Veterans Affairs facilities in the United States. Analogous questions about organizational structure that enhanced adherence to guideline-based care were compared between CHF and COPD surveys. We found large and notable differences in the organizational structure for disease management, with systematically less attention given to COPD than CHF. These differences were evident in multiple processes of care. Key differences included fewer facilities: having COPD clinics than CHF clinics (12.7% vs 50.8%; P < .01), relating performance measures with COPD providers than CHF providers (17.1% vs 70%; P < .01), and having home monitoring programs for COPD than for CHF (50.5% vs 87.4%; P < .01). Despite the growing burden of COPD, less organizational structure existed for COPD than CHF. Lack of organizational structure for COPD likely impedes an organization's abilities to encourage high-quality care and avoid recently implemented hospital readmission penalties. Our results suggest the need to develop a systematic approach for healthcare systems to provide essential organizational structure based on the burden of disease in the population.

Study on drug costs associated with COPD prescription medicine in Denmark.

PubMed

Jakobsen, Marie; Anker, Niels; Dollerup, Jens; Poulsen, Peter Bo; Lange, Peter

2013-10-01

Spirometric studies of the general population estimate that 430 000 Danes have chronic obstructive pulmonary disease (COPD). COPD is mainly caused by smoking, and smoking cessation is the most important intervention to prevent disease progression. Cost-of-illness studies conclude that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed. To analyse the societal costs associated with prescription medicine for COPD in Denmark. The study was designed as a nationwide retrospective register study of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who had been either hospitalised with a COPD diagnosis or had at least one prescription for drugs primarily used for COPD. The study population comprised 166 462 individuals of which 97 916 were alive on 31 December 2010. The average annual drug costs (R03) were DKK 7842 (EUR 1055) per patient in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70 000-75 000 (EUR 9416-10 089) per patient (2010 prices). The costs associated with prescription medicine for COPD in Denmark are significant. © 2012 John Wiley & Sons Ltd.

Chronic Pain in People With Chronic Obstructive Pulmonary Disease: Prevalence, Clinical and Psychological Implications.

PubMed

Lee, Annemarie L; Goldstein, Roger S; Brooks, Dina

2017-05-21

Background: Although pain is a common symptom in chronic obstructive pulmonary disease (COPD), pain characteristics such as frequency, duration and type are unclear. The primary study aim was to identify these pain characteristics in individuals with COPD versus healthy control participants. The secondary aim was to explore the clinical and psychological associations with pain in those with COPD. Methods : Participants with COPD and age and gender-matched, healthy controls completed questionnaires to elicit pain characteristics. Those with COPD also had assessments of dyspnea, health-related quality of life, psychological associations (anxiety and depression) and physical activity. Results: Sixty-four participants with COPD (mean [standard deviation (SD)] age 71[10] , forced expiratory volume in 1 second [FEV 1 ] 38% predicted) and 64 control participants (mean [SD] age 67 [13] , FEV 1 91% predicted) were included. Chronic pain was more prevalent in individuals with COPD compared to control participants (41% versus 29%, p =0.03). The pain was more prevalent in the chest and upper back ( p =0.04). COPD participants with chest or upper back pain had a higher total lung capacity (mean difference 2.0L, 95% confidence interval [CI] 0.6 to 3.0L) compared to COPD participants without pain. Greater dyspnea ( p <0.001), more depression ( p =0.02) and lower physical activity levels ( p =0.03) were also present in people with COPD experiencing pain. Conclusions: Chronic pain is common in COPD. It is associated with higher dyspnea and depression and lower physical activity.

Up-regulation of Pim-3 in Chronic Obstructive Pulmonary Disease (COPD) patients and its potential therapeutic role in COPD rat modeling.

PubMed

Yang, Cheng; Li, Li; Guo, Junhua; Zhang, Weiqiang; Zhu, Wenbiao; Rao, Xinhui; Huang, Wenjie

2017-04-01

Pim-3 belongs to the PIM kinase family and plays an important role in promoting inflammation, which is essential in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Immunohistochemistry (IHC), western blot, and RT-PCR analyses were performed to assess the expression of Pim-3 in both COPD and healthy lung tissue samples. SMA (Smooth Muscle Actin) and Cyclin D1 expression were detected by IHC. We also constructed animal models for the control, COPD, and Pim-3 inhibition groups, in order to analyze the effects of Pim-3 inhibition on COPD, and the role of Pim-3 in the p38 pathway. Compared with normal lung tissue, Pim-3 mRNA and protein were up-regulated in COPD tissue. Expression of Cyclin D1 and SMA were also up-regulated in the COPD group. In the animal model experiment, we found that suppression of Pim-3 decreased Pim-3, Cyclin D1, and SMA expression, as well as ameliorated lung damage in COPD patients. The inhibition of Pim-3 also resulted in the suppression of the p38 pathway. Our study suggests that up-regulation of Pim-3 successfully accelerated COPD development, and aggravated lung damage. The molecular mechanism of Pim-3 in COPD might be related to the p38 pathway, and is correlated with Cyclin D1 and SMA expression. Copyright © 2017 Elsevier GmbH. All rights reserved.

Comparison of Multiple Chronic Obstructive Pulmonary Disease (COPD) Indices in Chinese COPD Patients.

PubMed

Zhang, Jinsong; Miller, Anastasia; Li, Yongxia; Lan, Qinqin; Zhang, Ning; Chai, Yanling; Hai, Bing

2018-04-01

Chronic obstructive pulmonary disease (COPD) is a serious chronic condition with a global impact. Symptoms of COPD include progressive dyspnea, breathlessness, cough, and sputum production, which have a considerable impact on the lives of patients. In addition to the human cost of living with COPD and the resulting death, COPD entails a huge economic burden on the Chinese population, with patients spending up to one-third of the average family income on COPD management in some regions is clinically beneficial to adopt preventable measures via prudent COPD care utilization, monetary costs, and hospitalizations. Toward this end, this study compared the relative effectiveness of six indices in predicting patient healthcare utilization, cost of care, and patient health outcome. The six assessment systems evaluated included the three multidimensional Body mass index, Obstruction, Dyspnea, Exercise capacity index, Dyspnea, Obstruction, Smoking, Exacerbation (DOSE) index, and COPD Assessment Test index, or the unidimensional measures that best predict the future of patient healthcare utilization, cost of care, and patient health outcome among Chinese COPD patients. Multiple linear regression models were created for each healthcare utilization, cost, and outcome including a single COPD index and the same group of demographic variables for each of the outcomes. We conclude that the DOSE index facilitates the prediction of patient healthcare utilization, disease expenditure, and negative clinical outcomes. Our study indicates that the DOSE index has a potential role beyond clinical predictions. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

Comorbidities of COPD.

PubMed

Cavaillès, Arnaud; Brinchault-Rabin, Graziella; Dixmier, Adrien; Goupil, François; Gut-Gobert, Christophe; Marchand-Adam, Sylvain; Meurice, Jean-Claude; Morel, Hugues; Person-Tacnet, Christine; Leroyer, Christophe; Diot, Patrice

2013-12-01

By 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately.

Multidimensional approach for the proper management of a complex chronic patient with chronic obstructive pulmonary disease.

PubMed

Rogliani, Paola; Brusasco, Vito; Fabbri, Leonardo; Ungar, Andrea; Muscianisi, Elisa; Barisone, Ilaria; Corsini, Alberto; De Angelis, Giuseppe

2018-02-01

Chronic obstructive pulmonary disease (COPD) is frequently associated with comorbidities occurring either independently or as consequences of COPD. Areas covered: This review examines the interactions between the pathophysiology of COPD and the most frequent comorbidities, and highlights the need for multidimensional clinical strategies to manage COPD patients with comorbidities. Expert commentary: Most COPD patients need to be approached in a complex and multifactorial scenario. The diagnosis of COPD is necessarily based on the presence of chronic respiratory symptoms and poorly reversible airflow obstruction, but exacerbations and comorbidities need to be considered in the evaluation of disease severity and prognosis in individual patients. More importantly, defining the precise relationship between COPD and comorbidities for each patient is the basis for a correct therapeutic approach.

Long-term efficacy of a rural community-based integrated intervention for prevention and management of chronic obstructive pulmonary disease: a cluster randomized controlled trial in China's rural areas.

PubMed

Yuan, X; Tao, Y; Zhao, J P; Liu, X S; Xiong, W N; Xie, J G; Ni, W; Xu, Y J; Liu, H G

2015-11-01

This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD.

Multicenter study of the COPD-6 screening device: feasible for early detection of chronic obstructive pulmonary disease in primary care?

PubMed

Kjeldgaard, Peter; Lykkegaard, Jesper; Spillemose, Heidi; Ulrik, Charlotte Suppli

2017-01-01

Early detection of COPD may reduce the future burden of the disease. We aimed to investigate whether prescreening with a COPD-6 screening device (measuring FEV 1 and FEV 6 ) facilitates early detection of COPD in primary care. In primary care, individuals at high risk of COPD (ie, age ≥35 years, relevant exposure, and at least one respiratory symptom) and no previous diagnosis of obstructive lung disease were examined with a COPD-6 screening device. In prioritized order, the criteria for proceeding to confirmatory spirometry were FEV 1 /FEV 6 <0.7, FEV 1 <80%pred, or clinical suspicion of COPD regardless of test result (medical doctor's [MD] decision). Based on spirometry, including bronchodilator (BD) reversibility test, individuals were classified as COPD (post-BD FEV 1 /FVC <0.70), asthma (ΔFEV 1 ≥0.50 L), or no obstructive lung disease. A total of 2,990 subjects (54% men, mean age 59 years, and mean 28 pack-years) were enrolled, of whom 949 (32%) proceeded from COPD-6 screening to confirmative spirometry based on the following criteria: 510 (54%) FEV 1 /FEV 6 <0.70, 382 (40%) FEV 1 <80%pred, and 57 (6%) MD decision. Following confirmative spirometry, the 949 individuals were diagnosed as having COPD (51%), asthma (3%), and no obstructive lung disease (45%). COPD was diagnosed in 487 (16%) of the enrolled subjects in whom confirmative spirometry was performed in 69% based on FEV 1 /FEV 6 <0.7 and in 29% based on FEV 1 ≤80%pred. Prescreening with the COPD-6 device showed acceptable specificity for the selection of subjects for diagnostic spirometry and is likely to be a useful alternative to current practice in primary care.

Cysteinyl Leukotriene 1 Receptor Expression Associated With Bronchial Inflammation in Severe Exacerbations of COPD

PubMed Central

Zhu, Jie; Bandi, Venkata; Qiu, Shengyang; Figueroa, David J.; Evans, Jilly F.; Barnes, Neil; Guntupalli, Kay K.

2012-01-01

Background: Cysteinyl leukotriene 1 (CysLT1) receptor expression is known to be increased in the airway mucosa of patients with asthma, especially during exacerbations; however, nothing is known of its expression in COPD. Methods: We applied immunohistochemistry and in situ hybridization to endobronchial biopsies to determine inflammatory cell CysLT1 receptor protein and mRNA expression in the following: (1) 15 nonsmoker control subjects (NSC), (2) 16 smokers with moderate to severe COPD in its stable phase (S-COPD), and (3) 15 smokers with COPD hospitalized for a severe exacerbation (SE-COPD). Results: The total number of bronchial mucosal inflammatory cells (CD45+) and those expressing CysLT1 receptor protein were significantly greater in SE-COPD (CysLT1 receptor protein: median [range] = 139 [31-634]) as compared with S-COPD (32 [6-114]) or NSC (16 [4-66]) (P < .001 for both). CysLT1 receptor gene expression showed similar differences. A greater proportion of CD451 cells expressed CysLT1 receptor protein in SE-COPD (median [range] = 22% [8-81]) compared with S-COPD (10% [4-32]) (P < .03) or NSC (7% [1-19]) (P < .002). In SE-COPD, the relative frequencies of CysLT1 receptor-expressing cells were as follows: tryptase1 mast cells > CD681 monocytes/macrophage > neutrophils > CD201 B lymphocytes = EG21 eosinophils. Moreover, there were positive correlations between the numbers of cells expressing CysLT1 receptor protein and the numbers of CD451 cells (r = 0.78; P < .003) and tryptase1 mast cells (r = 0.62; P < .02). Conclusions: Bronchial mucosal CysLT1 receptor-positive inflammatory cells are present in the bronchial mucosa in COPD in greatest number in those experiencing a severe exacerbation. PMID:22871757

COPD prevalence and hospital admissions in Galicia (Spain). An analysis using the potential of new health information systems.

PubMed

Barbosa-Lorenzo, R; Ruano-Ravina, A; Fernández-Villar, A; López-Pardo, E; Carballeira-Roca, C; Barros-Dios, J M

2018-05-05

Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to ascertain the prevalence of COPD and whether such prevalence was positively or negatively associated with COPD admissions, using all the data of a regional health care system. We designed a descriptive cross-sectional study which included all subjects aged over 45 years, diagnosed with COPD in primary care in 2013. We also calculated the number of such patients who had a record of hospital admissions due to this disease. COPD prevalence and incidence of admissions were calculated. Poisson regression models were then used to analyse the association between cases with diagnosis of COPD and admissions due to COPD, by sex, adjusting for socio-demographic variables and distance to hospital. Sensitivity subanalyses were performed by reference to the respective municipal rurality indices. Median municipal prevalence of COPD was 5.29% in men and 2.19% in women. Among patients with COPD, 28.22% of men and 16.00% of women had at least one hospital admission. The relative risk of admission per unit of the standardised prevalence ratio was 0.37 (95% CI 0.34-0.41) for men and 0.39 (95% CI 0.34-0.45) for women. There is a significant negative association between COPD prevalence and hospital admissions due to this disease. The proportion of admissions is lower in municipalities lying furthest from hospitals. There is considerable municipal variability in terms of COPD prevalence and proportion of admissions. In-depth attention should be given to disease-management training programmes. Copyright © 2018 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Paid employment in subjects with and without chronic obstructive pulmonary disease in five Latin American cities: the PLATINO study.

PubMed

Montes de Oca, M; Halbert, R J; Talamo, C; Perez-Padilla, R; Lopez, M V; Muiño, A; Jardim, J R B; Valdivia, G; Pertuzé, J; Moreno, D; Menezes, A M B

2011-09-01

Chronic obstructive pulmonary disease (COPD) is a costly condition that frequently causes permanent work disabilities. Little information exists regarding the impact of COPD on work force participation and the indirect costs of the disease in developing countries. To examine the frequency of paid employment and factors influencing it in a Latin-American population-based study. Post-bronchodilator FEV(1)/FVC < 0.70 (forced expiratory volume in 1 s/forced vital capacity) was used to define COPD. Information regarding paid work was assessed by the question 'At any time in the past year, have you worked for payment?' Interviews were conducted with 5571 subjects; 5314 (759 COPD and 4554 non-COPD) subjects underwent spirometry. Among the COPD subjects, 41.8% reported having paid work vs. 57.1% of non-COPD (P < 0.0001). The number of months with paid work was reduced in COPD patients (10.5 ± 0.17 vs. 10.9 ± 0.06, P < 0.05). The main factors associated with having paid work in COPD patients were male sex (OR 0.33, 95%CI 0.23-0.47), higher education level (OR 1.05, 95%CI 1.01-1.09) and younger age (OR 0.90, 95%CI 0.88-0.92). COPD was not a significant contributor to employment (OR 0.83, 95%CI 0.69-1.00, P = 0.054) in the entire population. Although the proportion of persons with paid work is lower in COPD, having COPD appears not to have a significant impact on obtaining paid employment in the overall population of developing countries.

Comparison of fenspiride with beclomethasone as adjunctive anti-inflammatory treatment in patients with chronic obstructive pulmonary disease.

PubMed

Shmelev, E I; Kunicina, Yu L

2006-01-01

This study aimed to compare the clinical efficacy of two anti-inflammatory medications (fenspiride and inhaled beclomethasone [beclomethasone dipropionate]) in patients with stable chronic obstructive pulmonary disease (COPD) over 6 months. DESIGN, METHODS AND PATIENTS: This was a randomised comparison of 58 patients with COPD, divided into five treatment groups: fenspiride (stages 1 and 2), beclomethasone (stage 2), and two control groups (stages 1 and 2). In addition, 64 patients with exacerbations of COPD were evaluated over a 2-week treatment period during which they received either fenspiride or prednisolone. Clinical signs and symptoms of COPD were evaluated every 2 months (aggregated numerical index of signs and symptoms), as were lung function tests (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], FEV1/FVC) and a 6-minute walking test. Statistically significant reductions in all evaluated COPD signs and symptoms were achieved with fenspiride in stage 1 COPD. Fenspiride therapy significantly reduced the indices of sputum parameters (8-fold decrease), incidence of dry rales (6-fold decrease), dyspnoea (4-fold decrease) and cough (2.5-fold decrease). In comparison with beclomethasone, fenspiride was superior in stage 2 COPD. In patients with stage 2 COPD, reductions were less marked, but remained significantly superior in the fenspiride group in comparison with the beclomethasone group and the control groups. In patients with exacerbations of COPD, fenspiride had equivalent efficacy to that of systemic corticosteroids. Anti-inflammatory therapy with fenspiride in addition to bronchodilators significantly improved clinical signs and symptoms, external respiratory function tests and physical activity tests in patients with stage 1 COPD. Adjunctive fenspiride therapy was superior to inhaled beclomethasone in stage 2 COPD. Anti-inflammatory therapy in COPD may be more effective at an early stage of this disease.

GOLD assessment of COPD severity in the Clinical Practice Research Datalink (CPRD).

PubMed

Rebordosa, Cristina; Plana, Estel; Aguado, Jaume; Thomas, Steven; García-Gil, Esther; Perez-Gutthann, Susana; Castellsague, Jordi

2018-05-08

To evaluate availability of spirometry and symptom data in the Clinical Practice Research Datalink (United Kingdom) to assess COPD severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 definition and comparing it with an algorithm used in other studies. This was a descriptive, noninterventional, secondary database cohort study of patients with COPD aged 40 years or older, who initiated treatment with specific COPD medications. Patients were classified according to COPD severity (1) in GOLD 2016 "ABCD" categories based on symptoms (Medical Research Council dyspnea grade, COPD Assessment Test, breathlessness), percent predicted FEV1, and exacerbation history and (2) as mild, moderate, severe, or very severe based on treatment and exacerbation history. The study included 63 900 patients with COPD aged 40 years or older that were new users of 1 or more COPD medication of interest. Percent predicted FEV1 was available for 80.9% of patients; symptoms for 75.6% of patients. Classification into GOLD 2016 ABCD categories was possible for 75.6% of the patients. The GOLD 2016 ABCD definition classified more patients under the high-risk categories (22.1%, A; 18.8%, B; 21.3%, C; 37.9%, D) than did the adapted algorithm (7.9%, mild; 48.6%, moderate; 42.1%, severe; 1.4%, very severe). Using our adaptation of the GOLD 2016 COPD severity classification, the information in the Clinical Practice Research Datalink allowed us to ascertain COPD severity in approximately 75% of patients with COPD. Algorithms that include medication use tend to misclassify patients with the extreme COPD severity categories. Copyright © 2018 John Wiley & Sons, Ltd.

Socio-Economic and Clinical Factors as Predictors of Disease Evolution and Acute Events in COPD Patients

PubMed Central

Pandolfi, Paolo; Zanasi, Alessandro; Musti, Muriel Assunta; Stivanello, Elisa; Pisani, Lara; Angelini, Sabrina; Maffei, Francesca; Hrelia, Silvana; Angeloni, Cristina; Zenesini, Corrado; Hrelia, Patrizia

2015-01-01

Background Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients. Methods Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant’Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines. Results 229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival curves by COPD stage with lower event-free probability in very severe COPD stage. Significant risk factors for acute events were: underweight (HR = 4.08; 95% CI 1.01–16.54), having two or more comorbidities (HR = 4.71; 95% CI 2.52–8.83), belonging to moderate (HR = 3.50; 95% CI 1.01–12.18) or very severe COPD stage (HR = 8.23; 95% CI 2.35–28.85). Conclusions Our findings indicate that fragility is associated with COPD stage and that comorbidities and the low body mass index are predictors of mortality or hospitalization. Besides spirometric analyses, FeNO measure and comorbidities, body mass index could also be considered in the management and monitoring of COPD patients. PMID:26252571

Impact of COPD on outcome among patients with complicated peptic ulcer.

PubMed

Christensen, Steffen; Thomsen, Reimar W; Tørring, Marie Louise; Riis, Anders; Nørgaard, Mette; Sørensen, Henrik T

2008-06-01

COPD is associated with an increased risk of peptic ulcer disease, but limited data exist on whether COPD influences short-term mortality among patients with bleeding and a perforated peptic ulcer. We examined the association between COPD and 30-day mortality following bleeding and perforation of a peptic ulcer. We identified all patients who had been hospitalized with a first-time diagnosis of peptic ulcer perforation (n = 2,033) or bleeding (n = 7,486) in northern Denmark between 1991 and 2004. Information on COPD, comorbidities, and filled prescriptions was obtained from medical databases. Mortality was ascertained using the Danish Civil Registration System. We computed the cumulative 30-day mortality rates for ulcer patients with COPD and for other ulcer patients, and used regression analysis to obtain the 30-day mortality rate ratios (MRRs), controlling for potential confounding factors. Among patients who were hospitalized with perforated peptic ulcers, 218 (10.7%) had previously been hospitalized with COPD. The 30-day mortality rate was 44.0% among perforated ulcer patients with COPD vs 25.5% among other ulcer patients (adjusted MRR, 1.48; 95% confidence interval [CI], 1.18 to 1.85). Among patients hospitalized with a bleeding peptic ulcer, 759 (10.1%) had previously been hospitalized with COPD. The 30-day mortality rate was 16.5% among bleeding peptic ulcer patients with COPD vs 10.8% among other ulcer patients (adjusted MRR, 1.38; 95% CI, 1.14 to 1.68). The use of oral glucocorticoids among COPD patients was associated with higher MRRs for both perforated and bleeding peptic ulcers. COPD substantially increased 30-day mortality among patients with bleeding and perforated peptic ulcers.

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

Subclinical carotid atherosclerosis in patients with chronic obstructive pulmonary disease: a meta-analysis of literature studies.

PubMed

Ambrosino, Pasquale; Lupoli, Roberta; Cafaro, Giovanni; Iervolino, Salvatore; Carone, Mauro; Pappone, Nicola; Di Minno, Matteo Nicola Dario

2017-09-01

Chronic obstructive pulmonary disease (COPD) patients have an increased cardiovascular (CV) morbidity and mortality. Common carotid intima-media thickness (CCA-IMT) and carotid plaques are surrogate markers of subclinical atherosclerosis and predictors of CV events. We performed a meta-analysis to evaluate the association between COPD and subclinical atherosclerosis. Studies evaluating the impact of COPD on CCA-IMT and on the prevalence of carotid plaques were systematically searched. Twenty studies (2082 COPD patients and 4844 controls) were included, 12 studies with data on CCA-IMT (13 data-sets on 1180 COPD patients and 2312 controls) and 12 studies reporting on the prevalence of carotid plaques (1231 COPD patients and 4222 controls). Compared to controls, COPD patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.201 mm; 95%CI: 0.142, 0.260; p < .001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.503; 95%CI: 1.333, 2.175; p < .0001). Meta-regression models showed a direct association between disease severity [as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) class] and the difference in the risk of carotid plaques presence between COPD patients and controls. COPD is significantly associated with subclinical atherosclerosis. These findings may be useful to plan adequate CV prevention strategies. Key messages COPD patients show a higher CCA-IMT and an increased prevalence of carotid plaques compared with controls. A more severe pulmonary disease is associated with a higher prevalence of carotid plaques in COPD patients. Screening for subclinical atherosclerosis may be worthy in COPD patients to plan specific prevention strategies.

