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

PubMed

Bhome, Arvind B; Brashier, Bill

2014-03-01

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

Obstructive Lung Diseases in HIV: A Clinical Review and Identification of Key Future Research Needs

PubMed Central

Drummond, M. Bradley; Kunisaki, Ken M.; Huang, Laurence

2016-01-01

HIV infection has shifted from what was once a disease directly impacting short-term mortality to what is now a chronic illness controllable in the era of effective combination antiretroviral therapy (ART). In this setting, life expectancy for HIV-infected individual is nearly comparable to that of individuals without HIV. Subsequent to this increase in life expectancy, there has been recognition of increased multimorbidity among HIV-infected persons, with prevalence of comorbid chronic illnesses now approaching 65%. Obstructive lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma, are prevalent conditions associated with substantial morbidity and mortality in the United States. There is overlap in risk factors for HIV acquisition and chronic lung diseases, including lower socioeconomic status and the use of tobacco and illicit drugs. Objectives of this review are to (1) summarize the current state of knowledge regarding COPD and asthma among HIV-infected persons, (2) highlight implications for clinicians caring for patients with these combined comorbidities, and (3) identify key research initiatives to reduce the burden of obstructive lung diseases among HIV-infected persons. PMID:26974304

Oxymorphone

MedlinePlus

... ever had lung disease such as chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema), a head injury, brain tumor, any condition that ...

[Evaluation of the course of chronic obstructive lung diseases according to the classifications of the European Respiratory Society and the Global Initiative on Chronic Obstructive Lung Disease].

PubMed

Nefedov, V B; Shergina, E A; Popova, L A

2006-01-01

In 91 patients with chronic obstructive lung disease (COLD), the severity of this disease according to the Classifications of the European Respiratory Society (ERS) and the Global Initiative on Chronic Obstructive Lung Disease (GOLD) was compared with that of pulmonary dysfunction according to the data of a comprehensive study, involving the determination of bronchial patency, lung volumes, capacities, and gas-exchange function. This follows that the ERS and GOLD classifications are to be positively appraised as they provide an eligible group of patients for clinical practice in terms of the severity of pulmonary dysfunction and that of COLD. However, the concomitant clinical use of both classifications cannot be regarded as justifiable due to that there are differences in the number of detectable grades (stages) of COLD and borderline (COLD differentiating grades (stages) values of EFV1). In this connection, both classifications have approximately equally significant merits and shortcomings and it is practically impossible to give preference to one of them as the best one. The optimal way out of the established situation is to develop a new (improved) classification of the severity of COLD on the bases of these two existing classifications.

Occupational exposure to dust and lung disease among sheet metal workers.

PubMed Central

Hunting, K L; Welch, L S

1993-01-01

A previous large medical survey of active and retired sheet metal workers with 20 or more years in the trade indicated an unexpectedly high prevalence of obstructive pulmonary disease among both smokers and non-smokers. This study utilised interviews with a cross section of the previously surveyed group to explore occupational risk factors for lung disease. Four hundred and seven workers were selected from the previously surveyed group on the basis of their potential for exposure to fibreglass and asbestos. Selection was independent of health state, and excluded welders. A detailed history of occupational exposure was obtained by telephone interview for 333 of these workers. Exposure data were analysed in relation to previously collected data on chronic bronchitis, obstructive lung disease, and personal characteristics. Assessment of the effects of exposure to fibreglass as distinct from the effects of exposure to asbestos has been difficult in previous studies of construction workers. The experienced workers studied here have performed a diversity of jobs involving exposure to many different types of materials, and this enabled exposure to each dust to be evaluated separately. The risk of chronic bronchitis increased sharply by pack-years of cigarettes smoked; current smokers had a double risk compared with those who had never smoked or had stopped smoking. The occurrence of chronic bronchitis also increased with increasing duration of exposure to asbestos. Workers with a history of high intensity exposure to fibreglass had a more than doubled risk of chronic bronchitis. Obstructive lung disease, defined by results of pulmonary function tests at the medical survey, was also related to both smoking and occupational risk factors. Number of pack years smoked was the strongest predictor of obstructive lung disease. Duration of direct and indirect exposure to welding fume was also a positive predictor of obstructive lung disease. Duration of exposure to asbestos was significantly associated with obstructive lung disease but the dose-response relation was inconsistent, especially for those with higher pack-years of smoking exposure. Exposure to fibreglass was not a risk factor for obstructive lung disease. PMID:8507596

Outpatient Chronic Obstructive Pulmonary Disease Management: Going for the GOLD.

PubMed

Bellinger, Christina R; Peters, Stephen P

2015-01-01

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States with a burden of $50 billion in direct health care costs. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines airflow obstruction as spirometry where the ratio of forced expiratory volume in the first second to forced vital capacity after bronchodilation is less than 0.70. The guidelines also provided graded recommendations on current therapy for COPD. Treatment can be guided based on severity of disease and severity of symptoms. We review the GOLD guidelines to provide an overview of treatment modalities aimed at improving lung function, reducing hospitalization, and reducing mortality. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Development and validation of the Salzburg COPD-screening questionnaire (SCSQ): a questionnaire development and validation study.

PubMed

Weiss, Gertraud; Steinacher, Ina; Lamprecht, Bernd; Kaiser, Bernhard; Mikes, Romana; Sator, Lea; Hartl, Sylvia; Wagner, Helga; Studnicka, M

2017-01-26

Chronic obstructive pulmonary disease prevalence rates are still high. However, the majority of subjects are not diagnosed. Strategies have to be implemented to overcome the problem of under-diagnosis. Questionnaires could be used to pre-select subjects for spirometry and thereby help reducing under-diagnosis. We report a brief, simple, self-administrable and validated chronic obstructive pulmonary disease questionnaire to increase the pre-test probability for chronic obstructive pulmonary disease diagnosis in subjects undergoing confirmatory spirometry. In 2005, we completed the Austrian Burden of Obstructive Lung Disease-study in 1258 subjects aged >40 years. Post-bronchodilator spirometry was performed, and non-reversible airflow limitation defined by FEV 1 /FVC ratio below the lower limit of normal. Questions from the Salzburg chronic obstructive pulmonary disease screening-questionnaire were selected using a logistic regression model, and risk scores were based on regression-coefficients. A training sub-sample (n = 800) was used to create the score, and a test sub-sample (n = 458) was used to test it. In 2008, an external validation study was done, using the same protocol in 775 patients from primary care. The Salzburg chronic obstructive pulmonary disease screening questionnaire was composed of items related to "breathing problems", "wheeze", "cough", "limitation of physical activity", and "smoking". At the >=2 points cut-off of the Salzburg chronic obstructive pulmonary disease screening questionnaire, sensitivity was 69.1% [95%CI: 56.6%; 79.5%], specificity 60.0% [95%CI: 54.9%; 64.9%], the positive predictive value 23.2% [95%CI: 17.7%; 29.7%] and the negative predictive value 91.8% [95%CI: 87.5%; 95.7%] to detect post bronchodilator airflow limitation. The external validation study in primary care confirmed these findings. The Salzburg chronic obstructive pulmonary disease screening questionnaire was derived from the highly standardized Burden of Obstructive Lung Disease study. This validated and easy to use questionnaire can help to increase the efficiency of chronic obstructive pulmonary disease case-finding. QUESTIONNAIRE FOR PRE-SCREENING POTENTIAL SUFFERERS: Scientists in Austria have developed a brief, simple questionnaire to identify patients likely to have early-stage chronic lung disease. Chronic obstructive pulmonary disease (COPD) is notoriously difficult to diagnose, and the condition often causes irreversible lung damage before it is identified. Finding a simple, cost-effective method of pre-screening patients with suspected early-stage COPD could potentially improve treatment responses and limit the burden of extensive lung function ('spirometry') tests on health services. Gertraud Weiss at Paracelsus Medical University, Austria, and co-workers have developed and validated an easy-to-use, self-administered questionnaire that could prove effective for pre-screening patients. The team trialed the five-point Salzburg COPD-screening questionnaire on 1258 patients. Patients scoring 2 points or above on the questionnaire underwent spirometry tests. The questionnaire seems to provide a sensitive and cost-effective way of pre-selecting patients for spirometry referral.

Computed Tomographic Airway Morphology in Chronic Obstructive Pulmonary Disease. Remodeling or Innate Anatomy?

PubMed

Diaz, Alejandro A; Estépar, Raul San José; Washko, George R

2016-01-01

Computed tomographic measures of central airway morphology have been used in clinical, epidemiologic, and genetic investigation as an inference of the presence and severity of small-airway disease in smokers. Although several association studies have brought us to believe that these computed tomographic measures reflect airway remodeling, a careful review of such data and more recent evidence may reveal underappreciated complexity to these measures and limitations that prompt us to question that belief. This Perspective offers a review of seminal papers and alternative explanations of their data in the light of more recent evidence. The relationships between airway morphology and lung function are observed in subjects who never smoked, implying that native airway structure indeed contributes to lung function; computed tomographic measures of central airways such as wall area, lumen area, and total bronchial area are smaller in smokers with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease; and the airways are smaller as disease severity increases. The observations suggest that (1) native airway morphology likely contributes to the relationships between computed tomographic measures of airways and lung function; and (2) the presence of smaller airways in those with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease as well as their decrease with disease severity suggests that smokers with chronic obstructive pulmonary disease may simply have smaller airways to begin with, which put them at greater risk for the development of smoking-related disease.

Tiotropium Oral Inhalation

MedlinePlus

... and chest tightness in patients with chronic obstructive pulmonary disease (COPD, a group of diseases that affect the lungs and airways) such as chronic bronchitis (swelling of the air passages that lead to the lungs) and emphysema (damage to air sacs in the lungs). Tiotropium ...

Aclidinium Oral Inhalation

MedlinePlus

... and chest tightness in patients with chronic obstructive pulmonary disease (COPD, a group of diseases that affect the lungs and airways) such as chronic bronchitis (swelling of the air passages that lead to the lungs) and emphysema (damage to air sacs in the lungs). Aclidinium ...

Lung surgery - discharge

MedlinePlus

... Read More Bronchiectasis Chronic obstructive pulmonary disease Lung cancer Lung cancer - non-small cell Lung cancer - small cell ... team. Related MedlinePlus Health Topics COPD Emphysema Lung Cancer Lung Diseases Pleural Disorders Browse the Encyclopedia A.D. ...

Albuterol and Ipratropium Oral Inhalation

MedlinePlus

... tightness, and coughing in people with chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways) such as chronic bronchitis (swelling of the air passages that lead to the lungs) and emphysema (damage to the air sacs in the lungs). ...

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

PubMed

Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

2017-02-01

Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

Analysis of the absorption spectra of gas emission of patients with lung cancer and chronic obstructive pulmonary disease by laser optoacoustic spectroscopy

NASA Astrophysics Data System (ADS)

Bukreeva, Ekaterina B.; Bulanova, Anna A.; Kistenev, Yurii V.; Kuzmin, Dmitry A.; Tuzikov, Sergei A.; Yumov, Evgenii L.

2013-02-01

It is important to identify patients with chronic obstructive pulmonary disease (COPD) and lung cancer in the early stages of the disease. The method of laser opto-acoustic gas analysis, in this case, can act as a promising tool for diagnostics. The material for this study were the gas emission samples collected from patients and healthy volunteers - samples of exhaled air, swabs from teeth and cheeks. A set of material was formed three groups: healthy volunteers, patients with COPD, lung cancer patients. The resulting samples were analyzed by means of laser opto-acoustic gas analyzers: with intracavity location detector (ILPA-1), with extracavity location detector (LGA-2). Presentation of the results in an easy to visual form was performed using the method of elastic maps, based on the principal component analysis. The results of analysis show potentialities of usage of laser optoacoustic spectroscopy application to assess the status of patients with chronic obstructive pulmonary disease and lung cancer.

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

PubMed Central

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

2017-01-01

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

Parameters affecting inhalation therapy adherence in elderly patients with chronic obstructive lung disease and asthma.

PubMed

Turan, Onur; Turan, Pakize Ayse; Mirici, Arzu

2017-06-01

One of the most significant problems in the treatment of elderly patients is incorrect use of inhaler devices. The purpose of the present study was to assess the parameters affecting treatment adherence among elderly patients. Spirometry, the Mini-Mental State Examination for cognitive impairment and the Morisky Medication Adherence Scale-4 were carried out in 121 (88 chronic obstructive lung disease patients according to the Global Initiative for Chronic Obstructive Lung Disease, 33 asthma patients according to The Global Initiative for Asthma (GINA) criteria) participants aged over 65 years. The patients with cognitive impairment, low socioeconomic status, a high number of admissions to an emergency service in past year and the presence of dyspnea or sputum had significantly lower inhalation device use scores (P = 0.017, 0.03, 0.025, 0.03 and 0.02). The patients with high Mini-Mental State Examination scores and forced expiratory volume in 1 s (as liter and percentage) were found to be more successful in using inhaler devices (P = 0.005, 0.007 and 0.022). There was a negative correlation between number of hospitalizations and inhalation device score (P = 0.021).The participants without education/training by a doctor about the inhaler device had a significantly poorer treatment adherence (P < 0.001). Older chronic obstructive lung disease and asthmatic patients have more difficulty with the correct use of inhaler devices. Cognitive impairment might be an important parameter that can affect inhalation device technique. Socioeconomic status, smoking, pulmonary symptoms and admissions to hospital were also thought to have effects on the adherence to inhalation therapy. The type of chronic respiratory disease (chronic obstructive lung disease/asthma) is not a major factor influencing therapy adherence. Assessment of cognitive functions, choosing suitable inhalation devices and educational programs for inhaler use could improve the success of inhaler technique in elderly patients. Geriatr Gerontol Int 2017; 17: 999-1005. © 2016 Japan Geriatrics Society.

Small-airway obstruction and emphysema in chronic obstructive pulmonary disease.

PubMed

McDonough, John E; Yuan, Ren; Suzuki, Masaru; Seyednejad, Nazgol; Elliott, W Mark; Sanchez, Pablo G; Wright, Alexander C; Gefter, Warren B; Litzky, Leslie; Coxson, Harvey O; Paré, Peter D; Sin, Don D; Pierce, Richard A; Woods, Jason C; McWilliams, Annette M; Mayo, John R; Lam, Stephen C; Cooper, Joel D; Hogg, James C

2011-10-27

The major sites of obstruction in chronic obstructive pulmonary disease (COPD) are small airways (<2 mm in diameter). We wanted to determine whether there was a relationship between small-airway obstruction and emphysematous destruction in COPD. We used multidetector computed tomography (CT) to compare the number of airways measuring 2.0 to 2.5 mm in 78 patients who had various stages of COPD, as judged by scoring on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale, in isolated lungs removed from patients with COPD who underwent lung transplantation, and in donor (control) lungs. MicroCT was used to measure the extent of emphysema (mean linear intercept), the number of terminal bronchioles per milliliter of lung volume, and the minimum diameters and cross-sectional areas of terminal bronchioles. On multidetector CT, in samples from patients with COPD, as compared with control samples, the number of airways measuring 2.0 to 2.5 mm in diameter was reduced in patients with GOLD stage 1 disease (P=0.001), GOLD stage 2 disease (P=0.02), and GOLD stage 3 or 4 disease (P<0.001). MicroCT of isolated samples of lungs removed from patients with GOLD stage 4 disease showed a reduction of 81 to 99.7% in the total cross-sectional area of terminal bronchioles and a reduction of 72 to 89% in the number of terminal bronchioles (P<0.001). A comparison of the number of terminal bronchioles and dimensions at different levels of emphysematous destruction (i.e., an increasing value for the mean linear intercept) showed that the narrowing and loss of terminal bronchioles preceded emphysematous destruction in COPD (P<0.001). These results show that narrowing and disappearance of small conducting airways before the onset of emphysematous destruction can explain the increased peripheral airway resistance reported in COPD. (Funded by the National Heart, Lung, and Blood Institute and others.).

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

PubMed

McGeachie, M J; Yates, K P; Zhou, X; Guo, F; Sternberg, A L; Van Natta, M L; Wise, R A; Szefler, S J; Sharma, S; Kho, A T; Cho, M H; Croteau-Chonka, D C; Castaldi, P J; Jain, G; Sanyal, A; Zhan, Y; Lajoie, B R; Dekker, J; Stamatoyannopoulos, J; Covar, R A; Zeiger, R S; Adkinson, N F; Williams, P V; Kelly, H W; Grasemann, H; Vonk, J M; Koppelman, G H; Postma, D S; Raby, B A; Houston, I; Lu, Q; Fuhlbrigge, A L; Tantisira, K G; Silverman, E K; Tonascia, J; Weiss, S T; Strunk, R C

2016-05-12

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Alpha-1 antitrypsin blood test

MedlinePlus

... the lungs ( bronchiectasis ) Scarring of the liver ( cirrhosis ) Chronic obstructive pulmonary disease (COPD) Liver tumors Yellowing of the skin and eyes due to blocked bile flow ( obstructive ...

Role of the Lung Microbiome in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

PubMed

Wang, Lei; Hao, Ke; Yang, Ting; Wang, Chen

2017-09-05

The development of culture-independent techniques for microbiological analysis shows that bronchial tree is not sterile in either healthy or chronic obstructive pulmonary disease (COPD) individuals. With the advance of sequencing technologies, lung microbiome has become a new frontier for pulmonary disease research, and such advance has led to better understanding of the lung microbiome in COPD. This review aimed to summarize the recent advances in lung microbiome, its relationships with COPD, and the possible mechanisms that microbiome contributed to COPD pathogenesis. Literature search was conducted using PubMed to collect all available studies concerning lung microbiome in COPD. The search terms were "microbiome" and "chronic obstructive pulmonary disease", or "microbiome" and "lung/pulmonary". The papers in English about lung microbiome or lung microbiome in COPD were selected, and the type of articles was not limited. The lung is a complex microbial ecosystem; the microbiome in lung is a collection of viable and nonviable microbiota (bacteria, viruses, and fungi) residing in the bronchial tree and parenchymal tissues, which is important for health. The following types of respiratory samples are often used to detect the lung microbiome: sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa. Disordered bacterial microbiome is participated in pathogenesis of COPD; there are also dynamic changes in microbiota during COPD exacerbations. Lung microbiome may contribute to the pathogenesis of COPD by manipulating inflammatory and/or immune process. Normal lung microbiome could be useful for prophylactic or therapeutic management in COPD, and the changes of lung microbiome could also serve as biomarkers for the evaluation of COPD.

Advantage of impulse oscillometry over spirometry to diagnose chronic obstructive pulmonary disease and monitor pulmonary responses to bronchodilators: An observational study.

PubMed

Saadeh, Constantine; Saadeh, Charles; Cross, Blake; Gaylor, Michael; Griffith, Melissa

2015-01-01

This retrospective study was a comparative analysis of sensitivity of impulse oscillometry and spirometry techniques for use in a mixed chronic obstructive pulmonary disease group for assessing disease severity and inhalation therapy. A total of 30 patients with mild-to-moderate chronic obstructive pulmonary disease were monitored by impulse oscillometry, followed by spirometry. Lung function was measured at baseline after bronchodilation and at follow-up (3-18 months). The impulse oscillometry parameters were resistance in the small and large airways at 5 Hz (R5), resistance in the large airways at 15 Hz (R15), and lung reactance (area under the curve X; AX). After the bronchodilator therapy, forced expiratory volume in 1 second (FEV1) readings evaluated by spirometry were unaffected at baseline and at follow-up, while impulse oscillometry detected an immediate improvement in lung function, in terms of AX (p = 0.043). All impulse oscillometry parameters significantly improved at follow-up, with a decrease in AX by 37% (p = 0.0008), R5 by 20% (p = 0.0011), and R15 by 12% (p = 0.0097). Impulse oscillometry parameters demonstrated greater sensitivity compared with spirometry for monitoring reversibility of airway obstruction and the effect of maintenance therapy. Impulse oscillometry may facilitate early treatment dose optimization and personalized medicine for chronic obstructive pulmonary disease patients.

The Contribution of Small Airway Obstruction to the Pathogenesis of Chronic Obstructive Pulmonary Disease.

PubMed

Hogg, James C; Paré, Peter D; Hackett, Tillie-Louise

2017-04-01

The hypothesis that the small conducting airways were the major site of obstruction to airflow in normal lungs was introduced by Rohrer in 1915 and prevailed until Weibel introduced a quantitative method of studying lung anatomy in 1963. Green repeated Rohrer's calculations using Weibels new data in 1965 and found that the smaller conducting airways offered very little resistance to airflow. This conflict was resolved by seminal experiments conducted by Macklem and Mead in 1967, which confirmed that a small proportion of the total lower airways resistance is attributable to small airways <2 mm in diameter. Shortly thereafter, Hogg, Macklem, and Thurlbeck used this technique to show that small airways become the major site of obstruction in lungs affected by emphysema. These and other observations led Mead to write a seminal editorial in 1970 that postulated the small airways are a silent zone within normal lungs where disease can accumulate over many years without being noticed. This review provides a progress report since the 1970s on methods for detecting chronic obstructive pulmonary disease, the structural nature of small airways' disease, and the cellular and molecular mechanisms that are thought to underlie its pathogenesis. Copyright © 2017 the American Physiological Society.

Improving Communication About Serious Illness

ClinicalTrials.gov

2017-01-07

Critical Illness; Chronic Disease; Terminal Care; Palliative Care; Communication; Advance Care Planning; Neoplasm Metastasis; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Heart Failure; End Stage Liver Disease; Kidney Failure, Chronic

The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease

PubMed Central

Pragman, Alexa A.; Kim, Hyeun Bum; Reilly, Cavan S.; Wendt, Christine; Isaacson, Richard E.

2012-01-01

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. PMID:23071781

[Epidemiology of chronic non-specific pulmonary diseases in Yugoslavia (author's transl)].

PubMed

Goldmann, S; Zrilić, V; Acketa, M

1977-01-01

In Yugoslavia the diseases of the respiratory system (without tuberculosis) ranges with 23% in front of all other organ-localised diseases. 53--95% of all chronic non-specific lung diseases are registrated in the chest clinics of the different republics. 67% of all lung diseases registrated belong to the obstructive syndrom, 6% are bronchial carcinomas and 27% represent the group of other chronic pulmonary diseases. 31,5% of all patients with chronic obstructive bronchitis are younger than 50 years old, 34,7% are in the age-group between 50-65 years. Assuming the best registered incidence and prevalence rates of bronchial carcinoma, chronic bronchitis, asthma and emphysema in Slowenia as a basis, the expected morbidity of these diseases in each autonomic republic are compared.

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

PubMed

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

2011-10-01

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

State-of-the-art MS technology applications in lung disease.

PubMed

Végvári, Ákos; Döme, Balázs

2011-12-01

Two frontline MS technologies, which have recently gained much attention, are discussed within the scope of this review. Besides a brief summary on the contemporary state of lung cancer and chronic obstructive pulmonary disease, the principles of multiple reaction monitoring and matrix assisted laser desorption ionization (MALDI) MS imaging are presented. A comprehensive overview of quantitative mass spectrometry applications is provided, covering multiple reaction monitoring assay developments for analysis of proteins (biomarkers) and low-molecular-weight compounds (drugs) with a special focus on the disease areas of lung cancer and chronic obstructive pulmonary disease. The MALDI-MS imaging applications are discussed similarly, providing references to studies conducted on lung tissues in order to localize drug compounds and protein biomarkers.

CFTR gene variant IVS8-5T in disseminated bronchiectasis

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

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

1996-04-01

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

Impact of residual pulmonary obstruction on the long-term outcome of patients with pulmonary embolism.

PubMed

Pesavento, Raffaele; Filippi, Lucia; Palla, Antonio; Visonà, Adriana; Bova, Carlo; Marzolo, Marco; Porro, Fernando; Villalta, Sabina; Ciammaichella, Maurizio; Bucherini, Eugenio; Nante, Giovanni; Battistelli, Sandra; Muiesan, Maria Lorenza; Beltramello, Giampietro; Prisco, Domenico; Casazza, Franco; Ageno, Walter; Palareti, Gualtiero; Quintavalla, Roberto; Monti, Simonetta; Mumoli, Nicola; Zanatta, Nello; Cappelli, Roberto; Cattaneo, Marco; Moretti, Valentino; Corà, Francesco; Bazzan, Mario; Ghirarduzzi, Angelo; Frigo, Anna Chiara; Miniati, Massimo; Prandoni, Paolo

2017-05-01

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2-54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23-4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension. Copyright ©ERS 2017.

Hydromorphone Rectal

MedlinePlus

... affects your breathing such as asthma, chronic obstructive pulmonary disease (COPD; a group of diseases including chronic bronchitis and emphysema that affect the lungs and airways), or kyphoscoliosis ( ...

[Efficacy of nebulizer therapy with acetylcystein in outpatients with chronic obstructive lung disease].

PubMed

Stepanishcheva, L A; Ignatova, G L; Blinova, E V

2005-01-01

Chronic obstructive lung disease (COLD) is a widespread illness with constantly growing mortality. Mucolytic therapy plays a significant role in treatment of patients with COLD. The paper contains the results of nebulization with acetyl-cystein as part of rehabilitation program in outpatients with stable clinical course of I-II stage of COLD. The results demonstrated significant clinical improvement, as well as positive changes in external respiration parameters (1 sforced expiratory volume), increase of physical activity tolerance, and disappearance of acute inflammation phase reactants in saliva.

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

PubMed Central

Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

2013-01-01

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

Diagnostic Instability and Reversals of Chronic Obstructive Pulmonary Disease Diagnosis in Individuals with Mild to Moderate Airflow Obstruction.

PubMed

Aaron, Shawn D; Tan, Wan C; Bourbeau, Jean; Sin, Don D; Loves, Robyn H; MacNeil, Jenna; Whitmore, George A

2017-08-01

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease, and reversal of COPD diagnosis is thought to be uncommon. To determine whether a spirometric diagnosis of mild or moderate COPD is subject to variability and potential error. We examined two prospective cohort studies that enrolled subjects with mild to moderate post-bronchodilator airflow obstruction. The Lung Health Study (n = 5,861 subjects; study duration, 5 yr) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study (n = 1,551 subjects; study duration, 4 yr) were examined to determine frequencies of (1) diagnostic instability, represented by how often patients initially met criteria for a spirometric diagnosis of COPD but then crossed the diagnostic threshold to normal and then crossed back to COPD over a series of annual visits, or vice versa; and (2) diagnostic reversals, defined as how often an individual's COPD diagnosis at the study outset reversed to normal by the end of the study. Diagnostic instability was common and occurred in 19.5% of the Lung Health Study subjects and 6.4% of the CanCOLD subjects. Diagnostic reversals of COPD from the beginning to the end of the study period occurred in 12.6% and 27.2% of subjects in the Lung Health Study and CanCOLD study, respectively. The risk of diagnostic instability was greatest for subjects whose baseline FEV 1 /FVC value was closest to the diagnostic threshold, and the risk of diagnostic reversal was greatest for subjects who quit smoking during the study. A single post-bronchodilator spirometric assessment may not be reliable for diagnosing COPD in patients with mild to moderate airflow obstruction at baseline.

[Chronic obstructive pulmonary disease (COPD). Current concepts and new therapeutic options].

