Features of asthma which provide meaningful insights for understanding the disease heterogeneity.

PubMed

Deliu, M; Yavuz, T S; Sperrin, M; Belgrave, D; Sahiner, U M; Sackesen, C; Kalayci, O; Custovic, A

2018-01-01

Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic: (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Obesity and adiposity indicators, asthma, and atopy in Puerto Rican children

PubMed Central

Forno, Erick; Acosta-Pérez, Edna; Brehm, John M.; Han, Yueh-Ying; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2013-01-01

Background: Whether adiposity indicators other than body mass index should be used in studies of childhood asthma is largely unknown. The role of atopy in “obese asthma” is also unclear. Objective: To examine the relation among adiposity indicators, asthma, and atopy in Puerto Rican children, and to assess whether atopy mediates the obesity-asthma association. Methods: In a study of Puerto Rican children with (n=351) and without (n=327) asthma, we measured body mass index (BMI), percent body fat (PBF), waist circumference (WC), and waist-to-hip ratio (WHR). The outcomes studied included asthma, lung function, measures of atopy, and, among cases, indicators of asthma severity or control. We performed mediation analysis to assess the contribution of atopy to the relationship between adiposity and asthma. Results: BMI, PBF, and WC were associated with increased odds of asthma. Among cases, all three measures were generally associated with lung function, asthma severity/control, and atopy; however, there were differences depending on the adiposity indicator analyzed. Atopy considerably mediated the adiposity-asthma association in this population: allergic rhinitis accounted for 22-53% of the association with asthma, and sensitization to cockroach mediated 13-20% of the association with FVC and 29-42% of the association with emergency room visits for asthma. Conclusions: Adiposity indicators are associated with asthma, asthma severity/control, and atopy in Puerto Rican children. Atopy significantly mediates the effect of adiposity on asthma outcomes. Longitudinal studies are needed to further investigate the causal role, if any, of adiposity distribution and atopy on “obese asthma” in childhood. Clinical Implications: Assessment of adiposity rather than sole reliance on BMI may be important in studies of childhood asthma. Atopy is an important mediator of the relation between obesity and asthma in Puerto Rican children. Capsule Summary: In a cohort of Puerto Rican children, measures of adiposity were associated with asthma, asthma severity/control, and atopy; however, some differences existed depending on the adiposity indicator utilized. Atopy significantly mediated the association between adiposity indicators and asthma. PMID:24290290

Depression, asthma and bronchodilator response in a nationwide study of U.S. adults

PubMed Central

Han, Yueh-Ying; Forno, Erick; Marsland, Anna L.; Miller, Gregory E.; Celedón, Juan C.

2015-01-01

Background Little is known about the relation between two common co-morbidities (depression and anxiety) and asthma or bronchodilator response (BDR). Objective To examine the association between depressive symptoms and asthma or BDR in U.S. adults. Methods Cross-sectional study of 20,272 adults 20–79 years from the 2007–2012 National Health and Nutrition Examination Survey. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9), and classified as: none to minimal, mild, moderate, moderately severe, and severe. Major depression (comprising moderately severe to severe symptoms) was defined as a PHQ-9 ≥15. Anxiety was defined as ≥5 days feeling anxious in the prior month. Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and ≥1 asthma attack in the previous year. BDR (as percentage of baseline FEV1) was measured in 1,356 participants with FEV1/FVC<0.70 and/or FEV1<70% of predicted. Logistic or linear regression was used for the multivariable analysis. Results Depressive symptoms were significantly and linearly associated with asthma, independently of anxiety symptoms. Subjects with major depression had 3.4 higher odds of asthma than those with minimal or no depressive symptoms (95% confidence interval 2.6–4.5, P<0.01). Among adults with asthma, major depression was associated with a 4.2% reduction in BDR (95% CI=−7.5% to −0.8%, P=0.02). Major depression was not associated with BDR among adults without asthma. Anxiety was not associated with asthma or BDR. Conclusion Depressive symptoms are associated with asthma in adults, independently of anxiety symptoms. Major depression is associated with reduced BDR in adults with asthma. PMID:26563676

Obstructive Sleep Apnea Risk, Asthma Burden and Lower Airway Inflammation in Adults in the Severe Asthma Research Program (SARP) II

PubMed Central

Teodorescu, Mihaela; Broytman, Oleg; Curran-Everett, Douglas; Sorkness, Ronald L.; Crisafi, Gina; Bleecker, Eugene R.; Erzurum, Serpil; Gaston, Benjamin M.; Wenzel, Sally E.; Jarjour, Nizar N.

2015-01-01

Background Obstructive sleep apnea (OSA) may worsen asthma, but large studies are lacking and the underlying mechanisms are unknown. Objective Determine the prevalence of OSA risk among patients with asthma of different severity compared to normal controls (NC), and among asthmatics, test the relationship of OSA risk with asthma burden and airway inflammation. Methods Subjects with severe (SA, n=94) and non-severe asthma (NSA, n=161), and NC (n=146) were recruited in an add-on sub-study, to the observational Severe Asthma Research Program (SARP) II; subjects completed sleep quality, sleepiness and OSA risk (Sleep Apnea scale of the Sleep Disorders Questionnaire [SA-SDQ]) questionnaires and clinical assessments. Sputum was induced in a subset of asthmatics. Results Relative to NC, despite similar sleep duration, the SA and NSA subjects had worse sleep quality, were sleepier and had higher SA-SDQ scores. Among asthmatics, higher SA-SDQ was associated with increased asthma symptoms, β-agonist use, health care utilization, and worse asthma quality of life. Significant association of SA-SDQ with sputum polymorphonuclear cells% was noted: each increase in SA-SDQ by its standard deviation (6.85 units) was associated with a rise in % sputum neutrophils of 7.78 (95 % CI 2.33-13.22, p = 0.0006), independent of obesity and other confounders. Conclusions OSA symptoms are more prevalent among asthmatics, in whom they are associated with higher disease burden. OSA risk is associated with a neutrophilic airway inflammation in asthma, suggesting that OSA may be an important contributor to the neutrophilic asthma. Further studies are necessary to confirm these findings and better understand the mechanistic underpinnings of this relationship. PMID:26004304

Phenotypes Determined by Cluster Analysis in Moderate to Severe Bronchial Asthma.

PubMed

Youroukova, Vania M; Dimitrova, Denitsa G; Valerieva, Anna D; Lesichkova, Spaska S; Velikova, Tsvetelina V; Ivanova-Todorova, Ekaterina I; Tumangelova-Yuzeir, Kalina D

2017-06-01

Bronchial asthma is a heterogeneous disease that includes various subtypes. They may share similar clinical characteristics, but probably have different pathological mechanisms. To identify phenotypes using cluster analysis in moderate to severe bronchial asthma and to compare differences in clinical, physiological, immunological and inflammatory data between the clusters. Forty adult patients with moderate to severe bronchial asthma out of exacerbation were included. All underwent clinical assessment, anthropometric measurements, skin prick testing, standard spirometry and measurement fraction of exhaled nitric oxide. Blood eosinophilic count, serum total IgE and periostin levels were determined. Two-step cluster approach, hierarchical clustering method and k-mean analysis were used for identification of the clusters. We have identified four clusters. Cluster 1 (n=14) - late-onset, non-atopic asthma with impaired lung function, Cluster 2 (n=13) - late-onset, atopic asthma, Cluster 3 (n=6) - late-onset, aspirin sensitivity, eosinophilic asthma, and Cluster 4 (n=7) - early-onset, atopic asthma. Our study is the first in Bulgaria in which cluster analysis is applied to asthmatic patients. We identified four clusters. The variables with greatest force for differentiation in our study were: age of asthma onset, duration of diseases, atopy, smoking, blood eosinophils, nonsteroidal anti-inflammatory drugs hypersensitivity, baseline FEV1/FVC and symptoms severity. Our results support the concept of heterogeneity of bronchial asthma and demonstrate that cluster analysis can be an useful tool for phenotyping of disease and personalized approach to the treatment of patients.

Working while unwell: Workplace impairment in people with severe asthma.

PubMed

Hiles, S A; Harvey, E S; McDonald, V M; Peters, M; Bardin, P; Reynolds, P N; Upham, J W; Baraket, M; Bhikoo, Z; Bowden, J; Brockway, B; Chung, L P; Cochrane, B; Foxley, G; Garrett, J; Hew, M; Jayaram, L; Jenkins, C; Katelaris, C; Katsoulotos, G; Koh, M S; Kritikos, V; Lambert, M; Langton, D; Lara Rivero, A; Marks, G B; Middleton, P G; Nanguzgambo, A; Radhakrishna, N; Reddel, H; Rimmer, J; Southcott, A M; Sutherland, M; Thien, F; Wark, P A B; Yang, I A; Yap, E; Gibson, P G

2018-06-01

Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age. © 2018 John Wiley & Sons Ltd.

Family Relational Factors in Pediatric Depression and Asthma: Pathways of Effect

ERIC Educational Resources Information Center

Wood, Beatrice L.; Miller, Bruce D.; Lim, Jungha; Lillis, Kathleen; Ballow, Mark; Stern, Trudy; Simmens, Samuel

2006-01-01

Objective: This study tested a multilevel biobehavioral family model proposing that negative family emotional climate contributes to child depressive symptoms, which in turn contribute to asthma disease severity. Parent-child relational insecurity is proposed as a mediator. Method: Children with asthma (N = 112; ages 7-18; 55% male) reported…

A Multiomics Approach to Identify Genes Associated with Childhood Asthma Risk and Morbidity.

PubMed

Forno, Erick; Wang, Ting; Yan, Qi; Brehm, John; Acosta-Perez, Edna; Colon-Semidey, Angel; Alvarez, Maria; Boutaoui, Nadia; Cloutier, Michelle M; Alcorn, John F; Canino, Glorisa; Chen, Wei; Celedón, Juan C

2017-10-01

Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.

Estimated cost of asthma in outpatient treatment: a real-world study

PubMed Central

Costa, Eduardo; Caetano, Rosangela; Werneck, Guilherme Loureiro; Bregman, Maurício; Araújo, Denizar Vianna; Rufino, Rogério

2018-01-01

ABSTRACT OBJECTIVE To estimate the cost of diagnosis and treatment of asthma. METHODS We used the perspective of society. We sequentially included for 12 months, in 2011-2012, 117 individuals over five years of age who were treated for asthma in the Pneumology and Allergy-Immunology Services of the Piquet Carneiro Polyclinic, Universidade do Estado do Rio de Janeiro. All of them were interviewed twice with a six-month interval for data collection, covering 12 months. The cost units were identified and valued according to defined methods. We carried out a sensitivity analysis and applied statistical methods with a significance level of 5% for cost comparisons between subgroups. RESULTS The study consisted of 108 patients, and 73.8% of them were women. Median age was 49.5 years. Rhinitis was present in 83.3% of the individuals, and more than half were overweight or obese. Mean family income was U$915.90/month (SD = 879.12). Most workers and students had absenteeism related to asthma. Total annual mean cost was U$1,291.20/patient (SD = 1,298.57). The cost related to isolated asthma was U$1,155.43/patient-year (SD = 1,305.58). Obese, severe, and uncontrolled asthmatic patients had higher costs than non-obese, non-severe, and controlled asthmatics, respectively. Severity and control level were independently associated with higher cost (p = 0.001 and 0.000, respectively). The direct cost accounted for 82.3% of the estimated total cost. The cost of medications for asthma accounted for 62.2% of the direct costs of asthma. CONCLUSIONS Asthma medications, environmental control measures, and long-term health leaves had the greatest potential impact on total cost variation. The results are an estimate of the cost of treating asthma at a secondary level in the Brazilian Unified Health System, assuming that the treatment used represents the ideal approach to the disease. PMID:29641652

Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children

PubMed Central

Blatter, Joshua; Brehm, John M.; Sordillo, Joanne; Forno, Erick; Boutaoui, Nadia; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Weiss, Scott T.; Litonjua, Augusto A.; Canino, Glorisa

2016-01-01

Background: Little is known about folate and atopy or severe asthma exacerbations. We examined whether folate deficiency is associated with number of positive skin tests to allergens or severe asthma exacerbations in a high-risk population and further assessed whether such association is explained or modified by vitamin D status. Methods: Cross-sectional study of 582 children aged 6 to 14 years with (n = 304) and without (n = 278) asthma in San Juan, Puerto Rico. Folate deficiency was defined as plasma folate less than or equal to 20 ng/ml. Our outcomes were the number of positive skin tests to allergens (range, 0–15) in all children and (in children with asthma) one or more severe exacerbations in the previous year. Logistic and negative binomial regression models were used for the multivariate analysis. All multivariate models were adjusted for age, sex, household income, residential proximity to a major road, and (for atopy) case/control status; those for severe exacerbations were also adjusted for use of inhaled corticosteroids and vitamin D insufficiency (a plasma 25[OH]D < 30 ng/ml). Measurements and Main Results: In a multivariate analysis, folate deficiency was significantly associated with an increased degree of atopy and 2.2 times increased odds of at least one severe asthma exacerbation (95% confidence interval for odds ratio, 1.1–4.6). Compared with children who had normal levels of both folate and vitamin D, those with both folate deficiency and vitamin D insufficiency had nearly eightfold increased odds of one or more severe asthma exacerbation (95% confidence interval for adjusted odds ratio, 2.7–21.6). Conclusions: Folate deficiency is associated with increased degree of atopy and severe asthma exacerbations in school-aged Puerto Ricans. Vitamin D insufficiency may further increase detrimental effects of folate deficiency on severe asthma exacerbations. PMID:26561879

Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children

PubMed Central

Brehm, John M.; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael; Boutaoui, Nadia; Forno, Erick; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Litonjua, Augusto A.; Cabana, Michael; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa

2012-01-01

Rationale: Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. Objectives: To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. Methods: A cross-sectional study was conducted of 560 children ages 6–14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Measurements and Main Results: Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5–4.9; P = 0.001) and atopy, and a lower FEV1/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2–21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1–4.1; P = 0.04) cases. Conclusions: Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control. PMID:22652028

Adiposity, Fractional Exhaled Nitric Oxide, and Asthma in U.S. Children

PubMed Central

Han, Yueh-Ying; Forno, Erick

2014-01-01

Rationale: Whether allergic airway inflammation mediates the association between overweight or obesity and childhood asthma is unknown. Objectives: To examine adiposity, asthma, and fractional exhaled nitric oxide (FeNO) in U.S. children. Methods: Cross-sectional study of indicators of adiposity or obesity, FeNO (a biomarker of eosinophilic airway inflammation), and asthma in 2,681 children aged 6–17 years in the 2007–2010 National Health and Nutrition Examination Survey. Adiposity measures included body mass index (BMI), percent body fat (PBF), and waist circumference (WC). Measurements and Main Results: BMI, PBF, and WC were associated with asthma among children with low FeNO (odds ratio, 1.54–1.68; P < 0.01), but not among children with increased FeNO. Among children without asthma, BMI, PBF, and WC were associated with higher FEV1 and FVC, and lower FEV1/FVC. Among children with asthma and a high FeNO, all adiposity indicators were associated with decreased FEV1/FVC (β = −1.5% to −1.7% per z score) but not with FEV1 or FVC. Higher BMI or PBF was associated with worse asthma severity or control in children with asthma and increased FeNO, but not in children with asthma and low FeNO. Similar results were obtained in a secondary multivariate analysis of overweight or obesity (defined as BMI ≥85th percentile) and asthma or indicators of asthma severity or control, stratified by FeNO level. Conclusions: Adiposity indicators are associated with asthma in children with low FeNO. Among children with asthma, adiposity indicators are associated with worse asthma severity or control in those with high FeNO. PMID:24922361

Weekly Monitoring of Children with Asthma for Infections and Illness During Common Cold Seasons

PubMed Central

Olenec, Jaime P; Kim, Woo Kyung; Lee, Wai-Ming; Vang, Fue; Pappas, Tressa E; Salazar, Lisa EP; Evans, Michael D; Bork, Jack; Roberg, Kathleen; Lemanske, Robert F; Gern, James E

2010-01-01

Background Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity. Objectives To evaluate rhinovirus infections during peak seasons in children with asthma, and to analyze relationships between viral infection and illness severity. Methods Fifty-eight children with asthma ages 6-8 years provided 5 consecutive weekly nasal lavage samples during September and April; symptoms, medication use, and peak flow were recorded. Rhinoviruses were identified using multiplex PCR and partial sequencing of viral genomes. Results Viruses were detected in 36-50% of the specimens, and, 72-99% of the viruses were rhinoviruses. There were 52 different strains (including 16 HRV-C) among the 169 rhinovirus isolates; no strains found in more than two collection periods, and all but two children had a respiratory infection. Virus-positive weeks were associated with greater cold and asthma severity (p<0.0001 and p=0.0002 respectively). Furthermore, virus-positive illnesses had increased duration and severity of cold and asthma symptoms, and more frequent loss of asthma control (47% vs. 22%, p=0.008). While allergen-sensitized vs. non-sensitized children had the same number of viral infections, the former had 47% more symptomatic viral illnesses (1.19 vs. 0.81 per month, p=0.03). Conclusions Rhinovirus infections are nearly universal in children with asthma during common cold seasons, likely due to a plethora of new strains appearing each season. Illnesses associated with viruses have greater duration and severity. Finally, atopic asthmatic children experienced more frequent and severe viral-induced illnesses. Clinical Implications The combination of viral infection and allergy increases the morbidity of respiratory illness in children with asthma. PMID:20392488

The relationship between combination inhaled corticosteroid and long-acting beta-agonist use and severe asthma exacerbations in a diverse population

PubMed Central

Wells, Karen E.; Peterson, Edward L.; Ahmedani, Brian K.; Severson, Richard K.; Gleason-Comstock, Julie; Williams, L. Keoki

2012-01-01

Background Safety concerns surround the use of long-acting beta agonists (LABA) for the treatment of asthma, even in combination with inhaled corticosteroids (ICS) and particularly in high-risk subgroups. Objective To estimate the effect ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population. Methods Inhaled corticosteroid and ICS/LABA exposure was estimated from pharmacy data for patients with asthma age 12 to 56 years who were members of a large health maintenance organization. Inhaled corticosteroid and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (i.e., use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization). Results Among the 1,828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio [HR]=0.65 vs. HR=0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy. Conclusion Treatment with ICS/LABA fixed combination therapy appeared to perform as well or better than ICS alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups. PMID:22281166

Passive Smoking Impairs Histone Deacetylase-2 in Children With Severe Asthma

PubMed Central

Kobayashi, Yoshiki; Bossley, Cara; Gupta, Atul; Akashi, Kenichi; Tsartsali, Lemonia; Mercado, Nicolas; Barnes, Peter J.; Bush, Andrew

2014-01-01

Background: Parental smoking is known to worsen asthma symptoms in children and to make them refractory to asthma treatment, but the molecular mechanism is unclear. Oxidative stress from tobacco smoke has been reported to impair histone deacetylase-2 (HDAC2) via phosphoinositide-3-kinase (PI3K)/Akt activation and, thus, to reduce corticosteroid sensitivity. The aim of this study was to investigate passive smoking-dependent molecular abnormalities in alveolar macrophages (AMs) by comparing passive smoke-exposed children and non-passive smoke-exposed children with uncontrolled severe asthma. Methods: BAL fluid (BALF) was obtained from 19 children with uncontrolled severe asthma (10 non-passive smoking-exposed subjects and nine passive smoking-exposed subjects), and HDAC2 expression/activity, Akt/HDAC2 phosphorylation levels, and corticosteroid responsiveness in AMs were evaluated. Results: Parental smoking reduced HDAC2 protein expression by 54% and activity by 47%, with concomitant enhancement of phosphorylation of Akt1 and HDAC2. In addition, phosphorylation levels of Akt1 correlated positively with HDAC2 phosphorylation levels and negatively with HDAC2 activity. Furthermore, passive smoke exposure reduced the inhibitory effects of dexamethasone on tumor necrosis factor-α-induced CXCL8 release in AMs. There were relatively higher neutrophil counts and CXCL8 concentrations in BALF and lower Asthma Control Test scores compared with non-passive smoke-exposed children with uncontrolled severe asthma. Conclusions: Passive smoking impairs HDAC2 function via PI3K signaling activation, which could contribute to corticosteroid-insensitive inflammation in children with severe asthma. This novel mechanism will be a treatment target in children with severe asthma and stresses the need for a smoke-free environment for asthmatic children. PMID:24030221

Advances in Pediatric Asthma in 2013: Coordinating Asthma Care

PubMed Central

Szefler, Stanley J.

2014-01-01

Last year’s Advances in Pediatric Asthma: Moving Toward Asthma Prevention concluded that: “We are well on our way to creating a pathway around wellness in asthma care and also to utilize new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.” This year’s summary will focus on recent advances in pediatric asthma on pre- and postnatal factors altering the natural history of asthma, assessment of asthma control, and new insights regarding potential therapeutic targets for altering the course of asthma in children as indicated in Journal of Allergy and Clinical Immunology publications in 2013 and early 2014. Recent reports continue to shed light on methods to understand factors that influence the course of asthma, methods to assess and communicate levels of control, and new targets for intervention as well as new immunomodulators. It will now be important to carefully assess risk factors for the development of asthma as well as the risk for asthma exacerbations and to improve the way we communicate this information in the health care system. This will allow parents, primary care physicians, specialists and provider systems to more effectively intervene in altering the course of asthma and to further reduce asthma morbidity and mortality. PMID:24581430

Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines.

PubMed

Brasier, Allan R; Victor, Sundar; Boetticher, Gary; Ju, Hyunsu; Lee, Chang; Bleecker, Eugene R; Castro, Mario; Busse, William W; Calhoun, William J

2008-01-01

Asthma is a heterogeneous clinical disorder. Methods for objective identification of disease subtypes will focus on clinical interventions and help identify causative pathways. Few studies have explored phenotypes at a molecular level. We sought to discriminate asthma phenotypes on the basis of cytokine profiles in bronchoalveolar lavage (BAL) samples from patients with mild-moderate and severe asthma. Twenty-five cytokines were measured in BAL samples of 84 patients (41 severe, 43 mild-moderate) using bead-based multiplex immunoassays. The normalized data were subjected to statistical and informatics analysis. Four groups of asthmatic profiles could be identified on the basis of unsupervised analysis (hierarchical clustering) that were independent of treatment. One group, enriched in patients with severe asthma, showed differences in BAL cellular content, reductions in baseline pulmonary function, and enhanced response to methacholine provocation. Ten cytokines were identified that accurately predicted this group. Classification methods for predicting methacholine sensitivity were developed. The best model analysis predicted hyperresponders with 88% accuracy in 10 trials by using a 10-fold cross-validation. The cytokines that contributed to this model were IL-2, IL-4, and IL-5. On the basis of this classifier, 3 distinct hyperresponder classes were identified that varied in BAL eosinophil count and PC20 methacholine. Cytokine expression patterns in BAL can be used to identify distinct types of asthma and identify distinct subsets of methacholine hyperresponders. Further biomarker discovery in BAL may be informative.

Asthma and Fungus: Role in Allergic Bronchopulmonary Aspergillosis (ABPA) and Other Conditions.

PubMed

Singh, Meenu; Paul, Nandini; Singh, Shreya; Nayak, Gyan Ranjan

2018-03-17

Asthma is an allergic, respiratory disorder characterized by hyper responsiveness of the airway to external stimuli. Considerable research is currently being directed towards understanding the role of environmental and genetic factors contributing to the development of asthma and its severity. Recent years have seen a substantial rise in evidence linking fungi to asthma. Few major clinical conditions associated with fungal sensitization and hypersensitive immune response are Allergic bronchopulmonary aspergillosis (ABPA), Allergic fungal rhinosinusitis (AFRS) and Severe asthma with fungal sensitization (SAFS). The most common fungi implicated in these conditions belong to genus Aspergillus, although an association with several other fungi has been described. In this review authors discuss the varying clinical characteristics of fungus induced respiratory complications in individuals with asthma. They also highlight the epidemiology of these conditions including their prevalence in children and their fungal etiological profile. Laboratory diagnostic methods and clinical case definitions have also been discussed. Future studies evaluating the role of fungal exposure and susceptibility to asthma are required. Till date there are no guidelines for the diagnosis and treatment of ABPA in pediatric population, thus it is also imperative to establish validated clinical definitions of fungal allergic manifestations in pediatric patients with asthma to fully understand this complex interaction.

Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression.

PubMed

Sandberg, S; Järvenpää, S; Penttinen, A; Paton, J Y; McCann, D C

2004-12-01

A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress. Sixty children with verified chronic asthma were followed prospectively for 18 months with continuous monitoring of asthma by daily symptom diaries and peak flow measurements, accompanied by repeated interview assessments of life events. The key outcome measures were asthma exacerbations and severely negative life events. An immediate effect evident within the first 2 days following a severely negative life event increased the risk of a new asthma attack by a factor of 4.69, 95% confidence interval 2.33 to 9.44 (p<0.001) [corrected] In the period 3-10 days after a severe event there was no increased risk of an asthma attack (p = 0.5). In addition to the immediate effect, an increased risk of 1.81 (95% confidence interval 1.24 to 2.65) [corrected] was found 5-7 weeks after a severe event (p = 0.002). This is consistent with earlier findings. There was a statistically significant variation due to unobserved factors in the incidence of asthma attacks between the children. The use of statistical methods capable of investigating short time lags showed that stressful life events significantly increase the risk of a new asthma attack immediately after the event; a more delayed increase in risk was also evident 5-7 weeks later.

Allergy in severe asthma.

PubMed

Del Giacco, S R; Bakirtas, A; Bel, E; Custovic, A; Diamant, Z; Hamelmann, E; Heffler, E; Kalayci, Ö; Saglani, S; Sergejeva, S; Seys, S; Simpson, A; Bjermer, L

2017-02-01

It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity

PubMed Central

Naveed, Shams-un-nisa; Clements, Debbie; Jackson, David J.; Philp, Christopher; Billington, Charlotte K.; Soomro, Irshad; Reynolds, Catherine; Harrison, Timothy W.; Johnston, Sebastian L.; Shaw, Dominick E.

2017-01-01

Rationale: Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of people with asthma. Objectives: To investigate whether MMP-1 could be activated by mast cells and increase asthma severity. Methods: Patients with stable asthma and healthy control subjects underwent spirometry, methacholine challenge, and bronchoscopy, and their airway smooth muscle cells were grown in culture. A second asthma group and control subjects had symptom scores, spirometry, and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extracellular matrix was prepared from decellularized airway smooth muscle cultures. MMP-1 protein and activity were assessed. Measurements and Main Results: Airway smooth muscle cells generated pro–MMP-1, which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extracellular matrix, which enhanced subsequent airway smooth muscle growth by 1.5-fold (P < 0.05), which was dependent on MMP-1 activation. In asthma, airway pro–MMP-1 was 5.4-fold higher than control subjects (P = 0.002). Mast cell numbers were associated with airway smooth muscle proliferation and MMP-1 protein associated with bronchial hyperresponsiveness. During exacerbations, MMP-1 activity increased and was associated with fall in FEV1 and worsening asthma symptoms. Conclusions: MMP-1 is activated by mast cell tryptase resulting in a proproliferative extracellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, MMP-1 levels are associated with bronchial hyperresponsiveness, and MMP-1 activation are associated with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing MMP activation, airway smooth muscle growth, and airway responsiveness. PMID:27967204

Atopy, but not obesity is associated with asthma severity among children with persistent asthma.

PubMed

Lu, Kim D; Phipatanakul, Wanda; Perzanowski, Matthew S; Balcer-Whaley, Susan; Matsui, Elizabeth C

2016-12-01

Obesity is associated with an increased risk of asthma in children. Atopic sensitization is a major risk factor for asthma including severe asthma in children. It is unclear if obesity is associated with worse asthma control or severity in children and how its effects compare to atopy. We sought to examine relationships of weight status and atopy to asthma control and severity among a population of predominantly low income, minority children and adolescents with persistent asthma. A cross-sectional analysis of 832 children and adolescents, age range 5-17 years, with persistent asthma was performed. Clinical assessments included asthma questionnaires of symptoms, asthma severity score, health care utilization and medication treatment step, lung function testing, and skin prick testing as well as measures of adiposity. Data were collected between December 2010 and August 2014 from Johns Hopkins Hospital in Baltimore, MD and Children's Hospital of Boston, MA. Obesity was not associated with worse asthma control or severity in this group of predominantly low income, minority children and adolescents with persistent asthma. However, a greater degree of atopy was associated with lower lung function, higher asthma severity score, and higher medication treatment step. Atopy may be a more important risk factor for asthma severity than obesity among low-income minority children and adolescents with persistent asthma living in Northeastern cities in the United States.

Opportunities and obstacles in translating evidence to policy in occupational asthma

PubMed Central

Tarlo, Susan M.; Arif, Ahmed A.; Delclos, George L.; Henneberger, Paul; Patel, Jenil

2018-01-01

Purpose Occupational asthma (OA), a common respiratory disorder in Western countries, is caused by exposures at the workplace. It is part of a broader definition of work-related asthma (WRA) that also includes pre-existing asthma aggravated by substances present in the workplace environment, and it is potentially preventable. The purpose of this paper is to illustrate preventive measures for occupational asthma by case studies. Methods In three case studies we discuss preventive measures that have been associated with reductions in incidence of occupational asthma from natural rubber latex and from diisocyanates as supported by published literature. We also discuss challenges in relation to asthma from cleaning products in healthcare work. Results and conclusions Several preventive measures have been associated with reduction in incidence of occupational asthma from natural rubber latex and from diisocyanates, and may provide lessons for prevention of other causes of occupational asthma. Cleaning products remain an unresolved problem at present with respect to asthma risks but potential measures include the use of safer products and safer applications such as avoidance of spray products, use of occupational hygiene methods such as improving local ventilation, and when appropriate, the use of personal protective devices. PMID:28434545

The Association of Health Literacy with Adherence and Outcomes in Moderate-Severe Asthma

PubMed Central

Apter, Andrea J.; Wan, Fei; Reisine, Susan; Bender, Bruce; Rand, Cynthia; Bogen, Daniel K.; Bennett, Ian M.; Bryant-Stephens, Tyra; Roy, Jason; Gonzalez, Rodalyn; Priolo, Chantel; Have, Thomas Ten; Morales, Knashawn H.

2013-01-01

Background Low health literacy is associated with poor outcomes in asthma and other diseases but the mechanisms governing this relationship are not well-defined. Objective To assess whether literacy is related to subsequent asthma self-management, measured as adherence to inhaled steroids, and asthma outcomes. Methods In a prospective longitudinal cohort study, numeric (Asthma Numeracy Questionnaire (ANQ)) and print literacy (Short Test of Functional Health Literacy in Adults (S-TOFHLA)) were assessed at baseline in adults with moderate or severe asthma for their impact on subsequent electronically monitored adherence and asthma outcomes (asthma control, asthma-related quality of life, and FEV1) over 26 weeks, using mixed-effects linear regression models. Results 284 adults participated: 48±14 years, 71% female, 70% African American, 6% Latino, mean FEV1 66% ± 19%, 86 (30%) with hospitalizations and 148 (52%) with ED visits for asthma in the prior year. Mean ANQ score (range 0–4) was 2.3 ± 1.2; mean S-TOFHLA score 31 ± 8 (range 0–36). In unadjusted analyses numeric and print literacy were associated with better adherence (p=0.01, p=0.08), asthma control (p=0.005, p <0.001), and quality of life (p<0.001, p<0.001). After controlling for age, sex, and race/ethnicity, the associations diminished and only quality of life (numeric: p=0.03, print p=0.006) and asthma control (print p=0.005) remained significantly associated with literacy. Race/ethnicity, income, and educational attainment were correlated (p<0.001). Conclusion While the relationship between literacy and health is complex, interventions which account for and address the literacy needs of patients may improve asthma outcomes. Clinical Implications/Key Summary In adults with moderate or severe asthma, higher health literacy scores were associated with better subsequent quality of life and asthma control. PMID:23591273

Are Physician Estimates of Asthma Severity Less Accurate in Black than in White Patients?

PubMed Central

Wu, Albert W.; Merriman, Barry; Krishnan, Jerry A.; Diette, Gregory B.

2007-01-01

Background Racial differences in asthma care are not fully explained by socioeconomic status, care access, and insurance status. Appropriate care requires accurate physician estimates of severity. It is unknown if accuracy of physician estimates differs between black and white patients, and how this relates to asthma care disparities. Objective We hypothesized that: 1) physician underestimation of asthma severity is more frequent among black patients; 2) among black patients, physician underestimation of severity is associated with poorer quality asthma care. Design, Setting and Patients We conducted a cross-sectional survey among adult patients with asthma cared for in 15 managed care organizations in the United States. We collected physicians’ estimates of their patients’ asthma severity. Physicians’ estimates of patients’ asthma as being less severe than patient-reported symptoms were classified as underestimates of severity. Measurements Frequency of underestimation, asthma care, and communication. Results Three thousand four hundred and ninety-four patients participated (13% were black). Blacks were significantly more likely than white patients to have their asthma severity underestimated (OR = 1.39, 95% CI 1.08–1.79). Among black patients, underestimation was associated with less use of daily inhaled corticosteroids (13% vs 20%, p < .05), less physician instruction on management of asthma flare-ups (33% vs 41%, p < .0001), and lower ratings of asthma care (p = .01) and physician communication (p = .04). Conclusions Biased estimates of asthma severity may contribute to racially disparate asthma care. Interventions to improve physicians’ assessments of asthma severity and patient–physician communication may minimize racial disparities in asthma care. PMID:17453263

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

PubMed Central

Porsbjerg, Celeste; Ulrik, Charlotte; Skjold, Tina; Backer, Vibeke; Laerum, Birger; Lehman, Sverre; Janson, Crister; Sandstrøm, Thomas; Bjermer, Leif; Dahlen, Barbro; Lundbäck, Bo; Ludviksdottir, Dora; Björnsdóttir, Unnur; Altraja, Alan; Lehtimäki, Lauri; Kauppi, Paula; Karjalainen, Jussi; Kankaanranta, Hannu

2018-01-01

ABSTRACT Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma (‘difficult asthma’) should undergo systematic assessment, in order to differentiate between true severe asthma, and ‘difficult-to-treat’ patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care. PMID:29535852

IL6R Variation Asp358Ala Is a Potential Modifier of Lung Function in Asthma

PubMed Central

Hawkins, Gregory A; Robinson, Mac B; Hastie, Annette T; Li, Xingnan; Li, Huashi; Moore, Wendy C; Howard, Timothy D; Busse, William W.; Erzurum, Serpil C.; Wenzel, Sally E.; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

2012-01-01

Background The IL6R SNP rs4129267 has recently been identified as an asthma susceptibility locus in subjects of European ancestry but has not been characterized with respect to asthma severity. The SNP rs4129267 is in linkage disequilibrium (r2=1) with the IL6R coding SNP rs2228145 (Asp358Ala). This IL6R coding change increases IL6 receptor shedding and promotes IL6 transsignaling. Objectives To evaluate the IL6R SNP rs2228145 with respect to asthma severity phenotypes. Methods The IL6R SNP rs2228145 was evaluated in subjects of European ancestry with asthma from the Severe Asthma Research Program (SARP). Lung function associations were replicated in the Collaborative Study on the Genetics of Asthma (CSGA) cohort. Serum soluble IL6 receptor (sIL6R) levels were measured in subjects from SARP. Immunohistochemistry was used to qualitatively evaluate IL6R protein expression in BAL cells and endobronchial biopsies. Results The minor C allele of IL6R SNP rs2228145 was associated with lower ppFEV1 in the SARP cohort (p=0.005), the CSGA cohort (0.008), and in combined cohort analysis (p=0.003). Additional associations with ppFVC, FEV1/FVC, and PC20 were observed. The rs2228145 C allele (Ala358) was more frequent in severe asthma phenotypic clusters. Elevated serum sIL6R was associated with lower ppFEV1 (p=0.02) and lower ppFVC (p=0.008) (N=146). IL6R protein expression was observed in BAL macrophages, airway epithelium, vascular endothelium, and airway smooth muscle. Conclusions The IL6R coding SNP rs2228145 (Asp358Ala) is a potential modifier of lung function in asthma and may identify subjects at risk for more severe asthma. IL6 transsignaling may have a pathogenic role in the lung. PMID:22554704

Correlation of total serum immunoglobulin E level, sputum, and peripheral eosinophil count in assessing the clinical severity in bronchial asthma.

PubMed

Kumar, Roshan M; Pajanivel, R; Koteeswaran, G; Menon, Surendra K; Charles, Pravin Mv

2017-01-01

Asthma is a chronic inflammatory disorder of the airway with involvement of various cellular populations and release of many inflammatory mediators. Eosinophils and serum immunoglobulin E (IgE) are considered a good marker of airway inflammation in asthma. The correlation of clinical assessment with various markers of airway inflammation in asthma is not well established in the Indian population. This study aims to study the correlation of serum IgE, sputum eosinophil count, and peripheral eosinophil count with clinical severity of Asthma. This is a cross-sectional study involving 76 stable asthmatic patients of 18-60 years of age attending the pulmonary medicine OPD. Spirometry measured at baseline. Participants were categorized according to the GINA criteria based on clinical symptoms and pulmonary function test. Blood samples were collected for peripheral eosinophil count, serum IgE levels, and sputum samples for eosinophil count. All three parameters were compared with severity of asthma. The correlation of sputum eosinophil count, peripheral eosinophil count, and serum IgE with severity of asthma was analyzed by Pearson's Chi-square test, Fisher's exact test, and the correlation coefficient was reported together with standard error of the estimate. The mean age of patients in our study was 37.42 years and 56.6% were male. There was a significant inverse correlation between serum IgE levels and predicted forced expiratory volume 1 s (FEV1). Sputum eosinophilia was significantly seen in severe persistent asthma patients (19.7%). There was a significant inverse correlation between sputum eosinophil count and predicted FEV1and forced vital capacity. We also found there was a significant association between peripheral eosinophil count, sputum eosinophil count, and elevated serum IgE (g100 IU/mL) with severe persistent asthma. The assessment of sputum eosinophil count is simple, inexpensive, noninvasive, and direct measurement of airway inflammation. It could be the preferred method in monitoring airway inflammation and guided management in day-to-day practice.

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease

PubMed Central

Modena, Brian D.; Bleecker, Eugene R.; Busse, William W.; Erzurum, Serpil C.; Gaston, Benjamin M.; Jarjour, Nizar N.; Meyers, Deborah A.; Milosevic, Jadranka; Tedrow, John R.; Wu, Wei; Kaminski, Naftali

2017-01-01

Rationale: Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Objectives: Identify networks of genes reflective of underlying biological processes that define SA. Methods: Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Measurements and Main Results: Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12–21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. Conclusions: In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes. PMID:27984699

Cluster analysis in phenotyping a Portuguese population.

PubMed

Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J

2015-09-03

Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.

Evaluation of quality of life according to asthma control and asthma severity in children and adolescents.

PubMed

Matsunaga, Natasha Yumi; Ribeiro, Maria Angela Gonçalves de Oliveira; Saad, Ivete Alonso Bredda; Morcillo, André Moreno; Ribeiro, José Dirceu; Toro, Adyléia Aparecida Dalbo Contrera

2015-01-01

To evaluate quality of life according to the level of asthma control and degree of asthma severity in children and adolescents. We selected children and adolescents with asthma (7-17 years of age) from the Pediatric Pulmonology Outpatient Clinic of the State University of Campinas Hospital de Clínicas, located in the city of Campinas, Brazil. Asthma control and asthma severity were assessed by the Asthma Control Test and by the questionnaire based on the Global Initiative for Asthma, respectively. The patients also completed the Paediatric Asthma Quality of Life Questionnaire (PAQLQ), validated for use in Brazil, in order to evaluate their quality of life. The mean age of the patients was 11.22 ± 2.91 years, with a median of 11.20 (7.00-17.60) years. We selected 100 patients, of whom 27, 33, and 40 were classified as having controlled asthma (CA), partially controlled asthma (PCA), and uncontrolled asthma (UA), respectively. As for asthma severity, 34, 19, and 47 were classified as having mild asthma (MiA), moderate asthma (MoA), and severe asthma (SA), respectively. The CA and the PCA groups, when compared with the NCA group, showed higher values for the overall PAQLQ score and all PAQLQ domains (activity limitation, symptoms, and emotional function; p < 0.001 for all). The MiA group showed higher scores for all of the PAQLQ components than did the MoA and SA groups. Quality of life appears to be directly related to asthma control and asthma severity in children and adolescents, being better when asthma is well controlled and asthma severity is lower.

Household biomass fuel use, asthma symptoms severity, and asthma underdiagnosis in rural schoolchildren in Nigeria: a cross-sectional observational study.

PubMed

Oluwole, Oluwafemi; Arinola, Ganiyu O; Huo, Dezheng; Olopade, Christopher O

2017-01-05

In 2014, the International Study of Asthma and Allergies in Childhood (ISAAC) reported that the highest prevalence of symptoms of severe asthma was found in the low- and middle-income countries (LMICs), including Nigeria. While exposure to biomass fuel use may be an important risk factor in the development of asthma, its association with asthma symptoms severity has not been well-established. The aim of this study is to extend the spectrum of environmental risk factors that may be contributing towards increasing asthma morbidity, especially asthma symptoms severity in rural schoolchildren in Nigeria and to examine possible asthma underdiagnosis among this population. Authors conducted a cross-sectional survey in three rural communities in Nigeria. Asthma symptoms were defined according to the ISAAC criteria. Information on the types of household fuel used for cooking was used to determine household cooking fuel status. Asthma symptoms severity was defined based on frequencies of wheeze, day- and night-time symptoms, and speech limitations. Logistic regression analyses were used to explore associations. A total of 1,690 Nigerian schoolchildren participated in the study. Overall, 37 (2.2%) had diagnosed asthma and 413 (24.4%) had possible asthma (asthma-related symptoms but not diagnosed asthma). Children from biomass fuel households had higher proportion of possible asthma (27.7 vs. 22.2%; p < 0.05) and symptoms of severe asthma (18.2 vs. 7.6%; p = 0.048). In adjusted analyses, biomass fuel use was associated with increased odds of severe symptoms of asthma [odds ratios (OR) = 2.37; 95% CI: 1.16-4.84], but not with possible asthma (OR = 1.22; 95% CI: 0.95-1.56). In rural Nigerian children with asthma symptoms, the use of biomass fuel for cooking is associated with an increased risk of severe asthma symptoms. There is additional evidence that rural children might be underdiagnosed for asthma.

Audit of acute asthma management at the Paediatric Emergency Department at Wad Madani Children’s Hospital, Sudan

PubMed Central

Haroun, Huda M.; Ali, Hassan M.; Tag Eldeen, Imad Eldeen M.

2012-01-01

This audit of hospital care of acute wheeze and asthma aimed to assess the degree of adherence of the acute care of the asthma patients to the published international guidelines. Information was collected in six key areas: patient demographics; initial asthma severity assessment; in-hospital treatment; asthma prophylaxis; asthma education and emergency planning; and follow-up arrangements. The area of initial asthma severity assessment showed defciencies in the clinical measures currently used to verify case severity. In- hospital treatment on the other hand was consistent with recommendations in the use of the inhaled β-2 agonist salbutamol as bronchodilator, the discrete use of aminophylline and the small number of patients ordered chest X-ray. However, the treatment was incoherent with recommendations in the delivery method used for inhaled bronchodilator in relation to the age group of treated patients, absence of ipratropium bromide as a bronchodilator in the management and the large use of antibiotics. Assessment of the areas of asthma prophylaxis, asthma education and emergency- planning and follow-up arrangements illustrated that little efforts were made to assure safe discharge, although these measures have been shown to reduce morbidity after the exacerbation and reduce relapse rates and signifcantly reduce hospitalizations, unscheduled acute visits, missed work days, as well as improving quality of life. This audit emphasizes the need for the adoption of a management protocol for acute asthma care in the emergency department based on published international guidelines and the assurance of its implementation, monitoring and evaluation using the right tools to improve patient care. PMID:27493337

ALX receptor ligands define a biochemical endotype for severe asthma

PubMed Central

Ricklefs, Isabell; Barkas, Ioanna; Duvall, Melody G.; Grossman, Nicole L.; Israel, Elliot; Bleecker, Eugene R.; Castro, Mario; Erzurum, Serpil C.; Fahy, John V.; Gaston, Benjamin M.; Denlinger, Loren C.; Mauger, David T.; Wenzel, Sally E.; Comhair, Suzy A.; Coverstone, Andrea M.; Fajt, Merritt L.; Hastie, Annette T.; Johansson, Mats W.; Peters, Michael C.; Phillips, Brenda R.; Levy, Bruce D.

2017-01-01

BACKGROUND. In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). METHODS. ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] or healthy donors [HDs, n = 47]). RESULTS. Bronchoalveolar lavage (BAL) fluid LXA4 and 15-epi-LXA4 were decreased and SAA was increased in SA relative to NSA. BAL macrophage ALX expression was increased in SA. Subjects with LXA4loSAAhi levels had increased BAL neutrophils, more asthma symptoms, lower lung function, increased relative risk for asthma exacerbation, sinusitis, and gastroesophageal reflux disease, and were assigned more frequently to SA clinical clusters. SAA and aliquots of LXA4loSAAhi BAL fluid induced IL-8 production by lung epithelial cells expressing ALX receptors, which was inhibited by coincubation with 15-epi-LXA4. CONCLUSIONS. Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation. TRIAL REGISTRATION. Severe Asthma Research Program-3 (SARP-3; ClinicalTrials.gov NCT01606826) FUNDING Sources. National Heart, Lung and Blood Institute, the NIH, and the German Society of Pediatric Pneumology. PMID:28724795

Serum Vitamin D Levels and Markers of Severity of Childhood Asthma in Costa Rica

PubMed Central

Brehm, John M.; Celedón, Juan C.; Soto-Quiros, Manuel E.; Avila, Lydiana; Hunninghake, Gary M.; Forno, Erick; Laskey, Daniel; Sylvia, Jody S.; Hollis, Bruce W.; Weiss, Scott T.; Litonjua, Augusto A.

2009-01-01

Rationale: Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood. Objectives: To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. Methods: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses. Measurements and Main Results: Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log10 unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004–0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05–0.67; P = 0.01), and increased airway responsiveness (a ≤8.58-μmol provocative dose of methacholine producing a 20% fall in baseline FEV1 [OR, 0.15; 95% CI, 0.024–0.97; P = 0.05]). Conclusions: Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity. PMID:19179486

Estimated cost of asthma in outpatient treatment: a real-world study.

PubMed

Costa, Eduardo; Caetano, Rosangela; Werneck, Guilherme Loureiro; Bregman, Maurício; Araújo, Denizar Vianna; Rufino, Rogério

2018-04-09

To estimate the cost of diagnosis and treatment of asthma. We used the perspective of society. We sequentially included for 12 months, in 2011-2012, 117 individuals over five years of age who were treated for asthma in the Pneumology and Allergy-Immunology Services of the Piquet Carneiro Polyclinic, Universidade do Estado do Rio de Janeiro. All of them were interviewed twice with a six-month interval for data collection, covering 12 months. The cost units were identified and valued according to defined methods. We carried out a sensitivity analysis and applied statistical methods with a significance level of 5% for cost comparisons between subgroups. The study consisted of 108 patients, and 73.8% of them were women. Median age was 49.5 years. Rhinitis was present in 83.3% of the individuals, and more than half were overweight or obese. Mean family income was U$915.90/month (SD = 879.12). Most workers and students had absenteeism related to asthma. Total annual mean cost was U$1,291.20/patient (SD = 1,298.57). The cost related to isolated asthma was U$1,155.43/patient-year (SD = 1,305.58). Obese, severe, and uncontrolled asthmatic patients had higher costs than non-obese, non-severe, and controlled asthmatics, respectively. Severity and control level were independently associated with higher cost (p = 0.001 and 0.000, respectively). The direct cost accounted for 82.3% of the estimated total cost. The cost of medications for asthma accounted for 62.2% of the direct costs of asthma. Asthma medications, environmental control measures, and long-term health leaves had the greatest potential impact on total cost variation. The results are an estimate of the cost of treating asthma at a secondary level in the Brazilian Unified Health System, assuming that the treatment used represents the ideal approach to the disease.

Asthma and subjective sleep disordered breathing in a large cohort of urban adolescents.

PubMed

Zandieh, Stephanie O; Cespedes, Amarilis; Ciarleglio, Adam; Bourgeois, Wallace; Rapoport, David M; Bruzzese, Jean-Marie

2017-01-02

Sleep disordered breathing (SDB) has not been well studied in urban adolescents with asthma in community settings. Nor has the association of SDB symptoms and asthma severity been studied. We characterized self-reported symptoms suggesting SDB and investigated the association of SDB symptoms, probable asthma, and asthma severity. 9,565 adolescents from 21 inner-city high schools were screened for an asthma intervention study. Students reported on symptoms suggesting SDB using questions from the 2007 NHANES, if they were ever diagnosed with asthma, and on asthma symptoms. Using generalized linear mixed models with logit link with school as a random intercept and adjusting for age, gender, and race/ethnicity, we examined associations of SDB symptoms, and demographic characteristics, probable asthma, and asthma severity. 12% reported SDB symptoms. Older and bi-racial participants (compared to Caucasian) had higher odds of symptoms suggesting SDB (p <.001). Compared to those without probable asthma, adolescents with probable asthma had 2.63 greater odds of reporting SDB symptoms (p <.001). Among those with probable asthma, the odds of reporting SDB symptoms increased with asthma severity. When exploring daytime severity and severity due to night wakening separately, results were similar. All results remained significant when controlling for age, gender, and ethnicity. In a large urban community cohort of predominately ethnic minority adolescents, self-reported SDB symptoms were associated with probable asthma and increased asthma severity. This study highlights the importance of SDB as a modifiable co-morbidity of asthma.

KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma

PubMed Central

Cahill, Katherine N.; Katz, Howard R.; Cui, Jing; Lai, Juying; Kazani, Shamsah; Crosby-Thompson, Allison; Garofalo, Denise; Castro, Mario; Jarjour, Nizar; DiMango, Emily; Erzurum, Serpil; Trevor, Jennifer L.; Shenoy, Kartik; Chinchilli, Vernon M.; Wechsler, Michael E.; Laidlaw, Tanya M.; Boyce, Joshua A.; Israel, Elliot

2017-01-01

BACKGROUND Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyper-responsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma. METHODS We conducted a randomized, double-blind, placebo-controlled, 24-week trial of imatinib in patients with poorly controlled severe asthma who had airway hyperresponsiveness despite receiving maximal medical therapy. The primary end point was the change in airway hyperresponsiveness, measured as the concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20% (PC20). Patients also underwent bronchoscopy. RESULTS Among the 62 patients who underwent randomization, imatinib treatment reduced airway hyperresponsiveness to a greater extent than did placebo. At 6 months, the methacholine PC20 increased by a mean (±SD) of 1.73±0.60 doubling doses in the imatinib group, as compared with 1.07±0.60 doubling doses in the placebo group (P = 0.048). Imatinib also reduced levels of serum tryptase, a marker of mast-cell activation, to a greater extent than did placebo (decrease of 2.02±2.32 vs. 0.56±1.39 ng per milliliter, P = 0.02). Airway mast-cell counts declined in both groups. Muscle cramps and hypophosphatemia were more common in the imatinib group than in the placebo group. CONCLUSIONS In patients with severe asthma, imatinib decreased airway hyperresponsiveness, mast-cell counts, and tryptase release. These results suggest that KIT-dependent processes and mast cells contribute to the pathobiologic basis of severe asthma. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01097694.) PMID:28514613

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

PubMed

Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

2017-11-01

Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

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

Clinical evolution and nutritional status in asthmatic children and adolescents enrolled in Primary Health Care

PubMed Central

Morishita, Rosinha Yoko Matsubayaci; Strufaldi, Maria Wany Louzada; Puccini, Rosana Fiorini

2015-01-01

Objective: To evaluate the clinical evolution and the association between nutritional status and severity of asthma in children and adolescents enrolled in Primary Health Care. Methods: A retrospective cohort study of 219 asthmatic patients (3-17 years old) enrolled in Primary Care Services (PCSs) in Embu das Artes (SP), from 2007 to 2011. Secondary data: gender, age, diagnosis of asthma severity, other atopic diseases, family history of atopy, and body mass index. To evaluate the clinical outcome of asthma, data were collected on number of asthma exacerbations, number of emergency room consultations and doses of inhaled corticosteroids at follow-up visits in the 6th and 12th months. The statistical analysis included chi-square and Kappa agreement index, with 5% set as the significance level. Results: 50.5% of patients started wheezing before the age of 2 years, 99.5% had allergic rhinitis and 65.2% had a positive family history of atopy. Regarding severity, intermittent asthma was more frequent (51.6%) and, in relation to nutritional status, 65.8% of patients had normal weight. There was no association between nutritional status and asthma severity (p=0.409). After 1 year of follow-up, 25.2% of patients showed reduction in exacerbations and emergency room consultations, and 16.2% reduced the amount of inhaled corticosteroids. Conclusions: The monitoring of asthmatic patients in Primary Care Services showed improvement in clinical outcome, with a decreased number of exacerbations, emergency room consultations and doses of inhaled corticosteroids. No association between nutritional status and asthma severity was observed in this study. PMID:26316387

Interleukin-5 Inhibitors for Severe Asthma: Rationale and Future Outlook.

PubMed

Shrimanker, Rahul; Pavord, Ian D

2017-04-01

In this review, we outline the pathophysiology of severe asthma and discuss the role of anti-interleukin (IL)-5 inhibitors for the treatment of asthma. Anti-IL-5 treatments have shown efficacy in reducing the rate of severe asthma attacks in eosinophilic asthma. We review the history of the development of these agents, lessons learnt about severe asthma along the way and key clinical trials supporting efficacy of the three anti-IL-5 treatments that are clinically available or undergoing clinical trials in asthma.

Asthma Symptom Utility Index: Reliability, validity, responsiveness and the minimal important difference in adult asthma patients

PubMed Central

Bime, Christian; Wei, Christine Y.; Holbrook, Janet T.; Sockrider, Marianna M.; Revicki, Dennis A.; Wise, Robert A.

2012-01-01

Background The evaluation of asthma symptoms is a core outcome measure in asthma clinical research. The Asthma Symptom Utility Index (ASUI) was developed to assess frequency and severity of asthma symptoms. The psychometric properties of the ASUI are not well characterized and a minimal important difference (MID) is not established. Objectives We assessed the reliability, validity, and responsiveness to change of the ASUI in a population of adult asthma patients. We also sought to determine the MID for the ASUI. Methods Adult asthma patients (n = 1648) from two previously completed multicenter randomized trials were included. Demographic information, spirometry, ASUI scores, and other asthma questionnaire scores were obtained at baseline and during follow-up visits. Participants also kept a daily asthma diary. Results Internal consistency reliability of the ASUI was 0.74 (Cronbach’s alpha). Test-retest reliability was 0.76 (intra-class correlation). Construct validity was demonstrated by significant correlations between ASUI scores and Asthma Control Questionnaire (ACQ) scores (Spearman correlation r = −0.79, 95% CI [−0.85, −0.75], P<0.001) and Mini Asthma Quality of Life Questionnaire (Mini AQLQ) scores (r = 0.59, 95% CI [0.51, 0.61], P<0.001). Responsiveness to change was demonstrated, with significant differences between mean changes in ASUI score across groups of participants differing by 10% in the percent predicted FEV1 (P<0.001), and by 0.5 points in ACQ score (P < 0.001). Anchor-based methods and statistical methods support an MID for the ASUI of 0.09 points. Conclusions The ASUI is reliable, valid, and responsive to changes in asthma control over time. The MID of the ASUI (range of scores 0–1) is 0.09. PMID:23026499

Asthma Diagnosis, Severity, Control and Medication Use In Low Income Minority Preteens

PubMed Central

Clark, Noreen M.; Dodge, Julia A.; Shah, Smita; Thomas, Lara J.; Andridge, Rebecca R.; Awad, Daniel

2010-01-01

Background Asthma severity, control, type of medical regimen provided and compliance with it are not well understood in minority patients at the transition stage from childhood to adolescence. Objective Identify factors in clinical practice and patient behavior associated with negative outcomes for children at this developmentally significant period. Methods Parents of 1292 children with asthma among 6827 pre-teens in 19 middle schools in predominantly African American (94%), low income neighborhoods in Detroit, Michigan were enrolled. Data collected through self administered survey and telephone interviews were useable for 936 parents. Study queries related to demographics, asthma symptoms, and medication use. Mixed effects models with a random intercept for school used to determine severity and control and association of medical regimens to these. Results Sixty-seven percent children with probable asthma had received a physician's diagnosis. Being female was associated with being undiagnosed (p=0.02); 47% with no diagnosis had persistent asthma and 68% with a diagnosis and asthma medicines were not controlled. Over half with a diagnosis and no medicine were not controlled. Thirty nine percent had controller medicine; 40% were not compliant with controller use; 9% nebulized controller medicine. Compliant use of controller medicine was not associated with asthma control (p=0.001). Conclusions Lack of an asthma diagnosis was significant in these low income communities. Adolescent girls were at risk for not receiving a diagnosis. Regimens provided children at an important stage in their development were not consistent with therapies recommended for asthma control. Patient compliance with asthma regimens was low. Both clinical and patient education regarding effective asthma management is needed regarding pre teens in low income minority communities. Clinical Implications Diagnosis and medical therapy choices for low income, African American pre-adolescents may not account for the actual level of their symptoms. Asthma is likely to be uncontrolled at this significant developmental stage in this population. Girls may be at risk for diagnosis failure. PMID:20170321

A randomised controlled feasibility trial of Group Cognitive Behavioural Therapy for people with severe asthma.

PubMed

Yorke, Janelle; Adair, Pauline; Doyle, Anne-Marie; Dubrow-Marshall, Linda; Fleming, Sharon; Holmes, Leanne; Menzies-Gow, Andrew; Niven, Rob; Pilling, Mark; Shuldham, Caroline

2017-06-01

Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group. This study aimed to assess the feasibility and acceptability of Group-CBT in severe asthma. This was a two-centre, randomised controlled parallel group feasibility study. Eligible participants (patients with severe asthma and a clinically significant diagnosis of anxiety and/or depression - Hospital Anxiety and Depression Scale (HAD) score greater than 8 for the anxiety or depression sub-scale) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only. Follow-up was for 16 weeks and end points were: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea-12, EuroQual-5D and EuroQuol-VAS. 51 patients were randomised: 36% (51 out of 140) consent rate and attrition at week 16 was 12. Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly demands of the programme. Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health. Participants who contributed to focus group discussions reported that Group-CBT contributed to a better understanding of their illness and related approaches to anxiety management and acceptance of their asthma condition. Although weekly face-to-face sessions were challenging, this was the preferred method of delivery for these participants. This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma. It has been possible but not easy to recruit and retain the sample. Options for a less demanding intervention schedule, such as less frequent face-to-face visits and the use of web-based interventions, require careful consideration.

Sensitization to pets is a major determinant of persistent asthma and new asthma onset in Sweden

PubMed Central

Uddenfeldt, Monica; Janson, Christer; Lampa, Erik

2013-01-01

Introduction Our knowledge about atopy as a longitudinal predictor of asthma is limited. The purpose of this study was to investigate the prognosis of asthma and risk factors for asthma onset, especially sensitization of specific allergens in a population sample. Material and methods A cohort responded to a respiratory questionnaire in 1990 and 2003. At baseline, 2,060 subjects who, in the screening questionnaire, reported respiratory symptoms and 482 controls were investigated with interviews, spirometry, and skin-prick test. A total of 721 asthmatics and 976 subjects without respiratory disease were clinically verified. At follow-up in 2003, 340 subjects with persistent asthma and 186 subjects with asthma remission were identified, while 76 subjects reported new asthma onset. Results Sensitization to pets and a high symptom score were significant determinants of persistent asthma (odds ratio (OR) 3.2 (95% CI 1.9–5.6) and 5.7 (2.5–13.3), respectively) and onset of asthma (OR 2.6 (1.1–6.0), and 1.7 (1.2–2.3)). A high self-reported responsiveness to airway irritants (OR 1.6 (1.1–2.2)), and more asthma medications (OR 2.0 (1.3–2.9)) were additional indicators of persistent asthma at the follow-up. Belonging to the older age group decreased the risk both of having persistent asthma and asthma onset. Discussion Asthmatics sensitized to pets have a more severe outcome than asthmatics not sensitized to pets. Sensitization to pets was also a strong predictor for onset of asthma. Special attention should be given to asthmatics who report having severe symptoms and problems with airway irritants as such patients are more likely to have persistent problems. PMID:23339512

Sleep-disordered breathing in children with asthma: a systematic review on the impact of treatment

PubMed Central

Sánchez, Trinidad; Castro-Rodríguez, José A; Brockmann, Pablo E

2016-01-01

Background The objective was to perform a systematic review in order to describe the relationship between asthma and sleep-disordered breathing (SDB) in children, especially regarding the impact of treatment and management. Methods We performed an electronic search in MEDLINE, EMBASE, and LILACS database. Study inclusion criteria were the following: 1) studies that examined the relationship between asthma/wheezing and SDB/obstructive sleep apnea (OSA); and 2) studies conducted in children <18 years of age. Primary outcomes were the prevalence of asthma and SDB, the tests used for diagnosis, and the influence of their treatment and management. Results One thousand and twenty studies were identified, among which 32 were selected (n=143,343 children; 51% males; age [mean ± standard deviation] 8.4±2.5 years). Most studies (n=26) diagnosed SDB using questionnaires or clinical history. Nine studies performed a sleep study for diagnosing OSA. The diagnosis of asthma was based on clinical history (n=16), previous medical diagnosis (n=4), questionnaires (n=12), and spirometry (n=5). Children with asthma were more likely to develop habitual snoring and OSA, and children with SDB were more likely to develop asthma. Moreover, asthma was associated with more severe OSA, and the presence of SDB was associated with severe asthma. Treatment of SDB with adenotonsillectomy was associated with significant asthma improvement. Conclusion The relationship between asthma and SDB appears to be bidirectional, and adenotonsillectomy appears to improve asthma control. Future trials on how asthma treatment could impact on SDB are needed. PMID:27143940

Nasal polyps and the severity of asthma.

PubMed

Ceylan, Erkan; Gencer, Mehmet; San, Imran

2007-03-01

Upper airway pathologies often accompany asthma. Because this represents a single airway, the diagnosis, follow up and treatment of both upper and lower respiratory diseases is essential. Samter Syndrome (SS) is known to be associated with more severe asthma. The presence of nasal polyps (NPs) is also associated with asthma. However, the incidence of NPs in asthma and the effect of NPs on asthma severity are not well documented. Three hundred and forty-two asthma patients were evaluated by endoscopic nasal examination, pulmonary function test, skin prick tests and paranasal sinus tomography. Three hundred and eleven patients with asthma without NP, 19 asthma patients with NP and 12 patients with SS were included. It was found that 54.3% of patients without NPs, 63.2% with NP and 66.7% with SS were at step 3 on the Global Initiative for Asthma scale of severity, and 1.9%, 15.8% and 33.3% were at step 4, respectively. The presence of NPs in asthma patients is associated with an increase in asthma severity. In patients with asthma, the possibility of NPs should be investigated and treatment planned accordingly.

The epidemiology of asthma and its comorbidities in Poland--Health problems of patients with severe asthma as evidenced in the Province of Lodz.

PubMed

Panek, Michał; Mokros, Łukasz; Pietras, Tadeusz; Kuna, Piotr

2016-03-01

Population studies supply interesting data regarding the epidemiology, comorbidity and risk factors of asthma, which have direct clinical implications for patients. The aim of the work was to evaluate the degree of severity of asthma in the studied group, the levels of anti-asthma treatment, the prevalence of asthma comorbidities and their influence on the clinical course of the illness. The study encompassed 451 participants: 52.11% were asthma patients (study group) and 47.89% were healthy subjects (controls). Respiratory function tests, ACT™ test and skin prick tests were performed. Asthma severity was mild in 14.89%, moderate in 49.36% and severe in 35.74%. Oral GCS were used by 29%, inhalers 44%, LABA 68%, SABA 67%, LAMA 6%, SAMA 14% and MX 16%. Rhinitis and allergy were significantly more common in patients. GERD and neurological diseases were risk factors for asthma, and GERD significantly intensified the risk of severe asthma. GERD, atherosclerosis, hypertension, ischaemic heart disease and other cardiac diseases, lipid disorders, COPD, and the presence of any neoplastic disease significantly worsened the degree of asthma control. Severe asthma was a significant clinical issue in over 35% of cases. The most commonly-used group of drugs were LABAs, while inhaled GCS and LAMA were uncommon, especially among severe cases. A significant problem was the high percentage of systemic GCS used by severe cases. The most important risk factor for asthma, including its severe form, is GERD. Numerous comorbid conditions significantly worsen the degree of asthma control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Managing problematic severe asthma: beyond the guidelines.

PubMed

Pike, Katharine C; Levy, Mark L; Moreiras, John; Fleming, Louise

2018-04-01

This review discusses issues related to managing problematic severe asthma in children and young people. A small minority of children have genuinely severe asthma symptoms which are difficult to control. Children with genuinely severe asthma need investigations and treatments beyond those described within conventional guidelines. However, the majority of children with poor symptom control despite high-intensity treatment achieve improvement in their asthma control once attention has been paid to the basics of asthma management. Basic asthma management requires optimisation of inhaler technique and treatment adherence, avoidance of environmental triggers and self-management education. It is also important that clinicians recognise risk factors that predispose patients to asthma exacerbations and potentially life-threatening attacks. These correctable issues need to be tackled in partnership with children and young people and their families. This requires a coordinated approach between professionals across healthcare settings. Establishing appropriate infrastructure for coordinated asthma care benefits not only those with problematic severe asthma, but also the wider asthma population as similar correctable issues exist for children with asthma of all severities. Investigation and management of genuine severe asthma requires specialist multidisciplinary expertise and a systematic approach to characterising patients' asthma phenotypes and delivering individualised care. While inhaled corticosteroids continue to play a leading role in asthma therapy, new treatments on the horizon might further support phenotype-specific therapy. © 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.

Organising primary health care for people with asthma: the patient's perspective.

PubMed Central

Paterson, C; Britten, N

2000-01-01

BACKGROUND: The 1993 chronic disease management contract encourages United Kingdom general practices to implement a standardised package of care with an emphasis on regular visits to an asthma clinic. AIM: To explore the views of people with asthma about the organisation of asthma care in general practice. METHOD: Semi-structured interviews with 20 patients registered with one practice with a nurse-run asthma clinic. The sample was selected to provide people with a wide range of ages and disease severity, and included parents of children. RESULTS: The age range of the interviewees was five to 87 years (parents of children were interviewed) and half of the interviewees had attended the asthma clinic at some time. In describing how they managed their asthma, people identified their medical care alongside other important factors, such as avoiding smoking and pollution, and a decision to seek medical help was made in the context of all of life's other priorities. People expressed diverse views about the organisation of care, describing how their needs changed over time and how they balanced up several factors in deciding what was best for them. These factors were encompassed by four themes: the accessibility of care, severity of asthma and dealing with uncertainty, self-knowledge and self-management, and expert knowledge and therapeutic relationships. Interviewees were evenly split between wishing to be seen regularly in the clinic and wishing only to attend when needing help. CONCLUSION: Patients required asthma services that allow individual choice and flexibility, and eight service objectives were identified that would cover most people's needs. PMID:10897514

Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma.

PubMed

Schatz, Michael; Hsu, Jin-Wen Y; Zeiger, Robert S; Chen, Wansu; Dorenbaum, Alejandro; Chipps, Bradley E; Haselkorn, Tmirah

2014-06-01

Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies. To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma. Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy. Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001). Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Towards tailored and targeted adherence assessment to optimise asthma management

PubMed Central

van Boven, Job FM; Trappenburg, Jaap CA; van der Molen, Thys; Chavannes, Niels H

2015-01-01

In this paper, we aim to emphasise the need for a more comprehensive and tailored approach to manage the broad nature of non-adherence, to personalise current asthma management. Although currently several methods are available to measure the extent of asthma patients’ adherence, the vast majority do not incorporate confirmation of the actual inhalation, dose and inhalation technique. Moreover, most current measures lack detailed information on the individual consequences of non-adherence and on when and how to take action if non-adherence is identified. Notably, one has to realise there are several forms of non-adherence (erratic non-adherence, intelligent non-adherence and unwitting non-adherence), each requiring a different approach. To improve asthma management, more accurate methods are needed that integrate measures of non-adherence, asthma disease control and patient preferences. Integrating information from the latest inhaler devices and patient-reported outcomes using mobile monitoring- and feedback systems (‘mHealth’) is considered a promising strategy, but requires careful implementation. Key issues to be considered before large-scale implementation include patient preferences, large heterogeneity in patient and disease characteristics, economic consequences, and long-term persistence with new digital technologies. PMID:26181850

Targeted therapy in severe asthma today: focus on immunoglobulin E.

PubMed

Pelaia, Girolamo; Canonica, Giorgio Walter; Matucci, Andrea; Paolini, Rossella; Triggiani, Massimo; Paggiaro, Pierluigi

2017-01-01

Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard "one size fits all" approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma.

Targeted therapy in severe asthma today: focus on immunoglobulin E

PubMed Central

Pelaia, Girolamo; Canonica, Giorgio Walter; Matucci, Andrea; Paolini, Rossella; Triggiani, Massimo; Paggiaro, Pierluigi

2017-01-01

Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard “one size fits all” approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma. PMID:28721017

Asthma, hay fever, and food allergy are associated with caregiver-reported speech disorders in US children

PubMed Central

Strom, Mark A.; Silverberg, Jonathan I.

2016-01-01

Background Children with asthma, hay fever, and food allergy may have several factors that increase their risk of speech disorder, including allergic inflammation, ADD/ADHD, and sleep disturbance. However, few studies have examined a relationship between asthma, allergic disease, and speech disorder. We sought to determine whether asthma, hay fever, and food allergy are associated with speech disorder in children and whether disease severity, sleep disturbance, or ADD/ADHD modified such associations. Methods We analyzed cross-sectional data on 337,285 children aged 2–17 years from 19 US population-based studies, including the 1997–2013 National Health Interview Survey and the 2003/4 and 2007/8 National Survey of Children’s Health. Results In multivariate models, controlling for age, demographic factors, healthcare utilization, and history of eczema, lifetime history of asthma (odds ratio [95% confidence interval]: 1.18 [1.04–1.34], p = 0.01), and one-year history of hay fever (1.44 [1.28–1.62], p < 0.0001) and food allergy (1.35 [1.13–1.62], p = 0.001) were associated with increased odds of speech disorder. Children with current (1.37 [1.15–1.59] p = 0.0003) but not past (p = 0.06) asthma had increased risk of speech disorder. In one study that assessed caregiver-reported asthma severity, mild (1.58 [1.20–2.08], p = 0.001) and moderate (2.99 [1.54–3.41], p < 0.0001) asthma were associated with increased odds of speech disorder; however, severe asthma was associated with the highest odds of speech disorder (5.70 [2.36–13.78], p = 0.0001). Conclusion Childhood asthma, hay fever, and food allergy are associated with increased risk of speech disorder. Future prospective studies are needed to characterize the associations. PMID:27091599

An algorithmic approach for the treatment of severe uncontrolled asthma

PubMed Central

Zervas, Eleftherios; Samitas, Konstantinos; Papaioannou, Andriana I.; Bakakos, Petros; Loukides, Stelios; Gaga, Mina

2018-01-01

A small subgroup of patients with asthma suffers from severe disease that is either partially controlled or uncontrolled despite intensive, guideline-based treatment. These patients have significantly impaired quality of life and although they constitute <5% of all asthma patients, they are responsible for more than half of asthma-related healthcare costs. Here, we review a definition for severe asthma and present all therapeutic options currently available for these severe asthma patients. Moreover, we suggest a specific algorithmic treatment approach for the management of severe, difficult-to-treat asthma based on specific phenotype characteristics and biomarkers. The diagnosis and management of severe asthma requires specialised experience, time and effort to comprehend the needs and expectations of each individual patient and incorporate those as well as his/her specific phenotype characteristics into the management planning. Although some new treatment options are currently available for these patients, there is still a need for further research into severe asthma and yet more treatment options. PMID:29531957

Asthma in inner city children: recent insights: United States.

PubMed

Dutmer, Cullen M; Kim, Haejin; Searing, Daniel A; Zoratti, Edward M; Liu, Andrew H

2018-04-01

Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016-2017) advances in the understanding of asthma in US inner city children. Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children.

The Tempest: Difficult to Control Asthma in Adolescence.

PubMed

Burg, Gregory T; Covar, Ronina; Oland, Alyssa A; Guilbert, Theresa W

Severe asthma is associated with significant morbidity and is a highly heterogeneous disorder. Severe asthma in adolescence has some unique elements compared with the features of severe asthma a medical provider would see in younger children or adults. A specific focus on psychological issues and adherence highlights some of the challenges in the management of asthma in adolescents. Treatment of adolescents with severe asthma now includes 3 approved biologic phenotype-directed therapies. Therapies available to adults may be beneficial to adolescents with severe asthma. Research into predictors of specific treatment response by phenotypes is ongoing. Optimal treatment strategies are not yet defined and warrant further investigation. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Obesity increases the prevalence and the incidence of asthma and worsens asthma severity.

PubMed

Barros, R; Moreira, P; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Moreira, A

2017-08-01

We aimed to explore the association between obesity and asthma prevalence, incidence and severity. The study included 32,644 adults, 52.6% female, from a representative sample of the 4th Portuguese National Health Survey. The following asthma definitions were used: ever asthma (ever medical doctor asthma diagnosis), current asthma (asthma within the last 12 months), current persistent asthma (required asthma medication within the last 12 months), current severe asthma (attending an emergency department because of asthma within the last 12 months), and incident asthma (asthma diagnosis within the last 12 months). Body mass index was calculated based on self-reported weight and height and categorised according to WHO classification. Logistic regression models adjusted for confounders were performed. Prevalence of ever asthma was 5.3%, current asthma 3.5%, current persistent asthma 3.0%, current severe asthma 1.4%, and incident asthma 0.2%. Prevalence of obesity was 16%, overweight 37.6%, normal weight 44.6% and underweight 0.2%. Being overweight, obesity class I and II, and obesity class III were associated with an OR (95% CI) with ever asthma 1.22 (1.21-1.24), 1.39 (1.36-1.41), 3.24 (3.08-3.40) respectively; current asthma 1.16 (1.14-1.18), 1.86 (1.82-1.90), 4.73 (4.49-4.98) respectively; current persistent asthma 1.08 (1.06-1.10), 2.06 (2.01-2.10), 5.24 (4.96-5.53), and current severe asthma 1.36 (1.32-1.40), 1.50 (1.45-1.55) and 3.70 (3.46-3.95), respectively. Considering the incidence of asthma, obesity more than quadrupled the odds (OR = 4.46, 95% CI 4.30, 4.62). Obesity is associated in a dose dependent way with an increase of prevalent and incident asthma, and it seems to increase the odds of a more persistent and severe asthma phenotype independently of socio-demographic determinants, physical activity, and dietary patterns. Our results provide rational for future lifestyle intervention studies for weight reduction in the obesity-asthma phenotype. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The natural history of severe asthma and influences of early risk factors: a population-based cohort study.

PubMed

Chen, Wenjia; Marra, Carlo A; Lynd, Larry D; FitzGerald, J Mark; Zafari, Zafar; Sadatsafavi, Mohsen

2016-03-01

Severe asthma is associated with disproportionately high morbidity, but little is known about its natural history and how risk factors at first year of diagnosis modify its subsequent development. Using administrative health data, we retrospectively followed patients 14-55 years of age with newly diagnosed severe asthma in British Columbia, Canada. Based on intensity of resource use (drug therapy) and occurrence of exacerbations, each patient-year was classified into mild, moderate, or severe asthma. We estimated the probability of transition between severity levels or to death over the study period using a four-state Markov model, and used this to assess the 10-year trajectory of severe asthma and the influence of baseline risk factors. We followed 13,467 patients. Ten years after incident severe asthma, 83% had transitioned to a less severe level (mild: 43%, moderate: 40%). Low socioeconomic status, high comorbidity burden, and high adherence (proportion of days covered (PDC) by asthma controller therapy) in the first year were independently associated with, respectively, 10%, 24% and 35% more time in severe asthma over the next 10 years. Sex was not associated with the clinical course. Most patients with incident severe asthma used fewer resources over time, indicating a long-term transition to milder asthma. Potentially modifiable risk factors for poor prognosis of severe asthma include low socioeconomic status and high comorbidity burden. The association between PDC and future asthma severity is likely due to residual confounding by disease severity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Occupational exposures associated with severe exacerbation of asthma.

PubMed

Henneberger, P K; Liang, X; Lillienberg, L; Dahlman-Höglund, A; Torén, K; Andersson, E

2015-02-01

The exacerbation of asthma by workplace conditions is common, but little is known about which agents pose a risk. We used data from an existing survey of adults with asthma to identify occupational exposures associated with severe exacerbation of asthma. Questionnaires were completed by 557 working adults with asthma. Severe exacerbation of asthma in the past 12 months was defined as asthma-related hospitalization, or reports of both unplanned asthma care and treatment with a short course of oral corticosteroids. Occupational exposures for the same time period were assessed using an asthma-specific job exposure matrix. We modeled severe exacerbation to yield prevalence ratios (PRs) for exposures while controlling for potential confounders. A total of 164 participants (29%) were positive for severe exacerbation, and 227 (40.8%) were assessed as being exposed to asthma agents at work. Elevated PRs were observed for several specific agents, notably the irritant subcategories of environmental tobacco smoke (PR 1.84, 95%CI 1.34-2.51) among all participants, inorganic dusts (PR 2.53, 95%CI 1.37-4.67) among men, and the low molecular weight subcategory of other highly reactive agents (PR 1.97, 95%CI 1.08-3.60) among women. Among working adults with asthma, severe exacerbation was associated with several occupational agents.

Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma.

PubMed

Boita, Monica; Heffler, Enrico; Omedè, Paola; Bellocchia, Michela; Bussolino, Claudia; Solidoro, Paolo; Giorgis, Veronica; Guerrera, Francesco; Riva, Giuseppe; Brussino, Luisa; Bucca, Caterina; Rolla, Giovanni

2018-01-01

Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity. © 2018 S. Karger AG, Basel.

The relationship between the Leicester cough questionnaire, eosinophilic airway inflammation and asthma patient related outcomes in severe adult asthma.