Frequency of COPD in health care workers who smoke

PubMed Central

Kopitovic, Ivan; Bokan, Aleksandar; Andrijevic, Ilija; Ilic, Miroslav; Marinkovic, Sanja; Milicic, Dragana; Vukoja, Marija

2017-01-01

ABSTRACT Objective: COPD is one of the major causes of morbidity and mortality worldwide. Health care providers should counsel their smoking patients with COPD to quit smoking as the first treatment step. However, in countries with high prevalences of smoking, health care workers may also be smokers. The aim of this study was to determine the frequency and severity of COPD in health care workers who smoke. Methods: This was a cross-sectional study. All health care workers who smoke, from nine health care centers in Serbia, were invited to participate in the study and perform spirometry. The diagnosis of COPD was based on a post-bronchodilator FEV1/FVC ratio of < 0.70. All patients completed the COPD Assessment Test and the Fagerström Test for Nicotine Dependence. Results: The study involved 305 subjects, and 47 (15.4%) were male. The mean age of the participants was 49.0 ± 6.5 years. Spirometry revealed obstructive ventilatory defect in 33 subjects (10.8%); restrictive ventilatory defect, in 5 (1.6%); and small airway disease, in 96 (31.5%). A diagnosis of COPD was made in 29 patients (9.5%), 25 (86.2%) of whom were newly diagnosed. On the basis of the Global Initiative for COPD guidelines, most COPD patients belonged to groups A or B (n = 14; 48.2%, for both); 1 belonged to group D (3.6%); and none, to group C. Very high nicotine dependence was more common in those with COPD than in those without it (20.7% vs. 5.4%, p = 0.01). Conclusions: In this sample of health care workers, the frequency of COPD was comparable with that in the general population. The presence of COPD in health care workers who smoke was associated with higher nicotine dependence. PMID:29160380

Current care services provided for patients with COPD in the Eastern province in Saudi Arabia: a descriptive study.

PubMed

Alsubaiei, Mohammed E; Cafarella, Paul A; Frith, Peter A; McEvoy, R Doug; Effing, Tanja W

2015-01-01

COPD is a leading cause of morbidity and mortality worldwide. The prevalence rate of COPD in the general Saudi population is estimated to be 2.4% and 14.2% among smokers. Not much is known about current health care services for patients with COPD in Saudi Arabia. The objective of this study was to determine the current care services for patients with COPD provided by government hospitals in the Eastern province of Saudi Arabia. A cross-sectional study was conducted in the Eastern province of Saudi Arabia. Directors of the Department of Internal Medicine from all 22 general government hospitals that are under the responsibility of the Ministry of Health or the Ministry of Higher Education in this region were asked to participate. Data were collected using a questionnaire. The study results indicated that there are limited hospital facilities for patients with COPD: no respiratory departments in any of the included hospitals, no spirometry in 77.3% of the hospitals, no intensive care units in 63.7% of the hospitals, and no pulmonary rehabilitation program in any of the hospitals. Among the included 22 hospitals, 24 respiratory physicians, 29 respiratory therapists, and three physiotherapists were involved in COPD care. In conclusion, current care services provided by government hospitals in the Eastern province of Saudi Arabia for patients with COPD do not meet international recommendations for COPD management. Increased awareness, knowledge, and implementation of COPD guidelines by health care providers will most probably improve COPD management in Saudi Arabia. In addition, the government could improve dissemination of information about COPD management through national programs and by offering specific education regarding respiratory diseases.

HELPing older people with very severe chronic obstructive pulmonary disease (HELP-COPD): mixed-method feasibility pilot randomised controlled trial of a novel intervention.

PubMed

Buckingham, Susan; Kendall, Marilyn; Ferguson, Susie; MacNee, William; Sheikh, Aziz; White, Patrick; Worth, Allison; Boyd, Kirsty; Murray, Scott A; Pinnock, Hilary

2015-04-16

Extending palliative care to those with advanced non-malignant disease is advocated, but the implications in specific conditions are poorly understood. We piloted a novel nurse-led intervention, HELPing older people with very severe chronic obstructive pulmonary disease (HELP-COPD), undertaken 4 weeks after discharge from hospital, which sought to identify and address the holistic care needs of people with severe COPD. This 6-month mixed-method feasibility pilot trial randomised (ratio 3:1) patients to HELP-COPD or usual care. We assessed the feasibility of using validated questionnaires as outcome measures and analysed the needs/actions recorded in the HELP-COPD records. Semi-structured interviews with a purposive sample of patients, carers and professionals explored the perceptions of HELP-COPD. Verbatim transcriptions and field notes were analysed using Normalisation Process Theory as a framework. We randomised 32 patients (24 to HELP-COPD); 19 completed the study (death=3, ill-health=4, declined=6). The HELP-COPD record noted a mean of 1.6 actions/assessment, mostly provision of information or self-help actions: only five referrals were made. Most patients were positive about HELP-COPD, discussing their concerns and coping strategies in all domains, but the questionnaires were burdensome for some patients. Adaptation to their slowly progressive disability and a strong preference to rely on family support was reflected in limited acceptance of formal services. Professionals perceived HELP-COPD as addressing an important aspect of care, although timing overlapped with discharge planning. The HELP-COPD intervention was well received by patients and the concept resonated with professionals, although delivery post discharge overlapped with existing services. Integration of brief holistic care assessments in the routine primary care management of COPD may be more appropriate.

Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease.

PubMed

Christenson, Stephanie A; Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S; Postma, Dirkje S; Lenburg, Marc E; Spira, Avrum; Woodruff, Prescott G

2015-04-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and "asthma-like" features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.

Trends in Epidemiology of COPD in HIV-Infected Patients in Spain (1997–2012)

PubMed Central

de Miguel-Díez, Javier; López-de-Andrés, Ana; Jiménez-García, Rodrigo; Puente-Maestu, Luis; Jiménez-Trujillo, Isabel; Hernández-Barrera, Valentín

2016-01-01

Purpose The aim of this study was to estimate trends of incidence of hospital admissions and in-hospital mortality (IHM) in HIV-infected patients with COPD in the combination antiretroviral therapy (cART) era in Spain (1997–2012). Methods A retrospective study with data from nationwide population-based COPD diagnoses in the Spanish Minimum Basic Data Set (MBDS) was performed. We established groups according to their HIV and HCV infections: 1) HIV-uninfected patients; 2) HIV-infected patients (with or without HCV coinfection). Results 1,580,207 patients discharge with a COPD diagnosis were included in the study, 8902 of them were HIV-infected patients (5000 HIV-monoinfected patients and 3902 HIV/HCV-coinfected patients). The HIV-infected patients had higher incidence rates of hospital admissions for COPD than the HIV-uninfected patients during the study period. The HIV-monoinfected patients had higher rates of hospitalizations for COPD than the HIV/HCV-coinfected patients in the early-period cART (1997–1999), but these rates decreased in the first group and increased in the second, being even similar in both groups in the late-period cART (2004–2011). On the other hand, the HIV-infected patients with COPD had higher IHM than the HIV-uninfected patients with COPD. The mortality rates were higher in the HIV-monoinfected patients with COPD than in the HIV/HCV-coinfected patients with COPD in the early-period cART; however, in the late-period cART, the mortality rates trends seems higher in the HIV/HCV group. The likelihood of death in HIV/HCV-coinfected patients with COPD was similar to than in HIV-monoinfected patients with COPD. Conclusions Incidence of hospital admissions for COPD and IHM have decreased among HIV-monoinfected individuals but have increased steadily among HIV/HCV-coinfected individuals in the cART era. PMID:27846297

Oxidative stress regulates autophagy in cultured muscle cells of patients with chronic obstructive pulmonary disease.

PubMed

Gouzi, Fares; Blaquière, Marine; Catteau, Matthias; Bughin, François; Maury, Jonathan; Passerieux, Emilie; Ayoub, Bronia; Mercier, Jacques; Hayot, Maurice; Pomiès, Pascal

2018-06-26

The proteolytic autophagy pathway is enhanced in the lower limb muscles of patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen species (ROS) have been shown to regulate autophagy in the skeletal muscles, but the role of oxidative stress in the muscle autophagy of patients with COPD is unknown. We used cultured myoblasts and myotubes from the quadriceps of eight healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and 32.0%, respectively; p < 0.0001). We compared the autophagosome formation, the expression of autophagy markers, and the autophagic flux in healthy subjects and the patients with COPD, and we evaluated the effects of the 3-methyladenine (3-MA) autophagy inhibitor on the atrophy of COPD myotubes. Autophagy was also assessed in COPD myotubes treated with an antioxidant molecule, ascorbic acid. Autophagosome formation was increased in COPD myoblasts and myotubes (p = 0.011; p < 0.001), and the LC3 2/LC3 1 ratio (p = 0.002), SQSTM1 mRNA and protein expression (p = 0.023; p = 0.007), BNIP3 expression (p = 0.031), and autophagic flux (p = 0.002) were higher in COPD myoblasts. Inhibition of autophagy with 3-MA increased the COPD myotube diameter (p < 0.001) to a level similar to the diameter of healthy subject myotubes. Treatment of COPD myotubes with ascorbic acid decreased ROS concentration (p < 0.001), ROS-induced protein carbonylation (p = 0.019), the LC3 2/LC3 1 ratio (p = 0.037), the expression of SQSTM1 (p < 0.001) and BNIP3 (p < 0.001), and increased the COPD myotube diameter (p < 0.001). Thus, autophagy signaling is enhanced in cultured COPD muscle cells. Furthermore, the oxidative stress level contributes to the regulation of autophagy, which is involved in the atrophy of COPD myotubes in vitro. © 2018 Wiley Periodicals, Inc.

Incapacity, Handicap, and Oxidative Stress Markers of Male Smokers With and Without COPD.

PubMed

Ben Moussa, Syrine; Rouatbi, Sonia; Ben Saad, Helmi

2016-05-01

Mechanisms of incapacity and quality of life (QOL) of smokers with COPD and those free from COPD (non-COPD) are still unclear. The aims of this work were to compare the submaximal exercise, the QOL, and the blood and lung oxidative stress biomarker data of smokers without and with COPD. Thirty-two male-smokers 40-60 y old were included (16 with COPD). QOL (Saint George Respiratory Questionnaire) and physical activity (Voorrips questionnaire) scores were determined. Blood sample levels of malondialdehyde, protein sulfhydryl, and glutathione were measured. Fraction of exhaled nitric oxide, plethysmographic data, and 6-min walk distance (6MWD) were collected. All data are presented as mean ± SD, except oxidative stress biomarkers expressed as mean ± SE. Correlation coefficient (r) evaluated the association between oxidative stress biomarkers and 6MWD, QOL, and physical activity data. Two age- and amount of tobacco used-matched groups of smokers were included. Compared with the non-COPD group, the COPD group had significantly lower 6MWD (573 ± 63 vs 476 ± 53 m) and physical activity score (7.14 ± 1.50 vs 2.86 ± 1.50) and significantly worse QOL (19.47 ± 15.33 vs 47.70 ± 16.73) and lower glutathione level (39.44 ± 6.28 vs 24.67 ± 5.41 μg/mL). The COPD group malondialdehyde level was significantly correlated with 6MWD, symptoms, and QOL scores (good r value between 0.50 and 0.70). The non-COPD group fraction of exhaled nitric oxide and glutathione levels were significantly correlated with leisure activity score and 6MWD, respectively (good r value between 0.50 and 0.70). Compared with the non-COPD group, the COPD group had a marked decrease in submaximal exercise data and in QOL score. Oxidative stress could be one explanation of incapacity and handicap observed in the COPD group. Copyright © 2016 by Daedalus Enterprises.

[Systemic inflammatory profile of smokers with and without COPD].

PubMed

Mosrane, Y; Bougrida, M; Alloui, A S; Martani, M; Rouabah, L; Bourahli, M K; Mehdioui, H; Ben Saad, H

2017-09-01

Studies comparing the systemic inflammatory profiles of smokers with and without COPD present discordant findings. To compare the systemic inflammatory profile of smokers with and without COPD. This is a cross-sectional comparative study. Two groups of active smokers of more than 10 pack-years were included: 56 consecutives stable COPD (postbronchodilator FEV 1 /FVC<0.70) and 32 consecutives non-COPD (postbronchodilator FEV 1 /FVC≥0.70). Smoking and clinical, anthropometric and spirometric data were noted. The following blood biomarkers were identified: leukocytes, hemoglobin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR). According to the levels (normal/abnormal) of these markers, two groups of smokers were formed. Quantitative and qualitative data were expressed, respectively, as means±SD and percentages. Compared to the non-COPD group, the COPD group was older (56±12 vs. 65±8 years) and had a higher smoking consumption (30±18 vs. 52±31 pack-years). Compared to the non-COPD group, the COPD group had higher values of CRP (2.06±1.24 vs. 11.32±11.03mg/L), of ESR (9.59±8.29 vs. 15.96±11.56), of IL-6 (9.28±4.69 vs. 20.27±5.31ng/L) and of TNF-α (18.38±7.98ng/L vs. 8.62±3.72ng/L). Compared to the non-COPD group, the COPD group included higher percentages of smokers with elevated CRP (0 % vs. 32 %), with leukocytosis (6 % vs. 16 %), with higher levels of IL-6 (81 % vs. 98 %) or TNF-α (91 % vs. 100 %). Smokers with COPD, compared to smokers free from COPD, have a marked systemic inflammation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Assessment of cognitive impairment in long-term oxygen therapy-dependent COPD patients.

PubMed

Karamanli, Harun; Ilik, Faik; Kayhan, Fatih; Pazarli, Ahmet Cemal

2015-01-01

A number of studies have shown that COPD, particularly in its later and more severe stages, is associated with various cognitive deficits. Thus, the primary goal of the present study was to elucidate the extent of cognitive impairment in patients with long-term oxygen therapy-dependent (LTOTD) COPD. In addition, this study aimed to determine the effectiveness of two cognitive screening tests, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), for COPD patients and the ability of oxygen therapy to mitigate COPD-related deficits in cognitive function. The present study enrolled 45 subjects: 24 nonuser and 21 regular-user LTOTD-COPD patients. All subjects had a similar grade of education, and there were no significant differences regarding age or sex. The MoCA (cutoff: <26 points) and MMSE (cutoff: ≤24 points) scores were compared between these two groups. The nonuser LTOTD-COPD group had a significantly lower MoCA score than that of the regular-user LTOTD-COPD group (19.38±2.99 vs 21.68±2.14, respectively) as well as a significantly lower MMSE score. Moreover, the absence of supplemental oxygen therapy increased the risk of cognitive impairment (MoCA, P=0.007 and MMSE, P=0.014), and the MoCA and MMSE scores significantly correlated with the number of emergency admissions and the number of hospitalizations in the last year. In the present study, the nonuser LTOTD-COPD group exhibited a significant decrease in cognitive status compared with the regular-user LTOTD-COPD group. This suggests that the assessment of cognitive function in nonuser LTOTD-COPD patients and the use of protective strategies, such as continuous supplemental oxygen treatment, should be considered during the management of COPD in this population. In addition, the MoCA score was superior to the MMSE score for the determination of cognitive impairment in the nonuser LTOTD-COPD patients.

Perception of symptoms and quality of life – comparison of patients’ and physicians’ views in the COPD MIRROR study

PubMed Central

Celli, Bartolome; Blasi, Francesco; Gaga, Mina; Singh, Dave; Vogelmeier, Claus; Pegoraro, Valeria; Caputo, Nicoletta; Agusti, Alvar

2017-01-01

Objectives The aim of this study was to compare potential differences between the perception that COPD patients have of their disease and the perception that physicians have of how the disease affects their patients. Methods Surveys in COPD patients and physicians caring for COPD patients were conducted in Spain, Italy, and Germany. Online questionnaires mirrored to explore the same domains, were administered to patients and physicians. Physicians were asked to respond to the questionnaire taking a recently seen patient who represents the majority of COPD patients usually managed, as a reference. Patients with COPD completed a survey containing the same questions offered to the physicians (Medical Investigation of Respiratory COPD Perception [MIRROR] survey). Comparisons between the responses of patients and general practitioners (GPs) and between patients and pulmonologists (PULs) were run separately using the chi-square, Fisher’s exact, or Student’s t-tests. Results A total of 334 COPD patients, 333 GPs, and 333 PULs participated in the surveys. The typical perception that PULs have of the COPD patient was that of an older man with more severe disease and less likely to be a smoker, than the included COPD patients. COPD was regarded as a major health problem by patients and physicians, but its impact on overall quality of life among more severe patients was less strongly perceived by physicians than by patients. Instead, physicians paid more attention to domains related to clinical features (cough, phlegm, and dyspnea), while underestimating COPD impact on leisure and social activities. The majority of patients stated not being completely frank with their doctors during visits. Both GPs and PULs seemed to recognize this issue but underestimated its extent. Conclusion To improve the doctor–patient communication, a more frank reporting by the patients of their symptoms and feelings and an increased awareness of physicians about the impact on nonconventional domains that patients perceive as importantly affected by COPD should be encouraged. PMID:28794623

Sex discrepancies in COPD patients and burden of the disease in females: a nationwide study in Greece (Greek Obstructive Lung Disease Epidemiology and health ecoNomics: GOLDEN study)

PubMed Central

Papaioannou, Andriana I; Bania, Eleni; Alexopoulos, Evangelos C; Mitsiki, Eirini; Malli, Foteini; Gourgoulianis, Konstantinos I

2014-01-01

Background The prevalence of chronic obstructive pulmonary disease (COPD) in females appears to be increasing. Recent studies have revealed that the percentage of women with COPD in Greece is approximately 12.5%. Aims To evaluate the burden of COPD among males and females in Greece through a nationwide cross-sectional survey and to explore sex differences regarding functional characteristics and exacerbation frequency. Methods Data collection was completed in a 6-month period. The present study followed a nationwide sampling approach of respiratory medicine physicians. The sampling approach included three steps: 1) estimation of expected incidence and prevalence of COPD cases in each prefecture of Greece and in total; 2) estimation of expected incidence of COPD cases per physician in each prefecture; and 3) creation of a frame of three different sampling zones. Following this sampling, data were provided by 199 respiratory physicians. Results The participating physicians provided data from 6,125 COPD patients. Female patients represented 28.7% of the study participants. Female COPD patients were, on average, 5 years younger than male COPD patients. Never smokers accounted for 9.4% within female patients, compared to 2.7% of males (P<0.001). Female patients were characterized by milder forms of the disease. Comorbidities were more prevalent in men, with the exception of gastroesophageal reflux (14.6% versus 17.1% for men and women, respectively, P=0.013). Female COPD patients had a higher expected number of outpatient visits per year (by 8.9%) than males (P<0.001), although hospital admissions did not differ significantly between sexes (P=0.116). Females had fewer absences from work due to COPD per year, by 19.0% (P<0.001), compared to males. Conclusion The differences observed between male and female COPD patients provide valuable information which could aid the prevention and management of COPD in Greece. PMID:24600217

Measurement of COPD Severity Using a Survey-Based Score

PubMed Central

Omachi, Theodore A.; Katz, Patricia P.; Yelin, Edward H.; Iribarren, Carlos; Blanc, Paul D.

2010-01-01

Background: A comprehensive survey-based COPD severity score has usefulness for epidemiologic and health outcomes research. We previously developed and validated the survey-based COPD Severity Score without using lung function or other physiologic measurements. In this study, we aimed to further validate the severity score in a different COPD cohort and using a combination of patient-reported and objective physiologic measurements. Methods: Using data from the Function, Living, Outcomes, and Work cohort study of COPD, we evaluated the concurrent and predictive validity of the COPD Severity Score among 1,202 subjects. The survey instrument is a 35-point score based on symptoms, medication and oxygen use, and prior hospitalization or intubation for COPD. Subjects were systemically assessed using structured telephone survey, spirometry, and 6-min walk testing. Results: We found evidence to support concurrent validity of the score. Higher COPD Severity Score values were associated with poorer FEV1 (r = −0.38), FEV1% predicted (r = −0.40), Body mass, Obstruction, Dyspnea, Exercise Index (r = 0.57), and distance walked in 6 min (r = −0.43) (P < .0001 in all cases). Greater COPD severity was also related to poorer generic physical health status (r = −0.49) and disease-specific health-related quality of life (r = 0.57) (P < .0001). The score also demonstrated predictive validity. It was also associated with a greater prospective risk of acute exacerbation of COPD defined as ED visits (hazard ratio [HR], 1.31; 95% CI, 1.24-1.39), hospitalizations (HR, 1.59; 95% CI, 1.44-1.75), and either measure of hospital-based care for COPD (HR, 1.34; 95% CI, 1.26-1.41) (P < .0001 in all cases). Conclusion: The COPD Severity Score is a valid survey-based measure of disease-specific severity, both in terms of concurrent and predictive validity. The score is a psychometrically sound instrument for use in epidemiologic and outcomes research in COPD. PMID:20040611

Perception of symptoms and quality of life - comparison of patients' and physicians' views in the COPD MIRROR study.

PubMed

Celli, Bartolome; Blasi, Francesco; Gaga, Mina; Singh, Dave; Vogelmeier, Claus; Pegoraro, Valeria; Caputo, Nicoletta; Agusti, Alvar

2017-01-01

The aim of this study was to compare potential differences between the perception that COPD patients have of their disease and the perception that physicians have of how the disease affects their patients. Surveys in COPD patients and physicians caring for COPD patients were conducted in Spain, Italy, and Germany. Online questionnaires mirrored to explore the same domains, were administered to patients and physicians. Physicians were asked to respond to the questionnaire taking a recently seen patient who represents the majority of COPD patients usually managed, as a reference. Patients with COPD completed a survey containing the same questions offered to the physicians (Medical Investigation of Respiratory COPD Perception [MIRROR] survey). Comparisons between the responses of patients and general practitioners (GPs) and between patients and pulmonologists (PULs) were run separately using the chi-square, Fisher's exact, or Student's t -tests. A total of 334 COPD patients, 333 GPs, and 333 PULs participated in the surveys. The typical perception that PULs have of the COPD patient was that of an older man with more severe disease and less likely to be a smoker, than the included COPD patients. COPD was regarded as a major health problem by patients and physicians, but its impact on overall quality of life among more severe patients was less strongly perceived by physicians than by patients. Instead, physicians paid more attention to domains related to clinical features (cough, phlegm, and dyspnea), while underestimating COPD impact on leisure and social activities. The majority of patients stated not being completely frank with their doctors during visits. Both GPs and PULs seemed to recognize this issue but underestimated its extent. To improve the doctor-patient communication, a more frank reporting by the patients of their symptoms and feelings and an increased awareness of physicians about the impact on nonconventional domains that patients perceive as importantly affected by COPD should be encouraged.