PubMed

Klemmer, A; Greulich, T; Koczulla, A R; Vogelmeier, C F

2014-04-01

Chronic obstructive pulmonary disease (COPD) is a very common chronic disease with increasing prevalence. Inhaled particles and gases (in particular tobacco smoke) induce chronic inflammation of the airways accompanied by a not fully reversible airflow limitation. Destruction of lung tissue and deterioration of gas exchange may follow. In parallel, several comorbidities can be observed. The COPD assessment was revised and now takes into account lung function, the patients' symptoms, and history of exacerbations. More recently, several new long-acting bronchodilators received approval. Combination products, consisting of long-acting β2-agonists and long-acting anticholinergics, and a new combination of a long-acting β-agonist and an inhaled corticosteroid will follow in the near future. Smoking cessation is of central importance.

Pulmonary hypertensive vasculopathy in parenchymal lung diseases and/or hypoxia: Number 1 in the Series "Pathology for the clinician" Edited by Peter Dorfmüller and Alberto Cavazza.

PubMed

Ghigna, Maria Rosa; Mooi, Wolter J; Grünberg, Katrien

2017-06-30

Pulmonary hypertension (PH) with complicating chronic lung diseases and/or hypoxia falls into group 3 of the updated classification of PH. Patients with chronic obstructive lung disease (COPD), diffuse lung disease (such as idiopathic pulmonary fibrosis (IPF)) and with sleep disordered breathing are particularly exposed to the risk of developing PH. Although PH in such a context is usually mild, a minority of patients exhibit severe haemodynamic impairment, defined by a mean pulmonary arterial pressure (mPAP) of ≥35 mmHg or mPAP values ranging between 25 mmHg and 35 mmHg with a low cardiac index (<2 L·min -1 ·m -2 ). The overlap between lung parenchymal disease and PH heavily affects life expectancy in such a patient population and complicates their therapeutic management. In this review we illustrate the pathological features and the underlying pathophysiological mechanisms of pulmonary circulation in chronic lung diseases, with an emphasis on COPD, IPF and obstructive sleep apnoea syndrome. Copyright ©ERS 2017.

Arformoterol Oral Inhalation

MedlinePlus

... coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases, which includes chronic bronchitis and emphysema). Arformoterol is in a class of medications called ...

Salmeterol Oral Inhalation

MedlinePlus

... chest tightness caused by asthma and chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema). It also is used to prevent bronchospasm (breathing ...

Formoterol Oral Inhalation

MedlinePlus

... breath, and breathing difficulties caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema) in adults. Formoterol inhalation powder is also used ...

Detection of chronic obstructive pulmonary disease in community-based annual lung cancer screening: Chiba Chronic Obstructive Pulmonary Disease Lung Cancer Screening Study Group.

PubMed

Sekine, Yasuo; Fujisawa, Takehiko; Suzuki, Kiminori; Tsutatani, Shuko; Kubota, Kazuko; Ikegami, Hiroshi; Isobe, Yuji; Nakamura, Mitsugu; Takiguchi, Yuichi; Tatsumi, Koichiro

2014-01-01

Detection of chronic obstructive pulmonary disease (COPD) is crucial in the management of COPD. The aim of this study was to establish the utility of a community-based lung cancer screening for detecting COPD. In Japan, community-based lung cancer screening for residents who are 40 years or older using chest radiography is well established. A screening system in Chiba City, Japan, was used to detect COPD. The criteria to consider COPD at screening included age of 60 years or older, a smoking history and chronic respiratory symptoms. Participants fulfilling these criteria were referred for diagnostic evaluation consisting of pulmonary function testing (PFT) and chest computed tomography (CT). Of 89,100 Chiba City residents who underwent lung cancer screening, 72,653 residents were 60 years or older. Among them, 878 (1.0%) were identified with suspected COPD and referred for further evaluation. Of those identified, a total of 567 residents (64.6%, 567/878) underwent further evaluations, and 161 (28.4%) were reported to have COPD, with 38.5% of them requiring COPD treatment. To verify the diagnoses from the secondary evaluation centres, PFT and CT data were collected from 228 study participants, and 24.9% were diagnosed with COPD. CT findings classified according to the Goddard classification revealed that 20.1% of these participants had moderate to severe emphysema. COPD screening added to a community-based lung cancer screening programme may be effective in the detection of patients with COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression

DTIC Science & Technology

2011-09-01

such as that which occurs in chronic obstructive pulmonary disease (COPD) and emphysema , is associated with increased risk of lung cancer. These...effect of the fibronectin III-1c peptide on the expression of inflammatory genes by human lung fibroblasts, lung cancer cells, and pulmonary ...CXCR2 in bleomycin-induced pulmonary inflammation and fibrosis. Am J Respir Cell Mol Biol. 2009; 40:410-21. 7. Barnes PJ. New therapies for chronic

CFTR and lung homeostasis

PubMed Central

Matalon, Sadis

2014-01-01

CFTR is a cAMP-activated chloride and bicarbonate channel that is critical for lung homeostasis. Decreases in CFTR expression have dire consequences in cystic fibrosis (CF) and have been suggested to be a component of the lung pathology in chronic obstructive pulmonary disease. Decreases or loss of channel function often lead to mucus stasis, chronic bacterial infections, and the accompanying chronic inflammatory responses that promote progressive lung destruction, and, eventually in CF, lung failure. Here we discuss CFTR's functional role airway surface liquid hydration and pH, in regulation of other channels such as the epithelial sodium channel, and in regulating inflammatory responses in the lung. PMID:25381027

Chronic Obstructive Pulmonary Disease Exacerbations in the COPDGene Study: Associated Radiologic Phenotypes

PubMed Central

Kazerooni, Ella A.; Lynch, David A.; Liu, Lyrica X.; Murray, Susan; Curtis, Jeffrey L.; Criner, Gerard J.; Kim, Victor; Bowler, Russell P.; Hanania, Nicola A.; Anzueto, Antonio R.; Make, Barry J.; Hokanson, John E.; Crapo, James D.; Silverman, Edwin K.; Martinez, Fernando J.; Washko, George R.

2011-01-01

Purpose: To test the hypothesis—given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)—that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease. Materials and Methods: This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a −950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements. Results: In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047). Conclusion: Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110173/-/DC1 PMID:21788524

Asymptomatic peripheral artery disease can limit maximal exercise capacity in chronic obstructive pulmonary disease patients regardless of airflow obstruction and lung hyperinflation.

PubMed

Crisafulli, Ernesto; Scelfo, Chiara; Tzani, Panagiota; Aiello, Marina; Bertorelli, Giuseppina; Chetta, Alfredo

2017-06-01

Background Silent/asymptomatic peripheral artery disease may occur in patients with chronic obstructive pulmonary disease, but it is poorly investigated. The primary aim of this study was to evaluate in chronic obstructive pulmonary disease patients the impact of asymptomatic/silent peripheral artery disease on maximal exercise capacity; the secondary aim was to search for predictors of peripheral artery disease. Methods We prospectively enrolled chronic obstructive pulmonary disease outpatients. Data on anthropometric characteristics, lung function, cardiopulmonary exercise test and ankle-brachial index were recorded. The cut-off of ankle-brachial index used to define patients with peripheral artery disease was ≤0.90. Results We studied 47 patients and found 24 patients (51%) who showed peripheral artery disease. As compared to patients without peripheral artery disease, patients with peripheral artery disease had lower values of peak oxygen uptake, peak workload, energy expenditure (metabolic equivalents) and heart rate recovery, but showed the same degree of airflow obstruction and static and dynamic hyperinflation. In a multivariate linear regression model performed to identify variables predicting metabolic equivalents, ankle-brachial index (β 2.59; 95% confidence interval 0.51-4.67; p = 0.016) was an independent variable. In the search for predictors of peripheral artery disease, heart rate recovery (odds ratio 8.80; 95% confidence interval 1.30-59.35; p = 0.026) increased the risk of peripheral artery disease, whereas metabolic equivalents (odds ratio 0.50; 95% confidence interval 0.26-0.94, p = 0.033) and inhaled corticosteroids+long-acting β 2 agonists (odds ratio 0.13; 95% confidence interval 0.02-0.83; p = 0.030) reduced this risk. Conclusions In chronic obstructive pulmonary disease outpatients, asymptomatic/silent peripheral artery disease affects the maximal exercise capacity regardless of airflow obstruction and lung hyperinflation. A delay of heart rate recovery increase the risk of peripheral artery disease, whereas high values of metabolic equivalents and the use of inhaled corticosteroids+long-acting β 2 agonists reduces this risk.

[Lung dysfunction in patients with severe chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2005-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Raw, Rin, Rex, DLCO-SS, PaO2, and PaCO2 were determined in 36 patients with severe chronic obstructive lung disease (FEV1 < 50% of the normal value). All the patients were found to have impaired bronchial patency and changes in lung volumes and capacities; 83.3% of the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, Raw, Rin, Rex; altered lung volumes and capacities manifested by increased RV, TGV, and TLC, and by decreased VC and FVC; pulmonary gas exchange dysfunction showed up as lowered PaO2 and DLCO-SS, as decreased or increased PaCO2. The observed bronchial patency disorders varied from significant to severe; functional changes in lung volumes and capacities were mild to severe.

Fluticasone and Salmeterol Oral Inhalation

MedlinePlus

... coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema). The combination of fluticasone and salmeterol (Advair Diskus) ...

Persistent activation of an innate immune axis translates respiratory viral infection into chronic lung disease

PubMed Central

Kim, Edy Y.; Battaile, John T.; Patel, Anand C.; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H.; Benoit, Loralyn A.; Byers, Derek E.; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W.; Morton, Jeffrey D.; Castro, Mario; Polineni, Deepika; Patterson, G. Alexander; Schwendener, Reto A.; Allard, John D.; Peltz, Gary; Holtzman, Michael J.

2008-01-01

To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of a chronic lung disease that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after infection with a common type of respiratory virus is cleared to trace levels of noninfectious virus. Unexpectedly, the chronic inflammatory disease arises independently of an adaptive immune response and is driven by IL-13 produced by macrophages stimulated by CD1d-dependent TCR-invariant NKT cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a novel NKT cell-macrophage innate immune axis. PMID:18488036

Integrating Behavioral Health and Primary Care for Comorbid Behavioral and Medical Problems

ClinicalTrials.gov

2018-01-10

Arthritis; Asthma; Chronic Obstructive Lung Disease; Diabetes; Heart Failure; Hypertension; Anxiety; Chronic Pain; Depression; Fibromyalgia; Insomnia; Irritable Bowel Syndrome; Problem Drinking; Substance Use Disorder

The Unfolded Protein Response in Chronic Obstructive Pulmonary Disease

PubMed Central

2016-01-01

Accumulation of nonfunctional and potentially cytotoxic, misfolded proteins in chronic obstructive pulmonary disease (COPD) is believed to contribute to lung cell apoptosis, inflammation, and autophagy. Because of its fundamental role as a quality control system in protein metabolism, the “unfolded protein response” (UPR) is of potential importance in the pathogenesis of COPD. The UPR comprises a series of transcriptional, translational, and post-translational processes that decrease protein synthesis while enhancing protein folding capacity and protein degradation. Several studies have suggested that the UPR contributes to lung cell apoptosis and lung inflammation in at least some subjects with human COPD. However, information on the prevalence of the UPR in subjects with COPD, the lung cells that manifest a UPR, and the role of the UPR in the pathogenesis of COPD is extremely limited and requires additional study. PMID:27115948

The Unfolded Protein Response in Chronic Obstructive Pulmonary Disease.

PubMed

Kelsen, Steven G

2016-04-01

Accumulation of nonfunctional and potentially cytotoxic, misfolded proteins in chronic obstructive pulmonary disease (COPD) is believed to contribute to lung cell apoptosis, inflammation, and autophagy. Because of its fundamental role as a quality control system in protein metabolism, the "unfolded protein response" (UPR) is of potential importance in the pathogenesis of COPD. The UPR comprises a series of transcriptional, translational, and post-translational processes that decrease protein synthesis while enhancing protein folding capacity and protein degradation. Several studies have suggested that the UPR contributes to lung cell apoptosis and lung inflammation in at least some subjects with human COPD. However, information on the prevalence of the UPR in subjects with COPD, the lung cells that manifest a UPR, and the role of the UPR in the pathogenesis of COPD is extremely limited and requires additional study.

Lung Mass in Smokers.

PubMed

Washko, George R; Kinney, Gregory L; Ross, James C; San José Estépar, Raúl; Han, MeiLan K; Dransfield, Mark T; Kim, Victor; Hatabu, Hiroto; Come, Carolyn E; Bowler, Russell P; Silverman, Edwin K; Crapo, James; Lynch, David A; Hokanson, John; Diaz, Alejandro A

2017-04-01

Emphysema is characterized by airspace dilation, inflammation, and irregular deposition of elastin and collagen in the interstitium. Computed tomographic studies have reported that lung mass (LM) may be increased in smokers, a finding attributed to inflammatory and parenchymal remodeling processes observed on histopathology. We sought to examine the epidemiologic and clinical associations of LM in smokers. Baseline epidemiologic, clinical, and computed tomography (CT) data (n = 8156) from smokers enrolled into the COPDGene Study were analyzed. LM was calculated from the CT scan. Changes in lung function at 5 years' follow-up were available from 1623 subjects. Regression analysis was performed to assess for associations of LM with forced expiratory volume in 1 second (FEV 1 ) and FEV 1 decline. Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 chronic obstructive pulmonary disease had greater LM than either smokers with normal lung function or those with GOLD 2-4 chronic obstructive pulmonary disease (P < 0.001 for both comparisons). LM was predictive of the rate of the decline in FEV 1 (decline per 100 g, -4.7 ± 1.7 mL/y, P = 0.006). Our cross-sectional data suggest the presence of a biphasic radiological remodeling process in smokers: the presence of such nonlinearity must be accounted for in longitudinal computed tomographic studies. Baseline LM predicts the decline in lung function. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients.

PubMed

Voskrebenzev, Andreas; Gutberlet, Marcel; Klimeš, Filip; Kaireit, Till F; Schönfeld, Christian; Rotärmel, Alexander; Wacker, Frank; Vogel-Claussen, Jens

2018-04-01

In this feasibility study, a phase-resolved functional lung imaging postprocessing method for extraction of dynamic perfusion (Q) and ventilation (V) parameters using a conventional 1H lung MRI Fourier decomposition acquisition is introduced. Time series of coronal gradient-echo MR images with a temporal resolution of 288 to 324 ms of two healthy volunteers, one patient with chronic thromboembolic hypertension, one patient with cystic fibrosis, and one patient with chronic obstructive pulmonary disease were acquired at 1.5 T. Using a sine model to estimate cardiac and respiratory phases of each image, all images were sorted to reconstruct full cardiac and respiratory cycles. Time to peak (TTP), V/Q maps, and fractional ventilation flow-volume loops were calculated. For the volunteers, homogenous ventilation and perfusion TTP maps (V-TTP, Q-TTP) were obtained. The chronic thromboembolic hypertension patient showed increased perfusion TTP in hypoperfused regions in visual agreement with dynamic contrast-enhanced MRI, which improved postpulmonary endaterectomy surgery. Cystic fibrosis and chronic obstructive pulmonary disease patients showed a pattern of increased V-TTP and Q-TTP in regions of hypoventilation and decreased perfusion. Fractional ventilation flow-volume loops of the chronic obstructive pulmonary disease patient were smaller in comparison with the healthy volunteer, and showed regional differences in visual agreement with functional small airways disease and emphysema on CT. This study shows the feasibility of phase-resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med 79:2306-2314, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

United in prevention-electrocardiographic screening for chronic obstructive pulmonary disease.

PubMed

Lazovic, Biljana; Mazic, Sanja; Stajic, Zoran; Djelic, Marina; Zlatkovic-Svenda, Mirjana; Putnikovic, Biljana

2013-01-01

NONE DECLARED. P-wave abnormalities on the resting electrocardiogram have been associated with cardiovascular or pulmonary disease. So far, "Gothic" P wave and verticalization of the frontal plane axis is related to lung disease, particularly obstructive lung disease. We tested if inverted P wave in AVl as a lone criteria of P wave axis >70° could be screening tool for emphysema. 1095 routine electrocardiograms (ECGs) were reviewed which yielded 478 (82,1%) ECGs with vertical P-axis in sinus rhythm. Charts were reviewed for the diagnosis of COPD and emphysema based on medical history and pulmonary function tests. Electrocardiogram is very effective screening tool not only in cardiovascular field but in chronic obstructive pulmonary disease. The verticality of the P axis is usually immediately apparent, making electrocardiogram rapid screening test for emphysema.

Musculoskeletal Disorders in Chronic Obstructive Pulmonary Disease

PubMed Central

Cielen, Nele; Maes, Karen

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airway obstruction and inflammation but also accompanied by several extrapulmonary consequences, such as skeletal muscle weakness and osteoporosis. Skeletal muscle weakness is of major concern, since it leads to poor functional capacity, impaired health status, increased healthcare utilization, and even mortality, independently of lung function. Osteoporosis leads to fractures and is associated with increased mortality, functional decline, loss of quality of life, and need for institutionalization. Therefore, the presence of the combination of these comorbidities will have a negative impact on daily life in patients with COPD. In this review, we will focus on these two comorbidities, their prevalence in COPD, combined risk factors, and pathogenesis. We will try to prove the clustering of these comorbidities and discuss possible preventive or therapeutic strategies. PMID:24783225

Glycopyrrolate Oral Inhalation

MedlinePlus

... and chest tightness in patients with chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, that includes chronic bronchitis and emphysema). Glycopyrrolate is in a class of medications called ...

RAGE and tobacco smoke: insights into modeling chronic obstructive pulmonary disease

PubMed Central

Robinson, Adam B.; Stogsdill, Jeffrey A.; Lewis, Joshua B.; Wood, Tyler T.; Reynolds, Paul R.

2012-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and airspace remodeling, leading to airflow limitation that is not completely reversible. Smoking is the leading risk factor for compromised lung function stemming from COPD pathogenesis. First- and second-hand cigarette smoke contain thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic lung inflammation and destructive alveolar remodeling. Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors primarily expressed by diverse lung cells. RAGE expression increases following cigarette smoke exposure and expression is elevated in the lungs of patients with COPD. RAGE is responsible in part for inducing pro-inflammatory signaling pathways that culminate in expression and secretion of several cytokines, chemokines, enzymes, and other mediators. In the current review, new transgenic mouse models that conditionally over-express RAGE in pulmonary epithelium are discussed. When RAGE is over-expressed throughout embryogenesis, apoptosis in the peripheral lung causes severe lung hypoplasia. Interestingly, apoptosis in RAGE transgenic mice occurs via conserved apoptotic pathways also known to function in advanced stages of COPD. RAGE over-expression in the adult lung models features of COPD including pronounced inflammation and loss of parenchymal tissue. Understanding the biological contributions of RAGE during cigarette smoke-induced inflammation may provide critically important insight into the pathology of COPD. PMID:22934052

Pulmonary Hypertension in Parenchymal Lung Disease

PubMed Central

Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E.

2012-01-01

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases. PMID:23094153

Prevalence of airflow obstruction and reduced forced vital capacity in an Aboriginal Australian population: The cross-sectional BOLD study.

PubMed

Cooksley, Nathania A J B; Atkinson, David; Marks, Guy B; Toelle, Brett G; Reeve, David; Johns, David P; Abramson, Michael J; Burton, Deborah L; James, Alan L; Wood-Baker, Richard; Walters, E Haydn; Buist, A Sonia; Maguire, Graeme P

2015-07-01

Mortality and hospital separation data suggest a higher burden of chronic obstructive pulmonary disease (COPD) in indigenous than non-indigenous subpopulations of high-income countries. This study sought to accurately measure the true prevalence of post-bronchodilator airflow obstruction and forced vital capacity reduction in representative samples of Indigenous and non-Indigenous Australians. This study applies cross-sectional population-based survey of Aboriginal and non-Indigenous residents of the Kimberley region of Western Australia aged 40 years or older, following the international Burden Of Lung Disease (BOLD) protocol. Quality-controlled spirometry was conducted before and after bronchodilator. COPD was defined as Global initiative for chronic Obstructive Lung Disease (GOLD) Stage 2 and above (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) ratio <0.7 and FEV1  < 80% predicted). Complete data were available for 704 participants. The prevalence of COPD, adjusted for age, gender and body weight in Aboriginal participants (7.2%, 95% confidence interval (CI) 3.9 to 10.4) was similar to that seen in non-Indigenous Kimberley participants (8.2%, 95% CI 5.7 to 10.7) and non-Indigenous residents of the remainder of Australia (7.1%, 95% CI 6.1 to 8.0). The prevalence of low FVC (<80% predicted) was substantially higher in Aboriginal compared with non-Indigenous participants (74.0%, 95% CI 69.1 to 78.8, vs 9.7%, 95% CI 7.1 to 12.4). Low FVC, rather than airflow obstruction, characterizes the impact of chronic lung disease previously attributed to COPD in this population subject to significant social and economic disadvantage. Environmental risk factors other than smoking as well as developmental factors must be considered. These findings require further investigation and have implications for future prevention of chronic lung disease in similar populations. © 2015 Asian Pacific Society of Respirology.

Club Cell Protein 16 (CC16) Augmentation: A Potential Disease-modifying Approach for Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Laucho-Contreras, Maria E; Polverino, Francesca; Tesfaigzi, Yohannes; Pilon, Aprile; Celli, Bartolome R; Owen, Caroline A

2016-07-01

Club cell protein 16 (CC16) is the most abundant protein in bronchoalveolar lavage fluid. CC16 has anti-inflammatory properties in smoke-exposed lungs, and chronic obstructive pulmonary disease (COPD) is associated with CC16 deficiency. Herein, we explored whether CC16 is a therapeutic target for COPD. We reviewed the literature on the factors that regulate airway CC16 expression, its biologic functions and its protective activities in smoke-exposed lungs using PUBMED searches. We generated hypotheses on the mechanisms by which CC16 limits COPD development, and discuss its potential as a new therapeutic approach for COPD. CC16 plasma and lung levels are reduced in smokers without airflow obstruction and COPD patients. In COPD patients, airway CC16 expression is inversely correlated with severity of airflow obstruction. CC16 deficiency increases smoke-induced lung pathologies in mice by its effects on epithelial cells, leukocytes, and fibroblasts. Experimental augmentation of CC16 levels using recombinant CC16 in cell culture systems, plasmid and adenoviral-mediated over-expression of CC16 in epithelial cells or smoke-exposed murine airways reduces inflammation and cellular injury. Additional studies are necessary to assess the efficacy of therapies aimed at restoring airway CC16 levels as a new disease-modifying therapy for COPD patients.

Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review.

PubMed

Aziz, Fahad; Penupolu, Sudheer; Xu, Xin; He, Jianxing

2010-06-01

Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Among the different complications, re-implantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.

Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review

PubMed Central

Aziz, Fahad; Penupolu, Sudheer; Xu, Xin; He, Jianxing

2010-01-01

Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Among the different complications, re-implantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict. PMID:22263028

[Rehabilitation of chronic obstructive pulmonary diseases at the lung hospital (author's transl)].

PubMed

Meister, W

1979-12-01

The modern lung hospital offers favorable conditions for the rehabilitation of patients suffering from chronic obstructive pulmonary diseases. In the years from 1972 to 1976 2398 patients suffering from chronic bronchitis, bronchial asthma and pulmonary emphysema were subjected to a rehabilitation process at the central hospital for heart and lung diseases Bad Berka. A long-term therapy plan based on a most accurate investigation possible of all the factors which trigger off the complaint in each case was used as baseline. An account is given of the resulting diagnostic and therapeutic program carried out. In the case of chronic obstructive pulmonary diseases it is particularly difficult to assess the effectiveness of rehabilitation measures. One aspect dealt with is the restoration of working capacity. 56.7% of the men and 56.8% of the women were capable of working when they were dismissed. 31.6% of male and 26.4% of female patients were invalids, 11.7% and 16.8% respectively were old age pensioners. Rehabilitation success depended on variables such as age, degree of cardio-pulmonary limitation in performance, as well as on certain concomitant diseases and the patient's cooperation. A decisive factor in some cases was also whether suitable employment could be found for these patients whose age ranges between 40 and 60.

Determining the diagnostic value of endogenous carbon monoxide in chronic obstructive pulmonary disease exacerbations.

PubMed

Dogan, Nurettin Özgür; Corbacioglu, Seref Kerem; Bildik, Fikret; Kilicaslan, Isa; Günaydin, Gül Pamukcu; Cevik, Yunsur; Ülker, Volkan; Hakoglu, Onur; Gökcen, Emre

2014-09-01

To determine whether endogenous carbon monoxide levels in exacerbations of Chronic Obstructive Pulmonary Disease patients were higher compared to healthy individuals and to investigate alteration of carbon monoxide levels across the three different severity stages of Global Initiative for Chronic Obstructive Lung Disease criteria related to Chronic Obstructive Pulmonary Disease exacerbations. The prospective study was conducted from January to March 2011 at two medical institutions in Ankara, Turkey, and comprised patients of acute Chronic Obstructive Pulmonary Disease exacerbations. The severity of the exacerbations was based on the Global Initiative for Chronic Obstructive Lung Disease criteria. Patients with active tobacco smoking, suspicious carbon monoxide poisoning and uncertain diagnosis were excluded. healthy control subjects who did not have any comorbid diseases and smoking habitus were also enrolled to compare the differences between carboxyhaemoglobin levels A two-tailed Mann-Whitney U test with Bonferroni correction was done following a Kruskal-Wallis test for statistical purposes. There were 90 patients and 81 controls in the study. Carboxyhaemoglobin levels were higher in the patients than the controls (p < 0.001). As for the three severity stages, Group 1 had a median carboxyhaemoglobin of 1.6 (0.95- 2.00). The corresponding levels in Group 2 (1.8 [1.38-2.20]) and Group 3 (1.9 [1.5-3.0]) were higher than the controls (p < 0.001 and p < 0.005 respectively). No statistically significant difference between Group 1 and the controls (1.30 [1.10-1.55]) was observed (p < 0.434). Carboxyhaemoglobin levels were significantly higher in exacerbations compared with the normal population. Also, in more serious exacerbations, carboxyhaemoglobin levels were significantly increased compared with healthy individuals and mild exacerbations.

Bronchopulmonary levage to remove pulmonary casts and plugs.

PubMed

Passy, V; Ermshar, C

1976-04-01

Therapy for such obstructive pulmonary lung diseases as alveolar proteinosis, pneumonia, asthma, bronchiectasis, and cystic fibrosis, ranges from medical therapy to inhalation therapy to direct bronchoscopy and irrigation. The basic pathophysiologic feature is the retention of mucous secretions and foreign material within the lungs and therapy directed to removal of these secretions. Bronchopulmonary lavage recently has been suggested as an effective tool toward resolution of these illnesses. The otolaryngologist, who is adept in endoscopy, is asked to perform bronchoscopic procedures with washings to aid in the alleviation of these obstructive pulmonary diseases. This paper deals with the effectiveness of massive bronchopulmonary lavage in the elimination of severe chronic obstructive pulmonary lung diseases.

Non-invasive assessment of respiratory muscle function and its relationship to exercise tolerance in patients with chronic obstructive pulmonary disease.