PubMed

Natarajan, Sushiladevi; Free, Robert C; Bradding, Peter; McGarvey, Lorcan; Siddiqui, Salman

2017-03-04

Severe asthma is characterised by a variety of symptoms, which include chronic cough, however the mechanisms responsible for cough reflex hypersensitivity in asthma remain poorly elucidated. Current asthma patient-related outcome instruments such as the six-point Juniper Asthma Control Score (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) were not primarily designed to capture cough and its related morbidity in asthma. The Leicester Cough Questionnaire (LCQ) is a patient-related outcome instrument designed to capture the health-related quality of life associated with cough. To date the LCQ has not been evaluated in a severe asthma population. We evaluated 262 extensively characterised adult patients with severe asthma attending the Leicester Severe Asthma Service. All patients had a clinician diagnosis of asthma and objective physiological evidence and met the ATS/ERS criterion for servere asthma. In all patients we evaluated a) the LCQ distribution and b) the relationships between the LCQ and ACQ-6, AQLQ, airway inflammation in sputum. The LCQ demonstrated the following properties; mean: 15.0, standard deviation: 4.54, median: 15.48, and range: 11.6-19.2. We found a moderate correlation between LCQ and ACQ-6 (r = - 0.605, p < 0.0001) and a LCQ and AQLQ (r = 0.710, p < 0.0001). There was no relationship between LCQ and log 10 sputum percentage eosinophils (%). A proportion of patients with severe asthma have a significant degree of cough-related morbidity that appears independent of eosinophilic airway inflammation and is not captured fully by existing asthma patient-reported outcome instruments. Our preliminary findings suggest that further research is now required to validate the LCQ and its responsiveness in severe asthma populations to capture cough-related morbidity and response to specific interventions.

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

Identification and characterization of near-fatal asthma phenotypes by cluster analysis.

PubMed

Serrano-Pariente, J; Rodrigo, G; Fiz, J A; Crespo, A; Plaza, V

2015-09-01

Near-fatal asthma (NFA) is a heterogeneous clinical entity and several profiles of patients have been described according to different clinical, pathophysiological and histological features. However, there are no previous studies that identify in a unbiased way--using statistical methods such as clusters analysis--different phenotypes of NFA. Therefore, the aim of the present study was to identify and to characterize phenotypes of near fatal asthma using a cluster analysis. Over a period of 2 years, 33 Spanish hospitals enrolled 179 asthmatics admitted for an episode of NFA. A cluster analysis using two-steps algorithm was performed from data of 84 of these cases. The analysis defined three clusters of patients with NFA: cluster 1, the largest, including older patients with clinical and therapeutic criteria of severe asthma; cluster 2, with an high proportion of respiratory arrest (68%), impaired consciousness level (82%) and mechanical ventilation (93%); and cluster 3, which included younger patients, characterized by an insufficient anti-inflammatory treatment and frequent sensitization to Alternaria alternata and soybean. These results identify specific asthma phenotypes involved in NFA, confirming in part previous findings observed in studies with a clinical approach. The identification of patients with a specific NFA phenotype could suggest interventions to prevent future severe asthma exacerbations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between Allergic Rhinitis and Asthma Control in Peruvian School Children: A Cross-Sectional Study

PubMed Central

Uceda, Mónica; Ziegler, Otto; Lindo, Felipe; Herrera-Pérez, Eder

2013-01-01

Background. Asthma and allergic rhinitis are highly prevalent conditions that cause major illness worldwide. This study aimed to assess the association between allergic rhinitis and asthma control in Peruvian school children. Methods. A cross-sectional study was conducted among 256 children with asthma recruited in 5 schools from Lima and Callao cities. The outcome was asthma control assessed by the asthma control test. A score test for trend of odds was used to evaluate the association between allergic rhinitis severity and the prevalence of inadequate asthma control. A generalized linear regression model was used to estimate the adjusted prevalence ratios of inadequate asthma control. Results. Allergic rhinitis was present in 66.4% of the population with asthma. The trend analysis showed a positive association between allergic rhinitis and the probability of inadequate asthma control (P < 0.001). It was associated with an increased prevalence of inadequate asthma control, with adjusted prevalence ratios of 1.53 (95% confidence interval: 1.19−1.98). Conclusion. This study indicates that allergic rhinitis is associated with an inadequate level of asthma control, giving support to the recommendation of evaluating rhinitis to improve asthma control in children. PMID:23984414

Co-morbidities in severe asthma: Clinical impact and management.

PubMed

Porsbjerg, Celeste; Menzies-Gow, Andrew

2017-05-01

Patients with severe asthma represent a minority of the total asthma population, but carry a majority of the morbidity and healthcare costs. Achieving better asthma control in this group of patients is therefore of key importance. Systematic assessment of patients with possible severe asthma to identify treatment barriers and triggers of asthma symptoms, including co-morbidities, improves asthma control and reduces healthcare costs and is recommended by international guidelines on management of severe asthma. This review provides the clinician with an overview of the prevalence and clinical impact of the most common co-morbidities in severe asthma, including chronic rhinosinusitis, nasal polyposis, allergic rhinitis, dysfunctional breathing, vocal cord dysfunction, anxiety and depression, obesity, obstructive sleep apnoea syndrome (OSAS), gastroesophageal reflux disease (GERD), bronchiectasis, allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatous with polyangiitis (EGPA). Furthermore, the review offers a summary of recommended diagnostic and management approaches for each co-morbidity. Finally, the review links co-morbid conditions to specific phenotypes of severe asthma, in order to guide the clinician on which co-morbidities to look for in specific patients. © 2017 Asian Pacific Society of Respirology.

GWAS and admixture mapping identify different asthma-associated loci in Latinos: The GALA II Study

PubMed Central

Galanter, Joshua M; Gignoux, Christopher R; Torgerson, Dara G; Roth, Lindsey A; Eng, Celeste; Oh, Sam S; Nguyen, Elizabeth A; Drake, Katherine A; Huntsman, Scott; Hu, Donglei; Sen, Saunak; Davis, Adam; Farber, Harold J.; Avila, Pedro C.; Brigino-Buenaventura, Emerita; LeNoir, Michael A.; Meade, Kelley; Serebrisky, Denise; Borrell, Luisa N; Rodríguez-Cintrón, William; Estrada, Andres Moreno; Mendoza, Karla Sandoval; Winkler, Cheryl A.; Klitz, William; Romieu, Isabelle; London, Stephanie J.; Gilliland, Frank; Martinez, Fernando; Bustamante, Carlos; Williams, L Keoki; Kumar, Rajesh; Rodríguez-Santana, José R.; Burchard, and Esteban G.

2013-01-01

Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations and replication of positive associations has been inconsistent. Objective To identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1,893) and healthy controls (n = 1,881) were recruited from five sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest p-value: rs2523924, p < 5 × 10−6). This association replicates in a meta-analysis of the EVE Asthma Consortium (p = 0.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between the 17q21 asthma in Latinos (IKZF3, lowest p-value: rs90792, OR: 0.67, 95% CI 0.61 – 0.75, p = 6 × 10−13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, while genome-wide association confirms the previously identified locus on 17q21. PMID:24406073

Assessment of variations in control of asthma over time.

PubMed

Combescure, C; Chanez, P; Saint-Pierre, P; Daurès, J P; Proudhon, H; Godard, P

2003-08-01

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

Airway lipoxin A4 generation and lipoxin A4 receptor expression are decreased in severe asthma.

PubMed

Planagumà, Anna; Kazani, Shamsah; Marigowda, Gautham; Haworth, Oliver; Mariani, Thomas J; Israel, Elliot; Bleecker, Eugene R; Curran-Everett, Douglas; Erzurum, Serpil C; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Gaston, Benjamin; Jarjour, Nizar N; Busse, William W; Wenzel, Sally E; Levy, Bruce D

2008-09-15

Airway inflammation is common in severe asthma despite antiinflammatory therapy with corticosteroids. Lipoxin A(4) (LXA(4)) is an arachidonic acid-derived mediator that serves as an agonist for resolution of inflammation. Airway levels of LXA(4), as well as the expression of lipoxin biosynthetic genes and receptors, in severe asthma. Samples of bronchoalveolar lavage fluid were obtained from subjects with asthma and levels of LXA(4) and related eicosanoids were measured. Expression of lipoxin biosynthetic genes was determined in whole blood, bronchoalveolar lavage cells, and endobronchial biopsies by quantitative polymerase chain reaction, and leukocyte LXA(4) receptors were monitored by flow cytometry. Individuals with severe asthma had significantly less LXA(4) in bronchoalveolar lavage fluids (11.2 +/- 2.1 pg/ml) than did subjects with nonsevere asthma (150.1 +/- 38.5 pg/ml; P < 0.05). In contrast, levels of cysteinyl leukotrienes were increased in both asthma cohorts compared with healthy individuals. In severe asthma, 15-lipoxygenase-1 mean expression was decreased fivefold in bronchoalveolar lavage cells. In contrast, 15-lipoxgenase-1 was increased threefold in endobronchial biopsies, but expression of both 5-lipoxygenase and 15-lipoxygenase-2 in these samples was decreased. Cyclooxygenase-2 expression was decreased in all anatomic compartments sampled in severe asthma. Moreover, LXA(4) receptor gene and protein expression were significantly decreased in severe asthma peripheral blood granulocytes. Mechanisms underlying pathological airway responses in severe asthma include lipoxin underproduction with decreased expression of lipoxin biosynthetic enzymes and receptors. Together, these results indicate that severe asthma is characterized, in part, by defective lipoxin counterregulatory signaling circuits.

Airway Inflammation and Illness Severity in Response to Experimental Rhinovirus Infection in Asthma

PubMed Central

Zhu, Jie; Message, Simon D.; Qiu, Yusheng; Mallia, Patrick; Kebadze, Tatiana; Contoli, Marco; Ward, Christine K.; Barnathan, Elliot S.; Mascelli, Mary Ann; Kon, Onn M.; Papi, Alberto; Stanciu, Luminita A.; Jeffery, Peter K.

2014-01-01

Background: The nature of bronchial mucosal inflammation and its physiologic and clinical significance in rhinovirus-induced asthma exacerbations is unclear. We investigated bronchial mucosal inflammatory response and its association with physiologic and clinical outcomes in an experimental model of rhinovirus-induced asthma exacerbations. Methods: We used immunohistochemistry methods to detect phenotypes of inflammatory cells infiltrating the bronchial mucosa before and after experimental rhinovirus infection in 10 subjects with asthma and 15 normal subjects. Results: Compared with baseline, rhinovirus infection significantly increased the number of epithelial (P = .005) and subepithelial (P = .017) neutrophils in subjects with asthma only and subepithelial CD68+ macrophages in both subjects with asthma (P = .009) and normal subjects (P = .018) but more so in those with asthma (P = .021). Numbers of CD45+, CD68+, and CD20+ cells; neutrophils; and eosinophils at day 4 postinfection were positively associated with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects with asthma, CD4+ cells correlated with chest symptom scores (r = 0.69, P = .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = −0.89, P = .029), the PC10 correlated inversely with CD4+ (r = −0.67, P = .023) and CD8+ cells (r = −0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = −0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = −0.72, P = .03), whereas higher subepithelial mast cell counts were significantly associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P = .024). Conclusions: In subjects with asthma, rhinovirus infection induces bronchial mucosal neutrophilia and more severe monocyte/macrophage infiltration than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes during infection are related to virus load and physiologic and clinical severity, whereas mast cells are related to greater lung function. PMID:24457412

Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma

PubMed Central

Greenwald, Roby; Fitzpatrick, Anne M.; Gaston, Benjamin; Marozkina, Nadzeya V.; Erzurum, Serpil; Teague, W. Gerald

2010-01-01

Background Children with severe asthma have poor symptom control and elevated markers of airway oxidative and nitrosative stress. Paradoxically, they have decreased airway levels of S-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism. Methods and Findings We collected EBC samples from children and adolescents, including 38 with severe asthma, 46 with mild-to-moderate asthma and 16 healthy adolescent controls, and the concentration of ionic constituents was quantified using ion chromatography. The concentrations of EBC components with volatile conjugates were log-normally distributed. Formate was the principal ion that displayed a significant difference between asthma status classifications. The mean EBC formate concentration was 40% higher in samples collected from all asthmatics than from healthy controls (mean = 5.7 µM, mean±standard deviation = 3.1−10.3 µM vs. 4.0, 2.8−5.8 µM, p = 0.05). EBC formate was higher in severe asthmatics than in mild-to-moderate asthmatics (6.8, 3.7−12.3 µM vs. 4.9, 2.8−8.7 µM, p = 0.012). In addition, formate concentration was negatively correlated with methacholine PC20 (r = −0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose. Conclusions We conclude that EBC formate concentration is significantly higher in the breath of children with asthma than in those without asthma. In addition, amongst asthmatics, formate is elevated in the breath of those with severe asthma compared to those with mild-to-moderate asthma. We suggest that this difference is related to asthma pathology and may be a product of increased catabolism of endogenous S-nitrosothiols. PMID:20689836

[Predictive factors associated with severity of asthma exacerbations].

PubMed

Atiş, Sibel; Kaplan, Eylem Sercan; Ozge, Cengiz; Bayindir, Suzan

2008-01-01

Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

Factors that influence quality of life in rural children with asthma and their parents.

PubMed

Walker, Jennifer; Winkelstein, Marilyn; Land, Cassia; Lewis-Boyer, Lapricia; Quartey, Ruth; Pham, Luu; Butz, Arlene

2008-01-01

Among rural children with asthma and their parents, this study examined the relationship between parental and child reports of quality of life and described the relationship of several factors such as asthma severity, missed days of work, and asthma education on their quality of life. Two hundred one rural families with asthma were enrolled in a school-based educational program. Intervention parents and children participated in interactive asthma workshop(s) and received asthma devices and literature. Parent and child quality of life measurements were obtained before and after the intervention using Juniper's Paediatric Caregivers Quality of Life and Juniper's Paediatric Quality of Life Questionnaires. Asthma severity was measured using criteria from the National Asthma Education and Prevention Program guidelines. There was no association between parent and child total quality of life scores, and mean parental total quality of life scores were higher at baseline and follow-up than those of the children. All the parents' quality of life scores were correlated with parental reports of missed days of work. For all children, emotional quality of life (EQOL) was significantly associated with parental reports of school days missed (P = .03) and marginally associated with parental reports of hospitalizations due to asthma (P = .08). Parent's EQOL and activity quality of life (AQOL) were significantly associated with children's asthma severity (EQOL, P = .009; AQOL, P = .03), but not the asthma educational intervention. None of the child quality of life measurements was associated with asthma severity. Asthma interventions for rural families should help families focus on gaining and maintaining low asthma severity levels to enjoy an optimal quality of life. Health care providers should try to assess the child's quality of life at each asthma care visit independently of the parents.

The association between endotoxin and beta-(1 → 3)-D-glucan in house dust with asthma severity among schoolchildren.

PubMed

Oluwole, Oluwafemi; Rennie, Donna C; Senthilselvan, Ambikaipakan; Dyck, Roland; Afanasieva, Anna; Kirychuk, Shelley; Katselis, George; Lawson, Joshua A

2018-05-01

Asthma severity can be affected by microbial exposures. However, less is known about the specific indoor agents aggravating the disease in children. We examined the associations between indoor endotoxin and beta-(1 → 3)-D-glucan exposures and asthma severity in children with asthma. A clinical cross-sectional study of schoolchildren (aged 7-17 years) was conducted in the province of Saskatchewan, Canada. Children with asthma (n = 116) were identified from 335 participants using a combination of survey responses and objective clinical assessments. We then ascertained asthma severity based on recommended guidelines (continuous daytime asthma symptoms, frequent nighttime asthma symptoms, and ≤ 60% predicted FEV 1 ). Levels of indoor endotoxin and beta-(1 → 3)-D-glucan were measured in dust samples obtained from play area floors and child's mattresses. The study population of 116 children with asthma was comprised of 75.9% mild asthma and 24.1% moderate/severe asthma. Higher mattress endotoxin concentration was associated with increased odds of moderate/severe asthma [adjusted odds ratio (aOR) = 11.40, 95% confidence interval (CI): 1.45-89.43] while higher beta-(1 → 3)-D-glucan concentration (aOR = 0.16, 95% CI: 0.03-0.89) and load (aOR = 0.10, 95% CI: 0.02-0.72) in play areas were inversely associated with moderate/severe asthma. Furthermore, higher mattress endotoxin concentration was associated with lower FVC (p = 0.01) and FEV 1 (p = 0.03). These associations were not seen for beta-(1 → 3)-D-glucan. Our results showed differential effects of microbial exposures on childhood asthma severity and further highlight domestic endotoxin exposure effects on respiratory health outcomes in children with asthma. Copyright © 2018 Elsevier Ltd. All rights reserved.

Alterations of the arginine metabolome in asthma.

PubMed

Lara, Abigail; Khatri, Sumita B; Wang, Zeneng; Comhair, Suzy A A; Xu, Weiling; Dweik, Raed A; Bodine, Melanie; Levison, Bruce S; Hammel, Jeffrey; Bleecker, Eugene; Busse, William; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar; Moore, Wendy; Peters, Stephen P; Teague, W Gerald; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2008-10-01

As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation. We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity. Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated. Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma. Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.

Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis.

PubMed

Moore, Wendy C; Hastie, Annette T; Li, Xingnan; Li, Huashi; Busse, William W; Jarjour, Nizar N; Wenzel, Sally E; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

2014-06-01

Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation. Published by Mosby, Inc.

Bronchial Thermoplasty – Long Term Safety and Effectiveness in Severe Persistent Asthma

PubMed Central

Wechsler, Michael E.; Laviolette, Michel; Rubin, Adalberto S.; Fiterman, Jussara; Lapa e Silva, Jose R.; Shah, Pallav L.; Fiss, Elie; Olivenstein, Ronald; Thomson, Neil C.; Niven, Robert M.; Pavord, Ian D.; Simoff, Michael; Hales, Jeff B.; McEvoy, Charlene; Slebos, Dirk-Jan; Holmes, Mark; Phillips, Martin J.; Erzurum, Serpil C.; Hanania, Nicola A.; Sumino, Kaharu; Kraft, Monica; Cox, Gerard; Sterman, Daniel H.; Hogarth, Kyle; Kline, Joel N.; Mansur, Adel H.; Louie, Brian E.; Leeds, William M.; Barbers, Richard G.; Austin, John H.M.; Shargill, Narinder S.; Quiring, John; Armstrong, Brian; Castro, Mario

2014-01-01

Background Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. Objective To assess effectiveness and safety of BT in asthma patients 5 years post therapy. Methods BT-treated subjects from the Asthma Intervention Research 2 (AIR2) Trial (ClinicalTrials.gov NCT01350414) were evaluated annually for 5 years to assess long-term safety of BT and durability of treatment effect. Outcomes assessed post-BT included severe exacerbations, adverse events, healthcare utilization, spirometry data, and high resolution computed tomography (HRCT) scans. Results 162/190 BT-treated subjects (85.3%) from the AIR2 Trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and Emergency Room visits, and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months prior to BT treatment (average 5 year reduction in proportions: 44% for exacerbations and 78% for ER visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in Years 2 through 5 as compared to the first year after BT. Pre-BD FEV1 values remained stable between years 1 and 5 after BT, despite a 17% reduction in average daily inhaled corticosteroid dose. HRCT scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. Conclusions These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ER visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking ICS (inhaled corticosteroids) and LABA (long-acting-β2-agonists). PMID:23998657

Body Mass Index and Comorbidities in Adult Severe Asthmatics

PubMed Central

Bruno, Andreina; Pace, Elisabetta; Cibella, Fabio; Chanez, Pascal

2014-01-01

Both severe asthma and obesity are growing health problems. Severe asthma leads to a poor quality of life. The relationship among BMI, comorbidities, and severe asthma control in adults is still unclear. The aim of the study is to better understand the effect of the comorbidities as atopy, type II diabetes, OSAS, gastroesophageal reflux, hypertension, cardiovascular diseases, osteoporosis, infections, and psychological factors with BMI on asthma control in a cohort of adult severe asthmatics. One hundred and two patients were enrolled in a cross-sectional study assessing asthma control, treatments, pulmonary function, inflammatory markers, and comorbidities. Patients were divided into 3 classes according to BMI: normal weight, overweight, and obese. We found that the optimal state of asthma control is lower. whereas the score of Asthma Control Questionnaire, the number of asthma exacerbations during last year, the oral corticosteroids requirement during the previous year, and the LABA treatments are higher in obese than in overweight and normal weight severe asthmatics. The number of subjects with type II diabetes and OSAS are higher among obese and overweight patients than in normal weight asthmatics. In conclusion, BMI represents per se a factor for the deterioration in disease control in severe asthma. PMID:24987694

Advances in pediatric asthma and atopic dermatitis.

PubMed

Foroughi, Shabnam; Thyagarajan, Ananth; Stone, Kelly D

2005-10-01

Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.

Validity of two common asthma-specific quality of life questionnaires: Juniper mini asthma quality of life questionnaire and Sydney asthma quality of life questionnaire

PubMed Central

2012-01-01

Background This study explored the psychometric properties (internal consistency, construct validity, discriminative ability) of the Juniper Mini Asthma Quality of Life Questionnaire (Mini AQLQ-J) and the Sydney Asthma Quality of Life Questionnaire (AQLQ-S). Methods One hundred fourty-six adults (18–45 years) with asthma requiring regular inhaled corticosteroids were recruited to a trial of written emotional disclosure. Correlational analyses were performed to understand the relationship of the two measures with each other, with symptoms, lung function, asthma control, asthma bother and generic quality of life. Median quality of life scores were compared according to gender, health care usage and levels of asthma severity. Results AQLQ-J and AQLQ-S total scores correlated strongly with each other (rho = −0.80) and moderately with the EuroQol Current Health Status Scale (AQLQ-J: rho = 0.35; AQLQ-S: rho = −0.40). Domain score correlations between AQLQ-J and AQLQ-S were mostly moderate (0.50 < rho < 0.80). Both QoL measures were significantly correlated with symptom score. Correlations with the symptom score asthma module (AQLQ-J: rho = −0.69; AQLQ-S: rho = 0.50) were stronger compared with the total symptom score and the symptom score rhinitis module (AQLQ-J: rho = −0.41; AQLQ-S: rho =0.31). Neither QoL measure was significantly correlated with FEV1, % predicted at the total or the domain level. Total scores of both measures were significantly correlated with subjective asthma control (AQLQ-J: rho = 0.68; AQLQ-S: rho = −0.61) and asthma bother (AQLQ-J: rho = −0.73; AQLQ-M: rho = 0.73). Total AQLQ-J score and total AQLQ-S score were significantly associated with perceived asthma severity (AQLQ-J: p=0.004, AQLQ-S: p=0.002) and having visited a GP in the past four months (AQLQ-J: p=0.003, AQLQ-S: p=0.002). Conclusions This study provides further evidence for the validity of the AQLQ-J and the AQLQ-S in a British population of adult patients with asthma managed in primary care. Correlations with lung function parameters were weak or absent. Correlations with generic quality of life were moderate, those with asthma symptoms, asthma control and asthma bother were strong. Both measures are able to discriminate between levels of asthma severity and health care usage. PMID:22906054

Usefulness of induced sputum eosinophil count to assess severity and treatment outcome in asthma patients

PubMed Central

Bandyopadhyay, Ankan; Roy, Partha P.; Saha, Kaushik; Chakraborty, Semanti; Jash, Debraj; Saha, Debabrata

2013-01-01

Context: Currently treatment decisions in asthma are governed by clinical assessment and spirometry. Sputum eosinophil, being a marker of airway inflammation, can serve as a tool for assessing severity and response to treatment in asthma patients. Aims: To establish correlation between change in sputum eosinophil count and forced expiratory volume in one second (FEV1)% predicted value of asthma patients in response to treatment. In this study, we also predicted prognosis and treatment outcome of asthma patients from baseline sputum eosinophil count. Settings and Design: A longitudinal study was conducted to determine the treatment outcome among newly diagnosed asthma patients who were classified into A (n = 80) and B (n = 80) groups on the basis of initial sputum eosinophil count (A ≥ 3% and B < 3%). Materials and Methods: After starting treatment according to Global Initiative for Asthma Guideline, both A and B groups were evaluated every 15 days interval for the 1st month and monthly thereafter for a total duration of 12 months. In each follow-up visit detailed history, induced sputum eosinophil count and spirometry were done to evaluate severity and treatment outcome. Results: FEV1% predicted of group A asthma patients gradually increased and sputum eosinophil count gradually decreased on treatment. Longer time was required to achieve satisfactory improvement (FEV1% predicted) in asthma patients with sputum eosinophil count ≥3%. There was statistically significant negative correlation between FEV1% predicted and sputum eosinophil count (%) in of group A patients in each follow-up visit, with most significant negative correlation found in 8th visit (r = −0.9237 and P = < 0.001). Change in mean FEV1% (predicted) from baseline showed strong positive correlation (r = 0.976) with change in reduction of mean sputum eosinophil count at each follow-up visits in group A patients. Conclusions: Sputum eosinophil count, being an excellent biomarker of airway inflammation, can serve as a useful marker to assess disease severity, treatment outcome, and prognosis in asthma patients. PMID:23741092

Positive exercise test and obstructive spirometry in young male conscripts associated with persistent asthma 20 years later.

PubMed

Lindström, Irmeli; Suojalehto, Hille; Lindholm, Harri; Pallasaho, Paula; Luukkonen, Ritva; Karjalainen, Jouko; Lauerma, Antti; Karjalainen, Antti

2012-12-01

Asthma often begins in childhood or early adulthood and is a common disease among conscripts. The identification of long-term predictive factors for persistent asthma may lead to improved treatment opportunities and better disease control. Our aim was to study the prognostic factors of the severity of asthma among 40-year-old male conscripts whose asthma began in youth. We studied 119 conscripts who were referred to the Central Military Hospital during 1987-1990 due to asthma and who attended a follow-up visit approximately 20 years later. Asthma severity was evaluated during military service according to the medical records, and 20 years later during a follow-up visit using Global Initiative for Asthma guidelines. We used the results of lung function and allergy tests at baseline as predictors of current persistent asthma. Compared with baseline, asthma was less severe at follow-up: 11.8% of subjects were in remission, 42.0% had intermittent asthma, 10.9% had mild persistent asthma, and 35.3% had moderate/severe persistent asthma (p < .001). In multivariate models, a positive exercise test at baseline yielded an odds ratio (OR) of 3.2 (95% CI 1.0-9.8, p = .046), a decreased FEV1/FVC % predicted an OR of 4.0 (95% CI 1.7-9.3, p = .002), and a decreased FEF50% % predicted an OR of 2.8 (95% CI 1.3-6.4, p = .012) for current persistent asthma. About half of the men had persistent asthma at the 20-year follow-up. Positive exercise tests and obstructive spirometry results were related to the persistence of asthma and may be useful long-term prognostic factors for asthma severity.

Prevalence of gastro-oesophageal reflux disease symptoms and reflux-associated respiratory symptoms in asthma

PubMed Central

2010-01-01

Background Gastro-oesophageal reflux disease (GORD) symptoms are common in asthma and have been extensively studied, but less so in the Asian continent. Reflux-associated respiratory symptoms (RARS) have, in contrast, been little-studied globally. We report the prevalence of GORD symptoms and RARS in adult asthmatics, and their association with asthma severity and medication use. Methods A cross-sectional analytical study. A validated interviewer-administered GORD scale was used to assess frequency and severity of seven GORD symptoms. Subjects were consecutive asthmatics attending medical clinics. Controls were matched subjects without respiratory symptoms. Results The mean (SD) composite GORD symptom score of asthmatics was significantly higher than controls (21.8 (17.2) versus 12.0 (7.6); P < 0.001) as was frequency of each symptom and RARS. Prevalence of GORD symptoms in asthmatics was 59.4% (95% CI, 59.1%-59.6%) versus 28.5% in controls (95% CI, 29.0% - 29.4%). 36% of asthmatics experienced respiratory symptoms in association with both typical and atypical GORD symptoms, compared to 10% of controls (P < 0.001). An asthmatic had a 3.5 times higher risk of experiencing a GORD symptom after adjusting for confounders (OR 3.5; 95% CI 2.5-5.3). Severity of asthma had a strong dose-response relationship with GORD symptoms. Asthma medication use did not significantly influence the presence of GORD symptoms. Conclusions GORD symptoms and RARS were more prevalent in a cohort of Sri Lankan adult asthmatics compared to non-asthmatics. Increased prevalence of RARS is associated with both typical and atypical symptoms of GORD. Asthma disease and its severity, but not asthma medication, appear to influence presence of GORD symptoms. PMID:20843346

Rubbing ointments and asthma morbidity in adolescents.

PubMed

Reznik, Marina; Sharif, Iman; Ozuah, Philip O

2004-12-01

To determine the relationship between the use of rubbing ointments and asthma morbidity in adolescents. Cross-sectional study. Inner-city high school in the Bronx, New York. 165 adolescents with asthma. Asthma morbidity, defined as emergency department (ED) use for asthma in the past year and over the lifetime. While 127 (77%) of subjects used albuterol as the first treatment for their last asthma attack, 18 (11%) used rubbing ointments. The rubs and albuterol groups were similar in asthma severity, mean age, gender, and ethnicity. However, subjects in the the rubs group were less likely than subjects in the albuterol group to have made an ED visit over the past 12 months or over their lifetime. Regression analysis revealed that, after controlling for asthma severity, use of rubs independently predicted less lifetime ED use. After controlling for asthma severity, use of rubs by adolescents with asthma was associated with lower asthma morbidity as measured by ED use.

Expression of the T Helper 17-Associated Cytokines IL-17A and IL-17F in Asthma and COPD

PubMed Central

Doe, Camille; Bafadhel, Mona; Siddiqui, Salman; Desai, Dhananjay; Mistry, Vijay; Rugman, Paul; McCormick, Margaret; Woods, Joanne; May, Richard; Sleeman, Matthew A.; Anderson, Ian K.

2010-01-01

Background: Asthma and COPD are characterized by airway dysfunction and inflammation. Neutrophilic airway inflammation is a common feature of COPD and is recognized in asthma, particularly in severe disease. The T helper (Th) 17 cytokines IL-17A and IL-17F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain. Methods: We assessed IL-17A and IL-17F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild to moderate COPD, and 27 nonsmoking and 14 smoking control subjects. Sputum IL-17 concentration was measured in 165 subjects with asthma and 27 with COPD. Results: The median (interquartile range) IL-17A cells/mm2 submucosa was increased in mild to moderate asthma (2.1 [2.4]) compared with healthy control subjects (0.4 [2.8]) but not in severe asthma (P = .04). In COPD, IL-17A+ cells/mm2 submucosa were increased (0.5 [3.7]) compared with nonsmoking control subjects (0 [0]) but not compared with smoking control subjects (P = .046). IL-17F+ cells/mm2 submucosa were increased in severe asthma (2.7 [3.6]) and mild to moderate asthma (1.6 [1.0]) compared with healthy controls subjects (0.7 [1.4]) (P = .001) but was not increased in subjects with COPD. IL-17A and IL-17F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs = 0.5, P = .005). The sputum IL-17 concentration in COPD was increased compared with asthma (2 [0-7] pg/mL vs 0 [0-2] pg/mL, P < .0001) and was correlated with post-bronchodilator FEV1% predicted (r = −0.5, P = .008) and FEV1/FVC (r = −0.4, P = .04). Conclusions: Our findings support a potential role for the Th17 cytokines IL-17A and IL-17F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation. PMID:20538817

Adapting and implementing an evidence-based asthma counseling intervention for resource-poor populations

PubMed Central

Thornton, Eleanor; Kennedy, Suzanne; Hayes-Watson, Claire; Krouse, Rebecca Z.; Mitchell, Herman; Cohn, Richard D.; Wildfire, Jeremy; Mvula, Mosanda M.; Lichtveld, Maureen; Grimsley, Faye; Martin, William J.; Stephens, Kevin U.

2016-01-01

Objective To report implementation strategies and outcomes of an evidence-based asthma counseling intervention. The Head-off Environmental Asthma in Louisiana (HEAL) intervention integrated asthma counseling (AC) capacity and addressed challenges facing children with asthma in post-disaster New Orleans. Methods The HEAL intervention enrolled 182 children (4–12 years) with moderate-to-severe persistent asthma. Recruitment occurred from schools in the Greater New Orleans area for one year. Participants received home environmental assessments and tailored asthma counseling sessions during the study period based on the National Cooperative Inner City Asthma Study and the Inner City Asthma Study. Primary (i.e. asthma symptoms) and secondary outcomes (i.e. healthcare utilization) were captured. During the study, changes were made to meet the demands of a post-hurricane and resource-poor environment which included changes to staffing, training, AC tools, and AC sessions. Results After study changes were made, the AC visit rate increased by 92.3%. Significant improvements were observed across several adherence measures (e.g., running out of medications (p=0.009), financial/insurance problems for appointments (p=0.006), worried about medication side-effects (p=0.01), felt medications did not work (p<0.001)). Additionally, an increasing number of AC visits was modestly associated with a greater reduction in symptoms (test-for-trend p=0.059). Conclusion By adapting to the needs of the study population and setting, investigators successfully implemented a counseling intervention that improved participant behaviors and clinical outcomes. The strategies for implementing the AC intervention may serve as a guide for managing asthma and other chronic conditions in resource-poor settings. PMID:27049234

Effect of catastrophic wildfires on asthmatic outcomes in obese children

PubMed Central

Tse, Kevin; Chen, Lie; Tse, Mabel; Zuraw, Bruce; Christiansen, Sandra

2015-01-01

Background Air pollutants from wildfires and obesity independently exacerbate asthma, yet no study has determined the combined effects of these 2 variables on asthma outcomes. Objective To determine the effect of 2 catastrophic wildfires affecting the Southern California region (in 2003 and 2007) on several asthma outcomes in a cohort of children. Methods To investigate the association between wildfire exposure and asthma outcomes, we stratified our study population by body mass index categories (underweight, normal, overweight, and obese) and zip codes (to distinguish individuals who were closer to the fires vs farther away). The primary outcome was the prevalence of physician-dispensed short-acting β-agonist (SABAs). Secondary outcomes included the rate of emergency department visits and/or hospitalizations for asthma, the frequency of oral corticosteroid use for asthma, and number of new diagnoses of asthma. Results A total of 2,195 and 3,965 asthmatic children were analyzed as part of our retrospective cohort during the 2003 and 2007 wildfires, respectively. SABA dispensing increased the most in the obese group after the 2003 wildfires (P <.05). Increased prevalence of SABA dispensing was also noted in the obese group in 2007, but this was not statistically higher than the increases seen in other body mass index groups. There was no observed increase in emergency department and/or hospitalization rates, oral corticosteroid dispensing frequency, or new asthma diagnoses after either wildfire. Conclusion Catastrophic wildfires lead to worsening asthma outcomes, particularly in obese individuals. This study gives further evidence of a link between obesity and asthma severity and suggests that air pollutants released during wildfires can have substantial detrimental effects on asthma control. PMID:25747784

Phenotype-Driven Therapeutics in Severe Asthma.

PubMed

Opina, Maria Theresa D; Moore, Wendy C

2017-02-01

Inhaled corticosteroids are the mainstay of asthma treatment using a step-up approach with incremental dosing and additional controller medications in order to achieve symptom control and prevent exacerbations. While most patients respond well to this treatment approach, some patients remain refractory despite high doses of inhaled corticosteroids and a long-acting β-agonist. The problem lies in the heterogeneity of severe asthma, which is further supported by the emergence of severe asthma phenotypes. This heterogeneity contributes to the variability in treatment response. Randomized controlled trials involving add-on therapies in poorly controlled asthma have challenged the idea of a "one size fits all" approach targeting specific phenotypes in their subject selection. This review discusses severe asthma phenotypes from unbiased clustering approaches and the most recent scientific evidence on novel treatments to provide a guide in personalizing severe asthma treatment.

Prevalence of asthma in Galway school children 2004.

PubMed

Shabu, A; Flanagan, O; Dineen, B; Loftus, B G

2007-06-01

We aimed to ascertain the prevalence of asthma amongst Galway schoolchildren aged 9-10, and to compare the results to a similar study carried out in 1992. A questionnaire was distributed to parents of all children attending 4th class in Galway city schools. 652 of 750(87%) questionnaires were returned. Prevalence of "wheeze ever" was 27.6%, and "current wheeze" 16.3%. The prevalence of asthma was 18.5%. Of those with asthma there was a 2 to 1 male preponderance, 80% had mild asthma, 14% moderate, and 6% severe asthma. 80% were taking anti-asthma therapy, with 48% taking regular inhaled steroids. 84% had a diagnosis of asthma made by a doctor. Comparison with the study of 1992 shows little change in the prevalence of current wheeze, or asthma. There has however been a significant decline in the severity of asthma, and an increase in the use of prophylactic anti-asthma medication. Asthma prevalence appears to be stable in the age group studied. There is a much greater willingness to diagnose, and treat asthma in the community. The severity of asthma, as measured by attack frequency, has declined.

Impact of asthma medication and familial factors on the association between childhood asthma and attention-deficit/hyperactivity disorder: a combined twin- and register-based study: Epidemiology of Allergic Disease.

PubMed

Holmberg, K; Lundholm, C; Anckarsäter, H; Larsson, H; Almqvist, C

2015-05-01

Asthma and attention-deficit/hyperactivity disorder (ADHD) are prevalent in childhood and may cause functional impairment and stress in families. Previous research supports an association between asthma and ADHD in children, but several aspects of this relationship are unclear. Our aim was to study whether the association between asthma and ADHD is restricted to either the inattentive or the hyperactive/impulsive symptoms of ADHD, to explore the impact of asthma severity and asthma medication and the contribution of shared genetic and environmental risk factors on the asthma-ADHD relationship. Data on asthma, ADHD, zygosity and possible confounders were collected from parental questionnaires at 9 or 12 years on 20 072 twins through the Swedish Twin Register, linked to the Swedish Medical Birth Register, the National Patient Register and the Prescribed Drug Register. The association between asthma and ADHD, the impact of asthma severity and medication, was assessed by generalized estimating equations. Cross-twin-cross-trait correlations (CTCT) were estimated to explore the relative importance of genes and environment for the association. Asthmatic children had a higher risk of also having ADHD [odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02]. The association was not restricted to either of the two dimensions of ADHD. The magnitude of the association increased with asthma severity (OR 2.84, 95% CI: 1.86-4.35) for ≥ 4 asthma attacks in the last 12 months and was not affected by asthma treatment. The CTCTs possibly indicate that the genetic component in overlap of the disorders is weak. Childhood asthma, especially severe asthma, is associated with ADHD. Asthma medication seems not to increase the risk of ADHD. Clinicians should be aware of the potential of ADHD in asthma. Optimal asthma care needs to be integrated with effective evaluation and treatment of ADHD in children with co-existing disorders. © 2015 John Wiley & Sons Ltd.

Self-management of multiple chronic conditions among African American women with asthma: A qualitative study

PubMed Central

Janevic, Mary R.; Ellis, Katrina R.; Sanders, Georgiana M.; Nelson, Belinda W.; Clark, Noreen M.

2014-01-01

Objective African American women are disproportionately burdened by asthma morbidity and mortality, and may be more likely than asthma patients in general to have comorbid health conditions. This study sought to identify the self-management challenges faced by African American women with asthma and comorbidities, how they prioritize their conditions, and behaviors perceived as beneficial across conditions. Methods In-depth interviews were conducted with 25 African-American women (mean age 52 years) with persistent asthma and at least one of the following: diabetes, heart disease, or arthritis. Information was elicited on women’s experiences managing asthma and concurrent health conditions. The constant-comparison analytic method was used to develop and apply a coding scheme to interview transcripts. Key themes and subthemes were identified. Results Participants reported an average of 5.7 comorbidities. Fewer than half of the sample considered asthma their main health problem; these perceptions were influenced by beliefs about the relative controllability, predictability, and severity of their health conditions. Participants reported ways in which comorbidities affected asthma management, including that asthma sometimes took a ‘backseat’ to conditions considered more troublesome or worrisome. Mood problems, sometimes attributed to pain or functional limitations resulting from comorbidities, reduced motivation for self-management. Women described how asthma affected comorbidity management; e.g., by impeding recommended exercise. Some self-management recommendations, such as physical activity and weight control, were seen as beneficial across conditions. Conclusions Multiple chronic conditions that include asthma may interact to complicate self-management of each condition. Additional clinical attention and self-management support may help reduce multimorbidity-related challenges. PMID:24161047

p38 Mitogen-Activated Protein Kinase-γ Inhibition by Long-Acting β2 Adrenergic Agonists Reversed Steroid Insensitivity in Severe Asthma

PubMed Central

Mercado, Nicholas; To, Yasuo; Kobayashi, Yoshiki; Adcock, Ian M.; Barnes, Peter J.

2011-01-01

Corticosteroid insensitivity (CI) is a major barrier to treating severe asthma. Despite intensive research, the molecular mechanism of CI remains uncertain. The aim of this study was to determine abnormality in corticosteroid action in severe asthma and to identify the molecular mechanism of the long-acting β2-adrenergic agonists (LABAs) formoterol and salmeterol on restoration of corticosteroid sensitivity in severe asthma in vitro. Peripheral blood mononuclear cells (PBMCs) were obtained from 16 subjects with severe corticosteroid-insensitive asthma, 6 subjects with mild corticosteroid-sensitive asthma, and 11 healthy volunteers. Corticosteroid (dexamethasone) sensitivity was determined on tumor necrosis factor-α (TNF-α)-induced interleukin (IL)-8 production. Glucocorticoid receptor (GR) phosphorylation and kinase phosphorylation were evaluated by immunoprecipitation-Western blotting analysis and kinase phosphorylation array in IL-2/IL-4-treated corticosteroid insensitive model in PBMCs. In vitro corticosteroid sensitivity on TNF-α-induced IL-8 production was significantly lower in patients with severe asthma than in healthy volunteers and patients with mild asthma. This CI seen in severe asthma was associated with reduced GR nuclear translocation and with hyperphosphorylation of GR, which were reversed by LABAs. In IL-2/IL-4-treated PBMCs, LABAs inhibited phosphorylation of Jun-NH2-terminal kinase and p38 mitogen-activated protein kinase-γ (p38MAPK-γ) as well as GR. In addition, cells with p38MAPK-γ knockdown by RNA interference did not develop CI in the presence of IL-2/IL-4. Furthermore, p38MAPK-γ protein expression was up-regulated in PBMCs from some patients with severe asthma. In conclusion, p38 MAPK-γ activation impairs corticosteroid action and p38 MAPK-γ inhibition by LABAs has potential for the treatment of severe asthma. PMID:21917909

Fetal growth and risk of childhood asthma and allergic disease

PubMed Central

Tedner, S G; Örtqvist, A K; Almqvist, C

2012-01-01

Introduction Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods PubMed-search on pre-defined terms and cross-references. Results Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases. PMID:22994341

Childhood asthma clusters and response to therapy in clinical trials.

PubMed

Chang, Timothy S; Lemanske, Robert F; Mauger, David T; Fitzpatrick, Anne M; Sorkness, Christine A; Szefler, Stanley J; Gangnon, Ronald E; Page, C David; Jackson, Daniel J

2014-02-01

Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility. To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials. A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P = .011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial). In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA.

PubMed

Suruki, Robert Y; Daugherty, Jonas B; Boudiaf, Nada; Albers, Frank C

2017-04-27

Asthma exacerbations are frequent in patients with severe disease. This report describes results from two retrospective cohort studies describing exacerbation frequency and risk, emergency department (ED)/hospital re-admissions, and asthma-related costs by asthma severity in the US and UK. Patients with asthma in the US-based Clinformatics™ DataMart Multiplan IMPACT (2010-2011; WEUSKOP7048) and the UK-based Clinical Practice Research Datalink (2009-2011; WEUSKOP7092) databases were categorized by disease severity (Global Initiative for Asthma [GINA]; Step and exacerbation history) during the 12 months pre-asthma medical code (index date). Outcomes included: frequency of exacerbations (asthma-related ED visit, hospitalization, or oral corticosteroid use with an asthma medical code recorded within ±2 weeks) 12 months post-index, asthma-related ED visits/hospitalization, and asthma-related costs 30 days post-index. Risk of a subsequent exacerbation was determined by proportional hazard model. Of the 222,817 and 211,807 patients with asthma included from the US and UK databases, respectively, 12.5 and 8.4% experienced ≥1 exacerbation during the follow-up period. Exacerbation frequency increased with disease severity. Among the 5,167 and 2,904 patients with an asthma-related ED visit/hospitalization in the US and UK databases, respectively, 9.2 and 4.7% had asthma-related re-admissions within 30 days. Asthma-related re-admission rates and costs increased with disease severity, approximately doubling between GINA Step 1 and 5 and in patients with ≥2 versus <2 exacerbations in the previous year. Risk of a subsequent exacerbation increased 32-35% for an exacerbation requiring ED visit/hospitalization versus oral corticosteroids. Increased disease severity was associated with higher exacerbation frequency, ED/hospitalization re-admission, costs and risk of subsequent exacerbation, indicating that these patients require high-intensity post-exacerbation management.

[Management of patients with bronchial asthma received general anesthesia and surgical intervention].

PubMed

To, Masako; Tajima, Makoto; Ogawa, Cyuhei; Otomo, Mamoru; Suzuki, Naohito; Sano, Yasuyuki

2002-01-01

Stimulation to bronchial mucosa is one of the major risk factor of asthma attack. When patients receive surgical intervention and general anesthesia, they are always exposed to stimulation to bronchial mucosa. Prevention method of bronchial asthma attack during surgical intervention is not established yet. We investigated that clinical course of patients with bronchial asthma who received general anesthesia and surgical intervention. Seventy-six patients with bronchial asthma were received general anesthesia and surgical intervention from 1993 to 1998. Twenty-four patients were mild asthmatic patients, 39 were moderate asthmatic patients and 13 were severe asthmatic patients. Preoperative treatment for preventing asthma attack was as follows; Eight patients were given intravenous infusion of aminophylline before operation. Fifty-two patients were given intravenous infusion of aminophylline and hydrocortisone before operation. Three patients were given intravenous infusion of hydrocortisone for consecutive 3 days before operation. Thirteen patients were given no treatment for preventing asthma attack. One patient was suffered from asthma attack during operation. She was given no preventing treatment for asthma attack before operation. Three patients were suffered from asthma attack after operation. No wound dehiscence was observed in all patients. To prevent asthma attack during operation, intravenous infusion of steroid before operation is recommended, when patients with asthma receive general anesthesia and surgical intervention.

Perinatal and Early Childhood Environmental Factors Influencing Allergic Asthma Immunopathogenesis

PubMed Central

Gaffin, Jonathan M.; Kanchongkittiphon, Watcharoot; Phipatanakul, Wanda

2014-01-01

Background The prevalence of asthma has increased dramatically over the past several decades. While hereditary factors are highly important, the rapid rise outstrips the pace of genomic variation. Great emphasis has been placed on potential modifiable early life exposures leading to childhood asthma. Methods We reviewed the recent medical literature for important studies discussing the role of the perinatal and early childhood exposures and the inception of childhood asthma. Results and Discussion Early life exposure to allergens (House dust mite (HDM), furred pets, cockroach, rodent and mold)air pollution (nitrogen dioxide (NO2), ozone (O3), volatile organic compounds (VOCs), and particulate matter (PM)) and viral respiratory tract infections (Respiratory syncytial virus (RSV) and human rhinovirus (hRV)) have been implicated in the development of asthma in high risk children. Conversely, exposure to microbial diversity in the perinatal period may diminish the development of atopy and asthma symptoms. PMID:24952205

Opportunities and obstacles in translating evidence to policy in occupational asthma.

PubMed

Tarlo, Susan M; Arif, Ahmed A; Delclos, George L; Henneberger, Paul; Patel, Jenil

2018-06-01

Occupational asthma (OA), a common respiratory disorder in Western countries, is caused by exposures at the workplace. It is part of a broader definition of work-related asthma (WRA) that also includes pre-existing asthma aggravated by substances present in the workplace environment, and it is potentially preventable. The purpose of this paper is to illustrate preventive measures for occupational asthma by case studies. In three case studies we discuss preventive measures that have been associated with reductions in incidence of occupational asthma from natural rubber latex and from diisocyanates as supported by published literature. We also discuss challenges in relation to asthma from cleaning products in healthcare work. Several preventive measures have been associated with reduction in incidence of occupational asthma from natural rubber latex and from diisocyanates, and may provide lessons for prevention of other causes of occupational asthma. Cleaning products remain an unresolved problem at present with respect to asthma risks but potential measures include the use of safer products and safer applications such as avoidance of spray products, use of occupational hygiene methods such as improving local ventilation, and when appropriate, the use of personal protective devices. Copyright © 2017 Elsevier Inc. All rights reserved.

Obese and Allergic Related Asthma Phenotypes Among Children Across the United States.

PubMed

Ross, Mindy K; Romero, Tahmineh; Sim, Myung S; Szilagyi, Peter G

2018-04-19

Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity and allergy related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and parent-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese. We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with parent-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes. Among 4,427 children with asthma in this NSCH cohort, the association between race and phenotype is statistically significant (p<0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-non-allergic phenotype (p<0.001). ADD/ADHD was more likely to be present in allergic-not-obese children (OR 1.50, CI 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p<0.001). Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the U.S. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.

Relationship of self-reported asthma severity and urgent health care utilization to psychological sequelae of the September 11, 2001 terrorist attacks on the World Trade Center among New York City area residents.

PubMed

Fagan, Joanne; Galea, Sandro; Ahern, Jennifer; Bonner, Sebastian; Vlahov, David

2003-01-01

Posttraumatic psychological stress may be associated with increases in somatic illness, including asthma, but the impact of the psychological sequelae of the September 11, 2001 terrorist attacks on physical illness has not been well documented. The authors assessed the relationship between the psychological sequelae of the attacks and asthma symptom severity and the utilization of urgent health care services for asthma since September 11. The authors performed a random digit dial telephone survey of adults in the New York City (NYC) metropolitan area 6 to 9 months after September 11, 2001. Two thousand seven hundred fifty-five demographically representative adults including 364 asthmatics were recruited. The authors assessed self-reported asthma symptom severity, emergency room (ER) visits, and unscheduled physician office visits for asthma since September 11. After adjustment for asthma measures before September 11, demographics, and event exposure in multivariate models posttraumatic stress disorder (PTSD) were a significant predictor of self-reported moderate-to-severe asthma symptoms (OR = 3.4; CI = 1.2-9.4), seeking care for asthma at an ER since September 11 (OR = 6.6; CI = 1.6-28.0), and unscheduled physician visits for asthma since September 11 (OR = 3.6; CI = 1.1-11.5). The number of PTSD symptoms was also significantly related to moderate-to-severe asthma symptoms and unscheduled physician visits since September 11. Neither a panic attack on September 11 nor depression since September 11 was an independent predictor of asthma severity or utilization in multivariate models after September 11. PTSD related to the September 11 terrorist attacks contributed to symptom severity and the utilization of urgent health care services among asthmatics in the NYC metropolitan area.

Asthma Management in New York City Schools: a Classroom Teacher Perspective

PubMed Central

Cain, Agnieszka; Reznik, Marina

2016-01-01

Objective Classroom teachers play an important role in facilitating asthma management in school but little is known about their perspectives around asthma management. We examined the perspectives of classroom teachers around barriers to school asthma management. Methods We conducted key informant interviews with 21 inner-city classroom teachers from 3rd to 5th grades in 10 Bronx, New York elementary schools. Sampling continued until thematic saturation was reached. Interviews were recorded, transcribed, and independently coded for common themes. We used thematic and content review to analyze interview data. Results Seven themes representing teachers’ perspectives on in-school asthma management emerged: (1) the problematic process of identifying students with asthma; (2) poor familiarity with the city health department’s asthma initiative and poor general knowledge of school policies on asthma management (3) lack of competency in managing an acute asthma attack in the classroom and poor recognition of symptoms of an asthma attack; (4) lack of confidence in dealing with a hypothetical asthma attack in the classroom; (5) lack of quick access to asthma medication in school; (6) limited communication between school staff; and (7) enthusiasm about learning more about asthma management. Conclusions Our results revealed several barriers contributing to suboptimal in-school asthma management: ineffective ways of identifying students with asthma, lack of teacher knowledge of guidelines on asthma management, lack of comfort in managing students’ asthma, inadequate access to asthma medication in school, and limited communication between school staff. These issues should be considered in the design of interventions to improve in-school asthma management. PMID:27031532

A Self-Regulation Theory–Based Asthma Management Mobile App for Adolescents: A Usability Assessment

PubMed Central

2017-01-01

Background Self-regulation theory suggests people learn to influence their own behavior through self-monitoring, goal-setting, feedback, self-reward, and self-instruction, all of which smartphones are now capable of facilitating. Several mobile apps exist to manage asthma; however, little evidence exists about whether these apps employ user-centered design processes that adhere to government usability guidelines for mobile apps. Objective Building upon a previous study that documented adolescent preferences for an asthma self-management app, we employed a user-centered approach to assess the usability of a high-fidelity wireframe for an asthma self-management app intended for use by adolescents with persistent asthma. Methods Individual interviews were conducted with adolescents (ages 11-18 years) with persistent asthma who owned a smartphone (N=8). Adolescents were asked to evaluate a PDF app wireframe consisting of 76 screen shots displaying app features, including log in and home screen, profile setup, settings and info, self-management features, and graphical displays for charting asthma control and medication. Preferences, comments, and suggestions for each set of screen shots were assessed using the audio-recorded interviews. Two coders reached consensus on adolescent evaluations of the following aspects of app features: (1) usability, (2) behavioral intentions to use, (3) confusing aspects, and (4) suggestions for improvement. Results The app wireframe was generally well received, and several suggestions for improvement were recorded. Suggestions included increased customization of charts and notifications, reminders, and alerts. Participants preferred longitudinal data about asthma control and medication use to be displayed using line graphs. All participants reported that they would find an asthma management app like the one depicted in the wireframe useful for managing their asthma. Conclusions Early stage usability tests guided by government usability guidelines (usability.gov) revealed areas for improvement for an asthma self-management app for adolescents. Addressing these areas will be critical to developing an engaging and effective asthma self-management app that is capable of improving adolescent asthma outcomes. PMID:28148471

Point-of-care blood eosinophil count in a severe asthma clinic setting.

PubMed

Heffler, Enrico; Terranova, Giovanni; Chessari, Carlo; Frazzetto, Valentina; Crimi, Claudia; Fichera, Silvia; Picardi, Giuseppe; Nicolosi, Giuliana; Porto, Morena; Intravaia, Rossella; Crimi, Nunzio

2017-07-01

One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. A significant correlation between blood eosinophils assessed by the 2 devices was found (R 2  = 0.854, P < .001); similar correlations were found also for white blood cells, neutrophils, and lymphocytes. The point-of-care device had the ability to predict blood eosinophil cutoffs used to select patients for biologic treatments for severe eosinophilic asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Economic evaluation of nebulized magnesium sulphate in acute severe asthma in children.

PubMed

Petrou, Stavros; Boland, Angela; Khan, Kamran; Powell, Colin; Kolamunnage-Dona, Ruwanthi; Lowe, John; Doull, Iolo; Hood, Kerry; Williamson, Paula

2014-10-01

The aim of this study was to estimate the cost-effectiveness of nebulized magnesium sulphate (MgSO4) in acute asthma in children from the perspective of the UK National Health Service and personal social services. An economic evaluation was conducted based on evidence from a randomized placebo controlled multi-center trial of nebulized MgSO4 in severe acute asthma in children. Participants comprised 508 children aged 2-16 years presenting to an emergency department or a children's assessment unit with severe acute asthma across thirty hospitals in the United Kingdom. Children were randomly allocated to receive nebulized salbutamol and ipratropium bromide mixed with either 2.5 ml of isotonic MgSO4 or 2.5 ml of isotonic saline on three occasions at 20-min intervals. Cost-effectiveness outcomes were constructed around the Yung Asthma Severity Score (ASS) after 60 min of treatment; whilst cost-utility outcomes were constructed around the quality-adjusted life-year (QALY) metric. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves at alternative cost-effectiveness thresholds for either: (i) a unit reduction in ASS; or (ii) an additional QALY. MgSO4 had a 75.1 percent probability of being cost-effective at a GBP 1,000 (EUR 1,148) per unit decrement in ASS threshold, an 88.0 percent probability of being more effective (in terms of reducing the ASS) and a 36.6 percent probability of being less costly. MgSO4 also had a 67.6 percent probability of being cost-effective at a GBP 20,000 (EUR 22,957) per QALY gained threshold, an 8.5 percent probability of being more effective (in terms of generating increased QALYs) and a 69.1 percent probability of being less costly. Sensitivity analyses showed that the results of the economic evaluation were particularly sensitive to the methods used for QALY estimation. The probability of cost-effectiveness of nebulized isotonic MgSO4, given as an adjuvant to standard treatment of severe acute asthma in children, is less than 70 percent across accepted cost-effectiveness thresholds for an additional QALY.

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.

PubMed

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin; Cameron, Lisa; Vliagoftis, Harissios

2015-01-01

Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma.

Systemic Corticosteroid Responses in Children with Severe Asthma: Phenotypic and Endotypic Features.

PubMed

Fitzpatrick, Anne M; Stephenson, Susan T; Brown, Milton R; Nguyen, Khristopher; Douglas, Shaneka; Brown, Lou Ann S

Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking. This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response. Asthma-related quality of life, exhaled nitric oxide, blood eosinophils, lung function, and inflammatory cytokine and chemokine mRNA gene expression in peripheral blood mononuclear cells were assessed in 56 children with severe asthma at baseline and 14 days after intramuscular triamcinolone injection. The Asthma Control Questionnaire was used to classify children with severe asthma into corticosteroid response groups. Three groups of children with severe asthma were identified: controlled severe asthma, children who achieved control after triamcinolone, and children who did not achieve control. At baseline, these groups were phenotypically similar. After triamcinolone, discordance between symptoms, lung function, exhaled nitric oxide, and blood eosinophils was noted. Clinical phenotypic predictors were of limited utility in predicting the triamcinolone response, whereas systemic mRNA expression of inflammatory cytokines and chemokines related to IL-2, IL-10, and TNF signaling pathways, namely, AIMP1, CCR2, IL10RB, and IL5, strongly differentiated children who failed to achieve control with triamcinolone administration. Systemic corticosteroid responsiveness in children with severe asthma is heterogeneous. Alternative prediction models that include molecular endotypic as well as clinical phenotypic features are needed to identify which children derive the most clinical benefit from systemic corticosteroid step-up therapy given the potential side effects. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Current concepts of severe asthma

PubMed Central

Raundhal, Mahesh; Oriss, Timothy B.; Ray, Prabir; Wenzel, Sally E.

2016-01-01

The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID:27367183

Adolescent girls with asthma have worse asthma control and health-related quality of life than boys-A population based study.

PubMed

Stridsman, Caroline; Backman, Helena; Eklund, Britt-Marie; Rönmark, Eva; Hedman, Linnea

2017-07-01

Population-based studies investigating health-related quality of life (HRQoL) among asthmatic adolescents are rare. Further, among subjects with asthma, HRQoL may be affected by asthma control and severity. To investigate HRQoL in relation to asthma control and asthma severity among adolescents. As a part of the population-based OLIN pediatric study, 266 adolescents with current asthma (14-15 yr) were identified. N = 247 completed the DISABKIDS HRQoL asthma module, including the domains impact and worry. The Asthma Control Test (ACT) was used and a disease severity score was calculated based on symptoms and medicine use. The prevalence of current asthma was 11%. Well-controlled asthma was reported by 15% of the adolescents, and 53% had partly controlled asthma. The prevalence of uncontrolled asthma was significantly higher among girls than boys (38% vs 25%), and girls also reported lower HRQoL scores. There was a fairly strong correlation between the ACT and DISABKIDS scores. Independent risk factors for low HRQoL impact (a score <67) were female sex (OR 4.66, 95%CI 1.82-9.54) and decreased ACT scores (1.38, 1.18-1.62). Risk factors for low HRQoL worry (a score <70) were female sex (3.33, 1.41-7.86), decreased ACT scores (1.35, 1.16-1.57), severe asthma (6.23, 1.46-16.50), and having current eczema (2.68, 1.00-7.24). Only a minority of the asthmatic adolescents reported well-controlled asthma, and poor asthma control and female sex were risk factors for low HRQoL. Our results demonstrate that evaluation of asthma control is of great importance for asthma management. © 2017 Wiley Periodicals, Inc.

Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics.

PubMed

Konradsen, Jon R; Nordlund, Björn; Onell, Annica; Borres, Magnus P; Grönlund, Hans; Hedlin, Gunilla

2014-03-01

Allergy to cats and dogs and polysensitization towards these animals are associated with severe childhood asthma. Molecular-based allergy diagnostics offers new opportunities for improved characterization and has been suggested to be particularly useful in patients with polysensitization and/or severe asthma. The aim was to use extract- and molecular-based allergy diagnostics to compare patterns of IgE sensitization towards aeroallergens in children with problematic severe and controlled asthma. Children with a positive ImmunoCAP towards any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish study on severe childhood asthma. Severe (n = 37, age 13 years) and controlled (n = 28, age 14 years) asthmatics underwent assessment of allergic sensitization by ImmunoCap (kUA /l) and immunosolid-phase allergen chip (ISAC). In addition, Asthma Control Test, spirometry and a methacholine challenge were performed. Children with severe asthma had lower asthma control (p < 0.001) and FEV1 (p = 0.001) and more bronchial hyper-responsiveness (p = 0.008) in spite of high doses of inhaled steroids (≥800 μg budesonide). Children with severe asthma displayed higher levels of IgE antibodies towards cat (17 vs. 3.9, p = 0.027), dog (3.8 vs. 1.2, p = 0.012) and horse (7.4 vs. 0.7, p = 0.014). Sensitization towards Can f 2 (22% vs. 0%, p = 0.009) and Equ c 1 (51% vs. 25%, p = 0.03) was more common in severe asthma. IgE levels towards Equ c 1 correlated with asthma control (r = -0.41, p = 0.04). Children with severe allergic asthma had higher sIgE levels to cat, dog and horse. Molecular-based allergy diagnostics revealed a more complex molecular spreading of allergen components in children with the most severe disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Advances in pediatric asthma in 2014: Moving toward a population health perspective.

PubMed

Szefler, Stanley J

2015-03-01

Last year's "Advances in pediatric asthma in 2013: Coordinating asthma care" concluded that, "Enhanced communication systems will be necessary among parents, clinicians, health care providers and the pharmaceutical industry so that we continue the pathway of understanding the disease and developing new treatments that address the unmet needs of patients who are at risk for severe consequences of unchecked disease persistence or progression." This year's summary will focus on further advances in pediatric asthma related to prenatal and postnatal factors altering the natural history of asthma, assessment of asthma control, and new insights regarding the management of asthma in children as indicated in Journal of Allergy and Clinical Immunology publications in 2014. A major theme of this review is how new research reports can be integrated into medical communication in a population health perspective to assist clinicians in asthma management. The asthma specialist is in a unique position to convey important messages to the medical community related to factors that influence the course of asthma, methods to assess and communicate levels of control, and new targets for intervention, as well as new immunomodulators. By enhancing communication among patients, parents, primary care physicians, and specialists within provider systems, the asthma specialist can provide timely information that can help to reduce asthma morbidity and mortality. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Medical Home Model and Pediatric Asthma Symptom Severity: Evidence from a National Health Survey.

PubMed

Rojanasarot, Sirikan; Carlson, Angeline M

2018-04-01

The objective was to investigate the association between receiving care under the medical home model and parental assessment of the severity of asthma symptoms. It was hypothesized that parents of children who received care under the medical home model reported less severe asthma symptoms compared with their counterparts, whose care did not meet the medical home criteria. Secondary analyses were conducted using cross-sectional data from the 2011-2012 National Survey of Children's Health. Children with asthma aged 0-17 years were included and classified as receiving care from the medical home if their care contained 5 components: a personal doctor, a usual source of sick care, family-centered care, no problems getting referrals, and effective care coordination. Ordinal logistic regression was used to examine the relationship between parent-rated severity of asthma symptoms (mild, moderate, and severe symptoms) and the medical home. Approximately 52% of 8229 children who reported having asthma received care from the medical home. Only 30.8% of children with severe asthma symptoms received care that met the medical home criteria, compared to 55.7% of children with mild symptoms. After accounting for confounding factors, obtaining care under the medical home model decreased the odds of parent-reported severe asthma symptoms by 31% (adjusted odds ratio 0.69; 95% CI, 0.56-0.85). Study results suggest that the medical home model can reduce parent-rated severity of asthma symptoms. The findings highlight the importance of providing medical home care to children with asthma to improve the outcomes that matter most to children and their families.

A Mechanistic Role for Type III IFN-λ1 in Asthma Exacerbations Mediated by Human Rhinoviruses

PubMed Central

Miller, E. Kathryn; Hernandez, Johanna Zea; Wimmenauer, Vera; Shepherd, Bryan E.; Hijano, Diego; Libster, Romina; Serra, M. Elina; Bhat, Niranjan; Batalle, Juan P.; Mohamed, Yassir; Reynaldi, Andrea; Rodriguez, Andrea; Otello, Monica; Pisapia, Nestor; Bugna, Jimena; Bellabarba, Miguel; Kraft, David; Coviello, Silvina; Ferolla, F. Martin; Chen, Aaron; London, Stephanie J.; Siberry, George K.; Williams, John V.

2012-01-01

Rationale: Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear. Objectives: To determine the role of HRV in pediatric asthma exacerbations and the mechanisms mediating wheezing. Methods: We prospectively studied 409 children with asthma presenting with upper respiratory infection in the presence or absence of wheezing. Candidate viral and immune mediators of illness were compared among children with asthma with different degrees of severity of acute asthma. Measurements and Main Results: HRV infections specifically associated with asthma exacerbations, even after adjusting for relevant demographic and clinical variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21–2.99; P = 0.005). No difference in virus titers, HRV species, and inflammatory or allergic molecules was observed between wheezing and nonwheezing children infected with HRV. Type III IFN-λ1 levels were higher in wheezing children infected with HRV compared with nonwheezing (P < 0.001) and increased with worsening symptoms (P < 0.001). Moreover, after adjusting for IFN-λ1, children with asthma infected with HRV were no longer more likely to wheeze than those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57–2.46; P = 0.66). Conclusions: Our findings suggest that HRV infections in children with asthma are specifically associated with acute wheezing, and that type III IFN-λ1 responses mediate exacerbations caused by HRV. Modulation of IFN- λ1 should be studied as a therapeutic target for exacerbations caused by HRV. PMID:22135341

Economic analysis of temperature-controlled laminar airflow (TLA) for the treatment of patients with severe persistent allergic asthma

PubMed Central

Brazier, Peter; Schauer, Uwe; Hamelmann, Eckard; Holmes, Steve; Pritchard, Clive; Warner, John O

2016-01-01

Introduction Chronic asthma is a significant burden for individual sufferers, adversely impacting their quality of working and social life, as well as being a major cost to the National Health Service (NHS). Temperature-controlled laminar airflow (TLA) therapy provides asthma patients at BTS/SIGN step 4/5 an add-on treatment option that is non-invasive and has been shown in clinical studies to improve quality of life for patients with poorly controlled allergic asthma. The objective of this study was to quantify the cost-effectiveness of TLA (Airsonett AB) technology as an add-on to standard asthma management drug therapy in the UK. Methods The main performance measure of interest is the incremental cost per quality-adjusted life year (QALY) for patients using TLA in addition to usual care versus usual care alone. The incremental cost of TLA use is based on an observational clinical study monitoring the incidence of exacerbations with treatment valued using NHS cost data. The clinical effectiveness, used to derive the incremental QALY data, is based on a randomised double-blind placebo-controlled clinical trial comprising participants with an equivalent asthma condition. Results For a clinical cohort of asthma patients as a whole, the incremental cost-effectiveness ratio (ICER) is £8998 per QALY gained, that is, within the £20 000/QALY cost-effectiveness benchmark used by the National Institute for Health and Care Excellence (NICE). Sensitivity analysis indicates that ICER values range from £18 883/QALY for the least severe patients through to TLA being dominant, that is, cost saving as well as improving quality of life, for individuals with the most severe and poorly controlled asthma. Conclusions Based on our results, Airsonett TLA is a cost-effective addition to treatment options for stage 4/5 patients. For high-risk individuals with more severe and less well controlled asthma, the use of TLA therapy to reduce incidence of hospitalisation would be a cost saving to the NHS. PMID:27026803

Asthma prevalence and severity in low-resource communities.

PubMed

Cruz, Álvaro A; Stelmach, Rafael; Ponte, Eduardo V

2017-06-01

The prevalence of asthma was thought to be low in most low-income countries, but several reports have indicated this is not always true. This is a narrative review of recent publications on the burden of asthma in low and middle-income countries (LMIC) and underprivileged communities from developed countries. Several studies have reported a low prevalence of asthma is LMIC, but indicate it is increasing. In the last few years, however, many surveys demonstrated this may not always be true. An analysis of the International Study for Asthma and Allergy in Childhood phase III database indicated although the prevalence of asthma among children and adolescents is higher in the developed countries, symptoms of asthma are often more severe in less affluent nations. The rate of uncontrolled asthma is also higher among underprivileged communities of developed countries. Secondary analysis of data generated by the WHO's world health survey performed among adults of 70 countries indicate symptoms of asthma are less frequent in middle-income countries and more frequent in the extremes, low income and high income. This sort of U shaped distribution suggests the disease (or syndrome) comprise more than one major phenotype related to diverse underlying mechanisms. In fact, recent reports show symptoms of asthma among the poor are associated with unhygienic living conditions, which may reduce the risk of atopy but increase the risk of nonatopic wheezing. Urbanization and exposure to air pollution also seem to contribute to an increasing prevalence severity of asthma in LMIC. Access to proper diagnosis and treatment with controller medications for asthma, specially with inhaled corticosteroids is feasible and cost-effective, reduce symptoms, health resource utilization, improves quality of life, and reduce mortality in low-resource settings. Prevalence of asthma was thought to be low in low-income countries, but several reports have indicated this is not always true. Under diagnosis, under treatment, exposure to air pollution, and unhygienic living conditions may contribute to a higher frequency and severity of symptoms of asthma among the poor. Proper diagnosis and treatment with controller medications for asthma is feasible and cost-effective in low-resource settings.

Advances in asthma 2015: Across the lifespan.

PubMed

Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2016-08-01

In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Predicting asthma exacerbations in children.

PubMed

Forno, Erick; Celedón, Juan C

2012-01-01

This review critically assesses recently published literature on predicting asthma exacerbations in children, while also providing general recommendations for future research in this field. Current evidence suggests that every effort should be made to provide optimal treatment to achieve adequate asthma control, as this will significantly reduce the risk of severe disease exacerbations. Children who have had at least one asthma exacerbation in the previous year are at highest risk for subsequent exacerbations, regardless of disease severity and/or control. Although several tools and biomarkers to predict asthma exacerbations have been recently developed, these approaches need further validation and/or have only had partial success in identifying children at risk. Although considerable progress has been made, much remains to be done. Future studies should clearly differentiate severe asthma exacerbations due to inadequate asthma control from those occurring in children whose asthma is well controlled, utilize standardized definitions of asthma exacerbations, and use a systematic approach to identify the best predictors after accounting for the multiple dimensions of the problem. Our ability to correctly predict the development of severe asthma exacerbations in an individual child should improve in parallel with increased knowledge and/or understanding of the complex interactions among genetic, environmental (e.g. viral infections) and lifestyle (e.g. adherence to treatment) factors underlying these events.

[Control of asthma symptoms and cellular markers of inflammation in induced sputum in children and adolescents with chronic asthma].

PubMed

Ciółkowski, Janusz; Stasiowska, Barbara; Mazurek, Henryk

2009-03-01

After the GINA 2006 publication, asthma therapy is based on control of symptoms. However there are suggestions of monitoring of airway inflammation. Aim of the study was to compare clinical criteria of asthma control with cellular markers of lower airway inflammation in induced sputum in a group of young asthmatics. To assess relationship between sputum eosinophilia, asthma severity and spirometry. A group of 154 young patients with chronic asthma (8-21 years) underwent sputum induction by inhalation of 4,5% saline solution. Sputum induction was effective in 121 patients (78%), and in this group control of clinical symptoms was assessed according to GINA 2006 criteria. Asthma was controlled in 82 subjects (67.8%) and uncontrolled in 39 (32.2%). Patients with controlled asthma had higher FEV1/FVC (79.8 +/- 7.1% vs 74.2 +/- 9.9%; p = 0.004) and MMEF (80.7 +/- 23.0% vs 65.3 +/- 21.8%; p < 0.001) than those with uncontrolled disease, but the average FEV1 (as percent predicted) did not differ between the two groups. Patients with controlled asthma had lower sputum eosinophil count than those with uncontrolled asthma (3.5 +/- 6.3% vs 7.2 +/- 8.7%; p = 0.01), but difference in neutrophil count was borderline (27.3 +/- 15.5% vs 34.5 +/- 21.0%; p = 0.05). High sputum eosinophil count (> 3%) was observed in 24.4% of patients with controlled asthma and in 61.5% with uncontrolled asthma (p < 0.001). Increased sputum neutrophil count was more frequent in a group of uncontrolled asthma (2.4 vs 15.4%; p = 0.022). Mean sputum eosinophil count was lower in patients with mild astma than in patients with moderate-severe disease (3.1 +/- 5.7% vs 7.1% +/- 8.8; p = 0.006). Patients with high sputum eosinophil count had lower FEV1 (89.4 +/- 14.9% vs 94.9 +/- 13.9%; p = 0.047), FEV1/FVC (74.5 +/- 10.1% vs 79.2 +/- 9.3%; p = 0.01) and MMEF (68.7 +/- 23.3% vs 81.7 +/- 23.1%; p = 0.004). In this study of young asthmatics, control of asthma symptoms was observed in 67.8% of patients. However, cellular markers of lower airway inflammation were present in 1/4 of patients with controlled asthma and in 3/4 with uncontrolled disease. Sputum eosinophilia was related to asthma severity. FEV1/FVC and MMEF were more important that FEV1 for estimating control of asthma. Improvement of asthma control scoring is needed as well as availability of simple methods of inflammation monitoring.

Severe or life-threatening asthma exacerbation: patient heterogeneity identified by cluster analysis.

PubMed

Sekiya, K; Nakatani, E; Fukutomi, Y; Kaneda, H; Iikura, M; Yoshida, M; Takahashi, K; Tomii, K; Nishikawa, M; Kaneko, N; Sugino, Y; Shinkai, M; Ueda, T; Tanikawa, Y; Shirai, T; Hirabayashi, M; Aoki, T; Kato, T; Iizuka, K; Homma, S; Taniguchi, M; Tanaka, H

2016-08-01

Severe or life-threatening asthma exacerbation is one of the worst outcomes of asthma because of the risk of death. To date, few studies have explored the potential heterogeneity of this condition. To examine the clinical characteristics and heterogeneity of patients with severe or life-threatening asthma exacerbation. This was a multicentre, prospective study of patients with severe or life-threatening asthma exacerbation and pulse oxygen saturation < 90% who were admitted to 17 institutions across Japan. Cluster analysis was performed using variables from patient- and physician-orientated structured questionnaires. Analysis of data from 175 patients with severe or life-threatening asthma exacerbation revealed five distinct clusters. Cluster 1 (n = 27) was younger-onset asthma with severe symptoms at baseline, including limitation of activities, a higher frequency of treatment with oral corticosteroids and short-acting beta-agonists, and a higher frequency of asthma hospitalizations in the past year. Cluster 2 (n = 35) was predominantly composed of elderly females, with the highest frequency of comorbid, chronic hyperplastic rhinosinusitis/nasal polyposis, and a long disease duration. Cluster 3 (n = 40) was allergic asthma without inhaled corticosteroid use at baseline. Patients in this cluster had a higher frequency of atopy, including allergic rhinitis and furred pet hypersensitivity, and a better prognosis during hospitalization compared with the other clusters. Cluster 4 (n = 34) was characterized by elderly males with concomitant chronic obstructive pulmonary disease (COPD). Although cluster 5 (n = 39) had very mild symptoms at baseline according to the patient questionnaires, 41% had previously been hospitalized for asthma. This study demonstrated that significant heterogeneity exists among patients with severe or life-threatening asthma exacerbation. Differences were observed in the severity of asthma symptoms and use of inhaled corticosteroids at baseline, and the presence of comorbid COPD. These findings may contribute to a deeper understanding and better management of this patient population. © 2016 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Acute severe asthma presenting in late pregnancy.

PubMed

Holland, S M; Thomson, K D

2006-01-01

Asthma is the commonest pre-existing medical condition to complicate pregnancy. Acute severe asthma in pregnancy is rare, but poses difficult problems. In particular, the decision about when and where to deliver the fetus is complex, since maternal response to asthma treatment is unpredictable. We report the successful management of a parturient presenting with acute severe asthma at 37 weeks' gestation. The controversies involved and the importance of adopting a multi-disciplinary team approach to optimise maternal and neonatal outcomes are discussed.

Internet-based self-management offers an opportunity to achieve better asthma control in adolescents.

PubMed

van der Meer, Victor; van Stel, Henk F; Detmar, Symone B; Otten, Wilma; Sterk, Peter J; Sont, Jacob K

2007-07-01

Internet and short message service are emerging tools for chronic disease management in adolescents, but few data exist on the barriers to and benefits of internet-based asthma self-management. Our objective was to reveal the barriers and benefits perceived by adolescents with well-controlled and poorly controlled asthma to current and internet-based asthma management. Ninety-seven adolescents with mild-to-moderate persistent asthma monitored their asthma control on a designated Web site. After 4 weeks, 35 adolescents participated in eight focus groups. Participants were stratified in terms of age, gender, and asthma control level. We used qualitative and quantitative methods to analyze the written focus group transcripts. Limited self-efficacy to control asthma was a significant barrier to current asthma management in adolescents with poor asthma control (65%) compared to adolescents with good asthma control (17%; p < 0.01). The former group revealed the following several benefits from internet-based asthma self-management: feasible electronic monitoring; easily accessible information; e-mail communication; and use of an electronic action plan. Personal benefits included the ability to react to change and to optimize asthma control. Patients with poor asthma control were able and ready to incorporate internet-based asthma self-management for a long period of time (65%), whereas patients with good control were not (11%; p < 0.01). Our findings reveal a need for the support of self-management in adolescents with poorly controlled asthma that can be met by the application of novel information and communication technologies. Internet-based self-management should therefore target adolescents with poor asthma control.

Environmental pollution and lung effects in children.

PubMed

Searing, Daniel A; Rabinovitch, Nathan

2011-06-01

Studies over the last 2 years have added important new information on the relationship between air pollution and asthma incidence and severity. Outdoor air pollution has been associated with asthma exacerbations, including emergency department visits and hospitalizations, as well as with the onset of asthma. Possible mechanisms mediating both incidence and severity effects include the induction of oxidative stress, and/or allergic sensitization, as well as increased susceptibility to viral infections. Some of these mechanisms may be occurring in utero including epigenetic changes that may increase risk for development of asthma. Factors related to increased susceptibility for air pollution-related asthma severity include age, season and genetic polymorphisms related to antioxidant enzymes. Ambient pollution levels may be associated with both asthma incidence and severity. Susceptibility to air pollution may be higher in children with genetic polymorphisms related to the 'oxidant stress pathways'. Potential interventions for susceptible children at risk for asthma development and/or severity include decreased exposure on high air pollution days, especially in the summer months, and antioxidant supplementation. On the population level, changes in school and home zoning to increase distance from busy roadways may help reduce both asthma incidence and severity.

Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population

PubMed Central

Kerkhof, Marjan; Tran, Trung N; Soriano, Joan B; Golam, Sarowar; Gibson, Danny; Hillyer, Elizabeth V

2018-01-01

Background Little is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs. Aims We sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population. Methods This cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×109/L) for patients prescribed long-acting β2-agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population. Results Of 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1). Conclusions Less than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma. PMID:28918400

Post-traumatic Stress Disorder, Bronchodilator Response, and Incident Asthma in World Trade Center Rescue and Recovery Workers

PubMed Central

Jeon, Yunho; Miller, Gregory E.; Wisnivesky, Juan P.