Missed diagnosis and overtreatment of COPD among smoking primary care population in Central Greece: old problems persist

PubMed Central

Kotsiou, Ourania S; Deskata, Konstantina; Gourgoulianis, Konstantinos I

2018-01-01

Background The diagnosis of COPD is not always consistent with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy in daily clinical practice, especially in primary care. This study aimed to estimate the overall COPD prevalence and severity, to identify differences between newly and previously diagnosed patients, and to evaluate the potential COPD overtreatment in a smoking population attending a primary care spirometry surveillance program. Methods A study was conducted in 10 primary health care centers of Central Greece during a 7-month period. Eligible participants were aged ≥40 years and were either current smokers or exsmokers. Results A total of 186 subjects were included (68% males, mean age 62.3±12.6 years, mean life-time tobacco exposure 50 pack-years). COPD prevalence was 17.8%, identified to be higher in elderly males. Forty-two percent of the COPD group were newly diagnosed patients, who were of younger age, current smokers, presented with less dyspnea and better health status, and mainly appeared with mild-to-moderate disease. Interestingly, 61.4% of non-COPD and 85.7% of newly diagnosed COPD individuals had been using inhaled medication under primary care provider’s prescription without ever undergoing spirometry or further evaluation by a pulmonologist; thus, the phenomena of COPD overdiagnosis and missed diagnosis came into the spotlight. Moreover, only 26.3% of known COPD patients were properly medicated according to GOLD guidelines, while half of them were inappropriately treated with triple inhaled therapy. Conclusion We reported a significant prevalence of COPD in smoking population attending this spirometry program. A remarkable proportion of COPD patients were undiagnosed and made case finding worthwhile. Underutilization of spirometry in the diagnosis and management of COPD as well as general practitioners’ nonadherence to the GOLD treatment guidelines was confirmed by our data. These findings highlight the need for a major overhaul and culture change in primary care settings of Central Greece. PMID:29440886

Impact of chronic obstructive pulmonary disease on patients undergoing laryngectomy for laryngeal cancer.

PubMed

Sylvester, Michael J; Marchiano, Emily; Park, Richard Chan Woo; Baredes, Soly; Eloy, Jean Anderson

2017-02-01

Although chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients undergoing laryngeal cancer surgery, the impact of this comorbidity in this setting is not well established. In this analysis, we used the Nationwide Inpatient Sample (NIS) to elucidate the impact of COPD on outcomes after laryngectomy for laryngeal cancer. The NIS was queried for patients admitted from 1998 to 2010 with laryngeal cancer who underwent total or partial laryngectomy. Patient demographics, type of admission, length of stay, hospital charges, and concomitant diagnoses were analyzed. Our inclusion criteria yielded a cohort of 40,441 patients: 3,051 with COPD and 37,390 without. On average, COPD was associated with an additional $12,500 (P < 0.001) in hospital charges and an additional 1.4 days (P < 0.001) of hospital stay. There was no significant difference in incidence of in-hospital mortality between the COPD and non-COPD groups after total laryngectomy (1.1% in COPD vs. 1.0% in non-COPD; P = 0.776); however, there was an increased incidence of in-hospital mortality in the COPD group compared to the non-COPD group after partial laryngectomy (3.4% in COPD vs. 0.4% in non-COPD; P < 0.001). Multivariate adjusted logistic regression revealed that COPD was associated with greater odds of pulmonary complications after both partial laryngectomy (odds ratio [OR] = 3.198; P < 0.001) and total laryngectomy (OR = 1.575; P < 0.001). Chronic obstructive pulmonary disease appears to be associated with greater hospital charges, length of stay, and postoperative pulmonary complications in patients undergoing laryngectomy for laryngeal cancer. Chronic obstructive pulmonary disease after partial, but not total, laryngectomy appears to be associated with increased risk of in-hospital mortality. 2C. Laryngoscope, 2016 127:417-423, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD).

PubMed

McCullagh, Brian N; Comellas, Alejandro P; Ballas, Zuhair K; Newell, John D; Zimmerman, M Bridget; Azar, Antoine E

2017-01-01

Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a potentially treatable risk factor for frequent COPD exacerbations; testing for antibody deficiency should be considered in difficult to manage frequently exacerbating COPD patients. Further prospective studies are warranted to further test this hypothesis.

Asthma–COPD Overlap. Clinical Relevance of Genomic Signatures of Type 2 Inflammation in Chronic Obstructive Pulmonary Disease

PubMed Central

Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S.; Postma, Dirkje S.; Lenburg, Marc E.; Spira, Avrum; Woodruff, Prescott G.

2015-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. Objectives: To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. Methods: We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). Measurements and Main Results: The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. Conclusions: These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and “asthma-like” features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma. PMID:25611785

Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD)

PubMed Central

McCullagh, Brian N.; Comellas, Alejandro P.; Ballas, Zuhair K.; Newell, John D.; Zimmerman, M. Bridget

2017-01-01

Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a potentially treatable risk factor for frequent COPD exacerbations; testing for antibody deficiency should be considered in difficult to manage frequently exacerbating COPD patients. Further prospective studies are warranted to further test this hypothesis. PMID:28212436

Oxygen desaturation during the six-minute walk test in COPD patients*

PubMed Central

Moreira, Maria Ângela Fontoura; de Medeiros, Gabriel Arriola; Boeno, Francesco Pinto; Sanches, Paulo Roberto Stefani; da Silva, Danton Pereira; Müller, André Frotta

2014-01-01

Objective: To evaluate the behavior of oxygen saturation curves throughout the six-minute walk test (6MWT) in patients with COPD. Methods: We included 85 patients, all of whom underwent spirometry and were classified as having moderate COPD (modCOPD, n = 30) or severe COPD (sevCOPD, n = 55). All of the patients performed a 6MWT, in a 27-m corridor with continuous SpO2 and HR monitoring by telemetry. We studied the SpO2 curves in order to determine the time to a 4% decrease in SpO2, the time to the minimum SpO2 (Tmin), and the post-6MWT time to return to the initial SpO2, the last designated recovery time (RT). For each of those curves, we calculated the slope. Results: The mean age in the modCOPD and sevCOPD groups was 66 ± 10 years and 62 ± 11 years, respectively. At baseline, SpO2 was > 94% in all of the patients; none received supplemental oxygen during the 6MWT; and none of the tests were interrupted. The six-minute walk distance did not differ significantly between the groups. The SpO2 values were lowest in the sevCOPD group. There was no difference between the groups regarding RT. In 71% and 63% of the sevCOPD and modCOPD group patients, respectively, a ≥ 4% decrease in SpO2 occurred within the first minute. We found that FEV1% correlated significantly with the ΔSpO2 (r = −0.398; p < 0.001), Tmin (r = −0.449; p < 0.001), and minimum SpO2 (r = 0.356; p < 0.005). Conclusions: In the sevCOPD group, in comparison with the modCOPD group, SpO2 was lower and the Tmin was greater, suggesting a worse prognosis in the former. PMID:25029644

Too ‘Stubborn’ to Give in to COPD | NIH MedlinePlus the Magazine

MedlinePlus

... Follow us Too ‘Stubborn’ to Give in to COPD Jim Nelson fights COPD with determination and advocacy Photo: Jim Nelson “I ... from cigarettes and helped him deal with his COPD. His commitment to exercise and good health helped ...

COPD and osteoporosis: links, risks, and treatment challenges.

PubMed

Inoue, Daisuke; Watanabe, Reiko; Okazaki, Ryo

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis. Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD. COPD-associated osteoporosis is however extremely undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients. Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described. It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks. Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis.

Prevalence, awareness, characteristics, and health outcomes associated with COPD at-risk status among adults in Japan.

PubMed

Omori, Hisamitsu; Yoshimoto, Daisuke; Kumar, Maya; Goren, Amir

2016-08-01

We examined the prevalence of chronic obstructive pulmonary disease (COPD) diagnosed and at-risk status, and public awareness of COPD among adults in Japan, as well as respondent characteristics and health outcomes compared with controls. Regression models used 2012 National Health and Wellness Survey in Japan data to compare COPD-diagnosed, at-risk, and healthy adults (aged ≥18) on demographics, health behaviors, health-related quality of life (HRQoL), productivity and healthcare resource use. Among n = 29,978 respondents, diagnosed COPD prevalence was 0.9%; 26.9% were at-risk. Relative to controls, those at-risk and diagnosed with COPD had significantly greater healthcare resource use, with lower productivity and HRQoL. Fewer than 20% of respondents were aware of COPD. Over 25% of adult Japanese respondents were at-risk for COPD and had health outcomes impairments relative to controls. Efforts to increase awareness among the general public are needed.

Flow characteristics in the airways of a COPD patient with a saber-sheath trachea

NASA Astrophysics Data System (ADS)

Jin, Dohyun; Choi, Haecheon; Lee, Changhyun; Choi, Jiwoong; Kim, Kwanggi

2016-11-01

The chronic obstructive pulmonary disease (COPD) is a lung disease characterized by the irreversible airflow limitation caused by the damaged small airways and air sacs. Although COPD is not a disease of the trachea, many patients with COPD have saber-sheath tracheas. The effects of this morphological change in the trachea geometry on airflow are investigated in the present study. An unstructured finite volume method is used for the simulations during tidal breathing in normal and COPD airways, respectively. During inspiration, local large pressure drop is observed in the saber-sheath region of the COPD patient. During expiration, vortical structures are observed at the right main bronchus of the COPD airway, while the flow in the normal airway remains nearly laminar. High wall shear stress exists at convex regions of both airways during inspiration and expiration. However, due to the morphological changes in the COPD airway, relatively higher wall shear stress is observed in the patient airways.

Inhaled therapies in patients with moderate COPD in clinical practice: current thinking

PubMed Central

Ariel, Amnon; Altraja, Alan; Belevskiy, Andrey; Boros, Piotr W; Danila, Edvardas; Fležar, Matjaz; Koblizek, Vladimir; Fridlender, Zvi G; Kostov, Kosta; Krams, Alvils; Milenkovic, Branislava; Somfay, Attila; Tkacova, Ruzena; Tudoric, Neven; Ulmeanu, Ruxandra; Valipour, Arschang

2018-01-01

COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups. PMID:29317810

Determination of the relationship between cognitive function and hand dexterity in patients with chronic obstructive pulmonary disease (COPD): a cross-sectional study.

PubMed

Soysal Tomruk, Melda; Ozalevli, Sevgi; Dizdar, Gorkem; Narin, Selnur; Kilinc, Oguz

2015-07-01

Hand dexterity is important for daily living activities and can be related to cognitive functions in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the relationship between cognitive dysfunction and hand dexterity in patients with COPD. 35 COPD patients and 36 healthy individuals were assessed. The Minnesota Hand Dexterity Test and Mini Mental State Examination (MMSE) were used for assessment of cognitive function and hand dexterity. Hand dexterity test scores and cognitive function of COPD patients' were significantly lower than the healthy group (p < 0.01). The MMSE scores were negatively correlated with hand dexterity scores in the COPD group (p < 0.05). There was a relationship between cognitive function and hand dexterity in the patients with COPD; however, hand dexterity did not alter according to hypoxemia severity. Hand dexterity which is important in daily living activities should be evaluated in greater detail with further studies in COPD patients.

Community pharmacy-based case finding for COPD in urban and rural settings is feasible and effective.

PubMed

Fathima, Mariam; Saini, Bandana; Foster, Juliet M; Armour, Carol L

2017-01-01

Case finding of patients at risk of COPD by community pharmacists could identify a substantial number of people with undiagnosed COPD, but little is known about the feasibility and effectiveness of pharmacy-based COPD case finding using microspirometry. The objective of this study was to assess the feasibility and effectiveness of COPD case-finding service provided by community pharmacists, utilizing a combination of risk assessment questionnaire and microspirometry. A 6-month service was conducted in 21 community pharmacies in Australia. Pharmacists trained in COPD case finding, including lung function test (LFT), invited their patients aged ≥35 years with a history of smoking and/or respiratory symptoms to participate. High-risk patients were identified via a COPD risk assessment questionnaire (Initial Screening Questionnaire [ISQ]) and underwent LFT. Pharmacists referred patients with a forced expiratory volume in 1 second (FEV 1 )/forced expiratory volume in 6 seconds (FEV 6 ) ratio <0.75 to their general practitioner (GP) for further assessment and diagnosis. In all, 91 of 167 (54%) patients had an ISQ score >3 indicating high COPD risk. Of the 157 patients who were able to complete LFT, 61 (39%) had an FEV 1 /FEV 6 ratio of <0.75 and were referred to their GP. Patients with high ISQ symptoms scores (>3) were at a significantly higher risk of an FEV 1 /FEV 6 ratio of <0.75, compared to patients with fewer COPD symptoms. A total of 15 (10%) patients were diagnosed with COPD by their GP. Another eight (5%) patients were diagnosed with other medical conditions and 87% of these were initiated on treatment. Although only half of all screened patients lived in regional areas, 93% of those diagnosed with COPD were from regional areas. A brief community pharmacy-based COPD case-finding service utilizing the ISQ, LFT and GP referral is feasible and may lead to identification and diagnosis of a substantial number of people with COPD. This might be an important strategy for reducing the burden of COPD, particularly for those living in rural locations.

Community pharmacy-based case finding for COPD in urban and rural settings is feasible and effective

PubMed Central

Fathima, Mariam; Saini, Bandana; Foster, Juliet M; Armour, Carol L

2017-01-01

Background and objective Case finding of patients at risk of COPD by community pharmacists could identify a substantial number of people with undiagnosed COPD, but little is known about the feasibility and effectiveness of pharmacy-based COPD case finding using microspirometry. The objective of this study was to assess the feasibility and effectiveness of COPD case-finding service provided by community pharmacists, utilizing a combination of risk assessment questionnaire and microspirometry. Methods A 6-month service was conducted in 21 community pharmacies in Australia. Pharmacists trained in COPD case finding, including lung function test (LFT), invited their patients aged ≥35 years with a history of smoking and/or respiratory symptoms to participate. High-risk patients were identified via a COPD risk assessment questionnaire (Initial Screening Questionnaire [ISQ]) and underwent LFT. Pharmacists referred patients with a forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) ratio <0.75 to their general practitioner (GP) for further assessment and diagnosis. Results In all, 91 of 167 (54%) patients had an ISQ score >3 indicating high COPD risk. Of the 157 patients who were able to complete LFT, 61 (39%) had an FEV1/FEV6 ratio of <0.75 and were referred to their GP. Patients with high ISQ symptoms scores (>3) were at a significantly higher risk of an FEV1/FEV6 ratio of <0.75, compared to patients with fewer COPD symptoms. A total of 15 (10%) patients were diagnosed with COPD by their GP. Another eight (5%) patients were diagnosed with other medical conditions and 87% of these were initiated on treatment. Although only half of all screened patients lived in regional areas, 93% of those diagnosed with COPD were from regional areas. Conclusion A brief community pharmacy-based COPD case-finding service utilizing the ISQ, LFT and GP referral is feasible and may lead to identification and diagnosis of a substantial number of people with COPD. This might be an important strategy for reducing the burden of COPD, particularly for those living in rural locations. PMID:29075108

Exacerbations and health care resource utilization in patients with airflow limitation diseases attending a primary care setting: the PUMA study

PubMed Central

Montes de Oca, Maria; Aguirre, Carlos; Lopez Varela, Maria Victorina; Laucho-Contreras, Maria E; Casas, Alejandro; Surmont, Filip

2016-01-01

Background COPD, asthma, and asthma–COPD overlap increase health care resource consumption, predominantly because of hospitalization for exacerbations and also increased visits to general practitioners (GPs) or specialists. Little information is available regarding this in the primary care setting. Objectives To describe the prevalence and number of GP and specialist visits for any cause or due to exacerbations in patients with COPD, asthma, and asthma–COPD overlap. Methods COPD was defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio <0.70; asthma was defined as prior medical diagnosis, wheezing in the last 12 months, or wheezing plus reversibility (post-bronchodilator FEV1 or FVC increase ≥200 mL and ≥12%); asthma–COPD overlap was defined as post-bronchodilator FEV1/FVC <0.70 plus prior asthma diagnosis. Health care utilization was evaluated as GP and/or specialist visits in the previous year. Results Among the 1,743 individuals who completed the questionnaire, 1,540 performed acceptable spirometry. COPD patients had a higher prevalence of any medical visits to any physician versus those without COPD (37.2% vs 21.8%, respectively) and exacerbations doubled the number of visits. The prevalence of any medical visits to any physician was also higher in asthma patients versus those without asthma (wheezing: 47.2% vs 22.7%; medical diagnosis: 54.6% vs 21.6%; wheezing plus reversibility: 46.2% vs 23.8%, respectively). Asthma patients with exacerbations had twice the number of visits versus those without an exacerbation. The number of visits was higher (2.8 times) in asthma–COPD overlap, asthma (1.9 times), or COPD (1.4 times) patients versus those without these respiratory diseases; the number of visits due to exacerbation was also higher (4.9 times) in asthma–COPD overlap, asthma (3.5 times), and COPD (3.8 times) patients. Conclusion COPD, asthma, and asthma–COPD overlap increase the prevalence of medical visits and, therefore, health care resource utilization. Attempts to reduce health care resource use in these patients require interventions aimed at preventing exacerbations. PMID:27994446

Exacerbations and health care resource utilization in patients with airflow limitation diseases attending a primary care setting: the PUMA study.

PubMed

Montes de Oca, Maria; Aguirre, Carlos; Lopez Varela, Maria Victorina; Laucho-Contreras, Maria E; Casas, Alejandro; Surmont, Filip

2016-01-01

COPD, asthma, and asthma-COPD overlap increase health care resource consumption, predominantly because of hospitalization for exacerbations and also increased visits to general practitioners (GPs) or specialists. Little information is available regarding this in the primary care setting. To describe the prevalence and number of GP and specialist visits for any cause or due to exacerbations in patients with COPD, asthma, and asthma-COPD overlap. COPD was defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV 1 /FVC) ratio <0.70; asthma was defined as prior medical diagnosis, wheezing in the last 12 months, or wheezing plus reversibility (post-bronchodilator FEV 1 or FVC increase ≥200 mL and ≥12%); asthma-COPD overlap was defined as post-bronchodilator FEV 1 /FVC <0.70 plus prior asthma diagnosis. Health care utilization was evaluated as GP and/or specialist visits in the previous year. Among the 1,743 individuals who completed the questionnaire, 1,540 performed acceptable spirometry. COPD patients had a higher prevalence of any medical visits to any physician versus those without COPD (37.2% vs 21.8%, respectively) and exacerbations doubled the number of visits. The prevalence of any medical visits to any physician was also higher in asthma patients versus those without asthma (wheezing: 47.2% vs 22.7%; medical diagnosis: 54.6% vs 21.6%; wheezing plus reversibility: 46.2% vs 23.8%, respectively). Asthma patients with exacerbations had twice the number of visits versus those without an exacerbation. The number of visits was higher (2.8 times) in asthma-COPD overlap, asthma (1.9 times), or COPD (1.4 times) patients versus those without these respiratory diseases; the number of visits due to exacerbation was also higher (4.9 times) in asthma-COPD overlap, asthma (3.5 times), and COPD (3.8 times) patients. COPD, asthma, and asthma-COPD overlap increase the prevalence of medical visits and, therefore, health care resource utilization. Attempts to reduce health care resource use in these patients require interventions aimed at preventing exacerbations.

COPD and levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes among coal workers: a case-control study.

PubMed

Cui, Xiuqing; Xing, Jingcai; Liu, Yuewei; Zhou, Yun; Luo, Xin; Zhang, Zhihong; Han, Wenhui; Wu, Tangchun; Chen, Weihong

2015-05-01

This case-control study aimed to investigate whether the levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes were associated with the risk of chronic obstructive pulmonary disease (COPD) among coal workers. A total of 76 COPD cases and 48 age-matched healthy controls from a group of coal workers were included. The case group consisted of 35 COPD patients whose condition was complicated with coal workers' pneumoconiosis (CWP) and 41 COPD patients without CWP. Heat shock proteins (Hsps) in plasma and lymphocytes were detected by ELISA and flow cytometry, respectively. Multiple logistic regression models were applied to estimate the association between Hsp levels and COPD risk. Our results showed that plasma Hsp70 and lymphocyte Hsp27 levels were significantly higher and plasma Hsp27 levels were significantly lower in COPD cases than in controls (p < 0.01). No significant differences in lymphocyte Hsp70 levels were found between COPD cases and the matched subjects. Higher plasma Hsp70 levels (odds ratio (OR) = 13.8, 95 % confidence interval (CI) = 5.7-33.5) and lower plasma Hsp27 levels (OR = 4.6, 95 % CI = 2.0-10.5) were significantly associated with an increased risk of COPD after adjusting for confounders. Higher lymphocyte Hsp27 levels were only associated with an increased risk of COPD with CWP (OR = 6.6, 95 % CI = 2.0-22.1) but not with an increased risk of COPD without CWP (OR = 3.0, 95 % CI = 0.9-8.9). Additionally, there were strong joint effects of different Hsps on COPD risk. These results showed that higher levels of plasma Hsp70 and lower levels of plasma Hsp27 might be associated with an increased risk of COPD among coal workers. They may have the potential to serve as monitoring markers for COPD in coal workers.

Chronic rhinosinusitis is associated with higher prevalence and severity of bronchiectasis in patients with COPD

PubMed Central

Yang, Xia; Xu, Yali; Jin, Jianmin; Li, Ruimin; Liu, Xiaofang; Sun, Yongchang

2017-01-01

Background and purpose Bronchiectasis revealed by high-resolution computed tomography (HRCT) is common in chronic obstructive pulmonary disease (COPD), but the causes and risk factors remain to be determined. Chronic rhinosinusitis (CRS) is closely associated with bronchiectasis or COPD, but whether it is associated with comorbid bronchiectasis in COPD (COPD-Bx) is unknown. Patients and methods Patients with stable COPD were enrolled consecutively and evaluated for the presence of CRS by questionnaire and paranasal sinus computed tomography. The presence and severity of bronchiectasis on lung HRCT were evaluated by the Smith and severity scores. COPD symptoms were evaluated by COPD Assessment Test (CAT) and Modified British Medical Research Council Questionnaire. The sputum cell differentials and concentrations of interleukin (IL)-6, IL-8, IL-5, matrix metalloproteinases-9 (MMP-9), and tissue inhibitor of matrix metalloproteinases-1 were measured. Results We enrolled 136 patients with stable COPD, of which 66 (48.5%) were diagnosed with CRS according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) criteria. The prevalence of bronchiectasis was 57.6% in patients with CRS, but 37.1% in those without CRS (P=0.017). COPD-Bx patients with CRS showed a significantly higher severity score of bronchiectasis than those without CRS (P=0.034). COPD patients with CRS had a higher percentage of eosinophils, higher levels of IL-8, IL-6, and MMP-9 in sputum as compared to those without CRS. In COPD-Bx patients with CRS, the percentage of eosinophils and the levels of IL-6 and MMP-9 in sputum were increased as compared to those without CRS. In all the subjects, Sino-Nasal Outcome Test-20 correlated with CAT score (r=0.315, P<0.01) and in COPD patients with CRS, Lund–MacKay scores correlated with forced expiratory volume in 1 s (% pred) (r=−0.251, P<0.05). Conclusions CRS was associated with COPD-Bx and this was probably due to increased airway inflammation. PMID:28260873

How do patients conceptualize chronic obstructive pulmonary disease?