PubMed

Chlumský, J; Filipova, P; Terl, M

2006-01-01

Most patients with chronic obstructive pulmonary disease (COPD) have impaired respiratory muscle function. Maximal oesophageal pressure correlates closely with exercise tolerance and seems to predict the distance walked during the 6-min walk test. This study assessed the non-invasive parameters of respiratory muscle function in 41 patients with COPD to investigate their relationship to pulmonary function tests and exercise tolerance. The COPD patients, who demonstrated the full range of airway obstruction severity, had a mean forced expiratory volume in 1 s of 42.5% predicted (range, 20 - 79% predicted). Both the maximal inspiratory muscle strength and non-invasive tension-time index were significantly correlated with the degree of lung hyperinflation, as expressed by the ratio of residual volume to total lung capacity, and the distance walked in 6 min. We conclude that respiratory muscle function was influenced mainly by lung hyperinflation and that it had an important effect on exercise tolerance in COPD patients.

Detection and follow-up of chronic obstructive pulmonary disease (COPD) and risk factors in the Southern Cone of Latin America: the pulmonary risk in South America (PRISA) study.

PubMed

Rubinstein, Adolfo L; Irazola, Vilma E; Bazzano, Lydia A; Sobrino, Edgardo; Calandrelli, Matías; Lanas, Fernando; Lee, Alison G; Manfredi, Jose A; Olivera, Héctor; Ponzo, Jacqueline; Seron, Pamela; He, Jiang

2011-06-01

The World Health Organization has estimated that by 2030, chronic obstructive pulmonary disease will be the third leading cause of death worldwide. Most knowledge of chronic obstructive pulmonary disease is based on studies performed in Europe or North America and little is known about the prevalence, patient characteristics and change in lung function over time in patients in developing countries, such as those of Latin America. This lack of knowledge is in sharp contrast to the high levels of tobacco consumption and exposure to biomass fuels exhibited in Latin America, both major risk factors for the development of chronic obstructive pulmonary disease. Studies have also demonstrated that most Latin American physicians frequently do not follow international chronic obstructive pulmonary disease diagnostic and treatment guidelines. The PRISA Study will expand the current knowledge regarding chronic obstructive pulmonary disease and risk factors in Argentina, Chile and Uruguay to inform policy makers and health professionals on the best policies and practices to address this condition. PRISA is an observational, prospective cohort study with at least four years of follow-up. In the first year, PRISA has employed a randomized three-staged stratified cluster sampling strategy to identify 6,000 subjects from Marcos Paz and Bariloche, Argentina, Temuco, Chile, and Canelones, Uruguay. Information, such as comorbidities, socioeconomic status and tobacco and biomass exposure, will be collected and spirometry, anthropometric measurements, blood sampling and electrocardiogram will be performed. In year four, subjects will have repeat measurements taken. There is no longitudinal data on chronic obstructive pulmonary disease incidence and risk factors in the southern cone of Latin America, therefore this population-based prospective cohort study will fill knowledge gaps in the prevalence and incidence of chronic obstructive pulmonary disease, patient characteristics and changes in lung function over time as well as quality of life and health care resource utilization. Information gathered during the PRISA Study will inform public health interventions and prevention practices to reduce risk of COPD in the region.

Personality traits, level of anxiety and styles of coping with stressin people with asthma and chronic obstructive pulmonary disease - a comparative analysis.

PubMed

Tabała, Klaudia; Wrzesińska, Magdalena; Stecz, Patryk; Kocur, Józef

2016-12-23

Chronic obstructive pulmonary disease (COPD) and asthma are a challenge to public health, with the sufferers experiencing a range of psychological factors affecting their health and behavior. The aim of the present study was to determine the level of anxiety, personality traits and stress-coping ability of patients with obstructive lung disease and comparison with a group of healthy controls. The research was conducted on a group of 150 people with obstructive lung diseases (asthma and COPD) and healthy controls (mean age = 56.0 ± 16.00). Four surveys were used: a sociodemographic survey, NEO-FFI Personality Inventory, State-Trait Anxiety Inventory (STAI), and Brief Cope Inventory. Logistic regression was used to identify the investigated variables which best differentiated the healthy and sick individuals. Patients with asthma or COPD demonstrated a significantly lower level of conscientiousness, openness to experience, active coping and planning, as well as higher levels of neuroticism and a greater tendency to behavioral disengagement. Logistic regression found trait-anxiety, openness to experience, positive reframing, acceptance, humor and behavioral disengagement to be best at distinguishing people with lung diseases from healthy individuals. The results indicate the need for intervention in the psychological functioning of people with obstructive diseases.

COPD

MedlinePlus

COPD (chronic obstructive pulmonary disease) makes it hard for you to breathe. The two main types are chronic bronchitis and emphysema. The main cause of COPD is long-term exposure to substances that irritate and damage the lungs. This is ...

Relationship between diminution of small pulmonary vessels and emphysema in chronic obstructive pulmonary disease.

PubMed

Mashimo, Shuko; Chubachi, Shotaro; Tsutsumi, Akihiro; Kameyama, Naofumi; Sasaki, Mamoru; Jinzaki, Masahiro; Nakamura, Hidetoshi; Asano, Koichiro; Reilly, John J; Betsuyaku, Tomoko

To investigate the relationship between small pulmonary vessels and extent of emphysema on CT in individual lungs with chronic obstructive pulmonary disease (COPD). Forty-nine patients were included. The percentage of cross-sectional area of vessels <5mm 2 (%CSA <5) and extent of emphysema were assessed. Less than half of the COPD patients demonstrated an inverse correlation between %CSA <5 and percentage of low attenuation area (LAA%). In the remaining patients, %CSA <5 was homogeneously distributed. Not all patients with COPD demonstrated an inverse correlation of the distributions between %CSA <5 and LAA% in individual lungs. Copyright © 2017 Elsevier Inc. All rights reserved.

Voluntary pulmonary function screening identifies high rates of undiagnosed asymptomatic chronic obstructive pulmonary disease.

PubMed

Wang, Shengyu; Gong, Wei; Tian, Yao

2016-05-01

Chronic obstructive pulmonary disease (COPD) is projected to be the third leading cause of death by 2020. Early detection and screening may alter the course and prognosis associated with lung disease. We investigated the effectiveness of a voluntary public lung function screening program and factors that had a predictive value for asymptomatic COPD in Xi'an, China. Pulmonary function testing (PFT) was conducted on volunteers recruited from four community centers in Xi'an, China, between July and August 2012. Participants underwent three forced vital capacity maneuvers. The maneuver with the best forced expiratory volume in first second was retained. Participants filled out a medical history and environmental exposure survey before undergoing the PFT. Patients who self-reported lung disease on the health survey were excluded from the analysis. Logistical regression was used to determine associations with airway obstruction. A total of 803 volunteers participated in this study, and 33 subjects were excluded as the participants did not meet the requirements of PFT. Of the 770 volunteers, 44 participants had been diagnosed with chronic respiratory diseases previously, and 144 participants (18.7%) met COPD criteria. Four hundred forty-four participants did not self-report any respiratory symptoms, and the remaining 282 participants self-reported respiratory symptoms. Of the asymptomatic participants, 98 volunteers had PFT results that were consistent with COPD and 68.1% of asymptomatic participants were undiagnosed. A greater percentage of women than men had moderate or severe airway obstruction (p = 0.004).Only smoking status (odds ratio = 2.64, 95% confidence interval 1.20-6.04) was associated with asymptomatic COPD. Voluntary public lung function screening programs in China are likely to identify a large number of undiagnosed, asymptomatic COPD. Smoking status is associated with airway obstruction and a greater percentage of women than men had moderate or severe airway obstruction. © The Author(s) 2016.

Infection-induced airway fibrosis in two rat strains with differential susceptibility.

PubMed Central

McIntosh, J C; Simecka, J W; Ross, S E; Davis, J K; Miller, E J; Cassell, G H

1992-01-01

Chronic infections play a significant role in the morbidity and mortality of patients with chronic airflow limitation. By stimulating airway inflammation, persistent infection has the potential to cause airway fibrosis. However, in patient this condition is most typically found in lungs damaged by other factors, such as smoking, abnormal secretions, or barotrauma. We report the characterization of Mycoplasma pulmonis infection-induced lung fibrosis in two immunocompetent rat strains with no preexisting lung disease. The fibrosis was predominantly in the airways, as demonstrated by the findings for infected animals of increased airway inflammation, airway fibrosis, and airway wall thickness, which correlated with the collagen content of the lungs. Also, the physiological alterations were the opposite of those found in interstitial fibrosis, with a positive correlation between lung compliance and collagen content. The airway fibrosis was noted earlier and to a greater extent in Lewis rats than in Fisher rats, and this result apparently was related to regulation of the inflammatory response. Airway wall thickness, airway inflammation, and airway fibrosis are commonly reported in tissue specimens from patients with chronic airway diseases and have been shown to correlate with airflow limitation in patients with chronic obstructive pulmonary disease. Thus, this model may be useful in furthering our understanding of the role of chronic infection and airway inflammation in airflow obstruction. Images PMID:1612760

Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

PubMed Central

2012-01-01

Chronic obstructive pulmonary disease, metabolic syndrome and diabetes mellitus are common and underdiagnosed medical conditions. It was predicted that chronic obstructive pulmonary disease will be the third leading cause of death worldwide by 2020. The healthcare burden of this disease is even greater if we consider the significant impact of chronic obstructive pulmonary disease on the cardiovascular morbidity and mortality. Chronic obstructive pulmonary disease may be considered as a novel risk factor for new onset type 2 diabetes mellitus via multiple pathophysiological alterations such as: inflammation and oxidative stress, insulin resistance, weight gain and alterations in metabolism of adipokines. On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations and worsened COPD outcomes. On the top of that, coexistent OSA may increase the risk for type 2 DM in some individuals. The current scientific data necessitate a greater outlook on chronic obstructive pulmonary disease and chronic obstructive pulmonary disease may be viewed as a risk factor for the new onset type 2 diabetes mellitus. Conversely, both types of diabetes mellitus should be viewed as strong contributing factors for the development of obstructive lung disease. Such approach can potentially improve the outcomes and medical control for both conditions, and, thus, decrease the healthcare burden of these major medical problems. PMID:23101436

Cognitive function in chronic obstructive pulmonary disease: relationship to global initiative for chronic obstructive lung disease 2011 categories.

PubMed

Tulek, Baykal; Atalay, Nart Bedin; Yildirim, Gulfem; Kanat, Fikret; Süerdem, Mecit

2014-08-01

Recently, comorbidities such as impaired cognitive function have been attracting more focus when considering the management of chronic obstructive pulmonary disease (COPD). Here we investigated the relationship between cognitive function and the categories given in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011. Specifically, after controlling for non-COPD covariates, we assessed the clinical features that may be predictive of cognitive impairment in patients with COPD. We recruited 119 stable patients with mild to very severe COPD. We administered a broad array of standardized neuropsychological tests that assessed cognitive functions in the domains of attention, memory, psychomotor coordination and language. Cognitive scores were significantly different between patients falling within GOLD 2011 categories. Scores were lower in patients with high future risk compared with low future risk. In parallel, there were significant differences in cognitive function between COPD patient subgroups when patients were grouped according to the forced expiratory volume in 1 s, exacerbation history and C-reactive protein levels. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. The number of exacerbation events in a year may be used as a predictor of cognitive impairment in patients with COPD. © 2014 Asian Pacific Society of Respirology.

Clinical utility of computed tomographic lung volumes in patients with chronic obstructive pulmonary disease.

PubMed

Lee, Jae Seung; Lee, Sang-Min; Seo, Joon Beom; Lee, Sei Won; Huh, Jin Won; Oh, Yeon-Mok; Lee, Sang-Do

2014-01-01

Published data concerning the utility of computed tomography (CT)-based lung volumes are limited to correlation with lung function. The aim of this study was to evaluate the clinical utility of the CT expiratory-to-inspiratory lung volume ratio (CT Vratio) by assessing the relationship with clinically relevant outcomes. A total of 75 stable chronic obstructive pulmonary disease (COPD) patients having pulmonary function testing and volumetric CT at full inspiration and expiration were retrospectively evaluated. Inspiratory and expiratory CT lung volumes were measured using in-house software. Correlation of the CT Vratio with patient-centered outcomes, including the modified Medical Research Council (MMRC) dyspnea score, the 6-min walk distance (6MWD), the St. George's Respiratory Questionnaire (SGRQ) score, and multidimensional COPD severity indices, such as the BMI, airflow obstruction, dyspnea, and exercise capacity index (BODE) and age, dyspnea, and airflow obstruction (ADO), were analyzed. The CT Vratio correlated significantly with BMI (r = -0.528, p < 0.001). The CT Vratio was also significantly associated with MMRC dyspnea (r = 0.387, p = 0.001), 6MWD (r = -0.459, p < 0.001), and SGRQ (r = 0.369, p = 0.001) scores. Finally, the CT Vratio had significant correlations with the BODE and ADO multidimensional COPD severity indices (r = 0.605, p < 0.001; r = 0.411, p < 0.001). The CT Vratio had significant correlations with patient-centered outcomes and multidimensional COPD severity indices. © 2013 S. Karger AG, Basel.

Relationship between Dysphagia and Exacerbations in Chronic Obstructive Pulmonary Disease: A Literature Review

PubMed Central

Steidl, Eduardo; Ribeiro, Carla Simone; Gonçalves, Bruna Franciele; Fernandes, Natália; Antunes, Vívian; Mancopes, Renata

2014-01-01

Introduction The literature presents studies correlating chronic obstructive pulmonary disease to dysphagia and suggesting that the aspiration laryngeal phenomenon related to changes in the pharyngeal phase contributes significantly to the exacerbation of symptoms of lung disease. Objectives This study aimed to conduct a literature review to identify the relation between dysphagia and exacerbations of chronic obstructive pulmonary disease. Data Synthesis We found 21 studies and included 19 in this review. The few studies that related to the subject agreed that the presence of dysphagia, due to lack of coordination between swallowing and breathing, may be one of the triggering factors of chronic obstructive pulmonary disease exacerbation. Conclusions The review noted that there is a relationship between dysphagia and exacerbations of chronic obstructive pulmonary disease, identified by studies demonstrating that the difficulties associated with swallowing may lead to exacerbation of the disease. There was difficulty in comparing studies by their methodological differences. More research is needed to clarify the relationship between dysphagia and exacerbations of chronic obstructive pulmonary disease, making it possible to develop multiprofessional treatment strategies for these patients, catered to specific needs due to the systemic manifestations of the disease. PMID:25992155

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

PubMed

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

2015-01-01

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

Guanylyl cyclase activation reverses resistive breathing-induced lung injury and inflammation.

PubMed

Glynos, Constantinos; Toumpanakis, Dimitris; Loverdos, Konstantinos; Karavana, Vassiliki; Zhou, Zongmin; Magkou, Christina; Dettoraki, Maria; Perlikos, Fotis; Pavlidou, Athanasia; Kotsikoris, Vasilis; Topouzis, Stavros; Theocharis, Stamatios E; Brouckaert, Peter; Giannis, Athanassios; Papapetropoulos, Andreas; Vassilakopoulos, Theodoros

2015-06-01

Inspiratory resistive breathing (RB), encountered in obstructive lung diseases, induces lung injury. The soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway is down-regulated in chronic and acute animal models of RB, such as asthma, chronic obstructive pulmonary disease, and in endotoxin-induced acute lung injury. Our objectives were to: (1) characterize the effects of increased concurrent inspiratory and expiratory resistance in mice via tracheal banding; and (2) investigate the contribution of the sGC/cGMP pathway in RB-induced lung injury. Anesthetized C57BL/6 mice underwent RB achieved by restricting tracheal surface area to 50% (tracheal banding). RB for 24 hours resulted in increased bronchoalveolar lavage fluid cellularity and protein content, marked leukocyte infiltration in the lungs, and perturbed respiratory mechanics (increased tissue resistance and elasticity, shifted static pressure-volume curve right and downwards, decreased static compliance), consistent with the presence of acute lung injury. RB down-regulated sGC expression in the lung. All manifestations of lung injury caused by RB were exacerbated by the administration of the sGC inhibitor, 1H-[1,2,4]oxodiazolo[4,3-]quinoxalin-l-one, or when RB was performed using sGCα1 knockout mice. Conversely, restoration of sGC signaling by prior administration of the sGC activator BAY 58-2667 (Bayer, Leverkusen, Germany) prevented RB-induced lung injury. Strikingly, direct pharmacological activation of sGC with BAY 58-2667 24 hours after RB reversed, within 6 hours, the established lung injury. These findings raise the possibility that pharmacological targeting of the sGC-cGMP axis could be used to ameliorate lung dysfunction in obstructive lung diseases.

Chronic obstructive pulmonary disease mortality and prevalence: the associations with smoking and poverty--a BOLD analysis.

PubMed

Burney, Peter; Jithoo, Anamika; Kato, Bernet; Janson, Christer; Mannino, David; Nizankowska-Mogilnicka, Ewa; Studnicka, Michael; Tan, Wan; Bateman, Eric; Koçabas, Ali; Vollmer, William M; Gislason, Thorarrin; Marks, Guy; Koul, Parvaiz A; Harrabi, Imed; Gnatiuc, Louisa; Buist, Sonia

2014-05-01

Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI). National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked. National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000. Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high 'COPD' mortality in poor countries.

Occupation, smoking, and chronic obstructive respiratory disorders: a cross sectional study in an industrial area of Catalonia, Spain

PubMed Central

Jaén, Ángeles; Zock, Jan Paul; Kogevinas, Manolis; Ferrer, Antonio; Marín, Albert

2006-01-01

Background Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction. We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain. Methods We interviewed 576 subjects of both sexes aged 20–70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire. Forced spirometry was performed by 497 subjects according to ATS normative. Results Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women). Textile industry was the most frequently reported job in relation to these exposures (39%). Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3). Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits. Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV1 -80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV1/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed. Conclusion Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry. Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking. PMID:16476167

Club Cell Protein 16 (CC16) Augmentation: A Potential Disease-modifying Approach for Chronic Obstructive Pulmonary Disease (COPD)

PubMed Central

Laucho-Contreras, Maria E.; Polverino, Francesca; Tesfaigzi, Yohannes; Pilon, Aprile; Celli, Bartolome R.; Owen, Caroline A.

2016-01-01

Introduction Club cell protein 16 (CC16) is the most abundant protein in bronchoalveolar lavage fluid. CC16 has anti-inflammatory properties in smoke-exposed lungs, and chronic obstructive pulmonary disease (COPD) is associated with CC16 deficiency. Herein, we explored whether CC16 is a therapeutic target for COPD. Areas Covered We reviewed the literature on the factors that regulate airway CC16 expression, its biologic functions and its protective activities in smoke-exposed lungs using PUBMED searches. We generated hypotheses on the mechanisms by which CC16 limits COPD development, and discuss its potential as a new therapeutic approach for COPD. Expert Opinion CC16 plasma and lung levels are reduced in smokers without airflow obstruction and COPD patients. In COPD patients, airway CC16 expression is inversely correlated with severity of airflow obstruction. CC16 deficiency increases smoke-induced lung pathologies in mice by its effects on epithelial cells, leukocytes, and fibroblasts. Experimental augmentation of CC16 levels using recombinant CC16 in cell culture systems, plasmid and adenoviral-mediated over-expression of CC16 in epithelial cells or smoke-exposed murine airways reduces inflammation and cellular injury. Additional studies are necessary to assess the efficacy of therapies aimed at restoring airway CC16 levels as a new disease-modifying therapy for COPD patients. PMID:26781659

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease.

PubMed

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

2018-05-11

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

Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease

PubMed Central

Richens, Joanna L; Urbanowicz, Richard A; Lunt, Elizabeth AM; Metcalf, Rebecca; Corne, Jonathan; Fairclough, Lucy; O'Shea, Paul

2009-01-01

Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease state, characterised by progressive airflow limitation that is not fully reversible. Although COPD is primarily a disease of the lungs there is now an appreciation that many of the manifestations of disease are outside the lung, leading to the notion that COPD is a systemic disease. Currently, diagnosis of COPD relies on largely descriptive measures to enable classification, such as symptoms and lung function. Here the limitations of existing diagnostic strategies of COPD are discussed and systems biology approaches to diagnosis that build upon current molecular knowledge of the disease are described. These approaches rely on new 'label-free' sensing technologies, such as high-throughput surface plasmon resonance (SPR), that we also describe. PMID:19386108

United in Prevention–Electrocardiographic Screening for Chronic Obstructive Pulmonary Disease

PubMed Central

Mazic, Sanja; Stajic, Zoran; Djelic, Marina; Zlatkovic-Svenda, Mirjana; Putnikovic, Biljana

2013-01-01

CONFLICT OF INTEREST: NONE DECLARED Introduction P-wave abnormalities on the resting electrocardiogram have been associated with cardiovascular or pulmonary disease. So far, “Gothic” P wave and verticalization of the frontal plane axis is related to lung disease, particularly obstructive lung disease. Aim We tested if inverted P wave in AVl as a lone criteria of P wave axis >70° could be screening tool for emphysema. Material and method 1095 routine electrocardiograms (ECGs) were reviewed which yielded 478 (82,1%) ECGs with vertical P-axis in sinus rhythm. Charts were reviewed for the diagnosis of COPD and emphysema based on medical history and pulmonary function tests. Conclusion Electrocardiogram is very effective screening tool not only in cardiovascular field but in chronic obstructive pulmonary disease. The verticality of the P axis is usually immediately apparent, making electrocardiogram rapid screening test for emphysema. PMID:24058253

Hypoxemia, hypercapnia, and breathing pattern in patients with chronic obstructive pulmonary disease.

PubMed

Parot, S; Miara, B; Milic-Emili, J; Gautier, H

1982-11-01

The results of lung function tests (total and functional residual capacities, residual volume/total lung capacity ratio, forced expiratory volume in one second) breathing patterns and arterial PO2 and PCO2 were studied in 651 ambulatory male patients with chronic obstructive pulmonary disease, functionally and clinically stable. Function tests were only loosely correlated with gas tensions: abnormalities in mechanics and in gas exchange are not necessarily related. In patients matched for the degree of obstruction, the breathing pattern depended upon both PaO2 and PaCO2. Isolated hypoxemia was accompanied by increased respiratory frequency without any variation in tidal volume: this suggests that the chemoreceptive systems still responded to changes in PaO2. Isolated hypercapnia was accompanied by a decrease in tidal volume and an increase in respiratory frequency. Consequently, the dead space/tidal volume ratio increased, leading to a drop in alveolar ventilation and to CO2 retention.

Breathtaking: Managing a COPD Diagnosis | NIH MedlinePlus the Magazine

MedlinePlus

... Managing a COPD Diagnosis Photo: iStock Chronic obstructive pulmonary disease (COPD) is a serious lung disease that makes it hard to breathe. It’s also known as emphysema or chronic bronchitis. In people who have COPD, ...

Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases.

PubMed

Iman, Maryam; Rezaei, Ramazan; Azimzadeh Jamalkandi, Sadegh; Shariati, Parvin; Kheradmand, Farrah; Salimian, Jafar

2017-12-01

Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4 + T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results.

PubMed

Amaral, André F S; Coton, Sonia; Kato, Bernet; Tan, Wan C; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D; Buist, Sonia; Burney, Peter G J

2015-10-01

In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19).A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. Copyright ©ERS 2015.

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results

PubMed Central

Amaral, André F. S.; Coton, Sonia; Kato, Bernet; Tan, Wan C.; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D.; Buist, Sonia; Burney, Peter G. J.

2015-01-01

Background In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. Objective To assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults. Methods The study was performed in adults, aged 40 and above, who took part in the multicentre cross-sectional, general population-based, Burden of Obstructive Lung Disease study, had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high and low/middle income countries, according to gross national income. Results A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio = 2.51, 95% confidence interval 1.83-3.42) and spirometric restriction (adjusted odds ratio = 2.13, 95% confidence interval 1.42-3.19). Conclusion A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. PMID:26113680

Worldwide Survey of Alcohol and Nonmedical Drug Use Among Military Personnel: 1985

DTIC Science & Technology

1986-06-01

medical /physical, mental health/emotional, family/ friends, legal, job/education, and financial problems as well as dependence, addiction, and...from lung cancer , 22,000 deaths from other cancers , 225,000 deaths from cardiovascular disease, and 19,000 deaths from chronic pulmonary disease...risk of death from lung cancer among smokers is 10 times greater than among nonsmokers, a fatal heart attack two times greater, and chronic obstructive

Oxidative Lung Injury in Virus-Induced Wheezing

DTIC Science & Technology

2011-05-01

chronic lung inflammatory diseases, such as asthma, cystic fibrosis , and chronic obstructive pulmonary disease (COPD) (5– 7). We have previously shown that...Vervaart P, Grimwood K, Phelan P. Pulmonary oxidative stress response in young children with cystic fibrosis . Thorax 1997; 52:557–560. 8. Casola A, Burger N...Emergency Department, the pediatrics outpatient clinics, or inpatient areas of Children’s Hospital. These subjects were assigned a diagnosis of upper

Nutritional status and patient characteristics for hospitalised older patients with chronic obstructive pulmonary disease.

PubMed

Odencrants, Sigrid; Ehnfors, Margareta; Ehrenberg, Anna

2008-07-01

The aim of the study was to describe and compare nutritional status and social and medical characteristics among older patients with chronic obstructive pulmonary disease admitted to an acute care hospital ward for respiratory medicine. Chronic obstructive pulmonary disease is a condition associated with risk of developing malnutrition. A body mass index <20 is predictive of hospitalisation for acute exacerbations of chronic obstructive pulmonary disease. Knowledge about patient characteristics is crucial for the identification of malnourished patients and the development of nursing care for these patients. Quantitative descriptive study. Thirty-three hospitalised women and 17 men with a mean age of 75.7 years (SD 6.9) were consecutively included. A very severe case of chronic obstructive pulmonary disease was indicated in 28 out of 39 patients who underwent a lung function test. Data were collected with measurement of nutritional status using Mini Nutritional Assessment, anthropometry and lung function. Nearly half of the patients (48%) were identified as malnourished, an equal part as at risk for malnutrition and two patients as well nourished. The mean Mini Nutritional Assessment score of 17.2 (SD 3.99) for all patients was near the Mini Nutritional Assessment cut-off score (i.e. 17) for malnutrition. Patients identified as malnourished had a mean body mass index of 18.9 and those at risk for malnutrition had a mean of 23.4. It was more common for those identified as malnourished to live singly, to not live in own property and to be dependent on daily community service. Seven patients identified as malnourished died during the data collection period. This study provides important knowledge about further risks of impaired nutritional status among older patients with chronic obstructive pulmonary disease. This knowledge can provide registered nurses with the necessary knowledge to make them aware of certain patients needing particular kinds of attention.

Relationship of senescence of pulmonary system to chronic obstructive pulmonary disease in the advanced life.