2016-01-01

Rationale: Post-traumatic stress disorder (PTSD) has been associated with asthma in cross-sectional studies. Whether PTSD leads to clinically significant bronchodilator response (BDR) or new-onset asthma is unknown. Objectives: We sought to determine the relationship between probable PTSD and both BDR and incident asthma in a high-risk cohort of World Trade Center workers in New York (NY). Methods: This study was conducted on data from a high-risk cohort of 11,481 World Trade Center workers in New York, including 6,133 never smokers without a previous diagnosis of asthma. Of the 6,133 never smokers without asthma, 3,757 (61.3%) completed a follow-up visit several years later (mean = 4.95 yr, interquartile range = 3.74–5.90 yr). At the baseline visit, probable PTSD was defined as a score 44 points or greater in the PTSD Checklist questionnaire, and BDR was defined as both a change of 12% or greater and an increment of 200 ml or greater in FEV1 after bronchodilator administration. Incident asthma was defined as a self-report of new physician-diagnosed asthma after the baseline visit. Multivariable logistic regression was used for the analysis of probable PTSD and baseline BDR or incident asthma. Measurements and Main and Results: At baseline, probable PTSD was associated with BDR among all participants (adjusted odds ratio = 1.43; 95% confidence interval = 1.19–1.72), with similar results among never smokers without asthma. Among 3,757 never smokers, probable PTSD at baseline was associated with incident asthma, even after adjustment for baseline BDR (odds ratio = 2.41; 95% confidence interval = 1.85–3.13). This association remained significant in a confirmatory analysis after excluding 195 subjects with baseline BDR. Conclusions: In a cohort of adult workers exposed to a severe traumatic event, probable PTSD is significantly associated with BDR at baseline and predicts incident asthma. PMID:27548615

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

Temperature-controlled laminar airflow in severe asthma for exacerbation reduction (The LASER Trial): study protocol for a randomised controlled trial.

PubMed

Storrar, Will; Fogg, Carole; Brown, Tom; Dennison, Paddy; Yu, Ly-Mee; Dewey, Ann; Luengo-Fernandez, Ramon; Dean, Tara; Rahman, Najib; Mansur, Adel; Howarth, Peter H; Bradding, Peter; Chauhan, Anoop J

2016-01-08

Asthma affects more than 5 million patients in the United Kingdom. Nearly 500,000 of these patients have severe asthma with severe symptoms and frequent exacerbations that are inadequately controlled with available treatments. The burden of severe asthma on the NHS is enormous, accounting for 80 % of the total asthma cost (£1 billion), with frequent exacerbations and expensive medications generating much of this cost. Of those patients with severe asthma, 70 % are sensitised to indoor aeroallergens, and the level of exposure to allergens determines the symptoms; patients exposed to high levels are therefore most at risk of exacerbations and hospital admissions. The LASER trial aims to assess whether a new treatment, temperature controlled laminar airflow (TLA) delivered by the Airsonett™ device, can reduce the frequency of exacerbations in patients with severe allergic asthma by reducing exposure to aeroallergens overnight. This multicentre study is a placebo-controlled, blinded, randomised controlled, parallel group trial. A total of 222 patients with a new or current diagnosis of severe allergic asthma will be assigned with a random element in a 1:1 ratio to receive either an active device for one year or a placebo device. The primary outcome is the frequency of severe asthma exacerbations occurring over a 12-month period, defined in accordance with the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Secondary outcomes include changes in asthma control, lung function, asthma-specific and global quality of life for participants and their carers, adherence to intervention, healthcare resource use and costs, and cost-effectiveness. Qualitative interviews will be conducted to elicit participant's and their partner's perceptions of the treatment. Effective measures of allergen avoidance have, to date, proved elusive. The LASER trial aims to address this. The study will ascertain whether home-based nocturnal TLA usage over a 12-month period can reduce the frequency of exacerbations and improve asthma control and quality of life as compared to placebo, whilst being cost-effective and acceptable to adults with poorly controlled, severe allergic asthma. The results of this study will be widely applicable to the many patients with allergic asthma both in the UK and internationally. Current controlled trials ISRCTN46346208 (Date assigned 22 January 2014).

Pharmacists' interventions on clinical asthma outcomes: a systematic review.

PubMed

Garcia-Cardenas, Victoria; Armour, Carol; Benrimoj, Shalom I; Martinez-Martinez, Fernando; Rotta, Inajara; Fernandez-Llimos, Fernando

2016-04-01

The objective of this systematic review was to evaluate the impact of pharmacists' interventions on clinical asthma outcomes on adult patients and to identify the outcome indicators used.PubMed, Scopus, Web of Science and Scielo were searched. Studies addressing pharmacists' interventions on adult asthma patients reporting clinical asthma outcomes were incorporated.11 clinical outcomes were identified in 21 studies. 10 studies measured the impact of the intervention on asthma control. Randomised controlled trials (RCT) and non-RCTs found positive results in percentages of controlled patients and Asthma Control Questionnaire (ACQ) scores. Discordant results were found for Asthma Control Test results. Asthma severity was assessed in four studies. One RCT found a significant decrease in the percentage of severe patients; two non-RCTs found significant improvements in severity scores. 11 studies reported pulmonary function indicators, showing inconsistent results. Eight studies measured asthma symptoms; three RCTs and four non-RCTs showed significant improvements.RCTs and non-RCTs generated similar results for most outcomes. Based on the evidence generated by RCTs, pharmacists' have a positive impact on the percentage of controlled patients, ACQ scores, severity and symptoms. Future research should report using the core outcome set of indicators established for asthma (PROSPERO CRD42014007019). Copyright ©ERS 2016.

Depressive symptomatology, quality of life and disease control among individuals with well-characterized severe asthma.

PubMed

Yonas, Michael A; Marsland, Anna L; Emeremni, Chetachi A; Moore, Charity G; Holguin, Fernando; Wenzel, Sally

2013-10-01

A thorough examination of the relationship of asthma severity and control with symptoms of depression is needed to identify groups of asthmatics at high risk for poor disease control outcomes. This study examines the relationship of symptoms of depression with severity and control in a well-characterized cohort of asthmatics and healthy controls. Depressive symptoms and quality of life were assessed using the Beck Depression Inventory. Disease control was measured by a composite index incorporating symptoms, activity limitation and rescue medication use. Individuals with asthma (n = 91) reported more symptoms of depression than controls (n = 36; p < 0.001). Those with severe asthma (n = 49) reported more symptoms of depression (p = 0.002) and poorer asthma control (p < 0.0001) than those with not severe asthma. Worse asthma control was associated with more depressive symptoms in severe (r = 0.46, p = 0.002) but not in not severe (r = 0.13, p = 0.40) asthmatics. The relationship of symptoms of depression among severe asthmatics was attenuated by disease control. Exploratory analyses identified specific disease symptom characteristics, as opposed to exacerbations, as associated with symptoms of depression. Among individuals with severe asthma, increased symptom burden is positively associated with risk for co-morbid depression. These findings point to a need for regular mood disorder screenings and treatment referrals among this group. Further research is warranted to examine whether treatment of comorbid depression improves treatment adherence and asthma-related quality of life.

Obstructive sleep apnea and asthma*

PubMed Central

Salles, Cristina; Terse-Ramos, Regina; Souza-Machado, Adelmir; Cruz, Álvaro A

2013-01-01

Symptoms of sleep-disordered breathing, especially obstructive sleep apnea syndrome (OSAS), are common in asthma patients and have been associated with asthma severity. It is known that asthma symptoms tend to be more severe at night and that asthma-related deaths are most likely to occur during the night or early morning. Nocturnal symptoms occur in 60-74% of asthma patients and are markers of inadequate control of the disease. Various pathophysiological mechanisms are related to the worsening of asthma symptoms, OSAS being one of the most important factors. In patients with asthma, OSAS should be investigated whenever there is inadequate control of symptoms of nocturnal asthma despite the treatment recommended by guidelines having been administered. There is evidence in the literature that the use of continuous positive airway pressure contributes to asthma control in asthma patients with obstructive sleep apnea and uncontrolled asthma. PMID:24310634

Is asthma associated with cognitive impairments? A meta-analytic review.

PubMed

Irani, Farzin; Barbone, Jordan Mark; Beausoleil, Janet; Gerald, Lynn

2017-12-01

Asthma is a chronic disease with significant health burden and socioeconomic and racial/ethnic disparities related to diagnosis and treatment. Asthma primarily affects the lungs, but can impact brain function through direct and indirect mechanisms. Some studies have suggested that asthma negatively impacts cognition, while others have failed to identify asthma-related cognitive compromise. We aimed to conduct a meta-analysis of cognition in individuals with asthma compared to that in healthy controls. We also examined the impact of some key potential moderators. Data on cognitive outcome measures and sociodemographic, illness-related, and study-related variables were extracted from studies reporting cognitive test performance in individuals with asthma compared to that in controls. There was no evidence of publication bias. A random-effects model examining differences in task performance between 2017 individuals with asthma and 2131 healthy controls showed significant effects in the small to medium range. Cognitive deficits associated with asthma were global, with strongest effects on broader measures involving academic achievement and executive functioning, but with additional impact on processing speed, global intellect, attention, visuospatial functioning, language, learning, and memory. Severity of asthma was a key moderator, with greatest cognitive deficits associated with severe asthma. Cognitive burden was also greatest in asthma patients who were younger, males, from low socioeconomic backgrounds, and from racial/ethnic minorities. Effects were independent of type of population (child versus adult), type of study (norm-referenced versus control-referenced), or reported use of oral or inhaled corticosteroid medications. There is cognitive burden associated with asthma, particularly among vulnerable groups with severe asthma. This could be due to increased risk of intermittent cerebral hypoxia in severe asthma. The clinical need to assess cognition in individuals with asthma is underscored.

Cohort Study of Severe Bronchiolitis during Infancy and Risk of Asthma by Age 5 Years.

PubMed

Balekian, Diana S; Linnemann, Rachel W; Hasegawa, Kohei; Thadhani, Ravi; Camargo, Carlos A

Severe bronchiolitis (ie, bronchiolitis requiring hospital admission) is thought to markedly increase asthma risk, with 30%-50% developing asthma by age 5 years. To date, studies of this association are small, and most are from outside the United States. The objective of this study was to investigate the association between severe bronchiolitis and risk of asthma in a US birth cohort. We studied a cohort nested within the Massachusetts General Hospital Obstetric Maternal Study (MOMS), a prospective cohort of pregnant women enrolled during 1998-2006. Children of mothers enrolled in MOMS were included in the analysis if they received care within our health system (n = 3653). Diagnoses and medications were extracted from the children's electronic health records; we also examined pregnancy and perinatal risk factors collected for the underlying pregnancy study. The birth cohort was 52% male, 49% white, and 105 infants (2.9%) had severe bronchiolitis. Overall, 421 children (11.5%) developed asthma by age 5 years. Among the children with severe bronchiolitis, 27.6% developed asthma by age 5 years. In multivariable logistic regression adjusting for 12 risk factors, severe bronchiolitis remained a strong risk factor for developing asthma by age 5 years (odds ratio 2.57; 95% confidence interval 1.61-4.09). In a large Boston birth cohort, the frequency of severe bronchiolitis and childhood asthma was similar to published data. Among children with severe bronchiolitis, the risk of developing asthma was lower than prior studies but still high (27.6%). This difference may be due to different study designs, populations, and outcome definitions studied. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Enhancing school asthma action plans: qualitative results from southeast Minnesota beacon stakeholder groups.

PubMed

Egginton, Jason S; Textor, Lauren; Knoebel, Erin; McWilliams, Deborah; Aleman, Marty; Yawn, Barbara

2013-12-01

This study explores ways southeast Minnesota schools currently address asthma problems, identifies areas for improvement, and assesses the potential value of asthma action plans (AAPs) in schools. Focus groups were used to query stakeholder groups on asthma care in schools. Groups were held separately for elementary school personnel, parents of elementary school children with asthma, and health professionals (N = 103). Transcripts were analyzed by hand and by using NVivo 9 software. Overall 103 stakeholders participated in focus groups. Major themes were (1) Communication; no uniform way of exchanging information between schools and health professionals. (2) Asthma Control Continuum; students require individualized instructions and information related to their asthma care. (3) Policy/Protocol; school staff roles and rules vary and are unclear. (4) Self-Reliance; older children self-manage their asthma and are unknown until they need emergent support. Solution recommended included AAPs used systematically with a method to communicate back from schools to physicians and parents. The AAP may solve several of the school's concerns regarding their ability to provide asthma support in school. However, the AAP must reach the school, and that is currently not happening. In addition, schools would like tools and systems to assess asthma control and share information back with parents and physicians. © 2013, American School Health Association.

[Study on the correlation between the severity of chronic rhinosinusitis and bronchial asthma and pulmonary function].

PubMed

Liu, Yonggang

2015-07-01

To explore the correlation between the severity of patients with rhinitis-nasosinusitis and the bronchial asthma and the pulmonary function. Sixty-four cases of patients with rhinitis-nasosinusitis and 53 cases of patients with chronic sinusitis from June 2012 to September 2013 were randomly selected, and the patients were divided into group of rhinitis-nasosinusitis with nasal polyps and group of chronic sinusitis according to disease species, and analyzed the correlation between the severity of the deseases and the changes of the pulmonary function respectively for the patients of two groups by using Spearman method. The incidence of asthma for patients with different levels of sinusitis and nasal polyps seemed no significant difference (P > 0.05); the incidence of allergic rhinitis also seemed no significant difference (P > 0.05); the incidence of asthma for patients with different lesion range of sinusitis and nasal polyps seemed no significant difference (P > 0.05); the incidence of allergic rhinitis also seemed no significant different (P < 0.05). The conditions of the patients with different levels of sinusitis and nasal polyps were directly related to the reduction of pulmonary function (r = 2.431, P < 0.05); The conditions of the patients with different lesion range of sinusitis were directly related to the reduction of pulmonary function (r = 2.641, P < 0.05). There was some correlation between the severity of patients with rhinitis-nasosinusitis and the bronchial asthma and the condition of pulmonary function of patients.

Mouse Sensitization and Exposure Are Associated with Asthma Severity in Urban Children.

PubMed

Grant, Torie; Aloe, Charles; Perzanowski, Matthew; Phipatanakul, Wanda; Bollinger, Mary E; Miller, Rachel; Matsui, Elizabeth C

Mouse sensitization and exposure are associated with uncontrolled asthma, but whether they are associated with asthma severity, an intrinsic disease characteristic and long-term outcome predictor, is unclear. To examine relationships between mouse sensitization and/or exposure and asthma severity in urban children. A total of 645 children (5-17 years) with uncontrolled asthma underwent mouse sensitization evaluation. Sensitized children had mouse allergen measured in bedroom dust. Relationships between mouse sensitization, allergen levels, and asthma severity measures (treatment step and Composite Asthma Severity Index [CASI]) were examined using regression models adjusted for age, sex, atopy, study site, race, ethnicity, and insurance. The study population was predominantly minority (69.6% black, 20.8% Hispanic), low income (61.8%), and mouse sensitized (54.4%). Mean ± SD treatment step was 3.2 ± 1.6, equivalent to medium-dose inhaled corticosteroid. Mean ± SD CASI was 6.5 ± 3.4, reflecting moderate persistent asthma. Mouse sensitization was associated with higher treatment step (3.5 vs 2.9, mouse-sensitized vs nonsensitized, P < .001), independent of potential confounders (β [95% CI], 0.36 [0.07-0.64]; P = .01). Mouse sensitization was associated independently with CASI (β [95% CI], 0.82 [0.16-1.47]; P = .02). Among mouse-sensitized participants, higher bedroom floor and bed Mus m 1 were independently associated with treatment step (β [95% CI], 0.26 [0.09-0.43]; P = .002 and β [95% CI], 0.22 [0.01-0.43]; P = .04), respectively. Higher bedroom floor Mus m 1 was independently associated with CASI (β [95% CI], 0.43 [0.05-0.81]; P = .03). Mouse sensitization and exposure are associated with asthma severity, among low-income, minority children. Further studies are needed to determine whether reducing allergen exposure among mouse-sensitized patients with asthma can reduce severity, ultimately altering childhood asthma natural history. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

326 Lung Age/Chronological Age Index as Indicator of Clinical Improvement or Severity in Asthma Patients

PubMed Central

Castrejon-Vázquez, Isabel; Vargas, Maria Eugenia; Sabido, Raúl Cicero; Tapía, Jorge Galicia

2012-01-01

Background Spirometry is a very useful clinical test to evaluate pulmonary function in asthma. However pulmonary function could be affected by the sex, time of clinical evolution, lung age (LA) and chronological age (CA). The aim of this study was to evaluate LA/CA as index of clinical improvement or severity in asthma patients. Methods The tenets of the Declaration of Helsinki were followed, and all patients gave their informed consent to participate in this study. Asthma severity was evaluated according with GINA classification. Spirometry was performed at the beginning of this study, at 46 days, 96 days, 192 days and after 8 months. Statistical analysis was performed using t test, 2-way ANOVA test, correlation and multiple regression models as well as ROC curves were also performed, a P < 0.05 was considered as significant. Results 70 asthma patients were included (22 male and 48 female), mean CA was 35-years old; mean LA was 48-years with a LA/CA index = 1.4, time of clinical evolution was 13 years. A LA/CA index = 1 (range 0.5 to 0.9) was observed in asymptomatic patients. LA/CA index over 1 were related with airway inflammation, and a LA/CA index more than 2 correlated with GINA step 3. Interestingly when we analyzed CA and LA, we observed that in female group more than 10 years of difference between CA and LA, (GINA Step2 and 3); while in male we observed (GINA Step1, Step2 and Step3). LA/CA index ≤ 1 was considered as normal. Conclusions LA/CA index is a good as clinical indicator of clinical improvement or severity in asthma patients in with excellent correlation of pulmonary function and age.

Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood

PubMed Central

Strachan, D P; Aït-Khaled, N; Foliaki, S; Mallol, J; Odhiambo, J; Pearce, N; Williams, H C

2015-01-01

Background Associations of larger families with lower prevalences of hay fever, eczema and objective markers of allergic sensitization have been found fairly consistently in affluent countries, but little is known about these relationships in less affluent countries. Methods Questionnaire data for 210 200 children aged 6–7 years from 31 countries, and 337 226 children aged 13–14 years from 52 countries, were collected by Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older and younger siblings, using mixed (multi-level) logistic regression models to adjust for individual covariates and at the centre level for region, language and national affluence. Results In both age groups, inverse trends (P < 0.0001) were observed for reported ‘hay fever ever’ and ‘eczema ever’ with increasing numbers of total siblings, and more specifically older siblings. These inverse associations were significantly (P < 0.005) stronger in more affluent countries. In contrast, symptoms of severe asthma and severe eczema were positively associated (P < 0.0001) with total sibship size in both age groups. These associations with disease severity were largely independent of position within the sibship and national GNI per capita. Conclusions These global findings on sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at least two distinct trends. Inverse associations with older siblings (observations which prompted the ‘hygiene hypothesis’ for allergic disease) are mainly a phenomenon of more affluent countries, whereas greater severity of symptoms in larger families is globally more widespread. PMID:24912652

Airway structural alterations selectively associated with severe asthma.

PubMed

Benayoun, Laurent; Druilhe, Anne; Dombret, Marie-Christine; Aubier, Michel; Pretolani, Marina

2003-05-15

To identify airway pathologic abnormalities selectively associated with severe asthma, we examined 10 control subjects, 10 patients with intermittent asthma, 15 patients with mild-to-moderate persistent asthma, 15 patients with severe persistent asthma, and 10 patients with chronic obstructive pulmonary disease. Bronchial biopsies were assessed for epithelial integrity; subepithelial basement membrane (SBM) thickness; collagen type III deposition; eosinophil, neutrophil, and fibroblast numbers; mucous gland and airway smooth muscle (ASM) areas; SBM-ASM distance; ASM hypertrophy (increased cell size); and the expression of the contractile proteins alpha-actin, smooth muscle myosin heavy-chain isoforms, myosin light-chain kinase, and the phosphorylated form of the regulatory light chain of myosin. Neither mucosal eosinophilia nor neutrophilia, epithelial damage, or SBM thickness reflected asthma severity. In contrast, higher numbers of fibroblasts (p < 0.001), an increase in collagen type III deposition (p < 0.020), larger mucous gland (p < 0.040) and ASM (p < 0.001) areas, augmented ASM cell size (p < 0.001), and myosin light-chain kinase expression (p < 0.005) distinguished patients with severe persistent asthma from patients with milder disease or with chronic obstructive pulmonary disease. Stepwise multivariate regression analysis established that fibroblast numbers and ASM cell size were negatively associated with prebronchodilator and postbronchodilator FEV1 values in patients with asthma. We conclude that fibroblast accumulation and ASM hypertrophy in proximal airways are selective determinants of severe persistent asthma.

Management of asthma: the essentials of good clinical practice.

PubMed

Aït-Khaled, N; Enarson, D A

2006-02-01

Asthma is a condition that affects all countries worldwide. It is a chronic, disabling condition that diminishes the quality of life and the economic prosperity of those who live with it. The majority of persons living with asthma are from developing countries. Asthma management necessitates long-term treatment that is expensive, making it less accessible to poor people. The cost of medications is the key factor preventing people living with asthma from having access to care that has the potential to relieve their suffering, improve their quality of life and enhance their economic status. Asthma is a disease caused by environmental exposures. Genetic factors predispose certain people to developing asthma once they are exposed to the causative agents, and certain factors can trigger symptomatic episodes of asthma in those who have already developed the disease. Certain clinical characteristics differentiate asthma from other chronic lung conditions. The most important of these is that the symptoms and functional disability caused by asthma vary from one occasion to another. In those with less severe asthma, they may be present on some occasions and not others; in those with more severe asthma, their degree of severity varies from one time to another.

Association of pediatric asthma severity with exposure to common household dust allergens

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

Gent, Janneane F., E-mail: janneane.gent@yale.edu; Belanger, Kathleen; Triche, Elizabeth W.

Background: Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. Objective: To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. Methods: Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collectedmore » in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother's education. Results: Der p 1 house dust mite allergen concentration of 2.0 {mu}g/g or more from the main room and the child's bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 {mu}g/g and OR 2.55 95% CI 1.13, 5.73 for {>=}10.0 {mu}g/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). Conclusion: Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.« less

Management of severe asthma: targeting the airways, comorbidities and risk factors.

PubMed

Gibson, Peter G; McDonald, Vanessa M

2017-06-01

Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out. Once a diagnosis of SRA is established, patients should undergo a systematic and multidimensional assessment to identify inflammatory endotypes, risk factors and comorbidities, with targeted and individualised management initiated. We describe a practical approach to assessment and management of patients with SRA. © 2017 Royal Australasian College of Physicians.

Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma.

PubMed

Singhania, Akul; Wallington, Joshua C; Smith, Caroline G; Horowitz, Daniel; Staples, Karl J; Howarth, Peter H; Gadola, Stephan D; Djukanović, Ratko; Woelk, Christopher H; Hinks, Timothy S C

2018-02-01

Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3 + T cells from sputum and BAL were obtained from healthy subjects (n = 19) and patients with asthma (mild, moderate, and severe asthma; n = 46). Gene expression was assessed using Affymetrix HT HG-U133 + PM GeneChips, and results were validated by real-time quantitative PCR. In the epithelium, IL-13 response genes (POSTN, SERPINB2, and CLCA1), mast cell mediators (CPA3 and TPSAB1), inducible nitric oxide synthase, and cystatins (CST1, CST2, and CST4) were upregulated in mild asthma, but, except for cystatins, were suppressed by corticosteroids in moderate asthma. In severe asthma-with predominantly neutrophilic phenotype-several distinct processes were upregulated, including neutrophilia (TCN1 and MMP9), mucins, and oxidative stress responses. The majority of the disease signature was evident in sputum T cells in severe asthma, where 267 genes were differentially regulated compared with health, highlighting compartmentalization of inflammation. This signature included IL-17-inducible chemokines (CXCL1, CXCL2, CXCL3, IL8, and CSF3) and chemoattractants for neutrophils (IL8, CCL3, and LGALS3), T cells, and monocytes. A protein interaction network in severe asthma highlighted signatures of responses to bacterial infections across tissues (CEACAM5, CD14, and TLR2), including Toll-like receptor signaling. In conclusion, the activation of innate immune pathways in the airways suggests that activated T cells may be driving neutrophilic inflammation and steroid-insensitive IL-17 response in severe asthma.

Admissions to Canadian hospitals for acute asthma: A prospective, multicentre study

PubMed Central

Rowe, Brian H; Villa-Roel, Cristina; Abu-Laban, Riyad B; Stenstrom, Rob; Mackey, Duncan; Stiell, Ian G; Campbell, Sam; Young, Bryan

2010-01-01

BACKGROUND: Asthma exacerbations constitute one of the most common causes of emergency department (ED) attendance in most developed countries. While severe asthma often requires hospitalization, variability in admission practices has been observed. OBJECTIVE: To describe the factors associated with admission to Canadian hospitals for acute asthma after ED treatment. METHODS: Subjects 18 to 55 years of age treated for acute asthma in 20 Canadian EDs prospectively underwent a structured ED interview (n=695) and telephone interview two weeks later. RESULTS: The median age of the patients was 30 years, and the majority were women (62.8%). The admission rate was 13.1% (95% CI 10.7% to 15.8%). Admitted patients were older, more often receiving oral or inhaled corticosteroids at presentation, and more frequently receiving systemic corticosteroids and magnesium sulphate in the ED. Similar proportions received beta-2 agonists and/or ipratropium bromide within 1 h of arrival. On multivariable analyses, factors associated with admission included age, previous admission in the past two years, more than eight beta-2 agonist puffs in the past 24 h, a Canadian Triage and Acuity Score of 1 to 2, a respiratory rate of greater than 22 breaths/min and an oxygen saturation of less than 95%. CONCLUSION: The admission rate for acute asthma from these Canadian EDs was lower than reported in other North American studies. The present study provides insight into practical factors associated with admission for acute asthma and highlights the importance of history and asthma severity markers on ED decision making. Further efforts to standardize ED management and expedite admission decision-making appear warranted. PMID:20186368

Improved asthma control in patients with severe, persistent allergic asthma after 12 months of nightly temperature-controlled laminar airflow: an observational study with retrospective comparisons

PubMed Central

Schauer, Uwe; Bergmann, Karl-Christian; Gerstlauer, Michael; Lehmann, Sylvia; Gappa, Monika; Brenneken, Amelie; Schulz, Christian; Ahrens, Peter; Schreiber, Jens; Wittmann, Michael; Hamelmann, Eckard

2015-01-01

Introduction Continuous or episodic allergen exposure is a major risk factor of frequent symptoms and exacerbations for patients with allergic asthma. It has been shown that temperature-controlled laminar airflow (TLA) significantly reduced allergen exposure and airway inflammation and improved quality of life of patients with poorly controlled allergic asthma. Objective The objective was to evaluate the effects of nighttime TLA when used during real-life conditions for 12 consecutive months in addition to the patients’ regular medication. Methods This multicenter, pre- and postretrospective observational study included patients with inadequately controlled moderate-to-severe allergic asthma who received add-on treatment with TLA for 12 consecutive months. Data on medication use, asthma control, asthma symptoms, lung function, use of hospital resources, and exacerbations were collected after 4 and 12 months and compared with corresponding data collected retrospectively from medical records during the year prior to inclusion in the study. Results Data from 30 patients (mean age 28; range 8–70) completing 4 months and 27 patients completing 12 months of TLA use are presented. The mean number of exacerbations was reduced from 3.6 to 1.3 (p<0.0001), and the ratio of asthma-related emergency room visits or hospitalizations diminished from 72.4 to 23.3% (p=0.001) or from 44.8 to 20.0% (p<0.05), respectively, after 12 months of TLA use. The Asthma Control Test index increased from 14.1 to 18.5 (p<0.0001). After 4 months of TLA use, clear improvements can be shown for most variables in line with the data collected after 12 months. Conclusions The addition of TLA to the patients’ regular medication significantly reduced exacerbations, asthma symptoms, and the utilization of hospital resources. The data support that TLA may be an important new non-pharmacological approach in the management of poorly controlled allergic asthma. PMID:26557252

Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children.

PubMed

Brehm, John M; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael; Boutaoui, Nadia; Forno, Erick; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Litonjua, Augusto A; Cabana, Michael; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2012-07-15

Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. A cross-sectional study was conducted of 560 children ages 6-14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P = 0.001) and atopy, and a lower FEV(1)/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P = 0.04) cases. Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.

Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children.

PubMed

Blatter, Joshua; Brehm, John M; Sordillo, Joanne; Forno, Erick; Boutaoui, Nadia; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Weiss, Scott T; Litonjua, Augusto A; Canino, Glorisa; Celedón, Juan C

2016-02-01

Little is known about folate and atopy or severe asthma exacerbations. We examined whether folate deficiency is associated with number of positive skin tests to allergens or severe asthma exacerbations in a high-risk population and further assessed whether such association is explained or modified by vitamin D status. Cross-sectional study of 582 children aged 6 to 14 years with (n = 304) and without (n = 278) asthma in San Juan, Puerto Rico. Folate deficiency was defined as plasma folate less than or equal to 20 ng/ml. Our outcomes were the number of positive skin tests to allergens (range, 0-15) in all children and (in children with asthma) one or more severe exacerbations in the previous year. Logistic and negative binomial regression models were used for the multivariate analysis. All multivariate models were adjusted for age, sex, household income, residential proximity to a major road, and (for atopy) case/control status; those for severe exacerbations were also adjusted for use of inhaled corticosteroids and vitamin D insufficiency (a plasma 25[OH]D < 30 ng/ml). In a multivariate analysis, folate deficiency was significantly associated with an increased degree of atopy and 2.2 times increased odds of at least one severe asthma exacerbation (95% confidence interval for odds ratio, 1.1-4.6). Compared with children who had normal levels of both folate and vitamin D, those with both folate deficiency and vitamin D insufficiency had nearly eightfold increased odds of one or more severe asthma exacerbation (95% confidence interval for adjusted odds ratio, 2.7-21.6). Folate deficiency is associated with increased degree of atopy and severe asthma exacerbations in school-aged Puerto Ricans. Vitamin D insufficiency may further increase detrimental effects of folate deficiency on severe asthma exacerbations.

Asthma Action Plan Receipt among Children with Asthma 2-17 Years of Age, United States, 2002-2013.

PubMed

Simon, Alan E; Akinbami, Lara J

2016-04-01

To examine national trends in the receipt of asthma action plans, an intervention recommended by the National Asthma Education and Prevention Program guidelines. We used data from the sample child component of the National Health Interview Survey from 2002, 2003, 2008, and 2013 to examine the percentage of children 2-17 years of age with asthma (n = 3714) that have ever received an asthma action plan. Bivariate and multivariate (with adjustment for sociodemographic characteristics and asthma outcomes consistent with greater disease severity) logistic regressions were conducted to examine trends from 2002 to 2013 and to examine, with 2013 data only, the relationship between having received an asthma action plan and both sociodemographic characteristics and indicators of asthma severity. The percentage of children with asthma that had ever received an asthma action plan increased from 41.7% in 2002 to 50.7% in 2013 (P < .001 for trend). In 2013, a greater percentage of non-Hispanic black (58.4%) than non-Hispanic white (47.4%) children (P = .028), privately insured (56.2%) vs those with public insurance only (46.3%) (P = .016), and users of inhaled preventive asthma medication vs those that did not (P < .001) had ever received an asthma action plan. Adjusted results were similar. The percentage of US children with asthma that had ever received an asthma action plan increased between 2002 and 2013, although one-half had never received an asthma action plan in 2013. Some sociodemographic and asthma severity measures are related to receipt of an asthma action plan. Published by Elsevier Inc.

Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry.

PubMed

Gibson, P G; Reddel, H; McDonald, V M; Marks, G; Jenkins, C; Gillman, A; Upham, J; Sutherland, M; Rimmer, J; Thien, F; Katsoulotos, G P; Cook, M; Yang, I; Katelaris, C; Bowler, S; Langton, D; Robinson, P; Wright, C; Yozghatlian, V; Burgess, S; Sivakumaran, P; Jaffe, A; Bowden, J; Wark, P A B; Yan, K Y; Kritikos, V; Peters, M; Hew, M; Aminazad, A; Bint, M; Guo, M

2016-09-01

Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting. © 2016 Royal Australasian College of Physicians.

Stepwise management of asthma.

PubMed

Khalid, Ayesha N

2015-09-01

Stepwise management of asthma remains an area of evolving research. Asthma is one of the most expensive chronic diseases in the United States; stepwise management is an important area of focus, with several recent guidelines recommending management. This is a review of published English language literature, focusing on management guidelines for asthma in adult and pediatric patients. Asthma is a chronic disease whose assessment of severity allows for therapeutic goals to match the impairment noted. Good evidence exists to aid risk reduction, leading to decreased emergency room visits, preventing loss of lung function in adults and lung growth in children, and optimizing pharmacotherapy with reduced side effects profile. Recent asthma management guidelines incorporate 4 components of asthma care including: monitoring of severity, patient education, controlling external triggers, and medications, including recent attention to medication adherence. Asthma is an expensive chronic disease with preventive measures leading to reduced healthcare costs. Future targeted cytokine therapy to decrease serum and blood eosinophils may become an integral part of asthma management. © 2015 ARS-AAOA, LLC.

Recent developments in the role of reactive oxygen species in allergic asthma

PubMed Central

Qu, Jingjing; Li, Yuanyuan; Zhong, Wen

2017-01-01

Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species (ROS) had been identified as a main reason for this respiratory inflammation. Many studies have shown that inhalation of different allergens can promote ROS generation. Recent studies have demonstrated that several pro-inflammatory mediators are responsible for the development of allergic asthma. Among these mediators, endogenous or exogenous ROS are responsible for the airway inflammation of allergic asthma. Furthermore, several inflammatory cells induce ROS and allergic asthma development. Airway inflammation, airway hyper-responsiveness, tissue injury, and remodeling can be induced by excessive ROS production in animal models. Based on investigations of allergic asthma and ROS formation mechanisms, we have identified several novel anti-inflammatory therapeutic treatments. This review describes the recent data linking ROS to the pathogenesis of allergic asthma. PMID:28203435

Fibromyalgia as a cause of uncontrolled asthma: a case-control multicenter study.

PubMed

Martinez-Moragon, Eva; Plaza, Vicente; Torres, Isabel; Rosado, Ana; Urrutia, Isabel; Casas, Xavier; Hinojosa, Belen; Blanco-Aparicio, Marina; Delgado, Julio; Quirce, Santiago; Sabadell, Carles; Cebollero, Pilar; Muñoz-Fernández, Ana

2017-12-01

Fibromyalgia can affect the control of asthma when both diseases are present in a single patient. To characterize asthma in patients with concomitant fibromyalgia to assess whether fibromyalgia is an independent factor of asthma severity that influences poor asthma control. We also evaluated how dyspnea is perceived by patients in order to demonstrate that alterations in the perception of airway obstruction may be responsible for poor asthma control. This was a cross-sectional case-control multicenter study, in which 56 patients in the asthma and fibromyalgia group were matched to 36 asthmatics by sex, approximate age, and asthma severity level. All patients were women. Study variables included the Asthma Control Test (ACT), the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), the Nijmegen hyperventilation syndrome questionnaire, the Hospital Anxiety and Depression Scale, and perception of dyspnea after acute bronchoconstriction. Although patients in both study groups showed similar asthma severity and use of anti-asthmatic drugs, patients in the asthma and fibromyalgia group showed lower scores on the ACT and MiniAQLQ questionnaires, and higher scores of anxiety and depression as well as hyperventilation compared to asthma patients without fibromyalgia. All these differences were statistically significant. Fibromyalgia in patients with asthma influences poor control of the respiratory disease and is associated with altered perception of dyspnea, hyperventilation syndrome, high prevalence of depression and anxiety, and impaired quality of life. Fibromyalgia may be considered a risk factor for uncontrolled asthma in patients suffering from asthma and fibromyalgia concomitantly.

Psychometric properties of a Chinese asthma quality of life questionnaire.

PubMed

Wang, Ningqun; Huang, Xiaobo; Chen, Wenqiang; Zhang, Xiaomei; Zhang, Yongsheng; Chen, Yujing

2017-12-01

To assess the acceptability, reliability, validity, and responsiveness of the Chinese Asthma Quality of Life Questionnaire (C-AQLQ) in a sample of Chinese asthma patients. The C-AQLQ and Short Form 36 Health Survey (SF-36) scales were administered to patients at baseline and 3 months later. Asthma severity condition and lung function were evaluated. Necessary data were gathered to assess the psychometric properties such as the feasibility, internal consistency, test-retest reliability, structural validity, discriminant validity, convergent validity, and responsiveness of the C-AQLQ. One hundred and thirty-seven patients completed the investigation. The Cronbach's alpha coefficient for the total scale was 0.96. Factor analysis yielded five factors that generally corresponded to the five proposed subscales. Patients with mild asthma reported higher scores than patients with moderate/severe asthma on all subscales other than environmental stimuli. Lung function measurement and the asthma severity score correlated significantly with domains of the C-AQOL but with fewer domains of the SF-36. The questionnaire detected within-subject changes in patients' asthma status during follow-up. Results indicated preliminary support that the C-AQLQ is a reliable, valid, discriminating, and responsive measure of quality of life in Chinese asthma patients. It is more sensitive than the generic SF-36 in detecting differences in asthma severity.

Prevalence of Mycoplasma pneumoniae infection in pediatric patients with acute asthma exacerbation.

PubMed

Kassisse, Elías; García, Hecmary; Prada, Linair; Salazar, Ixora; Kassisse, Jorge

2018-06-01

Mycoplasma pneumoniae may be involved in refractory asthma exacerbation. To determine the prevalence of Mycoplasma pneumoniae infection in patients with acute asthma exacerbation. Material and method. A prospective, crosssectional, observational, case-control study was carried out in patients older than 2 years old and younger than 12. Immunoglobulin M (IgM) antibodies were serologically determined for M. pneumoniae, using the NovaLisa® NovaTec kit for enzyme-linked immunosorbent assay (ELISA). Test results ≥ 11 NTU (NovaTec units) were regarded as positive. The statistical analysis was performed by means of the analysis of variance (ANOVA) and the χ² test, with a significance level of p < 0.05. One hundred and eighty children were studied, of which 130 had asthma and 50 comprised the control group. Specific IgM was positive for 60 patients, that is 46.15% of the asthmatic children (p < 0.001). The severity of the exacerbation was directly related to IgM levels (p < 0.001). Hospitalization rate was 75%, and it was significantly associated to specific IgM levels (p < 0.001). Our data suggest that children with acute asthma show a high prevalence (46%) of Mycoplasma pneumoniae infection and that there is a close relation between severe acute asthma exacerbation and the presence of Mycoplasma pneumoniae infection. These findings might result in therapeutic implications centered in the use of specific antibiotics to fight this atypical organism. Key words: acute asthma, exacerbation, Mycoplasma pneumoniae. Sociedad Argentina de Pediatría.

Obesity and adiposity indicators, asthma, and atopy in Puerto Rican children.

PubMed

Forno, Erick; Acosta-Pérez, Edna; Brehm, John M; Han, Yueh-Ying; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2014-05-01

Whether adiposity indicators other than body mass index (BMI) should be used in studies of childhood asthma is largely unknown. The role of atopy in "obese asthma" is also unclear. To examine the relationship among adiposity indicators, asthma, and atopy in Puerto Rican children, and to assess whether atopy mediates the obesity-asthma association. In a study of Puerto Rican children with (n = 351) and without (n = 327) asthma, we measured BMI, percent of body fat, waist circumference, and waist-to-hip ratio. The outcomes studied included asthma, lung function, measures of atopy, and, among cases, indicators of asthma severity or control. We performed mediation analysis to assess the contribution of atopy to the relationship between adiposity and asthma. BMI, percent of body fat, and waist circumference were associated with increased odds of asthma. Among cases, all 3 measures were generally associated with lung function, asthma severity/control, and atopy; however, there were differences depending on the adiposity indicator analyzed. Atopy considerably mediated the adiposity-asthma association in this population: allergic rhinitis accounted for 22% to 53% of the association with asthma, and sensitization to cockroach mediated 13% to 20% of the association with forced vital capacity and 29% to 42% of the association with emergency department visits for asthma. Adiposity indicators are associated with asthma, asthma severity/control, and atopy in Puerto Rican children. Atopy significantly mediates the effect of adiposity on asthma outcomes. Longitudinal studies are needed to further investigate the causal role, if any, of adiposity distribution and atopy on "obese asthma" in childhood. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Asthma severity, child security, and child internalizing: using story stem techniques to assess the meaning children give to family and disease-specific events.

PubMed

Winter, Marcia A; Fiese, Barbara H; Spagnola, Mary; Anbar, Ran D

2011-12-01

Children with persistent asthma are at increased risk for mental health problems. Although mechanisms of effect are not yet known, it may be that children are less trusting of the family as a source of support and security when they have more severe asthma. This study tested whether asthma severity is related to children's perceptions of insecurity in the family, and whether insecurity is in turn associated with child adjustment. Children (N = 168; mean age = 8 years) completed story stems pertaining to routine family events (e.g., mealtimes) and ambiguous but potentially threatening asthma events such as tightness in the chest. Responses were evaluated for the extent to which appraisals portrayed the family as responding in cohesive, security-provoking ways. Asthma severity was assessed by both objective lung function testing and primary caregiver report. Caregivers reported child symptomatology. Beyond medication adherence, caregiver education, and child age and gender, greater asthma severity predicted more internalizing and externalizing symptoms. Greater asthma severity, assessed using spirometry (but not parent report), was related to less secure child narratives of the family, which in turn related to more child internalizing symptoms. Results suggest that asthma can take a considerable toll on children's feelings of security and mental health. Furthermore, given the difficulty in assessing young children's perceptions, this study helps demonstrate the potential of story stem techniques in assessing children's appraisals of illness threat and management in the family.

Asthma Severity, Child Security, and Child Internalizing: Using Story Stem Techniques to Assess the Meaning Children Give to Family and Disease-Specific Events

PubMed Central

Winter, Marcia A.; Fiese, Barbara H.; Spagnola, Mary; Anbar, Ran D.

2016-01-01

Children with persistent asthma are at increased risk for mental health problems. Although mechanisms of effect are not yet known, it may be that children are less trusting of the family as a source of support and security when they have more severe asthma. This study tested whether asthma severity is related to children’s perceptions of insecurity in the family, and whether insecurity is in turn associated with child adjustment. Children (N = 168; mean age = 8 years) completed story stems pertaining to routine family events (e.g., mealtimes) and ambiguous but potentially threatening asthma events such as tightness in the chest. Responses were evaluated for the extent to which appraisals portrayed the family as responding in cohesive, security-provoking ways. Asthma severity was assessed by both objective lung function testing and primary caregiver report. Caregivers reported child symptomatology. Beyond medication adherence, caregiver education, and child age and gender, greater asthma severity predicted more internalizing and externalizing symptoms. Greater asthma severity, assessed using spirometry (but not parent report), was related to less secure child narratives of the family, which in turn related to more child internalizing symptoms. Results suggest that asthma can take a considerable toll on children’s feelings of security and mental health. Furthermore, given the difficulty in assessing young children’s perceptions, this study helps demonstrate the potential of story stem techniques in assessing children’s appraisals of illness threat and management in the family. PMID:22059557

Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study

PubMed Central

Li, Jing; Kang, Jian; Wang, Changzheng; Yang, Jing; Wang, Linda; Kottakis, Ioannis; Humphries, Michael

2016-01-01

Purpose Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. Methods This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). Results A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; P<0.001) and ACQ (49.5% vs 35.5%; LSM=-0.51 vs -0.34; P=0.002) scores vs placebo. Total and nighttime symptom scores reduced significantly with omalizumab vs placebo (LSM-TD=-0.21, P=0.048 and -0.12, P=0.011, respectively). Although the study was not powered to study differences in exacerbation rates (P=0.097), exacerbations in winter months were less frequent in the omalizumab vs placebo group (2 vs 21). Adverse event and severe adverse event rates were comparable between omalizumab and placebo. Conclusions Omalizumab improves lung function, quality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile. PMID:27126725

A tiered asthma hazard characterization and exposure assessment approach for evaluation of consumer product ingredients.

PubMed

Maier, Andrew; Vincent, Melissa J; Parker, Ann; Gadagbui, Bernard K; Jayjock, Michael

2015-12-01

Asthma is a complex syndrome with significant consequences for those affected. The number of individuals affected is growing, although the reasons for the increase are uncertain. Ensuring the effective management of potential exposures follows from substantial evidence that exposure to some chemicals can increase the likelihood of asthma responses. We have developed a safety assessment approach tailored to the screening of asthma risks from residential consumer product ingredients as a proactive risk management tool. Several key features of the proposed approach advance the assessment resources often used for asthma issues. First, a quantitative health benchmark for asthma or related endpoints (irritation and sensitization) is provided that extends qualitative hazard classification methods. Second, a parallel structure is employed to include dose-response methods for asthma endpoints and methods for scenario specific exposure estimation. The two parallel tracks are integrated in a risk characterization step. Third, a tiered assessment structure is provided to accommodate different amounts of data for both the dose-response assessment (i.e., use of existing benchmarks, hazard banding, or the threshold of toxicological concern) and exposure estimation (i.e., use of empirical data, model estimates, or exposure categories). Tools building from traditional methods and resources have been adapted to address specific issues pertinent to asthma toxicology (e.g., mode-of-action and dose-response features) and the nature of residential consumer product use scenarios (e.g., product use patterns and exposure durations). A case study for acetic acid as used in various sentinel products and residential cleaning scenarios was developed to test the safety assessment methodology. In particular, the results were used to refine and verify relationships among tiered approaches such that each lower data tier in the approach provides a similar or greater margin of safety for a given scenario. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Phagocytosis, bacterial killing, and cytokine activation of circulating blood neutrophils in horses with severe equine asthma and control horses.

PubMed

Vanderstock, Johanne M; Lecours, Marie-Pier; Lavoie-Lamoureux, Annouck; Gottschalk, Marcelo; Segura, Mariela; Lavoie, Jean-Pierre; Jean, Daniel

2018-04-01

OBJECTIVE To evaluate in vitro phagocytosis and bactericidal activity of circulating blood neutrophils in horses with severe equine asthma and control horses and to determine whether circulating blood neutrophils in horses with severe equine asthma have an increase in expression of the proinflammatory cytokine tumor necrosis factor (TNF)-α and the chemokine interleukin (IL)-8 and a decrease in expression of the anti-inflammatory cytokine IL-10 in response to bacteria. ANIMALS 6 horses with severe equine asthma and 6 control horses. PROCEDURES Circulating blood neutrophils were isolated from horses with severe equine asthma and control horses. Phagocytosis was evaluated by use of flow cytometry. Bactericidal activity of circulating blood neutrophils was assessed by use of Streptococcus equi and Streptococcus zooepidemicus as targets, whereas the cytokine mRNA response was assessed by use of a quantitative PCR assay. RESULTS Circulating blood neutrophils from horses with severe equine asthma had significantly lower bactericidal activity toward S zooepidemicus but not toward S equi, compared with results for control horses. Phagocytosis and mRNA expression of TNF-α, IL-8, and IL-10 were not different between groups. CONCLUSIONS AND CLINCAL RELEVANCE Impairment of bactericidal activity of circulating blood neutrophils in horses with severe equine asthma could contribute to an increased susceptibility to infections.

Mild, Moderate, Severe Asthma: What Do Grades Mean?

MedlinePlus

... Text Size Email Print Share Mild, Moderate, Severe Asthma: What Do Grades Mean? Page Content Article Body ... is when assessed at follow-up visits. Intermittent Asthma A child who has symptoms of wheezing and ...

Unravelling a Clinical Paradox - Why Does Bronchial Thermoplasty Work in Asthma?

PubMed

Donovan, Graham M; Elliot, John G; Green, Francis H Y; James, Alan L; Noble, Peter B

2018-04-18

Rationale Bronchial thermoplasty is a relatively new but effective treatment in asthmatic subjects who do not respond to conventional therapy. While the favoured mechanism is ablation of the airway smooth muscle layer, because bronchial thermoplasty treats only a small number of central airways, there is ongoing debate regarding its precise method of action. Objectives Elucidate the underlying method of action behind bronchial thermoplasty. Methods We employ a combination of extensive human lung specimens and novel computational methods. Whole left lungs were acquired from the Prairie Provinces Fatal Asthma Study. Subjects were classified as control (N=31), non-fatal asthma (N=32), or fatal asthma (N=25). Simulated lungs for each group were constructed stochastically, and flow distributions and functional indicators were quantified both before and after a 70% reduction in airway smooth muscle in the thermoplasty-treated airways. Main Results Bronchial thermoplasty triggers global redistribution of clustered flow patterns, wherein structural changes to the treated central airways lead to a re-opening cascade in the small airways and significant improvement in lung function via reduced spatial heterogeneity of flow patterns. This mechanism accounts for progressively greater efficacy of thermoplasty with both severity of asthma and degree of muscle activation, consistent with existing empirical results. Conclusions We report a probable mechanism of action for bronchial thermoplasty: alteration of lung-wide flow patterns in response to structural alteration of the treated central airways. This insight could lead to improved therapy via patient-specific, tailored versions of the treatment -- as well as implications for more conventional asthma therapies.

Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

PubMed

McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

2018-03-08

Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965 .).

Attendance for general practitioner asthma care by children with moderate to severe asthma in Auckland, New Zealand.

PubMed

Buetow, Stephen; Richards, Deborah; Mitchell, Ed; Gribben, Barry; Adair, Vivienne; Coster, Gregor; Hight, Makere

2004-11-01

Attendance for general practitioner (GP) care of childhood asthma varies widely in New Zealand (NZ). There is little current research to account for the variations, although groups such as Māori and Pacific peoples have traditionally faced barriers to accessing GP care. This paper aims to describe and account for attendance levels for GP asthma care among 6-9 year-olds with moderate to severe asthma in Auckland, NZ. During 2002, randomly selected schools identified all 6-9 year-olds with possible breathing problems. Completion of a questionnaire by each parent/guardian indicated which children had moderate to severe asthma, and what characteristics influenced their access to GP asthma care. A multilevel, negative binomial regression model (NBRM) was fitted to account for the number of reported GP visits for asthma, with adjustment for clustering within schools. Twenty-six schools (89.7 percent) identified 931 children with possible breathing problems. Useable questionnaires were returned to schools by 455 children (48.9 percent). Results indicated 209 children with moderate to severe asthma, almost one in every three reportedly making 5 or more GP visits for asthma in the previous year. Māori, Pacific and Asian children were disproportionately represented among these 'high attendees'. Low attendees (0-2 visits) were mainly NZ Europeans. The NBRM (n=155) showed that expected visits were increased by perceived need, ill-health, asthma severity and, in particular, Māori and Pacific child ethnicity. It may be that Māori and Pacific children no longer face significant barriers to accessing GP asthma care. However, more likely is that barriers apply only to accessing routine, preventative care, leading to poor asthma control, exacerbations requiring acute care, and paradoxically an increase in GP visits. That barriers may increase total numbers of visits challenges the assumption, for all health systems, that access can be defined in terms of barriers that must be overcome to obtain health care.

A current picture of asthma diagnosis, severity, and control in a low-income minority preteen population.

PubMed

Clark, Noreen M; Dodge, Julia A; Shah, Smita; Thomas, Lara J; Andridge, Rebecca R; Awad, Daniel

2010-03-01

Asthma severity, control, type of medical regimen provided, and compliance with it are not well understood in minority patients at the transition stage from childhood to adolescence. Describe the level of asthma severity and control and the clinical regimens provided to a large population of low-income, African American children at this developmentally significant period. Parents of 1292 children with asthma among 6827 preteens in 19 middle schools in predominantly African American (94%), low-income neighborhoods in Detroit, Michigan, were enrolled in the study. Data were collected through self-administered survey and telephone interviews and were useable for 936 participants. Study queries related to demographics, asthma symptoms, and medication use. Mixed effects models with a random intercept for school were used to determine severity and control and the association of medical regimens to these. Sixty-seven percent of children with probable asthma had received a physician's diagnosis. Being female was associated with being undiagnosed (p = .02). Forty-seven with no diagnosis had persistent asthma and 10% of these were classified as severe. Sixty-eight percent with a diagnosis and asthma medicine prescriptions were not controlled. Compliant use of controller medicine was associated with poorer asthma control compared to noncompliant controller users (p = .04) and reliever-only users (p < .001). Thirty-nine percent of children had controller medicine; of those 40% were not compliant with controller use; 9% nebulized their controller medicine. Care provided low-income minority children at an important stage in their development was not consistent with guidelines for asthma control. Therapy choices for treatment did not account for the actual level of their symptoms. Lack of an asthma diagnosis was significant in the population. Adolescent girls were at risk for not receiving a diagnosis. Patient compliance with asthma regimens was limited. Both clinician and patient education regarding effective asthma management appears needed regarding preteens in low-income minority communities.

Genetic polymorphisms and asthma: findings from a case-control study in the Madeira island population.

PubMed

Berenguer, Anabela Gonçalves; Fernandes, Ana Teresa; Oliveira, Susana; Rodrigues, Mariana; Ornelas, Pedro; Romeira, Diogo; Serrão, Tânia; Rosa, Alexandra; Câmara, Rita

2014-09-04

Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set. Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10 mm) to house dust (1.4-fold) and storage mite (7.8-fold). In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.

Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes.

PubMed

Pillai, S G; Tang, Y; van den Oord, E; Klotsman, M; Barnes, K; Carlsen, K; Gerritsen, J; Lenney, W; Silverman, M; Sly, P; Sundy, J; Tsanakas, J; von Berg, A; Whyte, M; Ortega, H G; Anderson, W H; Helms, P J

2008-03-01

Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the contribution of genes and environments to disease expression. To determine the minimum number of sets of features required to characterize subjects with asthma which will be useful in identifying important genetic and environmental contributors. Methods Probands aged 7-35 years with physician diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families from 11 centres in six countries forming the Genetics of Asthma International Network. Factor analysis was used to identify distinct phenotypes from questionnaire, clinical, and laboratory data, including baseline pulmonary function, allergen skin prick test (SPT). Five distinct factors were identified:(1) baseline pulmonary function measures [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], (2) specific allergen sensitization by SPT, (3) self-reported allergies, (4) symptoms characteristic of rhinitis and (5) symptoms characteristic of asthma. Replication in symptomatic siblings was consistent with shared genetic and/or environmental effects, and was robust across age groups, gender, and centres. Cronbach's alpha ranged from 0.719 to 0.983 suggesting acceptable internal scale consistencies. Derived scales were correlated with serum IgE, methacholine PC(20), age and asthma severity (interrupted sleep). IgE correlated with all three atopy-related factors, the strongest with the SPT factor whereas severity only correlated with baseline lung function, and with symptoms characteristic of rhinitis and of asthma. In children and adolescents with established asthma, five distinct sets of correlated patient characteristics appear to represent important aspects of the disease. Factor scores as quantitative traits may be better phenotypes in epidemiological and genetic analyses than those categories derived from the presence or absence of combinations of +ve SPTs and/or elevated IgE.

Parental Numeracy and Asthma Exacerbations in Puerto Rican Children

PubMed Central

Rosas-Salazar, Christian; Ramratnam, Sima K.; Brehm, John M.; Han, Yueh-Ying; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Apter, Andrea J.

2013-01-01

Background: Puerto Ricans share a disproportionate burden of childhood asthma in the United States. Little is known about the impact of low parental numeracy (a health literacy skill) on asthma morbidity in Puerto Rican children. Our objective was to examine whether low parental numeracy is associated with increased asthma morbidity in Puerto Rican children. Methods: This was a cross-sectional study of 351 children with asthma, aged 6 to 14 years, living in San Juan, Puerto Rico. Parents of study participants completed a modified version of the Asthma Numeracy Questionnaire. Multivariate linear or logistic regression was used to examine the relation between low parental numeracy (defined as no correct answers in the modified Asthma Numeracy Questionnaire) and indicators of asthma morbidity (severe asthma exacerbations, core measures of asthma exacerbations, and lung function measures). All multivariate models were adjusted for age, sex, household income, reported use of inhaled corticosteroids in the previous 6 months, and exposure to secondhand tobacco smoke. Results: Low parental numeracy was associated with increased odds of visits to the ED or urgent care for asthma (adjusted OR [aOR] = 1.7, 95% CI = 1.03-2.7, P = .04). The association between low parental numeracy and hospitalizations for asthma was significant only among children not using inhaled corticosteroids (aOR = 2.8, 95% CI = 1.4-5.6, P = .004). There was no association between low parental numeracy and use of systemic steroids or lung function measures. Conclusions: Low parental numeracy is associated with increased asthma morbidity in Puerto Rican children. PMID:23493983

Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level.

PubMed

Han, Wei; Li, Jun; Tang, Huaping; Sun, Lixin

2017-03-04

Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity.

PubMed

Park, So Young; Hong, Gyong Hwa; Park, Sunjoo; Shin, Bomi; Yoon, Sun-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

2016-12-01

Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. To investigate the association between serum progranulin levels and various clinical features in patients with asthma. Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma. Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P < .001) after adjustment for other variables, such as age, sex, smoking status, blood neutrophil count, and current use of systemic corticosteroids. Although the exact mechanism of the anti-inflammatory action of progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Targeting the interleukin pathway in the treatment of asthma.

PubMed

Chung, Kian Fan

2015-09-12

Asthma is a common heterogeneous disease with a complex pathophysiology. Current therapies based on inhaled corticosteroids and longacting β2 agonists are effective in controlling asthma in most, but not all patients, with a few patients falling into the severe asthma category. Severe asthma is characterised by poor asthma control, recurrent exacerbations, and chronic airflow obstruction despite adequate and, in many cases, high-dose treatments. There is strong evidence supporting the role for interleukins derived from T-helper-2 (Th2) cells and innate lymphoid cells, such as interleukins 4, 5, and 13, as underlying the eosinophilic and allergic inflammatory processes in nearly half of these patients. An anti-IgE antibody, omalizumab, which binds to circulating IgE, a product of B cells from the actions of interleukin 4 and interleukin 13, is used as treatment for severe allergic asthma. Studies examining cytokine blockers such as anti-interleukin-5, anti-interleukin-4Rα, and anti-interleukin-13 monoclonal antibodies in patients with severe asthma with recurrent exacerbations and high blood eosinophil counts despite use of inhaled corticosteroids have reported improved outcomes in terms of exacerbations, asthma control, and forced expiratory volume in 1 s. The US Food and Drug Administration's recommendation to use an anti-interleukin-5 antibody for the treatment of severe eosinophilic asthma suggests that there will be a therapeutic place for these anti-Th2 agents. Biomarkers should be used to identify the right patients for such targeted approaches. More guidance will be needed as to which patients should receive each of these classes of selective antibody-based treatments. Currently, there is no treatment that targets the cytokines driving asthma associated with non-eosinophilic inflammation and low Th2 expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Allergen aerosol from pollen-nucleated precipitation: A novel thunderstorm asthma trigger

NASA Astrophysics Data System (ADS)

Beggs, Paul John

2017-03-01

Thunderstorm asthma is the term used to describe epidemics of asthma exacerbation associated with thunderstorms. Most published reports of thunderstorm asthma have come from the United Kingdom, Canada, and Australia, although several studies have been published on the phenomenon in the USA and Europe (particularly Greece and Italy). Such reports usually consider changes in hospital admissions or emergency department attendances for asthma. For example, Celenza et al. (1996) studied an asthma epidemic in London in June 1994 where 40 patients presented to the accident and emergency department of St Mary's Hospital in the 24 hours after a thunderstorm compared to an average of just over 2 asthma presentations per day over the several weeks before and after this event. More recent examples include the 20 patients who presented to an emergency department in Puglia, Italy, for sudden and severe asthmatic symptoms immediately after a thunderstorm in May 2010, where the average daily emergency department presentations for asthma several weeks before and after this event was only 2 to 3 (Losappio et al., 2011); and the 36 emergency department presentations for acute asthma to the Austin Hospital in Melbourne, Australia, on 25 November 2010 immediately after a thunderstorm (with the number of such presentations on days prior to and following the epidemic ranging from 0 to 10) (Howden et al., 2011).

The economic impact of severe asthma to low-income families.

PubMed

Franco, R; Nascimento, H F; Cruz, A A; Santos, A C; Souza-Machado, C; Ponte, E V; Souza-Machado, A; Rodrigues, L C; Barreto, M L

2009-03-01

To estimate the direct and indirect costs of severe asthma and the economic impact of its management to low-income families in Salvador, Brazil. One hundred and ninety-seven patients with severe asthma and referred to a state-funded asthma center providing free treatment were evaluated. At registration, they were asked about family cost-events in the previous year and had a baseline assessment of lung function, symptoms and quality of life. During the subsequent year, they were reassessed prospectively. One hundred-eighty patients concluded a 12-month follow-up. Eighty-four percent were female patients, and the median family income was US$ 2955/year. Forty-seven percent of family members had lost their jobs because of asthma. Total cost of asthma management took 29% of family income. After proper treatment, asthma control scores improved by 50% and quality of life by 74%. The income of the families increased by US$ 711/year, as their members went back to work. The total cost of asthma to the families was reduced by a median US$ 789/family/year. Consequently, an annual surplus of US$ 1500/family became available. Family costs of severe asthma consumed over one-fourth of the family income of the underprivileged population in a middle-income country. Adequate management brings major economic benefit to individuals and families.

Anesthesia in children with asthma and rhinitis.

PubMed

Franceschini, F; De Benedictis, F M; Peroni, D G; Marseglia, G L; Caffarelli, C; Crisafulli, G; Indinnimeo, L

2011-01-01

The incidence of asthma is increasing worldwide, but morbidity and mortality are decreasing, because of improvements in medical care. Although the incidence of severe perioperative bronchospasm is relatively low in asthmatics undergoing anaesthesia, when it does occur it may be life-threatening. Preoperative assessment of asthma should include a specialized medical hystory and physical examination as well as pulmonary function testing. Potential trigger agents should be identified and avoided. In many asthmatic patients treatment with systemic corticosteroids and bronchodilators is indicated to prevent the inflammation and bronchocostriction associated with endotracheal intubation. Nonetheless, acute bronchospasm can still occur, especially at induction and emergence, and should be promptly and methodically managed.

The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis.

PubMed

Daugherty, Jonas; Lin, Xiwu; Baxter, Richard; Suruki, Robert; Bradford, Eric

2018-06-01

Systemic glucocorticoids (SGCs) are a treatment option for severe asthma but are associated with the development of adverse events (AEs). Evidence on the extent of SGC use and the relationship between SGC dose and AE risk in severe asthma is limited. Patients with severe asthma (Global Initiative for Asthma step 4/5), with no SGC use during the <6-12 months before severe asthma determination (index date) were identified in the UK-based Clinical Practice Research Datalink database (2004-2012). Patients were assessed for SGC exposure and an incident diagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI], osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. The dose-related risk of an SGC-related AE was determined using AE-specific Cox proportional hazards models. Overall, 75% of 60,418 patients identified with severe asthma received SGC during the 8-year follow-up, with the majority receiving an average of >0-≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidence interval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis (HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0-2.5 mg/day), with further risk increases at doses >2.5 mg/day versus no SGC use. Compared with no SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependent manner, but the risk of stroke was unchanged. Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.

Allergic sinusitis and severe asthma caused by occupational exposure to locust bean gum: Case report

PubMed Central

Hawley, Brie; Cummings, Kristin J.; Mohammed, Mohammed; Dimmock, Anne E.; Bascom, Rebecca

2017-01-01

We present a case that highlights the difficulties with diagnosis and the dangers of occupational allergic sinusitis and asthma left unrecognized. We describe the case history of a man who experienced work-related symptoms 1 year after beginning work as a cheesemaker at a creamery, and whose respiratory symptoms progressively worsened over 16 years before an occupational cause of his asthma was identified. His initial discrete episodes of sinusitis and acute bronchitis evolved into persistent asthma of increasing severity with exacerbations requiring repeated emergency room treatment. The case described in our report emphasizes the importance of clinician diagnosis of OA, and subsequent removal from exposure, such that asthma severity does not progress to near-fatal or fatal asthma in the sensitized worker. As demonstrated by this case report, identification of an occupational cause of asthma relies on a high degree of suspicion and excellent detective work by the clinician. PMID:28497854

Asthma-Related Outcomes in Patients Initiating Extrafine Ciclesonide or Fine-Particle Inhaled Corticosteroids

PubMed Central

Postma, Dirkje S.; Dekhuijzen, Richard; van der Molen, Thys; Martin, Richard J.; van Aalderen, Wim; Roche, Nicolas; Guilbert, Theresa W.; Israel, Elliot; van Eickels, Daniela; Khalid, Javaria Mona; Herings, Ron M.C.; Overbeek, Jetty A.; Miglio, Cristiana; Thomas, Victoria; Hutton, Catherine; Hillyer, Elizabeth V.

2017-01-01

Purpose Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). Methods This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. Results Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. Conclusions In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS. PMID:28102056

The Program for the Prevention of Childhood Asthma: a specialized care program for children with wheezing or asthma in Brazil

PubMed Central

Urrutia-Pereira, Marilyn; Avila, Jennifer; Solé, Dirceu

2016-01-01

Objective : To present the Programa Infantil de Prevenção de Asma (PIPA, Program for the Prevention of Childhood Asthma) and the characteristics of the patients followed in this program. Methods : Implemented in the city of Uruguaiana, Brazil, PIPA has as its target population children and adolescents (< 18 years of age) with asthma or suspected asthma. Patients either enroll in PIPA spontaneously or are referred by pediatricians or primary care physicians. In this retrospective study, we use a standardized protocol to assess PIPA patients. Results : By the end of the study period, 646 patients were being followed. Of those, 298 (46.1%) were ≤ 3 years of age. In this group of patients, recurrent wheezing was identified in 60.7%, and the first episode of wheezing occurred in the first six months of life in 86.0%. Severe wheezing was identified in 29.5% and 45.4% in the children ≤ 3 and > 3 years of age, respectively. Physician-diagnosed asthma was reported in 26.5% and 82.2%, respectively. In the sample as a whole, the prevalence of passive smoking was high (> 36%), occurring during pregnancy in > 15%; > 40% of the patients had been born by cesarean section; and 30% had a mother who had had < 8 years of schooling. Conclusions : A prevention program for children with asthma is an effective strategy for controlling the disease. Knowledge of local epidemiological and environmental characteristics is essential to reducing the prevalence of the severe forms of asthma, to improving the use of health resources, and to preventing pulmonary changes that could lead to COPD in adulthood. PMID:26982040

Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma.

PubMed

Castro, Mario; Corren, Jonathan; Pavord, Ian D; Maspero, Jorge; Wenzel, Sally; Rabe, Klaus F; Busse, William W; Ford, Linda; Sher, Lawrence; FitzGerald, J Mark; Katelaris, Constance; Tohda, Yuji; Zhang, Bingzhi; Staudinger, Heribert; Pirozzi, Gianluca; Amin, Nikhil; Ruddy, Marcella; Akinlade, Bolanle; Khan, Asif; Chao, Jingdong; Martincova, Renata; Graham, Neil M H; Hamilton, Jennifer D; Swanson, Brian N; Stahl, Neil; Yancopoulos, George D; Teper, Ariel

2018-05-21

Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. Methods We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV 1 ) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV 1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. Results The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV 1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. Conclusions In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .).

Adiposity, fractional exhaled nitric oxide, and asthma in U.S. children.

PubMed

Han, Yueh-Ying; Forno, Erick; Celedón, Juan C

2014-07-01

Whether allergic airway inflammation mediates the association between overweight or obesity and childhood asthma is unknown. To examine adiposity, asthma, and fractional exhaled nitric oxide (FeNO) in U.S. children. Cross-sectional study of indicators of adiposity or obesity, FeNO (a biomarker of eosinophilic airway inflammation), and asthma in 2,681 children aged 6-17 years in the 2007-2010 National Health and Nutrition Examination Survey. Adiposity measures included body mass index (BMI), percent body fat (PBF), and waist circumference (WC). BMI, PBF, and WC were associated with asthma among children with low FeNO (odds ratio, 1.54-1.68; P < 0.01), but not among children with increased FeNO. Among children without asthma, BMI, PBF, and WC were associated with higher FEV1 and FVC, and lower FEV1/FVC. Among children with asthma and a high FeNO, all adiposity indicators were associated with decreased FEV1/FVC (β = -1.5% to -1.7% per z score) but not with FEV1 or FVC. Higher BMI or PBF was associated with worse asthma severity or control in children with asthma and increased FeNO, but not in children with asthma and low FeNO. Similar results were obtained in a secondary multivariate analysis of overweight or obesity (defined as BMI ≥85th percentile) and asthma or indicators of asthma severity or control, stratified by FeNO level. Adiposity indicators are associated with asthma in children with low FeNO. Among children with asthma, adiposity indicators are associated with worse asthma severity or control in those with high FeNO.

Asthma control in Latin America: the Asthma Insights and Reality in Latin America (AIRLA) survey.

PubMed

Neffen, Hugo; Fritscher, Carlos; Schacht, Francisco Cuevas; Levy, Gur; Chiarella, Pascual; Soriano, Joan B; Mechali, Daniel

2005-03-01

The aims of this survey were (1) to assess the quality of asthma treatment and control in Latin America, (2) to determine how closely asthma management guidelines are being followed, and (3) to assess perception, knowledge and attitudes related to asthma in Latin America. We surveyed a household sample of 2,184 adults or parents of children with asthma in 2003 in 11 countries in Latin America. Respondents were asked about healthcare utilization, symptom severity, activity limitations and medication use. Daytime asthma symptoms were reported by 56% of the respondents, and 51% reported being awakened by their asthma at night. More than half of those surveyed had been hospitalized, attended a hospital emergency service or made unscheduled emergency visits to other healthcare facilities for asthma during the previous year. Patient perception of asthma control did not match symptom severity, even in patients with severe persistent asthma, 44.7% of whom regarded their disease as being well or completely controlled. Only 2.4% (2.3% adults and 2.6% children) met all criteria for asthma control. Although 37% reported treatment with prescription medications, only 6% were using inhaled corticosteroids. Most adults (79%) and children (68%) in this survey reported that asthma symptoms limited their activities. Absence from school and work was reported by 58% of the children and 31% of adults, respectively. Asthma control in Latin America falls short of goals in international guidelines, and in many aspects asthma care and control in Latin America suffer from the same shortcomings as in other areas of the world.

Predicting worsening asthma control following the common cold

PubMed Central

Walter, Michael J.; Castro, Mario; Kunselman, Susan J.; Chinchilli, Vernon M; Reno, Melissa; Ramkumar, Thiruvamoor P.; Avila, Pedro C.; Boushey, Homer A.; Ameredes, Bill T.; Bleecker, Eugene R.; Calhoun, William J.; Cherniack, Reuben M.; Craig, Timothy J.; Denlinger, Loren C.; Israel, Elliot; Fahy, John V.; Jarjour, Nizar N.; Kraft, Monica; Lazarus, Stephen C.; Lemanske, Robert F.; Martin, Richard J.; Peters, Stephen P.; Ramsdell, Joe W.; Sorkness, Christine A.; Rand Sutherland, E.; Szefler, Stanley J.; Wasserman, Stephen I.; Wechsler, Michael E.

2008-01-01

The asthmatic response to the common cold is highly variable and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multi-center cohort study of 413 adult subjects with asthma, we used the mini-Asthma Control Questionnaire (mini-ACQ) to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models examined demographic, physiologic, serologic, and cold-related characteristics for their relationship to changes in asthma control following a cold. We observed a clinically significant worsening of asthma control following a cold (increase in mini-ACQ of 0.69 ± 0.93). Univariate analysis demonstrated season, center location, cold length, and cold severity measurements all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed the day 2 and the cumulative sum of the day 1 and 2 WURSS-21 scores were significant predictors for the subsequent changes in asthma control. In asthmatic subjects the cold severity measured within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold. PMID:18768579

[The standardized perioperative treatment of chronic rhinosinusitis with nasal polyps and asthma].

PubMed

Li, Tingting; Ju, Jianbao; Yu, Hailing; Xie, Daoyu

2015-04-01

To discuss the perioperative treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma. Retrospective analysis of perioperative clinical data of 43 cases with CRSwNP and asthma. The admitted and under endoscopic surgery. Patients with preventing perioperative asthma attacks and corresponding standardized treatment were Observed. Thirty-five cases were stable during perioperative period and without asthma. Seven patients diagnosed as mild and moderate asthma attacks because of low pulse oximetry (SpO2 92%-95%) and scattered wheeze heard in the lungs. So these patients were sent to ICU for the treatment. They went back to ward after their conditions turned to stable and no asthma during perioperative. One patient diagnosed as severe asthma attack, because irritability and suffocation happened, SpO2 decreased from 99% to 84%-81%, diffuse wheeze could be heard in the whole lung . So we give him tracheal intubation and sent him to ICU for advanced treatment after breathing smooth. Five days later the patient retuned to the ward in stable condition and with no asthma attack again. Before operation the patients should be give some corresponding standardized comprehensive treatment according to the nasal symptoms and the degree of asthma attack, such as the application of topical steroid and antiallergic medicine. And some special treatment should be given to reduce airway hyperresponsiveness mucosa during anesthesia. These methods can reduce the risk of the asthma attacks and improve perioperative safety, prevent serious complications.

Sweat test practice in pediatric pulmonology after introduction of cystic fibrosis newborn screening.

PubMed

Grimaldi, Céline; Brémont, François; Berlioz-Baudoin, Michèle; Brouard, Jacques; Corvol, Harriet; Couderc, Laure; Lezmi, Guillaume; Pin, Isabelle; Petit, Isabelle; Reix, Philippe; Remus, Natacha; Schweitzer, Cyril; Thumerelle, Caroline; Dubus, Jean-Christophe

2015-12-01

The influence of the generalization of cystic fibrosis newborn screening (CFNBS) in France on sweat test (ST) prescription is unknown. In this French retrospective, descriptive, and multicenter study, we studied the indications, number, methods, and results of STs prescribed by a pediatric pulmonologist in children who had a negative CFNBS and an ST for respiratory symptoms in 2012. We included 502 children with 523 STs, performed with four different methods. The main indication was asthma (71.3 %), then chronic cough (52.4 %), atypical lower airway infections (42.2 %), and bronchiectasis (7 %). Four children had a diagnosis of CF (0.8 %), all presenting with chronic productive cough and recurrent respiratory infections. Asthma is the most frequent indication of ST in our cohort. Because of the systematic CFNBS in France, some prescriptions should be avoided, particularly in case of severe or moderate asthma with no other associated symptom. Moreover, methods of STs often do not follow the guidelines and need standardization. • Newborn screening (NBS) has become the most frequent circumstance of the diagnosis of cystic fibrosis (CF) in France after its generalization. • The prescription of sweat test (ST) in children with respiratory symptoms who already had a negative NBS has not been studied. • In children with a negative CF NBS referred to a university hospital for respiratory diseases, despite important variations of ST methods, only 4 children among 502 have been diagnosed as CF. • Despite recommendations, ST prescription should be avoided in children with moderate to severe asthma and no other associated symptom.

Dietary patterns and asthma prevalence, incidence and control.

PubMed

Barros, R; Moreira, A; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Lopes, C; Severo, M; Moreira, P

2015-11-01

The increased asthma prevalence in westernized societies has been suggested to be related to environment exposures and lifestyle changes, particularly diet. We aimed to explore the association between dietary patterns and asthma prevalence, incidence and control in a nationally representative population. Data from 32,644 adults, 53% female, from the 4th Portuguese National Health Survey were analysed. Prevalence of asthma was 5.3%; 'current asthma', defined by asthma symptoms within previous year, 3.5%; 'current medicated asthma' defined by use of asthma medication within previous year, 3.0%; 'current severe asthma' defined by emergency visit because of asthma within previous year, 1.4%; and 'incident asthma', 0.2%. Dietary patterns (DP) were identified by latent trait models based on dietary intake. Unconditional logistic regression models were performed to analyse association between DP and asthma. Age, gender, education, family income, proxy reporting information, smoking, body mass index and physical activity level were analysed as confounders. Two of the five identified DP were associated with asthma: 'high fat, sugar and salt' DP (positively correlated with pastry, chocolate and sweet desserts, candies, salty snacks, chips, fruit juices, soft drinks and alcoholic beverages consumption at snacks) was associated with asthma prevalence (OR = 1.13, 95% CI = 1.03, 1.24) and current severe asthma (OR = 1.23, 95% CI = 1.03, 1.48), while 'fish, fruit and vegetables' DP (positively correlated with fish, vegetables and fruit intake at meals) was negatively associated with current (OR = 0.84, 95% CI = 0.73, 0.98), and current medicated asthma (OR = 0.84, 95% CI = 0.72, 0.98), after adjustment for confounders. Our results suggest a protective association between 'fish, vegetables and fruit' DP and current asthma and current medicated asthma, and a detrimental association between 'high fat, sugar and salt' DP and severe asthma prevalence, further supporting the rational for diet and lifestyle intervention studies in asthma based on whole dietary patterns and physical activity. © 2015 John Wiley & Sons Ltd.

The effect of obesity, weight gain, and weight loss on asthma inception and control.

PubMed

Forno, Erick; Celedón, Juan C

2017-04-01

There is ample and growing evidence that obesity increases the risk of asthma and morbidity from asthma. Here, we review recent clinical evidence supporting a causal link between obesity and asthma, and the mechanisms that may lead to 'obese asthma'. Although in some children obesity and asthma simply co-occur, those with 'obese asthma' have increased asthma severity, lower quality of life, and reduced medication response. Underlying mechanistic pathways may include anatomical changes of the airways such as obstruction and dysanapsis, systemic inflammation, production of adipokines, impaired glucose-insulin metabolism, altered nutrient levels, genetic and epigenetic changes, and alterations in the airway and/or gut microbiome. A few small studies have shown that weight loss interventions may lead to improvements in asthma outcomes, but thus far research on therapeutic interventions for these children has been limited. Obesity increases the risk of asthma - and worsens asthma severity or control - via multiple mechanisms. 'Obese asthma' is a complex, multifactorial phenotype in children. Obesity and its complications must be managed as part of the treatment of asthma in obese children.

Association between sensitization to Aureobasidium pullulans (Pullularia sp) and severity of asthma.

PubMed

Niedoszytko, Marek; Chełmińska, Marta; Jassem, Ewa; Czestochowska, Eugenia

2007-02-01

Recent data indicate that fungi may contribute to increased severity of asthma. To determine the prevalence of allergy to 15 mold allergens among patients hospitalized because of exacerbation of asthma and to evaluate the relationship between the severity of the disease and allergy to particular molds. Skin prick tests with standard aeroallergens of airborne allergens, including grass, tree, Dermatophagoides pteronyssinus, Dermatophagoides farinae, feather, and cat and dog fur, and a panel of mold allergens, including Alternaria, Cladosporium, Aspergillus, Penicillium, Trichothecium, Chaetomium globosum, Epicoccum, Epidermophyton, Helminthosporium, Aureobasidium pullulans, Rhizopus nigricans, Fusarium, Mucor, Merulius lacrymans, and yeast mix, were performed in 105 asthmatic patients and 30 controls. Positive skin prick test results were found in 98% of asthmatic patients and 66% of controls. Sensitivity to A pullulans was significantly associated with more severe asthma (odds ratio, 1.4; 95% confidence interval, 1.09-1.75; P = .006). Sensitization to Helminthosporium was associated with an increased number of asthma exacerbations that required hospitalization (17% vs 38%; chi2 test P = .03). Sensitization to A pullulans is a risk factor for severe asthma. Sensitization to Helminthosporium may be related to asthma exacerbation that requires hospitalization.