PubMed

Goldman, R E; Mennillo, L; Stebbins, P; Parker, D R

2017-08-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, yet even at risk or diagnosed patients misunderstand COPD and its consequences for their quality of life and mortality. This study explored how patients conceptualize the causes, symptoms, consequences, treatment, and risk for developing COPD. The study consisted of six focus groups: 39 participants who were adults > 40 and current smoker or have COPD symptoms, family history, or exposures. Although many participants had some familiarity with the breathing, lung function, physical, emotional, and social consequences of COPD, confusion and misunderstanding prevailed. Few knew that COPD, chronic bronchitis, and emphysema are synonymous. Some participants claimed that they "only" had bronchitis and/or emphysema and not COPD. Some participants described behavioral adaptations to decrease symptom impact and others expressed strong interest in learning how to increase daily functioning. Insufficient knowledge and persisting misconceptions about COPD can prevent patients from accessing life-enhancing strategies. Patients can benefit from (1) providers clarifying COPD's connection to chronic bronchitis and emphysema to aid them in recognizing the need for mitigating action; (2) encouraging smoking cessation, specifically to stem worsening of disease; and (3) explaining lifestyle adaptations for easing daily life despite decreased lung function.

Health care use and economic burden of patients with diagnosed chronic obstructive pulmonary disease in Korea.

PubMed

Kim, C; Yoo, K H; Rhee, C K; Yoon, H K; Kim, Y S; Lee, S W; Oh, Y-M; Lee, S-D; Lee, J H; Kim, K-J; Kim, J-H; Park, Y B

2014-06-01

The prevalence and economic burden of chronic obstructive pulmonary disease (COPD) are increasing worldwide. However, little information is available concerning COPD-associated health care use and costs in Korea. To analyse 1) health care use, medical costs and medication use in 2009, and 2) changes in costs and medication use over 5 years (2006-2010). Using the database of the Korean Health Insurance Review and Assessment Service, COPD patients were identified by searching on both ICD-10 codes and COPD medication. RESULTS A total of 192,496 COPD patients were identified in 2009. Total medical costs per person were US$2803 ± 3865; the average annual number of days of out-patient care and days of hospitalisation were respectively 40 ± 36 and 11 ± 33. Methylxanthine and systemic beta-agonists were the most frequently used drugs. However, the number of prescriptions for long-acting muscarinic antagonist increased rapidly. The total cost of COPD-related medications increased by 33.1% over 5 years. The present study provides new insight into health care use and the economic burden of COPD in Korea. Changing patterns of COPD-related medication use could help inform COPD management policies.

Canadian practice assessment in chronic obstructive pulmonary disease: respiratory specialist physician perception versus patient reality.

PubMed

Hernandez, Paul; Balter, Meyer S; Bourbeau, Jean; Chan, Charles K; Marciniuk, Darcy D; Walker, Shannon L

2013-01-01

Chronic obstructive pulmonary disease (COPD) is a common respiratory condition and the fourth leading cause of death in Canada. Optimal COPD management requires patients to participate in their care and physician knowledge of patients' perceptions of their disease. A prospective study in which respiratory specialist physicians completed a practice assessment questionnaire and patient assessments for 15 to 20 consecutive patients with COPD. Patients also completed a questionnaire regarding their perceptions of COPD and its management. A total of 58 respiratory specialist physicians from across Canada completed practice assessments and 931 patient assessments. A total of 640 patients with COPD (96% with moderate, severe or very severe disease) completed questionnaires. Symptom burden was high and most patients had experienced a recent exacerbation. Potential COPD care gaps were identified with respect to appropriate medication prescription, lack of an action plan, and access to COPD educators and pulmonary rehabilitation. Perceived knowledge needs and gaps differed between physicians and patients. Despite the dissemination of Canadian and international COPD clinical practice guidelines for more than a decade, potential care gaps remain among patients seen by respiratory specialist physicians. Differing perceptions regarding many aspects of COPD among physicians and patients may contribute to these care gaps.

Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao Hongwei; Rahman, Irfan, E-mail: irfan_rahman@urmc.rochester.edu

Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-{kappa}B), autophagy and unfolded protein response leading to chronic lung inflammatorymore » response. Cigarette smoke also activates canonical/alternative NF-{kappa}B pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD.« less

Day-to-day living with severe chronic obstructive pulmonary disease: towards a family-based approach to the illness impacts.

PubMed

Gabriel, Raquel; Figueiredo, Daniela; Jácome, Cristina; Cruz, Joana; Marques, Alda

2014-01-01

This study explores the perspectives of both patients and family members regarding the impact of chronic obstructive pulmonary disease (COPD) in their family life. An exploratory qualitative study was conducted with patients and their family members in the chronic phase of COPD. Individual interviews were performed to explore participants' perspectives and submitted to thematic analysis. Six major themes emerged from patients' perspective: (1) impact of COPD symptoms on personal and family daily life; (2) (over)protective family support; (3) difficulties in couple communication; (4) sense of identity loss; (5) fear of COPD progression; and (6) coping resources. Five main themes emerged from the family members' perspective: (1) restrictions in family's social life; (2) emotional distress related to COPD exacerbations; (3) tension in couple relationship; (4) financial strain of COPD; and (5) coping resources. The overall findings illustrate the complex interaction between the experience of living with COPD and communication patterns, emotional states, social support and social roles within the family. The results highlight the need to develop family-based interventions to facilitate a functional adjustment to COPD. However, these interventions in COPD remain undeveloped and empirical evidence is needed.

Modern Innovative Solutions in Improving Outcomes in Chronic Obstructive Pulmonary Disease (MISSION COPD): A Comparison of Clinical Outcomes Before and After the MISSION Clinic

PubMed Central

Green, Ben; Brown, Thomas; Storrar, Will; Jones, Thomas; Fogg, Carole; Dewey, Ann; Longstaff, Jayne; Bassett, Paul

2017-01-01

Background Chronic obstructive pulmonary disorder (COPD) affects over 1 million people in the United Kingdom, and 1 person dies from COPD every 20 minutes. The cost to people with COPD and the National Health Service is huge – more than 24 million working days lost a year and the annual expenditure on COPD is £810 million and £930 million a year. Objective We aim to identify patients with COPD who are at risk of exacerbations and hospital admissions as well as those who have not been formally diagnosed, yet remain at risk. Methods This mixed-methods study will use both data and interviews from patients and health care professionals. The project Modern Innovative SolutionS in Improving Outcomes iN COPD (MISSION COPD) will hold multidisciplinary carousel style clinics to rapidly assess the patients’ COPD and related comorbidities, and enhance patient knowledge and skills for self-management. Results This study is ongoing. Conclusions This research will capture quantitative and qualitative outcomes to accompany a program of quality improvement through delivery of novel care models. PMID:28583907

Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study

PubMed Central

Koblizek, Vladimir; Milenkovic, Branislava; Barczyk, Adam; Tkacova, Ruzena; Somfay, Attila; Zykov, Kirill; Tudoric, Neven; Kostov, Kosta; Zbozinkova, Zuzana; Svancara, Jan; Sorli, Jurij; Krams, Alvils; Miravitlles, Marc

2017-01-01

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region. Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment. 3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma–COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma–COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes. The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes. PMID:28495687

The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease

PubMed Central

Pragman, Alexa A.; Kim, Hyeun Bum; Reilly, Cavan S.; Wendt, Christine; Isaacson, Richard E.

2012-01-01

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. PMID:23071781

Diagnostic accuracy of a pocket screening spirometer in diagnosing chronic obstructive pulmonary disease in general practice: a cross sectional validation study using tertiary care as a reference.

PubMed

Labor, Marina; Vrbica, Žarko; Gudelj, Ivan; Labor, Slavica; Plavec, Davor

2016-08-19

COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk. The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard. Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD. COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP's office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %). Significant agreement for forced expiratory volume in 1 s measured at GP's office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all). Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD). Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral. ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered.

Anti-p-benzoquinone antibody level as a prospective biomarker to identify smokers at risk for COPD.

PubMed

Banerjee, Santanu; Bhattacharyya, Parthasarathi; Mitra, Subhra; Kundu, Somenath; Panda, Samiran; Chatterjee, Indu B

2017-01-01

Identification of smokers having predisposition to COPD is important for early intervention to reduce the huge global burden of the disease. Using a guinea pig model, we have shown that p -benzoquinone ( p -BQ) derived from cigarette smoke (CS) in the lung is a causative factor for CS-induced emphysema. p -BQ is also derived from CS in smokers and it elicits the production of anti- p -BQ antibody in humans. We therefore hypothesized that anti- p -BQ antibody might have a protective role against COPD and could be used as a predictive biomarker for COPD in smokers. The objective of this study was to compare the serum anti- p -BQ antibody level between smokers with and without COPD for the evaluation of the hypothesis. Serum anti- p -BQ antibody concentrations of current male smokers with (n=227) or without (n=308) COPD were measured by an indirect enzyme-linked immunoabsorbent assay (ELISA) developed in our laboratory. COPD was diagnosed by spirometry according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. A significant difference was observed in the serum anti- p -BQ antibody level between smokers with and without COPD (Mann-Whitney U -test =4,632.5, P =0.000). Receiver operating characteristic (ROC) curve analysis indicated that the ELISA had significant precision (area under the curve [AUC] =0.934, 95% confidence interval [CI]: 0.913-0.935) for identifying smokers with COPD from their low antibody level. The antibody cutoff value of 29.4 mg/dL was constructed from the ROC coordinates to estimate the risk for COPD in smokers. While 90.3% of smokers with COPD had a low antibody value (≤29.4 mg/dL), the majority (86.4%) of smokers without COPD had a high antibody value (≤29.4 mg/dL); 13.6% of current smokers without COPD having an antibody level below this cutoff value (odds ratio [OR] =59.3, 95% CI: 34.15-101.99) were considered to be at risk for COPD. Our results indicate that serum anti- p -BQ antibody level may be used as a biomarker to identify asymptomatic smokers at risk for COPD for early intervention of the disease.

Anti-p-benzoquinone antibody level as a prospective biomarker to identify smokers at risk for COPD

PubMed Central

Banerjee, Santanu; Bhattacharyya, Parthasarathi; Mitra, Subhra; Kundu, Somenath; Panda, Samiran; Chatterjee, Indu B

2017-01-01

Background and objective Identification of smokers having predisposition to COPD is important for early intervention to reduce the huge global burden of the disease. Using a guinea pig model, we have shown that p-benzoquinone (p-BQ) derived from cigarette smoke (CS) in the lung is a causative factor for CS-induced emphysema. p-BQ is also derived from CS in smokers and it elicits the production of anti-p-BQ antibody in humans. We therefore hypothesized that anti-p-BQ antibody might have a protective role against COPD and could be used as a predictive biomarker for COPD in smokers. The objective of this study was to compare the serum anti-p-BQ antibody level between smokers with and without COPD for the evaluation of the hypothesis. Methods Serum anti-p-BQ antibody concentrations of current male smokers with (n=227) or without (n=308) COPD were measured by an indirect enzyme-linked immunoabsorbent assay (ELISA) developed in our laboratory. COPD was diagnosed by spirometry according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Results and discussion A significant difference was observed in the serum anti-p-BQ antibody level between smokers with and without COPD (Mann–Whitney U-test =4,632.5, P=0.000). Receiver operating characteristic (ROC) curve analysis indicated that the ELISA had significant precision (area under the curve [AUC] =0.934, 95% confidence interval [CI]: 0.913–0.935) for identifying smokers with COPD from their low antibody level. The antibody cutoff value of 29.4 mg/dL was constructed from the ROC coordinates to estimate the risk for COPD in smokers. While 90.3% of smokers with COPD had a low antibody value (≤29.4 mg/dL), the majority (86.4%) of smokers without COPD had a high antibody value (≤29.4 mg/dL); 13.6% of current smokers without COPD having an antibody level below this cutoff value (odds ratio [OR] =59.3, 95% CI: 34.15–101.99) were considered to be at risk for COPD. Conclusion and future directions Our results indicate that serum anti-p-BQ antibody level may be used as a biomarker to identify asymptomatic smokers at risk for COPD for early intervention of the disease. PMID:28684907

The clinical features of the overlap between COPD and asthma

PubMed Central

2011-01-01

Background The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. Methods We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study. Results 119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness. Conclusion Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history. Trial registration ClinicalTrials.gov: NCT00608764 PMID:21951550

Early Detection of Chronic Obstructive Pulmonary Disease in Apparently Healthy Attendants of Tertiary Care Hospital and Assessment of its Severity.

PubMed

Zubair, Tahira; Abbassi, Amanullah; Khan, Osama Ahsan

2017-05-01

Early detection of Chronic Obstructive Pulmonary Disease in apparently healthy attendants of tertiary care hospital and assessment of its severity. Cross-sectional, observational study. Study was conducted from January 2015 to July 2015 at Dow University Hospital, Ojha campus. Ascreening method was designed for apparently healthy individuals including attendants of patients, hospital staff, faculty and students, belonging to age group 18-60 years after excluding severe obesity and already diagnosed respiratory and cardiovascular diseases by means of history. Each participant performed pulmonary function tests via spirometer after filling a questionnaire based on various risk factors and symptoms of chronic obstructive pulmonary disease (COPD). Data was entered and analysed by SPSS-20. Out of the 517 participants, 122 (23.6%) were found to have COPD diagnosed by means of spirometry. Out of these, 23 (4.4%) had COPD stage I, 42 (8.1%) had COPD II, 34 (6.6%) had COPD III, and 23 (4.4%) had COPD IV. Exposure to smoking, wooden stoves, pesticides, biomass fuel, aerosol sprays, gas grill and vehicle exhaust were found to be statistically significant factors in relation to development of COPD. Apparently healthy individuals may have underlying COPD and active screening by means of spirometry plays vital role in early detection of COPD. Smoking and exposure to certain hazardous environmental pollutants are responsible for the development and progression of COPD.

The diagnostic value of history and physical examination for COPD in suspected or known cases: a systematic review.

PubMed

Broekhuizen, Berna D L; Sachs, Alfred P E; Oostvogels, Rimke; Hoes, Arno W; Verheij, Theo J M; Moons, Karel G M

2009-08-01

According to current guidelines, spirometry should be performed in patients suspected of chronic obstructive pulmonary disease (COPD) by the results of history taking and physical examination. However, little is known about the diagnostic value of patient history and physical examination for COPD. To review the existing evidence on the diagnostic value of history taking and physical examination in recognizing COPD in patients suspected of COPD. A systematic literature search was performed in electronic medical databases. Studies were included after using defined inclusion and exclusion criteria and judged on their methodological quality by using the Quality Assessment of Diagnostic Accuracy Studies criteria. A formal meta-analysis was not performed because all studied items of history and physical examination were investigated in only in a maximum of three studies. Six studies were included. The history items dyspnoea, wheezing, previous consultation for wheezing or cough, self-reported COPD, age and smoking and the physical examination items wheezing, forced expiratory time, laryngeal height and prolonged expiration were found to have diagnostic value for COPD. These items were studied in maximally three studies and study population studies were heterogenic. The reference test for COPD in five of the six studies concerned obstructive lung disease in general and not COPD. There is insufficient evidence to assess the value of history taking and physical examination for diagnosing COPD.

The Effects of Air Pollution and Temperature on COPD.

PubMed

Hansel, Nadia N; McCormack, Meredith C; Kim, Victor

2016-06-01

Chronic Obstructive Pulmonary Disease (COPD) affects 12-16 million people in the United States and is the third-leading cause of death. In developed countries, smoking is the greatest risk factor for the development of COPD, but other exposures also contribute to the development and progression of the disease. Several studies suggest, though are not definitive, that outdoor air pollution exposure is linked to the prevalence and incidence of COPD. Among individuals with COPD, outdoor air pollutants are associated with loss of lung function and increased respiratory symptoms. In addition, outdoor air pollutants are also associated with COPD exacerbations and mortality. There is much less evidence for the impact of indoor air on COPD, especially in developed countries in residences without biomass exposure. The limited existing data suggests that indoor particulate matter and nitrogen dioxide concentrations are linked to increased respiratory symptoms among patients with COPD. In addition, with the projected increases in temperature and extreme weather events in the context of climate change there has been increased attention to the effects of heat exposure. Extremes of temperature-both heat and cold-have been associated with increased respiratory morbidity in COPD. Some studies also suggest that temperature may modify the effect of pollution exposure and though results are not conclusive, understanding factors that may modify susceptibility to air pollution in patients with COPD is of utmost importance.

Epidemiology of chronic obstructive pulmonary disease: a population-based study in Krasnoyarsk region, Russia.

PubMed

Artyukhov, Ivan P; Arshukova, Irina L; Dobretsova, Elena A; Dugina, Tatyana A; Shulmin, Andrey V; Demko, Irina V

2015-01-01

Krasnoyarsk region is a territory with the widespread risk factors for chronic obstructive pulmonary disease (COPD) such as tobacco smoke, air pollution, and occupational exposure. An assessment of COPD prevalence based on medical diagnosis statistics underestimates the true COPD prevalence. This study aims to evaluate how medical examinations may increase the accuracy of estimates of COPD prevalence. True COPD prevalence was estimated as a number of patients with the established disease diagnosis supplemented by the additional disease cases detected during medical examinations per 1,000 inhabitants of the region. Official medical statistics data and the data collected from the Global Alliance against Chronic Respiratory Diseases program 2011 among 15,000 inhabitants of the region aged 18 years and older were analyzed. This study revealed the COPD cases without official medical diagnosis. The true prevalence of COPD is estimated to be two times higher than the prevalence estimates based on medical diagnosis statistics. Undiagnosed and untreated cases of COPD result in severe COPD forms as well as addition of severe comorbidities. Because of this, there is an increase in the index of potential years of life lost. Conducting special medical examinations may increase the number of COPD cases detected at the early stages of the disease. This, in turn, may reduce the overall burden of the disease for the population of the region.

COPD assessment test and severity of airflow limitation in patients with asthma, COPD, and asthma-COPD overlap syndrome.

PubMed

Kurashima, Kazuyoshi; Takaku, Yotaro; Ohta, Chie; Takayanagi, Noboru; Yanagisawa, Tsutomu; Sugita, Yutaka

2016-01-01

The COPD assessment test (CAT) consists of eight nonspecific scores of quality of life. The aim of this study was to compare the health-related quality of life and severity of airflow limitation in patients with asthma, COPD, and asthma-COPD overlap syndrome (ACOS) using the CAT. We examined CAT and lung functions in 138 patients with asthma, 99 patients with COPD, 51 patients with ACOS, and 44 patients with chronic cough as a control. The CAT score was recorded in all subjects, and the asthma control test was also administered to patients with asthma and ACOS. The CAT scores were compared, and the relationships between the scores and lung function parameters were analyzed. The total CAT scores and scores for cough, phlegm, and dyspnea were higher in patients with ACOS than in patients with asthma and COPD. The total CAT scores were correlated with the percent predicted forced expiratory volume in 1 second only in patients with COPD. The total CAT scores and dyspnea scores adjusted by the percent predicted forced expiratory volume in 1 second were higher in patients with ACOS than in patients with COPD and asthma. The CAT scores and asthma control test scores were more closely correlated in patients with ACOS than in patients with asthma. Patients with ACOS have higher disease impacts and dyspnea sensation unproportional to the severity of airflow limitation.

Implementing chronic care for COPD: planned visits, care coordination, and patient empowerment for improved outcomes.

PubMed

Fromer, Len

2011-01-01

Current primary care patterns for chronic obstructive pulmonary disease (COPD) focus on reactive care for acute exacerbations, often neglecting ongoing COPD management to the detriment of patient experience and outcomes. Proactive diagnosis and ongoing multifactorial COPD management, comprising smoking cessation, influenza and pneumonia vaccinations, pulmonary rehabilitation, and symptomatic and maintenance pharmacotherapy according to severity, can significantly improve a patient's health-related quality of life, reduce exacerbations and their consequences, and alleviate the functional, utilization, and financial burden of COPD. Redesign of primary care according to principles of the chronic care model, which is implemented in the patient-centered medical home, can shift COPD management from acute rescue to proactive maintenance. The chronic care model and patient-centered medical home combine delivery system redesign, clinical information systems, decision support, and self-management support within a practice, linked with health care organization and community resources beyond the practice. COPD care programs implementing two or more chronic care model components effectively reduce emergency room and inpatient utilization. This review guides primary care practices in improving COPD care workflows, highlighting the contributions of multidisciplinary collaborative team care, care coordination, and patient engagement. Each primary care practice can devise a COPD care workflow addressing risk awareness, spirometric diagnosis, guideline-based treatment and rehabilitation, and self-management support, to improve patient outcomes in COPD.

Value of systematic intervention for chronic obstructive pulmonary disease in a regional Japanese city based on case detection rate and medical cost.

PubMed

Tawara, Yuichi; Senjyu, Hideaki; Tanaka, Kenichiro; Tanaka, Takako; Asai, Masaharu; Kozu, Ryo; Tabusadani, Mitsuru; Honda, Sumihisa; Sawai, Terumitsu

2015-01-01

We established a COPD taskforce for early detection, diagnosis, treatment, and intervention. We implemented a pilot intervention with a prospective and longitudinal design in a regional city. This study evaluates the usefulness of the COPD taskforce and intervention based on COPD case detection rate and per capita medical costs. We distributed a questionnaire to all 8,878 inhabitants aged 50-89 years, resident in Matsuura, Nagasaki Prefecture in 2006. Potentially COPD-positive persons received a pulmonary function test and diagnosis. We implemented ongoing detection, examination, education, and treatment interventions, performed follow-up examinations or respiratory lessons yearly, and supported the health maintenance of each patient. We compared COPD medical costs in Matsuura and in the rest of Nagasaki Prefecture using data from 2004 to 2013 recorded by the association of Nagasaki National Health Insurance Organization, assessing 10-year means and annual change. As of 2014, 256 people have received a definitive diagnosis of COPD; representing 31% of the estimated total number of COPD patients. Of the cases detected, 87.5% were mild or moderate in severity. COPD medical costs per patient in Matsuura were significantly lower than the rest of Nagasaki Prefecture, as was rate of increase in cost over time. The COPD program in Matsuura enabled early detection and treatment of COPD patients and helped to lower the associated burden of medical costs. The success of this program suggests that a similar program could reduce the economic and human costs of COPD morbidity throughout Japan.

Altitude and COPD prevalence: analysis of the PREPOCOL-PLATINO-BOLD-EPI-SCAN study.

PubMed

Horner, Andreas; Soriano, Joan B; Puhan, Milo A; Studnicka, Michael; Kaiser, Bernhard; Vanfleteren, Lowie E G W; Gnatiuc, Louisa; Burney, Peter; Miravitlles, Marc; García-Rio, Francisco; Ancochea, Julio; Menezes, Ana M; Perez-Padilla, Rogelio; Montes de Oca, Maria; Torres-Duque, Carlos A; Caballero, Andres; González-García, Mauricio; Buist, Sonia; Flamm, Maria; Lamprecht, Bernd

2017-08-23

COPD prevalence is highly variable and geographical altitude has been linked to it, yet with conflicting results. We aimed to investigate this association, considering well known risk factors. A pooled analysis of individual data from the PREPOCOL-PLATINO-BOLD-EPI-SCAN studies was used to disentangle the population effect of geographical altitude on COPD prevalence. Post-bronchodilator FEV1/FVC below the lower limit of normal defined airflow limitation consistent with COPD. High altitude was defined as >1500 m above sea level. Undiagnosed COPD was considered when participants had airflow limitation but did not report a prior diagnosis of COPD. Among 30,874 participants aged 56.1 ± 11.3 years from 44 sites worldwide, 55.8% were women, 49.6% never-smokers, and 12.9% (3978 subjects) were residing above 1500 m. COPD prevalence was significantly lower in participants living at high altitude with a prevalence of 8.5% compared to 9.9%, respectively (p < 0.005). However, known risk factors were significantly less frequent at high altitude. Hence, in the adjusted multivariate analysis, altitude itself had no significant influence on COPD prevalence. Living at high altitude, however, was associated with a significantly increased risk of undiagnosed COPD. Furthermore, subjects with airflow limitation living at high altitude reported significantly less respiratory symptoms compared to subjects residing at lower altitude. Living at high altitude is not associated with a difference in COPD prevalence after accounting for individual risk factors. However, high altitude itself was associated with an increased risk of undiagnosed COPD.