PubMed

Donma, O; Donma, M M

2002-08-01

Chronic obstructive pulmonary disease (COPD) is a major worldwide health problem. There exists a relationship between COPD and increased oxidative stress, and oxidants may be involved in lung damage during the course of COPD. Polymorphonuclear (PMN) cell recruitment at lung level plays an important role in free radical overproduction, impact inflammatory processes and may alter oxidant-antioxidant balance. Biological aging is thought to be influenced by free radical generation, aging, and the diseases. All the components of the respiratory system are affected by aging. Nutrition, smoking habits and sleep-related disorders also affect the respiratory system. Whether these changes are due to aging or associated with aging is a matter of debate. Since alterations caused by aging and cigarette smoke in lungs of various species were informed to be partly simulated with age-related alterations in human lung, the effects of oxidative agents and antioxidative parameters on both COPD and aging were evaluated.

[Lung dysfunction in patients with mild chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2004-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Ravt, Riin, Rex, DLCO-SS, PaO2, and PaO2 were determined in 33 patients with mild chronic obstructive lung disease (FEV1 > 70% of the normal value). All the patients were found to have impaired bronchial patency; most (63.6%) patients had lung volume and capacity changes, almost half (45.5%) the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased MEF50, MEF15, and FEV1/VC%; altered lung volumes and capacities manifested chiefly by increased RV and decreased VC; pulmonary gas exchange dysfunction showed up primarily as lowered PaO2. The magnitude of the observed functional changes was generally slight. MEF50, MEF75, FEV1/VC%, and VC dropped to 59-20 and 79-70% of the normal value, respectively. RV increased up to 142-196% of the normal value; PaO2 reduced up to 79-60% mm Hg.

Clinical significance of laryngopharyngeal reflux in patients with chronic obstructive pulmonary disease.

PubMed

Jung, Young Ho; Lee, Doh Young; Kim, Dong Wook; Park, Sung Soo; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

2015-01-01

Although chronic obstructive pulmonary disease (COPD) is closely associated with gastroesophageal reflux disease (GERD), the clinical significance of laryngopharyngeal reflux (LPR) is not fully understood in COPD. Prospective cohorts were established among 118 patients with COPD from March 2013 to July 2014. Thirty-two age-matched and sex-matched normal controls, who had routine health check-ups during the study period, were included. Laryngopharyngeal reflux finding scores (RFS) and reflux symptom index (RSI) for LPR were subjected to association analysis with severity and acute exacerbation of COPD during the 1-year follow-up. The mean age of patients enrolled in the study was 69.2±8.8 years, with 93.2% being male. Positive RFS (>7) and RSI (>13) were observed in 51 (42.5%) and six patients (5.0%), respectively. RFS and RSI were significantly higher in patients with COPD than in normal, healthy patients (P<0.001). RFS was significantly correlated with residual volume/total lung capacity (%, P=0.048). Scores for diffuse laryngeal edema, erythema, and hyperemia were significantly higher in the high-risk group (Global Initiative for Chronic Obstructive Lung Disease classification C and D; P=0.025 and P=0.049, respectively), while RSI was significantly higher in the more symptomatic group (Global Initiative for Chronic Obstructive Lung Disease classification B and D; P=0.047). RSI and RFS were significant predictors for severe acute exacerbation of COPD (P=0.03 and P=0.047, respectively), while only RSI was associated with severity of dyspnea. Laryngeal examination and evaluation of laryngeal reflux symptom could be a surrogate clinical indicator related to severe acute exacerbation of COPD. Further studies of LPR in COPD patients should be considered.

Risks of on-pump coronary artery bypass grafting surgery in patients with chronic obstructive pulmonary disease due to sulfur mustard.

PubMed

Firoozabadi, Mehdi Dehghani; Sheikhi, Mohammad Ali; Rahmani, Hossein; Ebadi, Ahmad; Heidari, Amanollah; Gholizadeh, Behnam; Sharifi, Khosrow

2017-10-01

Sulfur mustard (SM) is a toxic chemical agent that belongs to a class of vesicant compounds. In the 1980s it was used by the Iraqi army against Iranian forces. Sulfur mustard severely irritates the skin, eyes and lungs. The highest side effects seen in patients affected by this gas are pulmonary complications including different types of lung diseases such as bronchiolitis. It has also led to a certain type of chronic obstructive pulmonary disease called mustard lung. Similar extra-pulmonary, molecular and hormonal effects can be observed in these patients and patients with chronic obstructive pulmonary disease. Here cardiovascular complications may be one of the most dangerous visible effects. And atherosclerosis is probable following the direct effects or consequential long-term effects of SM. The development of atherosclerosis in these patients is associated with an increased risk of cardiovascular and coronary artery disease. Coronary artery bypass grafting surgery is the treatment of coronary artery disease. Doing this surgery by bypass pump has its own morbidity and due to local and systemic inflammation changes in patients with SM pulmonary disorders it may have more side effects. Therefore, detailed knowledge of inflammatory diseases as well as the serum level or even the local lung fluid of the inflammatory factors in these patients before surgery are needed so that it would be possible to reduce the rate of morbidity and mortality by normalizing the inflammatory conditions of the patients before cardiac surgery.

Scaled experiments for improving diagnosis of pathological lower-airway obstruction

NASA Astrophysics Data System (ADS)

Liu, Chang; Kiger, Ken; Hariprasad, Daniel; Sul, Bora; Wallqvist, Anders; Reifman, Jaques

2017-11-01

Many lung diseases, such as asthma and chronic obstructive pulmonary disease, are characterized by obstructed airflow, particularly, in the lower airway branches in the lung. Existing diagnostic tools cannot detect some diseases due to a lack of instrumentation capable of resolving the flow in the lower airways. Recent developments in MRI techniques using hyperpolarized 3He now permit measurement of velocity profiles within the trachea. Motivated by these advances, we aim to provide a better understanding of the connection between lower-airway obstruction and velocity profiles within the trachea. Specifically, we asked whether the flow deficits created by lower-airway obstructions could be detected in the trachea to permit diagnosis of the pathology. To test this idea, we used refractive index-matched materials to construct a scaled, patient-specific, transparent lung model, and coupled it to 5 independently controlled piston pumps that could generate arbitrary flow histories (healthy or diseased) for the 5 different lung lobes. Results obtained by stereo PIV within various regions of the airway network will be presented documenting the system performance and examining the detectability of under-performing lobes within the tracheal flow profile. This work supported by the Henry M. Jackson Foundation under award #3270.

Total Airway Count on Computed Tomography and the Risk of Chronic Obstructive Pulmonary Disease Progression. Findings from a Population-based Study.

PubMed

Kirby, Miranda; Tanabe, Naoya; Tan, Wan C; Zhou, Guohai; Obeidat, Ma'en; Hague, Cameron J; Leipsic, Jonathon; Bourbeau, Jean; Sin, Don D; Hogg, James C; Coxson, Harvey O

2018-01-01

Studies of excised lungs show that significant airway attrition in the "quiet" zone occurs early in chronic obstructive pulmonary disease (COPD). To determine if the total number of airways quantified in vivo using computed tomography (CT) reflects early airway-related disease changes and is associated with lung function decline independent of emphysema in COPD. Participants in the multicenter, population-based, longitudinal CanCOLD (Canadian Chronic Obstructive Lung Disease) study underwent inspiratory/expiratory CT at visit 1; spirometry was performed at four visits over 6 years. Emphysema was quantified as the CT inspiratory low-attenuation areas below -950 Hounsfield units. CT total airway count (TAC) was measured as well as airway inner diameter and wall area using anatomically equivalent airways. Participants included never-smokers (n = 286), smokers with normal spirometry at risk for COPD (n = 298), Global Initiative for Chronic Obstructive Lung Disease (GOLD) I COPD (n = 361), and GOLD II COPD (n = 239). TAC was significantly reduced by 19% in both GOLD I and GOLD II compared with never-smokers (P < 0.0001) and by 17% in both GOLD I and GOLD II compared with at-risk participants (P < 0.0001) after adjusting for low-attenuation areas below -950 Hounsfield units. Further analysis revealed parent airways with missing daughter branches had reduced inner diameters (P < 0.0001) and thinner walls (P < 0.0001) compared with those without missing daughter branches. Among all CT measures, TAC had the greatest influence on FEV 1 (P < 0.0001), FEV 1 /FVC (P < 0.0001), and bronchodilator responsiveness (P < 0.0001). TAC was independently associated with lung function decline (FEV 1 , P = 0.02; FEV 1 /FVC, P = 0.01). TAC may reflect the airway-related disease changes that accumulate in the "quiet" zone in early/mild COPD, indicating that TAC acquired with commercially available software across various CT platforms may be a biomarker to predict accelerated COPD progression.

Chronic Obstructive Pulmonary Disease: From Injury to Genomic Stability.

PubMed

Sergio, Luiz Philippe da Silva; de Paoli, Flavia; Mencalha, Andre Luiz; da Fonseca, Adenilson de Souza

2017-08-01

Chronic obstructive pulmonary disease (COPD) is the fourth cause of death in the world and it is currently presenting a major global public health challenge, causing premature death from pathophysiological complications and rising economic and social burdens. COPD develops from a combination of factors following exposure to pollutants and cigarette smoke, presenting a combination of both emphysema and chronic obstructive bronchitis, which causes lung airflow limitations that are not fully reversible by bronchodilators. Oxidative stress plays a key role in the maintenance and amplification of inflammation in tissue injury, and also induces DNA damages. Once the DNA molecule is damaged, enzymatic mechanisms act in order to repair the DNA molecule. These mechanisms are specific to repair of oxidative damages, such as nitrogen base modifications, or larger DNA damages, such as double-strand breaks. In addition, there is an enzymatic mechanism for the control of telomere length. All these mechanisms contribute to cell viability and homeostasis. Thus, therapies based on modulation of DNA repair and genomic stability could be effective in improving repair and recovery of lung tissue in patients with COPD.

COPD management: role of symptom assessment in routine clinical practice

PubMed Central

van der Molen, Thys; Miravitlles, Marc; Kocks, Janwillem WH

2013-01-01

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life. Despite this, COPD treatment and its management are mainly based on lung function assessments. There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives. Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD. Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice. In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. PMID:24143085

The clinical use of regenerative therapy in COPD

PubMed Central

Lipsi, Roberto; Rogliani, Paola; Calzetta, Luigino; Segreti, Andrea; Cazzola, Mario

2014-01-01

Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation. PMID:25548520

Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease

PubMed Central

2014-01-01

The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and ’omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the “smoking gun” of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in chronic obstructive pulmonary disease.

PubMed

Bakerly, Nawar Diar; Woodcock, Ashley; New, John P; Gibson, J Martin; Wu, Wei; Leather, David; Vestbo, Jørgen

2015-09-04

New treatments need to be evaluated in real-world clinical practice to account for co-morbidities, adherence and polypharmacy. Patients with chronic obstructive pulmonary disease (COPD), ≥ 40 years old, with exacerbation in the previous 3 years are randomised 1:1 to once-daily fluticasone furoate 100 μg/vilanterol 25 μg in a novel dry-powder inhaler versus continuing their existing therapy. The primary endpoint is the mean annual rate of COPD exacerbations; an electronic medical record allows real-time collection and monitoring of endpoint and safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in COPD. Clinicaltrials.gov identifier NCT01551758.

[The effect of the inhalation of a single atrovent dose on pulmonary ventilation function and respiratory mechanics in patients with chronic obstructive bronchitis].

PubMed

Tetenev, F F; Cherniavskaia, G M

1989-01-01

A study was made of the action of inhalation of a single atrovent dose in 20 patients with chronic obstructive bronchitis. All the patients demonstrated a considerable abatement or disappearance of dyspnea, and a reduction of the number of dry rales. The vital capacity of the lungs, the volume of forced expiration, maximal pulmonary ventilation, MOCmax, MOC50, and MOC75 substantially increased. The respiratory work diminished on the average by 32.3% primarily due to the lessening of non-elastic lung resistance. The rise of pulmonary static extensibility and reduction of pulmonary elastic propulsion were recorded. In patients with and without clinical signs of bronchospasm, the action of atrovent was identical.

The Relationship of Bone Mineral Density in Men with Chronic Obstructive Pulmonary Disease Classified According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Combined Chronic Obstructive Pulmonary Disease (COPD) Assessment System.

PubMed

Sakurai-Iesato, Yoriko; Kawata, Naoko; Tada, Yuji; Iesato, Ken; Matsuura, Yukiko; Yahaba, Misuzu; Suzuki, Toshio; Ikari, Jun; Yanagawa, Noriyuki; Kasahara, Yasunori; West, James; Tatsumi, Koichiro

2017-01-01

Objective Osteoporosis, which is now recognized as a major comorbidity of chronic obstructive pulmonary disease (COPD), must be diagnosed by appropriate methods. The aims of this study were to clarify the relationships between bone mineral density (BMD) and COPD-related clinical variables and to explore the association of BMD with the updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification in men. Methods We enrolled 50 Japanese men with clinically stable COPD who underwent dual-energy X-ray absorptiometry (DEXA), pulmonary function testing, and computerized tomography (CT) and who had completed a questionnaire (COPD assessment test [CAT]). We determined the association between the T-score and other tested parameters and compared the BMD of patients in each GOLD category. Results Twenty-three of the 50 patients (46.0%) were diagnosed with osteopenia, and 7 (14.0%) were diagnosed with osteoporosis. The BMD findings were significantly correlated with the CAT score, forced expiratory volume in 1 second percentage predicted (FEV 1 % predicted), low attenuation volume percentage (LAV%), and percentage of cross-sectional area of small pulmonary vessels (%CSA) on CT images. Notably, the median T-score of the GOLD category D participants was significantly lower than that of the participants in each of the other categories (A [-0.98], B [-1.06], C [-1.05], and D [-2.19], p<0.05). Conclusion Reduced BMD was associated with airflow limitation, extent of radiographic findings, and a poor quality of life (QOL) in patients with COPD. The BMD of GOLD category D patients was the lowest of all of the patients evaluated, and category D patients may benefit from active intervention for osteoporosis.

The Relationship of Bone Mineral Density in Men with Chronic Obstructive Pulmonary Disease Classified According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Combined Chronic Obstructive Pulmonary Disease (COPD) Assessment System

PubMed Central

Sakurai-Iesato, Yoriko; Kawata, Naoko; Tada, Yuji; Iesato, Ken; Matsuura, Yukiko; Yahaba, Misuzu; Suzuki, Toshio; Ikari, Jun; Yanagawa, Noriyuki; Kasahara, Yasunori; West, James; Tatsumi, Koichiro

2017-01-01

Objective Osteoporosis, which is now recognized as a major comorbidity of chronic obstructive pulmonary disease (COPD), must be diagnosed by appropriate methods. The aims of this study were to clarify the relationships between bone mineral density (BMD) and COPD-related clinical variables and to explore the association of BMD with the updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification in men. Methods We enrolled 50 Japanese men with clinically stable COPD who underwent dual-energy X-ray absorptiometry (DEXA), pulmonary function testing, and computerized tomography (CT) and who had completed a questionnaire (COPD assessment test [CAT]). We determined the association between the T-score and other tested parameters and compared the BMD of patients in each GOLD category. Results Twenty-three of the 50 patients (46.0%) were diagnosed with osteopenia, and 7 (14.0%) were diagnosed with osteoporosis. The BMD findings were significantly correlated with the CAT score, forced expiratory volume in 1 second percentage predicted (FEV1% predicted), low attenuation volume percentage (LAV%), and percentage of cross-sectional area of small pulmonary vessels (%CSA) on CT images. Notably, the median T-score of the GOLD category D participants was significantly lower than that of the participants in each of the other categories (A [-0.98], B [-1.06], C [-1.05], and D [-2.19], p<0.05). Conclusion Reduced BMD was associated with airflow limitation, extent of radiographic findings, and a poor quality of life (QOL) in patients with COPD. The BMD of GOLD category D patients was the lowest of all of the patients evaluated, and category D patients may benefit from active intervention for osteoporosis. PMID:28717072

European hospital adherence to GOLD recommendations for chronic obstructive pulmonary disease (COPD) exacerbation admissions.

PubMed

Roberts, C Michael; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Hartl, Sylvia

2013-12-01

Understanding how European care of chronic obstructive pulmonary disease (COPD) admissions vary against guideline standards provides an opportunity to target appropriate quality improvement interventions. In 2010-2011 an audit of care against the 2010 'Global initiative for chronic Obstructive Lung Disease' (GOLD) standards was performed in 16 018 patients from 384 hospitals in 13 countries. Clinicians prospectively identified consecutive COPD admissions over a period of 8 weeks, recording clinical care measures on a web-based data tool. Data were analysed comparing adherence to 10 key management recommendations. Adherence varied between hospitals and across countries. The lack of available spirometry results and variable use of oxygen and non-invasive ventilation (NIV) are high impact areas identified for improvement.

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

PubMed Central

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

2016-01-01

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

Current Status of Stem Cells and Regenerative Medicine in Lung Biology and Diseases

PubMed Central

Weiss, Daniel J.

2014-01-01

Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPD), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the 3rd leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and chronic obstructive pulmonary disease (COPD) with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been utilized to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy based clinical trials in lung diseases. PMID:23959715

American Thoracic Society/National Heart, Lung, and Blood Institute Asthma-Chronic Obstructive Pulmonary Disease Overlap Workshop Report.

PubMed

Woodruff, Prescott G; van den Berge, Maarten; Boucher, Richard C; Brightling, Christopher; Burchard, Esteban G; Christenson, Stephanie A; Han, MeiLan K; Holtzman, Michael J; Kraft, Monica; Lynch, David A; Martinez, Fernando D; Reddel, Helen K; Sin, Don D; Washko, George R; Wenzel, Sally E; Punturieri, Antonello; Freemer, Michelle M; Wise, Robert A

2017-08-01

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic obstructive lung diseases with an associated high burden of disease. Asthma, which is often allergic in origin, frequently begins in infancy or childhood with variable airflow obstruction and intermittent wheezing, cough, and dyspnea. Patients with COPD, in contrast, are usually current or former smokers who present after the age of 40 years with symptoms (often persistent) including dyspnea and a productive cough. On the basis of age and smoking history, it is often easy to distinguish between asthma and COPD. However, some patients have features compatible with both diseases. Because clinical studies typically exclude these patients, their underlying disease mechanisms and appropriate treatment remain largely uncertain. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the American Thoracic Society, convened a workshop of investigators in San Francisco, California on May 14, 2016. At the workshop, current understanding of asthma-COPD overlap was discussed among clinicians, pathologists, radiologists, epidemiologists, and investigators with expertise in asthma and COPD. They considered knowledge gaps in our understanding of asthma-COPD overlap and identified strategies and research priorities that will advance its understanding. This report summarizes those discussions.

Chronic obstructive pulmonary disease

PubMed Central

Vijayan, V.K.

2013-01-01

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

Recent lung imaging studies. [Effectiveness for diagnosis of chronic obstructive pulmonary disease

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

Taplin, G.V.; Chopra, S.K.

1976-01-01

Radionuclide lung imaging procedures have been available for 11 years but only the perfusion examination has been used extensively and mainly for the diagnosis of pulmonary embolism (P.E.). Its ability to reveal localized ischemia makes it a valuable test of regional lung function as well as a useful diagnostic aid in P.E. Although it had been recognized for several years that chronic obstructive pulmonary disease (COPD) can cause lung perfusion defects which may simulate pulmonary embolism, relatively little use has been made of either the radioxenon or the radioaerosol inhalation lung imaging procedures until the last few years as amore » means of distinguishing P.E. from COPD. In this review emphasis is placed on our recent experience with both of these inhalation procedures in comparison with pulmonary function tests and roentgenography for the early detection of COPD in population studies. Equal emphasis is given to simultaneous aerosol ventilation-perfusion (V/P) imaging for a functional diagnosis of P.E. Two new developments in regional lung diffusion imaging, performed after the inhalation of radioactive gases and/or rapidly absorbed radioaerosols are described. The experimental basis for their potential clinical application in pulmonary embolism detection is presented.« less

Recovery of fluconazole sensitive Candida ciferrii in a diabetic chronic obstructive pulmonary disease patient presenting with pneumonia

PubMed Central

Saha, Kaushik; Sit, Niranjan Kr.; Maji, Arnab; Jash, Debraj

2013-01-01

Chronic obstructive pulmonary disease (COPD) exacerbations admitted in intensive care units (ICUs) occur rarely due to fungal respiratory tract infections, but may occur when associated co-morbidities like diabetes mellitus coexist. Candida ciferrii is a new agent, recently was isolated from lung infections but usually resistant to fluconazole. Here, we report a rare case of pneumonia due to fluconazole sensitive Candida ciferrii in a COPD patient with known diabetes, admitted in our ICU. PMID:24339494

Epigenetics in asthma and other inflammatory lung diseases.

PubMed

Durham, Andrew; Chou, Pai-Chien; Kirkham, Paul; Adcock, Ian M

2010-08-01

Asthma is a chronic inflammatory disease of the airways. The causes of asthma and other inflammatory lung diseases are thought to be both environmental and heritable. Genetic studies do not adequately explain the heritability and susceptabilty to the disease, and recent evidence suggests that epigentic changes may underlie these processes. Epigenetics are heritable noncoding changes to DNA and can be influenced by environmental factors such as smoking and traffic pollution, which can cause genome-wide and gene-specific changes in DNA methylation. In addition, alterations in histone acetyltransferase/deacetylase activities can be observed in the cells of patients with lung diseases such as severe asthma and chronic obstructive pulmonary disease, and are often linked to smoking. Drugs such as glucocorticoids, which are used to control inflammation, are dependent on histone deacetylase activity, which may be important in patients with severe asthma and chronic obstructive pulmonary disease who do not respond well to glucocorticoid therapy. Future work targeting specific histone acetyltransferases/deacetylases or (de)methylases may prove to be effective future anti-inflammatory treatments for patients with treatment-unresponsive asthma.

Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma

PubMed Central

Yates, Katherine P.; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L.; Van Natta, Mark L.; Wise, Robert A.; Szefler, Stanley J.; Sharma, Sunita; Kho, Alvin T.; Cho, Michael H.; Croteau-Chonka, Damien C.; Castaldi, Peter J.; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R.; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A.; Zeiger, Robert S.; Adkinson, N. Franklin; Williams, Paul V.; Kelly, H. William; Grasemann, Hartmut; Vonk, Judith M.; Koppelman, Gerard H.; Postma, Dirkje S.; Raby, Benjamin A.; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Silverman, Edwin K.; Tonascia, James; Strunk, Robert C.; Weiss, Scott T.

2016-01-01

Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. Objectives: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. Methods: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. Measurements and Main Results: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10−9; odds ratio, 2.8; 95% confidence interval, 2.0–4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. Conclusions: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575). PMID:27367781

[Anaesthesia for patients with obstructive airway diseases].

PubMed

Groeben, H; Keller, V; Silvanus, M T

2014-01-01

Obstructive lung diseases like asthma or chronic obstructive lung diseases have a high prevalence and are one of the four most frequent causes of death. Obstructive lung diseases can be significantly influenced by the choice of anesthetic techniques and anesthetic agents. Basically, the severity of the COPD and the degree of bronchial hyperreactivity will determine the perioperative anesthetic risk. This risk has to be assessed by a thorough preoperative evaluation and will give the rationale on which to decide for the adequate anaesthetic technique. In particular, airway instrumentation can cause severe reflex bronchoconstriction. The use of regional anaesthesia alone or in combination with general anaesthesia can help to avoid airway irritation and leads to reduced postoperative complications. Prophylactic antiobstructive treatment, volatile anesthetics, propofol, opioids, and an adequate choice of muscle relaxants minimize the anesthetic risk, when general anesthesia is required In case, despite all precautions intra-operative bronchospasm occurs, deepening of anaesthesia, repeated administration of beta2-adrenergic agents and parasympatholytics, and a single systemic dose of corticosteroids represent the main treatment options.

Survival significance of coexisting chronic obstructive pulmonary disease in patients with early lung cancer after curative surgery

PubMed Central

Miyazawa, Tomoyuki; Sakai, Hiroki; Kimura, Yusuke; Tsuda, Masataka; Wakiyama, Yoichi; Marushima, Hideki; Kojima, Koji; Nakamura, Haruhiko

2017-01-01

Background The impact of chronic obstructive pulmonary disease (COPD) severity on survival after curative resection of early‐stage lung cancer (NSCLC) has not been sufficiently elucidated. Methods We retrospectively reviewed 250 consecutive patients who underwent lobectomy with lymph nodal dissection for pathological stage I–II NSCLC. Results Among the COPD patients, 28 were classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 21 as GOLD 2, and one as GOLD 3. The cumulative overall survival (OS) of the non‐COPD, GOLD 1, and GOLD 2–3 groups at five years was 90.7%, 85.7%, and 55.3%, respectively, (P < 0.0001), while recurrence‐free survival (RFS) between the groups at five years was 84.7%, 80.7%, and 72.9%, respectively. Although RFS in the GOLD 2–3 group tended to indicate a poor prognosis, there was no statistical difference between the groups (P = 0.385). In multivariate analysis, age ≥75 years, pN1, and GOLD 2–3 COPD were independent factors for a poor prognosis (P = 0.034, P = 0.010, and P = 0.030, respectively). Conclusions Our results indicate that early stage NSCLC patients with COPD had a significantly increased risk of poorer OS and potentially an increased risk of poor RFS. PMID:28976075

Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease

PubMed Central

Kim, Joohae; Yoon, Ho Il; Oh, Yeon-Mok; Lim, Seong Yong; Lee, Ji-Hyun; Kim, Tae-Hyung; Lee, Sang Yeub; Lee, Jin Hwa; Lee, Sang-Do; Lee, Chang-Hoon

2015-01-01

Background Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A–D were introduced, the lung function changes according to group have been evaluated rarely. Objective We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines. Methods Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression. Results A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79). The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline. Conclusion There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. PMID:26379432

Roflumilast

MedlinePlus

... in people with severe chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... reduce the number of episodes or worsening of COPD symptoms. Roflumilast is in a class of medications ...

SMALL AIRWAYS FUNCTION RESPONSE IN SMOKERS AND PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE FOLLOWING EXPOSURE TO CONCENTRATED AMBIENT AIR PARTICLES

EPA Science Inventory

Numerous field and epidemiological studies have shown significant associations between particulate matter (PM) exposure and various morbidity outcomes including hospital admissions for bronchitis and asthma. These population based studies indicate that persons with chronic obstru...

Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

PubMed Central

McGrath-Morrow, Sharon; Malhotra, Deepti; Lauer, Thomas; Collaco, J. Michael; Mitzner, Wayne; Neptune, Enid; Wise, Robert; Biswal, Shyam

2016-01-01

The impact of early childhood cigarette smoke (CS) exposure on CS-induced chronic obstructive pulmonary disease (COPD) is unknown. This study was performed to evaluate the individual and combined effects of neonatal and adult CS exposure on lung structure, function, and gene expression in adult mice. To model a childhood CS exposure, neonatal C57/B6 mice were exposed to 14 days of CS (Neo CS). At 10 weeks of age, Neo CS and control mice were exposed to 4 months of CS. Pulmonary function tests, bronchoalveolar lavage, and lung morphometry were measured and gene expression profiling was performed on lung tissue. Mean chord lengths and lung volumes were increased in neonatal and/or adult CS-exposed mice. Differences in immune, cornified envelope protein, muscle, and erythrocyte genes were found in CS-exposed lung. Neonatal CS exposure caused durable structural and functional changes in the adult lung but did not potentiate CS-induced COPD changes. Cornified envelope protein gene expression was decreased in all CS-exposed mice, whereas myosin and erythrocyte gene expression was increased in mice exposed to both neonatal and adult CS, suggesting an adaptive response. Additional studies may be warranted to determine the utility of these genes as biomarkers of respiratory outcomes. PMID:21649527

Asthma-COPD overlap syndrome-Coexistence of chronic obstructive pulmonary disease and asthma in elderly patients and parameters for their differentiation.