Advances in asthma in 2016: Designing individualized approaches to management.

PubMed

Anderson, William C; Apter, Andrea J; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2017-09-01

In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone.

PubMed

Stempel, David A; Raphiou, Ibrahim H; Kral, Kenneth M; Yeakey, Anne M; Emmett, Amanda H; Prazma, Charlene M; Buaron, Kathleen S; Pascoe, Steven J

2016-05-12

The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.).

Cluster Analysis Identifies 3 Phenotypes within Allergic Asthma.

PubMed

Sendín-Hernández, María Paz; Ávila-Zarza, Carmelo; Sanz, Catalina; García-Sánchez, Asunción; Marcos-Vadillo, Elena; Muñoz-Bellido, Francisco J; Laffond, Elena; Domingo, Christian; Isidoro-García, María; Dávila, Ignacio

Asthma is a heterogeneous chronic disease with different clinical expressions and responses to treatment. In recent years, several unbiased approaches based on clinical, physiological, and molecular features have described several phenotypes of asthma. Some phenotypes are allergic, but little is known about whether these phenotypes can be further subdivided. We aimed to phenotype patients with allergic asthma using an unbiased approach based on multivariate classification techniques (unsupervised hierarchical cluster analysis). From a total of 54 variables of 225 patients with well-characterized allergic asthma diagnosed following American Thoracic Society (ATS) recommendation, positive skin prick test to aeroallergens, and concordant symptoms, we finally selected 19 variables by multiple correspondence analyses. Then a cluster analysis was performed. Three groups were identified. Cluster 1 was constituted by patients with intermittent or mild persistent asthma, without family antecedents of atopy, asthma, or rhinitis. This group showed the lowest total IgE levels. Cluster 2 was constituted by patients with mild asthma with a family history of atopy, asthma, or rhinitis. Total IgE levels were intermediate. Cluster 3 included patients with moderate or severe persistent asthma that needed treatment with corticosteroids and long-acting β-agonists. This group showed the highest total IgE levels. We identified 3 phenotypes of allergic asthma in our population. Furthermore, we described 2 phenotypes of mild atopic asthma mainly differentiated by a family history of allergy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Influence of β(2)-adrenergic receptor polymorphisms on asthma exacerbation in children with severe asthma regularly receiving salmeterol.

PubMed

Giubergia, Verónica; Gravina, Luis; Castaños, Claudio; Chertkoff, Lilien

2013-03-01

New evidence suggests that different β(2)-adrenergic receptor (β2AR) polymorphisms may influence asthma control in patients receiving long-acting β(2)agonists (LABAs) as regular therapy. To determine the influence of β2AR polymorphisms on asthma exacerbations in children with severe asthma from Argentina receiving inhaled corticosteroid (ICS) and LABAs regularly. Ninety-seven children with severe asthma were genotyped for polymorphisms of β2AR at codons 16 and 27. The number of severe exacerbations, the time of first asthma exacerbation, and the number of hospitalizations during 12 months were assessed. Changes on pulmonary function from the beginning to the end of the study were also evaluated. The number of overall asthma exacerbations and the proportion of children with these events were similar among β2AR genotypes at position 16 (Arg/Arg, Arg/Gly, and Gly/Gly) and at position 27 (Gln/Gln, Gln/Glu, and Glu/Glu). The time to first asthma exacerbation was similar among individuals carrying different β2AR polymorphisms. No β2AR genotype association was found in relation to the number of hospitalizations. Longitudinal analysis of forced expiratory volume in 1 second from baseline to the end of the study also showed no differences among β2AR genotypes at position 16 or 27. No association was observed among the 3 most common haplotypes (Arg/Arg-Gln/Gln, Gly/Gly-Gln/Gln, and Gly/Gly-Glu/Glu) and the number of participants with asthmatic crisis or with the overall number of exacerbations. β2AR polymorphisms were not associated with an increased risk of having asthma exacerbations or lung function decline in a population of Argentinian children with severe asthma receiving ICS and LABAs regularly. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Prevalence of Asthma in Children of Chemical Warfare Victims

PubMed Central

Mirsadraee, Majid; Mozaffari, Abolfazl; Attaran, Davood

2011-01-01

Objective Exposure of DNA to sulfur mustard gas may increase the inheritance of asthma in chemical warfare victims' (CWV) offspring. The objective of this study was to determine the prevalence of asthma in children of CWV and compare it to asthmatic children in the general population. Methods Four hundred and nine children from 130 CWV fathers and 440 children from 145 asthmatic parents from two cities in Iran participated in this study. The prevalence of asthma was determined by standard questionnaire released for epidemiological survey of asthma in children and compared between two groups. Findings The prevalence of asthma in the CWV group was 15%; this was not significantly different from the control group (12.5%). The children of the CWV group reported a significantly greater incidence of wheezing (1.2±3.1 attacks) per year, but the control group reported more severe attacks leading to speech difficulties (3%) and coughing (7%). Regression analysis showed that with increasing family size in the control group, the number of subjects suffering from asthmatic symptoms decreases significantly (r=0.86, P=0.001). Conclusion Chemical agents may increase the prevalence of asthma in the offspring of CWV. PMID:23056804

Enhancing Asthma Self-Management in Rural School-Aged Children: A Randomized Controlled Trial.

PubMed

Horner, Sharon D; Brown, Adama; Brown, Sharon A; Rew, D Lynn

2016-06-01

To test the effects of 2 modes of delivering an asthma educational intervention on health outcomes and asthma self-management in school-aged children who live in rural areas. Longitudinal design with data collected 4 times over 12 months. The target sample was composed of children in grades 2-5 who had a provider diagnosis of asthma. Elementary schools were stratified into high or low socioeconomic status based on student enrollment in the free or reduced-cost lunch program. Schools were then randomly assigned to 1 of 3 treatment arms: in-school asthma class, asthma day camp, or the attention-control group. Sample retention was good (87.7%) and equally distributed by study arm. Improvements in emergency department visits and office visits were related to attending either the asthma class or asthma day camp. Asthma severity significantly decreased in both asthma treatment groups. Other factors such as hospitalizations, parent asthma management, and child asthma management improved for all groups. Both asthma class and asthma day camp yielded significant reductions in asthma severity. There were reductions in the emergency department and office visits for the 2 asthma arms, and hospitalizations declined significantly for all groups. Asthma self-management also improved in all groups, while it was somewhat higher in the asthma arms. This may be due to the attention being drawn to asthma management by study participation and the action of completing questionnaires about asthma management, asthma symptoms, and health outcomes. © 2015 National Rural Health Association.

Depression, Asthma, and Bronchodilator Response in a Nationwide Study of US Adults.

PubMed

Han, Yueh-Ying; Forno, Erick; Marsland, Anna L; Miller, Gregory E; Celedón, Juan C

2016-01-01

Little is known about the relation between 2 common comorbidities (depression and anxiety) and asthma or bronchodilator response (BDR). To examine the association between depressive symptoms and asthma or BDR in US adults. Cross-sectional study of 20,272 adults aged 20 to 79 years from the 2007-2012 National Health and Nutrition Examination Survey. Depressive symptoms were measured using the 9-item Patient Health Questionnaire, and classified as none to minimal, mild, moderate, moderately severe, and severe. Major depression (comprising moderately severe to severe symptoms) was defined as a 9-item Patient Health Questionnaire score of 15 or more. Anxiety was defined as 5 or more days feeling anxious in the previous month. Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and 1 or more asthma attack in the previous year. BDR (as percentage of baseline FEV1) was measured in 1356 participants with FEV1/forced vital capacity of less than 0.70 and/or FEV1 less than 70% of predicted. Logistic or linear regression was used for the multivariable analysis. Depressive symptoms were significantly and linearly associated with asthma, independently of anxiety symptoms. Subjects with major depression had 3.4 times higher odds of asthma than did those with minimal or no depressive symptoms (95% CI, 2.6-4.5; P < .01). Among adults with asthma, major depression was associated with a 4.2% reduction in BDR (95% CI, -7.5% to -0.8%; P = .02). Major depression was not associated with BDR among adults without asthma. Anxiety was not associated with asthma or BDR. Depressive symptoms are associated with asthma in adults, independently of anxiety symptoms. Major depression is associated with reduced BDR in adults with asthma. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Asthma and Adolescents: Review of Strategies to Improve Control

ERIC Educational Resources Information Center

Hennessy-Harstad, Ellen

2013-01-01

One of every 10 adolescents in the United States has asthma. Adolescents who lack asthma control are at increased risk for severe asthma episodes and death. The National Heart, Lung, and Blood Institute 2007 asthma guidelines and research studies indicated that school nurses are instrumental in assisting adolescents to monitor their asthma, learn…

Association Between Severe Vitamin D Deficiency, Lung Function and Asthma Control.

PubMed

Beyhan-Sagmen, Seda; Baykan, Ozgur; Balcan, Baran; Ceyhan, Berrin

2017-04-01

To examine the relationship between severe vitamin D deficiency, asthma control, and pulmonary function in Turkish adults with asthma. One hundred six asthmatic patients underwent pulmonary function tests skin prick test, peripheral blood eosinophil counts, IgE, body mass index and vitamin D levels were determined. Patients were divided into 2 subgroups according to vitamin D levels (vitamin D level<10ng/ml and vitamin D level≥10 ng/ml). Asthma control tests were performed. The mean age of subgroup i (vitamin D level<10) was 37±10 and the mean age of subgroup ii (vitamin D level≥10ng/ml) was 34±8. Sixty-six percent of patients had severe vitamin D deficiency (vitamin D level<10 ng/ml). There was a significant trend towards lower absolute FEV 1 (L) values in patients with lower vitamin D levels (P=.001). Asthma control test scores were significantly low in the severe deficiency group than the other group (P=.02). There were a greater number of patients with uncontrolled asthma (asthma control test scores<20) in the severe vitamin D deficiency group (P=.040). Patients with severe vitamin D deficiency had a higher usage of inhaled corticosteroids than the group without severe vitamin D deficiency (P=.015). There was a significant trend towards lower absolute FEV 1 (L) (P=.005, r=.272) values in patients with lower vitamin D levels. Vitamin D levels were inversely related with body mass index (P=.046). The incidence of severe vitamin D deficiency was high in adult Turkish asthmatics. In addition, lower vitamin D levels were associated with poor asthma control and decreased pulmonary function. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

[Consensus-based approach for severe paediatric asthma in routine clinical practice].

PubMed

Plaza, A M; Ibáñez, M D P; Sánchez-Solís, M; Bosque-García, M; Cabero, M J; Corzo, J L; García-Hernández, G; de la Hoz, B; Korta-Murua, J; Sánchez-Salguero, C; Torres-Borrego, J; Tortajada-Girbés, M; Valverde-Molina, J; Zapatero, L; Nieto, A

2016-02-01

Accurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. An online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. Eleven paediatric chest disease physicians and allergy specialists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they have required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impairs their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. This paper provides consensus recommendations that may be useful in the management of severe paediatric asthma. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Role for NLRP3 Inflammasome-mediated, IL-1β-Dependent Responses in Severe, Steroid-Resistant Asthma.

PubMed

Kim, Richard Y; Pinkerton, James W; Essilfie, Ama T; Robertson, Avril A B; Baines, Katherine J; Brown, Alexandra C; Mayall, Jemma R; Ali, M Khadem; Starkey, Malcolm R; Hansbro, Nicole G; Hirota, Jeremy A; Wood, Lisa G; Simpson, Jodie L; Knight, Darryl A; Wark, Peter A; Gibson, Peter G; O'Neill, Luke A J; Cooper, Matthew A; Horvat, Jay C; Hansbro, Philip M

2017-08-01

Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1β responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma. To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1β in severe, steroid-resistant asthma. We developed mouse models of Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1β responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1β responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1β antibody. Roles for IL-1β-induced neutrophilic inflammation were examined using IL-1β and anti-Ly6G. Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1β responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1β expression. Treatment with anti-IL-1β, Ac-YVAD-cho, and MCC950 suppressed IL-1β responses and the important steroid-resistant features of disease in mice, whereas IL-1β administration recapitulated these features. Neutrophil depletion suppressed IL-1β-induced steroid-resistant airway hyperresponsiveness. NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.

Factors associated with severe disease in a population of asthmatic children of Bogota, Colombia.

PubMed

Rodriguez Martinez, Carlos; Sossa, Monica; Goss, Christopher H

2008-03-01

There is evidence that prevalence and severity of asthma in children has risen. Risk factors for severe asthma have been studied extensively in children living in developed countries, but little is known about factors determining the severity of asthma in Latin American countries. The aim of this study was to investigate the role of suspected, potential risk factors for asthma severity in a population of children living in urban Bogota. We studied 175 children, 2 to 16 years old, with asthma attending an asthma clinic. Severe cases and nonsevere asthmatic subjects were compared regarding suspected, potential pre-, peri-, and postnatal risk factors. After controlling for asthma duration, we found that children never breast fed (OR, 11.53; 95% CI, 2.35-56.50; p = 0.003), mothers 30 years or younger at the child's birth (OR, 3.44; 95% CI, 1.23-9.63; p = 0.019), usual use of acetaminophen for fever in the child in the 12 months previous to the survey application (OR, 3.13; 95% CI, 1.14-8.56; p = 0.026), older siblings at birth (OR, 3.81; 95% CI, 1.28-11.32; p = 0.016), and primary or secondary school as the highest level of education attained by mother (OR, 3.20; 95% CI, 1.01-10.07; p = 0.046) were all independent predictors of severe asthma. No breastfeeding, maternal age at child's birth of less than 30 years, routine use of acetaminophen for fever in the child in the 12 months previous to the survey application, older siblings at birth, and primary or secondary school as the highest level of education attained by mother were independent predictors of severe asthma. Some of these risk factors are clearly modifiable. Further prospective, population-based studies with a bigger sample size and a more representative sample of the general population residing in the city are needed to retest and clarify these associations.

Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma.

PubMed

Naik, Srilata Puru; P A, Mahesh; B S, Jayaraj; Madhunapantula, SubbaRao V; Jahromi, Sarah Raeiszadeh; Yadav, Manish Kumar

2017-08-01

Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p < 0.001), moderate versus severe persistent asthma (p < 0.001). A significant negative correlation was observed between MMP-9 and pre-bronchodilator FEV 1 and FVC, but not with IL-6. There was no association between IL-6 and MMP-9 with asthma duration, total IgE, AEC, number of allergens sensitized and degree of sensitization. No significant correlation (p > 0.5) was observed with IL-6 and MMP-9 levels and FEV 1 improvement after 2 months of ICS+LABA. Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions.

Weekly monitoring of children with asthma for infections and illness during common cold seasons.

PubMed

Olenec, Jaime P; Kim, Woo Kyung; Lee, Wai-Ming; Vang, Fue; Pappas, Tressa E; Salazar, Lisa E P; Evans, Michael D; Bork, Jack; Roberg, Kathleen; Lemanske, Robert F; Gern, James E

2010-05-01

Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity. We sought to evaluate rhinovirus infections during peak seasons in children with asthma and to analyze relationships between viral infection and illness severity. Fifty-eight children aged 6 to 8 years with asthma provided 5 consecutive weekly nasal lavage samples during September and April; symptoms, medication use, and peak flow were recorded. Rhinoviruses were identified by using multiplex PCR and partial sequencing of viral genomes. Viruses were detected in 36% to 50% of the specimens, and 72% to 99% of the viruses were rhinoviruses. There were 52 different strains (including 16 human rhinovirus C) among the 169 rhinovirus isolates; no strains were found in more than 2 collection periods, and all but 2 children had a respiratory tract infection. Virus-positive weeks were associated with greater cold and asthma symptom severity (P < .0001 and P = .0002, respectively). Furthermore, virus-positive illnesses had increased duration and severity of cold and asthma symptoms and more frequent loss of asthma control (47% vs 22%, P = .008). Although allergen-sensitized versus nonsensitized children had the same number of viral infections, the former had 47% more symptomatic viral illnesses (1.19 vs 0.81 per month, P = .03). Rhinovirus infections are nearly universal in children with asthma during common cold seasons, likely because of a plethora of new strains appearing each season. Illnesses associated with viruses have greater duration and severity. Finally, atopic asthmatic children experienced more frequent and severe virus-induced illnesses. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

The role of the indoor environment: Residential determinants of allergy, asthma and pulmonary function in children from a US-Mexico border community.

PubMed

Svendsen, Erik R; Gonzales, Melissa; Commodore, Adwoa

2018-03-01

The El Paso Children's Health Study examined environmental risk factors for allergy and asthma among fourth and fifth grade schoolchildren living in a major United States-Mexico border city. Complete questionnaire information was available for 5210 children, while adequate pulmonary function data were available for a subset of 1874. Herein we studied indoor environmental health risk factors for allergy and asthma. Several indoor environmental risk factors were associated with allergy and asthma. In particular, we found that ant and spider pest problems, pet dogs, fireplace heat, central air conditioning, humidifier use, and cooking with gas stoves were positively associated with both allergy and asthma prevalence. With regards to asthma severity, our analysis indicated that exposure to pet dogs increased monotonically with increasing asthma severity while the lack of any heat source and gas stove use for cooking decreased monotonically with increasing asthma severity. Lung function also decreased among children who lived in homes with reported cockroach pest problem in the past year without concurrent use of pesticides. These effects on pulmonary function were present even after excluding children with a current physician's diagnosis of asthma. Clinicians and public health professionals may need to look closely at the contribution of these indoor risk factors on pulmonary health and quality of life among susceptible populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeted anti-IL-13 therapies in asthma: current data and future perspectives.

PubMed

Ntontsi, Polyxeni; Papathanassiou, Evgenia; Loukides, Stelios; Bakakos, Petros; Hillas, Georgios

2018-02-01

The identification of patients with severe asthma who will benefit from a personalized management approach remains an unmet need. Interleukin-13 (IL-13) is a cytokine possessing a significant role in asthma pathogenesis and progression of disease. Humanised monoclonal antibodies against IL-13 and IL-13 and IL-4 receptors are mainly proposed as add-on therapy in patients with T H 2-high inflammation with uncontrolled asthma despite maximum therapy. Areas covered: The role of IL-13 in airway inflammation in severe asthma, the targeted anti-IL-13 therapies and biomarkers that predict response to anti-IL-13 treatment are discussed. Expert opinion: New effective individualized therapies in severe asthma are urgently needed to block specific inflammatory pathways using monoclonal antibodies. Studies on anti-IL-13 therapies showed that asthmatic patients could benefit from this novel targeted therapy as far as lung function and exacerbation rate are concerned. T H 2-high and especially periostin-high groups of asthmatics with moderate-to-severe uncontrolled asthma seem to compose the group that could benefit from anti-IL-13 therapy. Targeting IL-13 alone may not be sufficient to achieve asthma control. Inhibition of IL-13 and IL-4 with mabs may be more encouraging and patients will probably have additional benefits from these therapeutic interventions because of IL-13/IL-4 overlapping actions in asthma pathophysiology.

Home and allergic characteristics of children with asthma in seven U.S. urban communities and design of an environmental intervention: the Inner-City Asthma Study.

PubMed Central

Crain, Ellen F; Walter, Michelle; O'Connor, George T; Mitchell, Herman; Gruchalla, Rebecca S; Kattan, Meyer; Malindzak, George S; Enright, Paul; Evans, Richard; Morgan, Wayne; Stout, James W

2002-01-01

Most published environmental remediation interventions have been directed at single allergens and have employed demanding strategies; few have been performed in the homes of inner-city children disproportionately burdened by asthma. Our objective was a) to describe the allergen sensitivities, environmental tobacco smoke (ETS) exposure, and home environmental characteristics of a national sample of inner-city children with moderate to severe asthma and b) to develop and implement a multifaceted, home-based comprehensive intervention to reduce home allergens and ETS, tailored to the specific sensitization and exposure profiles of those children. Allergen skin testing and a home evaluation were performed to determine the presence of ETS and factors known to be associated with increased indoor allergen levels. Based on published remediation techniques, a home environmental intervention, organized into modules, each addressing one of five specific allergen groups or ETS, was designed. Of 994 allergic children from seven U.S. urban communities, 937 successfully completed baseline interviews and home allergen surveys and were enrolled. More than 50% of children had positive skin tests to three or more allergen groups. Cockroaches were reported in 58% of homes, wall-to-wall carpeting in the child's bedroom in 55%, a smoker in 48%, mice or rats in 40%, and furry pets in 28%. More than 60% of enrolled families received four or more modules, and between 94% and 98% of all modules were completed. We conclude that most inner-city children with moderate to severe asthma are sensitized to multiple indoor allergens and that environmental factors known to be associated with asthma severity are commonly present in their homes. The intervention developed for the Inner-City Asthma Study employs accepted methods to address an array of allergens and ETS exposure while ensuring that the intervention is tailored to the specific sensitization profiles and home characteristics of these children. PMID:12204830

Towards Excellence in Asthma Management: Final report of an eight-year program aimed at reducing care gaps in asthma management in Quebec

PubMed Central

Boulet, Louis-Philippe; Dorval, Eileen; Labrecque, Manon; Turgeon, Michel; Montague, Terrence; Thivierge, Robert L

2008-01-01

BACKGROUND AND OBJECTIVES: Asthma care in Canada and around the world persistently falls short of optimal treatment. To optimize care, a systematic approach to identifying such shortfalls or ‘care gaps’, in which all stakeholders of the health care system (including patients) are involved, was proposed. METHODS: Several projects of a multipartner, multidisciplinary disease management program, developed to optimize asthma care in Quebec, was conducted in a period of eight years. First, two population maps were produced to identify regional variations in asthma-related morbidity and to prioritize interventions for improving treatment. Second, current care was evaluated in a physician-patient cohort, confirming the many care gaps in asthma management. Third, two series of peer-reviewed outcome studies, targeting high-risk populations and specific asthma care gaps, were conducted. Finally, a process to integrate the best interventions into the health care system and an agenda for further research on optimal asthma management were proposed. RESULTS: Key observations from these studies included the identification of specific patterns of noncompliance in using inhaled corticosteroids, the failure of increased access to spirometry in asthma education centres to increase the number of education referrals, the transient improvement in educational abilities of nurses involved with an asthma hotline telephone service, and the beneficial effects of practice tools aimed at facilitating the assessment of asthma control and treatment needs by general practitioners. CONCLUSIONS: Disease management programs such as Towards Excellence in Asthma Management can provide valuable information on optimal strategies for improving treatment of asthma and other chronic diseases by identifying care gaps, improving guidelines implementation and optimizing care. PMID:18818784

Relationship between maternal asthma, its severity and control and abortion.

PubMed

Blais, Lucie; Kettani, Fatima-Zohra; Forget, Amélie

2013-04-01

Are women with asthma, and more specifically those with severe or uncontrolled asthma, at higher risk of spontaneous and induced abortions? Pregnant women with asthma, notably when uncontrolled, are at higher risk of spontaneous abortion. Only one study has examined the association between asthma and spontaneous and induced abortions and revealed a modest increase in the risk of spontaneous abortions, particularly in women with more severe asthma and those with previous exacerbations, and a marginal decrease in the risk of induced abortions. A cohort of pregnancies from asthmatic (n = 15,107) and non-asthmatic (n = 34,331) women was reconstructed by linking three administrative databases from Quebec (Canada), between 1992 and 2002. The cohort included 7870 spontaneous abortions, 14,596 induced abortions and 26,972 live births. Pregnant women with and without asthma were analyzed. Asthma was defined by at least one asthma diagnosis and one dispensed prescription for an asthma medication in the 2 years prior to or during pregnancy. Asthma severity and control were assessed using validated indexes in the year before the 20th week of pregnancy or the termination of the pregnancy. Logistic polytomous regression models were used to estimate the relationship between asthma and asthma severity and control on the risk of abortion, while adjusting for potential confounders. The prevalence of spontaneous and induced abortions was 15.9 and 29.5%, respectively. Maternal asthma was associated with an increased risk of a spontaneous abortion [odds ratio (OR) = 1.41; 95% confidence interval (CI): 1.33-1.49] and a decreased risk of induced abortions (OR = 0.92; 0.88-0.97). No association was observed between asthma severity and abortion, while uncontrolled asthma increased the risk of a spontaneous abortion by 26% (95% CI: 14-41%) and the risk of induced abortions by 11% (95% CI: 1-21%). It is possible that the study results were confounded by imbalances between groups in variables that are not recorded in the databases, but that are known to be associated with spontaneous abortions, such as alcohol consumption, obesity or maternal smoking. However, we performed sensitivity analyses which revealed that these factors are unlikely to explain the observed increased risk for a spontaneous abortion. It is also possible that women with asthma are more likely to have abortions recorded in the databases, because subjects with a chronic disease tend to visit a physician more often than those without asthma. Therefore, our odds estimates for these outcomes may be overestimated when asthmatic women were compared with non-asthmatic women. A further limitation of the study is that it would have been more appropriate to measure the severity and control of asthma only during the pregnancy. Our cohort is less representative of women in the upper socio-economic level. This is not a threat to internal validity, but it could limit the external validity if the impact of asthma on the risk of abortion differed according to the socio-economic status of the mother. Despite the absence of supporting data, this possibility cannot be completely excluded. This study was funded by the Canadian Institutes of Health Research and Genentech. L.B. received research grants from Astra-Zeneca, Pfizer, sanofi-aventis, Novartis and Merck for research projects and co-chairs the Astra-Zeneca Endowment Pharmaceutical Chair in Respiratory Health. F.Z.K and A.F. have no competing interests to declare.

Japanese Guideline for Adult Asthma 2014.

PubMed

Ohta, Ken; Ichinose, Masakazu; Nagase, Hiroyuki; Yamaguchi, Masao; Sugiura, Hisatoshi; Tohda, Yuji; Yamauchi, Kohei; Adachi, Mitsuru; Akiyama, Kazuo

2014-09-01

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting β2-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled β2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and cough-variant asthma are also important issues that need to be considered.

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.

The association between paracetamol use and asthma: causation or coincidence?

PubMed

Weatherall, M; Ioannides, S; Braithwaite, I; Beasley, R

2015-01-01

A better understanding of the causation of asthma and allergic disorders could potentially lead to intervention strategies that reduce their prevalence and severity. One potential causative factor is the use of paracetamol. Most of the evidence for the link with asthma is from non-experimental studies of paracetamol exposure in utero, infancy, childhood and adult life; however, it has been difficult to rule out confounding and bias in the associations observed. The two randomized clinical trials of the effect of paracetamol in patients with asthma have been difficult to interpret, due to methodological issues. There have been no randomized controlled trials of paracetamol use and the development of asthma. Both asthma and paracetamol use are common, and so even if there is a relatively small effect of paracetamol exposure on the development of asthma or its severity, then such an effect would be of major public health significance. It is proposed that randomized controlled trials of the effect of paracetamol on the development of asthma and its severity are a high research priority. © 2014 John Wiley & Sons Ltd.

P2X7-Regulated Protection from Exacerbations and Loss of Control Is Independent of Asthma Maintenance Therapy

PubMed Central

Manthei, David M.; Seibold, Max A.; Ahn, Kwangmi; Bleecker, Eugene; Boushey, Homer A.; Calhoun, William J.; Castro, Mario; Chinchili, Vernon M.; Fahy, John V.; Hawkins, Greg A.; Icitovic, Nicolina; Israel, Elliot; Jarjour, Nizar N.; King, Tonya; Kraft, Monica; Lazarus, Stephen C.; Lehman, Erik; Martin, Richard J.; Meyers, Deborah A.; Peters, Stephen P.; Sheerar, Dagna; Shi, Lei; Sutherland, E. Rand; Szefler, Stanley J.; Wechsler, Michael E.; Sorkness, Christine A.; Lemanske, Robert F.

2013-01-01

Rationale: The function of the P2X7 nucleotide receptor protects against exacerbation in people with mild-intermittent asthma during viral illnesses, but the impact of disease severity and maintenance therapy has not been studied. Objectives: To evaluate the association between P2X7, asthma exacerbations, and incomplete symptom control in a more diverse population. Methods: A matched P2RX7 genetic case-control was performed with samples from Asthma Clinical Research Network trial participants enrolled before July 2006, and P2X7 pore activity was determined in whole blood samples as an ancillary study to two trials completed subsequently. Measurements and Main Results: A total of 187 exacerbations were studied in 742 subjects, and the change in asthma symptom burden was studied in an additional 110 subjects during a trial of inhaled corticosteroids (ICS) dose optimization. African American carriers of the minor G allele of the rs2230911 loss-of-function single nucleotide polymorphism were more likely to have a history of prednisone use in the previous 12 months, with adjustment for ICS and long-acting β2-agonists use (odds ratio, 2.7; 95% confidence interval, 1.2–6.2; P = 0.018). Despite medium-dose ICS, attenuated pore function predicted earlier exacerbations in incompletely controlled patients with moderate asthma (hazard ratio, 3.2; confidence interval, 1.1–9.3; P = 0.033). After establishing control with low-dose ICS in patients with mild asthma, those with attenuated pore function had more asthma symptoms, rescue albuterol use, and FEV1 reversal (P < 0.001, 0.03, and 0.03, respectively) during the ICS adjustment phase. Conclusions: P2X7 pore function protects against exacerbations of asthma and loss of control, independent of baseline severity and the maintenance therapy. PMID:23144325

The discovery and development of omalizumab for the treatment of asthma.

PubMed

Licari, Amelia; Marseglia, GianLuigi; Castagnoli, Riccardo; Marseglia, Alessia; Ciprandi, Giorgio

2015-01-01

The evolution in immunological methods used to assess human allergic diseases has led to the identification of immunoglobulin E (IgE) as a diagnostic biomarker and a potential therapeutic target. Innovative technologies in molecular biology and immunogenetics contributed to the development of a selective blocking agent, disclosing new therapeutic perspectives in the treatment of allergic asthma. Omalizumab is the most advanced humanized anti-IgE monoclonal antibody that specifically binds serum-free IgE. Omalizumab also interrupts the allergic cascade by preventing binding of IgE with FcεRI receptors on mast cells, basophils, antigen-presenting cells and other inflammatory cells. This review discusses the discovery strategy and preclinical development of omalizumab. Furthermore, it also provides a clinical overview of the key trials leading to its launch and a detailed analysis of safety and post-marketing data. The clinical efficacy of omalizumab in allergic asthma has been well documented in clinical trials, involving adults, adolescents and children with moderate-to-severe and severe allergic asthma. To date, omalizumab has also been approved in chronic idiopathic urticaria for patients 12 years and older who remain symptomatic despite high dosages of H1 antihistamines. Omalizumab has also been investigated in many other different patient populations beyond allergic asthma and may yet have an application to other indications. While omalizumab is the only mAb available for treating allergic asthma, the authors anticipate that new mAbs will emerge in the future that overcome omalizumab's current limitations.

Surgical treatment of bronchial asthma by resection of the laryngeal nerve.

PubMed

Kurbon, Ubaidullo; Dodariyon, Hamza; Davlatov, Abdumalik; Janobilova, Sitora; Therwath, Amu; Mirshahi, Massoud

2015-10-08

Management of asthma in chronically affected patients is a serious health problem. Our aim was to show that surgical treatment of chronic bronchial asthma by unilateral resection of the internal branch of the superior laryngeal nerve (ib-SLN) is an adequateand lasting remedial response. In a retrospective study, 41 (26 male and 15 female) patients with bronchial chronic asthma were treated surgically during the period between 2005 and 2013. It consisted of a unilateral resection of the ib-SLN under optical zoom, on patients placed in supinator position. 35 patients (24 male and 11 female) who were un-operated were included as a control. In all patients, medication was reduced progressively. When the results were compared with the control group, it was seen that in 26% of the patients, both forced expiratory volume (FEV) and peak expiratory flow (PEF) increased significantly (p <05) and only modestly in 53.6% of patients (FEV, p <05 and PEF, p <05). In the remaining 20% of patients, these parameters remained however unchanged. Overall, in 80% of patients unilateral resection of the ib-SLN gave satisfactory results because it shortened the intervals and duration of asthmatic attacks, rendering thereby a reduction in medication. This minimal-invasive method helped prevent/cure asphyxias in chronic bronchial asthma without affecting cough reflex,respiratory control and phonation and it helped patients avoid severe crisis. This approach is of interest for patients with severe and/or uncontrolled bronchial asthma in settings with limited access to drug treatment.

A new model of wheezing severity in young children using the validated ISAAC wheezing module: A latent variable approach with validation in independent cohorts.

PubMed

Brunwasser, Steven M; Gebretsadik, Tebeb; Gold, Diane R; Turi, Kedir N; Stone, Cosby A; Datta, Soma; Gern, James E; Hartert, Tina V

2018-01-01

The International Study of Asthma and Allergies in Children (ISAAC) Wheezing Module is commonly used to characterize pediatric asthma in epidemiological studies, including nearly all airway cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) consortium. However, there is no consensus model for operationalizing wheezing severity with this instrument in explanatory research studies. Severity is typically measured using coarsely-defined categorical variables, reducing power and potentially underestimating etiological associations. More precise measurement approaches could improve testing of etiological theories of wheezing illness. We evaluated a continuous latent variable model of pediatric wheezing severity based on four ISAAC Wheezing Module items. Analyses included subgroups of children from three independent cohorts whose parents reported past wheezing: infants ages 0-2 in the INSPIRE birth cohort study (Cohort 1; n = 657), 6-7-year-old North American children from Phase One of the ISAAC study (Cohort 2; n = 2,765), and 5-6-year-old children in the EHAAS birth cohort study (Cohort 3; n = 102). Models were estimated using structural equation modeling. In all cohorts, covariance patterns implied by the latent variable model were consistent with the observed data, as indicated by non-significant χ2 goodness of fit tests (no evidence of model misspecification). Cohort 1 analyses showed that the latent factor structure was stable across time points and child sexes. In both cohorts 1 and 3, the latent wheezing severity variable was prospectively associated with wheeze-related clinical outcomes, including physician asthma diagnosis, acute corticosteroid use, and wheeze-related outpatient medical visits when adjusting for confounders. We developed an easily applicable continuous latent variable model of pediatric wheezing severity based on items from the well-validated ISAAC Wheezing Module. This model prospectively associates with asthma morbidity, as demonstrated in two ECHO birth cohort studies, and provides a more statistically powerful method of testing etiologic hypotheses of childhood wheezing illness and asthma.

Family functioning and child asthma severity: A bio-behavioral approach.

PubMed

Al Ghriwati, Nour; Winter, Marcia A; Everhart, Robin S; Fiese, Barbara H

2017-12-01

Family factors are directly associated with the psychosocial adjustment of children with chronic illnesses such as asthma (Kaugars, Klinnert, & Bender, 2004). Research indicates that negative family factors may also contribute to child disease severity via bio-behavioral mechanisms of effect. For instance, children from more conflicted families often experience greater internalizing symptoms that subsequently impact their asthma severity (Wood et al., 2006). These pathways have yet to be examined with a comprehensive focus on strength-based family factors. This study examined whether factors such as family cohesion, problem-solving abilities, and communication influence asthma severity via their effects on child depression and anxiety symptoms. Participants were 215 children (136 males and 79 females), ages 5 to 12 years old, and their families. Primary caregiver, child, and teacher ratings of child and family functioning in addition to objective measures of parent-child interactions and asthma severity were collected. Using structural equation modeling, the authors identified significant indirect associations between family factors and child asthma severity via child depressive symptoms; however, these associations were not present in models with child anxiety symptoms. Results suggest an indirect effect of family functioning on children's lung function, with differential roles of anxiety and depression in these pathways. This article also highlights the importance of incorporating multirater multimethod measures to understand children's experiences in pediatric asthma. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study.

PubMed

Morales, Daniel R; Lipworth, Brian J; Donnan, Peter T; Jackson, Cathy; Guthrie, Bruce

2017-01-27

Cardiovascular disease (CVD) is a common comorbidity in people with asthma. However, safety concerns have caused heterogeneity in clinical guideline recommendations over the use of cardioselective beta-blockers in people with asthma and CVD, partly because risk in the general population has been poorly quantified. The aim of this study was to measure the risk of asthma exacerbations with beta-blockers prescribed to a general population with asthma and CVD. Linked data from the UK Clinical Practice Research Datalink was used to perform nested case-control studies among people with asthma and CVD matched on age, sex and calendar time. Adjusted incidence rate ratios (IRR) were calculated for the association between oral beta-blocker use and moderate asthma exacerbations (rescue oral steroids) or severe asthma exacerbations (hospitalisation or death) using conditional logistic regression. The cohort consisted of 35,502 people identified with active asthma and CVD, of which 14.1% and 1.2% were prescribed cardioselective and non-selective beta-blockers, respectively, during follow-up. Cardioselective beta-blocker use was not associated with a significantly increased risk of moderate or severe asthma exacerbations. Consistent results were obtained following sensitivity analyses and a self-controlled case series approach. In contrast, non-selective beta-blockers were associated with a significantly increased risk of moderate asthma exacerbations when initiated at low to moderate doses (IRR 5.16, 95% CI 1.83-14.54, P = 0.002), and both moderate and severe exacerbations when prescribed chronically at high dose (IRR 2.68, 95% CI 1.08-6.64, P = 0.033 and IRR 12.11, 95% CI 1.02-144.11, P = 0.048, respectively). Cardioselective beta-blockers prescribed to people with asthma and CVD were not associated with a significantly increased risk of moderate or severe asthma exacerbations and potentially could be used more widely when strongly indicated.

Outcomes of childhood asthma to the age of 50 years.

PubMed

Tai, Andrew; Tran, Haily; Roberts, Mary; Clarke, Nadeene; Gibson, Anne-Marie; Vidmar, Suzanna; Wilson, John; Robertson, Colin F

2014-06-01

In 1964, The Melbourne Asthma Study was established to describe the spectrum and natural history of childhood asthma. To describe the clinical and lung function outcome of childhood asthma to the age of 50 years. Subjects were invited to complete an interviewer-administered questionnaire, skin prick testing, and measurement of lung function from the age of 7 years to the age of 50 years at 7-year intervals. Of 458 survivors (from the original 484 subjects at recruitment), 346 subjects (76%) participated, of whom, 197 completed lung function measurement. Asthma remission at the age of 50 years was 64% in those with wheezy bronchitis, 47% for those with persistent asthma, and 15% for those with severe asthma in childhood. Multivariable analysis identified severe asthma in childhood (odds ratio [OR] 11.9 [95% CI, 3.4-41.8]), female sex (OR 2.0 [95% CI, 1.1-3.6]), and childhood hay fever (OR 2.0 [95% CI, 1.0-4.0]) as risk factors for "current asthma" at age 50 years. There was no evidence of a difference in the rate of decline in FEV1 (mL/y, 95% CI) between the severe asthma group (15 mL/y [95% CI, 9-22 mL/y]) and all the other recruitment groups: control (16 mL/y [95% CI, 12-20 mL/y]), mild wheezy bronchitis (14 mL/y [95% CI, 8-19 mL/y]), wheezy bronchitis (16 mL/y [95% CI, 11-20 mL/y]), and persistent asthma (19 mL/y [95% CI, 13-24 mL/y]). The clinical and lung function outcome in adult life is strongly determined by asthma severity in childhood. The reduced lung function seen in adults is established in childhood and does not appear to decline more rapidly in adult years despite continuing symptoms. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Clinical and functional characteristics of patients two years after being affected by the soybean asthma epidemic in Barcelona.

PubMed Central

Sabrià, J.; Antó, J. M.; Sunyer, J.; Roca, J.; Morell, F.; Rodríguez-Roisín, R.; Rodrigo, M. J.; Codina, R.

1994-01-01

BACKGROUND--Patients affected during the asthma outbreaks caused by soybean dust inhalation in Barcelona presented with sudden onset of severe asthma followed by the rapid relief of symptoms after treatment. Two years after the epidemics ended, a case-control study was conducted in which the clinical, functional, and immunological characteristics of these asthma patients (a randomised sample of asthmatic patients admitted as emergency cases on epidemic days, n = 213) were compared with those of a control group (a random sample of asthmatic patients admitted as emergency cases for attacks of asthma on non-epidemic days, n = 170). METHODS--The study included the administration of the ATS-DLD78 standardised respiratory questionnaire, the measurement of atopy, and performance of spirometric tests and a methacholine inhalation test. RESULTS--Patients with epidemic asthma reported fewer symptoms of asthma, had attended emergency departments less frequently during the previous year for acute attacks of asthma, were taking fewer inhaled corticosteroids at the time of the study, and attended medical follow up less frequently than did the patients with non-epidemic asthma. However, the cases and controls showed no differences in ventilatory capacity or reactivity to the methacholine bronchoprovocation test. CONCLUSIONS--Two years after the end of the soybean epidemics, people affected by epidemic asthma had a favourable prognosis. This finding contrasts with a higher risk of life threatening asthma and death during the epidemics. This paradox could be the result of a complex interaction between host and conditions of exposure. Images PMID:7940432

Availability of Asthma Quick Relief Medication in Five Alabama School Systems

PubMed Central

Stroupe, Nancy; McClure, Leslie A.; Wheeler, Lani; Gerald, Lynn B.

2012-01-01

Objectives This paper documents individual asthma action plan presence and quick relief medication (albuterol) availability for elementary students enrolled in five Alabama school systems. Patients and Methods Data were obtained during baseline data collection (fall 2005) of a school-based supervised asthma medication trial. All students attended 1 of 36 participating elementary schools across five school systems in Jefferson County, Alabama. In addition, they had to have physician-diagnosed asthma requiring daily controller medication. Each school system had its own superintendent and elected school board. Asthma action plan presence and albuterol availability was confirmed by study personnel. Asthma action plans had to contain daily and acute asthma management instructions. Predictors of asthma action plan presence and albuterol availability were also investigated. Associations between albuterol availability and self-reported characteristics including health care utilization prior to study enrollment and outcomes during the study baseline period were also investigated. Results Enrolled students had a mean (SD) age of 11.0 (2.1) years, 91% were African American, and 79% had moderate persistent asthma. No student had a complete asthma action plan on file and only 14% had albuterol physically available at school. Albuterol availability was not predicted by gender, race, insurance status, second-hand smoke exposure, need for pre-exercise albuterol, asthma severity, or self-reported health care utilization prior to study enrollment. Albuterol availability did not predict school absences, red/yellow peak flow recordings, or medication adherence during the study's baseline period. Conclusion Despite policies permitting students to possess albuterol, few elementary students across five independent school systems in Alabama actually had it readily available at school. PMID:22454787

Intravenous ketamine in a dissociating dose as a temporizing measure to avoid mechanical ventilation in adult patient with severe asthma exacerbation.

PubMed

Shlamovitz, Gil Z; Hawthorne, Tracy

2011-11-01

Patients experiencing severe asthma exacerbations occasionally deteriorate to respiratory failure requiring endotracheal intubation and mechanical ventilation. Mechanical ventilation in this setting exposes the patients to substantial iatrogenic risk and should be avoided if at all possible. To describe the use of intravenous ketamine in acute asthma exacerbation. We present a case of severe asthma exacerbation in an adult female patient who failed to improve with standard therapies, but promptly improved with the administration of intravenous ketamine (0.75 mg/kg i.v. bolus followed by continuous drip of 0.15 mg/kg/h). This case suggests that intravenous ketamine given in a dissociative dose may be an effective temporizing measure to avoid mechanical ventilation in adult patients with severe asthma exacerbations. Copyright © 2011 Elsevier Inc. All rights reserved.

Rhinoviruses, Allergic Inflammation, and Asthma

PubMed Central

Gavala, Monica; Bertics, Paul J.; Gern, James E.

2011-01-01

Summary Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma. PMID:21682739

Obesity in children with poorly controlled asthma: Sex differences.

PubMed

Lang, Jason E; Holbrook, Janet T; Wise, Robert A; Dixon, Anne E; Teague, W Gerald; Wei, Christine Y; Irvin, Charles G; Shade, David; Lima, John J

2013-09-01

Obesity increases asthma risk, and may alter asthma severity. In adults, sex appears to modify the effect of obesity on asthma. Among children, the effect of sex on the relationship between obesity and asthma severity remains less clear, particularly when considering race. To determine how obesity affects disease characteristics in a diverse cohort of children with poorly controlled asthma, and if obesity effects are altered by sex. We analyzed 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month trial assessing lansoprazole for asthma control. In this secondary analysis, we determined associations between obesity and symptom severity, spirometry, exacerbation risk, airway biomarkers, bronchial reactivity, and airflow perception. We used both a multivariate linear regression and longitudinal mixed-effect model to determine if obesity interacted with sex to affect asthma severity. Regardless of sex, BMI >95th percentile did not affect asthma control, exacerbation risk or airway biomarkers. Sex changed the effect of obesity on lung function (sex × obesity FEV1%, interaction P-value < 0.01, sex × obesity FEV1/FVC, interaction P-value = 0.03). Obese males had significantly worse airflow obstruction compared to non-obese males, while in females there was no obesity effect on airflow obstruction. In females, obesity was associated with significantly greater FEV1 and FVC, and a trend toward reduced airway reactivity. Obesity did not affect asthma control, airway markers or disease stability; however obesity did affect lung function in a sex-dependent manner. In males, obesity associated with reduced FEV1/FVC, and in females, obesity associated with substantially improved lung function. Copyright © 2012 Wiley Periodicals, Inc.

Omalizumab improves asthma-related quality of life in patients with severe allergic asthma.

PubMed

Finn, Albert; Gross, Gary; van Bavel, Julius; Lee, Theodore; Windom, Hugh; Everhard, François; Fowler-Taylor, Angel; Liu, Jeen; Gupta, Niroo

2003-02-01

We have previously shown that omalizumab, a recombinant humanized monoclonal anti-IgE antibody, reduces asthma exacerbations and decreases inhaled corticosteroid (ICS) requirement in patients with severe allergic asthma who were symptomatic despite moderate-to-high doses of ICSs. The aim of the present study was to assess the effects of omalizumab on asthma-related quality of life (QOL). These analyses were part of a multicenter, 52-week, randomized, double-blind, placebo-controlled study assessing the efficacy, safety, and tolerability of subcutaneous omalizumab (> or =0.016 mg/kg of IgE [in international unit per milliliter] per 4 weeks) in 525 adults with severe allergic asthma. A 16-week steroid-stable phase was followed by a 12-week steroid-reduction phase and a 24-week double-blind extension phase. The effect of treatment on asthma-related QOL was evaluated by using the Asthma Quality of Life Questionnaire (AQLQ) administered at baseline and at weeks 16, 28, and 52. The 2 treatment groups were comparable in terms of baseline AQLQ scores. At weeks 16, 28, and 52, omalizumab-treated patients demonstrated statistically significant improvements across all AQLQ domains, as well as in overall score. Moreover, a greater proportion of patients receiving omalizumab achieved a clinically meaningful improvement in asthma-related QOL during each phase of the study. Greater than 50% of both patients and investigators rated treatment similarly with omalizumab as excellent or good compared with less than 40% of placebo recipients. In patients requiring moderate-to-high doses of ICSs for severe allergic asthma, the measurably improved disease control afforded by add-on omalizumab therapy is paralleled by clinically meaningful improvements in asthma-related QOL.

NOD2 expression, DNA damage and oxido-inflammatory status in atopic bronchial asthma: Exploring their nexus to disease severity.

PubMed

Gaballah, Hanaa H; Gaber, Rasha A; Sharshar, Ragia S; Elshweikh, Samah A

2018-06-20

Allergic asthma is a chronically relapsing inflammatory airway disease with a complex pathophysiology. This study was undertaken to investigate the potential contribution of NOD2 signaling, proinflammatory cytokines, chitotriosidase (CHIT1) activity, oxidative stress and DNA damage to atopic asthma pathogenesis, as well as to explore their possible role as surrogate noninvasive biomarkers for monitoring asthma severity. Sixty patients with atopic bronchial asthma who were divided according to asthma severity into 40 mild-moderate, 20 severe atopic asthmatics, in addition to thirty age-matched healthy controls were enrolled in this study. NOD2 expression in PBMCs was assessed by quantitative real-time RT-PCR. DNA damage indices were assessed by alkaline comet assay. Serum IgE, IL-17, IL-8 and 3-Nitrotyrosine levels were estimated by ELISA. Serum CHIT1and GST activities, as well as MDA levels, were measured. NOD2 mRNA relative expression levels were significantly decreased in atopic asthmatic cases relative to controls with lower values among severe atopic asthmatics. On the other hand, IL-17 and IL-8 serum levels, CHIT1 activity, DNA damage indices and oxidative stress markers were significantly increased in atopic asthmatic cases relative to controls with higher values among severe atopic asthmatics. The change in these parameters correlated significantly with the degree of decline in lung function. The interplay between NOD2 signaling, proinflammatory cytokines, CHIT1 activity, heightened oxidative stress and DNA damage orchestrates allergic airway inflammation and thus contributing to the pathogenesis of atopic asthma. These parameters qualified for measurement as part of new noninvasive biomarker panels for monitoring asthma severity. Copyright © 2018 Elsevier B.V. All rights reserved.

DNA methylation levels associated with race and childhood asthma severity.

PubMed

Chan, Marcia A; Ciaccio, Christina E; Gigliotti, Nicole M; Rezaiekhaligh, Mo; Siedlik, Jacob A; Kennedy, Kevin; Barnes, Charles S

2017-10-01

Asthma is a common chronic childhood disease worldwide. Socioeconomic status, genetic predisposition and environmental factors contribute to its incidence and severity. A disproportionate number of children with asthma are economically disadvantaged and live in substandard housing with potential indoor environmental exposures such as cockroaches, dust mites, rodents and molds. These exposures may manifest through epigenetic mechanisms that can lead to changes in relevant gene expression. We examined the association of global DNA methylation levels with socioeconomic status, asthma severity and race/ethnicity. We measured global DNA methylation in peripheral blood of children with asthma enrolled in the Kansas City Safe and Healthy Homes Program. Inclusion criteria included residing in the same home for a minimum of 4 days per week and total family income of less than 80% of the Kansas City median family income. DNA methylation levels were quantified by an immunoassay that assessed the percentage of 5-methylcytosine. Our results indicate that overall, African American children had higher levels of global DNA methylation than children of other races/ethnicities (p = 0.029). This difference was more pronounced when socioeconomic status and asthma severity were coupled with race/ethnicity (p = 0.042) where low-income, African American children with persistent asthma had significantly elevated methylation levels relative to other races/ethnicities in the same context (p = 0.006, Hedges g = 1.14). Our study demonstrates a significant interaction effect among global DNA methylation levels, asthma severity, race/ethnicity, and socioeconomic status.

Accuracy of a computerized clinical decision-support system for asthma assessment and management.

PubMed

Hoeksema, Laura J; Bazzy-Asaad, Alia; Lomotan, Edwin A; Edmonds, Diana E; Ramírez-Garnica, Gabriela; Shiffman, Richard N; Horwitz, Leora I

2011-05-01

To evaluate the accuracy of a computerized clinical decision-support system (CDSS) designed to support assessment and management of pediatric asthma in a subspecialty clinic. Cohort study of all asthma visits to pediatric pulmonology from January to December, 2009. CDSS and physician assessments of asthma severity, control, and treatment step. Both the clinician and the computerized CDSS generated assessments of asthma control in 767/1032 (74.3%) return patients, assessments of asthma severity in 100/167 (59.9%) new patients, and recommendations for treatment step in 66/167 (39.5%) new patients. Clinicians agreed with the CDSS in 543/767 (70.8%) of control assessments, 37/100 (37%) of severity assessments, and 19/66 (29%) of step recommendations. External review classified 72% of control disagreements (21% of all control assessments), 56% of severity disagreements (37% of all severity assessments), and 76% of step disagreements (54% of all step recommendations) as CDSS errors. The remaining disagreements resulted from pulmonologist error or ambiguous guidelines. Many CDSS flaws, such as attributing all 'cough' to asthma, were easily remediable. Pediatric pulmonologists failed to follow guidelines in 8% of return visits and 18% of new visits. The authors relied on chart notes to determine clinical reasoning. Physicians may have changed their assessments after seeing CDSS recommendations. A computerized CDSS performed relatively accurately compared to clinicians for assessment of asthma control but was inaccurate for treatment. Pediatric pulmonologists failed to follow guideline-based care in a small proportion of patients.

Relationship between recent short-acting β-agonist use and subsequent asthma exacerbations

PubMed Central

Paris, Jason; Peterson, Edward L.; Wells, Karen; Pladevall, Manel; Burchard, Esteban G.; Choudhry, Shweta; Lanfear, David E.; Williams, L. Keoki

2009-01-01

Background US national guidelines recommend assessing short-acting β-agonist (SABA) medication use as a marker of asthma severity and control. However, the relationship between recent SABA use and asthma exacerbations is not currently known. Objective To evaluate the proximal relationship between the type and frequency of SABA use and asthma-related outcomes. Methods We evaluated SABA use among patients with asthma ages 5 to 56 years who were members of a large health maintenance organization in southeast Michigan. Frequency of use was estimated from pharmacy data assessing the timing and amount of SABA fills. Cox proportional hazards models were used to examine the prospective relationship between average daily SABA use for 3 months and outcomes associated with poor asthma control (ie, oral corticosteroids use, asthma-related emergency department visits, and asthma-related hospitalizations). We separately accounted for SABA metered-dose inhaler (MDI) and SABA nebulizer use. Results Of the 2,056 patients who met study criteria, 1,569 (76.3%) had used a SABA medication in their baseline year. After adjusting for potential confounders, SABA nebulizer use was associated with asthma-related emergency department visits (adjusted hazard ratio [aHR], 6.32; 95% confidence interval [CI], 2.38 to 16.80) and asthma-related hospitalizations (aHR, 21.62; 95% CI, 3.17 to 147.57). In contrast, frequency of SABA MDI use was not associated with these outcomes. Conclusions Frequency of SABA use during a 3-month period was associated with poor asthma outcomes. The relationship with poor asthma outcomes was strongest for SABA nebulizer use, suggesting that the type of SABA used is also of prognostic importance. PMID:19055201

Association Between Antibiotic Exposure, Bronchiolitis, and TLR4 (rs1927911) Polymorphisms in Childhood Asthma

PubMed Central

Lee, Eun; Kwon, Ji-Won; Kim, Hyo-Bin; Yu, Ho-Sung; Kang, Mi-Jin; Hong, Kyungmo; Yang, Song I; Jung, Young Ho; Lee, Seung-Hwa; Choi, Kil Young; Shin, Hye Lim; Hong, Seo Ah; Kim, Hyung Young; Seo, Ju-Hee; Kim, Byoung-Ju; Lee, So Yeon; Song, Dae Jin; Kim, Woo-Kyung; Jang, Gwang Cheon; Shim, Jung Yeon

2015-01-01

Purpose The complex interplay between environmental and genetic factors plays an important role in the development of asthma. Several studies have yielded conflicting results regarding the 2 asthma-related risk factors: antibiotic usage during infancy and/or a history of bronchiolitis during early life and the development of asthma. In addition to these risk factors, we also explored the effects of Toll-like receptor 4 (TLR4) polymorphism on the development of childhood asthma. Methods This cross-sectional study involved 7,389 middle school students who were from 8 areas of Seoul, Korea, and completed the International Study of Asthma and Allergies in Childhood questionnaire. The TLR4 polymorphism rs1927911 was genotyped in 1,395 middle school students from two areas using the TaqMan assay. Results Bronchiolitis in the first 2 years of life, antibiotic exposure during the first year of life, and parental history of asthma were independent risk factors for the development of asthma. When combined, antibiotic use and a history of bronchiolitis increased the risk of asthma (adjusted odds ratio [aOR]: 4.64, 95% confidence interval [CI]: 3.09-6.97, P value for interaction=0.02). In subjects with CC genotype of TLR4, antibiotic exposure and a history of bronchiolitis during infancy, the risk of asthma was increased, compared to subjects without these risk factors (aOR: 5.72, 95% CI: 1.74-18.87). Conclusions Early-life antibiotic exposures and a history of bronchiolitis are risk factors for asthma in young adolescents. Polymorphisms of TLR4 modified the influence of these environmental factors. Reducing antibiotic exposure and preventing bronchiolitis during infancy may prevent the development of asthma, especially in genetically susceptible subjects. PMID:25729624

A Multifactorial Weight Reduction Programme for Children with Overweight and Asthma: A Randomized Controlled Trial

PubMed Central

Willeboordse, Maartje; van de Kant, Kim D. G.; Tan, Frans E. S.; Mulkens, Sandra; Schellings, Julia; Crijns, Yvonne; van der Ploeg, Liesbeth; van Schayck, Constant P.; Dompeling, Edward

2016-01-01

Background There is increasing evidence that obesity is related to asthma development and severity. However, it is largely unknown whether weight reduction can influence asthma management, especially in children. Objective To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with (a high risk of developing) asthma. Methods An 18-month weight-reduction randomized controlled trial was conducted in 87 children with overweight/obesity and asthma. Every six months, measurements of anthropometry, lung function, lifestyle parameters and inflammatory markers were assessed. Analyses were performed with linear mixed models for longitudinal analyses. Results After 18 months, the body mass index-standard deviation score decreased by -0.14±0.29 points (p<0.01) in the intervention group and -0.12±0.34 points (p<0.01) in the control group. This change over time did not differ between groups (p>0.05). Asthma features (including asthma control and asthma-related quality of life) and lung function indices (static and dynamic) improved significantly over time in both groups. The FVC% predicted improved over time by 10.1 ± 8.7% in the intervention group (p<0.001), which was significantly greater than the 6.1 ± 8.4% in the control group (p<0.05). Conclusions & clinical relevance Clinically relevant improvements in body weight, lung function and asthma features were found in both the intervention and control group, although some effects were more pronounced in the intervention group (FVC, asthma control, and quality of life). This implies that a weight reduction intervention could be clinically beneficial for children with asthma. Trial Registration ClinicalTrials.gov NCT00998413 PMID:27294869

Role of Obesity in Asthma: Mechanisms and Management Strategies.

PubMed

Scott, Hayley A; Wood, Lisa G; Gibson, Peter G

2017-08-01

Obesity is a commonly reported comorbidity in asthma, particularly in severe asthma. Obese asthmatics are highly symptomatic with a poor quality of life, despite using high-dose inhaled corticosteroids. While the clinical manifestations have been documented, the aetiologies of obese-asthma remain unclear. Several potential mechanisms have been proposed, including poor diet quality, physical inactivity and consequent accrual of excess adipose tissue. Each of these factors independently activates inflammatory pathways, potentially exerting effects in the airways. Because the origins of obesity are multifactorial, it is now believed there are multiple obese-asthma phenotypes, with varied aetiologies and clinical consequences. In this review, we will describe the clinical implications of obesity in people with asthma, our current understanding of the mechanisms driving this association and describe recently proposed obese-asthma phenotypes. We will then discuss how asthma management is complicated by obesity, and provide graded recommendations for the management of obesity in this population.

Comparing high altitude treatment with current best care in Dutch children with moderate to severe atopic dermatitis (and asthma): study protocol for a pragmatic randomized controlled trial (DAVOS trial)

PubMed Central

2014-01-01

Background About 10 to 20% of children in West European countries have atopic dermatitis (AD), often as part of the atopic syndrome. The full atopic syndrome also consists of allergic asthma, allergic rhinitis and food allergy. Treatment approaches for atopic dermatitis and asthma include intermittent anti-inflammatory therapy with corticosteroids, health education and self-management training. However, symptoms persist in a subgroup of patients. Several observational studies have shown significant improvement in clinical symptoms in children and adults with atopic dermatitis or asthma after treatment at high altitude, but evidence on the efficacy when compared to treatment at sea level is still lacking. Methods/Design This study is a pragmatic randomized controlled trial for children with moderate to severe AD within the atopic syndrome. Patients are eligible for enrolment in the study if they are: diagnosed with moderate to severe AD within the atopic syndrome, aged between 8 and 18 years, fluent in the Dutch language, have internet access at home, able to use the digital patient system Digital Eczema Center Utrecht (DECU), willing and able to stay in Davos for a six week treatment period. All data are collected at the Wilhelmina Children’s Hospital and DECU. Patients are randomized over two groups. The first group receives multidisciplinary inpatient treatment during six weeks at the Dutch Asthma Center in Davos, Switzerland. The second group receives multidisciplinary treatment during six weeks at the outpatient clinic of the Wilhelmina Children’s Hospital, Utrecht, the Netherlands. The trial is not conducted as a blind trial. The trial is designed with three components: psychosocial, clinical and translational. Primary outcomes are coping with itch, quality of life and disease activity. Secondary outcomes include asthma control, medication use, parental quality of life, social and emotional wellbeing of the child and translational parameters. Discussion The results of this trial will provide evidence for the efficacy of high altitude treatment compared to treatment at sea level for children with moderate to severe AD. Trial Registration Current Controlled Trials ISRCTN88136485. PMID:24670079

A Patient Advocate to facilitate access and improve communication, care, and outcomes in adults with moderate or severe asthma: Rationale, design, and methods of a randomized controlled trial

PubMed Central

Apter, Andrea J.; Morales, Knashawn H.; Han, Xiaoyan; Perez, Luzmercy; Huang, Jingru; Ndicu, Grace; Localio, Anna; Nardi, Alyssa; Klusaritz, Heather; Rogers, Marisa; Phillips, Alexis; Cidav, Zuleyha; Schwartz, J. Sanford

2017-01-01

Few interventions to improve asthma outcomes have targeted low-income minority adults. Even fewer have focused on the real-world practice where care is delivered. We adapted a patient navigator, here called a Patient Advocate (PA), a term preferred by patients, to facilitate and maintain access to chronic care for adults with moderate or severe asthma and prevalent co-morbidities recruited from clinics serving low-income urban neighborhoods. We describe the planning, design, methodology (informed by patient and provider focus groups), baseline results, and challenges of an ongoing randomized controlled trial of 312 adults of a PA intervention implemented in a variety of practices. The PA coaches, models, and assists participants with preparations for a visit with the asthma clinician; attends the visit with permission of participant and provider; and confirms participants’ understanding of what transpired at the visit. The PA facilitates scheduling, obtaining insurance coverage, overcoming patients’ unique social and administrative barriers to carrying out medical advice and transfer of information between providers and patients. PA activities are individualized, take account of comorbidities, and are generalizable to other chronic diseases. PAs are recent college graduates interested in health-related careers, research experience, working with patients, and generally have the same race/ethnicity distribution as potential participants. We test whether the PA intervention, compared to usual care, is associated with improved and sustained asthma control and other asthma outcomes (prednisone bursts, ED visits, hospitalizations, quality of life, FEV1) relative to baseline. Mediators and moderators of the PA-asthma outcome relationship are examined along with the intervention’s cost-effectiveness. PMID:28315481

Factors associated with quality of life in patients with severe asthma: the impact of pharmacotherapy

PubMed Central

Souza, Daiane Silva; Noblat, Lúcia de Araújo Costa Beisl; Santos, Pablo de Moura

2015-01-01

ABSTRACT OBJECTIVE: To identify, characterize, and quantify associations of various factors with quality of life (QoL) in patients with asthma, according to the pharmacotherapy employed. METHODS: This was a cross-sectional study involving 49 patients (≥ 18 years of age) with severe uncontrolled or refractory asthma treated at a specialized outpatient clinic of the Brazilian Unified Health Care System, regularly using high doses of inhaled corticosteroids (ICs) or other medications, and presenting comorbidities. At a single time point, QoL was assessed with the Asthma Quality of Life Questionnaire (AQLQ). The overall AQLQ score and those of its domains were correlated with demographic variables (gender and age); Asthma Control Questionnaire score; pharmacotherapy (initial IC dose, inhaler devices, and polytherapy); and comorbidities. RESULTS: Better AQLQ scores were associated with asthma control-overall (OR = 0.38; 95% CI: 0.004-0.341; p < 0.001), "symptoms" domain (OR = 0.086; 95% CI: 0.016-0.476; p = 0.001), and "emotional function" domain (OR = 0.086; 95% CI: 0.016-0.476; p = 0.001)-and with IC dose ≤ 800 µg-"activity limitation" domain (OR = 0.249; 95% CI: 0.070-0.885; p = 0.029). Worse AQLQ scores were associated with polytherapy-"activity limitation" domain (OR = 3.651; 95% CI: 1.061-12.561; p = 0.036)-and number of comorbidities ≤ 5-"environmental stimuli" domain (OR = 5.042; 95% CI: 1.316-19.317; p = 0.015). CONCLUSIONS: Our results, the importance of this issue, and the lack of studies taking pharmacotherapy into consideration warrant longitudinal studies to establish a causal relationship between the identified factors and QoL in asthma patients. PMID:26785957

Japanese Guideline for Adult Asthma 2014.

PubMed

Ohta, Ken; Ichinose, Masakazu; Nagase, Hiroyuki; Yamaguchi, Masao; Sugiura, Hisatoshi; Tohda, Yuji; Yamauchi, Kohei; Adachi, Mitsuru; Akiyama, Kazuo

2014-01-01

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting 02-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled 02-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and coughvariant asthma are also important issues that need to be considered. © 2014 Japanese Society of Allergology.

Targeting patients with asthma for omalizumab therapy: choosing the right patient to get the best value for money

PubMed Central

Al Said, Abir; Cushen, Breda; Costello, Richard W

2017-01-01

The asthma syndrome has many manifestations, termed phenotypes, that arise by specific cellular and molecular mechanisms, termed endotypes. Understanding an individual’s asthma phenotype helps clinicians make rational therapeutic decisions while the understanding of endotypes has led to the development of specific precision medications. Allergic asthma is an example of an asthma phenotype and omalizumab, a monoclonal antibody that neutralizes serum immunoglobulin (Ig)E, is a specific targeted treatment which was developed as a result of an understanding of the endotype of allergic asthma. Omalizumab has been widely used in clinical practice in Europe for over a decade as an add-on therapy to treat patients who have severe refractory allergic asthma. Over this period, many centres have reported their experience with omalizumab as an add-on therapy in patients with severe asthma. These ‘real world’ clinical effectiveness studies have confirmed the benefits, cost-effectiveness and clinical utility of this medication. Combining the outcomes of both sources of research has yielded important insights that may benefit patients with severe asthma, clinicians who treat them, as well as the funding agencies that reimburse the cost of this medication. The purpose of this review is to describe how to identify and evaluate a patient with asthma for whom treatment with omalizumab may be of clinical and cost-effective benefit. The assessment and investigations used to confirm allergic asthma, the objective assessment of adherence to asthma therapy and the expected benefits of add-on omalizumab treatment are described. PMID:28348726

Incentive spirometry combined with expiratory positive airway pressure improves asthma control and quality of life in asthma: a randomised controlled trial.

PubMed

Rondinel, Tatiana Zacarias; Corrêa, Isadora Faraco; Hoscheidt, Luíza Machado; Bueno, Mirelle Hugo; Da Silva, Luciano Muller Corrêa; Reppold, Caroline Tozzi; Dal Lago, Pedro

2015-03-01

The use of the incentive spirometer (IS) and expiratory positive airway pressure (EPAP) provides several benefits in patients with respiratory disorders. However, the effects of the use of these devices coupled (IS + EPAP) are still unknown in asthmatic patients. The aim of this study was to evaluate the effect of IS associated with EPAP on exercise tolerance (six-minute walk test - 6MWT), lung function (by spirometry), asthma control (Asthma Control Questionnaire - ACQ) and quality of life (Asthma Quality of Life Questionnaire - AQLQ) in patients with severe asthma. Patients were randomised into two groups: IS + EPAP (n = 8) and control (n = 6). The IS + EPAP group performed breathing exercises at home, twice daily for 20 min, over a period of 5 weeks. There was no significant difference in spirometric variables and in the distance walked in the 6MWT in both groups. However, the IS + EPAP group showed an improvement in asthma control (p = 0.002) and quality of life (p = 0.02). These findings demonstrate that the IS + EPAP protocol, when performed at home, provides an improvement in asthma control and quality of life for patients with severe asthma when evaluated by ACQ and AQLQ, respectively.

Fevipiprant in the treatment of asthma.

PubMed

White, Christobelle; Wright, Adam; Brightling, Christopher

2018-02-01

Asthma is common and in many, particularly those with more severe disease, there remains a substantial unmet need. Success with biologics targeting eosinophilic inflammation underscore the value of treating inflammation in asthma beyond corticosteroids. Fevipiprant (QAW039) is an oral treatment for asthma. It competitively and reversibly antagonises the prostaglandin D2 receptor 2 (DP2) expressed on inflammatory and structural cells. Areas covered: We reviewed fevipiprant's mode of action and efficacy against other current and emerging pharmacological interventions for moderate-to-severe asthma. We undertook a literature review using the PubMed/Medline database, the U.S. National Library of Medicine's Clinical Trials website and from manufacturers' press releases with the search terms: 'QAW039', 'Fevipiprant', 'CRTH2 antagonists', 'DP2', 'DP1', 'monoclonal antibody', 'eosinophil' with 'asthma' plus the names of individual drugs. Three Phase 2 trials have been conducted and three Phase 3 trials (NCT02563067, NCT03052517, NCT02555683) are in progress. To date Fevipiprant's greatest success has been in targeting severe eosinophilic asthma. Expert opinion: Fevipiprant presents the possibility of a new orally active therapy for asthma. If successful in phase 3 trials it will have an enormous impact on the treatment paradigm for asthma and will potentially widen access for pre-biologic treatment to a larger population.

The Asthma Mobile Health Study, a large-scale clinical observational study using ResearchKit.

PubMed

Chan, Yu-Feng Yvonne; Wang, Pei; Rogers, Linda; Tignor, Nicole; Zweig, Micol; Hershman, Steven G; Genes, Nicholas; Scott, Erick R; Krock, Eric; Badgeley, Marcus; Edgar, Ron; Violante, Samantha; Wright, Rosalind; Powell, Charles A; Dudley, Joel T; Schadt, Eric E

2017-04-01

The feasibility of using mobile health applications to conduct observational clinical studies requires rigorous validation. Here, we report initial findings from the Asthma Mobile Health Study, a research study, including recruitment, consent, and enrollment, conducted entirely remotely by smartphone. We achieved secure bidirectional data flow between investigators and 7,593 participants from across the United States, including many with severe asthma. Our platform enabled prospective collection of longitudinal, multidimensional data (e.g., surveys, devices, geolocation, and air quality) in a subset of users over the 6-month study period. Consistent trending and correlation of interrelated variables support the quality of data obtained via this method. We detected increased reporting of asthma symptoms in regions affected by heat, pollen, and wildfires. Potential challenges with this technology include selection bias, low retention rates, reporting bias, and data security. These issues require attention to realize the full potential of mobile platforms in research and patient care.

Screening for obstructive sleep apnea syndrome in asthma patients: a prospective study based on Berlin and STOP-Bang questionnaires.

PubMed

Lu, Huan; Fu, Cuiping; Li, Wenjing; Jiang, Hong; Wu, Xiaodan; Li, Shanqun

2017-07-01

The bidirectional relationship of asthma and obstructive sleep apnea (OSA) has been confirmed in recent years. However, in the clinical practice, majority of asthma patients did not pay adequate attention to their sleep apnea condition. Berlin questionnaire (BQ) and STOP-Bang questionnaire (SBQ) are two most common OSA screening questionnaires to screen high-risk patients for OSA. This study aimed at evaluating the predictive performance of BQ and SBQ for OSA in asthma patients. Asthma outpatients of Zhongshan Hospital were enrolled into the study. All patients were asked to fill in the BQ and SBQ and clinical characteristics and asthma characteristics were recorded. Univariate and multivariate logistic regression analyses were applied to identify risk factors of OSA in asthma patients. With the gold standard of laboratory-based overnight polysomnography (PSG), the predictive performance of SBQ and BQ was evaluated and compared. The probability of OSA severity was predicted by various SBQ scores in asthma patients. A total of 123 asthma patients (average age 47.56±12.12 years; 57.72% males) were enrolled and underwent PSG diagnosis overnight at Sleep Center. Logistic regression analyses showed that rhinitis (adjusted OR =4.30; 95% CI: 1.50-12.37, P=0.007) and dyslipidemia (adjusted OR =2.75; 95% CI: 1.16-6.51, P=0.021) were associated with OSA in asthma patients after adjusting for known OSA risk factors. No asthma functional characteristic differences were found to be associated with OSA severity in the study. The prevalence of moderate-to-severe OSA (AHI ≥15) in the asthmatic population sample was 36.59% (45/123). Questionnaires predictive results showed that compared with BQ, SBQ has higher diagnostic sensitivity (84.4% vs. 60%), lower specificity (79.5% vs. 91%) lower positive predictive value (PPV): (70.4% vs. 79.4%) and higher negative predictive value (NPV) (90% vs. 80%) to detect moderate-to-severe OSA at the cut-off as AHI of 15/h. OSA probability results showed that with the increasing of the questionnaire scores, the moderate and severe OSA probability of SBQ rose significantly. SBQ is a preferable sleep questionnaire better than BQ for detecting moderate and severe OSA in asthma patients which should be validated in larger population sample.

The burden of unscheduled health care for asthma in Latin America.

PubMed

Neffen, H; Gonzalez, S N; Fritscher, C C; Dovali, C; Williams, A E

2010-01-01

To determine the level and cost of unscheduled health care resource use in adults and children across all asthma symptom severities in Latin America. The level and cost of health care resource use were analysed for 2074 patients with asthma included in the Asthma Insights and Reality in Latin America (AIRLA) survey from 10 Latin American countries. Health care resource use was multiplied by country-specific unit costs to estimate average per-patient annual costs. Patients were classified as adults (> or = 16 years) or children (<16 years), with disease severity categorized using a symptom severity index. Persistent asthma symptoms were experienced by 53.1% of patients (50.1% of children and 54.6% of adults). In the year preceding the survey, 57.1% of patients required unscheduled health care resource use and 45.1% reported at least 1 emergency hospital contact. The percentage of patients reporting unscheduled health care resource use was greatest amongst those with severe persistent symptoms (71.9%) but it was also high in those with mild intermittent symptoms (45.7%). An average of 73.2% of annual costs of asthma-related health care for the 10 countries was due to unscheduled health care. Expenditure on unscheduled care was greatest amongst both adults and children with severe persistent asthma symptoms (US $558 and US $769, respectively). Adults and children with mild intermittent symptoms also incurred considerable unscheduled costs (US $204 and US $215, respectively). Poorly controlled asthma imposes a considerable cost burden driven by unscheduled health care resource use in Latin America. Treatments to control asthma and reduce the need for unscheduled health care could reduce this cost in both adults and children.

Healthy Homes: In-Home Environmental Asthma Intervention in a Diverse Urban Community

PubMed Central

Turcotte, David A.; Alker, Heather; Chaves, Emily; Gore, Rebecca; Woskie, Susan

2014-01-01

Objectives. We evaluated health outcomes associated with in-home interventions in low-income urban households with children with asthma. Methods. A comprehensive health and environmental assessment and subsequent intervention were completed in 116 households with 170 enrolled children with asthma. Home health workers provided household safety, asthma prevention education, and targeted environmental intervention to decrease asthma triggers and improve household safety. We collected environmental data with questionnaire and dust samples and health information with a questionnaire incorporating the American Academy of Pediatrics Children’s Health Survey for Asthma and other instruments at baseline and at follow-up 11 to 12 months later to evaluate the impact of the intervention on the health of the child and family in Lowell, Massachusetts, from September 2009 to January 2012. Results. The diverse study population of low-income children showed a statistically significant health improvement from baseline to follow-up. The cost of the interventions (not including personnel) was $36 240, whereas the estimated medical savings over a 4-week assessment period was $71 162, resulting in an estimated annual savings of about $821 304. Conclusions. Low-cost, multicomponent interventions decrease all measures of asthma severity and health care utilization in a diverse population of urban children. PMID:24524511

The C-C motif chemokine ligands CCL5, CCL11, and CCL24 induce the migration of circulating fibrocytes from patients with severe asthma.

PubMed

Isgrò, M; Bianchetti, L; Marini, M A; Bellini, A; Schmidt, M; Mattoli, S

2013-07-01

The C-C motif chemokine ligand 5 (CCL5), CCL11, and CCL24 are involved in the pathogenesis of asthma, and their function is mainly associated with the airway recruitment of eosinophils. This study tested their ability to induce the migration of circulating fibrocytes, which may contribute to the development of irreversible airflow obstruction in severe asthma. The sputum fluid phase (SFP) from patients with severe/treatment-refractory asthma (PwSA) contained elevated concentrations of CCL5, CCL11, and CCL24 in comparison with the SFP from patients with non-severe/treatment-responsive asthma (PwNSA). The circulating fibrocytes from PwSA expressed the receptors for these chemokines at increased levels and migrated in response to recombinant CCL5, CCL11, and CCL24. The SFP from PwSA induced the migration of autologous fibrocytes, and its activity was significantly attenuated by neutralization of endogenous CCL5, CCL11, and CCL24. These findings suggest that CCL5, CCL11, and CCL24 may contribute to the airway recruitment of fibrocytes in severe asthma.

Momentary Assessment of Psychosocial Stressors, Context, and Asthma Symptoms in Hispanic Adolescents

PubMed Central

Dunton, Genevieve Fridlund; Dzubur, Eldin; Li, Marilyn; Huh, Jimi; McConnell, Rob; Intille, Stephen

2017-01-01

Objective The current study used a novel real-time data capture strategy, Ecological Momentary Assessment (EMA), to examine whether within-day variability in stress and context leads to exacerbations in asthma symptomatology in the everyday lives of ethnic minority adolescents. Methods Low-income, Hispanic adolescents (N = 20) (7th–12th grade) (54% male) with chronic asthma completed seven days of EMA on smartphones, with an average of five assessments per day during non-school time. EMA surveys queried about where (e.g., home, outdoors) and with whom (e.g., alone, with friends) participants were at the time of the prompt. EMA surveys also assessed over the past few hours whether participants had experienced specific stressors (e.g., being teased, arguing with anyone), asthma symptoms (e.g., wheezing, coughing), or used an asthma inhaler. Multilevel models tested the independent relations of specific stressors, and context to subsequent asthma symptoms adjusting for age, gender, and chronological day in the study. Results Being outdoors and experiencing disagreements with parents, teasing, or arguing were associated with more severe self-reported asthma symptoms in the next few hours (p’s < .05). Being alone and having too much to do were unrelated to the experience of subsequent self-reported asthma symptoms. Conclusions Using a novel real-time data capture strategy, results provide preliminary evidence that being outdoors and experiencing social stressors may induce asthma symptoms in low-income Hispanic children and adolescents with chronic asthma. The results of this preliminary study can serve as the basis for larger epidemiological and intervention studies. PMID:26438664

Racial Disparities in Asthma Morbidity Among Pediatric Patients Seeking Asthma Specialist Care.