Surveillance of chronic obstructive pulmonary disease in high-risk individuals by using regional lung cancer mass screening.

PubMed

Sekine, Yasuo; Yanagibori, Ryoko; Suzuki, Kiminori; Sugiyama, Sonomi; Yamaji, Haruko; Ishibashi, Michiko; Fujisawa, Takehiko

2014-01-01

Patients with chronic obstructive pulmonary disease (COPD) are at risk for lung cancer; the diseases have common etiologies, including cigarette smoking. We aimed to clarify the effectiveness of COPD detection using a regional mass-screening program for lung cancer. A total of 7,067 residents of Togane, Chiba, Japan received lung cancer screening between May and July, 2011. We defined four groups of possible COPD candidates: group A (n=358), positive smoking history, positive chronic respiratory symptoms; group B (n=766), positive smoking history, positive lifestyle-related disease; group C (n=75), passive smoking history, positive chronic respiratory symptoms; and group D (n=301), passive smoking history, positive lifestyle-related disease. Candidates underwent on-site pulmonary function testing (PFT). The criteria for COPD candidates were fulfilled in 1,686 of 7,067 individuals (23.9%); 1,500 participants underwent PFT (89%), and 171 (11.4%) were diagnosed with COPD. The overall COPD detection rate was 2.4%. The frequency of COPD was significantly higher in groups A and B than in groups C and D (P=0.048); however, the distribution of COPD grades was similar among the groups (P=0.372). Multiple logistic regression analysis identified male sex, age 60 years or greater, and positive smoking history as risk factors for COPD. COPD screening using a community-based lung cancer-screening program may be effective for disease detection. Individuals who are 60 years of age or older with a positive smoking history should undergo PFT to detect COPD.

Detection of chronic obstructive pulmonary disease in community-based annual lung cancer screening: Chiba Chronic Obstructive Pulmonary Disease Lung Cancer Screening Study Group.

PubMed

Sekine, Yasuo; Fujisawa, Takehiko; Suzuki, Kiminori; Tsutatani, Shuko; Kubota, Kazuko; Ikegami, Hiroshi; Isobe, Yuji; Nakamura, Mitsugu; Takiguchi, Yuichi; Tatsumi, Koichiro

2014-01-01

Detection of chronic obstructive pulmonary disease (COPD) is crucial in the management of COPD. The aim of this study was to establish the utility of a community-based lung cancer screening for detecting COPD. In Japan, community-based lung cancer screening for residents who are 40 years or older using chest radiography is well established. A screening system in Chiba City, Japan, was used to detect COPD. The criteria to consider COPD at screening included age of 60 years or older, a smoking history and chronic respiratory symptoms. Participants fulfilling these criteria were referred for diagnostic evaluation consisting of pulmonary function testing (PFT) and chest computed tomography (CT). Of 89,100 Chiba City residents who underwent lung cancer screening, 72,653 residents were 60 years or older. Among them, 878 (1.0%) were identified with suspected COPD and referred for further evaluation. Of those identified, a total of 567 residents (64.6%, 567/878) underwent further evaluations, and 161 (28.4%) were reported to have COPD, with 38.5% of them requiring COPD treatment. To verify the diagnoses from the secondary evaluation centres, PFT and CT data were collected from 228 study participants, and 24.9% were diagnosed with COPD. CT findings classified according to the Goddard classification revealed that 20.1% of these participants had moderate to severe emphysema. COPD screening added to a community-based lung cancer screening programme may be effective in the detection of patients with COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Prevalence and etiological profile of chronic obstructive pulmonary disease in nonsmokers

PubMed Central

Mahmood, Tariq; Singh, Ravindra Kumar; Kant, Surya; Shukla, Amitabh Das; Chandra, Alok; Srivastava, Rajneesh Kumar

2017-01-01

Background: Tobacco smoking has been recognized as the most important risk factor for chronic obstructive pulmonary disease (COPD) for a long time, but recent studies have shown that nonsmokers also contribute to a significant proportion of COPD. This study was performed to find out the proportion of nonsmoker individuals among COPD patients and to determine various etiologies in nonsmoker COPD patients. Materials and Methods: This study was an observational cross-sectional study conducted in Department of Pulmonary Medicine, MLN Medical College, Allahabad. A total of 200 COPD patients, aged >18 years of either gender with COPD, diagnosed by clinical and spirometric criteria (GOLD guideline) were included in the study. Results: Of the 200 COPD patients, the proportion of nonsmoker patients was 56.5%, and the smoker was 43.5%. Among 113 nonsmoker COPD patients, maximum number of patients (69.03%) belonged to low socioeconomic status but most important and statistically significant risk factor was exposure to biomass smoke (53.98%), other significant risk factors were treated pulmonary tuberculosis (32.74%), and long-standing asthma (14.16%). Risk factors that were not statistically significant were occupational exposure (9.73%), exposure to outdoor air pollution (3.54%), and lower respiratory tract infection during childhood (1.77%). The patients who were exposed to more than one risk factors, developed COPD at an earlier age. Conclusions: This study revealed that nonsmokers contribute a significant proportion of COPD patients. Multiple risk factors other than smoking also play a major role in the development of COPD, particularly exposure to biomass smoke, treated pulmonary tuberculosis, and long-standing asthma. PMID:28360458

Insight into Best Variables for COPD Case Identification: A Random Forests Analysis.

PubMed

Leidy, Nancy K; Malley, Karen G; Steenrod, Anna W; Mannino, David M; Make, Barry J; Bowler, Russ P; Thomashow, Byron M; Barr, R G; Rennard, Stephen I; Houfek, Julia F; Yawn, Barbara P; Han, Meilan K; Meldrum, Catherine A; Bacci, Elizabeth D; Walsh, John W; Martinez, Fernando

This study is part of a larger, multi-method project to develop a questionnaire for identifying undiagnosed cases of chronic obstructive pulmonary disease (COPD) in primary care settings, with specific interest in the detection of patients with moderate to severe airway obstruction or risk of exacerbation. To examine 3 existing datasets for insight into key features of COPD that could be useful in the identification of undiagnosed COPD. Random forests analyses were applied to the following databases: COPD Foundation Peak Flow Study Cohort (N=5761), Burden of Obstructive Lung Disease (BOLD) Kentucky site (N=508), and COPDGene® (N=10,214). Four scenarios were examined to find the best, smallest sets of variables that distinguished cases and controls:(1) moderate to severe COPD (forced expiratory volume in 1 second [FEV 1 ] <50% predicted) versus no COPD; (2) undiagnosed versus diagnosed COPD; (3) COPD with and without exacerbation history; and (4) clinically significant COPD (FEV 1 <60% predicted or history of acute exacerbation) versus all others. From 4 to 8 variables were able to differentiate cases from controls, with sensitivity ≥73 (range: 73-90) and specificity >68 (range: 68-93). Across scenarios, the best models included age, smoking status or history, symptoms (cough, wheeze, phlegm), general or breathing-related activity limitation, episodes of acute bronchitis, and/or missed work days and non-work activities due to breathing or health. Results provide insight into variables that should be considered during the development of candidate items for a new questionnaire to identify undiagnosed cases of clinically significant COPD.

Prevalence and incidence of COPD in smokers and non-smokers: the Rotterdam Study.

PubMed

Terzikhan, Natalie; Verhamme, Katia M C; Hofman, Albert; Stricker, Bruno H; Brusselle, Guy G; Lahousse, Lies

2016-08-01

COPD is the third leading cause of death in the world and its global burden is predicted to increase further. Even though the prevalence of COPD is well studied, only few studies examined the incidence of COPD in a prospective and standardized manner. In a prospective population-based cohort study (Rotterdam Study) enrolling subjects aged ≥45, COPD was diagnosed based on a pre-bronchodilator obstructive spirometry (FEV1/FVC < 0.70). In absence of an interpretable spirometry within the Rotterdam Study, cases were defined as having COPD diagnosed by a physician on the basis of clinical presentation and obstructive lung function measured by the general practitioner or respiratory physician. Incidence rates were calculated by dividing the number of incident cases by the total number of person years of subjects at risk. In this cohort of 14,619 participants, 1993 subjects with COPD were identified of whom 689 as prevalent ones and 1304 cases as incident ones. The overall incidence rate (IR) of COPD was 8.9/1000 person-years (PY); 95 % Confidence Interval (CI) 8.4-9.4. The IR was higher in males and in smokers. The proportion of female COPD participants without a history of smoking was 27.2 %, while this proportion was 7.3 % in males. The prevalence of COPD in the Rotterdam Study is 4.7 % and the overall incidence is approximately 9/1000 PY, with a higher incidence in males and in smokers. The proportion of never-smokers among female COPD cases is substantial.

Role of the Lung Microbiome in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

PubMed

Wang, Lei; Hao, Ke; Yang, Ting; Wang, Chen

2017-09-05

The development of culture-independent techniques for microbiological analysis shows that bronchial tree is not sterile in either healthy or chronic obstructive pulmonary disease (COPD) individuals. With the advance of sequencing technologies, lung microbiome has become a new frontier for pulmonary disease research, and such advance has led to better understanding of the lung microbiome in COPD. This review aimed to summarize the recent advances in lung microbiome, its relationships with COPD, and the possible mechanisms that microbiome contributed to COPD pathogenesis. Literature search was conducted using PubMed to collect all available studies concerning lung microbiome in COPD. The search terms were "microbiome" and "chronic obstructive pulmonary disease", or "microbiome" and "lung/pulmonary". The papers in English about lung microbiome or lung microbiome in COPD were selected, and the type of articles was not limited. The lung is a complex microbial ecosystem; the microbiome in lung is a collection of viable and nonviable microbiota (bacteria, viruses, and fungi) residing in the bronchial tree and parenchymal tissues, which is important for health. The following types of respiratory samples are often used to detect the lung microbiome: sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa. Disordered bacterial microbiome is participated in pathogenesis of COPD; there are also dynamic changes in microbiota during COPD exacerbations. Lung microbiome may contribute to the pathogenesis of COPD by manipulating inflammatory and/or immune process. Normal lung microbiome could be useful for prophylactic or therapeutic management in COPD, and the changes of lung microbiome could also serve as biomarkers for the evaluation of COPD.

The development of an integrated care model for patients with severe or very severe chronic obstructive pulmonary disease (COPD): the COPD-Home model.

PubMed

Sunde, Synnøve; Walstad, Rolf Aksel; Bentsen, Signe Berit; Lunde, Solfrid J; Wangen, Eva Marie; Rustøen, Tone; Henriksen, Anne Hildur

2014-09-01

Adherence to guidelines for managing stable chronic obstructive pulmonary disease (COPD) and its exacerbations is inadequate among healthcare workers and patients. An appropriate care model would meet patient needs, enhance their coping with COPD and improve their quality of life (QOL). This study aims to present the 'COPD-Home' as an integrated care model for patients with severe or very severe COPD. One principle of the COPD-Home model is that hospital treatment should lead to follow up in the patient's home. The model also includes education, improved coordination of levels of care, improved accessibility and a management plan. One of the main elements of the COPD-Home model is the clear role of the home-care nurse. Model development is based on earlier research and clinical experience. It comprises: (i) education provided through an education programme for patients and involved nurses, (ii) joint visits and telephone checks, (iii) a call centre for support and communication with a general practitioner and (iv) an individualised self-management plan including home monitoring and a plan for pharmacological and nonpharmacological interventions. The COPD-Home model attempts to cultivate competences and behaviours of patients and community nurses that better accord with guidelines for interventions. The next step in its development will be to evaluate its ability to assist both healthcare workers and planners to improve the management of COPD, reduce exacerbations and improve QOL and coping among patients with COPD. © 2013 Nordic College of Caring Science.

[Epidemiology and COPD screening in France. Workshop from the Société de Pneumologie de Langue Française (SPLF)].

PubMed

Patout, M; Zysman, M; Raherison Semjen, C; Perez, T; Cuvelier, A; Roche, N

2014-10-01

A workshop has been organized in April 2013 by the Société de Pneumologie de Langue Française about COPD epidemiology and COPD screening in France and other European countries. This article deals with epidemiological data and their consequences on the French screening strategy. According to the most recent data, spirometric prevalence of COPD in France is 7.5% in individuals over 45 years old. During 2000-2002, COPD was responsible for 1.4% of all causes of death in France and was mentioned to be an associated cause of death in 3% of all death certificates. The average medical costs for one COPD patient is estimated to be 4366 €/year, until 7502 €/year in very severe COPD patients. All clinical studies that have been performed in France show that COPD screening via mini-spirometry is feasible in general practice or in an ambulatory setting; however, a mass screening proved to be difficult to perform. A simple technique like the Piko-6(®) implies a concomitant formalized training. The non-reimbursement by the French Social Security is also a limiting factor, as the absence of medical and economical validation of this strategy. Therefore, COPD screening should be focused to individuals at risk and should include tobacco issues and cessation. COPD screening strategies have to be medically evaluated and experiments have to take the specificities of the French health organization into consideration. Any COPD screening strategy should be considered as an overall fight against the tobacco epidemics.

Comparison of Three Screening Questionnaires for Chronic Obstructive Pulmonary Disease in the Primary Care.

PubMed

Spyratos, Dionisios; Haidich, Anna-Bettina; Chloros, Diamantis; Michalopoulou, Dionisia; Sichletidis, Lazaros

2017-01-01

Even though the diagnosis of chronic obstructive pulmonary disease (COPD) is easy and based mainly on spirometry and symptoms, the prevalence of underdiagnosis is extremely high. The use of simple screening tools (e.g., questionnaires, hand-held spirometers) has been proved to be a simple method for case finding of COPD. Nevertheless the most appropriate target group of the general population has not been specified yet. The aim of the present study was to compare 3 screening questionnaires among smokers aged >40 years in the primary care setting. We excluded all subjects with a previous medical diagnosis of bronchial asthma or chronic pulmonary disease other than COPD. All participants were in a stable clinical condition, filled in the International Primary Care Airways Group (IPAG) questionnaire, the COPD Population Screener (COPD-PS) questionnaire, and the Lung Function Questionnaire (LFQ) and underwent spirometry. Medical diagnosis of COPD was established by an experienced pulmonologist. We studied 3,234 subjects during a 3.5-year period. COPD prevalence was 10.9% (52.1% underdiagnosis). All 3 questionnaires showed extremely high negative predictive values (94-96%), so in this case the diagnosis of COPD could be safely excluded. The area under the curve was similar across the 3 questionnaires (AUCROC: 0.794-0.809). The COPD-PS questionnaire demonstrated the highest positive predictive value (41%) compared to the other 2. On the other hand, the IPAG questionnaire and LFQ demonstrated higher sensitivities than COPD-PS resulting in lower percentages of missed cases. Three validated screening questionnaires for COPD demonstrated different diagnostic characteristics. © 2017 S. Karger AG, Basel.

Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments.

PubMed

Zuo, Li; He, Feng; Sergakis, Georgianna G; Koozehchian, Majid S; Stimpfl, Julia N; Rong, Yi; Diaz, Philip T; Best, Thomas M

2014-08-01

Cigarette smoking (CS) can impact the immune system and induce pulmonary disorders such as chronic obstructive pulmonary disease (COPD), which is currently the fourth leading cause of chronic morbidity and mortality worldwide. Accordingly, the most significant risk factor associated with COPD is exposure to cigarette smoke. The purpose of the present study is to provide an updated overview of the literature regarding the effect of CS on the immune system and lungs, the mechanism of CS-induced COPD and oxidative stress, as well as the available and potential treatment options for CS-induced COPD. An extensive literature search was conducted on the PubMed/Medline databases to review current COPD treatment research, available in the English language, dating from 1976 to 2014. Studies have investigated the mechanism by which CS elicits detrimental effects on the immune system and pulmonary function through the use of human and animal subjects. A strong relationship among continued tobacco use, oxidative stress, and exacerbation of COPD symptoms is frequently observed in COPD subjects. In addition, therapeutic approaches emphasizing smoking cessation have been developed, incorporating counseling and nicotine replacement therapy. However, the inability to reverse COPD progression establishes the need for improved preventative and therapeutic strategies, such as a combination of intensive smoking cessation treatment and pharmaceutical therapy, focusing on immune homeostasis and redox balance. CS initiates a complex interplay between oxidative stress and the immune response in COPD. Therefore, multiple approaches such as smoking cessation, counseling, and pharmaceutical therapies targeting inflammation and oxidative stress are recommended for COPD treatment. Copyright © 2014 the American Physiological Society.

The Effect of Incidental Consolidation on Management and Outcomes in COPD Exacerbations: Data from the European COPD Audit.

PubMed

Saleh, Aarash; López-Campos, José Luis; Hartl, Sylvia; Pozo-Rodríguez, Francisco; Roberts, C Michael

2015-01-01

There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD). While some studies into eCOPD exclude these cases, consolidation is a common feature of eCOPD admissions in real practice. This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes. The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD. In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph. Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality. 14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without. The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change. Previous treatment with inhaled steroids was not associated. Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up. Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis. We recommend that these patients be considered a distinct subset in COPD exacerbation.

Defining the relationship between COPD and CVD: what are the implications for clinical practice?

PubMed Central

Morgan, Ann D; Zakeri, Rosita; Quint, Jennifer K

2018-01-01

Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD). CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality. The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself. Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade. But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population. The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors. In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence. We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD. While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years. Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. PMID:29355081

A multicenter family practitioners' research on Chronic Obstructive Pulmonary Disease screening using the COPD Assessment Test.

PubMed

Demirci, Hakan; Eniste, Koncuy; Basaran, Ebru Onuker; Ocakoglu, Gokhan; Yilmaz, Zeynep; Tuna, Sumeyye

2017-11-01

Spirometry is known to be a gold standard for the diagnosis of chronic obstructive pulmonary disease (COPD). COPD Assessment Test (CAT) is an eight-item questionnaire currently in use to evaluate patients with COPD. In the present study, we aimed to evaluate if CAT is an adequate tool for screening COPD. In total, 600 persons aging ⩾40 years old were randomly selected from three different family practice units located in the city center. CAT was asked to the participants and a spirometry was used to assess pulmonary obstruction. Pulmonary obstruction was defined as forced expiratory volume in first second/forced vital capacity (FEV1/FVC)<70% and then COPD diagnosis was confirmed with the reversibility test. The relationship between CAT results and pulmonary function test values was evaluated. In this sampling, the prevalence of COPD was 4.2%. Reliability of the CAT in the study group was acceptable (Cronbach's α: 0.84). The CAT scores was significantly higher in patients with COPD (P<0.001). There was a significant negative correlation between CAT score and FEV1, FVC and FEV1/FVC ratio (r=-0.31, P<0.001; r=-0.26, P<0.001; r=0.18, P=0.001). Among smokers, phlegm was the predominating symptom (P=0.01). Sensitivity of CAT was 66.67% and its specificity was 75.15% to determine COPD. CAT is a reliable questionnaire and there is an apparent relationship between the total CAT scores and COPD. However, CAT's ability to screen COPD is limited since it may miss the symptom-free cases.

Living with chronic obstructive pulmonary disease: a survey of patients' knowledge and attitudes.

PubMed

Hernandez, Paul; Balter, Meyer; Bourbeau, Jean; Hodder, Rick

2009-07-01

Chronic obstructive pulmonary disease (COPD) is a common respiratory condition and the fourth leading cause of death in Canada. However, little is known about the impact of COPD on the lives and attitudes of individuals living with this condition. The purpose of this study was to determine whether Canadians with COPD are properly educated and supported, and to recommend solutions to any care gaps identified. A total of 389 Canadians were surveyed who were 40 years of age and older, physician diagnosed with COPD, and current or former smokers. The telephone survey contained 68 items and took 35 min to complete. COPD severity was classified according to symptom severity using the Medical Research Council (MRC) score. Respondents tended to overestimate their disease severity and reported substantial symptom burden and psychosocial impact of living with COPD. Most individuals claimed to be well informed about COPD; however, their knowledge was poor in several domains including the causes of COPD, the consequences of inadequate therapy and the management of exacerbations. Family physicians were the main health care providers. A minority of respondents had seen a lung health educator. Only 34% had ever received a written action plan and only 33% had been told how to prevent an exacerbation. The symptom burden and psychosocial impact of living with COPD is substantial. There are significant gaps in patients' knowledge about the management of COPD and little contact with lung health educators. Increased use of COPD-specific, self-management education programs may help rectify these care gaps.

Employment and activity limitations among adults with chronic obstructive pulmonary disease--United States, 2013.

PubMed

Wheaton, Anne G; Cunningham, Timothy J; Ford, Earl S; Croft, Janet B

2015-03-27

Chronic obstructive pulmonary disease (COPD) is a group of progressive respiratory conditions, including emphysema and chronic bronchitis, characterized by airflow obstruction and symptoms such as shortness of breath, chronic cough, and sputum production. COPD is an important contributor to mortality and disability in the United States. Healthy People 2020 has several COPD-related objectives,* including to reduce activity limitations among adults with COPD. To assess the state-level prevalence of COPD and the association of COPD with various activity limitations among U.S. adults, CDC analyzed data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS). Among U.S. adults in all 50 states, the District of Columbia (DC), and two U.S. territories, 6.4% (an estimated 15.7 million adults) had been told by a physician or other health professional that they have COPD. Adults who reported having COPD were more likely to report being unable to work (24.3% versus 5.3%), having an activity limitation caused by health problems (49.6% versus 16.9%), having difficulty walking or climbing stairs (38.4% versus 11.3%), or using special equipment to manage health problems (22.1% versus 6.7%), compared with adults without COPD. Smokers who have been diagnosed with COPD are encouraged to quit smoking, which can slow the progression of the disease and reduce mobility impairment. In addition, COPD patients should consider participation in a pulmonary rehabilitation program that combines patient education and exercise training to address barriers to physical activity, such as respiratory symptoms and muscle wasting.

Beta Blockers for the Prevention of Acute Exacerbations of COPD

DTIC Science & Technology

2017-10-01

beta blockers , cardiovascular disease , COPD, exacerbation , metoprolol succinate, placebo- controlled, randomized 16. SECURITY CLASSIFICATION OF...basis. KEYWORDS: beta blockers cardiovascular disease COPD exacerbation metoprolol succinate placebo-controlled randomized...pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a

Standards of suitability for the management of chronic obstructive respiratory diseases.