PubMed

Tochino, Yoshihiro; Asai, Kazuhisa; Shuto, Taichi; Hirata, Kazuto

2017-03-01

Japan is an aging society, and the number of elderly patients with asthma and chronic obstructive pulmonary disease (COPD) is consequently increasing, with an estimated incidence of approximately 5 million. In 2014, asthma-COPD overlap syndrome (ACOS) was defined by a joint project of Global Initiative for Asthma (GINA) committee and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee. The main aims of this consensus-based document are to assist clinicians, especially those in primary care or nonpulmonary specialties. In this article, we discussed parameters to differentiate asthma and COPD in elderly patients and showed prevalence, clinical features and treatment of ACOS on the basis of the guidelines of GINA and GOLD. Furthermore, we showed also referral for specialized investigations.

[Lung transplantation.].

PubMed

Guðmundsson, G

2000-09-01

Lung transplantation is an option in the treatment of end stage lung diseases, excluding lung cancer, that lead to short life expectancy and poor quality of life. Now they are mostly limited by shortage of donor organs and longterm complications. They are used for various lung diseases such as pulmonary vascular diseases, fibrosing diseases, chronic obstructive pulmonary diseases and diseases that cause chronic infections. Depending on the indication it is possible to perform heart and lung transplantation, single lung or double lung transplantation.Indications, contraindications, surgical methods, immunosuppression, complications and outcomes will be discussed. Survival is not as good as for other solid organ transplantation. Measurement of pulmonary function and quality of life improve with lung transplantation. Bronchiolitis obliterans is the most common complication and is the most limiting factor. A few Icelanders have undergone lung transplantation, most of them in Gothenburg, Sweden. The future of lung transplantation depends on limiting the incidence of bronchiolitis obliterans and finding more organ donors.

Persistent and Newly Developed Chronic Bronchitis Are Associated with Worse Outcomes in Chronic Obstructive Pulmonary Disease

PubMed Central

Zhao, Huaqing; Boriek, Aladin M.; Anzueto, Antonio; Soler, Xavier; Bhatt, Surya P.; Rennard, Stephen I.; Wise, Robert; Comellas, Alejandro; Ramsdell, Joe W.; Kinney, Gregory L.; Han, MeiLan K.; Martinez, Carlos H.; Yen, Andrew; Black-Shinn, Jennifer; Porszasz, Janos; Criner, Gerard J.; Hanania, Nicola A.; Sharafkhaneh, Amir; Crapo, James D.; Make, Barry J.; Silverman, Edwin K.; Curtis, Jeffrey L.

2016-01-01

Rationale: Chronic bronchitis is, by definition, a chronic condition, but the development and remission of this condition in cigarette smokers with or without chronic obstructive pulmonary disease (COPD) are poorly understood. Also, it is unclear how the persistence or new development of chronic bronchitis affects symptoms and outcomes. Objectives: To ascertain the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes. Methods: We analyzed 1,775 current or ex-smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0–IV COPD in phase 2 of the Genetic Epidemiology of COPD (COPDGene) Study, which included subjects after 5 years of follow-up from phase 1. We asked subjects at enrollment and at 5 years of follow-up about symptoms consistent with chronic bronchitis. We divided subjects into four groups: persistent chronic bronchitis– (negative at phase 1/negative at phase 2), resolved chronic bronchitis (positive/negative), new chronic bronchitis (negative/positive), and persistent chronic bronchitis+ (positive/positive). We analyzed respiratory symptoms, health-related quality of life, lung function, exacerbation frequency, and 6-minute walk distance. Measurements and Main Results: Compared with the persistent chronic bronchitis– group, members of the persistent chronic bronchitis+ group were more likely to have continued smoking (53.4%). Subjects with new chronic bronchitis were more likely to have resumed (6.6%) or continued smoking (45.6%), whereas subjects with resolved chronic bronchitis were more likely to have quit smoking (23.5%). Compared with the persistent chronic bronchitis– group, the other groups had a shorter 6-minute walk distance, worse lung function, greater exacerbation frequency, and worse respiratory symptoms. Modified Medical Research Council dyspnea and St. George’s Respiratory Questionnaire scores worsened between phase 1 and phase 2 in subjects with new chronic bronchitis but improved in the resolved chronic bronchitis group. On multinomial logistic regression, quitting smoking conferred an odds ratio (OR) of 4.289 (95% confidence interval [CI], 2.689–6.842) for resolved chronic bronchitis, whereas resuming smoking had an OR of 4.585 (95% CI, 2.008–10.471) for new chronic bronchitis. Persistent smoking had an OR of 2.621 (95% CI, 1.677–4.096) and 5.767 (95% CI, 3.702–8.983) for subjects with new chronic bronchitis and subjects with persistent chronic bronchitis, respectively. Conclusions: Persistent and newly developed chronic bronchitis are associated with continued or resumed smoking, greater respiratory symptoms, worse health-related quality of life, worse lung function, and greater exacerbation frequency. These findings stress the importance of repeatedly assessing chronic cough and sputum production in smokers to identify those at risk for poor outcomes. PMID:27158740

Persistent and Newly Developed Chronic Bronchitis Are Associated with Worse Outcomes in Chronic Obstructive Pulmonary Disease.

PubMed

Kim, Victor; Zhao, Huaqing; Boriek, Aladin M; Anzueto, Antonio; Soler, Xavier; Bhatt, Surya P; Rennard, Stephen I; Wise, Robert; Comellas, Alejandro; Ramsdell, Joe W; Kinney, Gregory L; Han, MeiLan K; Martinez, Carlos H; Yen, Andrew; Black-Shinn, Jennifer; Porszasz, Janos; Criner, Gerard J; Hanania, Nicola A; Sharafkhaneh, Amir; Crapo, James D; Make, Barry J; Silverman, Edwin K; Curtis, Jeffrey L

2016-07-01

Chronic bronchitis is, by definition, a chronic condition, but the development and remission of this condition in cigarette smokers with or without chronic obstructive pulmonary disease (COPD) are poorly understood. Also, it is unclear how the persistence or new development of chronic bronchitis affects symptoms and outcomes. To ascertain the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes. We analyzed 1,775 current or ex-smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0-IV COPD in phase 2 of the Genetic Epidemiology of COPD (COPDGene) Study, which included subjects after 5 years of follow-up from phase 1. We asked subjects at enrollment and at 5 years of follow-up about symptoms consistent with chronic bronchitis. We divided subjects into four groups: persistent chronic bronchitis- (negative at phase 1/negative at phase 2), resolved chronic bronchitis (positive/negative), new chronic bronchitis (negative/positive), and persistent chronic bronchitis+ (positive/positive). We analyzed respiratory symptoms, health-related quality of life, lung function, exacerbation frequency, and 6-minute walk distance. Compared with the persistent chronic bronchitis- group, members of the persistent chronic bronchitis+ group were more likely to have continued smoking (53.4%). Subjects with new chronic bronchitis were more likely to have resumed (6.6%) or continued smoking (45.6%), whereas subjects with resolved chronic bronchitis were more likely to have quit smoking (23.5%). Compared with the persistent chronic bronchitis- group, the other groups had a shorter 6-minute walk distance, worse lung function, greater exacerbation frequency, and worse respiratory symptoms. Modified Medical Research Council dyspnea and St. George's Respiratory Questionnaire scores worsened between phase 1 and phase 2 in subjects with new chronic bronchitis but improved in the resolved chronic bronchitis group. On multinomial logistic regression, quitting smoking conferred an odds ratio (OR) of 4.289 (95% confidence interval [CI], 2.689-6.842) for resolved chronic bronchitis, whereas resuming smoking had an OR of 4.585 (95% CI, 2.008-10.471) for new chronic bronchitis. Persistent smoking had an OR of 2.621 (95% CI, 1.677-4.096) and 5.767 (95% CI, 3.702-8.983) for subjects with new chronic bronchitis and subjects with persistent chronic bronchitis, respectively. Persistent and newly developed chronic bronchitis are associated with continued or resumed smoking, greater respiratory symptoms, worse health-related quality of life, worse lung function, and greater exacerbation frequency. These findings stress the importance of repeatedly assessing chronic cough and sputum production in smokers to identify those at risk for poor outcomes.

Pain management at the end of life: A comparative study of cancer, dementia, and chronic obstructive pulmonary disease patients.

PubMed

Romem, Anat; Tom, Sarah E; Beauchene, Michelle; Babington, Lynn; Scharf, Steven M; Romem, Ayal

2015-05-01

Limited data exist concerning the unique pain characteristics of patients with non-cancer terminal diseases referred for inpatient hospice care. To define the unique pain characteristics of patients admitted to an acute inpatient hospice setting with end-stage dementia or chronic obstructive lung disease (or chronic obstructive pulmonary disease) and to compare them to patients with end-stage cancer. Retrospective patient chart review. Demographic, physiological, pain parameters, and medication utilization data were extracted. Associations between pain characteristics, medication utilization, and admission diagnoses were assessed. Analyses included descriptive statistics. In total, 146 patients admitted to an acute inpatient hospice between 1 April 2011 and 31 March 2012 with an underlying primary diagnosis of chronic obstructive pulmonary disease (n = 51), dementia (n = 48), or cancer (n = 47). Pain was highly prevalent in all diagnostic groups, with cancer patients experiencing more severe pain on admission. Cancer patients received a significantly higher cumulative opioid dose compared with dementia and chronic obstructive pulmonary disease patients. Pain control within 24 h of pain onset was achieved in less than half of all patient groups with chronic obstructive pulmonary disease patients the least likely to achieve pain control. Despite the fact that pain is the most common complaint at the end of life, pain management may be suboptimal for some primary diagnoses. Admission diagnosis is the strongest predictor of pain control. Patient with cancer achieve the best pain control, and chronic obstructive pulmonary disease patients are the least likely to have their pain adequately treated. © The Author(s) 2015.

Methods for Measuring Lung Volumes: Is There a Better One?

PubMed

Tantucci, Claudio; Bottone, Damiano; Borghesi, Andrea; Guerini, Michele; Quadri, Federico; Pini, Laura

2016-01-01

Accurate measurement of lung volumes is of paramount importance to establish the presence of ventilatory defects and give insights for diagnostic and/or therapeutic purposes. It was the aim of this study to measure lung volumes in subjects with respiratory disorders and in normal controls by 3 different techniques (plethysmographic, dilutional and radiographic methods), in an attempt to clarify the role of each of them in performing such a task, without any presumptive 'a priori' superiority of one method above others. Patients andMethods: In different groups of subjects with obstructive and restrictive ventilatory defects and in a normal control group, total lung capacity, functional residual capacity (FRC) and residual volume were measured by body plethysmography, multi-breath helium (He) dilution and radiographic CT scan method with spirometric gating. The 3 methods gave comparable results in normal subjects and in patients with a restrictive defect. In patients with an obstructive defect, CT scan and plethysmography showed similar lung volumes, while on average significantly lower lung volumes were obtained with the He dilution technique. Taking into account that the He dilution technique does primarily measure FRC during tidal breathing, our data suggest that in some patients with an obstructive defect, a number of small airways can be functionally closed at end-expiratory lung volume, preventing He to reach the lung regions subserved by these airways. In all circumstances, both CT scan with spirometric gating and plethysmographic methods provide similar values of lung volumes. In contrast, the He dilution method can measure lower lung volumes in some patients with chronic airflow obstruction. © 2016 S. Karger AG, Basel.

The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop

PubMed Central

Budinger, GR Scott; Kohanski, Ronald A; Gan, Weiniu; Kobor, Michael S; Amaral, Luis A; Armanios, Mary; Kelsey, Karl T; Pardo, Annie; Tuder, Rubin; Macian, Fernando; Chandel, Navdeep; Vaughan, Douglas; Rojas, Mauricio; Mora, Ana L; Kovacs, Elizabeth; Duncan, Steven R; Finkel, Toren; Choi, Augustine; Eickelberg, Oliver; Chen, Danica; Agusti, Alvar; Selman, Moises; Balch, William E; Busse, Paula; Lin, Anning; Morimoto, Richard; Sznajder, Jacob I; Thannickal, Victor J

2017-01-01

Abstract Death from chronic lung disease is increasing and chronic obstructive pulmonary disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide population ages. Chronic lung diseases are associated with substantial morbidity, frequently resulting in exercise limiting dyspnea, immobilization, and isolation. Therefore, effective strategies to prevent or treat lung disease are likely to increase healthspan as well as life span. This review summarizes the findings of a joint workshop sponsored by the NIA and NHLBI that brought together investigators focused on aging and lung biology. These investigators encouraged the use of genetic systems and aged animals in the study of lung disease and the development of integrative systems-based platforms that can dynamically incorporate data sets that describe the genomics, transcriptomics, epigenomics, metabolomics, and proteomics of the aging lung in health and disease. Further research was recommended to integrate benchmark biological hallmarks of aging in the lung with the pathobiology of acute and chronic lung diseases with divergent pathologies for which advanced age is the most important risk factor. PMID:28498894

The emergence of Aspergillus species in chronic respiratory disease.

PubMed

Yii, Anthony Ca; Koh, Mariko S; Lapperre, Therese S; Tan, Gan L; Chotirmall, Sanjay H

2017-01-01

Chronic lung disease is recognized as an important risk factor for developing pulmonary aspergillosis. The development of specific aspergillus-associated syndromes depends on host immunity and underlying lung disease. In the setting of asthma, hypersensitivity to Aspergillus can lead to allergic bronchopulmonary aspergillosis (ABPA) or severe asthma with fungal sensitization (SAFS). Chronic use of systemic or inhaled corticosteroids coupled with recurrent antibiotic use for exacerbations prevalent in chronic obstructive pulmonary disease (COPD) predisposes to chronic pulmonary aspergillosis (CPA). Prior pulmonary tuberculosis is a risk factor for CPA, a syndrome with a wide range of presentations including a simple aspergilloma, chronic cavities, necrosis or fibrosis. Accumulating evidence suggests that the presence of or colonization by Aspergillus in the setting of chronic lung disease can worsen clinical course and outcomes even in the absence of overt pulmonary aspergillosis. We propose that understanding the complex interplay between host and fungi may provide key insights into the pathogenesis of Aspergillus -associated pulmonary syndromes in the setting of chronic lung disease, and provide novel therapeutic approaches to improve its identification and management.

Influence of Pulmonary Rehabilitation on Lung Function Changes After the Lung Resection for Primary Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Mujovic, Natasa; Mujovic, Nebojsa; Subotic, Dragan; Ercegovac, Maja; Milovanovic, Andjela; Nikcevic, Ljubica; Zugic, Vladimir; Nikolic, Dejan

2015-11-01

Influence of physiotherapy on the outcome of the lung resection is still controversial. Study aim was to assess the influence of physiotherapy program on postoperative lung function and effort tolerance in lung cancer patients with chronic obstructive pulmonary disease (COPD) that are undergoing lobectomy or pneumonectomy. The prospective study included 56 COPD patients who underwent lung resection for primary non small-cell lung cancer after previous physiotherapy (Group A) and 47 COPD patients (Group B) without physiotherapy before lung cancer surgery. In Group A, lung function and effort tolerance on admission were compared with the same parameters after preoperative physiotherapy. Both groups were compared in relation to lung function, effort tolerance and symptoms change after resection. In patients with tumors requiring a lobectomy, after preoperative physiotherapy, a highly significant increase in FEV1, VC, FEF50 and FEF25 of 20%, 17%, 18% and 16% respectively was registered with respect to baseline values. After physiotherapy, a significant improvement in 6-minute walking distance was achieved. After lung resection, the significant loss of FEV1 and VC occurred, together with significant worsening of the small airways function, effort tolerance and symptomatic status. After the surgery, a clear tendency existed towards smaller FEV1 loss in patients with moderate to severe, when compared to patients with mild baseline lung function impairment. A better FEV1 improvement was associated with more significant loss in FEV1. Physiotherapy represents an important part of preoperative and postoperative treatment in COPD patients undergoing a lung resection for primary lung cancer.

Impact of customized videotape education on quality of life in patients with chronic obstructive pulmonary disease.

PubMed

Petty, Thomas L; Dempsey, Edward C; Collins, Timothy; Pluss, William; Lipkus, Isaac; Cutter, Gary R; Chalmers, Robin; Mitchell, Amy; Weil, Kenneth C

2006-01-01

To compare the impact of a library of pulmonary rehabilitation videotapes versus an older videotape and usual care on quality of life and ability to perform activities of daily living in persons with chronic obstructive pulmonary disease. Two hundred fourteen patients diagnosed with chronic obstructive pulmonary disease, emphysema, or chronic bronchitis were recruited and randomized to receive customized videotapes, standard videotapes, or usual care. Outcome measures included the Fatigue Impact Scale, Seattle Obstructive Lung Disease Questionnaire, and the SF-36(R) Health Survey. Differences in coping skills and emotional functioning on the Seattle Obstructive Lung Disease Questionnaire were found among the 174 subjects who completed the study. The customized videotape group improved by 8.6 and 4.8 points, respectively, whereas the score of the other groups decreased by less than 1 point for the coping skills, and the scores of the standard video and the control groups decreased by 3.0 and 2.1 points, respectively, for emotional functioning (P < .05, all comparisons). The scores using the Fatigue Impact Scale also improved for the customized videotape group, whereas the scores of the others remained unchanged. Videotape users demonstrated better conversion to and retention of exercise habits, with over 80% of customized videotape subjects who reported exercise habits at baseline continuing the habits as compared with 40% in the usual care group. Sedentary subjects at baseline were more likely to begin and maintain exercise if randomized to videotapes. These findings demonstrate increased quality of life, lower fatigue, and better compliance with a prescribed exercise regimen among subjects using the customized videotapes. There was a significant improvement in emotional functioning and coping skills among customized videotape subjects.

Global Initiative for Chronic Obstructive Lung Disease strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: an Asia-Pacific perspective.

PubMed

2005-01-01

Chronic obstructive pulmonary disease (COPD) is a major public health problem and its prevalence and mortality are increasing throughout the world, including the Asia-Pacific region. To arrest these worldwide trends, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Expert Panel's global strategy for the diagnosis, management, and prevention of COPD was published in 2001. Based on recently published clinical trials, the GOLD statement was updated in 2003. The Asia-Pacific COPD Roundtable Group, a taskforce of expert respirologists from the Asia-Pacific region, has recently formulated a consensus statement on implementation of the GOLD strategy for COPD in the Asia-Pacific region. The key issues identified by the COPD Roundtable Group for comment are: (i) where there is no access to spirometry, diagnosis of COPD could be suspected on the basis of history, symptoms and physical signs; (ii) inhaled bronchodilators are the preferred regular treatment for COPD in the region, but oral bronchodilators may be considered if the cost of inhaled bronchodilators is a barrier to treatment; (iii) the use of a Metered Dose Inhaler with spacer in place of a nebulizer is recommended in the treatment of acute airflow obstruction in patients with COPD; (iv) influenza vaccination is recommended for all patients with COPD in communities where there is a high likelihood of Severe Acute Respiratory Syndrome; and (v) simplified pulmonary rehabilitation programmes should be established in areas where comprehensive programmes are unavailable. Physical exercise training and education on smoking cessation should be core elements of any rehabilitation program. In summary, the COPD Roundtable Group supports implementation of the GOLD strategy for the diagnosis, management and prevention of COPD in the Asia-Pacific region, subject to the additions and modifications to the guidelines suggested above.

Chronic Airflow Obstruction in a Black African Population: Results of BOLD Study, Ile-Ife, Nigeria.

PubMed

Obaseki, Daniel O; Erhabor, Gregory E; Gnatiuc, Louisa; Adewole, Olufemi O; Buist, Sonia A; Burney, Peter G

2016-01-01

Global estimates suggest that Chronic Obstructive Pulmonary Disease (COPD) is emerging as a leading cause of death in developing countries but there are few spirometry-based general population data on its prevalence and risk factors in sub-Saharan Africa. We used the Burden of Obstructive Lung Disease (BOLD) protocol to select a representative sample of adults aged 40 years and above in Ile-Ife, Nigeria. All the participants underwent spirometry and provided information on smoking history, biomass and occupational exposures as well as diagnosed respiratory diseases and symptoms. Chronic Airflow Obstruction (CAO) was defined as the ratio of post-bronchodilator (BD) one second Forced Expiratory Volume (FEV1) to Forced Vital Capacity (FVC) below the lower limit of normal (LLN) of the population distribution for FEV1/FVC. The overall prevalence of obstruction (post-BD FEV1/FVC < LLN) was 7.7% (2.7% above LLN) using Global Lung Function Initiative (GLI) equations. It was associated with few respiratory symptoms; 0.3% reported a previous doctor-diagnosed chronic bronchitis, emphysema or COPD. Independent predictors included a lack of education (OR 2.5, 95% CI: 1.0, 6.4) and a diagnosis of either TB (OR 23.4, 95% CI: 2.0, 278.6) or asthma (OR 35.4, 95%CI: 4.9, 255.8). There was no association with the use of firewood or coal for cooking or heating. The vast majority of this population (89%) are never smokers. We conclude that the prevalence of CAO is low in Ile-Ife, Nigeria and unrelated to biomass exposure. The key independent predictors are poor education, and previous diagnosis of tuberculosis or asthma.

Childhood Lung Function Predicts Adult Chronic Obstructive Pulmonary Disease and Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome.

PubMed

Bui, Dinh S; Burgess, John A; Lowe, Adrian J; Perret, Jennifer L; Lodge, Caroline J; Bui, Minh; Morrison, Stephen; Thompson, Bruce R; Thomas, Paul S; Giles, Graham G; Garcia-Aymerich, Judith; Jarvis, Debbie; Abramson, Michael J; Walters, E Haydn; Matheson, Melanie C; Dharmage, Shyamali C

2017-07-01

The burden of chronic obstructive pulmonary disease (COPD) is increasing, yet there are limited data on early life risk factors. To investigate the role of childhood lung function in adult COPD phenotypes. Prebronchodilator spirometry was performed for a cohort of 7-year-old Tasmanian children (n = 8,583) in 1968 who were resurveyed at 45 years, and a selected subsample (n = 1,389) underwent prebronchodilator and post-bronchodilator spirometry. For this analysis, COPD was spirometrically defined as a post-bronchodilator FEV 1 /FVC less than the lower limit of normal. Asthma-COPD overlap syndrome (ACOS) was defined as the coexistence of both COPD and current asthma. Associations between childhood lung function and asthma/COPD/ACOS were examined using multinomial regression. At 45 years, 959 participants had neither current asthma nor COPD (unaffected), 269 had current asthma alone, 59 had COPD alone, and 68 had ACOS. The reweighted prevalence of asthma alone was 13.5%, COPD alone 4.1%, and ACOS 2.9%. The lowest quartile of FEV 1 at 7 years was associated with ACOS (odds ratio, 2.93; 95% confidence interval, 1.32-6.52), but not COPD or asthma alone. The lowest quartile of FEV 1 /FVC ratio at 7 years was associated with ACOS (odds ratio, 16.3; 95% confidence interval, 4.7-55.9) and COPD (odds ratio, 5.76; 95% confidence interval, 1.9-17.4), but not asthma alone. Being in the lowest quartile for lung function at age 7 may have long-term consequences for the development of COPD and ACOS by middle age. Screening of lung function in school age children may identify a high-risk group that could be targeted for intervention. Further research is needed to understand possible modifiers of these associations and develop interventions for children with impaired lung function.

Role of macrophage migration inhibitory factor in age-related lung disease

PubMed Central

Sauler, Maor; Bucala, Richard

2015-01-01

The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease. PMID:25957294

Radioaerosol lung imaging in chronic obstructive pulmonary disease. Comparison with pulmonary function tests and roentgenography. [/sup 113m/In, /sup 99m/Tc, /sup 133/Xe tracer techniques

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

Ramanna, L.; Tashkin, D.P.; Taplin, G.V.

1975-11-01

Seventy subjects with either no, mild, or definite evidence of pulmonary abnormality on screening studies volunteered to have detailed pulmonary function tests (PFTs), respiratory questionnaires, physical examinations, and /sup 113m/indium aerosol-inhalation lung imaging performed. Also, 22 and 52 of these subjects underwent /sup 133/xenon ventilation and lung perfusion imaging with /sup 99m/technetium-labelled macroaggregated albumin, and 56 had chest x-ray examinations performed. Results of the radionuclide lung-imaging procedures were compared with those of conventional PFTs and other clinical diagnostic procedures used to identify chronic obstructive pulmonary disease (COPD). Abnormal radioaerosol patterns were found in 32 of 33 subjects with abnormal findingsmore » on PFTs, whereas results of PFTs were abnormal in only 32 of 46 subjects with abnormal aerosol deposition. Aerosol lung images were abnormal more frequently than respiratory questionnaire responses, findings on physical examination, chest x-ray films, and perfusion lung images and with approximately the same frequency as /sup 133/xenon ventilation scintiscans. These results suggest that radioaerosol lung imaging may be a more sensitive indicator of early COPD than other diagnostic procedures, including maximal midexpiratory flow rates, single-breath nitrogen washout, and closing volume. Further studies are required to determine the physiologic and pathologic significance of isolated aerosol lung-imaging abnormalities.« less

Non-smoking Chronic Obstructive Pulmonary Disease Attributed to Occupational Exposure to Silica Dust.

PubMed

Tsuchiya, Kazuo; Toyoshima, Mikio; Kamiya, Yosuke; Nakamura, Yutaro; Baba, Satoshi; Suda, Takafumi

2017-01-01

An 85-year-old, never-smoking man presented with exertional dyspnea. He had been exposed to silica dust in the work place. Chest computed tomography revealed bronchial wall thickening without emphysema. A pulmonary function test showed airflow obstruction without impaired gas transfer. Airway hyperresponsiveness and reversibility were not evident. A transbronchial lung biopsy showed findings suggestive of mineral dust exposure, such as fibrosis and slight pigmentation of bronchioles. He was diagnosed with non-smoking chronic obstructive pulmonary disease (COPD) due to occupational exposure to silica dust. His symptoms were improved using an inhaled long-acting bronchodilator. The clinical characteristics of non-smoking COPD are discussed in this report.

Outcome of domiciliary nasal intermittent positive pressure ventilation in restrictive and obstructive disorders.

PubMed Central

Simonds, A. K.; Elliott, M. W.