PubMed

Mitchell, Stephanie J; Bilderback, Andrew L; Okelo, Sande O

2016-01-01

To elucidate whether there may be a higher morbidity threshold for African American versus white children to be referred to or seek asthma specialist care. Secondary analysis of registry data captured from children presenting for an initial routine outpatient asthma consultation. Parents completed standard survey instruments, and spirometry was conducted when deemed appropriate by the provider. Wilcoxon rank sum tests revealed that African American patients had been hospitalized twice as often and admitted to the intensive care unit or intubated significantly more than 1½ times more frequently than their white patient counterparts. t tests indicated African American patients' forced expiratory volume in 1 second (FEV1) percentage predicted was significantly worse than that of whites, but there was no significant difference for FEV1/forced vital capacity ratio. t tests suggested that African American patients had statistically worse asthma control than did white patients at the time of initial presentation to the pulmonologist, but there was no difference in the distribution of asthma severity categories. Multivariate regression models indicated that racial differences in parent education did not explain the disparities in asthma morbidity. African American patients had significantly worse asthma morbidity than their white counterparts, including higher rates of hospitalization and intensive care unit admission and poorer lung functioning. Given that receipt of asthma specialist care can improve those outcomes that are disparately experienced by African American children, methods of increasing their access to and use of asthma specialist care need to be developed. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

METHODS FOR CLUSTERING TIME SERIES DATA ACQUIRED FROM MOBILE HEALTH APPS.

PubMed

Tignor, Nicole; Wang, Pei; Genes, Nicholas; Rogers, Linda; Hershman, Steven G; Scott, Erick R; Zweig, Micol; Yvonne Chan, Yu-Feng; Schadt, Eric E

2017-01-01

In our recent Asthma Mobile Health Study (AMHS), thousands of asthma patients across the country contributed medical data through the iPhone Asthma Health App on a daily basis for an extended period of time. The collected data included daily self-reported asthma symptoms, symptom triggers, and real time geographic location information. The AMHS is just one of many studies occurring in the context of now many thousands of mobile health apps aimed at improving wellness and better managing chronic disease conditions, leveraging the passive and active collection of data from mobile, handheld smart devices. The ability to identify patient groups or patterns of symptoms that might predict adverse outcomes such as asthma exacerbations or hospitalizations from these types of large, prospectively collected data sets, would be of significant general interest. However, conventional clustering methods cannot be applied to these types of longitudinally collected data, especially survey data actively collected from app users, given heterogeneous patterns of missing values due to: 1) varying survey response rates among different users, 2) varying survey response rates over time of each user, and 3) non-overlapping periods of enrollment among different users. To handle such complicated missing data structure, we proposed a probability imputation model to infer missing data. We also employed a consensus clustering strategy in tandem with the multiple imputation procedure. Through simulation studies under a range of scenarios reflecting real data conditions, we identified favorable performance of the proposed method over other strategies that impute the missing value through low-rank matrix completion. When applying the proposed new method to study asthma triggers and symptoms collected as part of the AMHS, we identified several patient groups with distinct phenotype patterns. Further validation of the methods described in this paper might be used to identify clinically important patterns in large data sets with complicated missing data structure, improving the ability to use such data sets to identify at-risk populations for potential intervention.

Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.

PubMed

Green, Benjamin J; Wiriyachaiporn, Surasa; Grainge, Christopher; Rogers, Geraint B; Kehagia, Valia; Lau, Laurie; Carroll, Mary P; Bruce, Kenneth D; Howarth, Peter H

2014-01-01

Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches. We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers. Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis. In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count. Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that responds less well to current asthma therapies.

Temporal Asthma Patterns Using Repeated Questionnaires over 13 Years in a Large French Cohort of Women

PubMed Central

Sanchez, Margaux; Bousquet, Jean; Le Moual, Nicole; Jacquemin, Bénédicte; Clavel-Chapelon, Françoise; Humbert, Marc; Kauffmann, Francine; Tubert-Bitter, Pascale; Varraso, Raphaëlle

2013-01-01

Variable expression is one aspect of the heterogeneity of asthma. We aimed to define a variable pattern, which is relevant in general health epidemiological cohorts. Our objectives were to assess whether: 1) asthma patterns defined using simple asthma questions through repeated measurements could reflect disease variability 2) these patterns may further be classified according to asthma severity/control. Among 70,428 French women, we used seven questionnaires (1992–2005) and a comprehensive reimbursement database (2004–2009) to define three reliable asthma patterns based on repeated positive answers to the ever asthma attack question: “never asthma” (n = 64,061); “inconsistent” (“yes” followed by “no”, n = 3,514); “consistent” (fully consistent positive answers, n = 2,853). The “Inconsistent” pattern was related to both long-term (childhood-onset asthma with remission in adulthood) and short-term (reported asthma attack in the last 12 months, associated with asthma medication) asthma variability, showing that repeated questions are relevant markers of the variable expression of asthma. Furthermore, in this pattern, the number of positive responses (1992–2005) predicted asthma drug consumption in subsequent years, a marker of disease severity. The “Inconsistent” pattern is a phenotype that may capture the variable expression of asthma. Repeated answers, even to a simple question, are too often neglected. PMID:23741466

More than a decade follow-up in patients with severe or difficult-to-treat asthma: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) II.

PubMed

Chipps, Bradley E; Haselkorn, Tmirah; Paknis, Brandee; Ortiz, Benjamin; Bleecker, Eugene R; Kianifard, Farid; Foreman, Aimee J; Szefler, Stanley J; Zeiger, Robert S

2018-05-01

The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR I) study demonstrated high morbidity in patients with severe or difficult-to-treat asthma despite standard-of-care treatment. We sought to determine the long-term natural history of disease and outcomes in patients in TENOR I after more than a decade. TENOR I was a multicenter observational study (2001-2004) of 4756 patients with severe or difficult-to-treat asthma. TENOR II was a follow-up study of TENOR I patients using a single cross-sectional visit in 2013/2014. Overall, the sites participating in TENOR II originally enrolled 1230 patients in TENOR I. Clinical and patient-reported outcomes were assessed, including very poorly controlled asthma based on National Heart, Lung, and Blood Institute guidelines. A total of 341 (27.7%) patients were enrolled in TENOR II and were representative of the TENOR I cohort. The most frequent comorbidities were rhinitis (84.0%), sinusitis (47.8%), and gastroesophageal reflux disease (46.3%). Mean percent predicted prebronchodilator and postbronchodilator FEV 1 were 72.7% (SD, 21.4%) and 78.2% (SD, 20.7%), respectively. A total of 231 (72.9%) of 317 patients had positive test responses to 1 or more allergen-specific IgEs. The mean blood eosinophil count was 200/μL (SD, 144/μL). Eighty-eight (25.8%) patients experienced an asthma exacerbation in the prior 3 months requiring hospital attention, oral corticosteroids, or both. More than half (197/339 [58.1%]) had very poorly controlled asthma. Medication use suggested undertreatment. TENOR II provides longitudinal data to characterize disease progression, heterogeneity, and severity in patients with severe or difficult-to-treat asthma. Findings show continued morbidity, including a high degree of comorbid conditions, allergic sensitization, exacerbations, and very poorly controlled asthma, including reduced lung function. Copyright © 2017. Published by Elsevier Inc.

Biologic Therapy and Asthma.

PubMed

Viswanathan, Ravi K; Busse, William W

2018-02-01

Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetic associations with viral respiratory illnesses and asthma control in children

PubMed Central

Loisel, Dagan A; Du, Gaixin; Ahluwalia, Tarunveer Singh; Tisler, Christopher J.; Evans, Michael D.; Myers, Rachel A.; Gangnon, Ronald E.; Kreiner-Møller, Eskil; Bønnelykke, Klaus; Bisgaard, Hans; Jackson, Daniel J.; Lemanske, Robert F.; Nicolae, Dan L.; Gern, James E.; Ober, Carole

2015-01-01

Background Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. Objective We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. Methods The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2,128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma birth cohort study (COAST). Results A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. Conclusions We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma. PMID:26399222

Nonprescription bronchodilator medication use in asthma.

PubMed

Kuschner, W G; Hankinson, T C; Wong, H H; Blanc, P D

1997-10-01

Many persons with asthma self-medicate with widely available and potentially hazardous nonprescription medicines. This study assessed the demographic and clinical covariates of self-treatment with over-the-counter asthma medications (OTCs). We conducted an analytical investigation using questionnaires and measures of lung function, comparing OTC and prescription medication users. We recruited adults with asthma by public advertisement. We studied 22 exclusive prescription asthma medication users, 15 exclusive OTC users, and 13 other subjects who combined prescription medication use with self-treatment with asthma OTCs. All but one OTC user self-medicated with a nonselective, sympathomimetic metered-dose inhaler. Taking income, access to care, and self-assessed disease severity into account, male gender was strongly associated with exclusive OTC use alone (odds ratio [OR]=8.9, 95% confidence interval [CI]= 1.3 to 61) and mixed OTC-prescription medication use (OR=9.7, 95% CI=1.1 to 83). The covariates of income, access to care, and self-assessed disease severity provided significant additional explanatory power to the model of exclusive OTC use (model chi2 difference 11.3, 5 df, p<0.05). Pulmonary function was similar among OTC and prescription medication users. However, prescription medication users' self-assessed asthma severity (mild compared to more severe) was associated with postbronchodilator reversibility of FEV1 obstruction (6% vs 18% reversibility, p<0.05) while exclusive OTC users' self-assessed severity showed the reverse pattern (19% vs 8%, p=0.2). Asthma education programs attempting to discourage unregulated bronchodilator use should give consideration to this profile of the "asthmatic-at-risk."

In-school asthma management and physical activity: children’s perspectives

PubMed Central

Walker, Timothy J.; Reznik, Marina

2014-01-01

OBJECTIVE Regular physical activity (PA) is an important component of pediatric asthma management. No studies have examined how in-school asthma management influences PA from children’s perspectives. The aim of this study was to explore children’s perceptions of the impact of in-school asthma management on PA. METHODS Qualitative interviews with 23 inner-city minority children with asthma (ages 8–10 yrs; 12 girls, 11 boys) were conducted in 10 Bronx, New York elementary schools. Sampling continued until saturation was reached. Interviews were recorded, transcribed and independently coded for common themes. RESULTS Interviews produced five themes representing students’ perceptions about 1) asthma symptoms during in-school PA; 2) methods to control asthma episodes during school PA; 3) methods to prevent asthma episodes during school; 4) limited accessibility of asthma medications; and 5) negative feelings about asthma and medication use. The majority of students experienced asthma symptoms while performing PA during school. Primary methods of managing asthma symptoms were sitting out during activity, drinking water, and visiting the nurse. Students lacked awareness or adherence to action plans to prevent or control asthma. Students reported limited access to medication during school and feelings of embarrassment and/or concerns of teasing when medicating in front of others. CONCLUSIONS Our results indicate inappropriate in-school management of asthma symptoms, poor asthma control, lack of accessible medication, and stigma around publicly using asthma medication. Thus, students often missed or were withheld from PA. Interventions to improve in-school asthma care must consider ways to address these issues. PMID:24796650

Effect of obesity and metabolic syndrome on severity, quality of life, sleep quality and inflammatory markers in patients of asthma in India.

PubMed

Singh, Mandeep; Gupta, Nitesh; Kumar, Raj

2016-01-01

The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients. 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study. The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p < 0.05), high risk of OSA (p< 0.05), decreased lung volumes (FRC) (p< 0.05), higher levels of inflammatory markers (leptin and IL-6) (p < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients. The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control.

Achieving and maintaining asthma control in an urban pediatric disease management program: the Breathmobile Program.

PubMed

Jones, Craig A; Clement, Loran T; Morphew, Tricia; Kwong, Kenny Yat Choi; Hanley-Lopez, Jean; Lifson, Francene; Opas, Lawrence; Guterman, Jeffrey J

2007-06-01

National guidelines suggest that, with appropriate care, most patients can control their asthma. The probabilities of children achieving and maintaining control with ongoing care are unknown. We sought to evaluate the degree to which children in a lower socioeconomic urban setting achieve and maintain control of asthma with regular participation in a disease management program that provides guideline-based care. Interdisciplinary teams of asthma specialists use mobile clinics to offer ongoing care at schools and county clinics. A guideline-derived construct of asthma control is recorded at each visit. Two thousand one hundred eighty-five enrollees were eligible to evaluate the time to first achieve control, and 1591 patients were eligible to evaluate subsequent control maintenance. Depending on severity, 70% to 87% of patients with persistent asthma achieved control by visit 3, and 89% to 98% achieved control by visit 6. Subsequent control maintenance was highly variable. Thirty-nine percent of patients displayed well-controlled asthma (control at >90% of subsequent visits), whereas 13% displayed difficult-to-control asthma (<50% of subsequent visits). Patients from each baseline severity category were found in each group. Maintenance of control was influenced by physician-estimated compliance with the treatment plan, baseline severity, and the interval between clinic visits. Many children can achieve asthma control with regular visit intervals and guideline-based care; however, long-term control can be highly variable among patients in all severity categories. These findings highlight the need and feasibility for systematically tracking each patient's clinical response to individualize therapy and guide the use of population management strategies.

Age is associated with asthma phenotypes.

PubMed

Ponte, Eduardo V; Lima, Aline; Almeida, Paula C A; de Jesus, Juliana P V; Lima, Valmar B; Scichilone, Nicola; Souza-Machado, Adelmir; Cruz, Álvaro A

2017-11-01

The relationship between age and asthma phenotypes is important as population is ageing, asthma is becoming common in older ages and recently developed treatments for asthma are guided by phenotypes. The aim of this study is to evaluate whether age is associated with specific asthma phenotypes. This is a cross-sectional study. We included subjects with asthma of varied degrees of severity. Subjects underwent spirometry, skin prick test to aeroallergens, answered the Asthma Control Questionnaire and had blood samples collected. We performed binary logistic regression analysis to evaluate whether age is associated with asthma phenotypes. We enrolled 868 subjects. In comparison with subjects ≤ 40 years, older subjects had high odds of irreversible airway obstruction (from 41 to 64 years, OR: 1.83 (95% CI: 1.32-2.54); ≥65 years, OR: 3.45 (2.12-5.60)) and severe asthma phenotypes (from 41 to 64 years, OR: 3.23 (2.26-4.62); ≥65 years, OR: 4.55 (2.39-8.67)). Older subjects had low odds of atopic (from 41 to 64 years, OR: 0.56 (0.39-0.79); ≥65 years, OR: 0.47 (0.27-0.84)) and eosinophilic phenotypes (from 41 to 64 years, OR: 0.63 (0.46-0.84); ≥65 years, OR: 0.39 (0.24-0.64)). Older subjects with asthma have low odds of atopic and eosinophilic phenotypes, whereas they present high odds of irreversible airway obstruction and severe asthma. © 2017 Asian Pacific Society of Respirology.

An evaluation of a community pharmacy-based rural asthma management service.

PubMed

Saini, Bandana; Filipovska, Julija; Bosnic-Anticevich, Sinthia; Taylor, Susan; Krass, Ines; Armour, Carol

2008-04-01

To compare the effect of a pharmacist-delivered rural asthma management service (RAMS) on health outcomes for people with asthma in a rural/regional area with 'standard care' delivered through community pharmacies. A parallel group controlled repeated measures study. Community pharmacies in Central West New South Wales. Standardised protocols and resources based on national asthma management guidelines, delivered by specially trained community pharmacists. Patients visited the pharmacy at baseline and 1, 3 and 6 months after baseline in the intervention group and at baseline plus 6 months after baseline in the control group. The intervention pharmacists (n = 12) were trained to deliver the RAMS model, while control pharmacists (n = 8) provided standard asthma care to their recruited patients. Fifty-one and 39 patients were recruited by intervention and control pharmacists. Asthma severity score which was a composite score based on recency, frequency and severity of asthma symptoms, and asthma history. Data compared at the final visit between groups indicated that the RAMS patient group demonstrated a significant reduction in the asthma severity scores (7.9 +/- 2.6 versus 10.4 +/- 2.6, P < 0.001); a reduction in the risk of non-adherence to medication scores (1.6 +/- 0.7 versus 2.3 +/- 1.1, P < 0.001); and an increase in the proportion of patients owning a written action plan (50% versus 23%, P = 0.04). These results indicated that the community pharmacy-based RAMS model can improve asthma outcomes for patients in rural settings, and similar models for asthma and other chronic diseases should be tested rigorously and adopted in rural primary care practice.

Pulmonary vasculature and critical asthma syndromes: a comprehensive review.

PubMed

Avdalovic, Mark

2015-02-01

One of the important factors and consequences in persistent asthma is the change in the vasculature of the airways and lung parenchyma. These changes could contribute to worsening asthma control and predispose asthmatics to critical asthma syndromes. For many years, the contribution of vasculature to severe asthma was limited to discussion of small and medium vessel vasculitis commonly referred to as Churg-Strauss syndrome. This comprehensive review will explore the known mechanisms that are associated with remodeling of the vasculature in a variety of critical asthma presentations. Inflammation of pulmonary and bronchial small blood vessels may contribute significantly but silently to asthma pathobiology. Inflammation in the vasculature of the lung parenchyma can decrease lung capacity while inflammation in airway vasculature can decrease airflow. This review will provide a modern perspective on Churg-Strauss syndromes with a focus on phenotyping, mechanism, and ultimately modern therapeutic approaches. Vascular remodeling and airway remodeling are not mutually exclusive concepts in understanding the progression of asthma and frequency of acute exacerbations. Furthermore, the contribution of vascular leak, particularly in the parenchymal vasculature, has become an increasingly recognized component of certain presentations of poorly controlled, severe persistent asthmatic and during exacerbations. We highlight how these mechanisms can contribute to some the severe presentations of influenza infection in patients with a history of asthma. The ultimate aim of this review is to summarize the current literature concerning vasculitis and the contribution of airway and parenchymal vascular remodeling to presentation of persistent asthma and its consequences during acute exacerbations and critical asthma syndromes.

Extracellular cyclophilin levels associate with parameters of asthma in phenotypic clusters.

PubMed

Stemmy, Erik J; Benton, Angela S; Lerner, Jennifer; Alcala, Sarah; Constant, Stephanie L; Freishtat, Robert J

2011-12-01

Leukocyte persistence during chronic (quiescent) phases of asthma is a major hallmark of the disease. The mechanisms regulating these persistent leukocyte populations are not clearly understood. An alternative family of chemoattracting proteins, cyclophilins (Cyps), has recently been shown to contribute to leukocyte recruitment in animal models of allergic asthma. The goals of this study were to determine whether Cyps are present in asthma patients during the chronic phase of the disease and to investigate whether levels of Cyps associate with clinical parameters of disease severity. Nasal wash samples from an urban cohort of 137 patients of age 6-20 years with physician-diagnosed asthma were examined for the presence of cyclophilin A (CypA), cyclophilin B (CypB), as well as several other classical chemokines. Linear, logistic, or ordinal regressions were performed to identify associations between Cyps, chemokines, and clinical parameters of asthma. The asthma cohort was further divided into previously established phenotypic clusters (cluster 1: n = 55; cluster 2: n = 31; and cluster 3: n = 51) and examined for associations. Levels of CypB in the asthma group were highly elevated compared to nonasthmatic controls, while a slight increase in Monocyte Chemotactic Protein-1 (MCP-1) was also observed. CypA and MCP-1 were associated with levels of eosinophil cationic protein (ECP; a marker of eosinophil activation). Cluster-specific associations were found for CypA and CypB and clinical asthma parameters [e.g. forced expiratory volume in 1 second (FEV(1)) and ECP]. Cyps are present in nasal wash samples of asthma patients and may be a novel biomarker for clinical parameters of asthma severity.

A nested case-control study: personal, social and environmental correlates of vigorous physical activity in adolescents with asthma.

PubMed

Westergren, Thomas; Ommundsen, Yngvar; Lødrup Carlsen, Karin C; Carlsen, Kai-Håkon; Mowinckel, Petter; Fegran, Liv; Berntsen, Sveinung

2015-03-01

Physical activity (PA) is associated with health benefits. Children and adolescents with asthma may be limited in their PA, particularly at vigorous intensity due to asthma symptoms or poor psychological adjustment to asthma. We aimed to investigate if self-perceived competence, enjoyment, support from others and social-physical environment were associated with vigorous physical activity (VPA) and secondarily to assess if such associations were modified by asthma and asthma severity. Data from a nested case-control study at 13 years of age within the birth-cohort Environment and Childhood Asthma Study were compiled from 95 participants with and 79 without asthma. The participants completed a questionnaire designed to capture self-perceived competence, enjoyment, support from others and social-physical environment. VPA, defined as ≥ 6 Metabolic Equivalents, was recorded objectively by SenseWear™ Pro2 Armband. Asthma severity was assessed pragmatically by lung function and use of inhaled glucocorticosteroids and β2-agonists and incidence of exacerbations in the last 14 days. Data were analysed using linear regression analysis. No significant differences between adolescents with and without asthma were identified in terms of VPA, competence-enjoyment, support from others and social-physical environment. Peer support (b = 0.29 (0.05-0.52)) and competence-enjoyment (b = 0.23 (0.01-0.44)) were significantly and positively associated with VPA, and teacher support (b = -0.26 (-0.50 to -0.02)) were inversely associated. The model explained 25% of the variance in VPA. Peer support and competence-enjoyment were positively associated with increased VPN in adolescents irrespectively of asthma and asthma severity.

Evaluation of selected immunological parameters and the concentration of vitamin D in children with asthma. Case-control study

PubMed Central

Wawrzyniak, Agata; Lipińska-Opałka, Agnieszka; Zdanowski, Robert; Murawski, Piotr; Kalicki, Bolesław

2017-01-01

Due to the increased incidence of allergic diseases and emerging effects of unsatisfactory control of asthma, new mechanisms for supervising the immune system should be searched. The aim of the study was to analyze the percentage of CD3, CD4, CD8, CD19, CD16/56, NKT, CD3 anti-HLADR3 and Foxp3 regulatory lymphocytes in patients with asthma. Additionally the correlation between immune parameters, severity of asthma and serum concentration of vitamin D was performed. 25 children diagnosed with asthma were enrolled. Disease severity was assessed with the Asthma Control Test (ACT) and spirometry. The control group consisted of 15 healthy children. Venous blood from each patient was collected on EDTA or on “clott”. Phenotypes of lymphocytes were evaluated by flow cytometry. Vitamin D concentration was assessed by chemiluminescent immunoassay (CLIA) technology. There was a significant decrease in the percentage of T regulatory cells (p < 0.006) in children with asthma compared to the control group. There were no significant differences in the other investigated immunological parameters. In addition, in asthma group statistically significant decreased of vitamin D concentration (p < 0.04) was observed. There were also no significant correlations between vitamin D3 concentration and the course of asthma or percentage of regulatory cells. The results confirmed the role of regulatory T cells in the pathogenesis of asthma. Effects of vitamin D on the severity of the disease has not been proven. PMID:28680338

Evaluation of selected immunological parameters and the concentration of vitamin D in children with asthma. Case-control study.

PubMed

Wawrzyniak, Agata; Lipińska-Opałka, Agnieszka; Zdanowski, Robert; Lewicki, Sławomir; Murawski, Piotr; Kalicki, Bolesław

2017-01-01

Due to the increased incidence of allergic diseases and emerging effects of unsatisfactory control of asthma, new mechanisms for supervising the immune system should be searched. The aim of the study was to analyze the percentage of CD3, CD4, CD8, CD19, CD16/56, NKT, CD3 anti-HLADR3 and Foxp3 regulatory lymphocytes in patients with asthma. Additionally the correlation between immune parameters, severity of asthma and serum concentration of vitamin D was performed. 25 children diagnosed with asthma were enrolled. Disease severity was assessed with the Asthma Control Test (ACT) and spirometry. The control group consisted of 15 healthy children. Venous blood from each patient was collected on EDTA or on "clott". Phenotypes of lymphocytes were evaluated by flow cytometry. Vitamin D concentration was assessed by chemiluminescent immunoassay (CLIA) technology. There was a significant decrease in the percentage of T regulatory cells (p < 0.006) in children with asthma compared to the control group. There were no significant differences in the other investigated immunological parameters. In addition, in asthma group statistically significant decreased of vitamin D concentration (p < 0.04) was observed. There were also no significant correlations between vitamin D3 concentration and the course of asthma or percentage of regulatory cells. The results confirmed the role of regulatory T cells in the pathogenesis of asthma. Effects of vitamin D on the severity of the disease has not been proven.

Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study.

PubMed

Loza, Matthew J; Djukanovic, Ratko; Chung, Kian Fan; Horowitz, Daniel; Ma, Keying; Branigan, Patrick; Barnathan, Elliot S; Susulic, Vedrana S; Silkoff, Philip E; Sterk, Peter J; Baribaud, Frédéric

2016-12-15

Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. NCT01274507 (ADEPT), registered October 28, 2010 and NCT01982162 (U-BIOPRED), registered October 30, 2013.

Preventive asthma care delivery in the primary care office: missed opportunities for children with persistent asthma symptoms.

PubMed

Yee, Alison B; Fagnano, Maria; Halterman, Jill S

2013-01-01

To describe which National Heart Lung and Blood Institute preventive actions are taken for children with persistent asthma symptoms at the time of a primary care visit and determine how care delivery varies by asthma symptom severity. We approached children (2 to 12 years old) with asthma from Rochester, NY, in the waiting room at their doctor's office. Eligibility required current persistent symptoms. Caregivers were interviewed via telephone within 2 weeks after the visit regarding specific preventive care actions delivered. Bivariate and regression analyses assessed the relationship between asthma symptom severity and actions taken during the visit. We identified 171 children with persistent asthma symptoms (34% black, 64% Medicaid) from October 2009 to January 2011 at 6 pediatric offices. Overall delivery of guideline-based preventive actions during visits was low. Children with mild persistent symptoms were least likely to receive preventive care. Regression analyses controlling for demographics and visit type (acute or follow-up asthma visit vs non-asthma-related visit) confirmed that children with mild persistent asthma symptoms were less likely than those with more severe asthma symptoms to receive preventive medication action (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.14-0.84), trigger reduction discussion (OR 0.39, 95% CI 0.19-0.82), recommendation of follow-up (OR 0.40, 95% CI 0.19-0.87), and receipt of action plan (OR 0.37, 95% CI 0.16-0.86). Many children with persistent asthma symptoms do not receive recommended preventive actions during office visits, and children with mild persistent symptoms are the least likely to receive care. Efforts to improve guideline-based asthma care are needed, and children with mild persistent asthma symptoms warrant further consideration. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Childhood asthma-predictive phenotype.

PubMed

Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

2014-01-01

Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Sleep Disorders in Patients with Bronchial Asthma

PubMed Central

Cukic, Vesna; Lovre, Vladimir; Dragisic, Dejan

2011-01-01

Respiratory disturbances during sleep are recognized as extremely common disorders with important clinical consequences. Breathing disorders during sleep can result in broad range of clinical manifestations, the most prevalent of which are unrefreshing sleep, daytime sleepiness and fatigue, and cognitive impairmant. There is also evidence that respiratory-related sleep disturbances can contribute to several common cardiovascular and metabolic disorders, including systemic hypertension, cardiac dysfunction, and insulin-resistance. Correlations are found between asthma-related symptoms and sleep disturbances. Difficulties inducing sleep, sleep fragmentation on polysomnography, early morning awakenings and daytime sleepiness are more common in asthmatics compared with subjects without asthma. The “morning deep” in asthma is relevant for the characterization of asthma severity, and impact drugs’ choices. Sleep and night control of asthma could be relevant to evaluate disease’s control. Appropriate asthma control recovering is guarantor for better sleep quality in these patients and less clinical consequences of respiratory disturbances during sleep. PMID:23678304

Assessment of public health impact of work-related asthma.

PubMed

Jaakkola, Maritta S; Jaakkola, Jouni J K

2012-03-05

Asthma is among the most common chronic diseases in working-aged populations and occupational exposures are important causal agents. Our aims were to evaluate the best methods to assess occurrence, public health impact, and burden to society related to occupational or work-related asthma and to achieve comparable estimates for different populations. We addressed three central questions: 1: What is the best method to assess the occurrence of occupational asthma? We evaluated: 1) assessment of the occurrence of occupational asthma per se, and 2) assessment of adult-onset asthma and the population attributable fractions due to specific occupational exposures. 2: What are the best methods to assess public health impact and burden to society related to occupational or work-related asthma? We evaluated methods based on assessment of excess burden of disease due to specific occupational exposures. 3: How to achieve comparable estimates for different populations? We evaluated comparability of estimates of occurrence and burden attributable to occupational asthma based on different methods. Assessment of the occurrence of occupational asthma per se can be used in countries with good coverage of the identification system for occupational asthma, i.e. countries with well-functioning occupational health services. Assessment based on adult-onset asthma and population attributable fractions due to specific occupational exposures is a good approach to estimate the occurrence of occupational asthma at the population level. For assessment of public health impact from work-related asthma we recommend assessing excess burden of disease due to specific occupational exposures, including excess incidence of asthma complemented by an assessment of disability from it. International comparability of estimates can be best achieved by methods based on population attributable fractions. Public health impact assessment for occupational asthma is central in prevention and health policy planning and could be improved by purposeful development of methods for assessing health benefits from preventive actions. Registry-based methods are suitable for evaluating time-trends of occurrence at a given population but for international comparisons they face serious limitations. Assessment of excess burden of disease due to specific occupational exposure is a useful measure, when there is valid information on population exposure and attributable fractions.

The relationship between migraine headache and asthma features.

PubMed

Dirican, Nigar; Demirci, Seden; Cakir, Munire

2017-06-01

Migraine and asthma are comorbid chronic disorders with episodic attacks thought to involve inflammatory and neurological mechanisms. The objective of the present study is to investigate the relationship of asthma features between the asthma patients with migraine and those without migraine headache. A cross-sectional study was conducted from October 2015 to June 2016. Physician-diagnosed asthma patients aged 18 years and above were included. Demographic data, pulmonary function test and treatment of asthma were recorded. Asthma control was assessed using the asthma control test (ACT) and asthma control questionnaire (ACQ). The diagnosis of migraine was made by the neurologist with face-to face examinations based on the International Classification of Headache Disorders, third edition beta (ICHD-III-beta) criteria. Data about the age at onset, frequency of headache attacks, duration of headache attack, the presence of aura, and severity of headache were recorded. The severity of headache was evaluated using visual analogue scale (VAS). Overall 121 asthma patients were included in this study. Migraine was found to be present in 32 (26.4%) of patients. No statistically significant difference was found between asthma group and asthma with migraine groups in terms of pulmonary function test parameters. The mean ACT score in asthma with migraine patients group was significantly lower than the asthma groups. Morever, in the group asthma with migraine, a negative significant correlations were found between ACT scores with VAS scores. This study demonstrates that migraine headache may be associated with poor asthma control. On the other hand, it should not be forgotten that ACT is a subjective test and can be affected from by many clinical parameters.

IL-13 and its genetic variants: effect on current asthma treatments.

PubMed

Townley, Robert G; Sapkota, Muna; Sapkota, Kiran

2011-12-01

Airway hyperresponsiveness is an essential part of the definition of asthma associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain organic chemicals. Interleukin-13 (IL-13) is implicated as a central regulator in immunoglobulin E (IgE) synthesis, mucus hypersecretion, airway hyperresponsiveness, and fibrosis. The importance of IL-13 in allergic disorders in humans is supported by consistent associations between tissue IL-13 levels and genetic variants in the IL-13 gene and asthma and related traits. Single-nucleotide polymorphisms in IL-13 are associated with allergic phenotypes in several ethnically diverse populations. Glucocorticoids are anti-inflammatory medications often used as maintenance therapy in acute and chronic asthma; however, some patients with severe asthma are steroid resistant. IL-13 remains elevated in glucocorticoid insensitive asthma but not in glucocorticoid sensitive asthma. Thus targeting IL-13 and its associated receptors may be a therapeutic approach to the treatment of asthma and/or allergy. This review focuses on the role of IL-13 on airway hyperresponsiveness and corticosteroids resistant asthma both preclinically and clinically. © Discovery Medicine

Prevalence and Severity of Asthma, Rhinitis, and Atopic Eczema in 13- to 14-Year-Old Schoolchildren from Southern Brazil

PubMed Central

2006-01-01

The objective of this study was to investigate the prevalence and severity of asthma, rhinitis, and atopic eczema in schoolchildren from southern Brazil. A cross-sectional study was carried out with the International Study of Asthma and Allergies in Childhood phase III written questionnaire. The questionnaire was self-applied by 2,948 randomly selected schoolchildren aged 13 to 14 years. The lifetime prevalence rates of symptoms were as follows: wheezing, 40.8%; rhinitis, 40.7%; eczema, 13.6%; self-reported asthma, 14.6%; rhinitis, 31.4%; eczema, 13.4%. Rhinitis was reported by 55% of adolescents with current asthma (60% females vs 46.9% males). Girls 13 to 14 years of age had higher prevalence rates of asthma, rhinitis, and eczema than boys had. Atopic eczema was reported by 42.7% of girls and 31.4% of boys with asthma. The prevalence rates were statistically significant for symptoms of asthma, rhinitis, and atopic eczema in females. However, there were no statistically significant differences between the sexes in regard to reported asthma and bronchospasm induced by exercise. PMID:20529214

Quantitative computed tomography measurements of emphysema for diagnosing asthma-chronic obstructive pulmonary disease overlap syndrome

PubMed Central

Xie, Mengshuang; Wang, Wei; Dou, Shuang; Cui, Liwei; Xiao, Wei

2016-01-01

Background The diagnostic criteria of asthma–COPD overlap syndrome (ACOS) are controversial. Emphysema is characteristic of COPD and usually does not exist in typical asthma patients. Emphysema in patients with asthma suggests the coexistence of COPD. Quantitative computed tomography (CT) allows repeated evaluation of emphysema noninvasively. We investigated the value of quantitative CT measurements of emphysema in the diagnosis of ACOS. Methods This study included 404 participants; 151 asthma patients, 125 COPD patients, and 128 normal control subjects. All the participants underwent pulmonary function tests and a high-resolution CT scan. Emphysema measurements were taken with an Airway Inspector software. The asthma patients were divided into high and low emphysema index (EI) groups based on the percentage of low attenuation areas less than −950 Hounsfield units. The characteristics of asthma patients with high EI were compared with those having low EI or COPD. Results The normal value of percentage of low attenuation areas less than −950 Hounsfield units in Chinese aged >40 years was 2.79%±2.37%. COPD patients indicated more severe emphysema and more upper-zone-predominant distribution of emphysema than asthma patients or controls. Thirty-two (21.2%) of the 151 asthma patients had high EI. Compared with asthma patients with low EI, those with high EI were significantly older, more likely to be male, had more pack-years of smoking, had more upper-zone-predominant distribution of emphysema, and had greater airflow limitation. There were no significant differences in sex ratios, pack-years of smoking, airflow limitation, or emphysema distribution between asthma patients with high EI and COPD patients. A greater number of acute exacerbations were seen in asthma patients with high EI compared with those with low EI or COPD. Conclusion Asthma patients with high EI fulfill the features of ACOS, as described in the Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. Quantitative CT measurements of emphysema may help in diagnosing ACOS. PMID:27226711

Drug Development and Biologics in Asthma. A New Era.

PubMed

Doyle, Ramona

2016-03-01

Considerable progress has been made toward developing targeted biological therapeutics for asthma, due in large part to a deeper understanding of asthma pathophysiology. This explosion of knowledge has revealed asthma to be a much more complex and heterogeneous entity than previously understood. The identification of particular asthma phenotypes with distinct pathophysiologic mechanisms has opened up a new era for patient populations not well served by current therapies, especially patients with severe asthma.

Feasibility, acceptability, and preliminary effectiveness of patient advocates for improving adult asthma outcomes

PubMed Central

Apter, Andrea J.; Wan, Fei; Reisine, Susan; Bogen, Daniel K.; Rand, Cynthia; Bender, Bruce; Bennett, Ian M.; Gonzalez, Rodalyn; Priolo, Chantel; Sonnad, Seema S.; Bryant-Stephens, Tyra; Ferguson, Monica; Boyd, Rhonda C.; Have, Thomas Ten; Roy, Jason

2014-01-01

Background Asthmatic adults from low-income urban neighborhoods have inferior health outcomes which in part may be due to barriers accessing care and with patient-provider communication. We adapted a patient advocate (PA) intervention to overcome these barriers. Objective To conduct a pilot study to assess feasibility, acceptability, and preliminary evidence of effectiveness. Methods A prospective randomized design was employed with mixed methods evaluation. Adults with moderate or severe asthma were randomized to 16 weeks of PA or a minimal intervention (MI) comparison condition. The PA, a nonprofessional, modeled preparations for a medical visit, attended the visit, and confirmed understanding. The PA facilitated scheduling, obtaining insurance coverage, and overcoming barriers to implementing medical advice. Outcomes included electronically-monitored inhaled corticosteroid adherence, asthma control, quality of life, FEV1, ED visits, and hospitalizations. Mixed-effects models guided an intention-to-treat analysis. Results 100 adults participated: age 47±14 years, 75% female, 71% African American, 16% white, baseline FEV1 69% ± 18%, 36% experiencing hospitalizations and 56% ED visits for asthma in the prior year. Ninety-three subjects completed all visits; 36 of 53 PA-assigned had a PA visit. Adherence declined significantly in the control (p= 0.001) but not significantly in the PA group (p=.30). Both PA and MI groups demonstrated improved asthma control (p=0.01 in both) and quality of life (p=0.001, p=0.004). Hospitalizations and ED visits for asthma did not differ between groups. The observed changes over time tended to favor the PA group, but this study was underpowered to detect differences between groups. Conclusion The PA intervention was feasible and acceptable and demonstrated potential for improving asthma control and quality of life. PMID:23800333

A systematic review of explanatory factors of barriers and facilitators to improving asthma management in South Asian children

PubMed Central

2014-01-01

Background South Asian children with asthma are less likely to receive prescriptions and more likely to suffer uncontrolled symptoms and acute asthma admissions compared with White British children. Understanding barriers are therefore vital in addressing health inequalities. We undertook a systematic review identifying explanatory factors for barriers and facilitators to asthma management in South Asian children. South Asians were defined as individuals of Indian, Pakistani or Bangladeshi descent. Methods Data Sources - Medline, HMIC, EMBASE, ASSIA, Web of Science, BNI, CINAHL, PsycINFO, OpenSIGLE, CRD, Scopus, NHS Evidence, Cochrane Library, Campbell Collaboration, RCPCH, ATS, ERS, Asthma UK, Google Scholar & Asthma Guidelines (BTS, GINA, ATS, Monash, NAEPP, Singapore & New Zealand) to August 2013. Inclusion Criteria – Qualitative, quantitative or mixed methods research with primary focus on identifying explanations for barriers and/or facilitators to asthma management in South Asian children aged 0–18 years with diagnosed/suspected asthma and/or carers and/or healthcare professionals. Data Extraction – Three authors independently reviewed, selected & extracted eligible articles with disagreements resolved by research team discussion. Results 15 studies encompassing 25,755 children, 18,483 parents/carers and 239 healthcare professionals were included. Barriers and explanatory factors identified were: 1. Lack of asthma knowledge in families and healthcare professionals. 2. Under-use of preventer medications. 3. Non-acceptance/denial of asthma. 4. Over-reliance on Emergency Department management. 5. Communication problems. 6. Non-adherence to medication. 7. Use of complementary therapies. Little facilitators regarding asthma management were identified. Conclusions Several key issues were identified as likely to be ethnic-specific to South Asian families, rather than a reflection of minority status: impact of parental and professional knowledge and beliefs, health service utilisation pattern explanations and the impact of prejudice and stigmatisation. Other explanations such as language barriers are not strictly ethnic specific but instead reflect a minority position. Further research is required to identify why barriers exist, the mechanisms by which they impact on asthma management and how they can be overcome. Furthermore, understanding the difference between barriers and explanations that are ethnic-specific and those that are related to being a minority will enable the application of generic system-wide interventions where ethnicity is not the issue and ethnically-tailored interventions where needed. PMID:24767303

Psychological treatment of comorbid asthma and panic disorder in Latino adults: Results from a randomized controlled trial

PubMed Central

Feldman, Jonathan M.; Matte, Lynne; Interian, Alejandro; Lehrer, Paul M.; Lu, Shou-En; Scheckner, Bari; Steinberg, Dara M.; Oken, Tanya; Kotay, Anu; Sinha, Sumita; Shim, Chang

2016-01-01

Confusion between panic and asthma symptoms can result in serious self-management errors. A cognitive behavior psychophysiological therapy (CBPT) intervention was culturally adapted for Latinos consisting of CBT for panic disorder (PD), asthma education, differentiation between panic and asthma symptoms, and heart rate variability biofeedback. An RCT compared CBPT to music and relaxation therapy (MRT), which included listening to relaxing music and paced breathing at resting respiration rates. Fifty-three Latino (primarily Puerto Rican) adults with asthma and PD were randomly assigned to CBPT or MRT for 8 weekly sessions. Both groups showed improvements in PD severity, asthma control, and several other anxiety and asthma outcome measures from baseline to post-treatment and 3-month follow-up. CBPT showed an advantage over MRT for improvement in adherence to inhaled corticosteroids. Improvements in PD severity were mediated by anxiety sensitivity in CBPT and by depression in MRT, although earlier levels of these mediators did not predict subsequent improvements. Attrition was high (40%) in both groups, albeit comparable to CBT studies targeting anxiety in Latinos. Additional strategies are needed to improve retention in this high-risk population. Both CBPT and MRT may be efficacious interventions for comorbid asthma-PD, and CBPT may offer additional benefits for improving medication adherence. PMID:27668723

How Do Storms Affect Asthma?

PubMed

D'Amato, Gennaro; Annesi-Maesano, Isabella; Vaghi, Adriano; Cecchi, Lorenzo; D'Amato, Maria

2018-03-24

There are observations in various geographical areas that thunderstorms occurring during pollen seasons can induce severe asthma attacks in pollinosis patients. An accredited hypothesis explaining the association between thunderstorms and asthma suggests that storms can concentrate pollen grains at ground level, which may then release allergenic particles of respirable size in the atmosphere after their imbibition of water and rupture by osmotic shock. During the first 20-30 min of a thunderstorm, patients affected by pollen allergy may inhale a high quantity of the allergenic material that is dispersed into the atmosphere as a bioaerosol of allergenic particles, which can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. A key message is that all subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe asthma exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm-related events. Patients with respiratory allergy induced by pollens and molds need to be informed about a correct therapeutic approach of bronchial asthma by inhalation, including the use of bronchodilators and inhaled corticosteroids. The purpose of this review is to focalize epidemiological, etiopathogenetic, and clinical aspects of thunderstorm-related asthma.

Advances in environmental and occupational disorders in 2013.

PubMed

Peden, David B; Bush, Robert K

2014-05-01

In this review of articles published in the Journal in 2013, we report on the significant advances in environmental and occupational disorders. Research advances have led to the identification and defined the structure and function of several major allergens. A meta-analysis confirmed the importance of mold exposure in patients with allergic rhinitis, and a new immunologic classification of aspergillosis emerged. Insights into the role of diesel exhaust particles in patients with severe asthma were clarified. Improvements in stinging insect allergy diagnostics were reported. Genetic, immunologic, and biomarker studies advanced the understanding of adverse drug reactions. New practice parameters for cockroach allergen control were presented. The pathologic role of viruses and bacterial agents in patients with asthma and chronic obstructive pulmonary disease were further defined. An excellent review of allergen bronchoprovocation testing was reported. The roles of bronchoprovocation and bronchodilator responsiveness in asthma diagnosis were further clarified. A biomarker for neutrophilic asthma was identified. Therapeutic advances in asthma research include the inhibition of IL-13 by lebrikizumab, use of montelukast in asthmatic smokers, and a thorough review of bronchial thermoplasty in patients with severe asthma. Lastly, maternal asthma was linked to a number of adverse neonatal outcomes. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

PubMed

Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

2017-06-01

Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

Strategies to alter the natural history of childhood asthma

PubMed Central

Lee-Sarwar, K; Bacharier, L; Litonjua, A

2017-01-01

Purpose of review Asthma exhibits significant heterogeneity in occurrence and severity over the lifespan. Our goal is to discuss recent evidence regarding determinants of the natural history of asthma during childhood, and review the rationale behind and status of major efforts to alter its course. Recent findings Variations in microbial exposures are associated with risk of allergic disease, and the use of bacterial lysates may be a promising preventive strategy. Exposure to air pollution appears to be particularly damaging in prenatal and early life, and interventions to reduce pollution are feasible and result in clinical benefit. E-cigarette use may have a role in harm reduction for conventional cigarette smokers with asthma, but has undefined short- and long-term effects that must be clarified. Vitamin D insufficiency over the first several years of life is associated with risk of asthma, and vitamin D supplementation reduces the risk of severe exacerbations. Summary The identification of risk factors for asthma occurrence, persistence and severity will continue to guide efforts to alter the natural history of the disease. We have reviewed several promising strategies that are currently under investigation. Vitamin D supplementation and air pollution reduction have been shown to be effective strategies and warrant increased investigation and implementation. PMID:28079559

Greater involvement of neurokinins found in Guinea pig models of severe asthma compared with mild asthma.

PubMed

Mukaiyama, Osamu; Morimoto, Kiyoshi; Nosaka, Emi; Takahashi, Sakiko; Yamashita, Makoto

2004-08-01

Involvement of neurokinins in asthma has been previously pointed out by several reports. However, the relationship between neurokinins and the severity of asthma has remained unclear. We developed a model of mild asthma (model I) and severe asthma (model II) in guinea pigs, and investigated the function of neurokinins in both models. In models I and II, systemically sensitized guinea pigs were made to inhale ovalbumin once and three times, respectively. Substance P (SP) and neurokinin A (NKA) concentrations in the bronchoalveolar lavage fluid (BALF) were measured in models I and II. Then, the effects of a capsaicin pretreatment, which depletes neurokinins, in both animal models on airway narrowing induced by the last ovalbumin inhalation, airway hyperresponsiveness to inhaled methacholine, and eosinophil accumulation in BALF, were investigated. SP concentration tended to increase and the NKA concentration increased significantly in model II, but not in model I. Capsaicin pretreatment significantly inhibited the late bronchial response that was observed 2-6 h after the last ovalbumin inhalation, airway hyperresponsiveness and eosinophil accumulation in model II. On the other hand, it had no effects on the responses in model I. It is suggested that the more severe the disease, the greater the involvement of neurokinins. Copyright 2004 S. Karger AG, Basel

Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in identifying severe asthma in children.

PubMed

Jochmann, Anja; Artusio, Luca; Jamalzadeh, Angela; Nagakumar, Prasad; Delgado-Eckert, Edgar; Saglani, Sejal; Bush, Andrew; Frey, Urs; Fleming, Louise J

2017-12-01

International guidelines recommend that severe asthma can only be diagnosed after contributory factors, including adherence, have been addressed. Accurate assessment of adherence is difficult in clinical practice. We hypothesised that electronic monitoring in children would identify nonadherence, thus delineating the small number with true severe asthma.Asthmatic children already prescribed inhaled corticosteroids were prospectively recruited and persistence of adherence assessed using electronic monitoring devices. Spirometry, airway inflammation and asthma control were measured at the start and end of the monitoring period.93 children (62 male; median age 12.4 years) were monitored for a median of 92 days. Median (range) monitored adherence was 74% (21-99%). We identified four groups: 1) good adherence during monitoring with improved control, 24% (likely previous poor adherence); 2) good adherence with poor control, 18% (severe therapy-resistant asthma); 3) poor adherence with good control, 26% (likely overtreated); and 4) poor adherence with poor control, 32%. No clinical parameter prior to monitoring distinguished these groups.Electronic monitoring is a useful tool for identifying children in whom a step up in treatment is indicated. Different approaches are needed in those who are controlled when adherent or who are nonadherent. Electronic monitoring is essential in a paediatric severe asthma clinic. Copyright ©ERS 2017.

Detrimental effects of environmental tobacco smoke in relation to asthma severity.

PubMed

Comhair, Suzy A A; Gaston, Benjamin M; Ricci, Kristin S; Hammel, Jeffrey; Dweik, Raed A; Teague, W Gerald; Meyers, Deborah; Ampleford, Elizabeth J; Bleecker, Eugene R; Busse, William W; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Israel, Elliot; Jarjour, W Nizar; Moore, Wendy; Peters, Stephen P; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2011-05-04

Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown. In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity. From 2002-2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage. ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma.

Geographic disparities of asthma prevalence in south-western United States of America.

PubMed

Chien, Lung-Chang; Alamgir, Hasanat

2014-11-01

Asthma is one of the most prevalent chronic diseases in the United States of America (USA), and many of its risk factors have so far been investigated and identified; however, evidence is limited on how spatial disparities impact the disease. The purpose of this study was to provide scientific evidence on the location influence on asthma in the four states of southwestern USA (California, Arizona, New Mexico and Texas) which, together, include 360 counties. The Behavioral Risk Factor Surveillance System database for these four states covering the period of 2000 to 2011 was used in this analysis, and a Bayesian structured additive regression model was applied to analyse by a geographical information system. After adjusting for individual characteristics, socioeconomic status and health behaviour, this study found higher odds associated with asthma and a likely cluster around the Bay Area in California, while lower odds appeared in several counties around the larger cities of Texas, such as Dallas, Houston and San Antonio. The significance map shows 43 of 360 counties (11.9%) to be high-risk areas for asthma. The level of geographical disparities demonstrates that the county risk of asthma prevalence varies significantly and can be about 19.9% (95% confidence interval: 15.3-25.8) higher or lower than the overall asthma prevalence. We provide an efficient method to utilise and interpret the existing surveillance data on asthma. Visualisation by maps may help deliver future interventions on targeted areas and vulnerable populations to reduce geographical disparities in the burden of asthma.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

PubMed

Larenas Linnemann, D E S; Del Río Navarro, B E; Luna Pech, J A; Romero Lombard, J; Villaverde Rosas, J; Cano Salas, M C; Fernández Vega, M; Ortega Martell, J A; López Estrada, E C; Mayorga Butrón, J L; Salas Hernández, J; Vázquez García, J C; Ortiz Aldana, I; Vargas Becerra, M H; Bedolla Barajas, M; Rodríguez Pérez, N; Aguilar Aranda, A; Jiménez González, C A; García Bolaños, C; Garrido Galindo, C; Mendoza Hernández, D A; Mendoza López, E; López Pérez, G; Wakida Kuzonoki, G H; Ruiz Gutiérrez, H H; León Molina, H; Martínez de la Lanza, H; Stone Aguilar, H; Gómez Vera, J; Olvera Salinas, J; Oyoqui Flores, J J; Gálvez Romero, J L; Lozano Saenz, J S; Salgado Gama, J I; Jiménez Chobillon, M A; García Avilés, M A; Guinto Balanzar, M P; Medina Ávalos, M A; Camargo Angeles, R; García Torrentera, R; Toral Freyre, S; Montes Narvaez, G; Solorio Gómez, H; Rosas Peña, J; Romero Tapia, S J; Reyes Herrera, A; Cuevas Schacht, F; Esquer Flores, J; Sacre Hazouri, J A; Compean Martínez, L; Medina Sánchez, P J; Garza Salinas, S; Baez Loyola, C; Romero Alvarado, I; Miguel Reyes, J L; Huerta Espinosa, L E; Correa Flores, M Á; Castro Martínez, R

With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma. Copyright © 2017. Published by Elsevier España, S.L.U.

Cytokine profile of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during seasonal H1N1 infection.

PubMed

Hasegawa, Shunji; Wakiguchi, Hiroyuki; Okada, Seigo; Gui Kang, Yu; Fujii, Nao; Hasegawa, Masanari; Hasegawa, Hideki; Ainai, Akira; Atsuta, Ryo; Shirabe, Komei; Toda, Shoichi; Wakabayashi-Takahara, Midori; Morishima, Tsuneo; Ichiyama, Takashi

2014-10-01

Several studies support the role of viral infections in the pathogenesis of asthma exacerbation. However, several pediatricians believe that influenza virus infection does not exacerbate bronchial asthma, except for influenza A H1N1 2009 pandemic [A(H1N1)pdm09] virus infection. We previously reported that A(H1N1)pdm09 infection possibly induces severe pulmonary inflammation or severe asthmatic attack in a mouse model of bronchial asthma and in asthmatic children. However, the ability of seasonal H1N1 influenza (H1N1) infection to exacerbate asthmatic attacks in bronchial asthma patients has not been previously reported, and the differences in the pathogenicity profiles, such as cytokine profiles, remains unclear in bronchial asthma patients after A(H1N1)pdm09 and H1N1 infections. The cytokine levels and viral titers in the bronchoalveolar lavage (BAL) fluid from mice with and without asthma after H1N1 infection (A/Yamagata and A/Puerto Rico strains) were compared. The interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, IL-5, interferon (IFN)-α, IFN-β, and IFN-γ levels were significantly higher in the BAL fluids from the control/H1N1 mice than from the asthmatic/H1N1 mice. The viral titers in the BAL fluid were also significantly higher in the control/H1N1mice than in the asthmatic/H1N1 mice infected with either A/Yamagata or A/Puerto Rico. A(H1N1)pdm09 infection, but not H1N1 infection, can induce severe pulmonary inflammation through elevated cytokine levels in a mouse model of asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prevalence of asthma, rhinitis and eczema symptoms in rural and urban school-aged children from Oropeza Province - Bolivia: a cross-sectional study

PubMed Central

2014-01-01

Background Asthma and allergies are world-wide common chronic diseases among children and young people. Little information is available about the prevalence of these diseases in rural areas of Latin America. This study assesses the prevalence of symptoms of asthma and allergies among children in urban and rural areas at Oropeza Province in Bolivia. Methods The Spanish version of the ISAAC standardized questionnaire and the ISAAC video questionnaire were implemented to 2584 children attending the fifth elementary grade in 36 schools in Oropeza province (response 91%). Lifetime, 12 months and severity prevalence were determined for asthma, rhinitis and eczema symptoms. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated adjusting for age using generalized linear mixed-effects models. Results Median age of children was 11 years, 74.8% attended public schools, and 52.1% were female. While children attending urban schools had lower prevalence of self-reported wheeze in the written questionnaire (adjusted OR 0.6; 95% CI 0.4-1.9), they were more likely than children attending rural schools to report wheeze in the video questionnaire (aOR 2.1; 95% CI 1.0-2.6). They also reported more frequently severe rhinoconjunctivitis (aOR 2.8; 95% CI 1.2-6.6) and severe eczema symptoms (aOR 3.3; 95% CI 1.0-11.0). Conclusion Overall in accordance with the hygiene hypothesis, children living in urban areas of Bolivia seem to have a higher prevalence of symptoms of asthma and allergies compared to children living in the country side. In order to develop primary prevention strategies, environmental factors need to be identified in future studies. PMID:24612913

Qualitative study of young people's and parents' beliefs about childhood asthma.

PubMed Central

Callery, Peter; Milnes, Linda; Verduyn, Chrissie; Couriel, Jonathan

2003-01-01

BACKGROUND: Asthma continues to be a common childhood chronic illness managed principally in primary care. Self-management requires co-ordinated efforts of young people, carers and health professionals. Non-compliance occurs even when parents are supervising care, suggesting that decisions are made on the basis of beliefs that contrast with professional advice. Health professionals therefore need to understand the views of parents (or other carers) and patients to promote good self-management. Little attention has been given to carers' and young people's perspectives on asthma. AIM: To gain insights into the beliefs of a group of 25 young people aged nine to 16 years old and their carers about asthma and its management. DESIGN OF STUDY: Qualitative study using conversational-style interviews. SETTING: Generally deprived urban areas of Greater Manchester. METHOD: Interviews were conducted with 25 young people with asthma and separately with their carers. The interviews were analysed using the principles and procedures of grounded theory. RESULTS: Carers reported assessing asthma symptoms through observed effects on the child and other family members, including emotions and behaviours that disrupted family life. Young people emphasised the effect of asthma on their everyday lives and in particular the extent to which they appeared different to their peers. Some young people reported continuing symptoms and restrictions of activity that differed widely from the reports of their carers. CONCLUSION: Differences between young people's and carers' criteria for assessment suggest explanations for some 'non-compliant' behaviour. Carers' assessment of asthma severity through the absence of acute attacks is consistent with managing asthma as intermittent acute episodes. Professionals should take account of differences between young people's, carers' and professionals' perceptions of asthma. PMID:14694693

A Halotyrosine Antibody that Detects Increased Protein Modifications in Asthma Patients

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

Jin, Hongjun; Hallstrand, Teal S.; Daly, Don S.

Background-Airway inflammation plays an important pathophysiological role in asthma. Eosinophils produce hypobromite and bromotyrosine while neutrophils produce hypochlorite and chlorotyrosine. Objective-To evaluate halotyrosine modifications of individual airway proteins as a marker of inflammation in asthma using an antibody-based assay. Methods-We developed a novel monoclonal antibody (BTK-94C) that binds halogenated tyrosine residues, and used this antibody in a custom enzyme-linked immunosorbent assay (ELISA) microarray platform to examine halotyrosine levels in 23 proteins in three independent sets of sputum samples (52 samples total). Results-In 15 subjects with either no asthma, or with asthma characterized by high or low sputum eosinophil counts, wemore » found associations between increased halotyrosine levels of at least three proteins and severity of airway hyperresponsiveness (AHR). Treatment with mepolizumab in 17 patients with sputum eosinophilia markedly reduced the sputum eosinophilia and significantly reduced halotyrosine levels in one sputum protein. Further analysis of 10 subjects with neutrophilic asthma and 10 health controls demonstrated a broad increase in halotyrosine in the patients with airway neutrophilia. Conclusions-Significantly higher levels of halotyrosine are associated with asthma in the asthma phenotypes we examined. The halotyrosine levels correlated with indirect AHR in the form of exercise-induced bronchoconstriction. Clinical Implication-An antibody-based assay for tyrosine halogenation in specific proteins may prove useful for assessing airway inflammation in asthma. Capsule Summary-An antibody to measure protein monobrominated tyrosine and other halotyrosine modifications was developed and used to evaluate halogenation in specific proteins in the airways for the first time. Associations were found between levels of halotyrosine and exercise-induced bronchoconstriction, and eosinophil and neutrophil inflammation in sputum from asthma patients. The ELISA developed here can be easily translated into a clinical test.« less

School-Based Asthma Case Finding: The Arkansas Experience

ERIC Educational Resources Information Center

Vargas, Perla A.; Magee, James S.; Bushmiaer, Margo; Simpson, Pippa M.; Jones, Craig A.; Feild, Charles R.; Jones, Stacie M.

2006-01-01

This population-based case-finding study sought to determine asthma prevalence and characterize disease severity and burden among school-aged children in the Little Rock School District. Asthma cases were identified by validated algorithm and parental report of asthma diagnosis. The overall response rate was low. Among schools with greater than…

Multidisciplinary treatment in children with problematic severe asthma: A prospective evaluation.

PubMed

Verkleij, Marieke; Beelen, Anita; van Ewijk, Bart E; Geenen, Rinie

2017-05-01

For children with problematic severe asthma, achieving adequate control of asthma is difficult. The aim of this prospective observational study was to evaluate the effects of intensive multidisciplinary inpatient treatment on multiple outcome variables in children with problematic severe asthma. Participants were 89 children with problematic severe asthma (mean age 13.6 ± 2.5 years) treated in tertiary care clinics at high altitude (Switzerland) or sea level (Netherlands) and their parents (85 mothers, 55 fathers). The primary outcome variable was the Childhood Asthma Control Test (C-ACT). Other outcome variables were forced expiratory volume in 1 sec (FEV 1 ), fractional concentration of exhaled nitric oxide (FeNO), quality of life [PAQLQ(S)], children's coping (UCL-A), parents' report of behavioral problems (CBCL), and parenting stress (PSI/NOSI). Evaluations were taken pre-treatment, post-treatment, and 3-6 months follow-up. Median [P25;P75] treatment duration 74 [56;80] days; Median follow-up interval 131 [103;177] days. The percentages of children showing controlled asthma (C-ACT) were 18% (pre-treatment), 69% (post-treatment), and 44% (follow-up). The vast majority of the children (80%) showed an improvement on C-ACT with 4% showing a deterioration. On C-ACT, FeNO, quality of life, and behavioral problems, improvements at post-treatment were highly significant. Improvements generally remained at a functional level at follow-up. Children's coping and parenting stress in parents did not change. The improvement in asthma control and other outcome variables suggests that multidisciplinary inpatient treatment is an effective approach for a heterogeneous group of children with asthma that remained uncontrolled in secondary care. Pediatr Pulmonol. 2017;52:588-597. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Integrating asthma hazard characterization methods for consumer products.

PubMed

Maier, A; Vincent, M J; Gadagbui, B; Patterson, J; Beckett, W; Dalton, P; Kimber, I; Selgrade, M J K

2014-10-01

Despite extensive study, definitive conclusions regarding the relationship between asthma and consumer products remain elusive. Uncertainties reflect the multi-faceted nature of asthma (i.e., contributions of immunologic and non-immunologic mechanisms). Many substances used in consumer products are associated with occupational asthma or asthma-like syndromes. However, risk assessment methods do not adequately predict the potential for consumer product exposures to trigger asthma and related syndromes under lower-level end-user conditions. A decision tree system is required to characterize asthma and respiratory-related hazards associated with consumer products. A system can be built to incorporate the best features of existing guidance, frameworks, and models using a weight-of-evidence (WoE) approach. With this goal in mind, we have evaluated chemical hazard characterization methods for asthma and asthma-like responses. Despite the wealth of information available, current hazard characterization methods do not definitively identify whether a particular ingredient will cause or exacerbate asthma, asthma-like responses, or sensitization of the respiratory tract at lower levels associated with consumer product use. Effective use of hierarchical lines of evidence relies on consideration of the relevance and potency of assays, organization of assays by mode of action, and better assay validation. It is anticipated that the analysis of existing methods will support the development of a refined WoE approach. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Asthma history, job type and job changes among US nurses.

PubMed

Dumas, Orianne; Varraso, Raphaëlle; Zock, Jan Paul; Henneberger, Paul K; Speizer, Frank E; Wiley, Aleta S; Le Moual, Nicole; Camargo, Carlos A

2015-07-01

Nurses are at increased risk of occupational asthma, an observation that may be related to disinfectants exposure. Whether asthma history influences job type or job changes among nurses is unknown. We investigated this issue in a large cohort of nurses. The Nurses' Health Study II is a prospective study of US female nurses enrolled in 1989 (ages 24-44 years). Job status and asthma were assessed in biennial (1989-2011) and asthma-specific questionnaires (1998, 2003). Associations between asthma history at baseline (diagnosis before 1989, n=5311) and job type at baseline were evaluated by multinomial logistic regression. The relations of asthma history and severity during follow-up to subsequent job changes were evaluated by Cox models. The analytic cohort included 98 048 nurses. Compared with nurses in education/administration (likely low disinfectant exposure jobs), women with asthma history at baseline were less often employed in jobs with likely high disinfectant exposure, such as operating rooms (odds ratio 0.73 (95% CI 0.63 to 0.86)) and emergency room/inpatient units (0.89 (0.82 to 0.97)). During a 22-year follow-up, nurses with a baseline history of asthma were more likely to move to jobs with lower exposure to disinfectants (HR 1.13 (1.07 to 1.18)), especially among those with more severe asthma (HR for mild persistent: 1.13; moderate persistent 1.26; severe persistent: 1.50, compared with intermittent asthma, p trend: 0.004). Asthma history was associated with baseline job type and subsequent job changes among nurses. This may partly reflect avoidance of tasks involving disinfectant use, and may introduce bias in cross-sectional studies on disinfectant exposure and asthma in nurses. 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.

Outdoor fungi and child asthma health service attendances.

PubMed

Tham, Rachel; Dharmage, Shyamali C; Taylor, Philip E; Katelaris, Constance H; Vicendese, Don; Abramson, Michael J; Erbas, Bircan

2014-08-01

Asthma is a significant global public health issue. Severe asthma exacerbations can be triggered by environmental factors and require medical care from health services. Although it is known that fungal exposure may lead to allergic sensitization, little is understood about its impact on asthma exacerbations. This review aims to examine whether outdoor fungi play a significant role in child asthma exacerbations. Systematic search of seven electronic databases and hand searching for peer-reviewed studies published in English, up to 31 August 2013. Inclusion criteria were study population aged <18 yr, diagnosis of asthma, attended a health service; outdoor fungi exposure was reported. Quality and risk of bias assessments were conducted. Due to significant heterogeneity, meta-analysis was not conducted. Of the 1896 articles found, 15 were eligible. Findings were not consistent, possibly due to methodological variations in exposure classifications, statistical methods and inclusion of confounders. Cross-sectional studies found no or weak associations. All but one time series studies indicated an association that varied between fungal species. Increasing evidence indicates that asthmatic children are susceptible to asthma exacerbations when exposed to outdoor fungal spores. There is limited understanding of the contributions of different fungal species. Research is needed to investigate interactions of outdoor fungi with pollen, air pollutants and respiratory viruses. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Asthma Outcomes: Healthcare Utilization and Costs

PubMed Central

Akinbami, Lara J.; Sullivan, Sean D.; Campbell, Jonathan D.; Grundmeier, Robert W.; Hartert, Tina V.; Lee, Todd A.; Smith, Robert A.

2014-01-01

Background Measures of healthcare utilization and indirect impact of asthma morbidity are used to assess clinical interventions and estimate cost. Objective National Institutes of Health (NIH) institutes and other federal agencies convened an expert group to propose standardized measurement, collection, analysis, and reporting of healthcare utilization and cost outcomes in future asthma studies. Methods We used comprehensive literature reviews and expert opinion to compile a list of asthma healthcare utilization outcomes that we classified as core (required in future studies), supplemental (used according to study aims and standardized) and emerging (requiring validation and standardization). We also have identified methodology to assign cost to these outcomes. This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011. Results We identified 3 ways to promote comparability across clinical trials for measures of healthcare utilization, resource use, and cost: (1) specify the study perspective (patient, clinician, payer, society), (2) standardize the measurement period (ideally, 12 months), and (3) use standard units to measure healthcare utilization and other asthma-related events. Conclusions Large clinical trials and observational studies should collect and report detailed information on healthcare utilization, intervention resources, and indirect impact of asthma, so that costs can be calculated and cost-effectiveness analyses can be conducted across several studies. Additional research is needed to develop standard, validated survey instruments for collection of provider-reported and participant-reported data regarding asthma-related health care. PMID:22386509

Markov Chain-Based Acute Effect Estimation of Air Pollution on Elder Asthma Hospitalization

PubMed Central

Luo, Li; Zhang, Fengyi; Sun, Lin; Li, Chunyang; Huang, Debin; Han, Gao; Wang, Bin

2017-01-01

Background Asthma caused substantial economic and health care burden and is susceptible to air pollution. Particularly, when it comes to elder asthma patient (older than 65), the phenomenon is more significant. The aim of this study is to investigate the Markov-based acute effects of air pollution on elder asthma hospitalizations, in forms of transition probabilities. Methods A retrospective, population-based study design was used to assess temporal patterns in hospitalizations for asthma in a region of Sichuan province, China. Approximately 12 million residents were covered during this period. Relative risk analysis and Markov chain model were employed on daily hospitalization state estimation. Results Among PM2.5, PM10, NO2, and SO2, only SO2 was significant. When air pollution is severe, the transition probability from a low-admission state (previous day) to high-admission state (next day) is 35.46%, while it is 20.08% when air pollution is mild. In particular, for female-cold subgroup, the counterparts are 30.06% and 0.01%, respectively. Conclusions SO2 was a significant risk factor for elder asthma hospitalization. When air pollution worsened, the transition probabilities from each state to high admission states increase dramatically. This phenomenon appeared more evidently, especially in female-cold subgroup (which is in cold season for female admissions). Based on our work, admission amount forecast, asthma intervention, and corresponding healthcare allocation can be done. PMID:29147496

The impact of alexithymia on asthma patient management and communication with health care providers: a pilot study.

PubMed

Chugg, Kelly; Barton, Christopher; Antic, Ral; Crockett, Alan

2009-03-01

Alexithymia is a personality trait associated with difficulty identifying and verbalizing feelings. It has been associated with poorly controlled asthma and near-fatal asthma. The primary objectives were to (1) determine the prevalence of alexithymia in a group of moderate to severe asthmatics who attended an Outpatient Clinic; and (2) investigate the relationship between alexithymia and asthma control, management, and communication. Twenty-five moderate to severe asthma patients were recruited from the Royal Adelaide Hospital Outpatient Respiratory Clinic. Participants were either mailed the questionnaire pack or completed it after a clinic appointment. Existing validated questionnaires were used to collect data. The primary outcome measures were alexithymia, asthma control, adherence to medication; patient satisfaction with communication with health care providers and health-related quality of life. Data were analyzed using Pearson correlations, linear regression and analysis of variance (ANOVA) in SPSS. A p value

Do young adults with childhood asthma avoid occupational exposures at first hire?

PubMed

Dumas, O; Smit, L A M; Pin, I; Kromhout, H; Siroux, V; Nadif, R; Vermeulen, R; Heederik, D; Hery, M; Choudat, D; Kauffmann, F; Le Moual, N

2011-05-01

Information on the healthy worker hire effect in relation to asthma is scant. We aimed to assess whether and how childhood asthma-related characteristics (before hire) relate to occupational exposures at first hire. Analyses were conducted in 298 children examined at the first survey of the Epidemiological Study on the Genetics and Environment of Asthma (1991-1995), who reported a training period or a job at follow-up in 2003-2007 (aged 17-29 yrs; 53% males). Exposure likelihood to dust, gases and/or fumes in their first occupation was estimated by the ALOHA job exposure matrix. Asthma before the first occupation and two asthma classifications for severity (Global Initiative for Asthma 2002 guidelines) and symptoms were defined by questionnaire. In their first job, 47% of subjects were exposed. After adjustment (age, sex and education), pre-hire onset asthmatics (59%) were nonsignificantly less likely to be exposed (OR 0.67, 95% CI 0.41-1.11). Associations were stronger when considering those with severe asthma or high symptom score in childhood (OR 0.27 (95% CI 0.11-0.63) and OR 0.49 (95% CI 0.25-0.99), respectively). The association was observed in those who completed a university degree (OR 0.55, 95% CI 0.29-1.04) but not in the others (OR 0.98, 95% CI 0.44-2.22), with consistent results for all asthma characteristics. Results suggest a healthy worker hire effect in subjects with more severe or more symptomatic asthma in childhood. Education may modulate self-selection.

Sleep-disordered breathing in children with asthma: a systematic review on the impact of treatment.

PubMed

Sánchez, Trinidad; Castro-Rodríguez, José A; Brockmann, Pablo E

2016-01-01

The objective was to perform a systematic review in order to describe the relationship between asthma and sleep-disordered breathing (SDB) in children, especially regarding the impact of treatment and management. We performed an electronic search in MEDLINE, EMBASE, and LILACS database. Study inclusion criteria were the following: 1) studies that examined the relationship between asthma/wheezing and SDB/obstructive sleep apnea (OSA); and 2) studies conducted in children <18 years of age. Primary outcomes were the prevalence of asthma and SDB, the tests used for diagnosis, and the influence of their treatment and management. One thousand and twenty studies were identified, among which 32 were selected (n=143,343 children; 51% males; age [mean ± standard deviation] 8.4±2.5 years). Most studies (n=26) diagnosed SDB using questionnaires or clinical history. Nine studies performed a sleep study for diagnosing OSA. The diagnosis of asthma was based on clinical history (n=16), previous medical diagnosis (n=4), questionnaires (n=12), and spirometry (n=5). Children with asthma were more likely to develop habitual snoring and OSA, and children with SDB were more likely to develop asthma. Moreover, asthma was associated with more severe OSA, and the presence of SDB was associated with severe asthma. Treatment of SDB with adenotonsillectomy was associated with significant asthma improvement. The relationship between asthma and SDB appears to be bidirectional, and adenotonsillectomy appears to improve asthma control. Future trials on how asthma treatment could impact on SDB are needed.

[A case of severe asthma exacerbation complicated with cerebral edema and diffuse multiple cerebral micro-bleeds].

PubMed

Ohkura, Noriyuki; Fujimura, Masaki; Sakai, Asao; Fujita, Kentaro; Katayama, Nobuyuki

2009-08-01

A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of severe asthma exacerbation. Her condition of asthma improved with systemic glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled anesthesia (isoflurane) under mechanical ventilation. Her consciousness was disturbed even after terminating isoflurane. Brain CT and MRI scan showed cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in saline, was administered to decrease cerebral edema. Her consciousness disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the 69th hospital day, she was discharged from hospital without sequelae. This case is a rare one in which severe asthma exacerbation was complicated with cerebral edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma exacerbation should be used carefully to avoid delay of diagnosis of central nervous system complications.

Outdoor air pollution and asthma

PubMed Central

Guarnieri, Michael; Balmes, John R.

2015-01-01

Traffic and power generation are the main sources of urban air pollution. The idea that outdoor air pollution can cause exacerbations of pre-existing asthma is supported by an evidence base that has been accumulating for several decades, with several studies suggesting a contribution to new-onset asthma as well. In this Series paper, we discuss the effects of particulate matter (PM), gaseous pollutants (ozone, nitrogen dioxide, and sulphur dioxide), and mixed traffic-related air pollution. We focus on clinical studies, both epidemiological and experimental, published in the previous 5 years. From a mechanistic perspective, air pollutants probably cause oxidative injury to the airways, leading to inflammation, remodelling, and increased risk of sensitisation. Although several pollutants have been linked to new-onset asthma, the strength of the evidence is variable. We also discuss clinical implications, policy issues, and research gaps relevant to air pollution and asthma. PMID:24792855

Identifying biomarkers for asthma diagnosis using targeted metabolomics approaches.

PubMed

Checkley, William; Deza, Maria P; Klawitter, Jost; Romero, Karina M; Klawitter, Jelena; Pollard, Suzanne L; Wise, Robert A; Christians, Uwe; Hansel, Nadia N

2016-12-01

The diagnosis of asthma in children is challenging and relies on a combination of clinical factors and biomarkers including methacholine challenge, lung function, bronchodilator responsiveness, and presence of airway inflammation. No single test is diagnostic. We sought to identify a pattern of inflammatory biomarkers that was unique to asthma using a targeted metabolomics approach combined with data science methods. We conducted a nested case-control study of 100 children living in a peri-urban community in Lima, Peru. We defined cases as children with current asthma, and controls as children with no prior history of asthma and normal lung function. We further categorized enrollment following a factorial design to enroll equal numbers of children as either overweight or not. We obtained a fasting venous blood sample to characterize a comprehensive panel of targeted markers using a metabolomics approach based on high performance liquid chromatography-mass spectrometry. A statistical comparison of targeted metabolites between children with asthma (n = 50) and healthy controls (n = 49) revealed distinct patterns in relative concentrations of several metabolites: children with asthma had approximately 40-50% lower relative concentrations of ascorbic acid, 2-isopropylmalic acid, shikimate-3-phosphate, and 6-phospho-d-gluconate when compared to children without asthma, and 70% lower relative concentrations of reduced glutathione (all p < 0.001 after Bonferroni correction). Moreover, a combination of 2-isopropylmalic acid and betaine strongly discriminated between children with asthma (2-isopropylmalic acid ≤ 13 077 normalized counts/second) and controls (2-isopropylmalic acid > 13 077 normalized counts/second and betaine ≤ 16 47 121 normalized counts/second). By using a metabolomics approach applied to serum, we were able to discriminate between children with and without asthma by revealing different metabolic patterns. These results suggest that serum metabolomics may represent a diagnostic tool for asthma and may be helpful for distinguishing asthma phenotypes. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Comparative analysis of the effectiveness of different methods of allergen-specific immunotherapy of bronchial asthma].

PubMed

Besh, O M; Radchenko, O M

2014-01-01

The article presents a comparative analysis of the effectiveness of different methods of allergen- specific immunotherapy of light and medium- severe persistent asthma using a special questionnaire of quality of life of patients. It is noted that traditional survey methods involving physical, laboratory and instrumental studies do not give an opportunity to get a complete assessment of the patient, because it does not provide information about its psychological and social adjustment to illness. It is proved that a comprehensive description of the physical, psychological and social components of the patient's condition allows the assessment of its quality of life. Established that chronic asthma affects the quality of life of patients, making certain psychological, emotional and social problems. The disease limits the vitality of patients, their performance, leading to social exclusion and psychological discomfort. Studies have shown that holding the base of treatment with different ways ASIT it positively affects the quality of life for patients. However, treatment of sublingual allergen patients perceive better adherence to such treatment was higher.

Innate lymphoid cells and asthma.

PubMed

Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

2014-04-01

Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Markers of Vascular Perturbation Correlate with Airway Structural Change in Asthma

PubMed Central

Kruger, Stanley J.; Schiebler, Mark L.; Evans, Michael D.; Sorkness, Ronald L.; Denlinger, Loren C.; Busse, William W.; Jarjour, Nizar N.; Montgomery, Robert R.; Mosher, Deane F.; Fain, Sean B.

2013-01-01

Rationale: Air trapping and ventilation defects on imaging are characteristics of asthma. Airway wall thickening occurs in asthma and is associated with increased bronchial vascularity and vascular permeability. Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma. Objectives: Determine whether reporters of vascular endothelial cell perturbation correlate with airway imaging metrics in patients with asthma of varying severity. Methods: Plasma from Severe Asthma Research Program subjects was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag) and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects were analyzed over 48 hours after whole-lung antigen challenge. We calculated ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging and areas of low signal density by multidetector computed tomography (less than −856 Hounsfield units [HU] at functional residual capacity and −950 HU at total lung capacity [TLC]). Measurements and Main Results: VWFpp and VWFpp/Ag ratio correlated with and predicted greater percentage defect volume on hyperpolarized helium-3 magnetic resonance imaging. P-selectin correlated with and predicted greater area of low density on chest multidetector computed tomography less than −950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was less than that among subjects, indicating stability and repeatability of the measurements. Conclusions: Plasma VWFpp and P-selectin may be useful as surrogates of functional and structural defects that are evident on imaging. The results raise important questions about why VWFpp and P-selectin are associated specifically with different imaging abnormalities. PMID:23855693

Triple selectin knockout (ELP-/-) mice fail to develop OVA-induced acute asthma phenotype

PubMed Central

2011-01-01

Objective The recruitment of leukocytes from circulation to sites of inflammation requires several families of adhesion molecules among which are selectins expressed on a variety of cells. In addition, they have also been shown to play key roles in the activation of cells in inflammation. Methods To explore the collective role of E-, L-, and P- selectins in OVA-induced Th2 mediated response in acute asthma pathophysiology, ELP-/- mice were used and compared with age-matched wildtype (WT). Results Asthma phenotype was assessed by measuring pulmonary function, inflammation and OVA-specific serum IgE, which were completely abrogated in ELP-/- mice. Adoptive transfer of sensitized L selectin+CD4+ T cells into naïve ELP-/- mice which post-OVA challenge, developed asthma, suggesting that L-selectin may be critically involved in the onset of Th2 response in asthma. Tissue resident ELP-deficient cells were otherwise functionally competent as proved by normal proliferative response. Conclusions: Comparative studies between ELP-/- and WT mice uncovered functional roles of these three integrins in inflammatory response in allergic asthma. All three selectins seem to impede inflammatory migration while only L-selectin also possibly regulates activation of specific T cell subsets in lung and airways. PMID:21835035

Identifying the heterogeneity of young adult rhinitis through cluster analysis in the Isle of Wight birth cohort.