PubMed

Sanguinetti, Claudio M; Ambrosino, Nicolino; Andò, Filippo; De Benedetto, Fernando; Donner, Claudio F; Nardini, Stefano; Polverino, Mario; Torchio, Roberto; Vagheggini, Guido; Visconti, Alberto

2014-01-01

Chronic Obstructive Pulmonary Disease (COPD) ranks third as cause of mortality and disability-adjusted life years (DALY) worldwide and also in Italy it imposes a huge health, social and economic load. Early symptoms of COPD are often disregarded by patients and physicians, spirometry is underutilized, and the diagnosis is delayed till the disease has reached a distinct severity level. Despite the availability of various guidelines, the behavior of health workers involved in the management of COPD is still rather unlike. These considerations are the reason why in October 2013 AIMAR (Interdisciplinary Scientific Association for Research in Lung Disease) devised and organized a "Third Consensus Conference", aimed at pointing out the standards of suitability for COPD management. In this context three important topics of discussion were identified: early and more widespread diagnosis, management of acute and subacute phases, long-term assistance to chronic patients. The procedure recommended by the Italian Health Superior Institute (ISS) for Consensus Conferences organization was applied. The Conference was structured in three sessions, each dealing with one of the above mentioned topics and including a short update of the subject-matter and presentation, discussion and voting of some statements with a choice ranging from total agreement to total disagreement or no knowledge. The results of voting were eventually recorded in the document, reviewed by an independent jury, that forms the substance of this paper. The essential role of spirometry, the need for distinguish between different COPD phenotypes, and the obligatoriness to base on the blood gas analysis findings the long-term oxygen therapy, were largely agreed, as well as the need for interventions aimed at decreasing the rate of acute exacerbations. More specific topics like the use of noninvasive ventilation, recognizing the factors affecting outcome and mortality, the choice of pharmacological and non pharmacological treatments in COPD patients led to lively discussing, but they did not always reach the total agreement, probably because of insufficient familiarity with these problems and of diversities in organization and instruments availability. The chronic respiratory assistance was treated with particular regard to smoking cessation, whose implementation is still insufficient. Many doubts rose due to uncertainty, lack of ability and standardization of procedures, insufficient institutional support, and difficulties to realize a network for assistance to chronic patients. The results of this Third Consensus Conference revealed some certainties and many doubts and diversities of view also on topics whose importance is well demonstrated in scientific literature. Thus, there is still a long distance to cover before reaching a suitable standardization of COPD management and such situation urges the need for improving not only the health professional's operativeness but also the organizational support by competent institutions. In this context some initiatives organized by AIMAR in cooperation with other respiratory scientific societies and patients' associations are going on.

Modeling the Normal and Neoplastic Cell Cycle with 'Realistic Boolean Genetic Networks': Their Application for Understanding Carcinogenesis and Assessing Therapeutic Strategies

NASA Technical Reports Server (NTRS)

Szallasi, Zoltan; Liang, Shoudan

2000-01-01

In this paper we show how Boolean genetic networks could be used to address complex problems in cancer biology. First, we describe a general strategy to generate Boolean genetic networks that incorporate all relevant biochemical and physiological parameters and cover all of their regulatory interactions in a deterministic manner. Second, we introduce 'realistic Boolean genetic networks' that produce time series measurements very similar to those detected in actual biological systems. Third, we outline a series of essential questions related to cancer biology and cancer therapy that could be addressed by the use of 'realistic Boolean genetic network' modeling.

River network architecture, genetic effective size and distributional patterns predict differences in genetic structure across species in a dryland stream fish community.

PubMed

Pilger, Tyler J; Gido, Keith B; Propst, David L; Whitney, James E; Turner, Thomas F

2017-05-01

Dendritic ecological network (DEN) architecture can be a strong predictor of spatial genetic patterns in theoretical and simulation studies. Yet, interspecific differences in dispersal capabilities and distribution within the network may equally affect species' genetic structuring. We characterized patterns of genetic variation from up to ten microsatellite loci for nine numerically dominant members of the upper Gila River fish community, New Mexico, USA. Using comparative landscape genetics, we evaluated the role of network architecture for structuring populations within species (pairwise F ST ) while explicitly accounting for intraspecific demographic influences on effective population size (N e ). Five species exhibited patterns of connectivity and/or genetic diversity gradients that were predicted by network structure. These species were generally considered to be small-bodied or habitat specialists. Spatial variation of N e was a strong predictor of pairwise F ST for two species, suggesting patterns of connectivity may also be influenced by genetic drift independent of network properties. Finally, two study species exhibited genetic patterns that were unexplained by network properties and appeared to be related to nonequilibrium processes. Properties of DENs shape community-wide genetic structure but effects are modified by intrinsic traits and nonequilibrium processes. Further theoretical development of the DEN framework should account for such cases. © 2017 John Wiley & Sons Ltd.

Protocols to Evaluate Cigarette Smoke-Induced Lung Inflammation and Pathology in Mice.

PubMed

Vlahos, Ross; Bozinovski, Steven

2018-01-01

Cigarette smoking is a major cause of chronic obstructive pulmonary disease (COPD). Inhalation of cigarette smoke causes inflammation of the airways, airway wall remodelling, mucus hypersecretion and progressive airflow limitation. Much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities and infectious (viral and bacterial) exacerbations (AECOPD). Comorbidities, in particular skeletal muscle wasting, cardiovascular disease and lung cancer markedly impact on disease morbidity, progression and mortality. The mechanisms and mediators underlying COPD and its comorbidities are poorly understood and current COPD therapy is relatively ineffective. Many researchers have used animal modelling systems to explore the mechanisms underlying COPD, AECOPD and comorbidities of COPD with the goal of identifying novel therapeutic targets. Here we describe a mouse model that we have developed to define the cellular, molecular and pathological consequences of cigarette smoke exposure and the development of comorbidities of COPD.

COPD management: role of symptom assessment in routine clinical practice

PubMed Central

van der Molen, Thys; Miravitlles, Marc; Kocks, Janwillem WH

2013-01-01

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life. Despite this, COPD treatment and its management are mainly based on lung function assessments. There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives. Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD. Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice. In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. PMID:24143085

Convergence in the Epidemiology and Pathogenesis of COPD and Pneumonia.

PubMed

Gautam, Sanjay S; O'Toole, Ronan F

2016-12-01

Chronic obstructive pulmonary disease (COPD) is one of the main causes of human mortalities globally after heart disease and stroke. There is increasing evidence of an aetiological association between COPD and pneumonia, the leading infectious cause of death globally in children under 5 years. In this review, we discuss the known risk factors of COPD that are also shared with pneumonia including smoking, air pollution, age and immune suppression. We review how lung pathology linked to a previous history of pneumonia may heighten susceptibility to the development of COPD in later life. Furthermore, we examine how specific aspects of COPD immunology could contribute to the manifestation of pneumonia. Based on the available evidence, a convergent relationship is becoming apparent with respect to the pathogenesis of COPD and pneumonia. This has implications for the management of both diseases, and the development of new interventions.

Comorbidities and Chronic Obstructive Pulmonary Disease: Prevalence, Influence on Outcomes, and Management

PubMed Central

Putcha, Nirupama; Drummond, M. Bradley; Wise, Robert A.; Hansel, Nadia N.

2016-01-01

Comorbidities impact a large proportion of patients with chronic obstructive pulmonary disease (COPD), with over 80% of patients with COPD estimated to have at least one comorbid chronic condition. Guidelines for the treatment of COPD are just now incorporating comorbidities to their management recommendations of COPD, and it is becoming increasingly clear that multimorbidity as well as specific comorbidities have strong associations with mortality and clinical outcomes in COPD, including dyspnea, exercise capacity, quality of life, healthcare utilization, and exacerbation risk. Appropriately, there has been an increased focus upon describing the burden of comorbidity in the COPD population and incorporating this information into existing efforts to better understand the clinical and phenotypic heterogeneity of this group. In this article, we summarize existing knowledge about comorbidity burden and specific comorbidities in COPD, focusing on prevalence estimates, association with outcomes, and existing knowledge about treatment strategies. PMID:26238643

Paradigms in Chronic Obstructive Pulmonary Disease: Phenotypes, Immunobiology, and Therapy with a Focus on Vascular Disease

PubMed Central

Schivo, Michael; Albertson, Timothy E.; Haczku, Angela; Kenyon, Nicholas J.; Zeki, Amir A.; Kuhn, Brooks T.; Louie, Samuel; Avdalovic, Mark V.

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a complex and heterogenous syndrome that represents a major global health burden. COPD phenotypes have recently emerged based on large cohort studies addressing the need to better characterize the syndrome. Though comprehensive phenotyping is still at an early stage, factors such as ethnicity and radiographic, serum, and exhaled breath biomarkers have shown promise. COPD is also an immunological disease where innate and adaptive immune responses to the environment and tobacco smoke are altered. The frequent overlap between COPD and other systemic diseases, such as cardiovascular disease, have influenced COPD therapy, and treatments for both conditions may lead to improved patient outcomes. Here we discuss current paradigms that center on improving the definition of COPD, understanding the immunological overlap between COPD and vascular inflammation, and the treatment of COPD—with a focus on comorbid cardiovascular disease. PMID:28258130

COPD and occupational exposures: a case-control study.

PubMed

Weinmann, Sheila; Vollmer, William M; Breen, Victor; Heumann, Michael; Hnizdo, Eva; Villnave, Jacqueline; Doney, Brent; Graziani, Monica; McBurnie, Mary Ann; Buist, A Sonia

2008-05-01

Evidence demonstrates that occupational exposures are causally linked with chronic obstructive pulmonary disease (COPD). This case-control study evaluated the association between occupational exposures and prevalent COPD based on lifetime occupational history. Cases (n = 388) aged 45 years and older with COPD were compared with controls (n = 356), frequency matched on age, sex, and cigarette smoking history. Odds ratios for exposure to each of eight occupational hazard categories and three composite measures of exposure were computed using logistic regression. RESULTSOccupational exposures most strongly associated with COPD were diesel exhaust, irritant gases and vapors, mineral dust, and metal dust. The composite measures describing aggregate exposure to gases, vapors, solvents, or sensitizers (GVSS) and aggregate exposure to dust, GVSS, or diesel exhaust were also associated with COPD. In the small group of never-smokers, a similar pattern was evident. These population-based findings add to the literature linking occupational exposures to COPD.

COPD: Are You at Risk?

MedlinePlus

... trademark of HHS. 2 CoulD you be at risk For CoPD? yes, iF you: useD to smoke, or still Do COPD most often occurs in people age 40 and over who are current or former smokers. Smoking is the most common cause of COPD, accounting for as many as 9 out of 10 ...

Determinants of dynamic hyperinflation during metronome-paced tachypnea in COPD and normal subjects.

PubMed

Cooper, C B; Calligaro, G L; Quinn, M M; Eshaghian, P; Coskun, F; Abrazado, M; Bateman, E D; Raine, R I

2014-01-01

In COPD, dynamic hyperinflation (DH) occurs during exercise and during metronome-paced tachypnea (MPT). We investigated the relationship of DH with breathing pattern and ventilation (V˙E) in COPD and normal subjects (NS). In 35 subjects with moderate COPD and 17 younger healthy volunteers we measured inspiratory capacity (IC), breathing frequency (fR), expiratory time (TE), ventilation (V˙E) and end-tidal carbon dioxide tension (PETCO2) at baseline and after 30s of MPT at 40breaths/min with metronome-defined I:E ratios of 1:1 and 1:2. A reduction in IC (ΔIC) was taken to indicate DH. In COPD subjects, DH correlated with TE but not with V˙E or PETCO2, and was best predicted by total lung capacity. NS also showed DH (although less than in COPD), which correlated with PETCO2 but not with fR, TE or V˙E. We conclude that MPT evokes DH in both NS and patients with COPD. TE is the most important determinant of DH during MPT in patients with COPD. Copyright © 2013 Elsevier B.V. All rights reserved.

Autoantibodies of IgM and IgG classes show differences in recognition of multiple autoantigens in chronic obstructive pulmonary disease.

PubMed

Shindi, Reham; Almehairi, Amna; Negm, Ola H; Kalsheker, Noor; Gale, Nichola S; Shale, Dennis J; Harrison, Timothy W; Bolton, Charlotte E; John, Michelle; Todd, Ian; Tighe, Patrick J; Fairclough, Lucy C

2017-10-01

Autoimmunity occurs in chronic obstructive pulmonary disease (COPD). We describe an antigen microarray for detecting serum autoantibodies (AAbs) to determine how IgM, as well as IgG, AAbs distinguish patients with COPD from controls with a history of smoking without COPD. All COPD patients' sera contained elevated levels of AAbs to some of 30 autoantigens. There were significant differences in the autoantigenic specificities of IgM AAbs compared to IgG AAbs in the COPD sera: for example, AAbs to histone and scl-70 were mainly IgG, whereas AAbs to CENP-B and La/ssB were mainly IgM; by contrast, IgM and IgG AAbs to collagen-V were equally prevalent. Thus, a combination of IgM and IgG AAbs specific for multiple autoantigens are detected in all cases of COPD at a level at which all non-COPD controls are negative for AAbs. This highlights the importance of different classes of AAbs to a range of autoantigens in COPD. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary prevention of chronic obstructive pulmonary disease in primary care.

PubMed

van der Molen, Thys; Schokker, Siebrig

2009-12-01

Chronic obstructive pulmonary disease (COPD) is a prevalent disease, with cigarette smoking being the main risk factor. Prevention is crucial in the fight against COPD. Whereas primary prevention is targeted on whole populations, patient populations are the focus of primary care; therefore, prevention in this setting is mainly aimed at preventing further deterioration of the disease in patients who present with the first signs of disease (secondary prevention). Prevention of COPD in primary care requires detection of COPD at an early stage. An accurate definition of COPD is crucial in this identification process. The benefits of detecting new patients with COPD should be determined before recommending screening and case-finding programs in primary care. No evidence is available that screening by spirometry results in significant health gains. Effective treatment options in patients with mild disease are lacking. Smoking cessation is the cornerstone of COPD prevention. Because cigarette smoking is not only a major cause of COPD but is also a major cause of many other diseases, a decline in tobacco smoking would result in substantial health benefits.

Electronic clinical records in primary care for estimating disease burden and management. An example of COPD.

PubMed

Verde-Remeseiro, Luis; López-Pardo, Estrella; Ruano-Ravina, Alberto; Gude-Sampedro, Francisco; Castro-Calvo, Ramón

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a significant health problem in developed countries. We aimed to estimate the prevalence of COPD in a single Spanish healthcare area. We also aimed to assess if there are any differences in prevalence and spirometry use among primary care services by utilizing already registered information. We designed a cross-sectional study to determine the prevalence of COPD and the performance of spirometries in each primary care service. A total of 8,444 patients were diagnosed with COPD, with a prevalence of 2.6% for individuals older than 39 years. The prevalence increased with age and was much higher in men. Significant heterogeneity was found in the prevalence of COPD and spirometry use among primary care services. COPD was underdiagnosed and there was wide variability in spirometry use in our area. Greater efforts are needed to diagnose COPD in order to improve its clinical outcomes and to refine registries so that they can be used as reliable sources of information. Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.

Cognitive impairment in COPD: a systematic review.

PubMed

Torres-Sánchez, Irene; Rodríguez-Alzueta, Elisabeth; Cabrera-Martos, Irene; López-Torres, Isabel; Moreno-Ramírez, Maria Paz; Valenza, Marie Carmen

2015-01-01

The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD.

The geography of chronic obstructive pulmonary disease: a population-based study of Norway.

PubMed

Halvorsen, Thomas; Martinussen, Pål E

2014-06-01

Research on chronic obstructive pulmonary disease (COPD) that includes geographic information is important in order to improve care and appropriate allocation of resources to patients suffering from COPD. The purpose of this study is to investigate the geography of COPD and factors associated with the spatial patterns of COPD prevalence. Particular emphasis is put on the role of the local socioeconomic environment. Utilising information from the Norwegian Prescription Database on all lung medication prescribed in 2009 we identified 62,882 persons with COPD in the Norwegian population. Patterns of spatial clustering in the prevalence of COPD are clearly evident, even when age and gender are controlled for. Gender and age are strongly related to COPD risk. Socio-economic characteristics of the community such as education and unemployment are also significantly correlated with COPD risk. People living in rural parts of the country are generally associated with less risk than people in urban settings, and in particular people living in communities with high levels of farm and fisheries employment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diseases Burden of Chronic Obstructive Pulmonary Disease (COPD) Attributable to Ground-Level Ozone in Thailand: Estimates Based on Surface Monitoring Measurements Data.

PubMed

Pinichka, Chayut; Bundhamcharoen, Kanitta; Shibuya, Kenji

2015-05-14

Ambient ozone (O3) pollution has increased globally since preindustrial times. At present, O3 is one of the major air pollution concerns in Thailand, and is associated with health impacts such as chronic obstructive pulmonary disease (COPD). The objective of our study is to estimate the burden of disease attributed to O3 in 2009 in Thailand based on empirical evidence. We estimated disability-adjusted life years (DALYs) attributable to O3 using the comparative risk assessment framework in the Global Burden of Diseases (GBD) study. We quantified the population attributable fraction (PAF), integrated from Geographic Information Systems (GIS)-based spatial interpolation, the population distribution of exposure, and the exposure-response coefficient to spatially characterize exposure to ambient O3 pollution on a national scale. Exposure distribution was derived from GIS-based spatial interpolation O3 exposure model using Pollution Control Department Thailand (PCD) surface air pollution monitor network sources. Relative risk (RR) and population attributable fraction (PAF) were determined using health impact function estimates for O3. PAF (%) of COPD attributable to O3 were determined by region: at approximately, Northern=2.1, Northeastern=7.1, Central=9.6, Eastern=1.75, Western=1.47 and Southern=1.74. The total COPD burden attributable to O3 for Thailand in 2009 was 61,577 DALYs. Approximately 0.6% of the total DALYs in Thailand is male: 48,480 DALYs; and female: 13,097 DALYs. This study provides the first empirical evidence on the health burden (DALYs) attributable to O3 pollution in Thailand. Varying across regions, the disease burden attributable to O3 was 0.6% of the total national burden in 2009. Better empirical data on local specific sites, e.g. urban and rural areas, alternative exposure assessment, e.g. land use regression (LUR), and a local concentration-response coefficient are required for future studies in Thailand.

Assessment of in vitro COPD models for tobacco regulatory science: Workshop proceedings, conclusions and paths forward for in vitro model use.

PubMed

Behrsing, Holger; Raabe, Hans; Manuppello, Joseph; Bombick, Betsy; Curren, Rodger; Sullivan, Kristie; Sethi, Sanjay; Phipps, Richard; Tesfaigzi, Yohannes; Yan, Sherwin; D'Ruiz, Carl; Tarran, Robert; Constant, Samuel; Phillips, Gary; Gaça, Marianna; Hayden, Patrick; Cao, Xuefei; Mathis, Carole; Hoeng, Julia; Braun, Armin; Hill, Erin

2016-05-01

The Family Smoking Prevention and Tobacco Control Act of 2009 established the Food and Drug Administration Center for Tobacco Products (FDA-CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 8-10 December 2014, IIVS organised a workshop conference, entitled Assessment of In Vitro COPD Models for Tobacco Regulatory Science, to bring together stakeholders representing regulatory agencies, academia, industry and animal protection, to address the research priorities articulated by the FDA-CTP. Specific topics were covered to assess the status of current in vitro technologies as they are applied to understanding the adverse pulmonary events resulting from tobacco product exposure, and in particular, the progression of chronic obstructive pulmonary disease (COPD). The four topics covered were: a) Inflammation and Oxidative Stress; b) Ciliary Dysfunction and Ion Transport; c) Goblet Cell Hyperplasia and Mucus Production; and d) Parenchymal/Bronchial Tissue Destruction and Remodelling. The 2.5 day workshop included 18 expert speakers, plus poster sessions, networking and breakout sessions, which identified key findings and provided recommendations to advance the in vitro technologies and assays used to evaluate tobacco-induced disease etiologies. The workshop summary was reported at the 2015 Society of Toxicology Annual Meeting, and the recommendations led to an IIVS-organised technical workshop in June 2015, entitled Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays, to assess these assays and to conduct a proof-of-principle multi-laboratory exercise to determine their suitability for standardisation. Here, we report on the proceedings, recommendations and outcomes of the December 2014 workshop, including paths forward to continue the development of non-animal methods to evaluate tissue responses that model the disease processes that may lead to COPD, a major cause of mortality worldwide. 2016 FRAME.

Stakeholder Priorities for Comparative Effectiveness Research in Chronic Obstructive Pulmonary Disease

PubMed Central

Lindenauer, Peter K.; Au, David H.; Carson, Shannon S.; Lee, Todd A.; McBurnie, Mary Ann; Naureckas, Edward T.; Vollmer, William M.; Mularski, Richard A.

2013-01-01

Comparative effectiveness research (CER) is intended to address the expressed needs of patients, clinicians, and other stakeholders. Representatives of 54 stakeholder groups with an interest in chronic obstructive pulmonary disease (COPD) participated in workshops convened by the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation (CONCERT) over a 2-year period. Year 1 focused on chronic care and care coordination. Year 2 focused on acute care and transitions in care between healthcare settings. Discussions and provisional voting were conducted via teleconferences and e-mail exchanges before the workshop. Final prioritization votes occurred after in-person discussions at the workshop. We used a modified Delphi approach to facilitate discussions and consensus building. To more easily quantify preferences and to evaluate the internal consistency of rankings, the Analytic Hierarchy Process was incorporated in Year 2. Results of preworkshop and final workshop voting often differed, suggesting that prioritization efforts relying solely on requests for topics from stakeholder groups without in-person discussion may provide different research priorities. Research priorities varied across stakeholder groups, but generally focused on studies to evaluate different approaches to healthcare delivery (e.g., spirometry for diagnosis and treatment, integrated healthcare strategies during transitions in care) rather than head-to-head comparisons of medications. This research agenda may help to inform groups intending to respond to CER funding opportunities in COPD. The methodologies used, detailed in the online supplement, may also help to inform prioritization efforts for CER in other health conditions. PMID:23155144

Stakeholder priorities for comparative effectiveness research in chronic obstructive pulmonary disease: a workshop report.

PubMed

Krishnan, Jerry A; Lindenauer, Peter K; Au, David H; Carson, Shannon S; Lee, Todd A; McBurnie, Mary Ann; Naureckas, Edward T; Vollmer, William M; Mularski, Richard A

2013-02-01

Comparative effectiveness research (CER) is intended to address the expressed needs of patients, clinicians, and other stakeholders. Representatives of 54 stakeholder groups with an interest in chronic obstructive pulmonary disease (COPD) participated in workshops convened by the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation (CONCERT) over a 2-year period. Year 1 focused on chronic care and care coordination. Year 2 focused on acute care and transitions in care between healthcare settings. Discussions and provisional voting were conducted via teleconferences and e-mail exchanges before the workshop. Final prioritization votes occurred after in-person discussions at the workshop. We used a modified Delphi approach to facilitate discussions and consensus building. To more easily quantify preferences and to evaluate the internal consistency of rankings, the Analytic Hierarchy Process was incorporated in Year 2. Results of preworkshop and final workshop voting often differed, suggesting that prioritization efforts relying solely on requests for topics from stakeholder groups without in-person discussion may provide different research priorities. Research priorities varied across stakeholder groups, but generally focused on studies to evaluate different approaches to healthcare delivery (e.g., spirometry for diagnosis and treatment, integrated healthcare strategies during transitions in care) rather than head-to-head comparisons of medications. This research agenda may help to inform groups intending to respond to CER funding opportunities in COPD. The methodologies used, detailed in the online supplement, may also help to inform prioritization efforts for CER in other health conditions.

Development of the Assessment of Burden of COPD tool: an integrated tool to measure the burden of COPD.