1995-01-01

BACKGROUND--Nasal intermittent positive pressure ventilation (NIPPV) is a new technique which has rapidly supplanted other non-invasive methods of ventilation over the last 5-10 years. Data on its effectiveness are limited. METHODS--The outcome of long term domiciliary NIPPV has been analysed in 180 patients with hypercapnic respiratory failure predominantly due to chest wall restriction, neuromuscular disorders, or chronic obstructive lung disease. One hundred and thirty eight patients were started on NIPPV electively, and 42 following an acute hypercapnic exacerbation. Outcome measures were survival (five year probability of continuing NIPPV), pulmonary function, and health status. A crossover study from negative pressure ventilation to NIPPV was carried out in a subgroup of patients. RESULTS--Five year acturial probability of continuing NIPPV for individuals with early onset scoliosis (n = 47), previous poliomyelitis (n = 30), following tuberculous lung disease (n = 20), general neuromuscular disorders (n = 29), and chronic obstructive pulmonary disease (n = 33) was 79% (95% CI 66 to 92), 100%, 94% (95% CI 83 to 100), 81% (95% CI 61 to 100), 43% (95% CI 6 to 80), respectively. Most of the patients with bronchiectasis died within two years. One year after starting NIPPV electively the mean (SD) PaO2 compared with the pretreatment value was +1.8 (1.9) kPa, mean PaCO2 -1.4 (1.3) kPa in patients with extrapulmonary restrictive disorders, and PaO2 +0.8 (1.0) kPa, PaCO2 -0.9 (0.8) kPa in patients with obstructive lung disease. Arterial blood gas tensions improved in patients transferred from negative pressure ventilation to NIPPV. Health status was ranked highest in patients with early onset scoliosis, previous poliomyelitis, and following tuberculous lung disease. In the group as a whole health perception was comparable to outpatients with other chronic disorders. CONCLUSIONS--The long term outcome of domiciliary NIPPV in patients with chronic respiratory failure due to scoliosis, previous poliomyelitis, and chest wall and pulmonary disease secondary to tuberculosis is encouraging. The results of NIPPV in patients with COPD and progressive neuromuscular disorders show benefit in some subgroups. The outcome in end stage bronchiectasis is poor. Images PMID:7638799

Outcome of domiciliary nasal intermittent positive pressure ventilation in restrictive and obstructive disorders.

PubMed

Simonds, A K; Elliott, M W

1995-06-01

Nasal intermittent positive pressure ventilation (NIPPV) is a new technique which has rapidly supplanted other non-invasive methods of ventilation over the last 5-10 years. Data on its effectiveness are limited. The outcome of long term domiciliary NIPPV has been analysed in 180 patients with hypercapnic respiratory failure predominantly due to chest wall restriction, neuromuscular disorders, or chronic obstructive lung disease. One hundred and thirty eight patients were started on NIPPV electively, and 42 following an acute hypercapnic exacerbation. Outcome measures were survival (five year probability of continuing NIPPV), pulmonary function, and health status. A crossover study from negative pressure ventilation to NIPPV was carried out in a subgroup of patients. Five year acturial probability of continuing NIPPV for individuals with early onset scoliosis (n = 47), previous poliomyelitis (n = 30), following tuberculous lung disease (n = 20), general neuromuscular disorders (n = 29), and chronic obstructive pulmonary disease (n = 33) was 79% (95% CI 66 to 92), 100%, 94% (95% CI 83 to 100), 81% (95% CI 61 to 100), 43% (95% CI 6 to 80), respectively. Most of the patients with bronchiectasis died within two years. One year after starting NIPPV electively the mean (SD) PaO2 compared with the pretreatment value was +1.8 (1.9) kPa, mean PaCO2 -1.4 (1.3) kPa in patients with extrapulmonary restrictive disorders, and PaO2 +0.8 (1.0) kPa, PaCO2 -0.9 (0.8) kPa in patients with obstructive lung disease. Arterial blood gas tensions improved in patients transferred from negative pressure ventilation to NIPPV. Health status was ranked highest in patients with early onset scoliosis, previous poliomyelitis, and following tuberculous lung disease. In the group as a whole health perception was comparable to outpatients with other chronic disorders. The long term outcome of domiciliary NIPPV in patients with chronic respiratory failure due to scoliosis, previous poliomyelitis, and chest wall and pulmonary disease secondary to tuberculosis is encouraging. The results of NIPPV in patients with COPD and progressive neuromuscular disorders show benefit in some subgroups. The outcome in end stage bronchiectasis is poor.

Abnormal heart rate recovery and chronotropic incompetence on exercise in chronic obstructive pulmonary disease.

PubMed

Gupta, Mansi; Bansal, Vishal; Chhabra, Sunil K

2013-08-01

Chronotropic incompetence (CI; failure to reach the targeted heart rate (HR) on exercise) and a delayed HR recovery (HRR; ≤12 beats decline within the first minute after cessation) reflect autonomic dysfunction (AD) and predict adverse cardiac prognosis. As chronic obstructive pulmonary disease (COPD) is known to be associated with AD, we hypothesized that these patients may manifest these responses on exercise. The prevalence and predictors of these responses in COPD and their association with its severity have not been evaluated. Normoxemic, stable male patients with COPD (n = 39) and 11 healthy controls underwent lung function testing and incremental leg ergometry. HR responses were monitored during exercise and recovery to compute the HRR and CI. Of all the patients, 33 (84.6%) had at least one of the two exercise responses as abnormal, with the majority (23, 58.9%) having both an abnormal HRR and CI. The frequency of abnormal responses increased with increasing Global Initiative for Chronic Obstructive Lung Disease stage and body mass index, airflow obstruction, dyspnoea and exercise capacity index. After adjusting for smoking history and post-bronchodilator forced expiratory volume in 1 second, only a reduced diffusion capacity for carbon monoxide predicted abnormal HRR, though weakly. We concluded that abnormal HRR and CI are common in patients with COPD. These responses are observed with increasing frequency as the severity of disease increases.

Association of emphysema-like lung on cardiac computed tomography and mortality in persons without airflow obstruction: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

PubMed Central

Oelsner, Elizabeth C.; Hoffman, Eric A.; Folsom, Aaron R.; Carr, J. Jeffrey; Enright, Paul L.; Kawut, Steven M.; Kronmal, Richard; Lederer, David; Lima, Joao A. C.; Lovasi, Gina S.; Shea, Steven; Barr, R. Graham

2015-01-01

Background Whereas low lung function is known to predict mortality in the general population, the prognostic significance of emphysema on computed tomography (CT) in persons without chronic obstructive pulmonary disease (COPD) remains uncertain. Objective To determine whether greater emphysema-like lung on CT is associated with all-cause mortality among persons without airflow obstruction or COPD in the general population. Design Prospective cohort study. Setting Population-based, multiethnic sample from 6 US communities. Participants 2965 participants ages 45-84 years without airflow obstruction on spirometry. Measurements Emphysema-like lung was defined on cardiac CT as the number of lung voxels less than -950 Hounsfield Units, and was adjusted for the number of total imaged lung voxels. Results Among 2965 participants, 50.9% of whom never smoked, there were 186 deaths over a median of 6.2 years. Greater emphysema-like lung was independently associated with increased mortality (adjusted hazard ratio [HR]1.14 per one-half of the interquartile range, 95% CI 1.04-1.24, P=0.004), adjusting for potential confounders including cardiovascular risk factors and the forced expiratory volume in one second. Generalized additive models supported a linear association between emphysema-like lung and mortality without evidence for a threshold. The association was of greatest magnitude among smokers, although multiplicative interaction terms did not support effect modification by smoking status. Limitations Cardiac CT scans did not include lung apices. The number of deaths was limited among subgroup analyses. Conclusions Emphysema-like lung on CT was associated with all-cause mortality among persons without airflow obstruction or COPD in a general population sample, particularly among smokers. Recognition of the independent prognostic significance of emphysema on CT among patients without COPD on spirometry is warranted. Primary Funding Source NIH/NHLBI. PMID:25506855

Regulatory T-Cell Distribution within Lung Compartments in COPD.

PubMed

Sales, Davi S; Ito, Juliana T; Zanchetta, Ivy A; Annoni, Raquel; Aun, Marcelo V; Ferraz, Luiz Fernando S; Cervilha, Daniela A B; Negri, Elnara; Mauad, Thais; Martins, Mílton A; Lopes, Fernanda D T Q S

2017-10-01

The importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF + cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17 + cells only in small airways. A decrease in the density of Treg + , TGF-β + and IL-10 + in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF + cells were also increased in COPD; however, changes in Treg inhibitory associated cytokines were not observed in this compartment. Therefore, our results suggest that difference in Treg + cell distributions in lung compartments and the decrease in TGF-β + and IL-10 + cells in the airways may lead to the obstruction in smokers.

CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society

PubMed Central

Austin, John H. M.; Hogg, James C.; Grenier, Philippe A.; Kauczor, Hans-Ulrich; Bankier, Alexander A.; Barr, R. Graham; Colby, Thomas V.; Galvin, Jeffrey R.; Gevenois, Pierre Alain; Coxson, Harvey O.; Hoffman, Eric A.; Newell, John D.; Pistolesi, Massimo; Silverman, Edwin K.; Crapo, James D.

2015-01-01

The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis. © RSNA, 2015 PMID:25961632

[Impaired lung function in patients with moderate chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2004-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, RV, Raw, Rin, Rex, DLCO-SS, paO2 and paCO2 were determined in 22 patients with moderate chronic obstructive bronchitis (FEV1, 79-50% of the normal value). All the patients were found to have impaired bronchial patency, 90.9% of the patients had lung volume and capacity changes; pulmonary gas exchange dysfunction was present in 72.7%. Bronchial patency impairments were manifested by a decrease in FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, and an increase in Raw, Rin, Rex. Changes in the lung volumes and capacities appeared as higher RV, TGV, TLC, lower VC and FVC. Pulmonary gas exchange dysfunction showed up as a reduction in pO2 and DLCO-SS a reduction and an increase in paCO2. The magnitude of the functional changes observed in most patients was low. Significant and pronounced disorders were seen in one third of the patients.

Reducing Disparities in the Quality of Advance Care Planning for Older Adults

ClinicalTrials.gov

2018-05-07

Metastatic Cancer; Congestive Heart Failure; Chronic Obstructive Pulmonary Disease; Parkinson Disease; Interstitial Lung Disease; Amyotrophic Lateral Sclerosis; End Stage Liver Disease; End Stage Renal Disease; Diabetes Complications

Surveillance of chronic obstructive pulmonary disease in high-risk individuals by using regional lung cancer mass screening.

PubMed

Sekine, Yasuo; Yanagibori, Ryoko; Suzuki, Kiminori; Sugiyama, Sonomi; Yamaji, Haruko; Ishibashi, Michiko; Fujisawa, Takehiko

2014-01-01

Patients with chronic obstructive pulmonary disease (COPD) are at risk for lung cancer; the diseases have common etiologies, including cigarette smoking. We aimed to clarify the effectiveness of COPD detection using a regional mass-screening program for lung cancer. A total of 7,067 residents of Togane, Chiba, Japan received lung cancer screening between May and July, 2011. We defined four groups of possible COPD candidates: group A (n=358), positive smoking history, positive chronic respiratory symptoms; group B (n=766), positive smoking history, positive lifestyle-related disease; group C (n=75), passive smoking history, positive chronic respiratory symptoms; and group D (n=301), passive smoking history, positive lifestyle-related disease. Candidates underwent on-site pulmonary function testing (PFT). The criteria for COPD candidates were fulfilled in 1,686 of 7,067 individuals (23.9%); 1,500 participants underwent PFT (89%), and 171 (11.4%) were diagnosed with COPD. The overall COPD detection rate was 2.4%. The frequency of COPD was significantly higher in groups A and B than in groups C and D (P=0.048); however, the distribution of COPD grades was similar among the groups (P=0.372). Multiple logistic regression analysis identified male sex, age 60 years or greater, and positive smoking history as risk factors for COPD. COPD screening using a community-based lung cancer-screening program may be effective for disease detection. Individuals who are 60 years of age or older with a positive smoking history should undergo PFT to detect COPD.

Stem cell therapy: the great promise in lung disease.

PubMed

Siniscalco, Dario; Sullo, Nikol; Maione, Sabatino; Rossi, Francesco; D'Agostino, Bruno

2008-06-01

Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and destruction of the normal lung architecture, have essentially symptomatic treatments and their management is costly to the health care system.Regeneration of tissue by stem cells from endogenous, exogenous, and even genetically modified cells is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation.

Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

PubMed

Stone, Ian S; Barnes, Neil C; James, Wai-Yee; Midwinter, Dawn; Boubertakh, Redha; Follows, Richard; John, Leonette; Petersen, Steffen E

2016-04-01

Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

Computational modeling of the obstructive lung diseases asthma and COPD

PubMed Central

2014-01-01

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow limitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling. There is an urgent need for improved diagnosis and assessment of obstructive lung diseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods. Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the current state-of-the-art in techniques developed for pulmonary image analysis, development of structural models of the respiratory system and predictions of function within these models. We discuss application of modeling techniques to obstructive lung diseases, namely asthma and emphysema and the use of models to predict response to therapy. Finally we introduce a large European project, AirPROM that is developing multiscale models to investigate structure-function relationships in asthma and COPD. PMID:25471125

Traveling with breathing problems

MedlinePlus

... obstructive lung disease - travel; Chronic bronchitis - travel; Emphysema - travel ... you: Are short of breath most of the time Get short of breath ... doctor if you plan to travel in a place at a high altitude (such ...

The Effect of Lt to Rt Shunt Using Veno-veno-arterial Extracorporeal Membrane Oxygenation (ECMO) on Coronary Oxygenation in Lung Transplantation Patients

ClinicalTrials.gov

2016-08-03

Interstitial Pulmonary Fibrosis ARDS; COPD (Chronic Obstructive Pulmonary Disease); Bronchiectasis; Lymphangioleiomyomatosis; Primary Pulmonary Hypertension; ARDS (Acute Respiratory Distress Syndrome)

COPD and other health problems

MedlinePlus

... 105. Global Initiative for Chronic Obstructive Lung Disease (GOLD) website. Global strategy for the diagnosis, management, and ... report. goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS. ...

Epithelial and endothelial cell plasticity in chronic obstructive pulmonary disease (COPD).

PubMed

Sohal, Sukhwinder Singh

2017-03-01

Chronic Obstructive Pulmonary Disease (COPD) is mainly caused by smoking and presents with shortness of breath that is progressive and irreversible. It is a worldwide health problem and the fourth most common cause of chronic disability and mortality (even in developed countries). It is a complex disease involving both the airway and lung parenchyma. Small-airway fibrosis is the main contributor to physiological airway dysfunction in COPD. One potential mechanism contributing to small-airway fibrosis is epithelial mesenchymal transition (EMT). When associated with angiogenesis (EMT-type-3), EMT may well also be linked to the development of airway epithelial cancer, which is closely associated with COPD and predominantly observed in large airways. Vascular remodeling has also been widely reported in smokers and patients with COPD but the mechanisms behind it are poorly understood. It is quite possible that the process of endothelial to mesenchymal transition (EndMT) is also active in COPD lungs, in addition to EMT. Understanding these pathological mechanisms will greatly enhance our knowledge of the immunopathology of smoking-related lung disease. Only by understanding these processes can new therapies be developed. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Is Chronic Obstructive Pulmonary Disease an Accelerated Aging Disease?

PubMed

MacNee, William

2016-12-01

Aging is one of the most important risk factors for most chronic diseases. The worldwide increase in life expectancy has been accompanied by an increase in the prevalence of age-related diseases that result in significant morbidity and mortality and place an enormous burden on healthcare and resources. Aging is a progressive degeneration of the tissues that has a negative impact on the structure and function of vital organs. The lung ages, resulting in decreased function and reduced capacity to respond to environmental stresses and injury. Many of the changes that occur in the lungs with normal aging, such as decline in lung function, increased gas trapping, loss of lung elastic recoil, and enlargement of the distal air spaces, also are present in chronic obstructive pulmonary disease (COPD). The prevalence of COPD is two to three times higher in people over the age of 60 years than in younger age groups. Indeed, COPD has been considered a condition of accelerated lung aging. Several mechanisms associated with aging are present in the lungs of patients with COPD. Cell senescence is present in emphysematous lungs and is associated with shortened telomeres and decreased antiaging molecules, suggesting accelerated aging in the lungs of patients with COPD. Increasing age leads to elevated basal levels of inflammation and oxidative stress (inflammaging) and to increased immunosenescence associated with changes in both the innate and adaptive immune responses. These changes are similar to those that occur in COPD and may enhance the activity of the disease as well as increase susceptibility to exacerbations in patients with COPD. Understanding the mechanism of age-related changes in COPD may identify novel therapies for this condition.

Use of the Draeger Apollo to Deliver Bilevel Positive Pressure Ventilation During Awake Frontal Craniotomy for a Patient with Severe Chronic Obstructive Pulmonary Disease.

PubMed

Lee, Susie So-Hyun; Berman, Mitchell F

2015-12-01

In this case report, we describe the use of the Draeger Apollo anesthesia machine to deliver bilevel positive airway pressure (BiPAP) to a patient with severe chronic obstructive pulmonary disease and a history of lung resection undergoing frontal craniotomy for the removal of a brain tumor under moderate to deep sedation. BiPAP in the perioperative period has been described for purposes of preoxygenation and postextubation recruitment. Although its utility as a mode of ventilation during moderate to deep sedation has been demonstrated, it has not come into widespread use. We describe the intraoperative use of pressure support mode on the anesthesia machine to deliver noninvasive positive pressure ventilation through a standard anesthesia mask. Given its ease of access and effectiveness, it is our belief that intraoperative BiPAP may reduce hypoxemia and/or hypercarbia in patients with chronic obstructive pulmonary disease and obstructive sleep apnea undergoing moderate to deep sedation.

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

PubMed

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

2017-03-15

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

Imaging and imagining chronic obstructive pulmonary disease (COPD): Uruguayans draw their lungs.

PubMed

Wainwright, Megan

2017-09-11

This anthropological study investigated what people imagined chronic obstructive pulmonary disease to look like in their lungs, what may be influencing these images and how this imagery shapes embodiment. Employing graphic elicitation, in one of multiple ethnographic interviews, participants were asked to draw their lungs: "If we could look inside your chest now, what would we see?" Lung drawings and accompanying narratives and fieldnotes from 14 participants were analyzed for themes and patterns. The theme of "imaging/imagining" emerged and three distinct patterns within this theme were identified: the microscope perspective, the X-ray perspective and the reduced pulmonary capacity perspective. These patterns demonstrate how embodiment can be shaped by an integration and reinterpretation of the medical images that form part of everyday clinic visits and pulmonary rehabilitation. Medical technology and images impact patients' embodiment. Understanding this is important for rehabilitation practitioners who work in a challenging space created by potentially conflicting medical narratives: on the one hand, chronic obstructive pulmonary disease is incurable permanent damage, and on the other, improvement is possible through rehabilitation. Drawing could be integrated into pulmonary rehabilitation and may help identify perceptions of the body that could hinder the rehabilitation process. Implications for rehabilitation Drawings, when combined with interviews, can lead to a deeper and more complex understanding of patients' perspectives and embodiment. Rehabilitation practitioners should be concerned with how patients embody the medical technology and imagery they are exposed to as part of the educational component of pulmonary rehabilitation and healthcare generally. Asking patients to visualize their illness through drawing may help pulmonary rehabilitation practitioners identify perceptions of the body which could hinder the patient's ability to reap the full benefit of their treatment.

Cathepsin E Promotes Pulmonary Emphysema via Mitochondrial Fission

PubMed Central

Zhang, Xuchen; Shan, Peiying; Homer, Robert; Zhang, Yi; Petrache, Irina; Mannam, Praveen; Lee, Patty J.

2015-01-01

Emphysema is characterized by loss of lung elasticity and irreversible air space enlargement, usually in the later decades of life. The molecular mechanisms of emphysema remain poorly defined. We identified a role for a novel cathepsin, cathepsin E, in promoting emphysema by inducing mitochondrial fission. Unlike previously reported cysteine cathepsins, which have been implicated in cigarette smoke-induced lung disease, cathepsin E is a nonlysosomal intracellular aspartic protease whose function has been described only in antigen processing. We examined lung tissue sections of persons with chronic obstructive pulmonary disease, a clinical entity that includes emphysematous change. Human chronic obstructive pulmonary disease lungs had markedly increased cathepsin E protein in the lung epithelium. We generated lung epithelial-targeted transgenic cathepsin E mice and found that they develop emphysema. Overexpression of cathepsin E resulted in increased E3 ubiquitin ligase parkin, mitochondrial fission protein dynamin-related protein 1, caspase activation/apoptosis, and ultimately loss of lung parenchyma resembling emphysema. Inhibiting dynamin-related protein 1, using a small molecule inhibitor in vitro or in vivo, inhibited cathepsin E-induced apoptosis and emphysema. To the best of our knowledge, our study is the first to identify links between cathepsin E, mitochondrial fission, and caspase activation/apoptosis in the pathogenesis of pulmonary emphysema. Our data expand the current understanding of molecular mechanisms of emphysema development and may provide new therapeutic targets. PMID:25239563

Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: a review.

PubMed

Razavi, Seyed-Mansour; Ghanei, Mostafa; Salamati, Payman; Safiabadi, Mehdi

2013-01-01

To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and Irandoc sites were searched. We accepted articles published in scientific journals as a quality criterion.The main pathogenic factors are free radical mediators. Prevalence of pulmonary involvement is approximately 42.5%. The most common complaints are cough and dyspnea. Major respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, and asthma. Spirometry results can reveal restrictive and obstructive pulmonary disease. Plain chest X-ray does not help in about 50% of lung diseases. High-resolution CT of the lung is the best modality for diagnostic assessment of parenchymal lung and bronchi. There is no definite curative treatment for mustard lung. The effective treatment regimens consist of oxygen administration, use of vaporized moist air, respiratory physiotherapy, administration of mucolytic agents, bronchodilators, corticosteroids, and long-acting beta-2 agonists, antioxidants, surfactant, magnesium ions, therapeutic bronchoscopy, laser therapy, placement of respiratory stents, early tracheostomy in laryngospasm, and ultimately lung transplantation. High-resolution CT of the lung is the most accurate modality for the evaluation of the lung parenchyma and bronchi. The treatment efficacy of patients exposed to mustard gas depends on patient conditions (acute or chronic, upper or lower respiratory tract involvement). There are various treatment protocols, but unfortunately none of them is definitely curable.

Classification of Chronic Obstructive Pulmonary Disease (COPD) according to the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017: Comparison with GOLD 2011.

PubMed

Marçôa, Raquel; Rodrigues, Daniela Marta; Dias, Margarida; Ladeira, Inês; Vaz, Ana Paula; Lima, Ricardo; Guimarães, Miguel

2018-02-01

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality worldwide. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) project has been working to improve awareness, prevention and management of this disease. The aim of this study is to evaluate how COPD patients are reclassified by the 2017 GOLD system (versus GOLD 2011), to calculate the level of agreement between these two classifications in allocation to categories and to compare the performance of each classification to predict future exacerbations. Two-hundred COPD patients (>40 years, post bronchodilator forced expiratory volume in one second/forced vital capacity<0.7) followed in pulmonology consultation were recruited into this prospective multicentric study. Approximately half of the patients classified as GOLD D [2011] changed to GOLD B [2017]. The extent of agreement between GOLD 2011 and GOLD 2017 was moderate (Cohen's Kappa = 0.511; p < 0.001) and the ability to predict exacerbations was similar (69.7% and 67.6%, respectively). GOLD B [2017] exacerbated 17% more than GOLD B [2011] and had a lower percent predicted post bronchodilator forced expiratory volume in one second (FEV1). GOLD B [2017] turned to be the predominant category, more heterogeneous and with a higher risk of exacerbation versus GOLD B [2011]. Physicians should be cautious in assessing the GOLD B [2017] patients. The assessment of patients should always be personalized. More studies are needed to evaluate the impact of the 2017 reclassification in predicting outcomes such as future exacerbations and mortality.

Integrated Genomics Reveals Convergent Transcriptomic Networks Underlying Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.

PubMed

Kusko, Rebecca L; Brothers, John F; Tedrow, John; Pandit, Kusum; Huleihel, Luai; Perdomo, Catalina; Liu, Gang; Juan-Guardela, Brenda; Kass, Daniel; Zhang, Sherry; Lenburg, Marc; Martinez, Fernando; Quackenbush, John; Sciurba, Frank; Limper, Andrew; Geraci, Mark; Yang, Ivana; Schwartz, David A; Beane, Jennifer; Spira, Avrum; Kaminski, Naftali

2016-10-15

Despite shared environmental exposures, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease are usually studied in isolation, and the presence of shared molecular mechanisms is unknown. We applied an integrative genomic approach to identify convergent transcriptomic pathways in emphysema and IPF. We defined the transcriptional repertoire of chronic obstructive pulmonary disease, IPF, or normal histology lungs using RNA-seq (n = 87). Genes increased in both emphysema and IPF relative to control were enriched for the p53/hypoxia pathway, a finding confirmed in an independent cohort using both gene expression arrays and the nCounter Analysis System (n = 193). Immunohistochemistry confirmed overexpression of HIF1A, MDM2, and NFKBIB members of this pathway in tissues from patients with emphysema or IPF. Using reads aligned across splice junctions, we determined that alternative splicing of p53/hypoxia pathway-associated molecules NUMB and PDGFA occurred more frequently in IPF or emphysema compared with control and validated these findings by quantitative polymerase chain reaction and the nCounter Analysis System on an independent sample set (n = 193). Finally, by integrating parallel microRNA and mRNA-Seq data on the same samples, we identified MIR96 as a key novel regulatory hub in the p53/hypoxia gene-expression network and confirmed that modulation of MIR96 in vitro recapitulates the disease-associated gene-expression network. Our results suggest convergent transcriptional regulatory hubs in diseases as varied phenotypically as chronic obstructive pulmonary disease and IPF and suggest that these hubs may represent shared key responses of the lung to environmental stresses.

Physical inactivity and obesity: relation to asthma and chronic obstructive pulmonary disease?

PubMed

ten Hacken, Nick H T

2009-12-01

Physical inactivity and obesity are modifiable risk factors for many chronic diseases, including cardiovascular disease, diabetes mellitus, osteoporosis, osteoarthritis, and depression. Both physical inactivity and obesity are associated with low-grade systemic inflammation that may contribute to the inflammatory processes present in many chronic diseases. In asthma, almost no studies are available in which physical inactivity has been studied using performance-based instruments. In contrast, the association between obesity and a higher prevalence of asthma has often been suggested in a large number of studies. In chronic obstructive pulmonary disease (COPD) physical inactivity has been demonstrated in a few studies that used performance-based instruments; this was associated with the higher COPD Global Initiative on Obstructive Lung Disease (GOLD) stages and a higher degree of systemic inflammation, independent of body mass index. In contrast to physical inactivity, obesity in COPD is associated with the lower GOLD stages. Additionally, obesity is associated with the chronic obstructive phenotype and features of the metabolic syndrome. To elucidate the independent relation of physical inactivity and obesity with systemic inflammation, performance-based studies of physical inactivity in asthma and COPD are highly needed.

Using oxygen at home - what to ask your doctor

MedlinePlus

... my house? What should I do in a restaurant or bar? Can my oxygen be in the ... Bronchiolitis Bronchitis - acute Chronic obstructive pulmonary disease Lung surgery Pneumonia - adults (community acquired) Patient Instructions Bronchiolitis - discharge ...

Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systemic review and meta-analysis.