PubMed

Kurukulaaratchy, Ramesh J; Zhang, Hongmei; Patil, Veeresh; Raza, Abid; Karmaus, Wilfried; Ewart, Susan; Arshad, S Hasan

2015-01-01

Rhinitis affects many young adults and often shows comorbidity with asthma. We hypothesized that young adult rhinitis, like asthma, exhibits clinical heterogeneity identifiable by means of cluster analysis. Participants in the Isle of Wight birth cohort (n = 1456) were assessed at 1, 2, 4, 10, and 18 years of age. Cluster analysis was performed on those with rhinitis at age 18 years (n = 468) by using 13 variables defining clinical characteristics. Four clusters were identified. Patients in cluster 1 (n = 128 [27.4%]; ie, moderate childhood-onset rhinitis) had high atopy and eczema prevalence and high total IgE levels but low asthma prevalence. They showed the best lung function at 18 years of age, with normal fraction of exhaled nitric oxide (Feno), low bronchial hyperresponsiveness (BHR), and low bronchodilator reversibility (BDR) but high rhinitis symptoms and treatment. Patients in cluster 2 (n = 199 [42.5%]; ie, mild-adolescence-onset female rhinitis) had the lowest prevalence of comorbid atopy, asthma, and eczema. They had normal lung function and low BHR, BDR, Feno values, and total IgE levels plus low rhinitis symptoms, severity, and treatment. Patients in cluster 3 (n = 59 [12.6%]; ie, severe earliest-onset rhinitis with asthma) had the youngest rhinitis onset plus the highest comorbid asthma (of simultaneous onset) and atopy. They showed the most obstructed lung function with high BHR, BDR, and Feno values plus high rhinitis symptoms, severity, and treatment. Patient 4 in cluster 4 (n = 82 [17.5%]; ie, moderate childhood-onset male rhinitis with asthma) had high atopy, intermediate asthma, and low eczema. They had impaired lung function with high Feno values and total IgE levels but intermediate BHR and BDR. They had moderate rhinitis symptoms. Clinically distinctive adolescent rhinitis clusters are apparent with varying sex and asthma associations plus differing rhinitis severity and treatment needs. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Asthma, hay fever, and food allergy are associated with caregiver-reported speech disorders in US children.

PubMed

Strom, Mark A; Silverberg, Jonathan I

2016-09-01

Children with asthma, hay fever, and food allergy may have several factors that increase their risk of speech disorder, including allergic inflammation, ADD/ADHD, and sleep disturbance. However, few studies have examined a relationship between asthma, allergic disease, and speech disorder. We sought to determine whether asthma, hay fever, and food allergy are associated with speech disorder in children and whether disease severity, sleep disturbance, or ADD/ADHD modified such associations. We analyzed cross-sectional data on 337,285 children aged 2-17 years from 19 US population-based studies, including the 1997-2013 National Health Interview Survey and the 2003/4 and 2007/8 National Survey of Children's Health. In multivariate models, controlling for age, demographic factors, healthcare utilization, and history of eczema, lifetime history of asthma (odds ratio [95% confidence interval]: 1.18 [1.04-1.34], p = 0.01), and one-year history of hay fever (1.44 [1.28-1.62], p < 0.0001) and food allergy (1.35 [1.13-1.62], p = 0.001) were associated with increased odds of speech disorder. Children with current (1.37 [1.15-1.59] p = 0.0003) but not past (p = 0.06) asthma had increased risk of speech disorder. In one study that assessed caregiver-reported asthma severity, mild (1.58 [1.20-2.08], p = 0.001) and moderate (2.99 [1.54-3.41], p < 0.0001) asthma were associated with increased odds of speech disorder; however, severe asthma was associated with the highest odds of speech disorder (5.70 [2.36-13.78], p = 0.0001). Childhood asthma, hay fever, and food allergy are associated with increased risk of speech disorder. Future prospective studies are needed to characterize the associations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Budesonide nebulization added to systemic prednisolone in the treatment of acute asthma in children: a double-blind, randomized, controlled trial.

PubMed

Alangari, Abdullah A; Malhis, Nidal; Mubasher, Mohamed; Al-Ghamedi, Najwa; Al-Tannir, Mohamad; Riaz, Muhammad; Umetsu, Dale T; Al-Tamimi, Saleh

2014-04-01

Inhaled corticosteroids, known to be effective as a maintenance medication in chronic asthma, have also been suggested as a therapy for acute asthma when given at high doses. A double-blind, randomized, placebo-controlled trial was conducted in children aged 2 to 12 years with moderate or severe acute asthma, as determined based on a clinical score of 5 to 15 points, where 15 is the most severe. We compared the addition of budesonide 1,500 μg vs placebo to standard acute asthma treatment, which included salbutamol, ipratropium bromide, and a single dose of prednisolone 2 mg/kg given at the beginning of therapy. The primary outcome was hospital admission rate within 4 h. A total of 906 ED visits by children with moderate or severe acute asthma were evaluated. Seventy-five cases out of 458 (16.4%) in the budesonide group vs 82 of 448 (18.3%) in the placebo group were admitted (OR, 0.84; 95% CI, 0.58-1.23; P=.38). However, among cases with high baseline clinical score (≥13), significantly fewer children were admitted in the budesonide group (27 of 76 [35.5%]) than in the placebo group (39 of 73 [53.4%]; OR, 0.42; 95% CI, 0.19-0.94; P=.03). The addition of budesonide nebulization did not decrease the admission rate of children with acute asthma overall. However, it may decrease the admission rate of children with severe acute asthma. ClinicalTrials.gov; No.: NCT01524198; URL: www.clinicaltrials.gov

Whole genome prediction and heritability of childhood asthma phenotypes.

PubMed

McGeachie, Michael J; Clemmer, George L; Croteau-Chonka, Damien C; Castaldi, Peter J; Cho, Michael H; Sordillo, Joanne E; Lasky-Su, Jessica A; Raby, Benjamin A; Tantisira, Kelan G; Weiss, Scott T

2016-12-01

While whole genome prediction (WGP) methods have recently demonstrated successes in the prediction of complex genetic diseases, they have not yet been applied to asthma and related phenotypes. Longitudinal patterns of lung function differ between asthmatics, but these phenotypes have not been assessed for heritability or predictive ability. Herein, we assess the heritability and genetic predictability of asthma-related phenotypes. We applied several WGP methods to a well-phenotyped cohort of 832 children with mild-to-moderate asthma from CAMP. We assessed narrow-sense heritability and predictability for airway hyperresponsiveness, serum immunoglobulin E, blood eosinophil count, pre- and post-bronchodilator forced expiratory volume in 1 sec (FEV 1 ), bronchodilator response, steroid responsiveness, and longitudinal patterns of lung function (normal growth, reduced growth, early decline, and their combinations). Prediction accuracy was evaluated using a training/testing set split of the cohort. We found that longitudinal lung function phenotypes demonstrated significant narrow-sense heritability (reduced growth, 95%; normal growth with early decline, 55%). These same phenotypes also showed significant polygenic prediction (areas under the curve [AUCs] 56% to 62%). Including additional demographic covariates in the models increased prediction 4-8%, with reduced growth increasing from 62% to 66% AUC. We found that prediction with a genomic relatedness matrix was improved by filtering available SNPs based on chromatin evidence, and this result extended across cohorts. Longitudinal reduced lung function growth displayed extremely high heritability. All phenotypes with significant heritability showed significant polygenic prediction. Using SNP-prioritization increased prediction across cohorts. WGP methods show promise in predicting asthma-related heritable traits.

Pregnancy-associated plasma protein-A (PAPP-A) levels in patients with severe allergic asthma are reduced by omalizumab.

PubMed

Bulut, Ismet; Ozseker, Zeynep F; Coskun, Abdurrahman; Serteser, Mustafa; Unsal, Ibrahim

2017-12-06

Remodeling is a crucial feature of severe asthma and may be associated with activation of the allergic cascade by immunoglobulin E (IgE). Omalizumab, an anti-IgE monoclonal antibody, effectively targets the severe allergic asthma phenotype. Pregnancy-associated plasma protein-A (PAPP-A) is an insulin-like growth factor binding protein-4 (IGFBP-4) protease, increasing local insulin-like growth factor (IGF)-1 concentrations, which in turn initiating a cascade involved in the regulation of cell growth, differentiation, and proliferation in various tissues. In the present study, we evaluated the effects of omalizumab on serum PAPP-A, IGFBP-4, and IGF-1 levels in subjects with severe allergic asthma. We studied 36 asthmatic subjects and 36 healthy controls. An ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit was used to measure serum PAPP-A levels, and routine commercial ELISA kits were employed to assess serum levels of IGF-1, IGFBP-4 in control subjects and asthmatic subjects before therapy (baseline) and after six months of omalizumab therapy in patients with severe asthma. Compared to control subjects, serum PAPP-A and IGFB-4 levels were significantly higher in asthmatic subjects (both p values < 0.001). However, the serum IGF-I levels of asthmatic subjects were similar to those of control subjects (p > 0.05). In asthma subjects, 6-month omalizumab treatment significantly decreased the serum PAPP-A (p < 0.001), IGF-I (p = 0.031), and IGFB4 (p = 0.025) levels. PAPP-A level may be a useful biomarker for predicting airway remodeling in patients with severe asthma receiving omalizumab, and may also reflect the response to treatment.

Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies.

PubMed

Chupp, Geoffrey; Laviolette, Michel; Cohn, Lauren; McEvoy, Charlene; Bansal, Sandeep; Shifren, Adrian; Khatri, Sumita; Grubb, G Mark; McMullen, Edmund; Strauven, Racho; Kline, Joel N

2017-08-01

Bronchial thermoplasty is an endoscopic therapy for severe asthma. The previously reported, randomised sham-controlled AIR2 (Asthma Intervention Research 2) trial showed a significant reduction in severe asthma exacerbations, emergency department visits and hospitalisations after bronchial thermoplasty. More "real-world" clinical outcome data is needed.This article compares outcomes in bronchial thermoplasty subjects with 3 years of follow-up from the ongoing, post-market PAS2 (Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma) study with those from the AIR2 trial.279 subjects were treated with bronchial thermoplasty in the PAS2 study. We compared the first 190 PAS2 subjects with the 190 bronchial thermoplasty-treated subjects in the AIR2 trial at 3 years of follow-up. The PAS2 subjects were older (mean age 45.9 versus 40.7 years) and more obese (mean body mass index 32.5 versus 29.3 kg·m -2 ) and took higher doses of inhaled corticosteroids (mean dose 2301 versus 1961 μg·day -1 ). More PAS2 subjects had experienced severe exacerbations (74% versus 52%) and hospitalisations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty. At year 3 after bronchial thermoplasty, the percentage of PAS2 subjects with severe exacerbations, emergency department visits and hospitalisations significantly decreased by 45%, 55% and 40%, respectively, echoing the AIR2 results.The PAS2 study demonstrates similar improvements in asthma control after bronchial thermoplasty compared with the AIR2 trial despite enrolling subjects who may have had poorer asthma control. Copyright ©ERS 2017.

Evaluation of the use of Swedish integrated electronic health records and register health care data as support clinical trials in severe asthma: the PACEHR study.

PubMed

Franzén, Stefan; Janson, Christer; Larsson, Kjell; Petzold, Max; Olsson, Urban; Magnusson, Gunnar; Telg, Gunilla; Colice, Gene; Johansson, Gunnar; Sundgren, Mats

2016-11-15

In the development of new drugs for severe asthma, it is a challenge from an ethical point of view to randomize severe asthma patients to placebo, and to obtain long-term safety data due to discontinuations. The aim of this study was to evaluate the feasibility of using electronic health record (EHR) data to create a real-world reference population of uncontrolled asthmatic patients to supplement the concurrent control/placebo group in long-term studies of asthma. EHR data from 36 primary care centres and a University hospital in Sweden were linked to Swedish mandatory health registers (2005-2013), creating a population covering 33 890 asthma patients, including data on co-morbidities, risk factors and laboratory/respiratory measurements. A severe asthma EHR reference cohort was established. We used logistic regression to estimate the propensity score (probability) of each RCT or EHR patient existing in the EHR cohort given their covariates. We created an EHR-derived reference cohort of 240 patients, matching the placebo group (N = 151) in an RCT of severe asthma. The exacerbation rate during follow-up in the EHR study population was 1.24 (weighted) compared to 0.9 in the RCT placebo group. Patients in the EHR cohort were of similar age as in the RCT placebo group, 50.6 years versus 50.1 years; had slightly higher body mass index 27.0 kg/m 2 versus 27.3 kg/m 2 ; and consisted of 40% versus 34% males. The results indicate that EHRs provide an opportunity to supplement the control group in RCTs of severe diseases.

Different effects of long-term exposures to SO2 and NO2 air pollutants on asthma severity in young adults.

PubMed

Greenberg, Nili; Carel, Rafael S; Derazne, Estela; Bibi, Haim; Shpriz, Manor; Tzur, Dorit; Portnov, Boris A

2016-01-01

Numerous studies demonstrated that exposure to ambient air pollutants contributes to severity and frequency of asthma exacerbations. However, whether common air pollutants, such as nitrogen dioxide (NO2) and sulfur dioxide (SO2), exert differential effects on asthma occurrence and severity is unclear. The aim of this investigation was to determine whether exposure to NO2 and/or SO2 may initiate different long-term effects on prevalence and severity of asthma in young adults. Medical records of 137,040 males, 17 years old, who underwent standard premilitary service health examinations during 1999-2008 were examined. Air-pollution data for NO2 and SO2 were linked to the place of residence of each subject. The influence of specific air pollutants on asthma prevalence and severity was evaluated using bivariate logistic regression, controlling for individuals' sociodemographic attributes. For both ambient air pollutants, there was a significant dose-response effect on severity of asthma at ambient concentrations below the current National Ambient Air Quality Standards. However, in residential areas with high levels of SO2 (13.3-592.7µg/m(3)) and high levels of NO2 (27.2-43.2µg/m(3)) the risk of asthma occurrence was significantly higher than that in residential areas with high levels of NO2 (27.2-43.2 µg/m(3)) and intermediate levels (6.7-13.3 µg/m(3)) of SO2 pollution. The effects of exposure to SO2 and NO2 air pollutants on the respiratory airways system appear to differ, with possible implications regarding medical management, even in cases of exposure to mixtures of these pollutants.

Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies

PubMed Central

Laviolette, Michel; Cohn, Lauren; McEvoy, Charlene; Bansal, Sandeep; Shifren, Adrian; Khatri, Sumita; Grubb, G. Mark; McMullen, Edmund; Strauven, Racho; Kline, Joel N.

2017-01-01

Bronchial thermoplasty is an endoscopic therapy for severe asthma. The previously reported, randomised sham-controlled AIR2 (Asthma Intervention Research 2) trial showed a significant reduction in severe asthma exacerbations, emergency department visits and hospitalisations after bronchial thermoplasty. More “real-world” clinical outcome data is needed. This article compares outcomes in bronchial thermoplasty subjects with 3 years of follow-up from the ongoing, post-market PAS2 (Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma) study with those from the AIR2 trial. 279 subjects were treated with bronchial thermoplasty in the PAS2 study. We compared the first 190 PAS2 subjects with the 190 bronchial thermoplasty-treated subjects in the AIR2 trial at 3 years of follow-up. The PAS2 subjects were older (mean age 45.9 versus 40.7 years) and more obese (mean body mass index 32.5 versus 29.3 kg·m−2) and took higher doses of inhaled corticosteroids (mean dose 2301 versus 1961 μg·day−1). More PAS2 subjects had experienced severe exacerbations (74% versus 52%) and hospitalisations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty. At year 3 after bronchial thermoplasty, the percentage of PAS2 subjects with severe exacerbations, emergency department visits and hospitalisations significantly decreased by 45%, 55% and 40%, respectively, echoing the AIR2 results. The PAS2 study demonstrates similar improvements in asthma control after bronchial thermoplasty compared with the AIR2 trial despite enrolling subjects who may have had poorer asthma control. PMID:28860266

Household mold and dust allergens: Exposure, sensitization and childhood asthma morbidity

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

Gent, Janneane F., E-mail: janneane.gent@yale.edu; Kezik, Julie M., E-mail: julie.colburn@yale.edu; Hill, Melissa E., E-mail: melissa.hill@yale.edu

Background: Few studies address concurrent exposures to common household allergens, specific allergen sensitization and childhood asthma morbidity. Objective: To identify levels of allergen exposures that trigger asthma exacerbations in sensitized individuals. Methods: We sampled homes for common indoor allergens (fungi, dust mites (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1) and cockroach (Bla g 1)) for levels associated with respiratory responses among school-aged children with asthma (N=1233) in a month-long study. Blood samples for allergy testing and samples of airborne fungi and settled dust were collected at enrollment. Symptoms and medication use were recordedmore » on calendars. Combined effects of specific allergen sensitization and level of exposure on wheeze, persistent cough, rescue medication use and a 5-level asthma severity score were examined using ordered logistic regression. Results: Children sensitized and exposed to any Penicillium experienced increased risk of wheeze (odds ratio [OR] 2.12 95% confidence interval [CI] 1.12, 4.04), persistent cough (OR 2.01 95% CI 1.05, 3.85) and higher asthma severity score (OR 1.99 95% CI 1.06, 3.72) compared to those not sensitized or sensitized but unexposed. Children sensitized and exposed to pet allergen were at significantly increased risk of wheeze (by 39% and 53% for Fel d 1>0.12 {mu}g/g and Can f 1>1.2 {mu}g/g, respectively). Increased rescue medication use was significantly associated with sensitization and exposure to Der p 1>0.10 {mu}g/g (by 47%) and Fel d 1>0.12 {mu}g/g (by 32%). Conclusion: Asthmatic children sensitized and exposed to low levels of common household allergens Penicillium, Der p 1, Fel d 1 and Can f 1 are at significant risk for increased morbidity. - Highlights: Black-Right-Pointing-Pointer Few studies address concurrent allergen exposures, sensitization and asthma morbidity. Black-Right-Pointing-Pointer Children with asthma were tested for sensitivity to common indoor allergens. Black-Right-Pointing-Pointer Homes were sampled for these allergens and asthma morbidity monitored during the subsequent month. Black-Right-Pointing-Pointer Children exposed and sensitized to Penicillium, Der p, Fel d, Can f risk increased asthma morbidity. Black-Right-Pointing-Pointer These children might benefit from targeted intervention strategies.« less

The asthma ePrompt: a novel electronic solution for chronic disease management.

PubMed

Lim, Kaiser G; Rank, Matthew A; Cabanela, Rosa L; Furst, Joseph W; Rohrer, James E; Liesinger, Juliette; Muller, Lisa; Wagie, Amy E; Naessens, James M

2012-03-01

This study tested the ability of an electronic prompt to promote an asthma assessment during primary care visits. We performed a prospective study of all eligible adult patients with previously diagnosed asthma in three geographically distinct ambulatory family medicine clinics within a 4-month period. The usual clinic visit process was performed at two geographically distinct control sites (n = 75 and n = 55 patients, respectively). The intervention group site (n = 64) had an electronic flag embedded in the Patient Check-in Locator field which prompted the distribution of a self-administered Asthma Management Questionnaire (AMQ) in the waiting room. The primary outcome measure was a documented asthma severity assessment. The front desk distributed the AMQ successfully in 100% of possible opportunities and the AMQ was completed by 84% of patients. Providers in the intervention group were significantly more likely than providers in the two non-intervention groups to document asthma severity in the medical record during a non-asthma ambulatory clinic visit (63.3% vs. 18.7% vs. 3.6%; p < .001). The provision of standardized asthma information triggered by an electronic prompt at the time of check-in effectively initiates an asthma assessment during the primary care visits.

A Biobehavioral Approach to Managing Childhood Asthma.

ERIC Educational Resources Information Center

Kohen, Daniel P.

1987-01-01

Describes childhood asthma and a program which teaches relaxation and mental imagery (RMI) exercises to children and adolescents as an adjunct in the management of asthma. Clinical experience indicates children who learn RMI rate their asthma as significantly reduced in severity, miss fewer days of school, and make fewer visits to emergency rooms.…

The Influence of Health Education on Family Management of Childhood Asthma.

ERIC Educational Resources Information Center

Brazil, Kevin; McLean, Leslie; Abbey, David; Musselman, Carol

1997-01-01

Differences in asthma management among families with a child who has moderate to severe asthma were examined when they participated in an in-patient versus a day-camp program. Two broad categories of outcome were examined: illness and self-management skills. Findings and observations regarding children's feelings about asthma are discussed.…

Asthma Status and Severity Affects Missed School Days

ERIC Educational Resources Information Center

Moonie, Sheniz A.; Sterling, David A.; Figgs, Larry; Castro, Mario

2006-01-01

Excessive school absence disrupts learning and is a strong predictor of premature school dropout. School-aged children with asthma are absent more often compared to their healthy peers without asthma; yet, the causes are inadequately documented. We sought to determine the difference in mean absence days between children with and without asthma,…

The Asthma Mobile Health Study, a large-scale clinical observational study using ResearchKit

PubMed Central

Chan, Yu-Feng Yvonne; Wang, Pei; Rogers, Linda; Tignor, Nicole; Zweig, Micol; Hershman, Steven G; Genes, Nicholas; Scott, Erick R; Krock, Eric; Badgeley, Marcus; Edgar, Ron; Violante, Samantha; Wright, Rosalind; Powell, Charles A; Dudley, Joel T; Schadt, Eric E

2017-01-01

The feasibility of using mobile health applications to conduct observational clinical studies requires rigorous validation. Here, we report initial findings from the Asthma Mobile Health Study, a research study, including recruitment, consent, and enrollment, conducted entirely remotely by smartphone. We achieved secure bidirectional data flow between investigators and 7,593 participants from across the United States, including many with severe asthma. Our platform enabled prospective collection of longitudinal, multidimensional data (e.g., surveys, devices, geolocation, and air quality) in a subset of users over the 6-month study period. Consistent trending and correlation of interrelated variables support the quality of data obtained via this method. We detected increased reporting of asthma symptoms in regions affected by heat, pollen, and wildfires. Potential challenges with this technology include selection bias, low retention rates, reporting bias, and data security. These issues require attention to realize the full potential of mobile platforms in research and patient care. PMID:28288104

Short-term ozone exposure and asthma severity: Weight-of-evidence analysis.

PubMed

Goodman, Julie E; Zu, Ke; Loftus, Christine T; Lynch, Heather N; Prueitt, Robyn L; Mohar, Isaac; Shubin, Sara Pacheco; Sax, Sonja N

2018-01-01

To determine whether evidence indicates that short-term exposure to ambient concentrations of ozone in the United States can affect asthma severity, we systematically reviewed published controlled human exposure, epidemiology, and animal toxicity studies. The strongest evidence for a potential causal relationship came from epidemiology studies reporting increased emergency department visits and hospital admissions for asthma following elevated ambient ozone concentrations. However, while controlled exposure studies reported lung function decrements and increased asthma symptoms following high ozone exposures 160-400 parts per billion [ppb]), epidemiology studies evaluating similar outcomes reported less consistent results. Animal studies showed changes in pulmonary function at high ozone concentrations (> 500ppb), although there is substantial uncertainty regarding the relevance of these animal models to human asthma. Taken together, the weight of evidence indicates that there is at least an equal likelihood that either explanation is true, i.e., the strength of the evidence for a causal relationship between short-term exposure to ambient ozone concentrations and asthma severity is "equipoise and above." Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical ventilation for severe asthma.

PubMed

Leatherman, James

2015-06-01

Acute exacerbations of asthma can lead to respiratory failure requiring ventilatory assistance. Noninvasive ventilation may prevent the need for endotracheal intubation in selected patients. For patients who are intubated and undergo mechanical ventilation, a strategy that prioritizes avoidance of ventilator-related complications over correction of hypercapnia was first proposed 30 years ago and has become the preferred approach. Excessive pulmonary hyperinflation is a major cause of hypotension and barotrauma. An appreciation of the key determinants of hyperinflation is essential to rational ventilator management. Standard therapy for patients with asthma undergoing mechanical ventilation consists of inhaled bronchodilators, corticosteroids, and drugs used to facilitate controlled hypoventilation. Nonconventional interventions such as heliox, general anesthesia, bronchoscopy, and extracorporeal life support have also been advocated for patients with fulminant asthma but are rarely necessary. Immediate mortality for patients who are mechanically ventilated for acute severe asthma is very low and is often associated with out-of-hospital cardiorespiratory arrest before intubation. However, patients who have been intubated for severe asthma are at increased risk for death from subsequent exacerbations and must be managed accordingly in the outpatient setting.

Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma.

PubMed

Agrawal, Swati; Townley, Robert G

2014-02-01

Asthma markedly diminishes quality of life due to limited activity, absences from work or school and hospitalizations. Patients with severe asthma which are not controlled despite taking effective therapy are most in need of new treatment approaches. IL-13 was demonstrated as 'central mediator of allergic asthma'. IL-13 has been implicated in the pathogenesis of asthma, idiopathic pulmonary fibrosis and COPD. IL-13 levels in the sputum and bronchial biopsy samples remain elevated in severe asthma despite the use of inhaled and systemic corticosteroids. Thus, IL-13 is a mediator involved in corticosteroid resistance. Periostin enhances profibrotic TGF-β signaling in subepithelial fibrosis associated with asthma. IL-13 induces bronchial epithelial cells to secrete periostin. Periostin may be a biomarker for Th2 induced airway inflammation. Lebrikizumab is a monoclonal antibody against IL-13. Lebrikizumab improved lung function in asthmatics who were symptomatic despite treatment with long acting beta agonist and inhaled corticosteroids and provided benefit in the treatment of severe uncontrolled asthma. Lebrikizumab block IL-13 signaling through the IL-13Rα1/IL-4Rα receptor. There was a larger reduction in FENO in the high periostin subgroup than in the low periostin subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the lebrikizumab group.

Respiratory reviews in asthma 2013.

PubMed

Kim, Tae-Hyung

2014-03-01

From January 2012 up until March 2013, many articles with huge clinical importance in asthma were published based on large numbered clinical trials or meta-analysis. The main subjects of these studies were the new therapeutic plan based on the asthma phenotype or efficacy along with the safety issues regarding the current treatment guidelines. For efficacy and safety issues, inhaled corticosteroid tapering strategy or continued long-acting beta agonists use was the major concern. As new therapeutic trials, monoclonal antibodies or macrolide antibiotics based on inflammatory phenotypes have been under investigation, with promising preliminary results. There were other issues on the disease susceptibility or genetic background of asthma, particularly for the "severe asthma" phenotype. In the era of genome and pharmacogenetics, there have been extensive studies to identify susceptible candidate genes based on the results of genome wide association studies (GWAS). However, for severe asthma, which is where most of the mortality or medical costs develop, it is very unclear. Moreover, there have been some efforts to find important genetic information in order to predict the possible disease progression, but with few significant results up until now. In conclusion, there are new on-going aspects in the phenotypic classification of asthma and therapeutic strategy according to the phenotypic variations. With more pharmacogenomic information and clear identification of the "severe asthma" group even before disease progression from GWAS data, more adequate and individualized therapeutic strategy could be realized in the future.

CDC Vital Signs: Asthma in the US

MedlinePlus

... for people with asthma. Promote improvements in indoor air quality for people with asthma through measures such as ... healthy schools and workplaces, and improvements in outdoor air quality. Health care providers can Determine the severity of ...

Myocardial ischemia induced by nebulized fenoterol for severe childhood asthma.

PubMed

Zanoni, L Z; Palhares, D B; Consolo, L C T

2005-10-01

We examined for myocardial ischemia induced by continuous inhalation of fenoterol in children with severe acute asthma. Thirty children with severe acute asthma were evaluated for signs of myocardial ischemia when treated with 0.5 mg kg dose (maximum 15 mg) of inhaled fenoterol for one hour. The heart rate was measured before and after inhalation. Cardiac enzymes (creatine kinase, creatine kinase MB fraction and troponin levels) were measured at admission and 12 hours later. An EKG was recorded before inhalation was started and immediately after its completion to detect the presence of any evidence of myocardial ischemia. All patients developed significant increase in heart rate. Six patients showed EKG changes compatible with myocardial ischemia, despite normal enzyme levels. Patients with severe acute asthma show tachycardia and may show EKG changes of myocardial ischemia.

Vaccines: could asthma in young children be a preventable disease? ‬‬‬‬‬‬‬.

PubMed

Elenius, Varpu; Jartti, Tuomas

2016-11-01

‬The long battle with asthma is far from over in developed countries. Its incidence, prevalence, and severity have been increasing for decades. By reducing the risk for asthma, significant healthcare costs can be saved. The desire to create a vaccine that might prevent asthma in young children is attractive and widely considered one of the main goals in translational asthma research. Several vaccination strategies have been tested. These include allergen-specific immunotherapy, vaccination against infectious pathogens, and modification of cell and cytokine responses. The lack of success in the prevention of asthma in young children lies on the complexity of the disease, which involves many genetic, epigenetic, and environmental interactions. This review provides a summary of current literature and aims to address key questions how to develop vaccines to prevent asthma in young children. ‬‬‬‬‬‬‬‬‬‬‬‬‬‬. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aryl Hydrocarbon Receptor activation by diesel exhaust particles mediates epithelium-derived cytokines expression in severe allergic asthma.

PubMed

Weng, Chih-Ming; Wang, Chun-Hua; Lee, Meng-Jung; He, Jung-Re; Huang, Hsin-Yu; Chao, Ming-Wei; Chung, Kian Fan; Kuo, Han-Pin

2018-04-19

Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium-derived thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma. Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation (NT), cytokine expression and gene activation. Cultured primary epithelial cells were stimulated with diesel exhausted particles (DEP) to determine AhR-mediated IL-33, Il-25 and TSLP synthesis and release. Primary bronchial epithelial cells exposed to DEP showed up-regulation of IL-33, IL-25 and TSLP. These effects were abolished by knock-down of AhR by siRNA. Increased AhR/ARNT binding to promoters of IL-33, IL-25, and TSLP was found using chromatin immunoprecipitation (ChIP) assay. Allergic severe asthma with high AhR NT had higher bronchial gene and protein expression of IL-33, IL-25 and TSLP. These patients derived clinical benefit from anti-IgE treatment. AhR activation by DEP mediates up-regulation of IL-33, IL-25 and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Impact of Goal Setting and Goal Attainment Methods on Asthma Outcomes: Findings From an Asthma Self-Management Intervention for African American Women

ERIC Educational Resources Information Center

Aaron, Micah; Nelson, Belinda W.; Kaltsas, Elena; Brown, Randall W.; Thomas, Lara J.; Patel, Minal R.

2017-01-01

Optimal use of goal-setting strategies in self-management efforts with high-risk individuals with asthma is not well understood. This study aimed to describe factors associated with goal attainment in an asthma self-management intervention for African American women with asthma and determine whether goal attainment methods proved beneficial to…

Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

PubMed

Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

2011-02-01

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

Association between Electronic Cigarette Use and Asthma among High School Students in South Korea

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

Cho, Jun Ho; Paik, Samuel Y.

Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma. The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student’s self-reported doctor diagnosis of asthma in the past 12 months. Results showed prevalence rates of asthmatics in ‘current EC users’ (n = 2,513), ‘former EC users’ (n = 2,078), and ‘never EC users’ (n = 31,313), were 3.9% (nmore » = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing ‘current EC’ users with ‘never EC’ users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89–2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the ‘never CC’ category, the unadjusted OR for asthma for ‘current EC’ users was 3.41 (95% CI: 1.79–6.49), and the adjusted OR was 2.74 (95% CI: 1.30–5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to ‘never EC’ users. In conclusion, when compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC.« less

Association between Electronic Cigarette Use and Asthma among High School Students in South Korea

DOE PAGES

Cho, Jun Ho; Paik, Samuel Y.

2016-03-04

Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma. The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student’s self-reported doctor diagnosis of asthma in the past 12 months. Results showed prevalence rates of asthmatics in ‘current EC users’ (n = 2,513), ‘former EC users’ (n = 2,078), and ‘never EC users’ (n = 31,313), were 3.9% (nmore » = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing ‘current EC’ users with ‘never EC’ users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89–2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the ‘never CC’ category, the unadjusted OR for asthma for ‘current EC’ users was 3.41 (95% CI: 1.79–6.49), and the adjusted OR was 2.74 (95% CI: 1.30–5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to ‘never EC’ users. In conclusion, when compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC.« less

Progression to Uncontrolled Severe Asthma: A Novel Risk Equation.

PubMed

Casciano, Julian; Krishnan, Jerry; Small, Mary Buatti; Li, Chenghui; Dotiwala, Zenobia; Martin, Bradley C

2017-01-01

Recently published asthma guidelines by the European Respiratory Society and the American Thoracic Society (ERS-ATS) define severe disease based on medication use and control level. These guidelines also emphasize that asthma severity involves certain biomarker phenotypes, one of them being eosinophilic phenotype. The quantification of the influence of eosinophil level toward predicting disease severity can help decision makers manage therapy better earlier. To develop a risk-scoring algorithm to identify patients at greater risk of developing uncontrolled severe asthma as defined by ERS-ATS guidelines. Data on asthma patients were extracted from the EMRClaims + database from January 2004 to July 2011. Patients with continuous enrollment 12 months before and after the date of the first encounter with a diagnosis of asthma (index date) with at least 1 blood eosinophil test result in the 12 months after the index date, but before the development of uncontrolled severe asthma or the study end date, were included. Uncontrolled severe asthma was defined as the first date on which all criteria of the ERS-ATS definition were first satisfied in the 12 months after the index date. Age (≥ 50 years vs. < 50 years), race, and sex were measured at index, and the Charlson Comorbidity Index (CCI) score (> 0 vs. 0) was measured in the pre-index period. Elevated eosinophil level was defined as a test result with ≥ 400 cells/µL. The study cohort was randomly split 50-50 into derivation and validation samples. Cox proportional hazards regression was used to develop the risk score for uncontrolled severe asthma using the derivation cohort with independent variables of eosinophil level, age, sex, race, and CCI. A bootstrapping procedure was used to generate 1,000 samples from the derivation cohort. Variables significant in ≥ 50% of the samples were retained in the final regression model. A risk score was then calculated based on the coefficient estimates of the final model. C-statistic was used to test the model's discrimination power. The study included 2,405 patients, 147 (6%) of whom developed uncontrolled severe asthma. Higher eosinophil level and CCI score > 0 were significantly and independently associated with an increased risk of uncontrolled severe asthma in the derivation cohort (HR = 1.90, 95% CI = 1.17-3.08 and HR = 2.00, 95% CI = 1.28-3.13, respectively); findings were similar in the validation cohort. Total risk score was categorized as 0, 2, and 4. All models showed good C-statistics (0.79-0.80), indicating favorable model discrimination. There was a significantly greater number of patients with uncontrolled severe asthma in the risk score segments of 2 and 4 compared with 0 (each P < 0.0001). A risk stratification tool using peripheral eosinophil counts and CCI can be used to predict the development of uncontrolled severe asthma. This study was funded by Teva Pharmaceuticals. eMAX Health Systems was a consultant to Teva Pharmaceuticals for this study and received payment from Teva Pharmaceuticals for work on this study. Casciano and Dotiwala are employed by eMAX Health Systems. Krishnan, Li, and Martin received payment from eMAX Health Systems for work on this study. Small was employed by Teva Pharmaceuticals at the time of this study. Study concept and design were contributed primarily by Casciano, Krishnan, Small, and Martin, along with Li and Dotiwala. Dotiwala, Casciano, Small, and Li collected the data, along with Martin and Li and Krishnan. Data interpretation was provided by Martin, Casciano, and Li, with assistance from the other authors. The manuscript was written by Li, Casciano, Dotiwala, and Small, with assistance from the other authors, and revised by Dotiwala, Small, Li, and Martin, with assistance from Krishnan and Casciano.

Association between severe eczema in children and multiple comorbid conditions and increased healthcare utilization

PubMed Central

Silverberg, Jonathan I.; Simpson, Eric L.

2015-01-01

Background Atopic dermatitis (AD) is associated with multiple comorbid conditions, such as asthma and food allergy. We sought to determine the impact of eczema severity on the development of these disorders and other non-atopic comorbidities in AD. Methods We used the 2007 National Survey of Children's Health, a prospective questionnaire-based study of a nationally representative sample of 91,642 children age 0-17 years. Prevalence and severity of eczema, asthma, hay fever and food allergy, sleep impairment, healthcare utilization, recurrent ear infections, visual and dental problems were determined. Results In general, more severe eczema correlated with poorer overall health, impaired sleep and increased healthcare utilization, including seeing a specialist, compared to children with mild or moderate disease (Rao-Scott Chi-square, P<0.0001). Severe eczema was associated with higher prevalence of comorbid chronic health disorders, including asthma, hay fever and food allergies (P<0.0001). In addition, the severity of eczema was directly related to the severity of the comorbidities. These associations remained significant in multivariate logistic regression models that included age, sex and race/ethnicity. Severe eczema was also associated with recent dental problems, including bleeding gums (P<0.0001), toothache (P=0.0004), but not broken teeth (P=0.04) or tooth decay (P=0.13). Conclusions These data indicate that severe eczema is associated with multiple comorbid chronic health disorders, impaired overall health and increased healthcare utilization. Further, these data suggest that children with eczema are at risk for decreased oral health. Future studies are warranted to verify this novel association. PMID:23773154

The effects of daily bathing on symptoms of patients with bronchial asthma

PubMed Central

Arimoto, Yoshihito; Homma, Chie; Takeoka, Shinjiro; Fukusumi, Munehisa; Mouri, Atsuto; Hamamoto, Yoichiro

2016-01-01

Background The influence of bathing in asthma patients is not yet fully known. Objective We conducted an observational study to investigate changes in symptoms and their degree by bathing in asthmatic patients. Methods A questionnaire focusing on ever experienced bathing-induced symptom changes and their degree, as well as contributing factors, was designed and administered to asthmatic patients in the outpatient department of our institute between January 2012 and November 2013. Results Two hundred fifteen cases were recruited. In 60 cases (27.9%), asthmatic symptoms appeared, including 20 cases of chest discomfort (33.3%), 19 cases of cough (31.7%), and 21 cases of wheezing (35.0%). The triggering factors included vapor inhalation (32 cases, 53.3%), hydrostatic pressure on the thorax due to body immersion in the bathtub (26 cases, 43.3%), and sudden change of air temperature (16 cases, 26.7%). Thirty-eight cases (17.7%) experienced improvement in active asthmatic symptoms by bathing. Vapor inhalation was the most common contributing factor (34 cases, 89.5%), followed by warming of the whole body (13 cases, 34.2%). There was no relationship between asthma severity and the appearance of bathing-induced symptoms or improvement of active asthmatic symptoms by bathing. Conclusion The effects of bathing in asthmatic patients widely differed from patient to patient and their etiology includes several factors. For those who suffer from bathing-induced asthma symptoms, preventive methods, such as premedication with bronchodilators before bathing, should be established. This study is registered in the University Hospital Medical Information Network (UMIN) clinical trials registry in Japan with the registration number UMIN000015641. PMID:27141485

Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities

PubMed Central

Jones, Dean P.; Brown, Lou Ann S.

2012-01-01

Abstract Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness and airflow limitation in response to specific triggers. Whereas inflammation is important for tissue regeneration and wound healing, the profound and sustained inflammatory response associated with asthma may result in airway remodeling that involves smooth muscle hypertrophy, epithelial goblet-cell hyperplasia, and permanent deposition of airway extracellular matrix proteins. Although the specific mechanisms responsible for asthma are still being unraveled, free radicals such as reactive oxygen species and reactive nitrogen species are important mediators of airway tissue damage that are increased in subjects with asthma. There is also a growing body of literature implicating disturbances in oxidation/reduction (redox) reactions and impaired antioxidant defenses as a risk factor for asthma development and asthma severity. Ultimately, these redox-related perturbations result in a vicious cycle of airway inflammation and injury that is not always amenable to current asthma therapy, particularly in cases of severe asthma. This review will discuss disruptions of redox signaling and control in asthma with a focus on the thiol, glutathione, and reduced (thiol) form (GSH). First, GSH synthesis, GSH distribution, and GSH function and homeostasis are discussed. We then review the literature related to GSH redox balance in health and asthma, with an emphasis on human studies. Finally, therapeutic opportunities to restore the GSH redox balance in subjects with asthma are discussed. Antioxid. Redox Signal. 17, 375–408. PMID:22304503

Risk factors for childhood asthma deaths from the UK Eastern Region Confidential Enquiry 2001-2006.

PubMed

Anagnostou, Katherine; Harrison, Brian; Iles, Richard; Nasser, Shuaib

2012-03-01

Confidential enquiries into asthma deaths can identify inadequacies in medical management and factors which contribute to patients' death. To identify risk factors for paediatric asthma deaths over a 6-year period. Observational case-series study of paediatric asthma deaths between 2001-2006 in the UK Eastern Region. Hospital, primary care and post-mortem data were obtained for every child (≤17 yrs) with asthma recorded on the death certificate, and a detailed questionnaire was completed. Information was obtained on asthma severity, medications, hospital admissions, GP and hospital follow-up, adherence, psychosocial / behavioural factors, allergies, details of the terminal attack and precipitating factors. 20 children (10 male; 8-17 yrs; median: 11.5 yrs) died of asthma between 2001-2006. 9/20 had mild to moderate asthma (BTS/ SIGN criteria), 10/20 had severe asthma and 1 child was not known to have asthma. 13/20 were clinically atopic. Only 3 had undergone allergy assessment. 10/20 died between June and August. 12/20 children had adverse psychosocial and behavioural factors. 7/20 children were on non-combination long-acting β2-agonist (LABA) treatment without inhaled corticosteroids (ICS). Almost half the deaths occurred in children with mild/moderate asthma. We recommend that allergic factors and seasonal allergy should be identified early, non-combination LABAs avoided, and speculate that overuse of short-acting β2-agonists (SABAs) may indicate non-adherence with ICS. Asthma deaths in children can be avoided if risk factors are identified early.

Accreditation of specialized asthma units for adults in Spain: an applicable experience for the management of difficult-to-control asthma

PubMed Central

Cisneros, Carolina; Díaz-Campos, Rocío Magdalena; Marina, Núria; Melero, Carlos; Padilla, Alicia; Pascual, Silvia; Pinedo, Celia; Trisán, Andrea

2017-01-01

This paper, developed by consensus of staff physicians of accredited asthma units for the management of severe asthma, presents information on the process and requirements for already-existing asthma units to achieve official accreditation by the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Three levels of specialized asthma care have been established based on available resources, which include specialized units for highly complex asthma, specialized asthma units, and basic asthma units. Regardless of the level of accreditation obtained, the distinction of “excellence” could be granted when more requirements in the areas of provision of care, technical and human resources, training in asthma, and teaching and research activities were met at each level. The Spanish experience in the process of accreditation of specialized asthma units, particularly for the care of patients with difficult-to-control asthma, may be applicable to other health care settings. PMID:28533690

Childhood asthma and indoor woodsmoke from cooking in Guatemala.

PubMed

Schei, Morten A; Hessen, Jens O; Smith, Kirk R; Bruce, Nigel; McCracken, John; Lopez, Victorina

2004-01-01

We estimated the prevalence and severity of asthma, and the association with cooking on open wood fires, as preparation for a large-scale randomized field trial on effects of indoor air pollution and child health. This is one of the first systematic studies of asthma and indoor wood-smoke pollution and to our knowledge the first asthma study in a purely indigeneous population in Latin America. The mothers of 1058 children aged 4-6 years were interviewed, using the standardized ISAAC (International Study of Asthma and Allergies in Childhood) procedures and questionnaire. The study population is a Mam-speaking (Maya), indigenous group living at relatively high altitude (2000 m) in Western Guatemalan Highlands. We found that asthma prevalence is low among indigenous children in Guatemala, compared to other populations in Latin America. Only 3.3% of the children reported wheezing symptoms in the last 12 months, and 72% wheezing symptoms ever. The majority of the current wheezers had at least one of the criteria for severe asthma. The prevalence of all the symptoms of asthma was higher in children from households that used open fires compared to improved stoves with chimneys. In a logistic regression model, use of open fire for cooking was a significant risk factor for a number of asthma symptoms, with odds ratios varying from 2.0 to 3.5. Among the different cooking technologies (1-improved stove with chimney, 2-mixture of gas and open fire, 3-open fire) trends of higher prevalence with more pollution was found for some of the symptoms. Hence use of open fire for cooking, may be an important risk factor for asthma symptoms and severity.

Jackie Joyner-Kersee: Living with Asthma | NIH MedlinePlus the Magazine

MedlinePlus

... top woman athlete in the heptathlon and long-jump competitions, despite severe asthma. While she was a ... asthma there was no way you could run, jump, or do the things I was doing athletically. ...

Validity of two common asthma-specific quality of life questionnaires: Juniper mini asthma quality of life questionnaire and Sydney asthma quality of life questionnaire.

PubMed

Apfelbacher, Christian Joachim; Jones, Christina; Hankins, Matthew; Smith, Helen

2012-08-20

This study explored the psychometric properties (internal consistency, construct validity, discriminative ability) of the Juniper Mini Asthma Quality of Life Questionnaire (Mini AQLQ-J) and the Sydney Asthma Quality of Life Questionnaire (AQLQ-S). One hundred fourty-six adults (18-45 years) with asthma requiring regular inhaled corticosteroids were recruited to a trial of written emotional disclosure. Correlational analyses were performed to understand the relationship of the two measures with each other, with symptoms, lung function, asthma control, asthma bother and generic quality of life. Median quality of life scores were compared according to gender, health care usage and levels of asthma severity. AQLQ-J and AQLQ-S total scores correlated strongly with each other (rho = -0.80) and moderately with the EuroQol Current Health Status Scale (AQLQ-J: rho = 0.35; AQLQ-S: rho = -0.40). Domain score correlations between AQLQ-J and AQLQ-S were mostly moderate (0.50 < rho < 0.80).Both QoL measures were significantly correlated with symptom score. Correlations with the symptom score asthma module (AQLQ-J: rho = -0.69; AQLQ-S: rho = 0.50) were stronger compared with the total symptom score and the symptom score rhinitis module (AQLQ-J: rho = -0.41; AQLQ-S: rho =0.31).Neither QoL measure was significantly correlated with FEV1, % predicted at the total or the domain level.Total scores of both measures were significantly correlated with subjective asthma control (AQLQ-J: rho = 0.68; AQLQ-S: rho = -0.61) and asthma bother (AQLQ-J: rho = -0.73; AQLQ-M: rho = 0.73).Total AQLQ-J score and total AQLQ-S score were significantly associated with perceived asthma severity (AQLQ-J: p=0.004, AQLQ-S: p=0.002) and having visited a GP in the past four months (AQLQ-J: p=0.003, AQLQ-S: p=0.002). This study provides further evidence for the validity of the AQLQ-J and the AQLQ-S in a British population of adult patients with asthma managed in primary care. Correlations with lung function parameters were weak or absent. Correlations with generic quality of life were moderate, those with asthma symptoms, asthma control and asthma bother were strong. Both measures are able to discriminate between levels of asthma severity and health care usage.

Polyclonal and allergen-induced cytokine responses in adults with asthma: resolution of asthma is associated with normalization of IFN-gamma responses.

PubMed

Smart, Joanne M; Horak, Elisabeth; Kemp, Andrew S; Robertson, Colin F; Tang, Mimi L K

2002-09-01

Atopic disease is associated with skewing of immune responses away from a T(H)1 toward a T(H)2 profile. Previous studies have implicated this cytokine imbalance in the development of disease. However, it is not known whether normalization of this imbalance is conversely associated with disease resolution. To further delineate the role of reduced T(H)1 and increased T(H)2 cytokine production in the pathogenesis of atopic disease and to determine whether disease resolution is associated with alteration of cytokine profiles, we investigated cytokine responses in a cohort of adult patients with asthma followed from childhood. A cohort of wheezy children and control subjects aged 7 to 10 years were recruited from 1964 to 1967. Subjects were reevaluated every 7 years to monitor the outcome of childhood asthma. At the 42-year follow-up, 89 subjects from this cohort were evaluated for mitogen and house dust mite (HDM)-induced T(H)1 (IFN-gamma) and T(H)2 (IL-4, IL-5, and IL-13) cytokine responses. Cytokine responses were compared in patients with ongoing asthma, patients with resolved asthma, and control subjects. Patients with severe ongoing asthma had significantly reduced HDM-induced IFN-gamma production compared with that of control subjects and patients with resolved asthma. In contrast, HDM-induced IFN-gamma production in patients with resolved asthma was equivalent to that seen in control subjects. Patients with ongoing and resolved asthma produced significantly higher levels of IL-5 in response to HDM compared with that seen in control subjects, with levels being equivalent in patients with active and resolved asthma. HDM-induced IL-13 production was significantly increased in the patients with resolved asthma when compared with that seen in the control subjects. PHA-induced cytokine responses did not parallel HDM-induced responses. Patients with persistent and severe atopic asthma have a reduced HDM-induced T(H)1 response, whereas those with resolved asthma do not. This suggests that reduced HDM-induced IFN-gamma production might be an important factor contributing to ongoing severe asthma and that normalization of allergen-induced T(H)1 responses might be important for disease resolution. The finding that all subjects with a history of asthma displayed increased HDM-induced T(H)2 (IL-5 and IL-13) cytokine responses, irrespective of the presence or absence of asthma, suggests that increased T(H)2 responses reflect the presence of the atopic state per se rather than being specifically linked to asthma.

Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK).

PubMed

Heaney, Liam G; Djukanovic, Ratko; Woodcock, Ashley; Walker, Samantha; Matthews, John G; Pavord, Ian D; Bradding, Peter; Niven, Robert; Brightling, Chris E; Chaudhuri, Rekha; Arron, Joseph R; Choy, David F; Cowan, Douglas; Mansur, Adel; Menzies-Gow, Andrew; Adcock, Ian; Chung, Kian F; Corrigan, Chris; Coyle, Peter; Harrison, Timothy; Johnston, Sebastian; Howarth, Peter; Lordan, James; Sabroe, Ian; Bigler, Jeannette; Smith, Dirk; Catley, Matthew; May, Richard; Pierre, Lisa; Stevenson, Chris; Crater, Glenn; Keane, Frank; Costello, Richard W; Hudson, Val; Supple, David; Hardman, Tim

2016-02-01

The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Pulmonary edema after electroconvulsive therapy in a patient treated for long-standing asthma with a beta2 stimulant.

PubMed

Hatta, Kotaro; Kitajima, Akiyoshi; Ito, Masanobu; Usui, Chie; Arai, Heii

2007-03-01

A 68-year-old man was scheduled to receive 8 treatments of electroconvulsive therapy (ECT) for severe depression. He was being treated for long-standing asthma with a beta2 stimulant, clenbuterol hydrochloride, and had experienced no asthma attack for 9 years. Although he experienced no adverse consequence in his 7 treatments, pulmonary edema ensued from his eighth treatment despite no change in anesthesia and in the technical parameters of ECT. He was treated with oxygen and intravenous hydrocortisone, after which he quickly recovered. Transient eosinophilia was observed, but clinical symptoms of asthma did not appear. Although the association between pulmonary edema and well-controlled asthma was unclear, thiopental as induction of anesthesia or esmolol as poststimulus delivery might have played a role in the event. There may be a possibility of pulmonary edema even after several uneventful ECT treatments in a patient with asthma.

Path to health asthma study: A survey of pediatric asthma in an urban community.

PubMed

Alicea-Alvarez, Norma; Foppiano Palacios, Carlo; Ortiz, Melanie; Huang, Diana; Reeves, Kathleen

2017-04-01

Minority children with asthma who live in low-income urban communities bear a disproportionate burden of the disease. This study explores the perceived health care needs related to asthma care, identifies asthma triggers, potential barriers to care, and assesses the need for additional community resources. We conducted a cross-sectional survey of Hispanic and African American adults (n = 53) who take care of a child with asthma and live in an urban community of North Philadelphia. Input from community leaders was obtained in the development the survey tool resulting in a unique 'community-centric' questionnaire. The survey was also available in Spanish. All surveys were conducted in the community setting. Variables were used to measure asthma severity and triggers. Children were categorized with intermittent (n = 24, 45.3%), mild persistent (n = 13, 24.5%), or moderate-to-severe persistent asthma (n = 16, 30.2%). Most children with persistent asthma were enrolled under Medicaid or CHIP (n = 24, p = 0.011) and reflected a low-income socioeconomic status. Persistent asthma was found to be associated with most triggers: pets, dust mites, mice, mold, and cockroaches. There was no significant association between environmental tobacco smoke and persistent asthma. Children with persistent asthma and 2 or more triggers were more likely to be hospitalized and go to the Emergency Department. Urban minority children living in low-income communities face neighborhood-specific asthma triggers and challenges to care. Studies conducted in urban neighborhoods, with collaboration from community members, will highlight the need of comprehensive services to account for community-centric social determinants.

The public health implications of asthma.

PubMed Central

Bousquet, Jean; Bousquet, Philippe J.; Godard, Philippe; Daures, Jean-Pierre

2005-01-01

Asthma is a very common chronic disease that occurs in all age groups and is the focus of various clinical and public health interventions. Both morbidity and mortality from asthma are significant. The number of disability-adjusted life years (DALYs) lost due to asthma worldwide is similar to that for diabetes, liver cirrhosis and schizophrenia. Asthma management plans have, however, reduced mortality and severity in countries where they have been applied. Several barriers reduce the availability, affordability, dissemination and efficacy of optimal asthma management plans in both developed and developing countries. The workplace environment contributes significantly to the general burden of asthma. Patients with occupational asthma have higher rates of hospitalization and mortality than healthy workers. The surveillance of asthma as part of a global WHO programme is essential. The economic cost of asthma is considerable both in terms of direct medical costs (such as hospital admissions and the cost of pharmaceuticals) and indirect medical costs (such as time lost from work and premature death). Direct costs are significant in most countries. In order to reduce costs and improve quality of care, employers and health plans are exploring more precisely targeted ways of controlling rapidly rising health costs. Poor control of asthma symptoms is a major issue that can result in adverse clinical and economic outcomes. A model of asthma costs is needed to aid attempts to reduce them while permitting optimal management of the disease. This paper presents a discussion of the burden of asthma and its socioeconomic implications and proposes a model to predict the costs incurred by the disease. PMID:16175830

Underrecognition of the severity of asthma and undertreatment of asthma in a rural area of Japan.

PubMed

Tomita, Katsuyuki; Hanaki, Keiichi; Hasegawa, Yasuyuki; Watanabe, Masanari; Sano, Hiroyuki; Igishi, Tadashi; Burioka, Naoto; Hitsuda, Yutaka; Horimukai, Kenta; Fukutani, Kouji; Sugimoto, Yuji; Yamamoto, Mitsunobu; Kato, Kazuhiro; Ikeda, Toshikazu; Konishi, Tatsuya; Tokuyasu, Hirokazu; Kawasaki, Yuji; Yajima, Hiroki; Sejima, Hitoshi; Isobe, Takeshi; Takabatake, Toshikazu; Shimizu, Eiji

2005-10-01

Revised guidelines were released in Japan in 2003 for the assessment, treatment, and management of adult asthmatics, and similar guidelines for child asthmatics were released in 2002. We reassessed the severity and possible undertreatment of asthma according to these guidelines in stable asthmatics. We reviewed medical records of 861 well-controlled asthmatic patients who, in April through June 2004 were cared for by 47 pulmonologists at 29 medical centers and 13 asthma clinics in a rural community in the San-in area of Japan. The physician obtained completed medical records about their symptoms and current treatment of the subjects, 726 adult and 135 children (aged 6 years or older) who were in stable condition and had had no exacerbations in the previous 3 months. The severity of asthma and current treatment for each patient were assessed according to the newly revised Japanese guidelines for the assessment, treatment, and management of adult and child asthmatics. In adult and child asthmatics, the percentage of predicted forced expiratory volume at 1 second (FEV1.0) was smaller and has a narrower distribution range than the percentage of predicted peak expiratory flow (PEF). When the severity of asthma was classified according to symptoms alone, 50% and 35% of those classified as mildly asthmatics patients with adults and children, respectively, had moderate to severe airflow limitation. Inhaled corticosteroids were prescribed to 90.6% of adult and 14.9% of child patients. When we compared the treatments that patients were actually receiving against the optimal treatments indexed according to a combined symptoms-FEV1.0 classification, we found that 49% of adult asthmatics were overtreated, 21% were properly treated, and 30% were undertreated. Among children, the respective percentages were 35%, 25%, and 40%. In well-controlled adult and child asthmatics, the severity of asthma is poorly judged when symptoms alone are considered. We suggest that the severity of asthma should be assessed through a combination of symptoms and the measurement of FEV1.0 during office visits. We also suggest that the proper dose of inhaled steroid needed to maintain stable conditions should be judged according to this combined symptoms-FEV1.0 classification.

Assessment of long-term omalizumab treatment in patients with severe allergic asthma long-term omalizumab treatment in severe asthma.

PubMed

Özgür, Eylem Sercan; Özge, Cengiz; Ïlvan, Ahmet; Naycı, Sibel Atış

2013-08-01

Several clinical studies have demonstrated the effectiveness of omalizumab in patients with severe allergic asthma but the treatment period has always been relatively short (4-12 months). In the literature, there are a few data about the long-term omalizumab therapy. We aimed to assess the long-term clinical and functional effectiveness of omalizumab treatment in severe allergic asthmatic patients, Medical records describing the patients' status before the start of treatment, and also having been registered at the end of 4th, 12th, and 36th months from the commencement of treatment, and at the last visit where the patient was evaluated were used for omalizumab effectiveness assessments. Twenty-six patients (female/male: 21/5) with severe allergic asthma, uncontrolled despite GINA 2006 Step 4 therapy, were included in the study. Effectiveness outcomes included spirometry measurements, level of asthma control measured by asthma control test (ACT), systemic glucocorticosteroid (sGCS) use, emergency room (ER) visits, and hospitalizations for severe exacerbations. In addition, the quality of life was assessed using the quality of life questionnaire AQLQ(S) before, 4, and 36 months after treatment, The mean age was 47.6 ± 13.9 and duration of allergic asthma was 22.7 ± 10.1 years. Serum total IgE levels were 322.0 ± 178.1 IU/mL. Mean duration of omalizumab treatment was 40.81 ± 8.2 months. FEV1 improved significantly at all control points versus baseline (p < .05). The level of asthma control as evaluated by ACT improved significantly after treatment (p < .05). We determined significantly reduced numbers of exacerbation, emergency visits, hospitalizations, sGCS, and SABA use by the end of 36 months (p < .05). The proportion of patients with improvements larger than 1.5 points in AQLQ(S) total score was 80.7% at the 4th month and 96.1% at the 36th month of treatment, This study showed that long-term therapy with omalizumab for up to 3 years was well tolerated with significant improvement both in symptoms and lung functions. Accordingly, long-term omalizumab treatment may be recommended for responders.

Uncovering Longitudinal Health Care Behaviors for Millions of Medicaid Enrollees: A Multistate Comparison of Pediatric Asthma Utilization.

PubMed

Hilton, Ross; Zheng, Yuchen; Fitzpatrick, Anne; Serban, Nicoleta

2018-01-01

This study introduces a framework for analyzing and visualizing health care utilization for millions of children, with a focus on pediatric asthma, one of the major chronic respiratory conditions. The data source is the 2005 to 2012 Medicaid Analytic Extract claims for 10 Southeast states. The study population consists of Medicaid-enrolled children with persistent asthma. We translate multiyear, individual-level medical claims into sequences of discrete utilization events, which are modeled using Markov renewal processes and model-based clustering. Network analysis is used to visualize utilization profiles. The method is general, allowing the study of other chronic conditions. The study population consists of 1.5 million children with persistent asthma. All states have profiles with high probability of asthma controller medication, as large as 60.6% to 90.2% of the state study population. The probability of consecutive asthma controller prescriptions ranges between 0.75 and 0.95. All states have utilization profiles with uncontrolled asthma with 4.5% to 22.9% of the state study population. The probability for controller medication is larger than for short-term medication after a physician visit but not after an emergency department (ED) visit or hospitalization. Transitions from ED or hospitalization generally have a lower probability into physician office (between 0.11 and 0.38) than into ED or hospitalization (between 0.20 and 0.59). In most profiles, children who take asthma controller medication do so regularly. Follow-up physician office visits after an ED encounter or hospitalization are observed at a low rate across all states. Finally, all states have a proportion of children who have uncontrolled asthma, meaning they do not take controller medication while they have severe outcomes.

Risk Factors and Predictive Clinical Scores for Asthma Exacerbations in Childhood

PubMed Central

Forno, Erick; Fuhlbrigge, Anne; Soto-Quirós, Manuel E.; Avila, Lydiana; Raby, Benjamin A.; Brehm, John; Sylvia, Jody M.; Weiss, Scott T.

2010-01-01

Background: Asthma is a major public health problem that affects millions of children worldwide, and exacerbations account for most of its morbidity and costs. Primary-care providers lack efficient tools to identify children at high risk for exacerbations. We aimed to construct a clinical score to help providers to identify such children. Methods: Our main outcome was severe asthma exacerbation, which was defined as any hospitalization, urgent visit, or systemic steroid course for asthma in the previous year, in children. A clinical score, consisting of a checklist questionnaire made up of 17 yes-no questions regarding asthma symptoms, use of medications and health-care services, and history, was built and validated in a cross-sectional study of Costa Rican children with asthma. It was then evaluated using data from the Childhood Asthma Management Program (CAMP), a longitudinal trial cohort of North American children. Results: Compared with children at average risk for an exacerbation in the Costa Rican validation set, the odds of an exacerbation among children in the low-risk (OR, 0.2; 95% CI, 0.1-0.4) and high-risk (OR, 5.4; 95% CI, 1.5-19.2) score categories were significantly reduced and increased, respectively. In CAMP, the hazard ratios for an exacerbation after 1-year follow-up in the low-risk and high-risk groups were 0.6 (95% CI, 0.5-0.7) and 1.9 (95% CI, 1.4-2.4), respectively, with similar results at 2 years. Conclusions: The proposed Asthma Exacerbation Clinical Score is simple to use and effective at identifying children at high and low risk for asthma exacerbations. The tool can easily be used in primary-care settings. PMID:20472862

Deaths certified as asthma and use of medical services: a national case-control study

PubMed Central

Sturdy, P; Butland, B; Anderson, H; Ayres, J; Bland, J; Harrison, B; Peckitt, C; Victor, C; on, b

2005-01-01

Background: Studies have linked asthma death to either increased or decreased use of medical services. Methods: A population based case-control study of asthma deaths in 1994–8 was performed in 22 English, six Scottish, and five Welsh health authorities/boards. All 681 subjects who died were under the age of 65 years with asthma in Part I on the death certificates. After exclusions, 532 hospital controls were matched to 532 cases for age, district, and date of asthma admission/death. Data were extracted blind from primary care records. Results: The median age of the subjects who died was 53 years; 60% of cases and 64% of controls were female. There was little difference in outpatient attendance (55% and 55%), hospital admission for asthma (51% and 54%), and median inpatient days (20 days and 15 days) in the previous 5 years. After mutual adjustment and adjustment for sex, using conditional logistic regression, three variables were independently associated with asthma death: fewer general practice contacts (odds ratio 0.82 (95% confidence interval (CI) 0.74 to 0.91) per 5 contacts) in the previous year, more home visits (1.14 (95% CI 1.08 to 1.21) per visit) in the previous year, and fewer peak expiratory flow recordings (0.83 (95% CI 0.74 to 0.92) per occasion) in the previous 3 months. These associations were similar after adjustment for markers of severity, psychosocial factors, systemic steroids, short acting bronchodilators and antibiotics, although the association with peak flow was weakened and just lost significance. Conclusion: Asthma death is associated with less use of primary care services. Both practice and patient factors may be involved and a better understanding of these may offer possibilities for reducing asthma death. PMID:16055628

Effect of Mindfulness Training on Asthma Quality of Life and Lung Function: A Randomized Controlled Trial

PubMed Central

Pbert, Lori; Madison, J. Mark; Druker, Susan; Olendzki, Nicholas; Magner, Robert; Reed, George; Carmody, James

2014-01-01

Background Improving asthma patients’ quality of life is an important clinical outcome. This study evaluated the efficacy of mindfulness-based stress reduction (MBSR) in improving quality of life and lung function in patients with asthma. Methods A randomized controlled trial compared an 8 week MBSR group-based program (n = 42) to an educational control program (n = 41) in adults with mild, moderate or severe persistent asthma recruited at a university hospital outpatient primary care and pulmonary care clinic. Primary outcomes were quality of life assessed by the Asthma Quality of Life Questionnaire (AQOL), and lung function assessed by change from baseline in two-week average morning peak expiratory flow (PEF). Secondary outcomes were asthma control assessed by 2007 NIH/NHLBI guidelines, and stress assessed by Perceived Stress Scale. Follow-up assessments were conducted at 10 weeks, 6 and 12 months. Results At 12 months MBSR resulted in clinically significant improvements in quality of life (intervention effect 0.55 (95% CI 0.21, 0.89, p=0.001)) and perceived stress (intervention effect −4.5 (95% CI −7.1, −1.9; p= 0.001)). No significant effect was found on lung function (morning PEF, PEF variability, and FEV1). At 12 months the percentage of patients in MBSR with well-controlled asthma showed a non-statistically significant increase (7.3% at baseline to 19.4%) compared to the control condition (7.5% and 7.9%, respectively) (p=0.30). Conclusions MBSR produced lasting clinically significant improvements in asthma-related quality of life and stress in patients with persistent asthma, even in the absence of improvements in lung function. PMID:22544892

The Role of the Microbiome in the Relationship of Asthma and Affective Disorders.

PubMed

Trueba, Ana F; Ritz, Thomas; Trueba, Gabriel

2016-01-01

The effect of stress, anxiety and other affective states on inflammatory conditions such as asthma is well documented. Although several immune pathway mechanisms have been proposed and studied, they cannot fully explain the relationship. In this chapter we present a new perspective on asthma development and exacerbation that integrates findings on the role of psychological factors in asthma with the microbiome and the hygiene hypothesis in asthma development.

Nonadherence in the era of severe asthma biologics and thermoplasty

PubMed Central

Lee, Joy; Tay, Tunn Ren; Radhakrishna, Naghmeh; Hore-Lacy, Fiona; Mackay, Anna; Hoy, Ryan; Dabscheck, Eli; O'Hehir, Robyn; Hew, Mark

2018-01-01

Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty. Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking >75% of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period. Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data; including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%). At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies. PMID:29519922

The Continuing Problem of Asthma in Very Young Children: A Community-Based Participatory Research Project

ERIC Educational Resources Information Center

Nelson, Belinda Wilburn; Awad, Daniel; Alexander, Jeffrey; Clark, Noreen

2009-01-01

Background: Asthma is a chronic health condition that has a disproportionate effect on low-income minority children who reside in large urban areas. African American children report significantly higher rates than the general population of children and have more-severe asthma and poorer outcomes. This article describes the prevalence of asthma in…

Identification and validation of asthma phenotypes in Chinese population using cluster analysis.

PubMed

Wang, Lei; Liang, Rui; Zhou, Ting; Zheng, Jing; Liang, Bing Miao; Zhang, Hong Ping; Luo, Feng Ming; Gibson, Peter G; Wang, Gang

2017-10-01

Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. To identify and prospectively validate asthma clusters in a Chinese population. Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07-3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26-40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02-4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95-69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission (P < .0001 for all comparisons). We identified 3 clinical clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Association between mental disorders and subsequent adult onset asthma

PubMed Central

Alonso, Jordi; de Jonge, Peter; Lim, Carmen C. W.; Aguilar-Gaxiola, Sergio; Bruffaerts, Ronny; Caldas-de-Almeida, Jose Miguel; Liu, Zhaorui; O'Neill, Siobhan; Stein, Dan J.; Viana, Maria Carmen; Al-Hamzawi, Ali Obaid; Angermeyer, Matthias C.; Borges, Guilherme; Ciutan, Marius; de Girolamo, Giovanni; Fiestas, Fabian; Haro, Josep Maria; Hu, Chiyi; Kessler, Ronald C.; Lépine, Jean Pierre; Levinson, Daphna; Nakamura, Yosikazu; Posada-Villa, Jose; Wojtyniak, Bogdan J; Scott, Kate M.

2016-01-01

Background and objectives Associations between asthma and anxiety and mood disorders are well established, but little is known about their temporal sequence. We examined associations between a wide range of DSM-IV mental disorders with adult onset of asthma and whether observed associations remain after mental comorbidity adjustments. Methods During face-to-face household surveys in community-dwelling adults (n = 52,095) of 19 countries, the WHO Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Asthma was assessed by self-report of physician’s diagnosis together with age of onset. Survival analyses estimated associations between first onset of mental disorders and subsequent adult onset asthma, without and with comorbidity adjustment. Results 1,860 adult onset (21 years+) asthma cases were identified, representing a total of 2,096,486 person-years of follow up. After adjustment for comorbid mental disorders several mental disorders were associated with subsequent adult asthma onset: bipolar (OR=1.8; 95%CI 1.3–2.4), panic (OR=1.4; 95%CI 1.0–2.0), generalized anxiety (OR=1.3; 95%CI 1.1–1.7), specific phobia (OR=1.4; 95%CI 1.2–1.6); post-traumatic stress (OR=1.5; 95%CI 1.1–2.0); binge eating (OR=1.9; 95%CI 1.2–2.9) and alcohol abuse (OR=1.5; 95%CI 1.2–2.0). Mental comorbidity linearly increased the association with adult asthma. The association with subsequent asthma was stronger for mental disorders with an early onset (before age 21). Conclusions A wide range of temporally prior mental disorders are significantly associated with subsequent onset of asthma in adulthood. The extent to which asthma can be avoided or improved among those with early mental disorders deserves study. PMID:25263276

Distinct endotypes of steroid-resistant asthma characterized by IL-17Ahigh and IFN-γhigh immunophenotypes: Potential benefits of calcitriol

PubMed Central

Chambers, Emma S.; Nanzer, Alexandra M.; Pfeffer, Paul E.; Richards, David F.; Timms, Peter M.; Martineau, Adrian R.; Griffiths, Christopher J.; Corrigan, Christopher J.; Hawrylowicz, Catherine M.

2015-01-01

Background A small population of patients with severe asthma does not respond to glucocorticoids (steroid resistant [SR]). They have high morbidity, highlighting an urgent need for strategies to enhance glucocorticoid responsiveness. Objective We investigated the immunologic differences between steroid-sensitive (SS) and SR asthmatic patients and the effect on immunophenotype of oral calcitriol treatment because it has been previously shown to beneficially modulate the clinical response to glucocorticoids in patients with SR asthma. Methods CD8-depleted PBMCs were isolated from 12 patients with SS and 23 patients with SR asthma and cultured for 7 days with anti-CD3 and IL-2 with or without dexamethasone. Cytokine production was assessed in supernatants by using the Cytometric Bead Array. Patients with SR asthma were subsequently randomized to oral calcitriol or placebo therapy, and identical studies were repeated. Results Patients with SR asthma produced significantly increased IL-17A and IFN-γ levels compared with those in patients with SS asthma, although it was evident that cells from individual patients might overproduce one or the other of these cytokines. Production of IL-17A was inversely and production of IL-13 was positively associated with the clinical response to prednisolone. Oral calcitriol, compared with placebo, therapy of the patients with SR asthma significantly improved dexamethasone-induced IL-10 production in vitro while suppressing dexamethasone-induced IL-17A production. This effect mirrored the previously demonstrated improvement in clinical response to oral glucocorticoids in calcitriol-treated patients with SR asthma. Conclusions IL-17Ahigh and IFN-γhigh immunophenotypes exist in patients with SR asthma. These data identify immunologic pathways that likely underpin the beneficial clinical effects of calcitriol in patients with SR asthma by directing the SR cytokine profile toward a more SS immune phenotype, suggesting strategies for identifying vitamin D responder immunophenotypes. PMID:25772594

Labial adhesions and outcomes of office management.

PubMed

Granada, Catalina; Sokkary, Nancy; Sangi-Haghpeykar, Haleh; Dietrich, Jennifer E

2015-04-01

To evaluate clinical outcomes of labial adhesions (LA) and to examine the association between LA, lichen sclerosus (LS), eczema (ECZ), or asthma. Retrospective study. Single pediatric and adolescent gynecology clinic, Houston, Texas. 50 girls diagnosed with LA from 2006-2011. Resolution, recurrence, single vs multiple treatments, need for surgery, and conditions such as LS, ECZ, and asthma were reviewed. Mean age was 19.6 months (range 0-84 months), and 48% were Caucasian. Most patients were symptomatic (62%) and all 50 patients chose estrogen treatment. The majority (74%) required multiple treatments, as opposed to a single treatment (26%). Patients with multiple treatments were more likely to be severely agglutinated (P = .05) and to need manual separation after failed topical treatment (P = .08). The prevalence of asthma, LS, and ECZ was 9.8%, 7.8%, and 3.9% respectively. There was no association between LS, ECZ, or asthma, and number of treatments. Both asthma (N = 3; 8%), and LS (N = 2; 5%) were present among the severe agglutinated group; however, this difference was not statistically significant (P values .59 and .99). No association with ECZ was seen in either group. Severe agglutination tends to be associated with need of multiple treatments and manual separation. A concurrent diagnosis of LS, ECZ, or asthma was not associated with number of treatments but there appears to be a trend towards severity of LA in patients with asthma and LS. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

An RGS4-mediated phenotypic switch of bronchial smooth muscle cells promotes fixed airway obstruction in asthma.

PubMed

Damera, Gautam; Druey, Kirk M; Cooper, Philip R; Krymskaya, Vera P; Soberman, Roy J; Amrani, Yassine; Hoshi, Toshinori; Brightling, Christopher E; Panettieri, Reynold A

2012-01-01

In severe asthma, bronchodilator- and steroid-insensitive airflow obstruction develops through unknown mechanisms characterized by increased lung airway smooth muscle (ASM) mass and stiffness. We explored the role of a Regulator of G-protein Signaling protein (RGS4) in the ASM hyperplasia and reduced contractile capacity characteristic of advanced asthma. Using immunocytochemical staining, ASM expression of RGS4 was determined in endobronchial biopsies from healthy subjects and those from subjects with mild, moderate and severe asthma. Cell proliferation assays, agonist-induced calcium mobilization and bronchoconstriction were determined in cultured human ASM cells and in human precision cut lung slices. Using gain- and loss-of-function approaches, the precise role of RGS proteins was determined in stimulating human ASM proliferation and inhibiting bronchoconstriction. RGS4 expression was restricted to a subpopulation of ASM and was specifically upregulated by mitogens, which induced a hyperproliferative and hypocontractile ASM phenotype similar to that observed in recalcitrant asthma. RGS4 expression was markedly increased in bronchial smooth muscle of patients with severe asthma, and expression correlated significantly with reduced pulmonary function. Whereas RGS4 inhibited G protein-coupled receptor (GPCR)-mediated bronchoconstriction, unexpectedly RGS4 was required for PDGF-induced proliferation and sustained activation of PI3K, a mitogenic signaling molecule that regulates ASM proliferation. These studies indicate that increased RGS4 expression promotes a phenotypic switch of ASM, evoking irreversible airway obstruction in subjects with severe asthma.

Implementation of evidence-based asthma interventions in post-Katrina New Orleans: the Head-off Environmental Asthma in Louisiana (HEAL) study.

PubMed

Mitchell, Herman; Cohn, Richard D; Wildfire, Jeremy; Thornton, Eleanor; Kennedy, Suzanne; El-Dahr, Jane M; Chulada, Patricia C; Mvula, Mosanda M; Grimsley, L Faye; Lichtveld, Maureen Y; White, LuAnn E; Sterling, Yvonne M; Stephens, Kevin U; Martin, William J

2012-11-01

Childhood asthma morbidity and mortality in New Orleans, Louisiana, is among the highest in the nation. In August 2005, Hurricane Katrina created an environmental disaster that led to high levels of mold and other allergens and disrupted health care for children with asthma. We implemented a unique hybrid asthma counselor and environmental intervention based on successful National Institutes of Health asthma interventions from the National Cooperative Inner City Asthma (NCICAS) and Inner-City Asthma (ICAS) Studies with the goal of reducing asthma symptoms in New Orleans children after Hurricane Katrina. Children (4-12 years old) with moderate-to-severe asthma (n = 182) received asthma counseling and environmental intervention for approximately 1 year. HEAL was evaluated employing several analytical approaches including a pre-post evaluation of symptom changes over the entire year, an analysis of symptoms according to the timing of asthma counselor contact, and a comparison to previous evidence-based interventions. Asthma symptoms during the previous 2 weeks decreased from 6.5 days at enrollment to 3.6 days at the 12-month symptom assessment (a 45% reduction, p < 0.001), consistent with changes observed after NCICAS and ICAS interventions (35% and 62% reductions in symptom days, respectively). Children whose families had contact with a HEAL asthma counselor by 6 months showed a 4.09-day decrease [95% confidence interval (CI): 3.25 to 4.94-day decrease] in symptom days, compared with a 1.79-day decrease (95% CI: 0.90, 2.67) among those who had not yet seen an asthma counselor (p < 0.001). The novel combination of evidence-based asthma interventions was associated with improved asthma symptoms among children in post-Katrina New Orleans. Post-intervention changes in symptoms were consistent with previous randomized trials of NCICAS and ICAS interventions.

Prevalence, severity and risk factors of asthma, rhinitis and eczema in a large group of Chinese schoolchildren.

PubMed

Song, Ning; Shamssain, Mohammed; Mohammed, Shamssain; Zhang, Jin; Wu, Jianling; Fu, Chunling; Hao, Shuting; Guan, Jitao; Yan, Xixin

2014-04-01

There is a lack of information on the prevalence, severity and risk factors of asthma, rhinitis and eczema in Chinese children. To establish baseline data for a major longitudinal study of factors affecting asthma, rhinitis and eczema in a large group of children from the industrialized city of Shijiazhuang, China. We used the International Study of Asthma and Allergies in Childhood questionnaire and studied 10 338 children, ages 6-18, from Shijiazhuang. The prevalence of childhood asthma, rhinitis and eczema is 1.2%, 13.5% and 11.8%, respectively. Boys had higher prevalence of these conditions than girls and younger children had higher prevalence of asthma and eczema but lower prevalence of rhinitis than older children. Breastfed children had lower prevalence of asthma and rhinitis, but not eczema, than non-breastfed children. Overweight children had higher prevalence of asthma and rhinitis than those who were not overweight. Children exposed to paternal smoking had higher prevalence of rhinitis and eczema than those not exposed; children exposed to pets had higher prevalence of asthma and rhinitis than those not exposed. The prevalence of asthma in this study group is low, but the prevalence of rhinitis is high, and could be considered a major public health problem. The prevalence of asthma, rhinitis and eczema is generally higher in boys and younger children generally have higher prevalence of asthma and eczema but lower prevalence of rhinitis. Exposure to pets is a risk factor for rhinitis, being overweight is a risk factor for asthma and rhinitis, and exposure to parental smoking is a risk factor for asthma, rhinitis and eczema in these children.