PubMed

Slok, Annerika H M; in 't Veen, Johannes C C M; Chavannes, Niels H; van der Molen, Thys; Rutten-van Mölken, Maureen P M H; Kerstjens, Huib A M; Salomé, Philippe L; Holverda, Sebastiaan; Dekhuijzen, P N Richard; Schuiten, Denise; Asijee, Guus M; van Schayck, Onno C P

2014-07-10

In deciding on the treatment plan for patients with chronic obstructive pulmonary disease (COPD), the burden of COPD as experienced by patients should be the core focus. It is therefore important for daily practice to develop a tool that can both assess the burden of COPD and facilitate communication with patients in clinical practice. This paper describes the development of an integrated tool to assess the burden of COPD in daily practice. A definition of the burden of COPD was formulated by a Dutch expert team. Interviews showed that patients and health-care providers agreed on this definition. We found no existing instruments that fully measured burden of disease according to this definition. However, the Clinical COPD Questionnaire meets most requirements, and was therefore used and adapted. The adapted questionnaire is called the Assessment of Burden of COPD (ABC) scale. In addition, the ABC tool was developed, of which the ABC scale is the core part. The ABC tool is a computer program with an algorithm that visualises outcomes and provides treatment advice. The next step in the development of the tool is to test the validity and effectiveness of both the ABC scale and tool in daily practice.

Development of the Assessment of Burden of COPD tool: an integrated tool to measure the burden of COPD

PubMed Central

Slok, Annerika H M; in ’t Veen, Johannes C C M; Chavannes, Niels H; van der Molen, Thys; Rutten-van Mölken, Maureen P M H; Kerstjens, Huib A M; Salomé, Philippe L; Holverda, Sebastiaan; Dekhuijzen, PN Richard; Schuiten, Denise; Asijee, Guus M; van Schayck, Onno C P

2014-01-01

In deciding on the treatment plan for patients with chronic obstructive pulmonary disease (COPD), the burden of COPD as experienced by patients should be the core focus. It is therefore important for daily practice to develop a tool that can both assess the burden of COPD and facilitate communication with patients in clinical practice. This paper describes the development of an integrated tool to assess the burden of COPD in daily practice. A definition of the burden of COPD was formulated by a Dutch expert team. Interviews showed that patients and health-care providers agreed on this definition. We found no existing instruments that fully measured burden of disease according to this definition. However, the Clinical COPD Questionnaire meets most requirements, and was therefore used and adapted. The adapted questionnaire is called the Assessment of Burden of COPD (ABC) scale. In addition, the ABC tool was developed, of which the ABC scale is the core part. The ABC tool is a computer program with an algorithm that visualises outcomes and provides treatment advice. The next step in the development of the tool is to test the validity and effectiveness of both the ABC scale and tool in daily practice. PMID:25010353

Nutritional deficits in elderly smokers with respiratory symptoms that do not fulfill the criteria for COPD

PubMed Central

Obase, Yasushi; Mouri, Keiji; Shimizu, Hiroki; Ohue, Yoshihiro; Kobashi, Yoshihiro; Kawahara, Kazue; Oka, Mikio

2011-01-01

Background and objective Whereas nutrition deficits are recognized as an expression of systemic inflammation in the elderly with diagnosed chronic obstructive pulmonary disease (COPD), if they occur in symptomatic elderly smokers, unfulfilled COPD criteria are not confirmed. Methods Respiratory function, anthropometry assessment, and diet intake evaluation of 13 COPD patients (COPD group), ten symptomatic elderly smokers (SYSM group), and 27 healthy volunteers (control group) were compared. All were 70 years old or older. Results The SYSM group had lower body weight, body mass index, percentage ideal body weight, body fat percentage, arm muscle circumference, tricep skin fold thickness, serum albumin, prealbumin, and transferrin than the control group and were similar to the COPD group (P < 0.05 each and nonsignificant each). Resting energy expenditure was no different among the groups. Intake of energy, vitamins (A, B1, B2, and C), calcium, iron, fiber, and sodium was also lower in the SYSM group than in the control group (P < 0.05 all) and was similar to the COPD group. Conclusion Elderly smokers who are symptomatic but who do not fulfill the COPD diagnostic criteria have nutritional deficits related to insufficient energy intake that are similar to those seen in COPD patients. PMID:22259244

Pulmonary rehabilitation in COPD - available resources and utilization in Swedish primary and secondary care.

PubMed

Sundh, Josefin; Lindgren, Helena; Hasselgren, Mikael; Montgomery, Scott; Janson, Christer; Ställberg, Björn; Lisspers, Karin

2017-01-01

Pulmonary rehabilitation is effective in all stages of COPD. The availability and utilization of pulmonary rehabilitation resources, and the characteristics of COPD patients receiving rehabilitation, were investigated in primary and secondary care in central Sweden. Data on available pulmonary rehabilitation resources were collected using questionnaires, to 14 hospitals and 54 primary health care centers, and information on utilization of different rehabilitation professionals was obtained from questionnaires completed by 1,329 COPD patients from the same centers. Multivariable logistic regression examined associations with having received rehabilitation in the previous year. In primary care, nurse-based asthma/COPD clinics were common (87%), with additional separate access to other rehabilitation professionals. In secondary care, rehabilitation was more often offered as part of a multidisciplinary teamwork (71%). In total, 36% of the patients met an asthma/COPD nurse in the previous year. Utilization was lower in primary than in secondary care for physiotherapists (7% vs 16%), occupational therapists (3% vs 10%), nutritionists (5% vs 13%), and counselors (1% vs 4%). A higher COPD Assessment Test score and frequent exacerbations were associated with higher utilization of all rehabilitation professionals. Pulmonary rehabilitation resources are available but underutilized, and receiving rehabilitation is more common in severe COPD. Treatment recommendations need to be better implemented, especially in mild and moderate COPD.

Electronic health records and improved nursing management of chronic obstructive pulmonary disease.

PubMed

Liu, Fengping; Zou, Yeqing; Huang, Qingmei; Zheng, Li; Wang, Wei

2015-01-01

This paper identifies evolving trends in the diagnosis and treatment of chronic obstructive pulmonary disease (COPD), and recommends the integration of nursing strategies in COPD management via widespread implementation of electronic health records. COPD is a complex lung disease with diverse origins, both physical and behavioral, manifested in a wide range of symptoms that further increase the patient's risk for comorbidities. Early diagnosis and effective management of COPD require monitoring of a dizzying array of COPD symptoms over extended periods of time, and nurses are especially well positioned to manage potential progressions of COPD, as frontline health care providers who obtain, record, and organize patient data. Developments in medical technology greatly aid nursing management of COPD, from the deployment of spirometry as a diagnostic tool at the family practice level to newly approved treatment options, including non-nicotine pharmacotherapies that reduce the cravings associated with tobacco withdrawal. Among new medical technologies, electronic health records have proven particularly advantageous in the management of COPD, enabling providers to gather, maintain, and reference more patient data than has ever been possible before. Thus, consistent and widespread implementation of electronic health records facilitates the coordination of diverse treatment strategies, resulting in increased positive health outcomes for patients with COPD.

Natural course of early COPD.

PubMed

Rhee, Chin Kook; Kim, Kyungjoo; Yoon, Hyoung Kyu; Kim, Jee-Ae; Kim, Sang Hyun; Lee, Sang Haak; Park, Yong Bum; Jung, Ki-Suck; Yoo, Kwang Ha; Hwang, Yong Il

2017-01-01

Few studies have examined the natural course of early COPD. The aim of this study was to observe the natural course of early COPD patients. We also aimed to analyze medical utilization and costs for early COPD during a 6-year period. Patients with early COPD were selected from Korean National Health and Nutrition Examination Survey (KNHANES) data. We linked the KNHANES data of patients with early COPD to National Health Insurance data. A total of 2,397 patients were enrolled between 2007 and 2012. The mean forced expiratory volume in 1 second (FEV 1 ) was 78.6%, and the EuroQol five dimensions questionnaire (EQ-5D) index value was 0.9. In total, 110 patients utilized health care for COPD in 2007, and this number increased to 179 in 2012. The total mean number of days used per person increased from 4.9 in 2007 to 7.8 in 2012. The total medical cost per person also increased from 248.8 US dollar (USD) in 2007 to 780.6 USD in 2013. A multiple linear regression revealed that age, lower body mass index, lower FEV 1 (%), and lower EQ-5D score were significantly associated with medical costs. Even in early COPD patients, some of them eventually progressed and utilized health care for COPD.

Identification of Oxidative Stress Related Proteins as Biomarkers for Lung Cancer and Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage

PubMed Central

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L.; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-01-01

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis. PMID:23389041

Identification of oxidative stress related proteins as biomarkers for lung cancer and chronic obstructive pulmonary disease in bronchoalveolar lavage.

PubMed

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-02-06

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.

Cigarette smoke-induced chronic obstructive pulmonary disease is attenuated by CCL20-blocker: a rat model.

PubMed

Sun, Desheng; Ouyang, Yao; Gu, Yanhui; Liu, Xiansheng

2016-08-31

To evaluate whether the effect of dendritic cells (DCs) on chronic obstructive pulmonary disease (COPD) can be relieved by blocking CCL20. 30 Wistar rats were randomly divided into three groups: control, COPD, and COPD treated with CCL20 monoclonal antibody. In the latter two groups, COPD was induced by four-week cigarette smoke exposure and trachea injection of lipopolysaccharide solution on two occasions. CCL20 monoclonal antibody was injected intraperitoneally on the first day. All animals were sacrificed on the 29th day. Pathomorphology of the lung and bronchiole was analyzed using hematoxylin and eosin staining. The CCR6 content in the bronchoalveolar lavage fluid was detected using ELISA. DC distribution in the lung was examined by immunohistochemistry for OX62. COPD rat models showed pathological alterations similar to those in COPD patients. DCs, CCR6, and the severity of emphysema were significantly increased in the COPD group than in controls (all P values <0.001), and they were significantly reduced after anti-CCL20 treatment compared with the COPD group (all P values <0.05). The interaction between CCR6 and its ligand CCL20 promotes the effect of DCs in the COPD pathogenesis, which can be reduced by blocking CCL20.

Burden of COPD, Asthma, and Concomitant COPD and Asthma Among Adults

PubMed Central

Shaya, Fadia T.; Maneval, Mark S.; Gbarayor, Confidence M.; Sohn, Kyongsei; Dalal, Anand A.; Du, Dongyi; Scharf, Steven M.

2009-01-01

Background: Asthma and COPD are characterized by substantial racial disparities in morbidity and mortality. We hypothesized that because African-American patients with these conditions experience greater mortality and morbidity than their white counterparts, they would use more health-care resources when no difference in health insurance exists. Methods: A retrospective, population-based cohort study was conducted using Maryland Medicaid Managed Care patient encounter data. We compared health services utilization and cost outcomes in both African-American and white patients with COPD, asthma, or coexisting COPD and asthma. Results: The study population consisted of 9,131 patients with COPD, asthma, or both conditions. Of the total population, 52% were African American (n = 4,723), and 44% were white (n = 4,021); all other races were combined into the “unknown race” category to account for the remaining 4% (n = 387). After controlling for age, gender, cohort allocation, and comorbidities, we found that African-American adults with COPD, asthma, or coexisting COPD and asthma actually used fewer medical services and accounted for lower medical costs than white adults. Conclusions: Lower health services utilization and medical costs among African-American patients with COPD and asthma may provide a possible explanation for the racial disparities in outcomes of patients with these conditions. PMID:19318663

The existence of bronchiectasis predicts worse prognosis in patients with COPD

PubMed Central

Mao, Bei; Lu, Hai-Wen; Li, Man-Hui; Fan, Li-Chao; Yang, Jia-Wei; Miao, Xia-Yi; Xu, Jin-Fu

2015-01-01

Bronchiectasis is prevalent in patients with COPD. The objective of this study was to assess the clinical characteristics and prognostic value of bronchiectasis in patients with COPD in China. Data from patients diagnosed with COPD at the Shanghai Pulmonary Hospital between January 2009 and December 2013 were retrospectively collected and analyzed. SPSS statistical software was used to analyze the data. Data from 896 patients with COPD were analyzed. Bronchiectasis was present in 311 patients. The isolation of pseudomonas aeruginosa (PA) from sputum was the variable most significantly associated with the presence of bronchiectasis in patients with COPD (hazard ratio (HR), 2.93; 95% confidence interval (CI), 1.35–6.37; P = 0.007). During follow-up (median of 21 months; interquartile range: 10-39 months), there were 75 deaths, of which 39 were in the bronchiectasis group. The presence of bronchiectasis (HR, 1.77; 95% CI, 1.02–3.08; P = 0.043) was associated with an increase in all-cause mortality in patients with COPD. These results suggest that bronchiectasis in patients with COPD was associated with the isolation of PA from the sputum. Bronchiectasis was an independent risk factor for all-cause mortality in patients with COPD. PMID:26077673

Modern Innovative Solutions in Improving Outcomes in Chronic Obstructive Pulmonary Disease (MISSION COPD): A Comparison of Clinical Outcomes Before and After the MISSION Clinic.

PubMed

Lanning, Eleanor; Roberts, Claire; Green, Ben; Brown, Thomas; Storrar, Will; Jones, Thomas; Fogg, Carole; Dewey, Ann; Longstaff, Jayne; Bassett, Paul; Chauhan, Anoop J

2017-06-05

Chronic obstructive pulmonary disorder (COPD) affects over 1 million people in the United Kingdom, and 1 person dies from COPD every 20 minutes. The cost to people with COPD and the National Health Service is huge - more than 24 million working days lost a year and the annual expenditure on COPD is £810 million and £930 million a year. We aim to identify patients with COPD who are at risk of exacerbations and hospital admissions as well as those who have not been formally diagnosed, yet remain at risk. This mixed-methods study will use both data and interviews from patients and health care professionals. The project Modern Innovative SolutionS in Improving Outcomes iN COPD (MISSION COPD) will hold multidisciplinary carousel style clinics to rapidly assess the patients' COPD and related comorbidities, and enhance patient knowledge and skills for self-management. This study is ongoing. This research will capture quantitative and qualitative outcomes to accompany a program of quality improvement through delivery of novel care models. ©Eleanor Lanning, Claire Roberts, Ben Green, Thomas Brown, Will Storrar, Thomas Jones, Carole Fogg, Ann Dewey, Jayne Longstaff, Paul Bassett, Anoop J Chauhan. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 05.06.2017.

Preclinical murine models of Chronic Obstructive Pulmonary Disease.

PubMed

Vlahos, Ross; Bozinovski, Steven

2015-07-15

Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and is the 4th leading cause of death worldwide. It is believed that an exaggerated inflammatory response to cigarette smoke causes progressive airflow limitation. This inflammation, where macrophages, neutrophils and T lymphocytes are prominent, leads to oxidative stress, emphysema, small airway fibrosis and mucus hypersecretion. Much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities and infectious (viral and bacterial) exacerbations (AECOPD). Comorbidities, defined as other chronic medical conditions, in particular skeletal muscle wasting and cardiovascular disease markedly impact on disease morbidity, progression and mortality. The mechanisms and mediators underlying COPD and its comorbidities are poorly understood and current COPD therapy is relatively ineffective. Thus, there is an obvious need for new therapies that can prevent the induction and progression of COPD and effectively treat AECOPD and comorbidities of COPD. Given that access to COPD patients can be difficult and that clinical samples often represent a "snapshot" at a particular time in the disease process, many researchers have used animal modelling systems to explore the mechanisms underlying COPD, AECOPD and comorbidities of COPD with the goal of identifying novel therapeutic targets. This review highlights the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and the recent advances in modelling infectious exacerbations and comorbidities of COPD. Copyright © 2015 Elsevier B.V. All rights reserved.

Overview of the prevalence, impact, and management of depression and anxiety in chronic obstructive pulmonary disease.

PubMed

Panagioti, Maria; Scott, Charlotte; Blakemore, Amy; Coventry, Peter A

2014-01-01

More than one third of individuals with chronic obstructive pulmonary disease (COPD) experience comorbid symptoms of depression and anxiety. This review aims to provide an overview of the burden of depression and anxiety in those with COPD and to outline the contemporary advances and challenges in the management of depression and anxiety in COPD. Symptoms of depression and anxiety in COPD lead to worse health outcomes, including impaired health-related quality of life and increased mortality risk. Depression and anxiety also increase health care utilization rates and costs. Although the quality of the data varies considerably, the cumulative evidence shows that complex interventions consisting of pulmonary rehabilitation interventions with or without psychological components improve symptoms of depression and anxiety in COPD. Cognitive behavioral therapy is also an effective intervention for managing depression in COPD, but treatment effects are small. Cognitive behavioral therapy could potentially lead to greater benefits in depression and anxiety in people with COPD if embedded in multidisciplinary collaborative care frameworks, but this hypothesis has not yet been empirically assessed. Mindfulness-based treatments are an alternative option for the management of depression and anxiety in people with long-term conditions, but their efficacy is unproven in COPD. Beyond pulmonary rehabilitation, the evidence about optimal approaches for managing depression and anxiety in COPD remains unclear and largely speculative. Future research to evaluate the effectiveness of novel and integrated care approaches for the management of depression and anxiety in COPD is warranted.

Changes in physical activity and all-cause mortality in COPD.

PubMed

Vaes, Anouk W; Garcia-Aymerich, Judith; Marott, Jacob L; Benet, Marta; Groenen, Miriam T J; Schnohr, Peter; Franssen, Frits M E; Vestbo, Jørgen; Wouters, Emiel F M; Lange, Peter; Spruit, Martijn A

2014-11-01

Little is known about changes in physical activity in subjects with chronic obstructive pulmonary disease (COPD) and its impact on mortality. Therefore, we aimed to study changes in physical activity in subjects with and without COPD and the impact of physical activity on mortality risk. Subjects from the Copenhagen City Heart Study with at least two consecutive examinations were selected. Each examination included a self-administered questionnaire and clinical examination. 1270 COPD subjects and 8734 subjects without COPD (forced expiratory volume in 1 s 67±18 and 91±15% predicted, respectively) were included. COPD subjects with moderate or high baseline physical activity who reported low physical activity level at follow-up had the highest hazard ratios of mortality (1.73 and 2.35, respectively; both p<0.001). In COPD subjects with low baseline physical activity, no differences were found in survival between unchanged or increased physical activity at follow-up. In addition, subjects without COPD with low physical activity at follow-up had the highest hazard ratio of mortality, irrespective of baseline physical activity level (p≤0.05). A decline to low physical activity at follow-up was associated with an increased mortality risk in subjects with and without COPD. These observational data suggest that it is important to assess and encourage physical activity in the earliest stages of COPD in order to maintain a physical activity level that is as high as possible, as this is associated with better prognosis. ©ERS 2014.

Chronic Obstructive Pulmonary Disease: official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care.

PubMed

Koblizek, Vladimir; Chlumsky, Jan; Zindr, Vladimir; Neumannova, Katerina; Zatloukal, Jakub; Zak, Jaroslav; Sedlak, Vratislav; Kocianova, Jana; Zatloukal, Jaromir; Hejduk, Karel; Pracharova, Sarka

2013-06-01

COPD is a global concern. Currently, several sets of guidelines, statements and strategies to managing COPD exist around the world. The Czech Pneumological and Phthisiological Society (CPPS) has commissioned an Expert group to draft recommended guidelines for the management of stable COPD. Subsequent revisions were further discussed at the National Consensus Conference (NCC). Reviewers' comments contributed to the establishment of the document's final version. The hallmark of the novel approach to COPD is the integrated evaluation of the patient's lung functions, symptoms, exacerbations and identifications of clinical phenotype(s). The CPPS defines 6 clinically relevant phenotypes: frequent exacerbator, COPD-asthma overlap, COPD-bronchiectasis overlap, emphysematic phenotype, bronchitic phenotype and pulmonary cachexia phenotype. Treatment recommendations can be divided into four steps. 1(st) step = Risk exposure elimination: reduction of smoking and environmental tobacco smoke (ETS), decrease of home and occupational exposure risks. 2(nd) step = Standard treatment: inhaled bronchodilators, regular physical activity, pulmonary rehabilitation, education, inhalation training, comorbidity treatment, vaccination. 3(rd) step = Phenotype-specific therapy: PDE4i, ICS+LABA, LVRS, BVR, AAT augmentation, physiotherapy, mucolytic, ABT. 4(th) step = Care for respiratory insufficiency and terminal COPD: LTOT, lung transplantation, high intensity-NIV and palliative care. Optimal treatment of COPD patients requires an individualised, multidisciplinary approach to the patient's symptoms, clinical phenotypes, needs and wishes. The new Czech COPD guideline reflects and covers these requirements.

Depression in patients with stable chronic obstructive pulmonary disease: a cross-sectional study in the national center for respiratory diseases in Indonesia.

PubMed

Rosrita, Nur Nina; Yunus, Faisal; Ginting, Tribowo Tuahta; Nurwidya, Fariz

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in the world, including Indonesia. It can cause comorbidities such as osteoporosis, heart failure, diabetes, and depression. Depression is a common. The purpose of this study is to reveal the prevalence of depression in stable COPD patients in Persahabatan Hospital Jakarta and its associated factors. This is a cross-sectional study in which stable COPD patients who visited COPD Outpatient Clinic in Persahabatan Hospital Jakarta and met the inclusion and exclusion criteria were asked for a history of disease, physical examination, lung function test and underwent Mini International Neuropsychiatric Interview Version (MINI) ICD 10. One hundred and forty-one patients were enrolled in this study. Prevalence of depression was 19.1%. Subjects with moderate-high COPD assessment test (CAT) score ≥ 10 have 14 times higher risk of having depression (p<0.001) compared to subjects with mild CAT score (< 10). There was a statistically significant association between symptoms-based COPD group (p<0.001), smoking status (p<0.007) and Brinkmann index (p<0.026) with depression. We found no statistically significant association between risk-based COPD group (p=0.799) and airflow limitation (p>1.000) with depression. The prevalence of depression in stable COPD patients in Persahabatan Hospital Jakarta was 19.1%. There was a statistically significant association between symptoms-based COPD group, smoking status, and Brinkmann index with depression in stable COPD patients.

Factors Influencing Cognitive Function in Subjects With COPD.

PubMed

Dag, Ersel; Bulcun, Emel; Turkel, Yakup; Ekici, Aydanur; Ekici, Mehmet

2016-08-01

The aim of this study was to assess the association between cognitive function and age, pulmonary function, comorbidity index, and the 6-min walk distance in subjects with COPD as well as to compare the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in terms of their ability to identify cognitive dysfunction in subjects with COPD. A total of 52 individuals with stable COPD were included in this study. Cognitive function was assessed using MMSE and MoCA. Age, body mass index, the Modified Cumulative Illness Rating Scale, 6-min walk distance, arterial blood gases, and pulmonary function tests were assessed and recorded. The range and SD of scores in subjects with COPD were larger with MoCA than with MMSE. MMSE and MoCA scores are associated with 6-min walk distance and comorbidity index in subjects with COPD. General cognitive function measured by MoCA was negatively correlated with the comorbidity index but was positively associated with 6-min walk distance in subjects with COPD after controlling for possible confounding factors in the multivariate model. However, general cognitive function measured by MMSE was not correlated with the comorbidity index and 6-min walk distance in subjects with COPD, after controlling for possible confounding factors in the multivariate model. MoCA may be a more reliable screening test than MMSE in detecting cognitive impairment in subjects with COPD. The addition of cognitive tests on assessment of subjects with COPD can provide further benefit. Copyright © 2016 by Daedalus Enterprises.