PubMed

Ni, Yingmeng; Shi, Guochao; Yu, Youchao; Hao, Jimin; Chen, Tiantian; Song, Huihui

2015-01-01

In the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD. The present meta-analysis was aimed at summarizing the impact of bronchiectasis on patients with COPD. Databases including Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched comprehensively to identify all relevant human clinical studies published until August 2014. Bronchiectasis was confirmed either by computed tomography or high-resolution computed tomography. One or more clinicopathological or demographical characteristics, including age, sex, smoking history, daily sputum production, exacerbations, inflammatory biomarkers, lung function, and colonization by potentially pathogenic microorganisms (PPMs), were compared between COPD patients with and without bronchiectasis. Six observational studies with 881 patients were included in the meta-analysis. The mean prevalence of bronchiectasis in patients with COPD was 54.3%, ranging from 25.6% to 69%. Coexistence of bronchiectasis and COPD occurred more often in male patients with longer smoking history. Patients with COPD and comorbid bronchiectasis had greater daily sputum production, more frequent exacerbation, poorer lung function, higher level of inflammatory biomarkers, more chronic colonization by PPMs, and higher rate of Pseudomonas aeruginosa isolation. In spite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of bronchiectasis in patients with COPD in all directions, indicating that coexistence of bronchiectasis should be considered a pathological phenotype of COPD, which may have a predictive value.

Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced lung injury.

PubMed

Lange, Matthias; Cox, Robert A; Enkhbaatar, Perenlei; Whorton, Elbert B; Nakano, Yoshimitsu; Hamahata, Atsumori; Jonkam, Collette; Esechie, Aimalohi; von Borzyskowski, Sanna; Traber, Lillian D; Traber, Daniel L

2011-05-01

Inhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, lung lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, lung lymph flow, and lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.

Cytotoxic potential of lung CD8(+) T cells increases with chronic obstructive pulmonary disease severity and with in vitro stimulation by IL-18 or IL-15.

PubMed

Freeman, Christine M; Han, MeiLan K; Martinez, Fernando J; Murray, Susan; Liu, Lyrica X; Chensue, Stephen W; Polak, Timothy J; Sonstein, Joanne; Todt, Jill C; Ames, Theresa M; Arenberg, Douglas A; Meldrum, Catherine A; Getty, Christi; McCloskey, Lisa; Curtis, Jeffrey L

2010-06-01

Lung CD8(+) T cells might contribute to progression of chronic obstructive pulmonary disease (COPD) indirectly via IFN-gamma production or directly via cytolysis, but evidence for either mechanism is largely circumstantial. To gain insights into these potential mechanisms, we analyzed clinically indicated lung resections from three human cohorts, correlating findings with spirometrically defined disease severity. Expression by lung CD8(+) T cells of IL-18R and CD69 correlated with severity, as did mRNA transcripts for perforin and granzyme B, but not Fas ligand. These correlations persisted after correction for age, smoking history, presence of lung cancer, recent respiratory infection, or inhaled corticosteroid use. Analysis of transcripts for killer cell lectin-like receptor G1, IL-7R, and CD57 implied that lung CD8(+) T cells in COPD do not belong to the terminally differentiated effector populations associated with chronic infections or extreme age. In vitro stimulation of lung CD8(+) T cells with IL-18 plus IL-12 markedly increased production of IFN-gamma and TNF-alpha, whereas IL-15 stimulation induced increased intracellular perforin expression. Both IL-15 and IL-18 protein expression could be measured in whole lung tissue homogenates, but neither correlated in concentration with spirometric severity. Although lung CD8(+) T cell expression of mRNA for both T-box transcription factor expressed in T cells and GATA-binding protein 3 (but not retinoic acid receptor-related orphan receptor gamma or alpha) increased with spirometric severity, stimulation of lung CD8(+) T cells via CD3epsilon-induced secretion of IFN-gamma, TNF-alpha, and GM-CSF, but not IL-5, IL-13, and IL-17A. These findings suggest that the production of proinflammatory cytokines and cytotoxic molecules by lung-resident CD8(+) T cells contributes to COPD pathogenesis.

Upper lobe fibrosis: a novel manifestation of chronic allograft dysfunction in lung transplantation.

PubMed

Pakhale, Smita Sakha; Hadjiliadis, Denis; Howell, David N; Palmer, Scott M; Gutierrez, Carlos; Waddell, Thomas K; Chaparro, Cecilia; Davis, R Duane; Keshavjee, Shaf; Hutcheon, Michael A; Singer, Lianne G

2005-09-01

Lung transplantation is an established treatment modality for a number of chronic lung diseases. Long-term survival after lung transplantation is limited by chronic allograft dysfunction, usually manifested by bronchiolitis obliterans syndrome. We describe a case series with upper lobe fibrosis, a novel presentation of chronic allograft dysfunction. We reviewed lung transplants at the Toronto General Hospital and Duke University Hospital from 1990 to 2002 and identified patients with upper lobe fibrosis. Thirteen of 686 patients (6 women) developed upper lobe fibrosis (Toronto, 9; Duke, 4); 12 of 13 had bilateral transplants. The median age at diagnosis was 42 years (range, 19-70). Primary diagnoses were cystic fibrosis, 6; emphysema, 4; sarcoidosis, 1; and pulmonary fibrosis, 2 patients. Radiographic diagnosis was made at a median of 700 days post-transplant (range, 150-2,920). Pulmonary function tests demonstrated predominantly a progressively worsening restrictive pattern. Open lung biopsy specimens revealed dense interstitial fibrosis, with occasional features of obliterative bronchitis, bronchiolitis obliterans obstructive pneumonia, and aspiration. Nine patients died at a median follow-up of 2,310 days (range, 266-3,740), 8 due to respiratory failure. Upper lobe fibrosis is a novel presentation of chronic allograft dysfunction in lung transplant recipients and is differentiated from bronchiolitis obliterans syndrome on the basis of physiologic and radiologic findings.

Marijuana and lung diseases.

PubMed

Joshi, Manish; Joshi, Anita; Bartter, Thaddeus

2014-03-01

Cannabis sativa (marijuana) is used throughout the world, and its use is increasing. In much of the world, marijuana is illicit. While inhalation of smoke generated by igniting dried components of the plant is the most common way marijuana is used, there is concern over potential adverse lung effects. The purpose of this review is to highlight recent studies that explore the impact upon the respiratory system of inhaling marijuana smoke. Smoking marijuana is associated with chronic bronchitis symptoms and large airway inflammation. Occasional use of marijuana with low cumulative use is not a risk factor for the development of chronic obstructive pulmonary disease. The heavy use of marijuana alone may lead to airflow obstruction. The immuno-histopathologic and epidemiologic evidence in marijuana users suggests biological plausibility of marijuana smoking as a risk for the development of lung cancer; at present, it has been difficult to conclusively link marijuana smoking and cancer development. There is unequivocal evidence that habitual or regular marijuana smoking is not harmless. A caution against regular heavy marijuana usage is prudent. The medicinal use of marijuana is likely not harmful to lungs in low cumulative doses, but the dose limit needs to be defined. Recreational use is not the same as medicinal use and should be discouraged.

Pathogenesis of hyperinflation in chronic obstructive pulmonary disease

PubMed Central

Gagnon, Philippe; Guenette, Jordan A; Langer, Daniel; Laviolette, Louis; Mainguy, Vincent; Maltais, François; Ribeiro, Fernanda; Saey, Didier

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease. PMID:24600216

Lung cancer in patients with chronic obstructive pulmonary disease. Development and validation of the COPD Lung Cancer Screening Score.

PubMed

de-Torres, Juan P; Wilson, David O; Sanchez-Salcedo, Pablo; Weissfeld, Joel L; Berto, Juan; Campo, Arantzazu; Alcaide, Ana B; García-Granero, Marta; Celli, Bartolome R; Zulueta, Javier J

2015-02-01

Patients with chronic obstructive pulmonary disease (COPD) are at high risk for lung cancer (LC) and represent a potential target to improve the diagnostic yield of screening programs. To develop a predictive score for LC risk for patients with COPD. The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) and the Pittsburgh Lung Screening Study (PLuSS) databases were analyzed. Only patients with COPD on spirometry were included. By logistic regression we determined which factors were independently associated with LC in PLuSS and developed a COPD LC screening score (COPD-LUCSS) to be validated in P-IELCAP. By regression analysis, age greater than 60, body mass index less than 25 kg/m(2), pack-years history greater than 60, and emphysema presence were independently associated with LC diagnosis and integrated into the COPD-LUCSS, which ranges from 0 to 10 points. Two COPD-LUCSS risk categories were proposed: low risk (scores 0-6) and high risk (scores 7-10). In comparison with low-risk patients, in both cohorts LC risk increased 3.5-fold in the high-risk category. The COPD-LUCSS is a good predictor of LC risk in patients with COPD participating in LC screening programs. Validation in two different populations adds strength to the findings.

Identification of Oxidative Stress Related Proteins as Biomarkers for Lung Cancer and Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage

PubMed Central

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L.; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-01-01

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis. PMID:23389041

Identification of oxidative stress related proteins as biomarkers for lung cancer and chronic obstructive pulmonary disease in bronchoalveolar lavage.

PubMed

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-02-06

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.

Using of laser spectroscopy and chemometrics methods for identification of patients with lung cancer, patients with COPD and healthy people from absorption spectra of exhaled air

NASA Astrophysics Data System (ADS)

Bukreeva, Ekaterina B.; Bulanova, Anna A.; Kistenev, Yury V.; Kuzmin, Dmitry A.; Nikiforova, Olga Yu.; Ponomarev, Yurii N.; Tuzikov, Sergei A.; Yumov, Evgeny L.

2014-11-01

The results of application of the joint use of laser photoacoustic spectroscopy and chemometrics methods in gas analysis of exhaled air of patients with chronic respiratory diseases (chronic obstructive pulmonary disease and lung cancer) are presented. The absorption spectra of exhaled breath of representatives of the target groups and healthy volunteers were measured; the selection by chemometrics methods of the most informative absorption coefficients in scan spectra in terms of the separation investigated nosology was implemented.

[Increased risk of chronic obstructive pulmonary disease among tunnel construction workers].

PubMed

Ulvestad, Bente; Lund, May Brit

2003-08-28

As tunnel workers are exposed to particles from drilling, blasting and diesel exhaust, we aimed to assess the occurrence of respiratory symptoms and lung function decline in underground construction workers and relate these findings to exposure. 212 tunnel workers and a reference group of 205 outdoor construction workers participated in a cross-sectional study. Respiratory symptoms and lung function were studied in relation to exposure. A subgroup of 29 non-smoking concrete workers who had been exposed to tunnel environment for one year, were examined by acoustic rhinometry, exhaled NO, spirometry and a questionnaire. Finally 122 tunnel workers were included in a prospective study in 1991 and re-examined in 1999. Among the tunnel workers the prevalence of chronic obstructive pulmonary disease (COPD) was 14% vs. 8% in the reference subjects. Compared to the reference subjects, the tunnel workers had a significant decrease in FEV1, related to years of exposure. Concrete workers from the tunnel site had significantly increased exhaled NO levels and nasal mucosal swelling compared to subjects who had performed similar tasks outdoors. The decrease in FEV1 was associated with cumulative exposure to respirable dust and quartz. Inhalation of construction-generated dust and gases enhances the risk of chronic obstructive pulmonary disease in tunnel workers.

Influence of lung function on course of disease and response to antibiotic therapy in adult primary care patients with acute cough: a post hoc analysis of patients enrolled in a prospective multicentre study.

PubMed

van Erp, Nicole; Little, Paul; Stuart, Beth; Moore, Michael; Thomas, Mike; Butler, Chris C; Hood, Kerenza; Coenen, Samuel; Goossens, Herman; Leven, Margareta; Verheij, Theo J M

2014-09-25

In acute cough patients, impaired lung function as present in chronic lung conditions like asthma and chronic obstructive pulmonary disease (COPD) are often thought to negatively influence course of disease, but clear evidence is lacking. To investigate the influence of lung function abnormalities on course of disease and response to antibiotic therapy in primary care patients with acute cough. A total of 3,104 patients with acute cough (⩽28 days) were included in a prospective observational study with a within-nested trial, of which 2,427 underwent spirometry 28-35 days after inclusion. Influence of the lung function abnormalities fixed obstruction (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7) and bronchodilator responsiveness (FEV1 increase of ⩾12% or 200 ml after 400 μg salbutamol) on symptom severity, duration and worsening were evaluated using uni- and multivariable regression models. Antibiotic use was defined as the reported use of antibiotics ⩾5 days in the first week. Interaction terms were calculated to investigate modifying effects of lung function on antibiotic effect. The only significant association was the effect of severe airway obstruction on symptom severity on days 2-4 (difference=0.31, 95% confidence interval (CI)=0.03-0.60, P=0.03). No evidence of a differential effect of lung function on the effect of antibiotics was found. Prior use of inhaled steroids was associated with a 30% slower resolution of symptoms rated 'moderately bad' or worse (hazard ratio=0.75, 95% CI=0.63-0.90, P=0.00). In adult patients with acute cough, lung function abnormalities were neither significantly associated with course of disease nor did they modify the effect of antibiotics.

Updates in the management of stable chronic obstructive pulmonary disease.

PubMed

Narsingam, Saiprasad; Bozarth, Andrew L; Abdeljalil, Asem

2015-01-01

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease state characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory process. It is increasingly recognized as a major public health problem, affecting more than 20 million adults in the US. It is also recognized as a leading cause of hospitalizations and is the fourth leading cause of death in the US. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) operates to promote evidence-based management of COPD, increase awareness and encourage research. In 2011, GOLD published a consensus report detailing evidence-based management strategies for COPD, which were last updated in 2015. In recent years, newer strategies and a growing number of new pharmacologic agents to treat symptoms of COPD have also been introduced and show promise in improving the management of COPD. We aim to provide an evidence-based review of the available and upcoming pharmacologic and non-pharmacologic treatment options for stable COPD, with continued emphasis on evidence-based management.

General practice variation in spirometry testing among patients receiving first-time prescriptions for medication targeting obstructive lung disease in Denmark: a population-based observational study

PubMed Central

2013-01-01

Background Spirometry testing is essential to confirm an obstructive lung disease, but studies have reported that a large proportion of patients diagnosed with COPD or asthma have no history of spirometry testing. Also, it has been shown that many patients are prescribed medication for obstructive lung disease without a relevant diagnosis or spirometry test registered. General practice characteristics have been reported to influence diagnosis and management of several chronic diseases. However, these findings are inconsistent, and it is uncertain whether practice characteristics influence spirometry testing among patients receiving medication for obstructive lung disease. The aim of this study was therefore to examine if practice characteristics are associated with spirometry testing among patients receiving first-time prescriptions for medication targeting obstructive lung disease. Methods A national register-based cohort study was performed. All patients over 18 years receiving first-time prescriptions for medication targeting obstructive lung disease in 2008 were identified and detailed patient-specific data on sociodemographic status and spirometry tests were extracted. Information on practice characteristics like number of doctors, number of patients per doctor, training practice status, as well as age and gender of the general practitioners was linked to each medication user. Results Partnership practices had a higher odds ratio (OR) of performing spirometry compared with single-handed practices (OR 1.24, CI 1.09-1.40). We found a significant association between increasing general practitioner age and decreasing spirometry testing. This tendency was most pronounced among partnership practices, where doctors over 65 years had the lowest odds of spirometry testing (OR 0.25, CI 0.10-0.61). Training practice status was significantly associated with spirometry testing among single-handed practices (OR 1.40, CI 1.10-1.79). Conclusion Some of the variation in spirometry testing among patients receiving first-time prescriptions for medication targeting obstructive lung disease was associated with practice characteristics. This variation in performance may indicate a potential for quality improvement. PMID:23923987

Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction

PubMed Central

Marcos, Veronica; Zhou-Suckow, Zhe; Önder Yildirim, Ali; Bohla, Alexander; Hector, Andreas; Vitkov, Ljubomir; Krautgartner, Wolf Dietrich; Stoiber, Walter; Griese, Matthias; Eickelberg, Oliver; Mall, Marcus A.; Hartl, Dominik

2015-01-01

Chronic obstructive lung disease determines morbidity and mortality of patients with cystic fibrosis (CF). CF airways are characterized by a nonresolving neutrophilic inflammation. After pathogen contact or prolonged activation, neutrophils release DNA fibres decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). NETs have been described to act in a beneficial way for innate host defense by bactericidal, fungicidal, and virucidal actions. On the other hand, excessive NET formation has been linked to the pathogenesis of autoinflammatory and autoimmune disease conditions. We quantified free DNA structures characteristic of NETs in airway fluids of CF patients and a mouse model with CF-like lung disease. Free DNA levels correlated with airflow obstruction, fungal colonization, and CXC chemokine levels in CF patients and CF-like mice. When viewed in combination, our results demonstrate that neutrophilic inflammation in CF airways is associated with abundant free DNA characteristic for NETosis, and suggest that free DNA may be implicated in lung function decline in patients with CF. PMID:25918476

Crosstalk between beta-2-adrenoceptor and muscarinic acetylcholine receptors in the airway.

PubMed

Pera, Tonio; Penn, Raymond B

2014-06-01

The M3 and M2 muscarinic acetylcholine receptors (mAChRs) and beta-2-adrenoceptors (β2ARs) are important regulators of airway cell function, and drugs targeting these receptors are among the first line drugs in the treatment of the obstructive lung diseases asthma and chronic obstructive lung disease (COPD). Cross-regulation or crosstalk between mAChRs and β2ARs in airway smooth muscle (ASM) helps determine the contractile state of the muscle, thus airway diameter and resistance to airflow. In this review we will detail mAChR and β2AR-signaling and crosstalk, focusing on events in the ASM cell but also addressing the function of these receptors in other cell types that impact airway physiology. We conclude by discussing how recent advances in GPCR pharmacology offer a unique opportunity to fine tune mAChR and β2AR signaling and their crosstalk, and thereby produce superior therapeutics for obstructive lung and other diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Randomised Vitamin E Supplementation and Risk of Chronic Lung Disease in the Women’s Health Study

PubMed Central

Agler, Anne H.; Kurth, Tobias; Gaziano, J. Michael; Buring, Julie E.; Cassano, Patricia A.

2011-01-01

Background The oxidant/antioxidant balance in lung tissue is hypothesised to contribute to chronic obstructive pulmonary disease (COPD) risk. Observational studies consistently report higher antioxidant status associated with lower COPD risk, but few randomised studies have been reported. Methods A post-hoc analysis of 38,597 women without chronic lung disease at baseline was conducted in the Women’s Health Study (WHS) to test the effect of vitamin E on risk of incident chronic lung disease. The WHS was a randomised, double-blind, placebo-controlled, factorial trial of vitamin E (600 IU every other day) and aspirin (100 mg every other day) in female health professionals aged ≥45. Using Cox proportional hazards models, the effect of randomised vitamin E assignment on self-reported, physician-diagnosed chronic lung disease was evaluated. Results During 10 years of follow-up (376,710 person-years), 760 first occurrences of chronic lung disease were reported in the vitamin E arm compared to 846 in the placebo arm (Hazard Ratio [HR] 0.90; 95% confidence interval [CI] 0.81–0.99; p=0.029). This 10% reduction in the risk of incident chronic lung disease was not modified by cigarette smoking, age, randomised aspirin assignment, multivitamin use, or dietary vitamin E intake (minimum P for interaction = 0.19). Current cigarette smoking was a strong predictor of chronic lung disease risk (HR 4.17; 95% CI 3.70–4.70; versus never smokers). Conclusions In this large, randomised trial, assignment to 600 IU of vitamin E led to a 10% reduction in the risk of chronic lung disease in women. PMID:21257986

Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.

PubMed

Zhu, Hai-Xing; Shi, Lin; Zhang, Yong; Zhu, Yi-Chun; Bai, Chun-Xue; Wang, Xiang-Dong; Zhou, Jie-Bai

2017-03-24

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis. Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement. Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.

Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology.

PubMed

Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

2015-02-01

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. © 2014 John Wiley & Sons Ltd.

Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology

PubMed Central

Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

2015-01-01

Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. PMID:25179236

Update on obstructive sleep apnea and its relation to COPD

PubMed Central

Mieczkowski, Brian; Ezzie, Michael E

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a common and preventable lung disease that affects millions of people in the United States. Sleep disorders including obstructive sleep apnea (OSA) are also common. It is not surprising that many people with COPD also suffer from OSA. This relationship, however, puts people at risk for more nocturnal desaturations and potential complications related to this, including pulmonary hypertension and heart rhythm disturbances. This update focuses on the physiology of sleep disturbances in COPD as well as the clinical implications of OSA in COPD. PMID:24748786

Identifying individuals with physician-diagnosed chronic obstructive pulmonary disease in primary care electronic medical records: a retrospective chart abstraction study.

PubMed

Lee, Theresa M; Tu, Karen; Wing, Laura L; Gershon, Andrea S

2017-05-15

Little is known about using electronic medical records to identify patients with chronic obstructive pulmonary disease to improve quality of care. Our objective was to develop electronic medical record algorithms that can accurately identify patients with obstructive pulmonary disease. A retrospective chart abstraction study was conducted on data from the Electronic Medical Record Administrative data Linked Database (EMRALD ® ) housed at the Institute for Clinical Evaluative Sciences. Abstracted charts provided the reference standard based on available physician-diagnoses, chronic obstructive pulmonary disease-specific medications, smoking history and pulmonary function testing. Chronic obstructive pulmonary disease electronic medical record algorithms using combinations of terminology in the cumulative patient profile (CPP; problem list/past medical history), physician billing codes (chronic bronchitis/emphysema/other chronic obstructive pulmonary disease), and prescriptions, were tested against the reference standard. Sensitivity, specificity, and positive/negative predictive values (PPV/NPV) were calculated. There were 364 patients with chronic obstructive pulmonary disease identified in a 5889 randomly sampled cohort aged ≥ 35 years (prevalence = 6.2%). The electronic medical record algorithm consisting of ≥ 3 physician billing codes for chronic obstructive pulmonary disease per year; documentation in the CPP; tiotropium prescription; or ipratropium (or its formulations) prescription and a chronic obstructive pulmonary disease billing code had sensitivity of 76.9% (95% CI:72.2-81.2), specificity of 99.7% (99.5-99.8), PPV of 93.6% (90.3-96.1), and NPV of 98.5% (98.1-98.8). Electronic medical record algorithms can accurately identify patients with chronic obstructive pulmonary disease in primary care records. They can be used to enable further studies in practice patterns and chronic obstructive pulmonary disease management in primary care. NOVEL ALGORITHM SEARCH TECHNIQUE: Researchers develop an algorithm that can accurately search through electronic health records to find patients with chronic lung disease. Mining population-wide data for information on patients diagnosed and treated with chronic obstructive pulmonary disease (COPD) in primary care could help inform future healthcare and spending practices. Theresa Lee at the University of Toronto, Canada, and colleagues used an algorithm to search electronic medical records and identify patients with COPD from doctors' notes, prescriptions and symptom histories. They carefully adjusted the algorithm to improve sensitivity and predictive value by adding details such as specific medications, physician codes related to COPD, and different combinations of terminology in doctors' notes. The team accurately identified 364 patients with COPD in a randomly-selected cohort of 5889 people. Their results suggest opportunities for broader, informative studies of COPD in wider populations.

Functional Image-Guided Radiotherapy Planning in Respiratory-Gated Intensity-Modulated Radiotherapy for Lung Cancer Patients With Chronic Obstructive Pulmonary Disease

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

Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp; Nishibuchi, Ikuno; Murakami, Yuji

2012-03-15

Purpose: To investigate the incorporation of functional lung image-derived low attenuation area (LAA) based on four-dimensional computed tomography (4D-CT) into respiratory-gated intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) in treatment planning for lung cancer patients with chronic obstructive pulmonary disease (COPD). Methods and Materials: Eight lung cancer patients with COPD were the subjects of this study. LAA was generated from 4D-CT data sets according to CT values of less than than -860 Hounsfield units (HU) as a threshold. The functional lung image was defined as the area where LAA was excluded from the image of the total lung.more » Two respiratory-gated radiotherapy plans (70 Gy/35 fractions) were designed and compared in each patient as follows: Plan A was an anatomical IMRT or VMAT plan based on the total lung; Plan F was a functional IMRT or VMAT plan based on the functional lung. Dosimetric parameters (percentage of total lung volume irradiated with {>=}20 Gy [V20], and mean dose of total lung [MLD]) of the two plans were compared. Results: V20 was lower in Plan F than in Plan A (mean 1.5%, p = 0.025 in IMRT, mean 1.6%, p = 0.044 in VMAT) achieved by a reduction in MLD (mean 0.23 Gy, p = 0.083 in IMRT, mean 0.5 Gy, p = 0.042 in VMAT). No differences were noted in target volume coverage and organ-at-risk doses. Conclusions: Functional IGRT planning based on LAA in respiratory-guided IMRT or VMAT appears to be effective in preserving a functional lung in lung cancer patients with COPD.« less

Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway

PubMed Central

Hwang, Jae-Woong; Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.; Rahman, Irfan

2014-01-01

Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100–300 mg/m3 particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 μM) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses.— Hwang, J.-W., Sundar, I. K., Yao, H., Sellix, M. T., Rahman, I. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. PMID:24025728

Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease.

PubMed

Sin, Don D; Miller, Bruce E; Duvoix, Annelyse; Man, S F Paul; Zhang, Xuekui; Silverman, Edwin K; Connett, John E; Anthonisen, Nicholas A; Wise, Robert A; Tashkin, Donald; Celli, Bartolome R; Edwards, Lisa D; Locantore, Nicholas; Macnee, William; Tal-Singer, Ruth; Lomas, David A

2011-05-01

There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD.

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

PubMed

Hobbs, Brian D; de Jong, Kim; Lamontagne, Maxime; Bossé, Yohan; Shrine, Nick; Artigas, María Soler; Wain, Louise V; Hall, Ian P; Jackson, Victoria E; Wyss, Annah B; London, Stephanie J; North, Kari E; Franceschini, Nora; Strachan, David P; Beaty, Terri H; Hokanson, John E; Crapo, James D; Castaldi, Peter J; Chase, Robert P; Bartz, Traci M; Heckbert, Susan R; Psaty, Bruce M; Gharib, Sina A; Zanen, Pieter; Lammers, Jan W; Oudkerk, Matthijs; Groen, H J; Locantore, Nicholas; Tal-Singer, Ruth; Rennard, Stephen I; Vestbo, Jørgen; Timens, Wim; Paré, Peter D; Latourelle, Jeanne C; Dupuis, Josée; O'Connor, George T; Wilk, Jemma B; Kim, Woo Jin; Lee, Mi Kyeong; Oh, Yeon-Mok; Vonk, Judith M; de Koning, Harry J; Leng, Shuguang; Belinsky, Steven A; Tesfaigzi, Yohannes; Manichaikul, Ani; Wang, Xin-Qun; Rich, Stephen S; Barr, R Graham; Sparrow, David; Litonjua, Augusto A; Bakke, Per; Gulsvik, Amund; Lahousse, Lies; Brusselle, Guy G; Stricker, Bruno H; Uitterlinden, André G; Ampleford, Elizabeth J; Bleecker, Eugene R; Woodruff, Prescott G; Meyers, Deborah A; Qiao, Dandi; Lomas, David A; Yim, Jae-Joon; Kim, Deog Kyeom; Hawrylkiewicz, Iwona; Sliwinski, Pawel; Hardin, Megan; Fingerlin, Tasha E; Schwartz, David A; Postma, Dirkje S; MacNee, William; Tobin, Martin D; Silverman, Edwin K; Boezen, H Marike; Cho, Michael H

2017-03-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10 -6 ) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

[Anesthetic care for fibrobronchoscopy in patients with chronic terminal respiratory insufficiency undergoing evaluation for isolated lung transplantation].