Achieving Symptom Control in Patients with Moderate Asthma

PubMed Central

Weir, Nargues A.; Levine, Stewart J.

2012-01-01

Disease severity in asthma can be classified as mild, moderate or severe based upon the frequency of symptoms or the severity of airflow obstruction. This review will focus on the treatment of youths greater than 12 years of age and adults with moderate persistent asthma. Moderate asthmatics may have daily symptoms that cause some limitation with normal daily activities and require use of a rescue inhaled short-acting beta2-agonist inhaler or experience nocturnal awakenings secondary to asthma that occur more than once per week. Furthermore, spirometry may reveal airflow obstruction with a reduction in FEV1 to between 60% and 80% of predicted. Although inhaled corticosteroids (ICS) are the primary controller medication used to modify symptoms in moderate asthmatics, additional controller medications, such as inhaled long-acting beta2-agonists (LABA), leukotriene receptor antagonists (LTRA) or theophylline, are often needed to obtain optimal disease control. While the addition of an inhaled LABA to an ICS is very effective at improving disease control in moderate asthma, concerns have arisen over the safety of LABAs, in particular the risk of asthma-related death. Therefore, consideration may be given to initially adding a LTRA, rather than a LABA, to ICS when asthma symptoms are not adequately controlled by ICS alone. Furthermore, individualization of medication regimens, treatment of co-morbid conditions, and patient education are crucial to optimizing compliance with therapy, improving disease control, and reducing the risk of exacerbations. Lastly, the development of new asthma treatments, perhaps based upon personalized medicine, may revolutionize the future treatment of moderate asthma. PMID:22259262

Severe and Moderate Asthma Exacerbations in Asthmatic Children and Exposure to Ambient Air Pollutants

PubMed Central

Tétreault, Louis-Francois; Doucet, Marieve; Gamache, Philippe; Fournier, Michel; Brand, Allan; Kosatsky, Tom; Smargiassi, Audrey

2016-01-01

Background: It is well established that short-term exposure to ambient air pollutants can exacerbate asthma, the role of early life or long-term exposure is less clear. We assessed the association between severe asthma exacerbations with both birth and annual exposure to outdoor air pollutants with a population-based cohort of asthmatic children in the province of Quebec (Canada). Method: Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were defined as one hospitalization or emergency room visit with a diagnosis of asthma for children (<13 years old) already diagnosed with asthma. Annual daily average concentrations of ozone (O3) and nitrogen dioxide (NO2) were estimated at the child’s residential postal code. Satellite based levels of fine particulate (PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes of residence for the whole province. Hazard ratios (HRs) were estimated from Cox models with a gap time approach for both birth and time-dependant exposure. Results: Of the 162,752 asthmatic children followed (1,020,280 person-years), 35,229 had at least one asthma exacerbation. The HRs stratified by age groups and adjusted for the year of birth, the ordinal number of exacerbations, sex, as well as material and social deprivation, showed an interquartile range increase in the time-dependant exposure to NO2 (4.95 ppb), O3 (3.85 ppb), and PM2.5 (1.82 μg/m3) of 1.095 (95% CI 1.058–1.131), 1.052 (95% CI 1.037–1.066) and 1.025 (95% CI 1.017–1.031), respectively. While a positive association was found to PM2.5, no associations were found between exposure at birth to NO2 or O3. Conclusions: Our results support the conclusion, within the limitation of this study, that asthma exacerbations in asthmatic children are mainly associated with time dependent residential exposures less with exposure at birth. PMID:27490556

Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases

PubMed Central

Li, Xingnan; Ampleford, Elizabeth J.; Howard, Timothy D.; Moore, Wendy C.; Torgerson, Dara G.; Li, Huashi; Busse, William W.; Castro, Mario; Erzurum, Serpil C.; Israel, Elliot; Nicolae, Dan L.; Ober, Carole; Wenzel, Sally E.; Hawkins, Gregory A.; Bleecker, Eugene R.; Meyers, Deborah A.

2013-01-01

Background Genome-wide association studies (GWASs) of asthma have consistently implicated the ORM1-like 3 and gasdermin B (ORMDL3-GSDMB), IL33, IL-1 receptor–like 1 and IL-18 receptor 1 (IL1RL1-IL18R1), RAD50-IL13, thymic stromal lymphopoietin and WD repeat domain 36 region (TSLP-WDR36), and HLA-DR/DQ regions. Objective A GWAS of asthma was performed in a non-Hispanic white population. Methods A GWAS was performed in 813 Severe Asthma Research Program/Collaborative Studies on the Genetics of Asthma/Chicago Asthma Genetics Study cases and 1564 control subjects. The GWAS results were compared with those of the published GWASs of autoimmune diseases. Result Multiple single nucleotide polymorphisms in the TNFAIP3 interacting protein 1 (TNIP1) gene, which interacts with TNFAIP3 and inhibits the TNF-α–induced nuclear factor κB inflammation pathway, were associated with asthma: rs1422673 (P = 3.44 × 10−7) and rs10036748 (P = 1.41 × 10−6, r2 = 0.67). rs1422673 was also associated with asthma in the published GABRIEL (P = .018) and EVE (P = 1.31 × 10−5) studies. The minor allele T of rs20541 in IL13 is the risk allele for asthma but the protective allele for psoriasis. The minor allele T of rs2395185 in HLA-DRA is the risk allele for asthma but the protective allele for ulcerative colitis. The minor allele A of rs2872507 in GSDMB is the protective allele for asthma but the risk allele for rheumatoid arthritis, Crohn disease, and ulcerative colitis. The T allele of rs10036748 in the TNIP1 gene is the minor protective allele for asthma but the minor or major risk allele for systemic lupus erythematosus and systemic sclerosis in non-Hispanic white or Chinese subjects, respectively. Conclusions Our study suggests that single nucleotide polymorphisms associated with both asthma and autoimmune diseases might have opposite effects on immunopathogenesis. (J Allergy Clin Immunol 2012;130:861-8.) PMID:22694930

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

PubMed

Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

2018-03-08

Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Influenza Vaccination Among US Children With Asthma, 2005–2013

PubMed Central

Simon, Alan E.; Ahrens, Katherine A.; Akinbami, Lara J.

2016-01-01

Background Children with asthma face higher risk of complications from influenza. Trends in influenza vaccination among children with asthma are unknown. Methods We used 2005–2013 National Health Interview Survey data for children 2 to 17 years of age. We assessed, separately for children with and without asthma, any vaccination (received August through May) during each of the 2005–2006 through 2012–2013 influenza seasons and, for the 2010–2011 through 2012–2013 seasons only, early vaccination (received August through October). We used April–July interviews each year (n = 31,668) to assess vaccination during the previous influenza season. Predictive margins from logistic regression with time as the independent and vaccination status as the dependent variable were used to assess time trends. We also estimated the association between several sociodemographic variables and the likelihood of influenza vaccination. Results From 2005 to 2013, among children with asthma, influenza vaccination receipt increased about 3 percentage points per year (P < .001), reaching 55% in 2012–2013. The percentage of all children with asthma vaccinated by October (early vaccination) was slightly above 30% in 2012–2013. In 2010–2013, adolescents, the uninsured, children of parents with some college education, and those living in the Midwest, South, and West were less likely to be vaccinated. Conclusions The percentage of children 2 to 17 years of age with asthma receiving influenza vaccination has increased since 2004–2005, reaching approximately 55% in 2012–2013. PMID:26518382

Summary of the 2008 BTS/SIGN British Guideline on the management of asthma.

PubMed

Levy, Mark L; Thomas, Mike; Small, Iain; Pearce, Linda; Pinnock, Hilary; Stephenson, Paul

2009-01-01

The 2008 BTS/SIGN British Guideline on the management of asthma provides comprehensive updated evidence-based guidance on asthma management for healthcare professionals. This primary care-focussed summary has been produced to aid dissemination and implementation of the key guideline messages into primary care. The section on diagnosis emphasises the new integrated symptom-based approach with clinicians using their deductive skills to determine the probability that the patient has asthma. The various tools used for monitoring asthma are discussed. There are sections on both non-pharmacological and pharmacological management of chronic asthma in adults and children. Treatment options for children are subdivided into the under-5s and children aged 5-12 years. Poor asthma control is manifested by exacerbations and acute asthma. Personalised asthma action plans for guided self management should be provided and used when levels of asthma control change. There are sections on difficult asthma and the treatment of exacerbations and acute severe asthma. Various outcome measures for auditing the quality of asthma care are discussed.

Effectiveness of Omalizumab in Severe Allergic Asthma: A Retrospective UK Real-World Study

PubMed Central

2013-01-01

Objective. The aim of this study was to evaluate the “real world” effects of the monoclonal antibody omalizumab (OMB) when used to treat severe persistent allergic asthma in UK clinical practice. Methods. A 10-center retrospective observational study was carried out to compare oral corticosteroid (OCS) use and exacerbation frequency in 12 months pre- versus post-OMB initiation in 136 patients aged ≥12 years with severe persistent allergic asthma. All patients received ≥1 dose of OMB. Patients who had received OMB in a clinical trial were excluded. Data were obtained from hospital and if necessary general practitioners’ (GPs’) records on OCS use, lung function, hospital resource use, and routinely used quality of life (QoL) measures at baseline (pre-OMB), 16 weeks, and up to 12 months post-OMB initiation. Results. Mean total quantity of OCS prescribed per year decreased by 34% between the 12 months pre- and post-OMB initiation. During the 12 months post-OMB initiation, 87 patients (64%) stopped/reduced OCS use by 20% or more and 66 (49%) stopped OCS completely. Mean percent predicted forced expiratory volume in one second (FEV1) increased from 66.0% at baseline to 75.2% at week 16 of OMB therapy. The number of asthma exacerbations decreased by 53% during the 12 months post-initiation. Accident and emergency visits reduced by 70% and hospitalizations by 61% in the 12 months post-OMB initiation. Conclusion. This retrospective analysis showed a reduction in exacerbations and improved QoL as per previous studies with OMB. However, the total reduction in annual steroid burden and improved lung function in this severely ill group of patients taking regular or frequent OCS is greater than that seen in previous trials. PMID:23574000

Relationships between severity of chronic rhinosinusitis and nasal polyposis, asthma, and atopy

PubMed Central

Pearlman, Aaron N.; Chandra, Rakesh K.; Chang, Dennis; Conley, David B.; Peters, Anju Tripathi; Grammer, Leslie C.; Schleimer, Robert T.; Kern, Robert C.

2013-01-01

Background The effect of comorbid conditions such as asthma and atopy on the severity of chronic rhinosinusitis (CRS) and the presence of nasal polyps (NPs) remains an area of investigation. We sought to elucidate the relationship among these entities. Methods The study population included 106 consecutive patients who were referred to a multidisciplinary, university-based allergy and sinus clinic that underwent computed tomography (CT) scan, skin-prick testing, and had CRS. Data were analyzed to determine Lund-MacKay score (LMS), presence of NPs, asthma status, and sensitivity to seven classes of aeroallergens. Results Skin tests were positive in 52 cases and negative in 54 cases. Although, there was no statistical relationship between LMS and atopic status in the entire group, among the asthmatic subgroup, mean LMS was greater in nona topic asthmatic patients than in atopic asthmatic patients. Asthmatic patients had a higher LMS than nonasthmatic patients (p < 0.0001). Asthmatic patients were more likely than nonasthmatic patients to have NPs (57.6% versus 25%; p = 0.0015), regardless of atopic status. Mean LMS was higher in NP patients compared with nonpolyp patients (p < 0.0001), independent of atopic status. Mean LMS was not affected by sensitivity to any particular allergen, with the exception of cockroach-allergic patients who were more likely to have an LMS of >10 (p = 0.0236) and had more severe maxillary sinus involvement (p = 0.0391). Conclusion These data indicate a strong relationship between CRS severity, as measured by LMS, and chronic airway inflammatory diseases, asthma, and NPs. The association between LMS and atopic status appears weak. The present study suggests that CRS is an inflammatory disease that occurs independently of systemic IgE-mediated pathways. PMID:19401038

The self-reported quality of life of Lithuanian children with asthma was comparable to Western populations.

PubMed

Taminskiene, Vaida; Vaitkaitiene, Egle; Valiulis, Algirdas; Turner, Steve; Hadjipanayis, Adamos; Stukas, Rimantas; Valiulis, Arunas

2018-02-01

Quality of life (QoL) has been widely researched among children with asthma in Western countries, but there is a lack of data from eastern Europe, where the prevalence is relatively low, but hospital admission rates are higher. We evaluated the overall level and major determinants of QoL in Lithuanian children aged 5-11 years with asthma. This study was carried out in six asthma outpatient clinics in the two largest cities of Lithuania from January 2015 to July 2016. The children's QoL was measured using the Pediatric Quality of Life Inventory (PedsQL) asthma module, which was completed by the child and one parent. We collected questionnaires from 226 children (68% boys) with a mean age of eight (±2) years: 65% had mild asthma, 31% had moderate asthma and 4% had severe asthma. One in 10 had been hospitalised in the preceding 6 months. The mean self-reported QoL score was 74 and the parent-reported QoL score was 73. QoL was associated with asthma severity and control, shortness of breath and the child's general health, but not socioeconomic factors. The overall level and major determinants of QoL in children with asthma in Lithuania were comparable with Western populations. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Multidimensional assessment of severe asthma: A systematic review and meta-analysis.

PubMed

Clark, Vanessa L; Gibson, Peter G; Genn, Grayson; Hiles, Sarah A; Pavord, Ian D; McDonald, Vanessa M

2017-10-01

The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes. © 2017 Asian Pacific Society of Respirology.

Pruning of the Pulmonary Vasculature in Asthma: The SARP Cohort.

PubMed

Ash, Samuel Y; Rahaghi, Farbod N; Come, Carolyn E; Ross, James C; Colon, Alysha G; Cardet-Guisasola, Juan Carlos; Dunican, Eleanor M; Bleecker, Eugene R; Castro, Mario; Fahy, John V; Fain, Sean B; Gaston, Benjamin M; Hoffman, Eric A; Jarjour, Nizar N; Mauger, David T; Wenzel, Sally E; Levy, Bruce D; San Jose Estepar, Raul; Israel, Elliot; Washko, George R

2018-04-19

Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease. To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations. We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5mm2 in cross sectional area (BV5) and of vessels less than 10mm2 (BV10) in cross sectional area on non-contrast computed tomographic scans of participants from the Severe Asthma Research Program. Lower values of the BV5 to TBV ratio (BV5/TBV) and the BV10 to TBV ratio (BV10/TBV) represented vascular pruning (loss of the peripheral pulmonary vasculature). Compared to healthy controls, severe asthmatics had more pulmonary vascular pruning. Among asthmatics, those with poor asthma control had more pruning than those well-controlled disease. Pruning of the pulmonary vasculature was also associated with lower percent predicted forced expiratory volume in one second and forced vital capacity, greater peripheral and sputum eosinophilia and higher bronchoalveolar lavage SAA/LXA4, but not with low attenuation area or with sputum neutrophilia. Compared with individuals with less pruning, individuals with the most vascular pruning had a 150% greater odds of reporting an asthma exacerbation (OR 2.50; CI: 1.05, 5.98; p=0.039 for BV10/TBV), and reported 45% more asthma exacerbations during follow-up (IRR 1.45; CI: 1.02, 2.06; p=0.036 for BV10/TBV). Pruning of the peripheral pulmonary vasculature is associated with asthma severity, control and exacerbations, as well as with lung function and eosinophilia.

The impact of gender on asthma in the daily clinical practice.

PubMed

Ciprandi, Giorgio; Gallo, Fabio

2018-03-01

It is up-to-date to consider the potential gender impact on a disease. There are few data about gender difference in asthma. Therefore, the present cross-sectional study tested this hypothesis in a real-life setting to investigate possible difference between genders. This study was cross-sectional, considering 554 consecutive outpatients suspected of asthma, who were referred for a first specialist visit. Clinical and functional parameters were evaluated. Females with asthma could have a worse perception of asthma control, assessed by asthma control test (ACT), and more anxiety than asthmatic males. However, there was no difference regarding asthma control grading, asthma severity, and asthma medication use between genders; the differences in lung function were without clinical relevance. In the daily clinical practice, it is relevant to consider gender in the management of asthma.

Internet Telehealth for Pediatric Asthma Case Management: Integrating Computerized and Case Manager Features for Tailoring a Web-Based Asthma Education Program

PubMed Central

Wise, Meg; Gustafson, David H.; Sorkness, Christine A.; Molfenter, Todd; Staresinic, Anthony; Meis, Tracy; Hawkins, Robert P.; Shanovich, Kathleen Kelly; Walker, Nola P.

2008-01-01

This article reports on the development of a personalized, Web-based asthma-education program for parents whose 4- to 12-year-old children have moderate to severe asthma. Personalization includes computer-based tailored messages and a human coach to build asthma self-management skills. Computerized features include the Asthma Manager, My Calendar/Reminder, My Goals, and a tailored home page. These are integrated with monthly asthma-education phone calls from an asthmanurse case manager. The authors discuss the development process and issues and describe the current randomized evaluation study to test whether the yearlong integrated intervention can improve adherence to a daily asthma controller medication, asthma control, and parent quality of life to reduce asthma-related healthcare utilization. Implications for health education for chronic disease management are raised. PMID:16928987

How should treatment approaches differ depending on the severity of asthma?

PubMed

Kupczyk, Maciej; Kuna, Piotr

2017-12-01

Asthma is nowadays regarded as a syndrome of various overlapping phenotypes with defined clinical characteristics, different underlying inflammatory mechanisms, identifiable genetic background, environmental risk factors and possible biomarkers. There are no doubts that due to the diversity of asthma, a 'one size fits all' management of the disease is no longer valid. Areas covered: Nowadays asthma management is based on the control of the disease, and the goals of asthma treatment are defined as good symptom control, decreased future risk of exacerbations, fixed airflow limitation, and side-effects of treatment. Alternative strategies for adjusting asthma treatment such as sputum or exhaled nitric oxide guided protocols have been evaluated and despite some effectiveness, are regarded as impractical in every-day clinical conditions. Further studies in the field of asthma phenotypes/endotypes and biomarkers are warranted with the main goal to define which of those possible subgroups will be useful in clinical practice in regards to the potential allocation of successful treatment. Expert commentary: Despite the availability of guidelines on the diagnosis and management of asthma, it seems that the disease is still not optimally controlled. Addressing unmet needs in every day care, improving education, adherence/compliance and inhalation technique may significantly improve asthma control across all severities of the disease.

Risk of psoriasis in patients with childhood asthma: a Danish nationwide cohort study.

PubMed

Egeberg, A; Khalid, U; Gislason, G H; Mallbris, L; Skov, L; Hansen, P R

2015-07-01

Psoriasis and asthma are disorders driven by inflammation. Psoriasis may carry an increased risk of asthma, but the reverse relationship has not been investigated. To investigate the risk of psoriasis in subjects with childhood asthma in a nationwide Danish cohort. Data on all Danish individuals aged 6-14 years at study entry between 1 January 1997 and 31 December 2011 (n = 1,478,110) were linked at an individual level in nationwide registers. Incidence rates per 10,000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, concomitant medication and comorbidity were estimated by Poisson regression models. There were 21,725 cases of childhood asthma and 6586 incident cases of psoriasis. There were 5697 and 889 incident cases of mild and severe psoriasis, respectively. The incidence rates of overall, mild and severe psoriasis were 4.49, 3.88 and 0.61 for the reference population, and 5.95, 5.18 and 0.83 for subjects with childhood asthma, respectively. The IRRs for overall, mild and severe psoriasis were 3.94 [95% confidence interval (CI) 2.16-7.17], 5.03 (95% CI 2.48-10.21) and 2.27 (95% CI 0.61-8.42) for patients with childhood asthma. Childhood asthma was associated with a significantly increased risk of psoriasis. Further studies are warranted to determine the clinical significance and effects of therapeutic interventions on this association. © 2015 British Association of Dermatologists.

Aerobic capacity and skeletal muscle function in children with asthma.

PubMed

Villa, Fabiane; Castro, Ana Paula Beltran Moschione; Pastorino, Antonio Carlos; Santarém, José Maria; Martins, Milton Arruda; Jacob, Cristina Miuki Abe; Carvalho, Celso Ricardo

2011-06-01

Peripheral muscle strength and endurance are decreased in patients with chronic pulmonary diseases and seem to contribute to patients' exercise intolerance. However, the authors are not aware of any studies evaluating peripheral muscle function in children with asthma. It seems to be implied that children with asthma have lower aerobic fitness, but there are limited studies comparing the aerobic capacity of children with and without asthma. The present study aimed to evaluate muscle strength and endurance in children with persistent asthma and their association with aerobic capacity and inhaled corticosteroid consumption. Forty children with mild persistent asthma (MPA) or severe persistent asthma (SPA) (N=20 each) and 20 children without asthma (control group) were evaluated. Upper (pectoralis and latissimus dorsi) and lower (quadriceps) muscle strength and endurance were assessed, and cardiopulmonary exercise testing was performed. Inhaled corticosteroid consumption during the last 6 and 24 months was also quantified. Children with SPA presented a reduction in peak oxygen consumption (VO(2)) (28.2±8.1 vs 34.7±6.9 ml/kg/min; p<0.01) and quadriceps endurance (43.1±6.7 vs 80.9±11.9 repetitions; p<0.05) compared with the control group, but not the MPA group (31.5±6.1 ml/kg/min and 56.7±47.7 repetitions respectively; p>0.05). Maximal upper and lower muscle strength was preserved in children with both mild and severe asthma (p>0.05). Finally, the authors observed that lower muscle endurance weakness was not associated with reductions in either peak VO(2) (r=0.22, p>0.05) or corticosteroid consumption (r=-0.31, p>0.05) in children with asthma. The findings suggest that cardiopulmonary exercise and lower limb muscle endurance should be a priority during physical training programs for children with severe asthma.

External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma.

PubMed

Wagener, A H; de Nijs, S B; Lutter, R; Sousa, A R; Weersink, E J M; Bel, E H; Sterk, P J

2015-02-01

Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic inflammation. Quantifying the mutual relationships of blood eosinophils, FE(NO), and serum periostin with sputum eosinophils by external validation in two independent cohorts across various severities of asthma. The first cohort consisted of 110 patients with mild to moderate asthma (external validation cohort). The replication cohort consisted of 37 patients with moderate to severe asthma. Both cohorts were evaluated cross-sectionally. Sputum was induced for the assessment of eosinophils. In parallel, blood eosinophil counts, serum periostin concentrations and FENO were assessed. The diagnostic accuracy of these markers to identify eosinophilic asthma (sputum eosinophils ≥3%) was calculated using receiver operating characteristics area under the curve (ROC AUC). In the external validation cohort, ROC AUC for blood eosinophils was 89% (p<0.001) and for FE(NO) level 78% (p<0.001) to detect sputum eosinophilia ≥3%. Serum periostin was not able to distinguish eosinophilic from non-eosinophilic airway inflammation (ROC AUC=55%, p=0.44). When combining these three variables, no improvement was seen. The diagnostic value of blood eosinophils was confirmed in the replication cohort (ROC AUC 85%, p<0.001). In patients with mild to moderate asthma, as well as patients with more severe asthma, blood eosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. The use of blood eosinophils can facilitate individualised treatment and management of asthma. NTR1846 and NTR2364. 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.

Impact of coping and socioeconomic factors on quality of life in adults with asthma.

PubMed

Adams, Robert J; Wilson, David; Smith, Brian J; Ruffin, Richard E

2004-03-01

The socioeconomic variables of income, race and employment status have been shown to influence health-related quality of life (HRQL) scores in persons with asthma. However, little is known about the impact of other psychological factors or perceptions of economic hardship on HRQL in asthma, despite the known influence these have on general activity levels and emotional perceptions. The aim of the present study was to assess the relationships between psychological and socioeconomic factors and HRQL and on subsequent changes to HRQL over 12 months. Consecutive adult patients with moderate or severe asthma attending outpatient clinics, emergency departments or who were inpatients at two teaching hospitals, completed surveys of clinical status, psychological and socioeconomic variables, and HRQL instruments (SF-36 and Modified Marks Asthma Quality of Life Questionnaire [MAQLQ-M]), at baseline and over 12-months follow-up. Of 343 eligible subjects, survey responses were received from 293 at baseline and 232 at 12-months. Mean age was 42 years (SD 18), 67% were female, 42% had moderate, and 58% severe current asthma clinical status according to the National Asthma Education and Prevention Program guidelines criteria. In random-effects multiple regression models, after adjusting for age, gender, education, income and hospital, significant independent variables associated with each of total MAQLQ-M, SF-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) scores were avoidance coping, perceived recent financial difficulties and clinical asthma status. Additional independent associations were, for total MAQLQ-M, patient concerns about costs delaying them from seeking care (overall model r(2) = 0.69); for PCS, active coping (r(2) = 0.69) and for MCS, positive evaluations/satisfaction with illness (r(2) = 0.54). Psychological factors, particularly coping styles, need to be taken into account when considering HRQL scores as outcome measures in asthma. Interventions to improve the coping capabilities of individuals with moderate-to-severe asthma may be potentially important areas for improvement of asthma-related HRQL.

Adipose tissue content and distribution in children and adolescents with bronchial asthma.

PubMed

Umławska, Wioleta

2015-02-01

The excess of adipose tissue and the pattern of adipose tissue distribution in the body seem to play an important role in the complicated dependencies between obesity and risk of developing asthma. The aim of the present study was to determine nutritional status in children and adolescents with bronchial asthma with special emphasis on adipose tissue distribution evaluated on the basis of skin-fold thicknesses, and to determine the relationships between patterns of adipose tissue distribution and the course of the disease. Anthropometric data on height, weight, circumferences and skin-fold thicknesses were extracted from the medical histories of 261 children diagnosed with asthma bronchitis. Values for children with asthma were compared to Polish national growth reference charts. Distribution of subcutaneous adipose tissue was evaluated using principal components analysis (PCA). Multivariate linear regression analyses tested the effect of three factors on subcutaneous adipose tissue distribution: type of asthma, the severity of the disease and the duration of the disease. Mean body height in the children examined in this study was lower than in their healthy peers. Mean BMI and skin-fold thicknesses were significantly higher and lean body mass was lower in the study group. Excess body fat was noted, especially in girls. Adipose tissue was preferentially deposited in the trunk in girls with severe asthma, as well as in those who had been suffering from asthma for a longer time. The type of asthma, atopic or non-atopic, had no observable effect on subcutaneous adipose tissue distribution in children examined. The data suggest that long-treated subjects and those with severe bronchial asthma accumulate more adipose tissue on the trunk. It is important to regularly monitor nutritional status in children with asthma, especially in those receiving high doses of systemic or inhaled glucocorticosteroids, and long-term treatment as well. Copyright © 2014 Elsevier Ltd. All rights reserved.

Asthma management in a specialist setting: Results of an Italian Respiratory Society survey.

PubMed

Braido, Fulvio; Baiardini, Ilaria; Alleri, Pietro; Bacci, Elena; Barbetta, Carlo; Bellocchia, Michela; Benfante, Alida; Blasi, Francesco; Bucca, Caterina; Busceti, Maria Teresa; Centanni, Stefano; Colanardi, Maria Cristina; Contoli, Marco; Corsico, Angelo; D'Amato, Maria; Di Marco, Fabiano; Marco, Dottorini; Ferrari, Marta; Florio, Giovanni; Fois, Alessandro Giuseppe; Foschino Barbaro, Maria Pia; Silvia, Garuti; Girbino, Giuseppe; Grosso, Amelia; Latorre, Manuela; Maniscalco, Sara; Mazza, Francesco; Mereu, Carlo; Molinengo, Giorgia; Ora, Josuel; Paggiaro, Pierluigi; Patella, Vincenzo; Pelaia, Girolamo; Pirina, Pietro; Proietto, Alfio; Rogliani, Paola; Santus, Pierachille; Scichilone, Nicola; Simioli, Francesca; Solidoro, Paolo; Terraneo, Silvia; Zuccon, Umberto; Canonica, Giorgio Walter

2017-06-01

Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources. to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting. A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society. The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients). The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately. Copyright © 2017 Elsevier Ltd. All rights reserved.

Economic analysis of temperature-controlled laminar airflow (TLA) for the treatment of patients with severe persistent allergic asthma.

PubMed

Brazier, Peter; Schauer, Uwe; Hamelmann, Eckard; Holmes, Steve; Pritchard, Clive; Warner, John O

2016-01-01

Chronic asthma is a significant burden for individual sufferers, adversely impacting their quality of working and social life, as well as being a major cost to the National Health Service (NHS). Temperature-controlled laminar airflow (TLA) therapy provides asthma patients at BTS/SIGN step 4/5 an add-on treatment option that is non-invasive and has been shown in clinical studies to improve quality of life for patients with poorly controlled allergic asthma. The objective of this study was to quantify the cost-effectiveness of TLA (Airsonett AB) technology as an add-on to standard asthma management drug therapy in the UK. The main performance measure of interest is the incremental cost per quality-adjusted life year (QALY) for patients using TLA in addition to usual care versus usual care alone. The incremental cost of TLA use is based on an observational clinical study monitoring the incidence of exacerbations with treatment valued using NHS cost data. The clinical effectiveness, used to derive the incremental QALY data, is based on a randomised double-blind placebo-controlled clinical trial comprising participants with an equivalent asthma condition. For a clinical cohort of asthma patients as a whole, the incremental cost-effectiveness ratio (ICER) is £8998 per QALY gained, that is, within the £20 000/QALY cost-effectiveness benchmark used by the National Institute for Health and Care Excellence (NICE). Sensitivity analysis indicates that ICER values range from £18 883/QALY for the least severe patients through to TLA being dominant, that is, cost saving as well as improving quality of life, for individuals with the most severe and poorly controlled asthma. Based on our results, Airsonett TLA is a cost-effective addition to treatment options for stage 4/5 patients. For high-risk individuals with more severe and less well controlled asthma, the use of TLA therapy to reduce incidence of hospitalisation would be a cost saving to the NHS.

IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression.

PubMed

Wenzel, Sally E; Balzar, Silvana; Ampleford, Elizabeth; Hawkins, Gregory A; Busse, William W; Calhoun, William J; Castro, Mario; Chung, K Fan; Erzurum, Serpil; Gaston, Benjamin; Israel, Elliot; Teague, W Gerald; Curran-Everett, Douglas; Meyers, Deborah A; Bleecker, Eugene R

2007-03-15

Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor alpha (IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown. Allelic substitutions in IL4Ralpha are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE. Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Ralpha. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE. In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately. SNPs in IL4Ralpha, which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.

Asthma--it hasn't gone away.

PubMed

Hull, James

2012-10-01

Asthma most definitely hasn't gone away. This article provides a review of the Royal College of Physician's conference in March 2012, which progressed attendees' understanding of both the basic science and clinical aspects of asthma care. The article highlights key clinical messages from the programme for general physicians--e.g., how best to approach the assessment of patients with severe asthma.

Occupational exposures associated with work-related asthma and work-related wheezing among U.S. workers.

PubMed

Arif, Ahmed A; Delclos, George L; Whitehead, Lawrence W; Tortolero, Susan R; Lee, Eun S

2003-10-01

National estimates of occupational asthma (OA) in the United States are sparse. Using data from the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, we analyzed associations between occupation and work-related asthma and work-related wheezing among U.S. workers. This study identified several occupations that were at risk of developing work-related asthma and/or wheezing, with cleaners and equipment cleaners showing the highest risks. Other major occupations identified were farm and agriculture; entertainment; protective services; construction; mechanics and repairers; textile; fabricators and assemblers; other transportation and material moving occupations; freight, stock, and material movers; and motor vehicle operators. The population attributable risks for work-related asthma and work-related wheezing were 26% and 27%, respectively. This study adds evidence to the literature that identifies work-related asthma as an important public health problem. Several occupations are targeted for additional evaluation and study. Of particular interest are cleaners, which are being increasingly reported as a risk group for asthma. Future intervention strategies need to be developed for effective control and prevention of asthma in the workplace. Copyright 2003 Wiley-Liss, Inc.

EVALUATION OF EXPOSURE MEASUREMENT METHODS AND APPROACHES FOR THE NATIONAL CHILDREN'S STUDY

EPA Science Inventory

Several hypotheses have been proposed for the National Children's Study to examine the role of environmental exposures to chemical pollutants in health outcomes including asthma and impaired neurobehaviorial or neurocognitive function. To address these hypotheses, it will be nec...

Mortality among subjects with chronic obstructive pulmonary disease or asthma at two respiratory disease clinics in Ontario

PubMed Central

Finkelstein, Murray M; Chapman, Kenneth R; McIvor, R Andrew; Sears, Malcolm R

2011-01-01

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma are common; however, mortality rates among individuals with these diseases are not well studied in North America. OBJECTIVE: To investigate mortality rates and risk factors for premature death among subjects with COPD. METHODS: Subjects were identified from the lung function testing databases of two academic respiratory disease clinics in Hamilton and Toronto, Ontario. Mortality was ascertained by linkage to the Ontario mortality registry between 1992 and 2002, inclusive. Standardized mortality ratios were computed. Poisson regression of standardized mortality ratios and proportional hazards regression were performed to examine the multivariate effect of risk factors on the standardized mortality ratios and mortality hazards. RESULTS: Compared with the Ontario population, all-cause mortality was approximately doubled among subjects with COPD, but was lower than expected among subjects with asthma. The risk of mortality in patients with COPD was related to cigarette smoking, to the presence of comorbid conditons of ischemic heart disease and diabetes, and to Global initiative for chronic Obstructive Lung Disease severity scores. Individuals living closer to traffic sources showed an elevated risk of death compared with those who lived further away from traffic sources. CONCLUSIONS: Mortality rates among subjects diagnosed with COPD were substantially elevated. There were several deaths attributed to asthma among subjects in the present study; however, overall, patients with asthma demonstrated lower mortality rates than the general population. Subjects with COPD need to be managed with attention devoted to both their respiratory disorders and related comorbidities. PMID:22187688

Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma*

PubMed Central

Pinto, Charleston Ribeiro; Almeida, Natalie Rios; Marques, Thamy Santana; Yamamura, Laira Lorena Lima; Costa, Lindemberg Assunção; Souza-Machado, Adelmir

2013-01-01

OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here. PMID:24068261

Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study.

PubMed

Albers, Frank C; Müllerová, Hana; Gunsoy, Necdet B; Shin, Ji-Yeon; Nelsen, Linda M; Bradford, Eric S; Cockle, Sarah M; Suruki, Robert Y

2018-02-01

Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice. This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible. The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31-41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (n = 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7-21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (n = 101), 27-37% were omalizumab-eligible and 18% were reslizumab-eligible. Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma.

Using the Inflammacheck Device to Measure the Level of Exhaled Breath Condensate Hydrogen Peroxide in Patients With Asthma and Chronic Obstructive Pulmonary Disease (The EXHALE Pilot Study): Protocol for a Cross-Sectional Feasibility Study

PubMed Central

Fogg, Carole; Brown, Thomas P; Jones, Thomas L; Lanning, Eleanor; Bassett, Paul; Chauhan, Anoop J

2018-01-01

Background Asthma and Chronic Obstructive Pulmonary Disease (COPD) are common conditions that affect over 5 million people in the United Kingdom. These groups of patients suffer significantly from breathlessness and recurrent exacerbations that can be difficult to diagnose and go untreated. A common feature of COPD and asthma is airway inflammation that increases before and during exacerbations. Current methods of assessing airway inflammation can be invasive, difficult to perform, and are often inaccurate. In contrast, measurement of exhaled breath condensate (EBC) hydrogen peroxide (H2O2) is performed during normal tidal breathing and is known to reflect the level of global inflammation in the airways. There is a need for novel tools to diagnose asthma and COPD earlier and to detect increased airway inflammation that precedes an exacerbation. Objective The aim of this study was to explore the use of a new handheld device (called Inflammacheck) in measuring H2O2 levels in EBC. We will study whether it can measure EBC H2O2 levels consistently and whether it can be used to differentiate asthma and COPD from healthy controls. Methods We will perform a cross-sectional, feasibility, pilot study of EBC H2O2 levels, as measured by Inflammacheck, and other markers of disease severity and symptom control in patients with asthma and COPD and volunteers with no history of lung disease. Participants will be asked to provide an exhaled breath sample for measurement of their EBC H2O2 using Inflammacheck. The result will be correlated with disease stage, spirometry, fractional exhaled nitric oxide (FeNO), and symptom control scores. Results This study’s recruitment is ongoing; it is anticipated that the results will be available in 2018. Conclusions The EXhaled Hydrogen peroxide As a marker of Lung diseasE (EXHALE) pilot study will provide an evaluation of a new method of measuring EBC H2O2. It will assess the device’s consistency and ability to distinguish airway inflammation in asthma and COPD compared with healthy controls. PMID:29382628

Trial of a "credit card" asthma self-management plan in a high-risk group of patients with asthma.

PubMed

D'Souza, W; Burgess, C; Ayson, M; Crane, J; Pearce, N; Beasley, R

1996-05-01

The "credit card" asthma self-management plan provides the adult asthmatic patient with simple guidelines for the self-management of asthma, which are based on the self-assessment of peak expiratory flow rate recordings and symptoms. The study was a trial of the clinical efficacy of the credit card plan in a high-risk group of asthmatic patients. In this "before-and-after" trial, patients discharged from the emergency department of Wellington Hospital, after treatment for severe asthma were invited to attend a series of hospital outpatient clinics at which the credit card plan was introduced. Questionnaires were used to compare markers of asthma morbidity, requirement for emergency medical care, and medication use during the 6-month period before and after intervention with the credit card plan. Of the 30 patients with asthma who attended the first outpatient clinic, 26 (17 women and 9 men) completed the program. In these 26 participants, there was a reduction in both morbidity and requirement for acute medical services: specifically, the proportion waking with asthma more than once a week decreased from 65% to 23% (p = 0.005) and the proportion visiting the emergency department for treatment of severe asthma decreased from 58% to 15% (p = 0.004). The patients attending the clinics commented favorably on the plan, in particular on its usefulness as an educational tool for monitoring and treating their asthma. Although the interpretation of this study is limited by the lack of a randomized control group, the findings are consistent with other evidence that the credit card asthma self-management plan can be an effective and acceptable system for improving asthma care in a high-risk group of adult patients with asthma.

CCL11 as a potential diagnostic marker for asthma?

PubMed

Wu, Dandan; Zhou, Ji; Bi, Hui; Li, Lingling; Gao, Wei; Huang, Mao; Adcock, Ian M; Barnes, Peter J; Yao, Xin

2014-10-01

Asthma is an inflammatory airway disease characterized by airway eosinophilia, in which CCL11 (eotaxin) plays a crucial role. The aim of study is to determine the elevation of CCL11 levels in bronchoalveolar lavage fluid (BALF), blood, exhaled breath condensate (EBC) and sputum in asthma patients and to identify which medium yields the most significant change in CCL11 level. The databases of PubMed, Embase and Cochrane Centre Register of Controlled Trials were systematically searched from inception to September 2013. Controlled clinical trials that focused on CCL11 concentrations in asthma patients and controls, and their correlations with other asthma indicators were obtained. Data were analysed using Stata 12.0. Thirty studies were included in this investigation. CCL11 levels in blood, EBC and sputum were significantly higher in asthma patients than in healthy subjects. Sputum CCL11 concentrations were significantly elevated in unstable asthma patients versus stable asthma patients and in uncontrolled asthma patients versus partially controlled asthma patients. CCL11 levels in sputum and blood were negatively correlated with the lung function as measured by FEV1% predicted, and were positively correlated with BALF, EBC and sputum eosinophil counts. Similarly, CCL11 concentrations were positively correlated with eosinophil cationic protein in EBC, blood and sputum as well as with interleukin-5 in sputum and fractional exhaled nitric oxide in EBC. Steroid treatment had no significant effect on CCL11 levels. CCL11 is a potentially useful biomarker for the diagnosis and assessment of asthma severity and control, especially in sputum. CCL11 is crucial in eosinophil chemoattraction and activation in asthma pathogenesis. Further studies using anti-CCL11 approaches are needed to confirm a role for CCL11 in asthma pathogenesis particularly in patients with more severe disease.

Long-term CPAP treatment improves asthma control in patients with asthma and obstructive sleep apnoea.

PubMed

Kauppi, Paula; Bachour, Patrick; Maasilta, Paula; Bachour, Adel

2016-12-01

Both asthma and obstructive sleep apnoea cause sleep disturbance, daytime sleepiness and diminished quality of life. Continuous positive airway pressure (CPAP) is efficient in reducing symptoms related to sleep apnoea. Here we report the impact of long-term use of CPAP on asthma symptoms. A survey questionnaire was distributed to all of our obstructive sleep apnoea patients with CPAP therapy in 2013. We used the Finnish version of the Asthma Control Test™ (ACT) and a visual analogue scale (0 = no symptoms, 100 = severe asthma symptoms). Asthma was defined as self-reported physician-diagnosed disease and a special reimbursement for asthma medication by the Social Insurance Institution. We sent 2577 questionnaires and received 1586 answers (61 %). One hundred ninety-seven patients were asthmatics with a prevalence of asthma among CPAP users of 13 %. We studied 152 patients (58 females) whose CPAP therapy was initiated after starting asthma medication. Their mean (SD) age was 62 (10) years, duration of CPAP 5.7 (4.7) years and their CPAP daily use was 6.3 (2.4) h. Self-reported asthma severity decreased significantly from 48.3 (29.6) to 33.1 (27.4) (p < 0.001), and ACT score increased significantly from 15.35 (5.3) to 19.8 (4.6) (p < 0.001) without a significant change in the body mass index (BMI). The percentage of patients using rescue medication daily reduced from 36 to 8 % with CPAP (P < 0.001). We noticed a significant decrease in asthma symptoms with long-term use of CPAP in patients with both asthma and obstructive sleep apnoea.

Compositions, antibodies, asthma diagnosis methods, and methods for preparing antibodies

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

Jin, Hongjun; Zangar, Richard C.

Methods for preparing an antibody are provided with the method including incorporating 3-bromo-4-hydroxy-benzoic acid into a protein to form an antigen, immunizing a mammalian host with the antigen, and recovering an antibody having an affinity for the antigen from the host. Antibodies having a binding affinity for a monohalotyrosine are provided as well as composition comprising an antibody bound with monohalotyrosine. Compositions comprising a protein having a 3-bromo-4-hydroxy-benzoic acid moiety are also provided. Methods for evaluating the severity of asthma are provide with the methods including analyzing sputum of a patient using an antibody having a binding affinity for monohalotyrosine,more » and measuring the amount of antibody bound to protein. Methods for determining eosinophil activity in bodily fluid are also provided with the methods including exposing bodily fluid to an antibody having a binding affinity for monohalotyrosine, and measuring the amount of bound antibody to determine the eosinophil activity.« less

Asthma and Ethnic Minorities: Socioeconomic Status and Beyond

PubMed Central

Forno, Erick; Celedón, Juan C.

2009-01-01

Purpose of review We aim to discuss current insights into our understanding of the mechanisms by which socioeconomic status (SES) influences the prevalence and severity of asthma in ethnic minorities. In addition, we review potential risk factors for ethnic disparities in asthma that are not mediated by SES. Recent findings Exposures and factors correlated with ethnicity through SES (e.g. indoor and outdoor air quality, smoke exposure, and access to healthcare) are likely to explain a significant proportion of the observed ethnic differences in asthma morbidity. However, other factors correlated with ethnicity (e.g., genetic variation) can impact ethnic disparities in asthma independently of and/or interacting with SES-related factors. Summary SES is a rough marker of a variety of environmental/behavioral exposures and a very important determinant of differences in asthma prevalence and severity among ethnic minorities in the U.S. However, SES is unlikely to be the sole explanation for ethnic disparities in asthma, which may also be due to differences in genetic variation and gene-by-environment interactions among ethnic groups. PMID:19326508

Cow milk induced allergies (CMA) and asthma in new born.

PubMed

Wang, W; Wu, H-W; Liu, J-F

2016-01-01

The prevalence of asthma and allergic diseases in childhood has increased in several industrialized countries since the second half of the twentieth century. In some countries, the prevalence is still rising, although in others it seems to have plateaued or even decreased. It has been suggested that environmental factors operating prenatally and in early life affect the development of asthma and allergic diseases. Particularly changes in microbial exposure are proposed to play an important role in the development and maturation of the immune system. Thus, the factors that affect microbial exposure, such as mode of delivery and the use of antibiotics, may influence the development of asthma and allergic diseases. Several studies have explored the associations between perinatal factors and children's use of antibiotics and the risk of asthma, with inconsistent findings. The present review article will be focused on the important findings related with factors responsible for above allergic reactions along with asthma in young infants. Also, the influence of cow milk intake will also be taken in account to cover the aspect of cow milk induced allergies and asthma in infants.

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma

PubMed Central

Xie, Yuran; Merkel, Olivia M

2015-01-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues has limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases and costimulatory factors that have been reported as targets of siRNA mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages and dendritic cells, which could potentially be applied in asthma therapy. PMID:26148454

Development of a prototype system for statewide asthma surveillance.

PubMed

Deprez, Ronald D; Asdigian, Nancy L; Oliver, L Christine; Anderson, Norman; Caldwell, Edgar; Baggott, Lee Ann

2002-12-01

We developed and evaluated a statewide and community-level asthma surveillance system. Databases and measures included a community prevalence survey, hospital admissions data, emergency department/outpatient clinic visit records, and a physician survey of diagnosis and treatment practices. We evaluated the system in 5 Maine communities varying in population and income. Asthma hospitalizations were high in the rural/low-socioeconomic-status communities studied, although diagnosed asthma was low. Males were more likely than females to experience asthma symptoms, although they were less likely to have been diagnosed with asthma or to have used hospital-based asthma care. Databases were useful for estimating asthma burden and identifying service needs as well as high-risk groups. They were less useful in estimating severity or in identifying environmental risks.

Air Pollutants, Climate, and the Prevalence of Pediatric Asthma in Urban Areas of China

PubMed Central

Zhang, Juanjuan; Yan, Li; Fu, Wenlong; Yi, Jing; Chen, Yuzhi; Liu, Chuanhe; Xu, Dongqun; Wang, Qiang

2016-01-01

Background. Prevalence of childhood asthma varies significantly among regions, while its reasons are not clear yet with only a few studies reporting relevant causes for this variation. Objective. To investigate the potential role of city-average levels of air pollutants and climatic factors in order to distinguish differences in asthma prevalence in China and explain their reasons. Methods. Data pertaining to 10,777 asthmatic patients were obtained from the third nationwide survey of childhood asthma in China's urban areas. Annual mean concentrations of air pollutants and other climatic factors were obtained for the same period from several government departments. Data analysis was implemented with descriptive statistics, Pearson correlation coefficient, and multiple regression analysis. Results. Pearson correlation analysis showed that the situation of childhood asthma was strongly linked with SO2, relative humidity, and hours of sunshine (p < 0.05). Multiple regression analysis indicated that, among the predictor variables in the final step, SO2 was found to be the most powerful predictor variable amongst all (β = −19.572, p < 0.05). Furthermore, results had shown that hours of sunshine (β = −0.014, p < 0.05) was a significant component summary predictor variable. Conclusion. The findings of this study do not suggest that air pollutants or climate, at least in terms of children, plays a major role in explaining regional differences in asthma prevalence in China. PMID:27556031

Physicians' preferences for asthma guidelines implementation.

PubMed

Kang, Min-Koo; Kim, Byung-Keun; Kim, Tae-Wan; Kim, Sae-Hoon; Kang, Hye-Ryun; Park, Heung-Woo; Chang, Yoon-Seok; Kim, Sun-Sin; Min, Kyung-Up; Kim, You-Young; Cho, Sang-Heon

2010-10-01

Patient care based on asthma guidelines is cost-effective and leads to improved treatment outcomes. However, ineffective implementation strategies interfere with the use of these recommendations in clinical practice. This study investigated physicians' preferences for asthma guidelines, including content, supporting evidence, learning strategies, format, and placement in the clinical workplace. We obtained information through a questionnaire survey. The questionnaire was distributed to physicians attending continuing medical education courses and sent to other physicians by airmail, e-mail, and facsimile. A total of 183 physicians responded (male to female ratio, 2.3:1; mean age, 40.4±9.9 years); 89.9% of respondents were internists or pediatricians, and 51.7% were primary care physicians. Physicians preferred information that described asthma medications, classified the disease according to severity and level of control, and provided methods of evaluation/treatment/monitoring and management of acute exacerbation. The most effective strategies for encouraging the use of the guidelines were through continuing medical education and discussions with colleagues. Physicians required supporting evidence in the form of randomized controlled trials and expert consensus. They preferred that the guidelines be presented as algorithms or flow charts/flow diagrams on plastic sheets, pocket cards, or in electronic medical records. This study identified the items of the asthma guidelines preferred by physicians in Korea. Asthma guidelines with physicians' preferences would encourage their implementation in clinical practice.

Asthma phenotypes modify the impact of environmetnal factors on lung function

EPA Science Inventory

Previous studies have examined the role of childhood asthma phenotypes based on clinical history on asthma severity and symptom aggravation by environmental risk factors. The current study focuses on the associations between lung function in childhood and environmental factors an...

The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children.

PubMed

Arikoglu, Tugba; Kuyucu, Semanur; Karaismailoglu, Eda; Batmaz, Sehra Birgul; Balci, Senay

2015-01-01

Recent evidence about the various effects of vitamin D (vit D) on innate and adaptive immunity has led to a search for the role of vit D in asthma. It is postulated that a decrease in cathelicidin, a multifunctional host defense molecule, production due to low vit D status may predispose to infectious complications in children with asthma. The aim of this study was to determine the association of vit D, vit D-binding protein (VDBP) and cathelicidin with acute asthma attacks among children with allergic asthma. This prospective study included 35 patients with acute asthma attack and 32 children with controlled asthma, and all were matched by sampling season, sensitization to mites, and previous severity of asthma. A comprehensive questionnaire about risk factors, blood sampling for 25-hydroxyvitamin D vit D, VDBP, and cathelicidin levels; spirometric indices were used. Factors that influence serum vit D and cathelicidin levels and the development of asthma attacks were evaluated with multivariate analysis. The mean serum vit D levels of the attack group was significantly lower than that of the controlled asthma group (p < 0.001). The mean cathelicidin level was significantly higher in the acute asthma group than with the controlled subjects with asthma (p = 0.002). There was no difference between the acute and controlled asthma groups in terms of markers of allergy and serum VDBP levels. Risk factors that may influence vit D levels revealed that body mass index (BMI) (p = 0.038), duration of sun exposure (p < 0.001), and amount of dietary vit D (p < 0.001) independently affected serum vit D levels. Risk factors that may result in acute asthma showed that low serum levels of vit D were significantly related to the risk of asthma attacks (p < 0.001, adjusted odds ratio 16.11). Cathelicidin levels showed a significant positive association with asthma attacks and BMI. Vit D deficiency showed a significant relationship to the development of asthma attacks independent of cathelicidin deficiency and other factors associated with the severity of chronic asthma.

Prevalence of gastro-esophageal reflux disease in patients with difficult to control asthma and effect of proton pump inhibitor therapy on asthma symptoms, reflux symptoms, pulmonary function and requirement for asthma medications.

PubMed

Sandur, V; Murugesh, M; Banait, V; Rathi, P M; Bhatia, S J; Joshi, J M; Kate, A

2014-01-01

The hypothesis that GER can trigger or exacerbate asthma is supported by several clinical trials that have shown amelioration in asthma symptoms and/or an improvement in pulmonary function after antireflux therapy. To investigate the prevalence of GER in patients with difficult to control asthma and to determine the effect of omeprazole on asthma symptoms, reflux symptoms, pulmonary function and on the requirement of asthma medications. Patients with difficult to control asthma were recruited into the study. All patients underwent esophageal manometry and 24 hour esophageal pH monitoring. Pulmonary function tests were done before and after treatment. The severity of asthma and reflux was assessed by a 1 week pulmonary symptom score(PSS) and reflux symptom score(RSS) respectively before and after treatment. Those who had an abnormal pH study (pH <4 in the distal esophagus for >5% of the time) underwent anti-GER treatment with lifestyle changes, and a proton pump inhibitor (omeprazole 40 mg, bid) for 3 months. Asthma medications were added or deleted based on severity of asthma. Out of 250 asthmatic patients screened, forty patients fulfilled the inclusion criteria. Twenty eight of 40 patients(70%) were diagnosed to have GERD. Of the patients 28 with GER, 8 patients(28.5%) had no reflux symptoms. On 24 hr pH metry, the percentage time pH <4.0 was 10.81 ± 4.72 and 1.11 ± 1.21; Deemester score was 37.65 ± 14.54 and 4.89 ± 6.39 (p-value is 0.0001) in GERD and non-GERD patients respectively.In GERD group, post treatment reflux symptom score(RSS) improved from 22.39 ± 14.99 to 1.04 ± 1.07, pulmonary symptom score(PSS) improved from 27.14 ± 7.49 to 13.82 ± 4.21 and night time asthma symptom score(NASS) improved from 6.71 ± 1.80 to 3.04 ± 1.23 (p-value <0.0001). After treatment, FEV1 and PEFR increased from 1.38 ± 0.57 and 4.14 ± 1.97 to 1.47 ± 0.54 and 5.56 ± 1.72, respectively (p-value 0.00114). PPI therapy improves nocturnal asthma symptoms, daytime asthma symptoms, pulmonary function and decreases requirement of asthma medications in these patients.

Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection

PubMed Central

Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco

2008-01-01

Background Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. Methods We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4–8 weeks. Results Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 ± 104 L/min vs 276 ± 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 ± 24.54 vs FEV1% 92.91 ± 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38–13.32). Conclusion Our data suggest an association between acute atypical infection and a more severe AEBA. PMID:18513407

Comparison of patterns of allergen sensitization among inner-city Hispanic and African American children with asthma.

PubMed

Rastogi, Deepa; Reddy, Mamta; Neugebauer, Richard

2006-11-01

Among Hispanics, the largest minority ethnic group in the United States, asthma prevalence is increasing, particularly in inner-city neighborhoods. Although allergen sensitization among asthmatic African Americans has been extensively studied, similar details are not available for Hispanic children. To examine patterns of allergen sensitization, including the association with illness severity, in asthmatic children overall and in Hispanic and African American children living in a socioeconomically disadvantaged area of New York City. A retrospective medical record review of asthmatic children attending a community hospital in the South Bronx area of New York City was performed. Information abstracted included demographics, asthma severity classification, reported exposures to indoor allergens, and results of allergy testing. Among 384 children in the analysis, 270 (70.3%) were Hispanic and 114 (29.7%) were African American. Sensitization to indoor and outdoor allergens, respectively, did not differ between Hispanic (58.5% and 27.0%) and African American (58.8% and 32.6%) children. Allergen sensitization exhibited a direct, significant association with asthma severity for indoor allergens for the 2 ethnic groups combined and for Hispanics separately but not between asthma severity and outdoor allergens (P < .01). No correlation was found between self-reported allergen exposure and sensitization. Patterns of allergen sensitization among inner-city Hispanic asthmatic children resemble those among African American children, a finding that is likely explained by the similarity in levels of environmental exposures. With the increasing prevalence of asthma among inner-city Hispanic children, skin testing should be used frequently for objective evaluation of asthma in this ethnic group.

Vitamin D and Bronchial Asthma: An overview of the last five years

PubMed Central

Hall, Sannette C.; Agrawal, Devendra K.

2017-01-01

Vitamin D is a potent immunomodulator capable of dampening inflammatory signals in several cell types involved in the asthmatic response. Its deficiency has been associated with increased inflammation, exacerbations and overall worse outcomes in patients with asthma. Given the increase in the prevalence of asthma over the last few decades, there has been enormous interest in the use of vitamin D supplementation as a potential therapeutic option. Several studies have found that low serum levels of vitamin D (< 20 ng/ml) are associated with increased exacerbations, increased airway inflammation, decreased lung function and poor prognosis in asthmatic patients. Results from the in vitro and in vivo studies in animals and human have suggested that supplementation with vitamin D can ameliorate several hallmark features of asthma. However, the findings obtained from clinical trials are controversial and do not unequivocally support the beneficial role of vitamin D in asthma. Largely, interventional studies in children, pregnant women and adults have primarily found little-to-no effect of vitamin D supplementation on improved asthma symptoms, onset or progression of the disease. This could be related to the severity of the disease process and other confounding factors. Despite the conflicting data obtained from clinical trials, vitamin D deficiency does influence the inflammatory response in the airways. Further studies are needed to determine the exact mechanisms by which vitamin D supplementation may induce anti-inflammatory effects. Here, we critically reviewed the most recent findings from in vitro studies, animal models, and clinical trials regarding the role of vitamin D in bronchial asthma. PMID:28449868

Medical emergencies: pulmonary embolism and acute severe asthma.

PubMed

Somasundaram, K; Ball, J

2013-01-01

In this, the second of two articles covering specific medical emergencies, we discuss the definitions, epidemiology, pathophysiology, acute and chronic management of pulmonary embolus and acute severe asthma. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

Association between Concentrations of Metals in Urine and Adult Asthma: A Case-Control Study in Wuhan, China

PubMed Central

Huang, Xiji; Xie, Jungang; Cui, Xiuqing; Zhou, Yun; Wu, Xiaojie; Lu, Wei; Shen, Yan; Yuan, Jing; Chen, Weihong

2016-01-01

Background Several metals have been reported to be associated with childhood asthma. However, the results on relationships between metals and risk of childhood asthma are inconclusive, and the research on adult asthma in the Chinese general population is rare. Objectives To investigate potential associations between levels of urinary metals and adult asthma. Methods A case-control study of 551 adult asthma cases and 551 gender- and age-matched controls was conducted in Wuhan, China. Demographic information was obtained, and lung function was assessed. The urinary concentrations of 22 metals were measured by inductively coupled plasma mass spectrometry. Results After adjusting for other metalsand other covariates, urinary cadmium, molybdenum, chromium, copper, uranium and selenium were positively associated with asthma, with odds ratios (95% CI) of 1.69 (1.00, 2.85), 3.76 (2.30, 6.16), 4.89 (3.04, 7.89), 6.06 (3.27, 11.21), 6.99 (4.37, 11.19) and 9.17 (4.16, 20.21), respectively. By contrast, urinary lead, barium, iron, zinc, nickel, manganese and rubidium were negatively associated with asthma, with odds ratios (95% CI) of 0.48 (0.29, 0.80), 0.44 (0.27, 0.71), 0.41 (0.26, 0.64), 0.40 (0.24, 0.66), 0.30 (0.22, 0.41), 0.23 (0.14, 0.39) and 0.07 (0.03, 0.15), respectively. When comparing urinary metals in different subgroups of cases with those in matched controls, the associations of above 13 metals with asthma prevalence were nearly the same. Conclusions Our results suggested that asthma prevalence in the Chinese adults was positively associated with urinary chromium, chromium, selenium, molybdenum, cadmium, and uranium, and negatively associated with urinary manganese, iron, nickel, zinc, rubidium, barium and lead. Additional research with larger populations in different regions is required to support our findings. PMID:27191859

Body mass index and risk of hospitalization among adults presenting with asthma exacerbation to the emergency department.

PubMed

Hasegawa, Kohei; Tsugawa, Yusuke; Lopez, Bernard L; Smithline, Howard A; Sullivan, Ashley F; Camargo, Carlos A

2014-11-01

Studies have linked obesity to incident asthma and worse chronic severity/control. However, the relationship between obesity and acute asthma morbidity remains unclear. To determine whether obese adults presenting to the emergency department (ED) with asthma exacerbation are at higher risk of hospitalization compared with normal-weight adults. Multicenter chart review study of 48 EDs across 23 U.S. states. We identified ED patients aged 18 to 54 years with asthma exacerbation during 2011 to 2012. Primary outcome was hospitalization. The analytic cohort comprised 1,227 patients. Of these, 323 patients (27%) were overweight (body mass index [BMI], 25-29.9 kg/m(2)), and 607 (50%) were obese (BMI ≥ 30 kg/m(2)). Among the 607 obese patients, 364 patients (60%) were severely obese (BMI ≥ 35 kg/m(2)). Several markers of chronic severity/control of asthma and acute severity did not differ across BMI groups. By contrast, compared with normal-weight patients, the risk of hospitalization was higher in patients who were overweight (11 vs. 18%; odds ratio [OR], 1.68; 95% confidence interval [CI], 1.05-2.68; P = 0.03) or obese (11 vs. 23%; OR, 2.30; 95% CI, 1.53-3.49; P < 0.001). In the adjusted analysis with multiple imputation, the association lost statistical significance in overweight patients (OR, 1.56; 95% CI, 0.90-2.71; P = 0.11) but persisted in obese patients (OR, 1.69; 95% CI, 1.02-2.81; P = 0.04). The latter finding was driven by an even higher risk of hospitalization in severely obese patients (OR, 1.95; 95% CI, 1.13-3.34; P = 0.02). In this multicenter study of ED patients with asthma exacerbation, we found that obese adults were at a higher risk of hospitalization compared with normal-weight adults.

Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma.

PubMed

Shi, Yu-heng; Shi, Guo-chao; Wan, Huan-ying; Jiang, Li-hua; Ai, Xiang-yan; Zhu, Hai-xing; Tang, Wei; Ma, Jia-yun; Jin, Xiao-yan; Zhang, Bo-ying

2011-07-05

Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4(+) T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells in patients with allergic asthma. Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells were determined by flow cytometry. The expression of cytokines in plasma and in the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4(+)CD25(+) Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Imbalances in Th1/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.

An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma

PubMed Central

Burden, Anne; Roche, Nicolas; Miglio, Cristiana; Hillyer, Elizabeth V; Postma, Dirkje S; Herings, Ron MC; Overbeek, Jetty A; Khalid, Javaria Mona; van Eickels, Daniela; Price, David B

2017-01-01

Background Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre–post historical database study to investigate asthma-related outcomes by treatment. Methods We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of <10% between cohorts. Results Of 4064 eligible patients, 1382 (34%) were prescribed ciclesonide and 2682 (66%) fine-particle ICS. The IPTW and propensity score-based methods retained more patients (96%–100%) than exact matching (90%); exact matching selected less severe patients. Standardized differences were >10% for four variables in the exact-matched dataset and <10% for both PSM algorithms and the weighted pseudo-dataset used in the IPTW method. With all methods, ciclesonide was associated with better 1-year asthma-related outcomes, at one-third the prescribed dose, than fine-particle ICS; results varied slightly by method, but direction and statistical significance remained the same. Conclusion We found that each method has its particular strengths, and we recommend at least two methods be applied for each matched cohort study to evaluate the robustness of the findings. Balance diagnostics should be applied with all methods to check the balance of confounders between treatment cohorts. If exact matching is used, the calculation of a propensity score could be useful to identify variables that require balancing, thereby informing the choice of matching criteria together with clinical considerations. PMID:28356782

Current practice in assessment and treatment of bronchial asthma in young males in Italy.

PubMed

Ferrante, E; Pantaleo, C; Quatela, M; Fuso, L; Basso, S; Pistelli, R

2000-10-01

The aim of the study was to evaluate, in a sample of young asthmatics in Italy, the current practice in assessment and treatment of asthma after the publication of guidelines. Young soldiers who declared bronchial asthma at the beginning of the compulsory military service were evaluated. One-hundred and thirty-eight subjects with confirmed asthma were selected. Sixty-seven subjects (48.5%) had had at last one spirometry, and only one subject had underwent peak flow monitoring at home; most of the subjects (96.8%) had had prick tests. More of the 50% of the subjects with bronchial obstruction or with severe bronchial hyperresponsiveness, with clinical moderate or severe asthma, had used only bronchodilators or no therapy at all in the preceding year. In this sample of young asthmatics, the lung function tests were still underutilized for the diagnosis and follow-up of bronchial asthma; moreover, the inhaled anti-inflammatory drugs were still underutilized.

[The impact of psychological variables on the presentation and progress of asthma and patient's cognitive functions].

PubMed

Talarowska, Monika; Florkowski, Antoni; Gałecki, Piotr; Szemraj, Janusz; Zboralski, Krzysztof; Pietras, Tadeusz; Górski, Paweł

2009-01-01

Chronic respiratory system diseases become serious public health problem all over the world. The most prevalent are obstructive diseases (asthma and COPD). The prevalence of asthma is still high and concern patients representing wide range of age and socio-economic status. Despite progress in diagnostic and therapeutic options several studies showed that asthma has an impact on health-related quality of life and patients' coping. Asthma as chronic condition results in limitations of patients activity and social relations. Thus psychosocial variables, which may have an impact on asthma symptoms presentation and disease progress, should be considered. There are only few reports concerning cognitive functions in asthma. The aim of the study was to assess the potential impact of psychosocial factors on asthma symptoms presentation, and cognitive function in asthma patients.

Acute asthma severity identification of expert system flow in emergency department

NASA Astrophysics Data System (ADS)

Sharif, Nurul Atikah Mohd; Ahmad, Norazura; Ahmad, Nazihah; Desa, Wan Laailatul Hanim Mat

2017-11-01

Integration of computerized system in healthcare management help in smoothening the documentation of patient records, highly accesses of knowledge and clinical practices guideline, and advice on decision making. Exploit the advancement of artificial intelligent such as fuzzy logic and rule-based reasoning may improve the management of emergency department in terms of uncertainty condition and medical practices adherence towards clinical guideline. This paper presenting details of the emergency department flow for acute asthma severity identification with the embedding of acute asthma severity identification expert system (AASIES). Currently, AASIES is still in preliminary stage of system validation. However, the implementation of AASIES in asthma bay management is hope can reduce the usage of paper for manual documentation and be a pioneer for the development of a more complex decision support system to smoothen the ED management and more systematic.

The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents.

PubMed

Lambert, Katrina A; Prendergast, Luke A; Dharmage, Shyamali C; Tang, Mimi; O'Sullivan, Molly; Tran, Thomas; Druce, Julian; Bardin, Philip; Abramson, Michael J; Erbas, Bircan

2017-10-11

It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender. Virus strain was determined for 113 children with HRV detectable at the time of admission for asthma exacerbation. Patient characteristics were collected on admission and exacerbation severity was scored using several validated scales. HRV species by itself was not associated with moderate/severe vs. mild exacerbations. Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2-13.4) to have a moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI: 1.8-47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9-11.8 vs 7 years old: OR: 1.2, 95% CI: 0.2-6.6). In contrast, children with HRV-C infection and sensitized to pollen during the pollen season were less likely to have moderate/severe exacerbations (p = 0.01 for the interaction term). Acute asthma exacerbations are more likely to be moderate/severe in boys under 5 years of age who had HRV-C infection on admission. The opposite was found in children with sensitization to pollen during pollen season.

Respiratory effect of beta‐blocker eye drops in asthma: population‐based study and meta‐analysis of clinical trials

PubMed Central

Dreischulte, Tobias; Lipworth, Brian J.; Donnan, Peter T.; Jackson, Cathy; Guthrie, Bruce

2016-01-01

Aims To measure the prevalence of beta‐blocker eye drop prescribing and respiratory effect of ocular beta‐blocker administration in people with asthma. Methods We measured the prevalence of ocular beta‐blocker prescribing in people with asthma and ocular hypertension, and performed a nested case–control study (NCCS) measuring risk of moderate exacerbations (rescue steroids in primary care) and severe exacerbations (asthma hospitalization) using linked data from the UK Clinical Practice Research Datalink. We then performed a systematic review and meta‐analysis of clinical trials evaluating changes in lung function following ocular beta‐blocker administration in people with asthma. Results From 2000 to 2012, the prevalence of non‐selective and selective beta‐blocker eye drop prescribing in people with asthma and ocular hypertension fell from 23.0% to 13.4% and from 10.5% to 0.9% respectively. In the NCCS, the relative incidence (IRR) of moderate exacerbations increased significantly with acute non‐selective beta‐blocker eye drop exposure (IRR 4.83, 95% CI 1.56–14.94) but not with chronic exposure. In the meta‐analysis, acute non‐selective beta‐blocker eye drop exposure caused significant mean falls in FEV1 of −10.9% (95% CI −14.9 to −6.9), and falls in FEV1 of ≥20% affecting one in three. Corresponding values for selective beta‐blockers in people sensitive to ocular non‐selective beta‐blockers was −6.3% (95% CI −11.7 to −0.8), and a non‐significant increase in falls in FEV1 of ≥20%. Conclusion Non‐selective beta‐blocker eye drops significantly affect lung function and increase asthma morbidity but are still frequently prescribed to people with asthma and ocular hypertension despite safer agents being available. PMID:27161880

Association between protozoa in sputum and asthma: a case-control study.

PubMed

van Woerden, Hugo C; Ratier-Cruz, Adriana; Aleshinloye, Olabode B; Martinez-Giron, Rafael; Gregory, Clive; Matthews, Ian P

2011-06-01

Atypical infectious agents have been proposed as potential contributors to asthma. A novel set of morphological and staining criteria permit the identification of flagellated protozoa in sputum. This case-control study was designed to use this novel method and to assess: (1) are protozoa more common in asthmatics than in non-asthmatics; (2) is the presence of protozoa associated with the use of steroid inhalers; and (3) is the presence of protozoa associated with living in damp housing? Induced sputum samples were collected from asthma patients and local non-atopic, non-smoking controls. Questionnaires assessed asthma severity and housing conditions. Sputum was examined for flagellated protozoa using a previously described staining technique. 96 participants were recruited for this study; 54 asthma patients and 42 controls, age range 21-62 years, 70% female participants. Limiting results to those who were clearly positive or negative for flagellated protozoa, 66.7% (20/30) of asthmatics and 30.8% (4/13) of controls had protozoa (p = 0.046). Among the asthma patients, prevalence of protozoa was not significantly different between those who had (10/18), and those who had not (10/12), used steroid inhaler in the preceding two weeks (p = 0.11). Similarly, the prevalence of protozoa was not significantly different between those who did (6/11) and those who did not (18/32), live in damp homes (p = 0.92). This case-control study demonstrates an association between flagellated protozoa in sputum and asthma. It is now necessary to confirm and characterise the protozoa using genetic techniques based on 18S ribosomal RNA. Once tis is established it would be worthwhile to determine if asthma symptoms improve when treated by anti-protozoal agents. Copyright © 2010 Elsevier Ltd. All rights reserved.

The effect of DPP-4 inhibitors on asthma control: an administrative database study to evaluate a potential pathophysiological relationship.

PubMed

Colice, Gene; Price, David; Gerhardsson de Verdier, Maria; Rabon-Stith, Karma; Ambrose, Christopher; Cappell, Katherine; Irwin, Debra E; Juneau, Paul; Vlahiotis, Anna

2017-01-01

DPP-4 may regulate immunological pathways implicated in asthma. Assessing whether DPP-4 inhibitor (DPP-4i) use might affect asthma control is clinically important because DPP-4i use in type 2 diabetes mellitus management (T2DM) is increasing. This study evaluated associations between DPP-4i use and asthma control. This was a retrospective, observational, matched cohort study using administrative claims in the MarketScan ® Commercial Claims and Encounters (Commercial) and Medicare Supplemental and Coordination of Benefits (Medicare Supplemental) databases. Adult asthma patients initiating an oral DPP-4i or a non-DPP-4i between November 1, 2006 and March 31, 2014 were included. Patients were followed for asthma-related outcomes for 12 months after initiation of the antidiabetes medication. Outcomes included risk-domain asthma control (RDAC), defined as no asthma hospitalizations, no lower respiratory tract infections, and no oral corticosteroid (OCS) prescriptions; overall asthma control (RDAC criteria plus limited short-acting beta agonist use); treatment stability (RDAC criteria plus no increase of ≥50% in inhaled corticosteroid dose or addition of other asthma therapy); and severe asthma exacerbation rates (asthma-related hospitalizations, emergency room visits, or acute treatments with OCS). Comparisons were made between two matched cohorts (DPP-4i vs. non-DPP-4i initiators) using multivariable logistic regression and generalized linear modeling. Covariates included baseline demographic and clinical characteristics related to asthma and T2DM. The adjusted odds of achieving RDAC (odds ratio [OR]: 1.05; 95% CI: 0.964 to 1.147), overall asthma control (OR: 1.04; 95% CI: 0.956 to 1.135), and treatment stability (OR: 1.04; 95% CI: 0.949 to 1.115) did not differ between the DPP-4i and non-DPP-4i cohorts. A difference was not found between cohorts in severe asthma exacerbation rates during the 12 months following initiation of antidiabetes treatment (mean = 0.32 vs. 0.34 exacerbations per subject-year, respectively; p =0.064). Asthma control was similar between patients initiating DPP-4i and non-DPP-4i antidiabetes medications, suggesting no association between DPP-4i use and asthma control.

Insulin resistance, metabolic syndrome, and lung function in US adolescents with and without asthma.

PubMed

Forno, Erick; Han, Yueh-Ying; Muzumdar, Radhika H; Celedón, Juan C

2015-08-01

Obesity increases both the risk of asthma and asthma severity and is a well-known risk factor for insulin resistance and the metabolic syndrome (MS) in children and adolescents. We aimed to examine the association among obesity, insulin sensitivity, MS, and lung function in US adolescents with and without asthma. We performed a cross-sectional study of 1429 adolescents aged 12 to 17 years in the 2007-2010 National Health and Nutrition Examination Survey. Adjusted regression was used to assess the relationships among obesity, insulin sensitivity/resistance, MS, and lung function in children with and without asthma. Insulin resistance was negatively associated with FEV1 and forced vital capacity (FVC) in adolescents with and without asthma, whereas MS was associated with lower FEV1/FVC ratios, with a more pronounced decrease found among asthmatic patients; these associations were driven by overweight/obese adolescents. Higher body mass index was associated with a decrease in FEV1/FVC ratios among adolescents with insulin resistance. Compared with healthy participants, adolescents with MS had an approximately 2% decrease in FEV1/FVC ratios, adolescents with asthma had an approximately 6% decrease, and those with MS and asthma had approximately 10% decreased FEV1/FVC ratios (P < .05). Insulin resistance and MS are associated with worsened lung function in overweight/obese adolescents. Asthma and MS synergistically decrease lung function, as do obesity and insulin resistance. These factors might contribute to the pathogenesis of asthma severity in obese patients and warrant further investigation. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Food allergy and asthma morbidity in children.

PubMed

Simpson, Alyson B; Glutting, Joe; Yousef, Ejaz

2007-06-01

Coexisting food allergy and asthma is a significant problem in the pediatric population. Studies have looked at the association between food sensitization and asthma severity. It is unknown whether specific food allergies are associated with increased asthma morbidity. We studied the independent effect that allergy to egg, milk, fish, and peanut has on the number of hospitalizations and courses of systemic steroids in children with asthma. We performed a medical record review to evaluate the effect food allergy to egg, fish, peanut, and milk has on asthma morbidity. We reviewed the records of 201 children aged 3 months to 14 years with the diagnosis of asthma (ICD-9 codes 493.90, 493.91, and 493.92), of which 88 had coexistent food allergy. All children in the food allergy group had food-specific IgE concentrations greater than the 95% positive predictive value. We compared the rate of hospitalizations and use of systemic steroids between children with asthma and food allergies and those without coexisting food allergy using direct-entry, multiple regression analysis. Patients were adjusted for the severity of their asthma based on symptoms documented at their first visit to the allergist according to the National Asthma Education and Prevention Program guidelines and presence of environmental allergy, eczema, smoke exposure, and gastroesophageal reflux. Peanut and milk allergies were both associated with increased number of hospitalizations (P=0.009, 0.016), and milk allergy was associated with increased use of systemic steroids (P=0.001). Peanut and milk allergies were associated with increased hospitalization and steroid use and may serve as early markers for increased asthma morbidity. (c) 2007 Wiley-Liss, Inc.

Prevalence of childhood asthma in Ulaanbaatar, Mongolia in 2009.

PubMed

Yoshihara, Shigemi; Munkhbayarlakh, Sonomjants; Makino, Sohei; Ito, Clyde; Logii, Narantsetseg; Dashdemberel, Sarangerel; Sagara, Hironori; Fukuda, Takeshi; Arisaka, Osamu

2016-01-01

Bronchial asthma is a common but important chronic disease in children in all over the world. To take measures against prevalence of childhood asthma, many researchers have surveyed the actual statuses of childhood asthma in developed countries, but in most Asia-Pacific developing countries including Mongolia such surveys have never been sufficiently conducted until now. We have thought that this survey, though performed in 2009, will give important and meaningful information even now in taking measures to prevent prevailing bronchial asthma in children in Mongolia or the countries under similar statuses. The asthma prevalence and patient background information in Mongolian children aged 6-7 living in Ulaanbaatar were examined using a written questionnaire modified for their parents from that prepared by the International Study of Asthma and Allergies in Childhood (ISAAC). The estimated prevalence of asthma in Mongolian children was 20.9%. The following 3 risk factors were found to be related to asthma: (1) having allergic rhinitis symptoms, (2) mothers' smoking, and (3) history of severe respiratory infection before 1-year-old. The asthma prevalence in Mongolian children was higher than that in the world and Asia-Pacific countries reported by ISAAC. The higher prevalence was probably attributable to households' (especially mothers) smoking in draft-free houses designed for the cold area and severe air-pollution due to rapid industrialization and urbanization in Mongolia. Smoking prohibition in the mother (including family members) and a reduction of exposure to air pollutants are urgently needed to prevent developing childhood asthma. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Age related IgG subclass concentrations in asthma.

PubMed

Hoeger, P H; Niggemann, B; Haeuser, G

1994-03-01

The prevalence of IgG subclass deficiency in asthma is still controversial. Earlier studies often included patients receiving treatment with systemic steroids which can induce hypogammaglobulinaemia. Concentrations of IgG subclasses were studies in 200 children (aged 2-17 years) with asthma (mean asthma severity score (ASS) 2, range 1-4) who had not received systemic steroids for at least six weeks before investigation, and in 226 healthy age matched controls. The mean concentrations of IgG subclasses in children with asthma were within the 1SD range of those of the control group. In the group with asthma there was a trend towards higher levels of IgG1 and IgG4, whereas the number of children with low concentrations of IgG2 (< 2 SD of control serum samples; absolute concentrations 0.08-1.25 g/l) was slightly greater than in the group who did not have asthma (4.5 v 2.2%). Patients with subnormal concentrations of IgG2 could not be distinguished clinically or on the basis of case history and additional immunological studies did not show further abnormalities. Patients with severe asthma (ASS 3-4) had significantly higher concentrations of IgG4 (mean (SE) 0.53 (0.09) v 0.26 (0.04) g/l) than patients with mild asthma (ASS 1). No significant difference in subclass concentration was found between patients with atopic and those with non-atopic asthma. It is concluded that in an unselected group of children with asthma the mean IgG subclass concentrations do not differ significantly from a group of healthy age matched controls.

Influence of obesity on bone mineral density in postmenopausal asthma patients undergoing treatment with inhaled corticosteroids.