Association of innate defense proteins BPIFA1 and BPIFB1 with disease severity in COPD

PubMed Central

De Smet, Elise G; Seys, Leen JM; Verhamme, Fien M; Vanaudenaerde, Bart M; Brusselle, Guy G; Bingle, Colin D; Bracke, Ken R

2018-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal inflammatory response in the lungs caused by the inhalation of noxious particles and gases. The airway epithelium has a protective function against these harmful agents by maintaining a physical barrier and by secreting defensive proteins, such as bactericidal/permeability-increasing fold-containing (BPIF) proteins, BPIFA1 and BPIFB1. However, inconsistent data regarding BPIFA1 expression in smokers and COPD patients have been reported to date. Therefore, we investigated the expression of BPIFA1 and BPIFB1 in a large cohort of never-smokers and smokers with and without COPD, both on the messenger RNA (mRNA) level in lung tissue and on the protein level in airway epithelium. Furthermore, we examined the correlation between BPIFA1 and BPIFB1 levels, goblet cell hyperplasia, and lung function measurements. BPIFA1 and BPIFB1 mRNA expressions were significantly increased in stage III–IV COPD patients compared with stage II COPD patients and subjects without COPD. In addition, protein levels in COPD patients were significantly increased in comparison with subjects without COPD. BPIFA1 and BPIFB1 levels were inversely correlated with measurements of airflow limitation and positively correlated with goblet cell hyperplasia. In addition, by the use of immunofluorescence double staining, we demonstrated the expression of BPIFB1 in goblet cells. In conclusion, we show that BPIFA1 and BPIFB1 levels are elevated in COPD patients and correlate with disease severity. PMID:29296079

Profiling cellular and inflammatory changes in the airway wall of mild to moderate COPD.

PubMed

Eapen, Mathew S; McAlinden, Kielan; Tan, Daniel; Weston, Steven; Ward, Chris; Muller, Hans K; Walters, Eugene H; Sohal, Sukhwinder S

2017-08-01

The objective of this study was to enumerate total cells and the number of inflammatory cell differentials in large airways (LAs) versus small airways (SAs) of mild-moderate COPD, and against appropriate controls. For LA, we used endobronchial biopsies and for SA resected lung tissues. Immunostaining was enumerated (cells per mm 2 ) for macrophages, neutrophils, CD4 and CD8 T cells in the lamina propria (LP) up to 150 µM deep for LA and full wall thickness for SA. We confirmed hypocellularity in the LA and in the SA wall in smokers and COPD (P < 0.001). LA cellularity was least in current smokers with COPD (COPD-CS) (P < 0.01), while SA cellularity was similar across smoker/COPD groups. LA neutrophils were decreased in COPD-CS (P < 0.01), while SA neutrophil counts were unchanged. Compared with controls, LA macrophage numbers in COPD were significantly lower (P < 0.05), with SA macrophage numbers unchanged. A significant increase was observed in SA CD8+ cells in both normal smokers (P < 0.01) and COPD-CS (P < 0.001) but not in LA. These unique data indicate that the current model for airway wall inflammation in COPD is oversimplified, and contrast with innate inflammatory activation in the lumen, at least in mild-moderate disease. Any abnormalities in airway wall cell differentials are small, although exaggerated in percentage terms. © 2017 Asian Pacific Society of Respirology.

The Clinical and Economic Impact of Exacerbations of Chronic Obstructive Pulmonary Disease: A Cohort of Hospitalized Patients

PubMed Central

Blasi, Francesco; Cesana, Giancarlo; Conti, Sara; Chiodini, Virginio; Aliberti, Stefano; Fornari, Carla; Mantovani, Lorenzo Giovanni

2014-01-01

Background Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences. This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs. Methods This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy. The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006. Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period. Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status. Results 15857 patients were enrolled –9911 males, mean age: 76 years (SD 10). Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%. A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD. On average, the healthcare system spent 6725€ per year per person (95%CI 6590–6863). Occurrence and type of exacerbations drove the direct healthcare cost. Less than one quarter of patients presented claims for pulmonary function tests. Conclusions COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes. A more tailored approach to the management of COPD patients is required. PMID:24971791

COPD Surveillance—United States, 1999-2011

PubMed Central

Croft, Janet B.; Mannino, David M.; Wheaton, Anne G.; Zhang, Xingyou; Giles, Wayne H.

2013-01-01

This report updates surveillance results for COPD in the United States. For 1999 to 2011, data from national data systems for adults aged ≥ 25 years were analyzed. In 2011, 6.5% of adults (approximately 13.7 million) reported having been diagnosed with COPD. From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (P = .019). In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) ED visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD. From 1999 to 2010, no significant overall trends were noted for physician office visits and ED visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (P = .001). In 2010 there were 312,654 (11.2 per 1,000) Medicare hospital discharge claims submitted for COPD. Medicare claims (1999-2010) declined overall (P = .045), among men (P = .022) and among enrollees aged 65 to 74 years (P = .033). There were 133,575 deaths (63.1 per 100,000) from COPD in 2010. The overall age-adjusted death rate for COPD did not change during 1999 to 2010 (P = .163). Death rates (1999-2010) increased among adults aged 45 to 54 years (P < .001) and among American Indian/Alaska Natives (P = .008) but declined among those aged 55 to 64 years (P = .002) and 65 to 74 years (P < .001), Hispanics (P = .038), Asian/Pacific Islanders (P < .001), and men (P = .001). Geographic clustering of prevalence, Medicare hospitalizations, and deaths were observed. Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States. PMID:23619732

Population-based burden of COPD-related visits in the ED: return ED visits, hospital admissions, and comorbidity risks.

PubMed

Yeatts, Karin B; Lippmann, Steven J; Waller, Anna E; Hassmiller Lich, Kristen; Travers, Debbie; Weinberger, Morris; Donohue, James F

2013-09-01

Little is known about the population-based burden of ED care for COPD. We analyzed statewide ED surveillance system data to quantify the frequency of COPD-related ED visits, hospital admissions, and comorbidities. In 2008 to 2009 in North Carolina, 97,511 COPD-related ED visits were made by adults ≥ 45 years of age, at an annual rate of 13.8 ED visits/1,000 person-years. Among patients with COPD (n = 33,799), 7% and 28% had a COPD-related return ED visit within a 30- and 365-day period of their index visit, respectively. Compared with patients on private insurance, Medicare, Medicaid, and noninsured patients were more likely to have a COPD-related return visit within 30 and 365 days and have three or more COPD-related visits within 365 days. There were no differences in return visits by sex. Fifty-one percent of patients with COPD were admitted to the hospital from the index ED visit. Subsequent hospital admission risk in the cohort increased with age, peaking at 65 to 69 years (risk ratio [RR], 1.41; 95% CI, 1.26-1.57); there was no difference by sex. Patients with congestive heart failure (RR, 1.29; 95% CI, 1.22-1.37), substance-related disorders (RR, 1.35; 95% CI, 1.13-1.60), or respiratory failure/supplemental oxygen (RR, 1.25; 95% CI, 1.19-1.31) were more likely to have a subsequent hospital admission compared with patients without these comorbidities. The population-based burden of COPD-related care in the ED is significant. Further research is needed to understand variations in COPD-related ED visits and hospital admissions.

Global Initiative for Chronic Obstructive Lung Disease strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: an Asia-Pacific perspective.

PubMed

2005-01-01

Chronic obstructive pulmonary disease (COPD) is a major public health problem and its prevalence and mortality are increasing throughout the world, including the Asia-Pacific region. To arrest these worldwide trends, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Expert Panel's global strategy for the diagnosis, management, and prevention of COPD was published in 2001. Based on recently published clinical trials, the GOLD statement was updated in 2003. The Asia-Pacific COPD Roundtable Group, a taskforce of expert respirologists from the Asia-Pacific region, has recently formulated a consensus statement on implementation of the GOLD strategy for COPD in the Asia-Pacific region. The key issues identified by the COPD Roundtable Group for comment are: (i) where there is no access to spirometry, diagnosis of COPD could be suspected on the basis of history, symptoms and physical signs; (ii) inhaled bronchodilators are the preferred regular treatment for COPD in the region, but oral bronchodilators may be considered if the cost of inhaled bronchodilators is a barrier to treatment; (iii) the use of a Metered Dose Inhaler with spacer in place of a nebulizer is recommended in the treatment of acute airflow obstruction in patients with COPD; (iv) influenza vaccination is recommended for all patients with COPD in communities where there is a high likelihood of Severe Acute Respiratory Syndrome; and (v) simplified pulmonary rehabilitation programmes should be established in areas where comprehensive programmes are unavailable. Physical exercise training and education on smoking cessation should be core elements of any rehabilitation program. In summary, the COPD Roundtable Group supports implementation of the GOLD strategy for the diagnosis, management and prevention of COPD in the Asia-Pacific region, subject to the additions and modifications to the guidelines suggested above.

Tiotropium and Salmeterol in COPD Patients at Risk of Exacerbations: A Post Hoc Analysis from POET-COPD(®).

PubMed

Vogelmeier, Claus F; Asijee, Guus M; Kupas, Katrin; Beeh, Kai M

2015-06-01

Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events. The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known. A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD(®)) database. Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk. With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478). For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol. With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968). This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk. Boehringer Ingelheim and Pfizer. ClinicalTrials.gov NCT00563381.

Risks of all-cause and site-specific fractures among hospitalized patients with COPD

PubMed Central

Liao, Kuang-Ming; Liang, Fu-Wen; Li, Chung-Yi

2016-01-01

Abstract Patients with chronic obstructive pulmonary disease (COPD) have a high prevalence of osteoporosis. The clinical sequel of osteoporosis is fracture. Patients with COPD who experience a fracture also have increased morbidity and mortality. Currently, the types of all-cause and site-specific fracture among patients with COPD are unknown. Thus, we elucidated the all-cause and site-specific fractures among patients with COPD. A retrospective, population-based, cohort study was conducted utilizing the Taiwan Longitudinal Health Insurance Database. Patients with COPD were defined as those who were hospitalized with an International Classification of Diseases, Ninth Revision, Clinical Modification code of 490 to 492 or 496 between 2001 and 2011. The index date was set as the date of discharge. The study patients were followed from the index date to the date when they sought care for any type of fracture, date of death, date of health insurance policy termination, or the last day of 2013. The types of fracture analyzed in this study included vertebral, rib, humeral, radial and ulnar/wrist, pelvic, femoral, and tibial and fibular fractures. The cohort consisted of 11,312 patients with COPD. Among these patients, 1944 experienced fractures. The most common site-specific fractures were vertebral, femoral, rib, and forearm fractures (radius, ulna, and wrist) at 32.4%, 31%, 12%, and 11.8%, respectively. The adjusted hazard ratios of fracture were 1.71 [95% confidence interval (95% CI) = 1.56–1.87] for female patient with COPD and 1.50 (95% CI = 1.39–1.52) for patients with osteoporosis after covariate adjustment. Vertebral and hip fractures are common among patients with COPD, especially among males with COPD. Many comorbidities contribute to the high risk of fracture among patients with COPD. PMID:27749576

Life event stress and chronic obstructive pulmonary disease (COPD): associations with mental well-being and quality of life in a population-based study

PubMed Central

Lu, Yanxia; Nyunt, Ma Shwe Zin; Gwee, Xinyi; Feng, Liang; Feng, Lei; Kua, Ee Heok; Kumar, Rajeev; Ng, Tze Pin

2012-01-01

Objectives To investigate whether life event stress was associated with greater psychological distress and poorer quality of life in older individuals with chronic obstructive pulmonary disease (COPD), in comparison with their counterparts without COPD. Design Cross-sectional study. Participants A population-based sample (N=497) of individuals aged 65 and above with COPD (postbronchodilatation FEV1/FVC<0.70, N=136) and without COPD (N=277). Measurements We measured life event stress, depressive symptoms (GDS, Geriatric Depression Scale), cognitive symptoms and function (CFQ, Cognitive Failures Questionnaire and MMSE, Mini-Mental State Examination), and physical and mental health functional status (SF36-PCS, Physical Health Component Summary and SF36-MCS, Mental Health Component Summary) in participants with and without COPD. Results In two-way analysis of variance controlling for potential confounders, life event stress was associated with significant main effects of worse GDS (p<0.001), SF36-PCS (p=0.008) and SF36-MCS scores (p<0.001), and with significant interaction effects on GDS score (p<0.001), SF36-PCS (p=0.045) and SF36-MCS (p=0.034) in participants with COPD, more than in non-COPD participants. The main effect of COPD was found for postbronchodilator FEV1 (p<0.001) and cognitive symptoms (p=0.02). Conclusions Our findings indicate that life event stress was associated with more depressive symptoms and worse quality of life in individuals with COPD, much more than in those without COPD. Further studies should explore the role of cognitive appraisal of stress, coping resources and psycho-social support in this relationship. PMID:23166130

Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers

PubMed Central

Chen, Qiuying; Deeb, Ruba S.; Ma, Yuliang; Staudt, Michelle R.; Crystal, Ronald G.; Gross, Steven S.

2015-01-01

COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US. Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease. Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD. A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentially-expressed in COPD-smokers vs. healthy-smokers. These 23 putative biomarkers were differentially-correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8% sensitivity and 86.5% specificity. In an independent validation set, this model correctly predicted COPD in 8/10 individuals. These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels. Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways. Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD. PMID:26674646

Smoking prevalence and cessation characteristics among U.S. adults with and without COPD: findings from the 2011 Behavioral Risk Factor Surveillance System.

PubMed

Schauer, Gillian L; Wheaton, Anne G; Malarcher, Ann M; Croft, Janet B

2014-12-01

Cigarette smoking is a major cause of chronic obstructive pulmonary disease, (COPD) but many persons with COPD continue to smoke. Quitting can help prevent the development of and complications from COPD. This study examined whether smoking and cessation behaviors differed among adults with a) COPD, b) asthma, c) other chronic conditions only, or d) no chronic conditions. Smoking and chronic disease status was obtained from 488,909 adults aged > 18 years using the Behavioral Risk Factor Surveillance System; 9,476 current smokers and recent quitters in 5 states responded to additional questions about cessation. We computed age-adjusted prevalence of smoking and past-year quit attempts, and used bivariate and multivariable logistic regression to identify correlates of past-year quit attempts. Similar to the overall sample, in the 5-state sample, 47.3% of adults with COPD were current smokers versus 23.1% of those with asthma, 28.8% of adults with other chronic conditions, and 20.0% of those with no chronic conditions. Those with COPD did not differ significantly from those with asthma, other chronic diseases, or no chronic disease in having made a past-year quit attempt (59.7% versus 64.0%, 61.5%, and 53.9%, respectively). Smokers with COPD were significantly more likely than those with no chronic disease to have used cessation treatment resources, including a quitline, counseling, or medication (p < 0.001). Adults with COPD were just as likely as those without COPD to make a past-year quit attempt; however, approximately 40% of smokers with COPD did not try to quit.

Health-care Provider Screening and Advice for Smoking Cessation Among Smokers With and Without COPD: 2009-2010 National Adult Tobacco Survey.

PubMed

Schauer, Gillian L; Wheaton, Anne G; Malarcher, Ann M; Croft, Janet B

2016-03-01

Cigarette smoking is the predominant cause of COPD. Quitting can prevent development of and complications from COPD. The gold standard in clinician delivery of smoking cessation treatments is the 5As (ask, advise, assess, assist, arrange). This study assessed prevalence and correlates of self-reported receipt of the 5A strategies among adult smokers with and without COPD. Data were analyzed from 20,021 adult past-year cigarette smokers in the 2009-2010 National Adult Tobacco Survey, a nationally representative telephone survey of US adults 18 years of age and older. Past-year receipt of the 5As was self-reported by participants who saw a clinician in the past year. Logistic regression was used to estimate the likelihood of receipt of each of the 5As by COPD status, adjusted for sociodemographic and smoking characteristics. Among smokers, those with COPD were more likely than those without COPD to report being asked about tobacco use (95.4% vs 85.8%), advised to quit (87.5% vs 59.4%), assessed for readiness to quit (63.8% vs 37.9%), offered any assistance to quit (58.6% vs 34.0%), and offered follow-up (14.9% vs 5.2%). In adjusted logistic regression models, those with COPD were significantly more likely than those without COPD to receive each of the 5As. Health professionals should continue to prioritize tobacco cessation counseling and treatment to smokers with COPD. Increased system-level changes and insurance coverage for cessation treatments could be used to improve the delivery of brief tobacco cessation counseling to all smokers, regardless of COPD status. Copyright © 2016 American College of Chest Physicians. All rights reserved.

Subphenotypes of mild-to-moderate COPD by factor and cluster analysis of pulmonary function, CT imaging and breathomics in a population-based survey.

PubMed

Fens, Niki; van Rossum, Annelot G J; Zanen, Pieter; van Ginneken, Bram; van Klaveren, Rob J; Zwinderman, Aeilko H; Sterk, Peter J

2013-06-01

Classification of COPD is currently based on the presence and severity of airways obstruction. However, this may not fully reflect the phenotypic heterogeneity of COPD in the (ex-) smoking community. We hypothesized that factor analysis followed by cluster analysis of functional, clinical, radiological and exhaled breath metabolomic features identifies subphenotypes of COPD in a community-based population of heavy (ex-) smokers. Adults between 50-75 years with a smoking history of at least 15 pack-years derived from a random population-based survey as part of the NELSON study underwent detailed assessment of pulmonary function, chest CT scanning, questionnaires and exhaled breath molecular profiling using an electronic nose. Factor and cluster analyses were performed on the subgroup of subjects fulfilling the GOLD criteria for COPD (post-BD FEV1/FVC < 0.70). Three hundred subjects were recruited, of which 157 fulfilled the criteria for COPD and were included in the factor and cluster analysis. Four clusters were identified: cluster 1 (n = 35; 22%): mild COPD, limited symptoms and good quality of life. Cluster 2 (n = 48; 31%): low lung function, combined emphysema and chronic bronchitis and a distinct breath molecular profile. Cluster 3 (n = 60; 38%): emphysema predominant COPD with preserved lung function. Cluster 4 (n = 14; 9%): highly symptomatic COPD with mildly impaired lung function. In a leave-one-out validation analysis an accuracy of 97.4% was reached. This unbiased taxonomy for mild to moderate COPD reinforces clusters found in previous studies and thereby allows better phenotyping of COPD in the general (ex-) smoking population.

Population-Based Burden of COPD-Related Visits in the ED

PubMed Central

Lippmann, Steven J.; Waller, Anna E.; Hassmiller Lich, Kristen; Travers, Debbie; Weinberger, Morris; Donohue, James F.

2013-01-01

Background: Little is known about the population-based burden of ED care for COPD. Methods: We analyzed statewide ED surveillance system data to quantify the frequency of COPD-related ED visits, hospital admissions, and comorbidities. Results: In 2008 to 2009 in North Carolina, 97,511 COPD-related ED visits were made by adults ≥ 45 years of age, at an annual rate of 13.8 ED visits/1,000 person-years. Among patients with COPD (n = 33,799), 7% and 28% had a COPD-related return ED visit within a 30- and 365-day period of their index visit, respectively. Compared with patients on private insurance, Medicare, Medicaid, and noninsured patients were more likely to have a COPD-related return visit within 30 and 365 days and have three or more COPD-related visits within 365 days. There were no differences in return visits by sex. Fifty-one percent of patients with COPD were admitted to the hospital from the index ED visit. Subsequent hospital admission risk in the cohort increased with age, peaking at 65 to 69 years (risk ratio [RR], 1.41; 95% CI, 1.26-1.57); there was no difference by sex. Patients with congestive heart failure (RR, 1.29; 95% CI, 1.22-1.37), substance-related disorders (RR, 1.35; 95% CI, 1.13-1.60), or respiratory failure/supplemental oxygen (RR, 1.25; 95% CI, 1.19-1.31) were more likely to have a subsequent hospital admission compared with patients without these comorbidities. Conclusions: The population-based burden of COPD-related care in the ED is significant. Further research is needed to understand variations in COPD-related ED visits and hospital admissions. PMID:23579283

Proteoglycan 4 is a diagnostic biomarker for COPD.

PubMed

Lee, Kang-Yun; Chuang, Hsiao-Chi; Chen, Tzu-Tao; Liu, Wen-Te; Su, Chien-Ling; Feng, Po-Hao; Chiang, Ling-Ling; Bien, Mauo-Ying; Ho, Shu-Chuan

2015-01-01

The measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported. However, CRP is a systemic inflammatory biomarker that is related to many other diseases. The objective of this study is to discover a diagnostic biomarker for COPD. Sixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study. Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected. CRP and the identified biomarkers were assessed in the validation COPD cohort patients and healthy subjects. Receiver operating characteristic values of CRP and the identified biomarkers were determined. A validation COPD cohort was used to reexamine the identified biomarker. Correlation of the biomarker with 1-year lung function decline was determined. Proteoglycan 4 (PRG4) was identified as a biomarker in COPD. The serum concentrations of PRG4 in COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stages 1+2 and 3+4 were 10.29 ng/mL and 13.20 ng/mL, respectively; 4.99 ng/mL for healthy controls (P<0.05); and 4.49 ng/mL for healthy smokers (P<0.05). PRG4 was more sensitive and specific than CRP for confirming COPD severity and acute exacerbation frequency. There was no correlation between CRP and PRG4 levels, and PRG4 was negatively correlated with the 1-year change in predicted forced vital capacity percent (R (2)=0.91, P=0.013). PRG4 may be a biomarker for identification of severity in COPD. It was related to the 1-year forced vital capacity decline in COPD patients.

Risks of all-cause and site-specific fractures among hospitalized patients with COPD.

PubMed

Liao, Kuang-Ming; Liang, Fu-Wen; Li, Chung-Yi

2016-10-01

Patients with chronic obstructive pulmonary disease (COPD) have a high prevalence of osteoporosis. The clinical sequel of osteoporosis is fracture. Patients with COPD who experience a fracture also have increased morbidity and mortality. Currently, the types of all-cause and site-specific fracture among patients with COPD are unknown. Thus, we elucidated the all-cause and site-specific fractures among patients with COPD.A retrospective, population-based, cohort study was conducted utilizing the Taiwan Longitudinal Health Insurance Database.Patients with COPD were defined as those who were hospitalized with an International Classification of Diseases, Ninth Revision, Clinical Modification code of 490 to 492 or 496 between 2001 and 2011. The index date was set as the date of discharge. The study patients were followed from the index date to the date when they sought care for any type of fracture, date of death, date of health insurance policy termination, or the last day of 2013. The types of fracture analyzed in this study included vertebral, rib, humeral, radial and ulnar/wrist, pelvic, femoral, and tibial and fibular fractures.The cohort consisted of 11,312 patients with COPD. Among these patients, 1944 experienced fractures. The most common site-specific fractures were vertebral, femoral, rib, and forearm fractures (radius, ulna, and wrist) at 32.4%, 31%, 12%, and 11.8%, respectively. The adjusted hazard ratios of fracture were 1.71 [95% confidence interval (95% CI) = 1.56-1.87] for female patient with COPD and 1.50 (95% CI = 1.39-1.52) for patients with osteoporosis after covariate adjustment.Vertebral and hip fractures are common among patients with COPD, especially among males with COPD. Many comorbidities contribute to the high risk of fracture among patients with COPD.

Occupational exposures are associated with worse morbidity in patients with chronic obstructive pulmonary disease.

PubMed

Paulin, Laura M; Diette, Gregory B; Blanc, Paul D; Putcha, Nirupama; Eisner, Mark D; Kanner, Richard E; Belli, Andrew J; Christenson, Stephanie; Tashkin, Donald P; Han, MeiLan; Barr, R Graham; Hansel, Nadia N

2015-03-01

Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. To determine the impact of occupational exposures on COPD morbidity. A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.