PubMed

Yanik, Burcu; Ayrim, Aylin; Ozol, Duygu; Koktener, Asli; Gokmen, Derya

2009-01-01

The etiology of osteoporosis in asthma is complex as various factors contribute to its pathogenesis. The purpose of our study was to investigate the effects of obesity and inhaled steroids, as well as the severity and duration of asthma, on osteoporosis in postmenopausal asthma patients as compared to healthy controls. A total of 46 patients with asthma and 60 healthy female controls, all postmenopausal, were enrolled in our study. Bone mineral density was assessed at the lumbar spine and hip using a Lunar DPX-L densitometer. Bone mineral density (BMD) scores were comparable between the asthmatic and control groups, with average scores of 0.95 +/- 0.29 and 0.88 +/- 0.14 g/cm(2), respectively. Likewise, osteoporosis was diagnosed in a similar percentage of patients in the asthmatic (39.1%) and control (43.3%) groups. Bone fracture was identified in four patients with asthma (8.6%) and in six patients from the control group (10%). We could not detect any relationship between BMD and duration of asthma, asthma severity, inhaled steroids or body mass index (BMI). There was no difference between the two groups with respect to age or years since menopause. Although asthma patients were more likely to be overweight and presented higher BMD scores on average than the control subjects, these differences were not statistically significant. There is a slight positive protective effect of high BMI against osteoporosis in asthma patients, but this effect is overcome by time and menopause status. Therefore, the protective effect of obesity against osteoporosis in asthma patients seems to not be significant.

Occupational agriculture organic dust exposure and its relationship to asthma and airway inflammation in adults.

PubMed

Wunschel, Javen; Poole, Jill A

2016-06-01

Recent studies have made advances into understanding the complex agriculture work exposure environment in influencing asthma in adults. The objective of this study is to review studies of occupational agricultural exposures including dust, animal, and pesticide exposures with asthma in adult populations. PubMed databases were searched for articles pertaining to farming, agriculture, asthma, occupational asthma, airway inflammation, respiratory disease, lung disease, pesticides, and organic dust. Studies chosen were published in or after 1999 that included adults and asthma and farming/agricultural work or agricultural exposures and airway inflammatory disease measurements. The data remain inconclusive. Several retrospective studies demonstrate agricultural work to be protective against asthma in adults, especially with increased farming exposure over time. In contrast, other studies find increased risk of asthma with farming exposures, especially for the non-atopic adult. Mechanistic and genetic studies have focused on defining the wide variety and abundance of microorganisms within these complex organic dusts that trigger several pattern recognition receptor pathways to modulate the hosts' response. Asthma risk depends on the interplay of genetic factors, gender, atopic predisposition, type of livestock, pesticide exposure, and magnitude and duration of exposure in the adult subject. Longer exposure to occupational farming is associated with decreased asthma risk. However, studies also suggest that agricultural work and multiple types of livestock are independent risk factors for developing asthma. Prospective and longitudinal studies focusing on genetic polymorphisms, objective assessments, and environmental sampling are needed to further delineate the influence of agriculture exposure in the adult worker.

Beginning school with asthma independently predicts low achievement in a prospective cohort of children.

PubMed

Liberty, Kathleen A; Pattemore, Philip; Reid, James; Tarren-Sweeney, Michael

2010-12-01

Concerns about the achievement of children with asthma and respiratory conditions are especially important in New Zealand, which has one of the world's highest rates of childhood asthma. The present study evaluated whether entering school with asthma was associated with low achievement after the first year. A child cohort was recruited to a prospective study at time of first enrollment into randomly selected schools in Christchurch. Parent interviews covered demographics and respiratory status. Physician reports were sought for children with asthma, and all respiratory information was clinically reviewed. The children's achievement in reading and math was individually assessed at school entry and reassessed after 12 months. Schools reported absences. Intelligence subtests were administered. Two hundred ninety-eight children were recruited, including 55 (18.5%) with current asthma. At 1-year follow-up, retention was 93.7%. Children who entered school with asthma were more likely to be ≥ 6 months behind other participants in reading words (P = .023) and books (P = .026), but not in math (P = .167) at the end of the first year of school. Achievement was not related to asthma severity. Entering school with asthma reliably predicted low reading achievement independent of other known covariates of low achievement (high absenteeism, minority status, male gender, single-parent family, poor academic skills at school entry, and low socioeconomic status). Entering school with asthma was a significant predictor of low achievement in reading at 12-month follow-up, independent of asthma severity, high absenteeism, or other covariates of low achievement.

Vitamin D as an adjunctive therapy in asthma. Part 2: A review of human studies.

PubMed

Kerley, Conor P; Elnazir, Basil; Faul, John; Cormican, Liam

2015-06-01

Vitamin D deficiency (VDD) is highly prevalent worldwide, with adverse effects on bone health but also potentially other unfavorable consequences. VDD and asthma-incidence/severity share many common risk factors, including winter season, industrialization, poor diet, obesity, dark skin pigmentation, and high latitude. Multiple anatomical areas relevant to asthma contain both the enzyme responsible for producing activated vitamin D and the vitamin D receptor suggesting that activated vitamin D (1,25-dihydroxyvitamin D) may have important local effects at these sites. Emerging evidence suggests that VDD is associated with increased airway hyperresponsiveness, decreased pulmonary function, worse asthma control, and possibly decreased response to standard anti-asthma therapy. However the effect is inconsistent with preliminary evidence from different studies suggesting vitamin D is both beneficial and detrimental to asthma genesis and severity. Current evidence suggests that supplementation with moderate doses of vitamin D may be appropriate for maintenance of bone health in asthmatics, particularly steroid users. However emerging data from an increasing number of randomized, controlled, intervention studies of vitamin D supplementation in pediatric and adult asthma are becoming available and should help determine the importance, if any of vitamin D for asthma pathogenesis. The purpose of this second of a two-part review is to review the current human literature on vitamin D and asthma, discussing the possible consequences of VDD for asthma and the potential for vitamin D repletion as adjunct therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Effect of catastrophic wildfires on asthmatic outcomes in obese children: breathing fire.

PubMed

Tse, Kevin; Chen, Lie; Tse, Mabel; Zuraw, Bruce; Christiansen, Sandra

2015-04-01

Air pollutants from wildfires and obesity independently exacerbate asthma, yet no study has determined the combined effects of these 2 variables on asthma outcomes. To determine the effect of 2 catastrophic wildfires affecting the Southern California region (in 2003 and 2007) on several asthma outcomes in a cohort of children. To investigate the association between wildfire exposure and asthma outcomes, we stratified our study population by body mass index categories (underweight, normal, overweight, and obese) and zip codes (to distinguish individuals who were closer to the fires vs farther away). The primary outcome was the prevalence of physician-dispensed short-acting β-agonist (SABAs). Secondary outcomes included the rate of emergency department visits and/or hospitalizations for asthma, the frequency of oral corticosteroid use for asthma, and number of new diagnoses of asthma. A total of 2,195 and 3,965 asthmatic children were analyzed as part of our retrospective cohort during the 2003 and 2007 wildfires, respectively. SABA dispensing increased the most in the obese group after the 2003 wildfires (P < .05). Increased prevalence of SABA dispensing was also noted in the obese group in 2007, but this was not statistically higher than the increases seen in other body mass index groups. There was no observed increase in emergency department and/or hospitalization rates, oral corticosteroid dispensing frequency, or new asthma diagnoses after either wildfire. Catastrophic wildfires lead to worsening asthma outcomes, particularly in obese individuals. This study gives further evidence of a link between obesity and asthma severity and suggests that air pollutants released during wildfires can have substantial detrimental effects on asthma control. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Clinical deterioration in pediatric asthmatic patients after September 11, 2001.

PubMed

Szema, Anthony M; Khedkar, Meera; Maloney, Patrick F; Takach, Patricia A; Nickels, Michael S; Patel, Harshit; Modugno, Francesmary; Tso, Alan Y; Lin, Deborah H

2004-03-01

New York City residents were exposed to a variety of inhaled substances after the collapse of the World Trade Center. Exposure to these substances might lead to an increase in asthma severity, with residential distance from Ground Zero predictive of the degree of change. We sought to assess the effect of the World Trade Center collapse on local pediatric asthmatic patients. We retrospectively reviewed the charts of 205 pediatric patients with established asthma from a clinic in lower Manhattan's Chinatown. Clinical data were obtained for the year before and the year after September 11, 2001. Measurements included numbers of visits, asthma medication prescriptions, oral corticosteroid prescriptions, weekly doses of rescue inhaler, and peak expiratory flow rates. Residential zip codes were used to compare the asthma severity of patients living within and beyond a 5-mile radius of Ground Zero. After September 11, 2001, these children had more asthma-related clinic visits (P = .002) and received more prescriptions for asthma medications (P = .018). No significant differences in oral steroid or rescue inhaler use were noted. Those living within 5 miles had more clinic visits after September 11, 2001 (P = .013); the increase in clinic visits for patients living more than 5 miles from Ground Zero was not significant. Mean percent predicted peak expiratory flow rates decreased solely for those patients living within 5 miles of Ground Zero during the 3 months after September 11, 2001. Asthma severity worsened after September 11, 2001, in pediatric asthmatic patients living near Ground Zero. Residential proximity to Ground Zero was predictive of the degree of decrease in asthma health.

Phenotypes of asthma revisited upon the presence of atopy.

PubMed

Nieves, Ana; Magnan, Antoine; Boniface, Stéphanie; Proudhon, Hervé; Lanteaume, André; Romanet, Stéphanie; Vervloet, Daniel; Godard, Philippe

2005-03-01

Immunological studies claimed that atopic and non-atopic asthma share more similarities than differences. However, these two phenotypes of asthma are considered to be distinguishable upon distinct clinical patterns, which were not systematically assessed before in a large population. We studied characteristics discriminating atopic from non-atopic asthma among 751 asthmatic patients and 80 factors were analysed in univariate and multivariate analysis. Age, age of onset of asthma, female/male ratio were higher in non-atopic (n=200) than in atopic (n=551) asthmatics. Familial asthma, seasonal symptoms, rhinitis, conjunctivitis, allergen-triggered symptoms, improvement in altitude, exercise-induced asthma were associated with atopy. Non-atopic asthmatics displayed lower FEV(1) and FVC. Smoking was more frequent and asthma was more severe in these patients. Younger age, early onset, male sex, rhinitis and smoking were independent factors discriminating atopic from non-atopic asthma. This study establishes in a large population of asthmatics that although similarities exist between atopic and non-atopic asthma, two clinical phenotypes can still distinguish both kinds of asthma.

An international observational prospective study to determine the cost of asthma exacerbations (COAX).

PubMed

Lane, Stephen; Molina, Jesus; Plusa, Tadeusz

2006-03-01

Asthma is a common chronic condition that places substantial burden on patients and healthcare services. Despite the standards of asthma control that international guidelines recommend should be achieved, many patients continue to suffer sub-optimal control of symptoms and experience exacerbations (acute asthma attacks). In addition to being associated with reduced quality of life, asthma exacerbations are a key cost driver in asthma management. Routine clinical practice for the management of asthma exacerbations varies in different healthcare systems, so healthcare providers require local costs to be able to assess the value of therapies that reduce the frequency and severity of exacerbations. This prospective study, conducted in a total of 15 countries, assessed the local cost of asthma exacerbations managed in either primary or secondary care. Healthcare resources used were costed using actual values appropriate to each country in local currency and in Euros. Results are presented for exacerbations managed in primary care in Brazil, Bulgaria, Croatia, Czech Republic, Hungary, Poland, Russia, Slovakia, Slovenia, Spain and Ukraine, and in secondary care in Croatia, Denmark, Ireland, Latvia, Norway, Poland, Russia, Slovakia, Slovenia and Spain. Multiple regression analysis of the 2052 exacerbations included in the economic analysis showed that the cost of exacerbations was significantly affected by country (P<0.0001). Mean costs were significantly higher in secondary care (euro 1349) than primary care (euro 445, P=0.0003). Age was a significant variable (P=0.0002), though the effect showed an interaction with care type (P<0.0001). As severity of exacerbation increased, so did secondary care costs, though primary care costs remained essentially constant. In conclusion, the study showed that asthma exacerbations are costly to manage, suggesting that therapies able to increase asthma control and reduce the frequency or severity of exacerbations may bring economic benefits, as well as improved quality of life.

A review of barriers to effective asthma management in Puerto Ricans: cultural, healthcare system and pharmacogenomic issues.

PubMed

Alicea-Alvarez, Norma; Swanson-Biearman, Brenda; Kelsen, Steven G

2014-02-01

Among the Hispanic community, Puerto Ricans have the highest prevalence of asthma and manifest the worst outcomes. The expected growth of the Hispanic population in the USA in the next several decades make elimination of disparate care in Puerto Rican asthmatics a matter of national importance. The purpose of this review of the literature (ROL) is to examine a variety of health system, genetic and cultural barriers in the Puerto Rican community which have created disparities in asthma care and outcomes among adult and pediatric Hispanic populations. In addition, this ROL describes several culturally sensitive, community-based educational interventions which can be used as a framework for future projects to improved asthma outcomes. Databases searched included Medline, PubMED, EBSCOhost, PsycINFO, CINAHL, Google Scholar and ERIC. Papers published in English from January 1990 to January 2012 were reviewed. Health system policies, insurer compensation patterns, clinician attitudes and cultural values/folk remedies in the Puerto Rican community represent barriers to effective asthma management, the use of controller medication and the implementation of educational interventions. In addition, genetic factors involving the beta-2 adrenergic receptor gene, which impair the response to albuterol, appear to contribute to poorer outcomes in Puerto Rican asthmatics. In contrast, several comprehensive, community-based, culturally sensitive educational interventions such as Controlling Asthma in American Cities Project (CAACP), the Racial and Ethnic Approach to Community Health in the US Program and Healthy Hoops programs (REACH) have been described. We believe that culturally sensitive community-based asthma education programs can serve as models for programs targeted toward Puerto Ricans to help decrease asthma morbidity. Moreover, greater sensitivity to Puerto Rican mores and folk remedies on the part of healthcare providers may improve the patient-clinician rapport and, hence, asthma outcomes. Finally, given ethnically based differences in pharmacogenomics, clinical trials targeting the Puerto Rican population may help to better define optimal asthma medication regimens in this ethnic group.

Functional variants of the sphingosine-1-phosphate receptor 1 gene associate with asthma susceptibility.

PubMed

Sun, Xiaoguang; Ma, Shwu-Fan; Wade, Michael S; Flores, Carlos; Pino-Yanes, Maria; Moitra, Jaideep; Ober, Carole; Kittles, Rick; Husain, Aliya N; Ford, Jean G; Garcia, Joe G N

2010-08-01

The genetic mechanisms underlying asthma remain unclear. Increased permeability of the microvasculature is a feature of asthma, and the sphingosine-1-phosphate receptor (S1PR1) is an essential participant regulating lung vascular integrity and responses to lung inflammation. We explored the contribution of polymorphisms in the S1PR1 gene to asthma susceptibility. A combination of gene resequencing for single nucleotide polymorphism (SNP) discovery, case-control association, functional evaluation of associated SNPs, and protein immunochemistry studies was used. Immunohistochemistry studies demonstrated significantly decreased S1PR1 protein expression in pulmonary vessels in lungs of asthmatic patients compared with those of nonasthmatic subjects (P < .05). Direct DNA sequencing of 27 multiethnic samples identified 39 S1PR1 variants (18 novel SNPs). Association studies were performed based on genotyping results from cosmopolitan tagging SNPs in 3 case-control cohorts from Chicago and New York totaling 1,061 subjects (502 cases and 559 control subjects). The promoter SNP rs2038366 (-1557G/T) was found to be associated with asthma (P = .03) in European Americans. In African Americans an association was found for both asthma and severe asthma for intronic SNP rs3753194 (c.-164+170A/G; P = .006 and P = .040, respectively) and for promoter SNP rs59317557 (-532C/G) with severe asthma (P = .028). Consistent with predicted in silico functionality, alleles of the promoter SNPs rs2038366 (-1557G/T) and rs59317557 (-532C/G) influenced the activity of a luciferase S1PR1 reporter vector in transfected endothelial cells exposed to growth factors (epidermal growth factor, platelet-derived growth factor, and vascular endothelial growth factor) known to be increased in asthmatic airways. These data provide strong support for a role for S1PR1 gene variants in asthma susceptibility and severity. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Decreased FOXP3 mRNA expression in children with atopic asthma and IgE-mediated food allergy.

PubMed

Krogulska, Aneta; Polakowska, Ewa; Wąsowska-Królikowska, Krystyna; Małachowska, Beata; Młynarski, Wojciech; Borowiec, Maciej

2015-11-01

The role of T regulatory lymphocytes has been investigated in various allergic diseases. However, the precise relation between the phenotype and severity of allergic diseases and the changes in FOXP3 mRNA expression are not fully understood. To compare the expression of FOXP3 mRNA in children with asthma with and without concomitant food allergy (FA) with healthy children and children with only FA. The study included 82 children: 15 with atopic asthma and IgE-dependent FA, 27 with atopic asthma without FA, 20 with IgE-dependent FA without asthma, and 20 healthy children without atopy. Reverse transcription was performed using a commercially available High Capacity cDNA Archive Kit (Applied Biosystems, Carlsbad, California). Analysis was carried out with a 7900HT real-time polymerase chain reaction system (Applied Biosystems). The average level of the FOXP3 gene expression in children with allergy was significantly lower compared with healthy children (2.2 ± 1.3 vs 4.2 ± 4.2; P = .014). The lowest mean level of FOXP3 mRNA expression (1.9 ± 1.6) was recorded in children with asthma and FA, and the highest level (4.2 ± 4.2) was recorded in healthy children without atopy (P = .036). A milder course of asthma or the degree of allergic reaction after a food challenge was associated with higher FOXP3 mRNA expression. Significantly lower levels of FOXP3 gene expression, observed more commonly in children with asthma and IgE-dependent FA than in healthy controls, were associated with a more severe clinical course. Therefore, FOXP3 expression could serve as an indicator of severe asthma with concomitant atopic conditions such as IgE-dependent FA. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Poor symptom control is associated with reduced CT scan segmental airway lumen area in smokers with asthma.

PubMed

Thomson, Neil C; Chaudhuri, Rekha; Spears, Mark; Messow, Claudia-Martina; MacNee, William; Connell, Martin; Murchison, John T; Sproule, Michael; McSharry, Charles

2015-03-01

Cigarette smoking is associated with worse symptoms in asthma and abnormal segmental airways in healthy subjects. We tested the hypothesis that current symptom control in smokers with asthma is associated with altered segmental airway dimensions measured by CT scan. In 93 subjects with mild, moderate, and severe asthma (smokers and never smokers), we recorded Asthma Control Questionnaire-6 (ACQ-6) score, spirometry (FEV1; forced expiratory flow rate, midexpiratory phase [FEF(25%-75%)]), residual volume (RV), total lung capacity (TLC), and CT scan measures of the right bronchial (RB) and left bronchial (LB) segmental airway dimensions (wall thickness, mm; lumen area, mm²) in the RB3/LB3, RB6/LB6, and RB10/LB10 (smaller) airways. The CT scan segmental airway (RB10 and LB10) lumen area was reduced in smokers with asthma compared with never smokers with asthma; RB10, 16.6 mm² (interquartile range, 12.4-19.2 mm²) vs 19.6 mm² (14.7-24.2 mm²) (P = .01); LB10, 14.8 mm² (12.1-19.0 mm²) vs 19.9 mm² (14.5-25.0 mm²) (P = .003), particularly in severe disease, with no differences in wall thickness or in larger airway (RB3 and LB3) dimensions. In smokers with asthma, a reduced lumen area in fifth-generation airways (RB10 or LB10) was associated with poor symptom control (higher ACQ-6 score) (-0.463 [-0.666 to -0.196], P = .001, and -0.401 [-0.619 to -0.126], P = .007, respectively) and reduced postbronchodilator FEF(25%-75%) (0.521 [0.292-0.694], P < .001, and [0.471 [0.236-0.654], P = .001, respectively) and higher RV/TLC %. The CT scan segmental airway lumen area is reduced in smokers with asthma compared with never smokers with asthma, particularly in severe disease, and is associated with worse current symptom control and small airway dysfunction.

Health Disparities in Pediatric Asthma: Comprehensive Tertiary Care Center Experience.

PubMed

Holmes, Laurens; Kalle, Fanta; Grinstead, Laura; Jimenez, Maritza; Murphy, Meghan; Oceanic, Pat; Fitzgerald, Diane; Dabney, Kirk

2015-03-01

Study conducted at Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE 19803 BACKGROUND: Although the treatment and management of asthma hasimproved over time, incidence and prevalence among children continues to rise in the United States. Asthma prevalence, health services utilization, and mortality rate demonstrate remarkable disparities. The underlying causes of these disparities are not fully understood. We aimed to examine racial/ethnic variances in pediatric asthma prevalence/admission. We retrospectively reviewed data on 1070 patients and applied a cross-sectional design to assess asthma admission between 2010 and 2011. Information was available on race/ethnicity, sex, insurance status, severity of illness (SOI), and length of stay/hospitalization (LOS).Chi-square statistic was used for the association between race and other variables in an attempt to explain the racial/ethnic variance. The proportionate morbidity of asthma was highest amongCaucasians (40.92%) and African Americans (40.54%), intermediate among others (16.57%), and lowest among Asian (0.56%), American Indian/Alaska Native (0.28%), and Hawaiian Native/Pacific Islander (0.28%). Overall there were disparities by sex, with more boys (61.80%) diagnosed with asthma than girls (38.20%), χ2(7)=20.1, p=0.005. Insurance status, and SOI varied by race/ethnicity, but not LOS. Caucasian children were more likely to have private insurance, while African Americans and Hispanics were more likely to have public insurance (p<0.005). Asthma was more severe among non-Hispanic children, χ2(14)=154.6, p<0.001. While the overall readmission proportion was 2.8%, readmission significantly varied by race/ethnicity. Racial/ethnic disparities in asthma admission exist among children in the Delaware Valley. There were racial/ethnic disparities in insurance status, asthma severity, and sex differed by race/ethnicity, but not in length of hospitalization. © 2015 National Medical Association. Published by Elsevier Inc. All rights reserved.

Impact of Asthma on the Sexual Functioning of Patients. A Case-Control Study.

PubMed

Soto Campos, José Gregorio; Rojas Villegas, Josefa; Padilla Galo, Alicia; Marina Malanda, Nuria; Garcia Rivero, Juan Luis; Pinedo Sierra, Celia; Garcia Salmones, Mercedes; Cabrera Galán, Carmen; Segura Molina, Esperanza; Plaza, Vicente; Pascual Erquicia, Silvia

2017-12-01

Sexual limitations play an important role in the quality of life of patients with chronic diseases. Very limited information is available on the impact of asthma on the sexual functioning of these individuals. Cross-sectional, observational, multicenter study. Asthma patients and healthy individuals were recruited. All subjects participated in an interview in which demographic and clinical data were recorded, and completed the Goldberg Anxiety-Depression Scale (GADS) to evaluate the presence of concomitant psychiatric disease. Men also completed the International Index of Erectile Function (IIEF), and women, the Female Sexual Function Index (FSFI). A total of 276cases were included, comprising 172asthma patients (63 men and 109 women) with a mean age of 42 (±14) years, and 104 controls (52men and 51women) with a mean age of 39 (±12) years. Time since onset of asthma was 15 years and severity distribution was: 6.4% intermittent, 17.9% mild persistent, 47.4% moderate, and 28.2% severe. Disease was considered controlled in 57.7%, partially controlled in 28.2%, and uncontrolled in 14.1%. Women with asthma had greater sexual limitations than women in the control group, with a total FSFI score of 22.1 (±9) compared to 26.5 (±6.8), respectively (P<.005). Men with asthma had significantly more severe erectile dysfunction with a total IIEF score of 59.5 (±12.5) compared to 64.3 (±8.2) in male controls (P<.05). An association was also observed between sexual problems and poorer asthma control. Asthma is associated with a poorer sexual quality of life among patients. These results should arouse the interest of healthcare professionals in detecting and alleviating possible sexual limitations among their asthma patients in routine clinical practice. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma.

PubMed

Turner, M O; Noertjojo, K; Vedal, S; Bai, T; Crump, S; Fitzgerald, J M

1998-06-01

We prospectively recruited patients admitted to the hospital with severe asthma to comprehensively evaluate the association of historical and physiologic features with the risk of near-fatal asthma (NFA). A case-control study design was used. All patients admitted with NFA (cases) were identified prospectively and compared with asthma patients admitted during the same period without respiratory failure (controls). Nineteen cases (age: 40.2 +/- 12.0 yr) (mean +/- SD) and 80 controls (age: 36 +/- 13.5 yr) were enrolled. Duration of asthma, gender, smoking status, ethnicity, and prevalence of atopy were similar in the case and control groups. More than 80% of patients in both groups reported worsening symptoms for more than 48 h before admission, and more than 50% were worse for longer than 7 d. There was no difference in degree of airways obstruction or bronchial hyperresponsiveness (PC20). Perception of dyspnea was similar in the cases and controls, but among cases the males had greater impairment than the females (Borg score: 1.9 +/- 1. 4 versus 3.9 +/- 1.2: p = 0.05). Univariate analysis identified a history of previous mechanical ventilation (OR: 27.5; 95% CI: 6.60 to 113.7), admission to the intensive care unit (ICU) (OR: 9.9; 95% CI: 3.0 to 32.9), history of worse asthma during January and February (OR: 3.5; 95% CI: 1.0 to 11.8), and use of air-conditioning (OR: 15.0; 95% CI: 1.3 to 166) as risk factors for NFA. Of concern was the dependence of most patients (59.8%) on the emergency department (ED) for initial care, and the small number of cases (16%) in which patients visited a physician before admission to the hospital. We have confirmed risk factors identified previously in retrospective studies of fatal and NFA, and have also shown that hospitalized patients with asthma, irrespective of severity of their asthma, share several characteristics, especially in terms of their failure to respond to worsening asthma.

Cleaning and asthma: A systematic review and approach for effective safety assessment.

PubMed

Vincent, Melissa J; Parker, Ann; Maier, Andrew

2017-11-01

Research indicates a correlative relationship between asthma and use of consumer cleaning products. We conduct a systematic review of epidemiological literature on persons who use or are exposed to cleaning products, both in occupational and domestic settings, and risk of asthma or asthma-like symptoms to improve understanding of the causal relationship between exposure and asthma. A scoring method for assessing study reliability is presented. Although research indicates an association between asthma and the use of cleaning products, no study robustly investigates exposure to cleaning products or ingredients along with asthma risk. This limits determination of causal relationships between asthma and specific products or ingredients in chemical safety assessment. These limitations, and a lack of robust animal models for toxicological assessment of asthma, create the need for a weight-of-evidence (WoE) approach to examine an ingredient or product's asthmatic potential. This proposed WoE method organizes diverse lines of data (i.e., asthma, sensitization, and irritation information) through a systematic, hierarchical framework that provides qualitatively categorized conclusions using hazard bands to predict a specific product or ingredient's potential for asthma induction. This work provides a method for prioritizing chemicals as a first step for quantitative and scenario-specific safety assessments based on their potential for inducing asthmatic effects. Acetic acid is used as a case study to test this framework. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma.

PubMed

Burden, Anne; Roche, Nicolas; Miglio, Cristiana; Hillyer, Elizabeth V; Postma, Dirkje S; Herings, Ron Mc; Overbeek, Jetty A; Khalid, Javaria Mona; van Eickels, Daniela; Price, David B

2017-01-01

Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre-post historical database study to investigate asthma-related outcomes by treatment. We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of <10% between cohorts. Of 4064 eligible patients, 1382 (34%) were prescribed ciclesonide and 2682 (66%) fine-particle ICS. The IPTW and propensity score-based methods retained more patients (96%-100%) than exact matching (90%); exact matching selected less severe patients. Standardized differences were >10% for four variables in the exact-matched dataset and <10% for both PSM algorithms and the weighted pseudo-dataset used in the IPTW method. With all methods, ciclesonide was associated with better 1-year asthma-related outcomes, at one-third the prescribed dose, than fine-particle ICS; results varied slightly by method, but direction and statistical significance remained the same. We found that each method has its particular strengths, and we recommend at least two methods be applied for each matched cohort study to evaluate the robustness of the findings. Balance diagnostics should be applied with all methods to check the balance of confounders between treatment cohorts. If exact matching is used, the calculation of a propensity score could be useful to identify variables that require balancing, thereby informing the choice of matching criteria together with clinical considerations.

Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of Patients with Severe Asthma.

PubMed

Konno, Satoshi; Taniguchi, Natsuko; Makita, Hironi; Nakamaru, Yuji; Shimizu, Kaoruko; Shijubo, Noriharu; Fuke, Satoshi; Takeyabu, Kimihiro; Oguri, Mitsuru; Kimura, Hirokazu; Maeda, Yukiko; Suzuki, Masaru; Nagai, Katsura; Ito, Yoichi M; Wenzel, Sally E; Nishimura, Masaharu

2015-12-01

Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).

Defining asthma and assessing asthma outcomes using electronic health record data: a systematic scoping review.

PubMed

Al Sallakh, Mohammad A; Vasileiou, Eleftheria; Rodgers, Sarah E; Lyons, Ronan A; Sheikh, Aziz; Davies, Gwyneth A

2017-06-01

There is currently no consensus on approaches to defining asthma or assessing asthma outcomes using electronic health record-derived data. We explored these approaches in the recent literature and examined the clarity of reporting.We systematically searched for asthma-related articles published between January 1, 2014 and December 31, 2015, extracted the algorithms used to identify asthma patients and assess severity, control and exacerbations, and examined how the validity of these outcomes was justified.From 113 eligible articles, we found significant heterogeneity in the algorithms used to define asthma (n=66 different algorithms), severity (n=18), control (n=9) and exacerbations (n=24). For the majority of algorithms (n=106), validity was not justified. In the remaining cases, approaches ranged from using algorithms validated in the same databases to using nonvalidated algorithms that were based on clinical judgement or clinical guidelines. The implementation of these algorithms was suboptimally described overall.Although electronic health record-derived data are now widely used to study asthma, the approaches being used are significantly varied and are often underdescribed, rendering it difficult to assess the validity of studies and compare their findings. Given the substantial growth in this body of literature, it is crucial that scientific consensus is reached on the underlying definitions and algorithms. Copyright ©ERS 2017.

Assessing patients' preferences for characteristics associated with homeopathic and conventional treatment of asthma: a conjoint analysis study

PubMed Central

Ratcliffe, J; Van Haselen, R; Buxton, M; Hardy, K; Colehan, J; Partridge, M

2002-01-01

Background: A study was undertaken to investigate the preferences of patients with asthma for attributes or characteristics associated with treatment for their asthma and to investigate the extent to which such preferences may differ between patient subgroups. Methods: The economic technique of conjoint analysis (CA) was used to investigate patients' strength of preference for several key attributes associated with services for the treatment of asthma. A CA questionnaire was administered to two groups of asthma outpatients aged 18 years or older, 150 receiving conventional treatment at Whipps Cross Hospital (WC) and 150 receiving homeopathic treatment at the Royal London Homoeopathic Hospital (RL). Results: An overall response rate of 47% (n=142) was achieved. Statistically significant attributes in influencing preferences for both the WC and RL respondents were (1) the extent to which the doctor gave sufficient time to listen to what the patient has to say, (2) the extent to which the treatment seemed to relieve symptoms, and (3) the travel costs of attending for an asthma consultation. The extent to which the doctor treated the patient as a whole person was also a statistically significant attribute for the RL respondents. Conclusions: This study has shown that aspects associated with the process of delivery of asthma services are important to patients in addition to treatment outcomes. The homeopathic respondents expressed stronger preferences for the doctor to treat them as a whole person than the patients receiving conventional treatment. Overall, the preferences for the attributes included in the study were similar for both groups. PMID:12037224

Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma

PubMed Central

Yan, Xiting; Chu, Jen-Hwa; Gomez, Jose; Koenigs, Maria; Holm, Carole; He, Xiaoxuan; Perez, Mario F.; Zhao, Hongyu; Mane, Shrikant; Martinez, Fernando D.; Ober, Carole; Nicolae, Dan L.; Barnes, Kathleen C.; London, Stephanie J.; Gilliland, Frank; Weiss, Scott T.; Raby, Benjamin A.; Cohn, Lauren

2015-01-01

Rationale: The airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma. Objectives: We analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA), gene signatures that discriminate phenotypes of disease. Methods: Gene expression in the sputum and blood of patients with asthma was measured using Affymetrix microarrays. Unsupervised clustering analysis based on pathways from the Kyoto Encyclopedia of Genes and Genomes was used to identify TEA clusters. Logistic regression analysis of matched blood samples defined an expression profile in the circulation to determine the TEA cluster assignment in a cohort of children with asthma to replicate clinical phenotypes. Measurements and Main Results: Three TEA clusters were identified. TEA cluster 1 had the most subjects with a history of intubation (P = 0.05), a lower prebronchodilator FEV1 (P = 0.006), a higher bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04) compared with the other TEA clusters. TEA cluster 2, the smallest cluster, had the most subjects that were hospitalized for asthma (P = 0.04). TEA cluster 3, the largest cluster, had normal lung function, low exhaled nitric oxide levels, and lower inhaled steroid requirements. Evaluation of TEA clusters in children confirmed that TEA clusters 1 and 2 are associated with a history of intubation (P = 5.58 × 10−6) and hospitalization (P = 0.01), respectively. Conclusions: There are common patterns of gene expression in the sputum and blood of children and adults that are associated with near-fatal, severe, and milder asthma. PMID:25763605

Posttraumatic Stress in Adolescents with Asthma and Their Parents

ERIC Educational Resources Information Center

Kean, Emily Millikan; Kelsay, Kimberly; Wamboldt, Frederick; Wamboldt, Marianne Z.

2006-01-01

Objective: To assess posttraumatic stress (PTS) symptoms in adolescents with and without asthma and their parents and the relationship between PTS symptoms and asthma morbidity. Method: Three groups of adolescents (12-18 years) participated: adolescents who had experienced a life-threatening asthma episode (n = 49), asthma controls (n = 71), and…

Asthma Risk Profiles of Children Participating in an Asthma Education and Management Program

ERIC Educational Resources Information Center

Wilson, Candice; Rapp, Kristi Isaac; Jack, Leonard, Jr.; Hayes, Sandra; Post, Robert; Malveaux, Floyd

2015-01-01

Background: Focused risk assessment is essential in the effective management of asthma. Purpose: This study identified and examined correlations among areas of pediatric asthma risk and determined associations between these risks and demographic characteristics. Methods: This exploratory study identified risk factors that affect asthma management…

Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations

PubMed Central

Ducharme, F M; Zemek, R; Gravel, J; Chalut, D; Poonai, N; Laberge, S; Quach, C; Krajinovic, M; Guimont, C; Lemière, C; Guertin, M C

2014-01-01

Introduction Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids. Methods and analysis The design is a prospective cohort study of 1008 children aged 1–17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. Ethics and dissemination Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host–environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations. Results Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists. Trial registration number This study is registered at Clinicaltrials.gov (NCT02013076). PMID:24710133

Omalizumab for pediatric asthma.

PubMed

Townley, Robert G; Agrawal, Swati; Sapkota, Kiran

2010-11-01

Omalizumab is of proven efficacy in the treatment of severe allergic bronchial asthma and works through inhibiting the activity of IgE and the allergic immune mechanism IgE mediates. It has been demonstrated to be efficacious in children with asthma but is not approved by the FDA for use in children below 12 years of age. Omalizumab is a 95% humanized monoclonal antibody that binds to circulating IgE at the same site on the Fc domain as the high-affinity IgE receptor, FcϵRI. This blocks the interaction between IgE and mast cells and basophils, thereby preventing the release of inflammatory mediators that cause allergic signs and symptoms. From the review of the literatures and statements from the FDA, Genentec and Novartis, the reader will gain a better appreciation of the value of omalizumab in treatment of severe asthma and the current status of its reported side effects. Omalizumab is of proven efficacy in adults and children with severe asthma and allows a markedly reduced dependence on oral and inhaled corticosteroids and decreased hospitalizations. A potential mechanism of omalizumab's effect on thrombus formation and cardiovascular effect is postulated.

The Potential of Mobile Apps for Improving Asthma Self-Management: A Review of Publicly Available and Well-Adopted Asthma Apps

PubMed Central

Tinschert, Peter; Jakob, Robert; Barata, Filipe; Kramer, Jan-Niklas

2017-01-01

Background Effective disease self-management lowers asthma’s burden of disease for both individual patients and health care systems. In principle, mobile health (mHealth) apps could enable effective asthma self-management interventions that improve a patient’s quality of life while simultaneously reducing the overall treatment costs for health care systems. However, prior reviews in this field have found that mHealth apps for asthma lack clinical evaluation and are often not based on medical guidelines. Yet, beyond the missing evidence for clinical efficacy, little is known about the potential apps might have for improving asthma self-management. Objective The aim of this study was to assess the potential of publicly available and well-adopted mHealth apps for improving asthma self-management. Methods The Apple App store and Google Play store were systematically searched for asthma apps. In total, 523 apps were identified, of which 38 apps matched the selection criteria to be included in the review. Four requirements of app potential were investigated: app functions, potential to change behavior (by means of a behavior change technique taxonomy), potential to promote app use (by means of a gamification components taxonomy), and app quality (by means of the Mobile Application Rating Scale [MARS]). Results The most commonly implemented functions in the 38 reviewed asthma apps were tracking (30/38, 79%) and information (26/38, 68%) functions, followed by assessment (20/38, 53%) and notification (18/38, 47%) functions. On average, the reviewed apps applied 7.12 of 26 available behavior change techniques (standard deviation [SD]=4.46) and 4.89 of 31 available gamification components (SD=4.21). Average app quality was acceptable (mean=3.17/5, SD=0.58), whereas subjective app quality lied between poor and acceptable (mean=2.65/5, SD=0.87). Additionally, the sum scores of all review frameworks were significantly correlated (lowest correlation: r36=.33, P=.04 between number of functions and gamification components; highest correlation: r36=.80, P<.001 between number of behavior change techniques and gamification components), which suggests that an app’s potential tends to be consistent across review frameworks. Conclusions Several apps were identified that performed consistently well across all applied review frameworks, thus indicating the potential mHealth apps offer for improving asthma self-management. However, many apps suffer from low quality. Therefore, app reviews should be considered as a decision support tool before deciding which app to integrate into a patient’s asthma self-management. Furthermore, several research-practice gaps were identified that app developers should consider addressing in future asthma apps. PMID:28768606

Maintenance inhaler preference, attribute importance, and satisfaction in prescribing physicians and patients with asthma, COPD, or asthma–COPD overlap syndrome consulting for routine care

PubMed Central

Ding, Bo; Small, Mark; Scheffel, Gina; Holmgren, Ulf

2018-01-01

Background In respiratory disorders, patient- and physician-perceived satisfaction with the maintenance inhaler device is an important factor driving treatment compliance and outcomes. We examine inhaler preferences in asthma and COPD from patient and physician perspectives, particularly focusing on the relative importance of individual device attributes and patient characteristics guiding inhaler choice. Materials and methods Real-world data from >7,300 patients with asthma, COPD, or asthma–COPD overlap syndrome (ACOS) consulting for routine care were derived from respiratory Disease Specific Programs conducted in Europe, USA, Japan, and China. Outcome variables included current pattern of inhaled maintenance therapy and device type, physician preference, patient-reported device attribute importance, and satisfaction. Results The most commonly prescribed inhalers for maintenance therapy of asthma, COPD, and ACOS were dry powder inhalers (62.8%–88.5% of patients) and pressurized metered dose inhalers (18.9%–35.3% of patients). One-third of physicians stated no preference for maintenance device when prescribing treatment, and less than one-third of patients reported being “extremely satisfied” with any attribute of their device. Instructions being “simple and easy to follow” was the inhaler attribute most commonly selected as important. For approximately one-third of patients across all groups, “ease of use/suitability of inhaler device” was a reason for the prescribing decision, as stated by the physician. Device characteristics were more likely to impact the prescribing decision in older patients (in asthma and COPD; P<0.01) and those with worse disease severity (in COPD; P<0.001). Conclusion A relatively high proportion of physicians had no preference for inhaler type across asthma, COPD, and ACOS. Simplicity of use was the most important inhaler attribute from a patient’s perspective. Physicians appeared to place most importance on ease of use and device suitability when selecting inhalers for older patients and those with more severe disease, particularly in COPD. PMID:29588581

Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal.

PubMed

Chapman, Kenneth R; Barnes, Neil C; Greening, Andrew P; Jones, Paul W; Pedersen, S

2010-08-01

The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting beta agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6-12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7-10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy.

Prevalence of gastro-oesophageal reflux disease symptoms and reflux-associated respiratory symptoms in asthma.

PubMed

Amarasiri, Lakmali D; Pathmeswaran, Arunasalam; de Silva, H Janaka; Ranasinha, Channa D

2010-09-15

Gastro-oesophageal reflux disease (GORD) symptoms are common in asthma and have been extensively studied, but less so in the Asian continent. Reflux-associated respiratory symptoms (RARS) have, in contrast, been little-studied globally. We report the prevalence of GORD symptoms and RARS in adult asthmatics, and their association with asthma severity and medication use. A cross-sectional analytical study. A validated interviewer-administered GORD scale was used to assess frequency and severity of seven GORD symptoms. Subjects were consecutive asthmatics attending medical clinics. Controls were matched subjects without respiratory symptoms. The mean (SD) composite GORD symptom score of asthmatics was significantly higher than controls (21.8 (17.2) versus 12.0 (7.6); P < 0.001) as was frequency of each symptom and RARS. Prevalence of GORD symptoms in asthmatics was 59.4% (95% CI, 59.1%-59.6%) versus 28.5% in controls (95% CI, 29.0% - 29.4%). 36% of asthmatics experienced respiratory symptoms in association with both typical and atypical GORD symptoms, compared to 10% of controls (P < 0.001). An asthmatic had a 3.5 times higher risk of experiencing a GORD symptom after adjusting for confounders (OR 3.5; 95% CI 2.5-5.3). Severity of asthma had a strong dose-response relationship with GORD symptoms. Asthma medication use did not significantly influence the presence of GORD symptoms. GORD symptoms and RARS were more prevalent in a cohort of Sri Lankan adult asthmatics compared to non-asthmatics. Increased prevalence of RARS is associated with both typical and atypical symptoms of GORD. Asthma disease and its severity, but not asthma medication, appear to influence presence of GORD symptoms.

[Acute asthma attacks introduced by anesthesia before nasal endoscopic surgery].

PubMed

Lü, Xiaofei; Han, Demin; Zhou, Bing; Ding, Bin

2004-05-01

In order to pay our attention to the perioperative treatment before nasal endoscopic surgery. Three patients with asthma accompanied chronic sinusitis were analyzed systemically, who had undergone acute attacks of asthma introduced by anesthesia. Anesthetic drugs and instruments can lead to acute attacks of asthma, because sinusitis with asthma means allergic airway inflammation, broncho-hyperreactivity and lower compensatory pulmonary function. Then all of the 3 cases had missed the preoperative treatment. Anesthetic drugs and instruments can lead to acute attacks of asthma. The perioperative treatment before nasal endoscopic surgery is very important for the prevention of the occurrences of this severe complication. Except emergency, the operation should be can celled for avoiding the acute attack of asthma introduced by anesthesia.

Risk and protective factors for the development of childhood asthma.

PubMed

Ding, Guodong; Ji, Ruoxu; Bao, Yixiao

2015-03-01

Childhood asthma prevalence worldwide has been increasing markedly over several decades. Various theories have been proposed to account for this alarming trend. The disease has a broad spectrum of potential determinants ranging from genetics to lifestyle and environmental factors. Epidemiological observations have demonstrated that several important lifestyle and environmental factors including obesity, urban living, dietary patterns such as food low in antioxidants and fast food, non-breastfeeding, gut flora imbalance, cigarette smoking, air pollution, and viral infection are associated with asthma exacerbations in children. However, only environmental tobacco smoke has been associated with the development of asthma. Despite epidemiological studies indicating that many other factors are probably associated with the development of asthma, the relationships are not considered causal due to the inadequate evidence and inconsistent results from recent studies. This may highlight that sufficient data and exact mechanisms of causality are still in need of further study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metabolic syndrome and asthma.

PubMed

Garmendia, Jenny V; Moreno, Dolores; Garcia, Alexis H; De Sanctis, Juan B

2014-01-01

Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

[Internalization disorders in children with asthma].

PubMed

Carrera-Bojorges, Xûchitl Beatriz; Pérez-Romero, Luis Francisco; Trujillo-Garcìa, José Ubaldo; Jiménez-Sandoval, Jaime Omar; Machorro-Muñoz, Olga Stephanie

2013-01-01

The presence of asthma may increase the risk for internalizing disorders such as major depression and anxiety. To determine if the diagnosis of asthma in children is associated with other internalizing disorders such as panic disorder, social phobia, separation anxiety, and total anxiety. In this analytical, descriptive and comparative cross sectional study, 144 asthmatic and 144 nonasthmatic patients, with ages between 8 and 17 years, were included. We used the GINA asthma diagnostic criteria. We applied the Hospital Anxiety and Depression Scale for diagnosis of internalizing disorders. Asthmatic children had a significant association with panic disorder P 0.001, RP 2.7; with social phobia P 0.026, RP 2.5; with separation anxiety P 0.002, RP 3.3; and with total anxiety P 0.017, RP 2.3. Nonasthmatic children did not have these associations. Asthma severity was intermittent in 36 cases (12.5%), mild persistent in 86 (29.9%) cases, and moderate persistent in 22 (7.6%) cases. We observed no statistically significant relationship between the severity of asthma and the diagnosis of an internalization disorder. We observed a meaningful association between asthma and internalizing disorders such as panic disorder, social phobia, separation anxiety and total anxiety in children.

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma.

PubMed

Xie, Yuran; Merkel, Olivia M

2015-10-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues have limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors that have been reported as targets of siRNA-mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages, and dendritic cells, which could potentially be applied in asthma therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications.

PubMed

Robinson, D; Humbert, M; Buhl, R; Cruz, A A; Inoue, H; Korom, S; Hanania, N A; Nair, P

2017-02-01

Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. type 2-driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines IL-4, IL-5 and IL-13 from cells of both the innate and adaptive immune systems. A number of well-recognized biomarkers have been linked to mechanisms involved in type 2 airway inflammation, including fractional exhaled nitric oxide, serum IgE, periostin, and blood and sputum eosinophils. These type 2 cytokines are targets for pharmaceutical intervention, and a number of therapeutic options are under clinical investigation for the management of patients with uncontrolled severe asthma. Anticipating and understanding the heterogeneity of asthma and subsequent improved characterization of different phenotypes and endotypes must guide the selection of treatment to meet individual patients' needs. © 2017 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years.

PubMed

Hall, Sannette C; Agrawal, Devendra K

2017-05-01

Vitamin D is a potent immunomodulator capable of dampening inflammatory signals in several cell types involved in the asthmatic response. Its deficiency has been associated with increased inflammation, exacerbations, and overall poor outcomes in patients with asthma. Given the increase in the prevalence of asthma over the past few decades, there has been enormous interest in the use of vitamin D supplementation as a potential therapeutic option. Here, we critically reviewed the most recent findings from in vitro studies, animal models, and clinical trials regarding the role of vitamin D in treating bronchial asthma. Using the key terms [Vitamin D, asthma, clinical trials, in vivo and in vitro studies], the [PubMed, Google Scholar] databases were searched for [clinical trials, original research articles, meta-analyses, and reviews], English-language articles published from [2012] to the present. Articles that were [Articles that did not meet these criteria were excluded] excluded from the analysis. Several studies have found that low serum levels of vitamin D (< 20 ng/mL) are associated with increased exacerbations, increased airway inflammation, decreased lung function, and poor prognosis in asthmatic patients. Results from in vitro and in vivo studies in animals and humans have suggested that supplementation with vitamin D may ameliorate several hallmark features of asthma. However, the findings obtained from clinical trials are controversial and do not unequivocally support a beneficial role of vitamin D in asthma. Largely, interventional studies in children, pregnant women, and adults have primarily found little to no effect of vitamin D supplementation on improved asthma symptoms, onset, or progression of the disease. This could be related to the severity of the disease process and other confounding factors. Despite the conflicting data obtained from clinical trials, vitamin D deficiency may influence the inflammatory response in the airways. Further studies are needed to determine the exact mechanisms by which vitamin D supplementation may induce antiinflammatory effects. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Families discovering asthma in their high-risk infants and toddlers with severe persistent disease.

PubMed

Koenig, Karel

2006-02-01

Interpretive phenomenology was used to discover the earliest experiences of families of children younger than 4 years hospitalized for severe persistent asthma. The children who were African American or Latino and living in poverty were at highest risk of morbidity and mortality. Three families with distinctly varied responses to early symptoms were chosen from an investigation of 11 families for this study. Each gave three home interviews and participated in home observations. All families experienced life-changing responses to their children's distressed breathing. All had experienced asthma in themselves or others that shaped their beliefs and management patterns. Family experiences prior to and following diagnosis are discussed. Findings suggest that understanding these experiences and respecting families' earliest responses will help clarify established family management patterns for severe asthma in infants and toddlers and will enhance the ability of providers to guide the care of these families and children.

Asthma and school commuting time.

PubMed

McConnell, Rob; Liu, Feifei; Wu, Jun; Lurmann, Fred; Peters, John; Berhane, Kiros

2010-08-01

This study examined associations of asthma with school commuting time. Time on likely school commute route was used as a proxy for on-road air pollution exposure among 4741 elementary school children at enrollment into the Children's Health Study. Lifetime asthma and severe wheeze (including multiple attacks, nocturnal, or with shortness of breath) were reported by parents. In asthmatic children, severe wheeze was associated with commuting time (odds ratio, 1.54 across the 9-minute 5% to 95% exposure distribution; 95% confidence interval, 1.01 to 2.36). The association was stronger in analysis restricted to asthmatic children with commuting times 5 minutes or longer (odds ratio, 1.97; 95% confidence interval, 1.02 to 3.77). No significant associations were observed with asthma prevalence. Among asthmatics, severe wheeze was associated with relatively short school commuting times. Further investigation of effects of on-road pollutant exposure is warranted.

Socioeconomic and Sociodemographic Factors Associated with Asthma Related Outcomes in Early Childhood: The Generation R Study

PubMed Central

Hafkamp-de Groen, Esther; Sonnenschein-van der Voort, Agnes M. M.; Mackenbach, Johan P.; Duijts, Liesbeth; Jaddoe, Vincent W. V.; Moll, Henriëtte A.; Hofman, Albert; de Jongste, Johan C.; Raat, Hein

2013-01-01

Rationale Few studies have analyzed the association of socioeconomic and sociodemographic factors with asthma related outcomes in early childhood, including Fraction of exhaled Nitric Oxide (FeNO) and airway resistance (Rint). We examined the association of socioeconomic and sociodemographic factors with wheezing, asthma, FeNO and Rint at age 6 years. Additionally, the role of potential mediating factors was studied. Methods The study included 6717 children participating in The Generation R Study, a prospective population-based cohort study. Data on socioeconomic and sociodemographic factors, wheezing and asthma were obtained by questionnaires. FeNO and Rint were measured at the research center. Statistical analyses were performed using logistic and linear regression models. Results At age 6 years, 9% (456/5084) of the children had wheezing symptoms and 7% (328/4953) had asthma. Children from parents with financial difficulties had an increased risk of wheezing (adjusted Odds Ratio (aOR) = 1.63, 95% Confidence Interval (CI):1.18–2.24). Parental low education, paternal unemployment and child's male sex were associated with asthma, independent of other socioeconomic or sociodemographic factors (aOR = 1.63, 95% CI:1.24–2.15, aOR = 1.85, 95% CI:1.11–3.09, aOR = 1.58, 95% CI:1.24–2.01, respectively). No socioeconomic or gender differences in FeNO were found. The risks of wheezing, asthma, FeNO and Rint measurements differed between ethnic groups (p<0.05). Associations between paternal unemployment, child's sex, ethnicity and asthma related outcomes remained largely unexplained. Conclusions This study showed differences between the socioeconomic and sociodemographic correlates of wheezing and asthma compared to the correlates of FeNO and Rint at age 6 years. Several socioeconomic and sociodemographic factors were independently associated with wheezing and asthma. Child's ethnicity was the only factor independently associated with FeNO. We encourage further studies on underlying pathways and public health intervention programs, focusing on reducing socioeconomic or sociodemographic inequalities in asthma. PMID:24244299

Perioperative considerations for the patient with asthma and bronchospasm.

PubMed

Woods, B D; Sladen, R N

2009-12-01

The incidence of asthma is increasing worldwide, but morbidity and mortality are decreasing because of improvements in medical care. Although the incidence of severe perioperative bronchospasm is relatively low in asthmatics undergoing anaesthesia, when it does occur it may be life-threatening. The keys to an uncomplicated perioperative course are assiduous attention to detail in preoperative assessment, and maintenance of the anti-inflammatory and bronchodilatory regimens through the perioperative period. Potential trigger agents should be identified and avoided. Many routinely used anaesthetic agents have an ameliorative effect on airway constriction. Nonetheless, acute bronchospasm can still occur, especially at induction and emergence, and should be promptly and methodically managed.

The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease.

PubMed Central

Bel, E. H.; Zwinderman, A. H.; Timmers, M. C.; Dijkman, J. H.; Sterk, P. J.

1991-01-01

Beta 2 agonists reduce airway hypersensitivity to bronchoconstrictor stimuli acutely in patients with asthma and chronic obstructive lung disease. To determine whether these drugs also protect against excessive airway narrowing, the effect of inhaled salbutamol on the position and shape of the dose-response curves for histamine or methacholine was investigated in 12 patients with asthma and 11 with chronic obstructive lung disease. After pretreatment with salbutamol (200 or 400 micrograms) or placebo in a double blind manner dose-response curves for inhaled histamine and methacholine were obtained by a standard method on six days in random order. Airway sensitivity was defined as the concentration of histamine or methacholine causing a 20% fall in FEV1 (PC20). A maximal response plateau on the log dose-response curve was considered to be present if two or more data points for FEV1 fell within a 5% response range. In the absence of a plateau, the test was continued until a predetermined level of severe bronchoconstriction was reached. Salbutamol caused an acute increase in FEV1 (mean increase 11.5% predicted in asthma, 7.2% in chronic obstructive lung disease), and increase in PC20 (mean 15 fold in asthma, fivefold in chronic obstructive lung disease), and an increase in the slope of the dose-response curves in both groups. In subjects in whom a plateau of FEV1 response could be measured salbutamol did not change the level of the plateau. In subjects without a plateau salbutamol did not lead to the development of a plateau, despite achieving a median FEV1 of 44% predicted in asthma and 39% in chronic obstructive lung disease. These results show that, although beta 2 agonists acutely reduce the airway response to a given strength of bronchoconstrictor stimulus, they do not protect against excessive airflow obstruction if there is exposure to relatively strong stimuli. This, together with the steepening of the dose-response curve, could be a disadvantage of beta 2 agonists in the treatment of moderate and severe asthma or chronic obstructive lung disease. PMID:1871705

Biomarker Surrogates Do Not Accurately Predict Sputum Eosinophils and Neutrophils in Asthma

PubMed Central

Hastie, Annette T.; Moore, Wendy C.; Li, Huashi; Rector, Brian M.; Ortega, Victor E.; Pascual, Rodolfo M.; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.

2013-01-01

Background Sputum eosinophils (Eos) are a strong predictor of airway inflammation, exacerbations, and aid asthma management, whereas sputum neutrophils (Neu) indicate a different severe asthma phenotype, potentially less responsive to TH2-targeted therapy. Variables such as blood Eos, total IgE, fractional exhaled nitric oxide (FeNO) or FEV1% predicted, may predict airway Eos, while age, FEV1%predicted, or blood Neu may predict sputum Neu. Availability and ease of measurement are useful characteristics, but accuracy in predicting airway Eos and Neu, individually or combined, is not established. Objectives To determine whether blood Eos, FeNO, and IgE accurately predict sputum eosinophils, and age, FEV1% predicted, and blood Neu accurately predict sputum neutrophils (Neu). Methods Subjects in the Wake Forest Severe Asthma Research Program (N=328) were characterized by blood and sputum cells, healthcare utilization, lung function, FeNO, and IgE. Multiple analytical techniques were utilized. Results Despite significant association with sputum Eos, blood Eos, FeNO and total IgE did not accurately predict sputum Eos, and combinations of these variables failed to improve prediction. Age, FEV1%predicted and blood Neu were similarly unsatisfactory for prediction of sputum Neu. Factor analysis and stepwise selection found FeNO, IgE and FEV1% predicted, but not blood Eos, correctly predicted 69% of sputum Eos

Indoor air quality and health problems associated with damp floor coverings.

PubMed

Tuomainen, Anneli; Seuri, Markku; Sieppi, Anne

2004-04-01

To study the relationship between a high incidence of bronchial asthma among employees working in an office building and an indoor air problem related to the degradation of polyvinyl chloride (PVC) floor coverings in the building. The indoor air measurements and results of renovations are also described. Employees' symptoms were surveyed by a questionnaire, and the incidence of asthma was calculated from the medical records for 1997-2000. The quality of indoor air was assessed by microbial sampling and by investigation of the building for possible moisture damage. Indoor air was sampled for volatile organic compounds (VOCs) through Tenax adsorbent tubes. In situ volatile emission measurements from the concrete floor were performed via the field and laboratory emission cell (FLEC) method. In an office with approximately 150 employees, eight new cases of asthma were found in 4 years. In addition, the workers complained of respiratory, conjunctival and nasal symptoms. Emissions indicating the degradation of plastic floor coverings (e.g. 2-ethyl-1-hexanol, 1-butanol) were found in the indoor air and floor material samples. The plastic floor coverings, adhesives and the levelling layers were carefully removed from 12 rooms. The VOCs had diffused into the underlying concrete slabs. The concrete was warmed to remove the diffused VOCs from these areas. After the repairs the concentrations of the VOCs indicating the degradation of PVC, decreased, as did the prevalence of the employees' symptoms and several asthma patients' need for medication. The workers in the office building complained of several respiratory, conjunctival and dermal symptoms. The incidence of adult-onset asthma was approximately nine-times higher than that among Finns employed in similar work. The most probable single cause of the indoor air problem was the degradation of the plastic floor coverings.

New insight into the assessment of asthma using xenon ventilation computed tomography.

PubMed

Jung, Jae-Woo; Kwon, Jae-Woo; Kim, Tae-Wan; Lee, So-Hee; Kim, Kyung-Mook; Kang, Hye-Ryun; Park, Heung-Woo; Lee, Chang-Hyun; Goo, Jin-Mo; Min, Kyung-Up; Cho, Sang-Heon

2013-08-01

Image analyses include computed tomography (CT), magnetic resonance imaging, and xenon ventilation CT, which is new modality to evaluate pulmonary functional imaging. To examine the usefulness of dual-energy xenon ventilation CT in asthmatic patients. A total of 43 patients 18 years or older who were nonsmokers were included in the study. Xenon CT images in wash-in and wash-out phases were obtained at baseline and after inhalation of methacholine and salbutamol. The degrees of ventilation defects and xenon trappings were evaluated through visual analysis. Ventilation defects and xenon trapping were significantly increased and decreased after methacholine challenge and salbutamol inhalation, respectively (P < .005). The ventilation abnormalities were not significantly related to the percentage of forced expiratory volume in 1 second (FEV1) or the ratio of FEV1 to forced vital capacity. Xenon trappings after salbutamol inhalation were negatively related to the scores of the asthma control test, wheezing, or night symptoms, with statistical significance (P < .05), whereas, FEV1 showed no significant correlation with symptom scores. Baseline FEV1 was significantly lower and dyspnea and wheezing were more severe in the non-full reversal group than in the full reversal group after salbutamol inhalation in xenon CT (P < .05). The degree of ventilation defects were positively correlated with FEV1 improvement after 3 months of treatment (P = .02). The results of this study suggest that xenon ventilation CT can be used as a new method to assess ventilation abnormalities in asthma, and these ventilation abnormalities can be used as novel parameters that reflect the status of asthma control and symptom severity. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

RItA: The Italian severe/uncontrolled asthma registry.

PubMed

Maio, S; Baldacci, S; Bresciani, M; Simoni, M; Latorre, M; Murgia, N; Spinozzi, F; Braschi, M; Antonicelli, L; Brunetto, B; Iacovacci, P; Roazzi, P; Pini, C; Pata, M; La Grasta, L; Paggiaro, P; Viegi, G

2018-03-01

The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV 1 % pred of 75.1%, median values of 300/mm 3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Acute severe asthma: performance of ventilator at simulated altitude.

PubMed

Tourtier, Jean-Pierre; Forsans, Emma; Leclerc, Thomas; Libert, Nicolas; Ramsang, Solange; Tazarourte, Karim; Man, Michel; Borne, Marc

2011-04-01

Exacerbation of asthma can be seen during air transport. Severe patients, not responding to conventional therapy, require ventilator support. We evaluated the performance of two transport ventilators, built with turbine technology, the T-birdVSO2 and the LTV-1000, for use during aeromedical evacuation of acute severe asthma. We have assessed the ability of both the ventilators to deliver to an acute severe asthma model a tidal volume (Vt) set at different simulated altitudes, by changing the ambient air pressure. The simulated cabin altitudes were 1500, 2500, and 3000 m (decompression chamber). Vt was set at 700 and 400 ml in an acute severe asthma lung model. Comparisons of the preset with the actual measured values were accomplished using a t-test. Comparisons between the actual delivered Vt and set Vt showed a significant difference starting at 1500 m for both the ventilators. The T-birdVSO2 showed a decrease in the volume delivered, with a negative variation of more than 10% compared with the Vt set. The LTV-1000 showed mostly an increase in the volume delivered. The delivered Vt remained within 10% of the set Vt. The accuracy of Vt delivery was superior with the LTV-1000 than with the T-birdVSO2, but the higher delivered Vt of the LTV-1000 are likely to be more harmful than lower delivered Vt of the T-birdVSO2.

Emerging mechanisms and novel targets in allergic inflammation and asthma.

PubMed

Weiss, Scott T

2017-12-04

Airway inflammation is key to the severity and persistence of asthma. Recent studies have revealed novel immune mechanisms that target dendritic cells, T helper 2 cytokines, regulatory T cells, and type 2 innate lymphoid cells in allergic inflammation, as well as novel approaches that target airway smooth muscle in asthma. These advances inform the development of new targeted treatments for allergic inflammation and asthma with the potential to provide therapeutic benefit.

Inflammation and asthma control in children with comorbid obstructive sleep apnea.

PubMed

Rogers, Valerie E; Bollinger, Mary E; Tulapurkar, Mohan E; Zhu, Shijun; Hasday, Jeffrey D; Pereira, Kevin D; Scharf, Steven M

2018-06-03

A bi-directional relationship exists between asthma and obstructive sleep apnea (OSA) in which presence of one is associated with increased prevalence and severity of the other. Our objective was to determine whether OSA accounted for differences in airway and systemic inflammation in asthmatic children and whether inflammation was associated with asthma control. We hypothesized that greater severity of SDB would correlate with increased upper airway and systemic inflammation and result in reduced asthma control. Non-obese children aged 4-12 years with persistent asthma, with or without OSA were recruited. Asthma control was measured with the Childhood Asthma Control Test. Children underwent polysomnography and blood sampling, and children with OSA underwent clinically indicated adenotonsillectomy. Tonsils and sera were analyzed for 11 cytokines. Twenty-seven children (20 with OSA, seven without OSA) participated, mean age 7.9 years, 55.6% female, 92.6% African American. Levels did not differ for any cytokine between children with and without OSA. Lower nadir oxygen saturation was associated with higher levels of tonsil TNF-α (P < 0.001) and IL-10 (P < 0.05). Higher REM-related apnea-hypopnea index was associated with higher levels of tonsil TNF-α (P < 0.05). Children with uncontrolled asthma had significantly higher levels of serum IL-10, IL-13, and TNF-α, and tonsil TNF-α (all P < 0.05) than well-controlled asthmatic children. There was no association between OSA, or any polysomnography variable, and asthma control. Despite the presence of OSA-associated airway inflammation, and asthma control-associated airway and systemic inflammation, OSA was not related to level of asthma control in this non-obese, largely minority, low income sample. © 2018 Wiley Periodicals, Inc.

Efficacy and Safety of Tiotropium in the Treatment of Severe Persistent Asthma:Meta-analysis.

PubMed

Lou, Li-li; Gong, Hai-hong; Zhang, Ming-qiang; Gao, Jin-ming

2016-02-01

To evaluate the efficacy and safety of tiotropium in treatment of severe persistent asthma. Reports of randomized controlled trials (RCTs) describing tiotropium for treatment of severe persistent asthma published from January 1946 to February 2015 were searched in Cochrane Library, ClinicalTrials.gov, PubMed, Ovid Medline, CNKI, and CSJD. The data of the included RCTs were extracted and the data quality was evaluated. Meta-analyses were performed with Revman 5.3 software. Five RCTs including 1433 patients were analyzed. Meta-analysis of the data showed that compared with the placebo group, tiotropium treatment significantly improved the patients' peak forced expiratory volume in one second (FEV1) [weighted mean difference (WMD): 0.13 L, 95% confidence interval (CI): 0.10-0.16 L, P<0.00001], trough FEV1 (WMD: 0.09 L, 95%CI: 0.06-0.12 L, P<0.00001), peak forced vital capacity (FVC) (WMD: 0.10 L, 95%CI: 0.06-0.14 L, P<0.00001), trough FVC (WMD: 0.12 L, 95%CI: 0.08-0.17 L, P<0.00001), morning peak expiratory flow (PEF) (WMD: 9.21 L/min, 95%CI: 4.2-14.23 L/min, P=0.0003), evening PEF (WMD: 22.06 L/min, 95%CI 13.05-31.08 L/min, P<0.00001). The scores of asthma control questionnaire (ACQ) (WMD: 0.01, 95% CI: -0.07-0.09, P=0.86) or asthma quality of life questionnaire (AQLQ)(WMD: 0.06, 95% CI:-0.18-0.06, P=0.33) were not affected by tiotropium. No significant difference with adverse events between tiotropium group and placebo group were reported in these included studies (P>0.05). Tiotropium for severe persistent asthma treatment can improve FEV1, FVC, and PEF but may not improve the quality of life of the patients. Tiotropium is well tolerated and can be an add-on therapy for severe persistent asthma.

MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2.

PubMed

Kim, Richard Y; Horvat, Jay C; Pinkerton, James W; Starkey, Malcolm R; Essilfie, Ama T; Mayall, Jemma R; Nair, Prema M; Hansbro, Nicole G; Jones, Bernadette; Haw, Tatt Jhong; Sunkara, Krishna P; Nguyen, Thi Hiep; Jarnicki, Andrew G; Keely, Simon; Mattes, Joerg; Adcock, Ian M; Foster, Paul S; Hansbro, Philip M

2017-02-01

Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle.

PubMed

Austin, Philip J; Tsitsiou, Eleni; Boardman, Charlotte; Jones, Simon W; Lindsay, Mark A; Adcock, Ian M; Chung, Kian Fan; Perry, Mark M

2017-03-01

The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma. Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to dexamethasone and FCS. mRNA and lncRNA expression was measured by using a microarray and quantitative real-time PCR. Bioinformatic analysis was used to examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small interfering RNAs, and the effect on ASMC phenotype was examined. The mRNA expression profile was significantly different between patient groups after exposure to dexamethasone and FCS, and these were associated with biological pathways that might be relevant to the pathogenesis of asthma, including cellular proliferation and pathways associated with glucocorticoid activity. We also observed a significant change in lncRNA expression, yet the expression of only one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive nonsevere asthma and increased in patients with corticosteroid-insensitive severe asthma. Subsequent targeting studies demonstrated the importance of this lncRNA in controlling both proliferation and IL-6 release in ASMCs from patients with severe asthma. lncRNAs are associated with the aberrant phenotype observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in reducing airway remodeling in asthmatic patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Socio-economic disadvantage, quality of medical care and admission for acute severe asthma.

PubMed

Kolbe, J; Vamos, M; Fergusson, W

1997-06-01

In asthma, socio-economic and health care factors may operate by a number of mechanisms to influence asthma morbidity and mortality. To determine the quality of medical care including the patient perception of the doctor-patient relationship, and the level of socio-economic disadvantage in patients admitted to hospital with acute severe asthma. One hundred and thirty-eight patients (15-50 years) admitted to hospital (general ward or intensive care unit) with acute asthma were prospectively assessed using a number of previously validated instruments. The initial subjects had severe asthma on admission (pH = 7.3 +/- 0.2, PaCO2 = 7.1 +/- 5.0 kPa, n = 90) but short hospital stay (3.7 +/- 2.6 days). Although having high morbidity (40% had hospital admission in the last year and 60% had moderate/severe interference with sleep and/or ability to exercise), they had indicators of good ongoing medical care (96% had a regular GP, 80% were prescribed inhaled steroids, 84% had a peak flow meter, GP measured peak flow routinely in 80%, 52% had a written crisis plan and 44% had a supply of steroids at home). However, they were severely economically disadvantaged (53% had experienced financial difficulties in the last year, and for 35% of households the only income was a social security benefit). In the last year 39% had delayed or put off GP visit because of cost. Management of the index attack was compromised by concern about medical costs in 16% and time off work in 20%. Patients admitted to hospital with acute asthma have evidence of good quality on-going medical care, but are economically disadvantaged. If issues such as financial barriers to health care are not acknowledged and addressed, the health care services for asthmatics will not be effectively utilised and the current reductions in morbidity and mortality may not be maintained.

Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood.

PubMed Central

Garrett, J.; Fenwick, J. M.; Taylor, G.; Mitchell, E.; Stewart, J.; Rea, H.

1994-01-01

BACKGROUND--Previous work has indicated a high rate of non-attendance at hospital based clinics among young, multiracial asthmatic patients of lower socioeconomic class. The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated. METHODS--A prospective controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were randomised to the usual follow up or the education centre plus usual follow up. Measurements were taken at entry into the study and again nine months later. RESULTS--At nine months patients randomised to the education centre had more preventive medications, more peak expiratory flow meters and better flow meter technique, more self-management plans, better knowledge of appropriate action to take when confronted with worsening asthma, less nocturnal awakening, and better self-reported asthma control than the control group. There was no difference between the study groups in measurements of compliance, hospital admission, days lost from school or work, or emergency room use. CONCLUSIONS--The main effects of education were on asthma knowledge and self-management skills, whilst improvements in asthma morbidity were small. Potential reasons for this include heterogeneous study population (in terms of baseline self-management skills, asthma severity, ethnicity and age), pragmatic study design, insensitivity of many of the measurements of morbidity, the modest effectiveness of a single time limited education programme, and inability to limit the effects of such a large community based study to the intervention group (there was a 67% reduction in asthma admissions during the study period from the geographical area targeted compared with a 22% reduction for the rest of Auckland). Images PMID:7974314

Disparities in assessments of asthma control between children, parents, and physicians.

PubMed

Shefer, Galit; Donchin, Milka; Manor, Orly; Levy-Hevroni, Revital; Schechter, Abraham; Cohen, Rinat; Cohen, Herman A; Kerem, Eitan; Engelhard, Dan

2014-10-01

Assessment of asthma control in children by physicians, patients and their parents was compared, assuming parents may underestimate symptoms in asthmatic children and exploring whether physicians tend to agree with them. Asthma control perception was assessed in 4- to 11-year-old asthmatic children and their parents, using C-ACT, during 2011-2012. Pediatric pulmonologists used GINA guidelines for their assessment; pediatricians, not having spirometry, used the information given in addition to physical examination. The C-ACT scores given by the children and their parents were further analyzed separately, and compared with their physicians' assessment. Statistical methods, which also measured possible influence of different variables, included kappa, Chi-square, linear-by-linear association, McNemar test and logistic regression. The study comprised 354 parents and children aged 4-11 years with moderate-severe asthma; 129 (36.4%) were treated by 23 pediatricians; 225 (63.6%) by 11 pediatric pulmonologists. The C-ACT was generally found valid in assessing asthma control (P < 0.001; κ 0.529; CI 0.441, 0.617) and showed that in 229/354 (53%) of children the asthma was uncontrolled. Nevertheless, of the 229 children who indicated their asthma was uncontrolled, 124 (54.1%) of their parents (κ 0.245; CI 0.15, 0.34) and 96 (41.9%) of their physicians believed it to be controlled (κ 0.331; 0.24, 0.43). Comparing the physician-child discordance vis-à-vis the parents, the significant difference was when 96/229 children (41.9%) and 34/126 parents (27.0%) indicated the asthma was uncontrolled while the physician determined it controlled (OR 1.95; 1.19, 3.24). There were no significant differences between pediatric pulmonologists and pediatricians. In addition to increasing awareness of parents to symptoms in their asthmatic children, physicians should question the child appropriately, as well as using the children's responses to C-ACT as an information source for properly assessing asthma control. © 2013 Wiley Periodicals, Inc.

Presence of Headache and Migraine in Asthma Patients

PubMed Central

Turan, Muzaffer Onur; Susuz, Çiğdem Çelik; Turan, Pakize Ayşe

2017-01-01

OBJECTIVES Migraine is a diseases characterized with severe headaches, with neurological and systemic findings. The purpose of this study is to investigate the prevalence of migraine and to examine whether there is a relationship between atopic disorders, parental history and migraine in asthma patients. MATERIAL AND METHODS A total of 288 asthma outpatients, who had the diagnosis by an early or late test of reversibility showing a reversible airway obstruction according to hospital database were included. The presence of headache, atopic symptoms and parental history about asthma, atopic disorders and migraine were asked. The patients with headache were consultated by neurology department and investigated about the presence of migraine. The diagnosis of migraine headache was made if patients fulfilled the International Headache Society (IHS) criteria. RESULTS 60.4% of patients described a headache. There were 94 patients (32.6%) with headaches meeting the IHS criteria for migraine. Only 12 patients had migraine with aura. There were atopic symptoms in 86.8% of patients. According to parental history, there were asthma in 47.9%, atopic symptoms in 39.6% and migraine in 22.2% of parents. Patients with atopic symptoms were found to have significantly high rate of headaches (65.3%) “p=0.007”. The prevalence of migraine was significantly high in patients with parental atopic symptoms (54%) “p=0.002”. Multiple logistic regression analysis identified that gender, parental history of asthma, allergia and migraine, and smoking were independent risk factors for presence of migraine in asthmatics. CONCLUSION There is a high prevalence of migraine headaches in patients with asthma. The coexistence of asthma and headaches may be related with a similar pathophysiological mechanism; parental history, common genetic compounds and smoking may play role in this mechanism. The headaches in asthma patients, atopic symptoms and family history should be questioned, and clinicians should be careful about the presence of migraine. PMID:29404159

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.

Sinus and adenoid inflammation in children with chronic rhinosinusitis and asthma.

PubMed

Anfuso, Antony; Ramadan, Hassan; Terrell, Andrew; Demirdag, Yesim; Walton, Cheryl; Skoner, David P; Piedimonte, Giovanni

2015-02-01

Chronic rhinosinusitis (CRS) and asthma frequently coexist in children and adults. However, the precise pathophysiologic mechanism of this interaction is still poorly understood, especially in children, owing to the lack of direct measurements of mucosal inflammation in the upper airways. To determine the pathophysiologic mechanism by analyzing the expression of a large array of inflammatory cytokines and chemokines in the sinus and adenoid tissues surgically removed from pediatric patients with CRS refractory to medical management. Twenty-eight children 2 to 12 years old diagnosed with CRS with or without asthma and 10 controls were included in this prospective, nonrandomized study. Mucosal expression of 40 inflammatory cytokines was measured with a multiplex assay and was normalized to total tissue protein. Compared with children with CRS and without asthma, children with CRS and asthma had significantly higher sinus levels of tumor necrosis factor-α and adenoid levels of epidermal growth factor, eotaxin, fibroblast growth factor-2, growth-related oncogene, and platelet-derived growth factor-AA. The inflammatory response in the upper airway mucosa of children with asthma and CRS was similar, but more severe, compared with children with CRS without asthma. This observation is consistent with the hypothesis that asthma in these patients is caused or exacerbated by severe upper airway disease and supports the concept that treating sinus disease is paramount in the management of chronic asthma in children using, for the first time, direct measurements of airway inflammation in children. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Th2 cytokine antagonists: potential treatments for severe asthma.

PubMed

Hansbro, Philip M; Scott, Grace V; Essilfie, Ama-Tawiah; Kim, Richard Y; Starkey, Malcolm R; Nguyen, Duc H; Allen, Paul D; Kaiko, Gerard E; Yang, Ming; Horvat, Jay C; Foster, Paul S

2013-01-01

Asthma is a major disease burden worldwide. Treatment with steroids and long acting β-agonists effectively manage symptoms in many patients but do not treat the underlying cause of disease and have serious side effects when used long term and in children. Therapies targeting the underlying causes of asthma are urgently needed. T helper type 2 (Th2) cells and the cytokines they release are clinically linked to the presentation of all forms of asthma. They are the primary drivers of mild to moderate and allergic asthma. They also play a pathogenetic role in exacerbations and more severe asthma though other factors are also involved. Much effort using animal models and human studies has been dedicated to the identification of the pathogenetic roles of these cells and cytokines and whether inhibition of their activity has therapeutic benefit in asthma. We discuss the current status of Th2 cytokine antagonists for the treatment of asthma. We also discuss the potential for targeting Th2-inducing cytokines, Th2 cell receptors and signaling as well as the use of Th2 cell antagonists, small interfering oligonucleotides, microRNAs, and combination therapies. Th2 antagonists may be most effective in particular asthma subtypes/endotypes where specific cytokines are known to be active through the analysis of biomarkers. Targeting common receptors and pathways used by these cytokines may have additional benefit. Animal models have been valuable in identifying therapeutic targets in asthma, however the results from such studies need to be carefully interpreted and applied to appropriately stratified patient cohorts in well-designed clinical studies and trials.

[Changes in the prevalence of asthma in Chilean school age children between 1994 and 2002. International Study of Asthma and Allergies in Childhood (ISAAC)--Chile phases I and III].

PubMed

Mallol, Javier; Aguirre, Viviana; Aguilar, Pedro; Calvo, Mario; Amarales, Lidia; Arellano, Pamela; Palma, Rodrigo

2007-05-01

In developed countries, the prevalence of asthma in children has significantly increased in the last decades. However, there is no information about the trends of asthma in Latin America. To determine changes in asthma prevalence between 1994 and 2002 in Chilean schoolchildren. The prevalence of asthma symptoms in schoolchildren aged 7 (n =18.697) and 13 years (n =18.939), from South Santiago, Valdivia and Punta Arenas, obtained during phases I and III of the ISAAC, carried out in 1994 and 2002, was compared. From 1994 to 2002, the mean national prevalence of "wheezing in the last 12 months" in the group aged 6-7 years, changed from 18.2% to 17.9% (p =NS); "asthma ever" from 12.5% to 10.7% (p =NS), and "severe episode" from 3.2% to 2.8% (p =NS). There was a significant increase of the prevalence of "wheezing in the last 12 months", in children aged 13-14 years, from 9.8% to 15.5% (p =0.01); in "asthma ever" from 10.2% to 14.9% (p =0.01), and for "severe episode" from 2.8% to 3.8% (p =0.01). There was a significant increase in the prevalence of respiratory symptoms related to asthma in children aged 13-14 years that was consistent in all the 3 participating centres of the ISAAC. However, the prevalence of asthma symptoms in children aged 6-7 years remained without significant changes between 1994 and 2002.