PubMed

Solca, M; Elena, A; Croci, M; Damia, G

1993-01-01

During the first 18 month operation of the isolated lung transplantation program at or Institution, eight patients with terminal chronic respiratory failure underwent fiberoptic bronchoscopy and broncho-alveolar lavage as part of their evaluation for isolated lung transplantation. Four patients had severe obstructive, three restrictive, and one mixed, obstructive and restrictive, disease; all of them were on continuous supplemental oxygen. Procedures were performed under topical anaesthesia, with either light sedation or simple monitored anaesthesia care. Monitoring included non-invasive blood pressure measurement, pulse oximeter and precordial stethoscope. No adverse events were recorded, except in one case, when pulse oximeter reading precipitously dropped below 80%, to a minimum of 68-69%. The procedures was terminated short of its completion, and the patient was briefly assisted with manual bag ventilation on oxygen 100%. Pulse oximeter quickly returned to normal levels (above 90%), and the patient promptly recovered, without complications. The importance of monitored anaesthesia care during fiberoptic bronchoscopy (a usually benign procedure) in critically ill patients is greatly emphasized.

[Isolated lung transplantation--evaluation of patients and initial results].

PubMed

Speich, R; Böhler, A; Zollinger, A; Stocker, R; Vogt, P; Carrel, T; Lang, T; Schmid, R; Stöhr, S; Vogt, P R

1995-04-22

Between November 1992 and May 1994 we performed 10 single and 5 double lung transplants in patients with end-stage lung diseases due to lymphangioleiomyomatosis (4), cystic fibrosis (3), pulmonary hypertension (3), pulmonary fibrosis (3) and chronic obstructive lung disease (2). In the 13 patients (87%) surviving for median 245 (19-567) days, FEV1 improved from median 640 ml to 1410 ml and the 12-minute walk distance from median 315 to 1100 meters. 10 patients (77%) enjoy a good or even excellent quality of life. 2 patients died 11 and 62 days postoperatively, due to multi-organ failure and invasive pulmonary aspergillosis respectively. The main postoperative problems are fungal and cytomegalovirus infections and chronic rejection in the form of bronchiolitis obliterans. In Switzerland as elsewhere, lung transplantation has become an established modality for the management of end-stage diseases of the lung and pulmonary circulation.

Prevalence of chronic obstructive pulmonary disease according to BTS, ERS, GOLD and ATS criteria in relation to doctor's diagnosis, symptoms, age, gender, and smoking habits.

PubMed

Lindberg, Anne; Jonsson, Ann-Christin; Rönmark, Eva; Lundgren, Rune; Larsson, Lars-Gunnar; Lundbäck, Bo

2005-01-01

Guidelines and standards for diagnosis and management of chronic obstructive pulmonary disease (COPD) have been presented by different national and international societies, but the spirometric criteria for COPD differ between guidelines. To estimate prevalence of COPD using the guidelines of the British Thoracic Society (BTS), the European Respiratory Society (ERS), the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and the American Thoracic Society (ATS). Further, to evaluate reported airway symptoms, contacts with health care providers, and physician diagnosis of COPD in relation to the respective criteria, and gender differences. In 1992 a postal questionnaire was sent to a random sample of adults aged 20-69 years, 4,851 (85%) out of 5,681 subjects responded. In 1994-1995 a random sample of the responders, 970 subjects, were invited to a structured interview and a lung function test; 666 (69%) participated. The prevalence of COPD was 7.6, 14.0, 14.1, 12.2 and 34.1% according to BTS, ERS, GOLD, clinical ATS (with symptoms or physician diagnosis), and spirometric ATS criteria, respectively. Prevalent COPD was related to age, smoking habits and family history of obstructive airway disease but not to gender. Physician diagnosis of chronic bronchitis or emphysema was only reported by 16.3, 12.2, 11.0, 23.4 and 8.2% of subjects fulfilling the respective criteria, though a majority reported airway symptoms. The main determinants for prevalent COPD were age, smoking habits and spirometric criteria of COPD. Though a majority reported airway symptoms and contact with health care providers due to respiratory complaints, only a minority was diagnosed as having COPD, indicating a large underdiagnosis. Copyright (c) 2005 S. Karger AG, Basel.

The Intersection of Aging Biology and the Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop.

PubMed

Budinger, G R Scott; Kohanski, Ronald A; Gan, Weiniu; Kobor, Michael S; Amaral, Luis A; Armanios, Mary; Kelsey, Karl T; Pardo, Annie; Tuder, Rubin; Macian, Fernando; Chandel, Navdeep; Vaughan, Douglas; Rojas, Mauricio; Mora, Ana L; Kovacs, Elizabeth; Duncan, Steven R; Finkel, Toren; Choi, Augustine; Eickelberg, Oliver; Chen, Danica; Agusti, Alvar; Selman, Moises; Balch, William E; Busse, Paula; Lin, Anning; Morimoto, Richard; Sznajder, Jacob I; Thannickal, Victor J

2017-10-12

Death from chronic lung disease is increasing and chronic obstructive pulmonary disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide population ages. Chronic lung diseases are associated with substantial morbidity, frequently resulting in exercise limiting dyspnea, immobilization, and isolation. Therefore, effective strategies to prevent or treat lung disease are likely to increase healthspan as well as life span. This review summarizes the findings of a joint workshop sponsored by the NIA and NHLBI that brought together investigators focused on aging and lung biology. These investigators encouraged the use of genetic systems and aged animals in the study of lung disease and the development of integrative systems-based platforms that can dynamically incorporate data sets that describe the genomics, transcriptomics, epigenomics, metabolomics, and proteomics of the aging lung in health and disease. Further research was recommended to integrate benchmark biological hallmarks of aging in the lung with the pathobiology of acute and chronic lung diseases with divergent pathologies for which advanced age is the most important risk factor. Published by Oxford University Press on behalf of The Gerontological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Comparing end-of-life care for hospitalized patients with chronic obstructive pulmonary disease and lung cancer in Taiwan.

PubMed

Chou, Wen-Chi; Lai, Yu-Te; Huang, Yun-Chin; Chang, Chen-Ling; Wu, Wei-Shan; Hung, Yu-Shin

2013-01-01

When it comes to end-of-life care, chronic obstructive pulmonary disease (COPD) patients are often treated differently from lung cancer patients. However, few reports have compared end-of-life care between these two groups. We investigated the differences between patients with end-stage COPD and end-stage lung cancer based on end-of-life symptoms and clinical practice patterns using a retrospective study of COPD and lung cancer patients who died in an acute care hospital in Taiwan. End-stage COPD patients had more comorbidities and spent more days in the intensive care unit (ICU) than end-stage lung cancer patients. They were more likely to die in the ICU and less likely to receive hospice care. COPD patients also had more invasive procedures, were less likely to use narcotic and sedative drugs, and were less likely to have given do-not-resuscitate consent. Symptoms were similar between these two groups. Differences in treatment management suggest that COPD patients receive more care aimed at prolonging life than care aimed at relieving symptoms and providing end-of-life support. It may be more difficult to determine when COPD patients are at the end-of-life stage than it is to identify when lung cancer patients are at that stage. Our findings indicate that in Taiwan, more effort should be made to give end-stage COPD patients the same access to hospice care as end-stage lung cancer patients.

Cathepsin E promotes pulmonary emphysema via mitochondrial fission.

PubMed

Zhang, Xuchen; Shan, Peiying; Homer, Robert; Zhang, Yi; Petrache, Irina; Mannam, Praveen; Lee, Patty J

2014-10-01

Emphysema is characterized by loss of lung elasticity and irreversible air space enlargement, usually in the later decades of life. The molecular mechanisms of emphysema remain poorly defined. We identified a role for a novel cathepsin, cathepsin E, in promoting emphysema by inducing mitochondrial fission. Unlike previously reported cysteine cathepsins, which have been implicated in cigarette smoke-induced lung disease, cathepsin E is a nonlysosomal intracellular aspartic protease whose function has been described only in antigen processing. We examined lung tissue sections of persons with chronic obstructive pulmonary disease, a clinical entity that includes emphysematous change. Human chronic obstructive pulmonary disease lungs had markedly increased cathepsin E protein in the lung epithelium. We generated lung epithelial-targeted transgenic cathepsin E mice and found that they develop emphysema. Overexpression of cathepsin E resulted in increased E3 ubiquitin ligase parkin, mitochondrial fission protein dynamin-related protein 1, caspase activation/apoptosis, and ultimately loss of lung parenchyma resembling emphysema. Inhibiting dynamin-related protein 1, using a small molecule inhibitor in vitro or in vivo, inhibited cathepsin E-induced apoptosis and emphysema. To the best of our knowledge, our study is the first to identify links between cathepsin E, mitochondrial fission, and caspase activation/apoptosis in the pathogenesis of pulmonary emphysema. Our data expand the current understanding of molecular mechanisms of emphysema development and may provide new therapeutic targets. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Therapeutic Potential of Medicinal Plants and Their Constituents on Lung Inflammatory Disorders

PubMed Central

Kim, Hyun Pyo; Lim, Hyun; Kwon, Yong Soo

2017-01-01

Acute bronchitis and chronic obstructive pulmonary diseases (COPD) are essentially lung inflammatory disorders. Various plant extracts and their constituents showed therapeutic effects on several animal models of lung inflammation. These include coumarins, flavonoids, phenolics, iridoids, monoterpenes, diterpenes and triterpenoids. Some of them exerted inhibitory action mainly by inhibiting the mitogen-activated protein kinase pathway and nuclear transcription factor-κB activation. Especially, many flavonoid derivatives distinctly showed effectiveness on lung inflammation. In this review, the experimental data for plant extracts and their constituents showing therapeutic effectiveness on animal models of lung inflammation are summarized. PMID:27956716

Hematopoietic and mesenchymal stem cells for the treatment of chronic respiratory diseases: role of plasticity and heterogeneity.

PubMed

Conese, Massimo; Piro, Donatella; Carbone, Annalucia; Castellani, Stefano; Di Gioia, Sante

2014-01-01

Chronic lung diseases, such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD) are incurable and represent a very high social burden. Stem cell-based treatment may represent a hope for the cure of these diseases. In this paper, we revise the overall knowledge about the plasticity and engraftment of exogenous marrow-derived stem cells into the lung, as well as their usefulness in lung repair and therapy of chronic lung diseases. The lung is easily accessible and the pathophysiology of these diseases is characterized by injury, inflammation, and eventually by remodeling of the airways. Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal (stem) cells (MSCs), encompass a wide array of cell subsets with different capacities of engraftment and injured tissue regenerating potential. Proof-of-principle that marrow cells administered locally may engraft and give rise to specialized epithelial cells has been given, but the efficiency of this conversion is too limited to give a therapeutic effect. Besides the identification of plasticity mechanisms, the characterization/isolation of the stem cell subpopulations represents a major challenge to improving the efficacy of transplantation protocols used in regenerative medicine for lung diseases.

Severity of Airflow Obstruction in Chronic Obstructive Pulmonary Disease (COPD): Proposal for a New Classification.

PubMed

Coton, Sonia; Vollmer, William M; Bateman, Eric; Marks, Guy B; Tan, Wan; Mejza, Filip; Juvekar, Sanjay; Janson, Christer; Mortimer, Kevin; P A, Mahesh; Buist, A Sonia; Burney, Peter G J

2017-10-01

Current classifications of Chronic Obstructive Pulmonary Disease (COPD) severity are complex and do not grade levels of obstruction. Obstruction is a simpler construct and independent of ethnicity. We constructed an index of obstruction severity based on the FEV 1 /FVC ratio, with cut-points dividing the Burden of Obstructive Lung Disease (BOLD) study population into four similarly sized strata to those created by the GOLD criteria that uses FEV 1 . We measured the agreement between classifications and the validity of the FEV 1 -based classification in identifying the level of obstruction as defined by the new groupings. We compared the strengths of association of each classification with quality of life (QoL), MRC dyspnoea score and the self-reported exacerbation rate. Agreement between classifications was only fair. FEV 1 -based criteria for moderate COPD identified only 79% of those with moderate obstruction and misclassified half of the participants with mild obstruction as having more severe COPD. Both scales were equally strongly associated with QoL, exertional dyspnoea and respiratory exacerbations. Severity assessed using the FEV 1 /FVC ratio is only in moderate agreement with the severity assessed using FEV 1 but is equally strongly associated with other outcomes. Severity assessed using the FEV 1 /FVC ratio is likely to be independent of ethnicity.

COPD prevalence in a random population survey: a matter of definition.

PubMed

Shirtcliffe, P; Weatherall, M; Marsh, S; Travers, J; Hansell, A; McNaughton, A; Aldington, S; Muellerova, H; Beasley, R

2007-08-01

A recent American Thoracic Society and European Respiratory Society joint Task Force report recommends using a lower limit of normal (LLN) of forced expiratory volume in one second/forced vital capacity as opposed to a fixed ratio of <0.7 to diagnose airflow obstruction, in order to reduce false positive diagnoses of chronic obstructive pulmonary disease (COPD) as defined by the Global Initiative for Obstructive Lung Disease (GOLD). To date, there is no reliable spirometry-based prevalence data for COPD in New Zealand and the effect of different definitions of airflow obstruction based on post-bronchodilator spirometry is not known. Detailed written questionnaires, full pulmonary function tests (including pre- and post-bronchodilator flow-volume loops) and atopy testing were completed in 749 subjects recruited from a random population sample. The GOLD-defined, age-adjusted prevalence (95% confidence interval) for adults aged >or=40 yrs was 14.2 (11.0-17.0)% compared with an LLN-defined, age-adjusted, post-bronchodilator prevalence in the same group of 9.0 (6.7-11.3)%. The prevalence of chronic obstructive pulmonary disease varied markedly depending on the definition used. Further research using longitudinal rather than cross-sectional data will help decide the preferred approach in chronic obstructive pulmonary disease prevalence surveys.

Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial-American College of Radiology Imaging Network Cohort.

PubMed

Hopkins, Raewyn J; Duan, Fenghai; Chiles, Caroline; Greco, Erin M; Gamble, Greg D; Aberle, Denise; Young, Robert P

2017-03-01

Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk. We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. In the National Lung Screening Trial-ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group). Compared with those with no airflow limitation, where lung cancer incidence was 3.78/1,000 person years, incidence rates increased in a simple linear relationship: GOLD 1 (6.27/1,000 person yr); GOLD 2 (7.86/1,000 person yr); GOLD 3 (10.71/1,000 person yr); and GOLD 4 (13.25/1,000 person yr). All relationships were significant versus the reference group at a P value of 0.0001 or less. In a large prospective study of high-risk cigarette smokers, we report a strong linear relationship between increasing severity of airflow limitation and risk of lung cancer.

How do patients conceptualize chronic obstructive pulmonary disease?

PubMed

Goldman, R E; Mennillo, L; Stebbins, P; Parker, D R

2017-08-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, yet even at risk or diagnosed patients misunderstand COPD and its consequences for their quality of life and mortality. This study explored how patients conceptualize the causes, symptoms, consequences, treatment, and risk for developing COPD. The study consisted of six focus groups: 39 participants who were adults > 40 and current smoker or have COPD symptoms, family history, or exposures. Although many participants had some familiarity with the breathing, lung function, physical, emotional, and social consequences of COPD, confusion and misunderstanding prevailed. Few knew that COPD, chronic bronchitis, and emphysema are synonymous. Some participants claimed that they "only" had bronchitis and/or emphysema and not COPD. Some participants described behavioral adaptations to decrease symptom impact and others expressed strong interest in learning how to increase daily functioning. Insufficient knowledge and persisting misconceptions about COPD can prevent patients from accessing life-enhancing strategies. Patients can benefit from (1) providers clarifying COPD's connection to chronic bronchitis and emphysema to aid them in recognizing the need for mitigating action; (2) encouraging smoking cessation, specifically to stem worsening of disease; and (3) explaining lifestyle adaptations for easing daily life despite decreased lung function.

Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease (COPD) Using an Ontario Policy Model

PubMed Central

Chandra, K; Blackhouse, G; McCurdy, BR; Bornstein, M; Campbell, K; Costa, V; Franek, J; Kaulback, K; Levin, L; Sehatzadeh, S; Sikich, N; Thabane, M; Goeree, R

2012-01-01

Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm. For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx. The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact. Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature. The inflammation causes repeated cycles of injury and repair in the airway wall— inflammatory cells release a variety of chemicals and lead to cellular damage. The inflammation process also contributes to the loss of elastic recoil pressure in the lung, thereby reducing the driving pressure for expiratory flow through narr

Childhood pneumonia increases risk for chronic obstructive pulmonary disease: the COPDGene study.

PubMed

Hayden, Lystra P; Hobbs, Brian D; Cohen, Robyn T; Wise, Robert A; Checkley, William; Crapo, James D; Hersh, Craig P

2015-09-21

Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers. COPD cases and control smokers between 45-80 years old from the United States COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Subjects with lung disease other than COPD or asthma were excluded. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans. Of 10,192 adult smokers, 854 (8.4%) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95% CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs. 77.1% predicted), FVC (82.7 vs. 87.4% predicted), FEV1/FVC ratio (0.63 vs. 0.67; p < 0.001 for all comparisons). Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema. Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95% CI 1.10-3.18). Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function. This association is supported by airway changes on chest CT scans. Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk. ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).

Inflammatory Role of Macrophage Xanthine Oxidoreductase in Pulmonary Hypertension: Implications for Novel Therapeutic Approaches

DTIC Science & Technology

2015-10-01

Lung Inflammation, Uric Acid, Chronic Obstructive Pulmonary Disease, Mononuclear Phagocyte , Monosodium Urate, XOR WT, XOR KO, Wistar Kyoto, Pulmonary...0451 Annual Report (Year 1) 4 Mononuclear Phagocyte XOR Activity and Superoxide Generation Were Reduced by

Hospital readmissions for COPD: a retrospective longitudinal study.

PubMed

Harries, Timothy H; Thornton, Hannah; Crichton, Siobhan; Schofield, Peter; Gilkes, Alexander; White, Patrick T

2017-04-27

Prevention of chronic obstructive pulmonary disease hospital readmissions is an international priority aimed to slow disease progression and limit costs. Evidence of the risk of readmission and of interventions that might prevent it is lacking. We aimed to determine readmission risk for chronic obstructive pulmonary disease, factors influencing that risk, and variation in readmission risk between hospitals across 7.5 million people in London. This retrospective longitudinal observational study included all chronic obstructive pulmonary disease admissions to any hospital in the United Kingdom among patients registered at London general practices who had emergency National Health Service chronic obstructive pulmonary disease hospital admissions between April 2006 and March 2010. Influence of patient characteristics, geographical deprivation score, length of stay, day of week of admission or of discharge, and admitting hospital, were assessed using multiple logistic regression. 38,894 chronic obstructive pulmonary disease admissions of 20,932 patients aged ≥ 45 years registered with London general practices were recorded. 6295 patients (32.2%) had at least one chronic obstructive pulmonary disease readmission within 1 year. 1993 patients (10.2%) were readmitted within 30 days and 3471 patients (17.8%) were readmitted within 90 days. Age and patient geographical deprivation score were very weak predictors of readmission. Rates of chronic obstructive pulmonary disease readmissions within 30 days and within 90 days did not vary among the majority of hospitals. The finding of lower chronic obstructive pulmonary disease readmission rates than was previously estimated and the limited variation in these rates between hospitals suggests that the opportunity to reduce chronic obstructive pulmonary disease readmission risk is small. LOWER RISK OF READMISSION FOR LONDON-BASED PATIENTS: A managed reduction of hospital readmissions for London-based chronic lung disease patients may not be needed. Preventing hospital readmissions for patients with chronic obstructive pulmonary disease (COPD) is a key priority to improve patient care and limit costs. However, few data are available to determine and ultimately reduce the risk of readmission. Timothy Harries at King's College, London, and co-workers conducted a longitudinal study incorporating all COPD admissions into UK hospitals for 20,932 patients registered at London general practitioners between 2006 and 2010. They found that 32% of patients were readmitted within a year, 17.8% within 90 days and 10% within 30 days. Neither age nor geographical deprivation were useful predictors of readmission. These represent lower than estimated levels of readmission, suggesting there may be fewer opportunities to reduce the risk of readmission further.

TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema.

PubMed

An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C; Ifedigbo, Emeka; Washko, George R; Ryter, Stefan W; Choi, Augustine M K

2012-11-01

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.

TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema

PubMed Central

An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C.; Ifedigbo, Emeka; Washko, George R.; Ryter, Stefan W.

2012-01-01

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS. PMID:22983353

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives.

PubMed

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

2017-03-20

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).

Influenza and Pneumonia Vaccination Rates and Factors Affecting Vaccination among Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Aka Aktürk, Ülkü; Görek Dilektaşlı, Aslı; Şengül, Aysun; Musaffa Salepçi, Banu; Oktay, Nuray; Düger, Mustafa; Arık Taşyıkan, Hale; Durmuş Koçak, Nagihan

2017-05-05

Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Multi-centre cross-sectional study. Patients admitted to the chest diseases clinics of six different centres between 1 February 2013 and 1 January 2014 with a pre-diagnosis of Chronic obstructive pulmonary disease according to the Global initiative for chronic obstructive lung disease criteria, who were in a stable condition were included in the study. The survey, which included demographic characteristics, socio-economic status, severity of disease and vaccination information, was first tested on a small patient population before the study. The survey was completed by the investigators after obtaining written informed consent. The average age of the 296 included patients was 66.3±9.3 years and 91.9% were male. Of these, 36.5% had the influenza vaccination and 14.1% had the pneumococcal vaccination. The most common reason for not being vaccinated was 'no recommendation by doctors': 57.2% in the case of influenza vaccinations, and 46.8% in the case of pneumococcal vaccinations. Both vaccination rates were significantly higher in those patients with comorbidities (influenza vaccination p<0.001; pneumococcal vaccination p=0.06). There was no significant correlation with age, gender, smoking and severity of disease (p>0.05). Vaccination rates were significantly higher in those with a white-collar occupation and higher education level, and who presented to a university hospital (p<0.001). Medical professionals do not request vaccinations as often as the International Guidelines suggest for chronic obstructive pulmonary disease patients. Awareness of the importance of these vaccinations among both doctors and patients needs to be addressed.

Excess Ventilation in Chronic Obstructive Pulmonary Disease-Heart Failure Overlap. Implications for Dyspnea and Exercise Intolerance.

PubMed

Rocha, Alcides; Arbex, Flavio F; Sperandio, Priscilla A; Souza, Aline; Biazzim, Ligia; Mancuso, Frederico; Berton, Danilo C; Hochhegger, Bruno; Alencar, Maria Clara N; Nery, Luiz E; O'Donnell, Denis E; Neder, J Alberto

2017-11-15

An increased ventilatory response to exertional metabolic demand (high [Formula: see text]e/[Formula: see text]co 2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure. We aimed to determine the mechanisms underlying high [Formula: see text]e/[Formula: see text]co 2 and its impact on operating lung volumes, dyspnea, and exercise tolerance in these patients. Twenty-two ex-smokers with combined chronic obstructive pulmonary disease and heart failure with reduced left ventricular ejection fraction undertook, after careful treatment optimization, a progressive cycle exercise test with capillary (c) blood gas collection. Regardless of the chosen metric (increased [Formula: see text]e-[Formula: see text]co 2 slope, [Formula: see text]e/[Formula: see text]co 2 nadir, or end-exercise [Formula: see text]e/[Formula: see text]co 2 ), ventilatory inefficiency was closely related to Pc CO 2 (r values from -0.80 to -0.84; P < 0.001) but not dead space/tidal volume ratio. Ten patients consistently maintained exercise Pc CO 2 less than or equal to 35 mm Hg (hypocapnia). These patients had particularly poor ventilatory efficiency compared with patients without hypocapnia (P < 0.05). Despite the lack of between-group differences in spirometry, lung volumes, and left ventricular ejection fraction, patients with hypocapnia had lower resting Pa CO 2 and lung diffusing capacity (P < 0.01). Excessive ventilatory response in this group was associated with higher exertional Pc O 2 . The group with hypocapnia, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate leading to poorer exercise tolerance compared with their counterparts (P < 0.05). Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased "wasted" ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease-heart failure overlap. Excessive ventilation led to better arterial oxygenation but at the expense of earlier critical mechanical constraints and intolerable dyspnea.

The Evaluation of Interstitial Abnormalities in Group B of the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Classification of Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Ohgiya, Masahiro; Matsui, Hirotoshi; Tamura, Atsuhisa; Kato, Takafumi; Akagawa, Shinobu; Ohta, Ken

2017-10-15

Objective In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification categorized chronic obstructive pulmonary disease (COPD) patients into 4 groups. A report demonstrated that the mortality in Group B was higher than that in Group C. Ischemic heart disease and cancer were suggested to be the cause. The aim of the present study was to test the hypothesis that interstitial lung abnormalities (ILAs) are more prevalent in Group B than Group C and that they may be responsible for the higher mortality in Group B. Methods Patients were selected based on their pulmonary function test results. The inclusion criterion was a forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) of <70% after the inhalation of a bronchodilator. Patients without a smoking history or computed tomography (CT) scan were excluded. The medical records of the patients were retrospectively reviewed, and the selected patients were categorized into Groups A to D. High-resolution CT scans were used to investigate the presence of ILAs and determine the low attenuation area (LAA). Results Among the 349 COPD patients, ILAs were detected in 10.3% of the patients in Group A, 22.5% of the patients in Group B, 5.6% of the patients in Group C, and 23.1% of the patients in Group D. In Group B, the frequency of ILAs was significantly higher and the area affected by the ILAs was significantly greater in comparison to Group C. Among the patterns of interstitial abnormalities, the area of honeycombing in Group B was significantly greater than that in Group C. Furthermore, among the patients in Group B, the LAA in the ILA-positive patients was significantly greater than that in the ILA-negative patients. Conclusion In Group B, the area occupied by ILAs-especially honeycombing-was greater than that in Group C. This contributed to the preserved %FEV 1 and possibly to the poorer prognosis of the patients in Group B.

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease

PubMed Central

Malhotra, Deepti; Boezen, H. Marike; Siedlinski, Mateusz; Postma, Dirkje S.; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E.; Anthonisen, Nicholas R.; Paré, Peter D.; Biswal, Shyam

2012-01-01

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function. PMID:22693272

NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.

PubMed

Sandford, Andrew J; Malhotra, Deepti; Boezen, H Marike; Siedlinski, Mateusz; Postma, Dirkje S; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Biswal, Shyam

2012-08-01

An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.

Multi-component assessment of chronic obstructive pulmonary disease: an evaluation of the ADO and DOSE indices and the global obstructive lung disease categories in international primary care data sets

PubMed Central

Jones, Rupert C; Price, David; Chavannes, Niels H; Lee, Amanda J; Hyland, Michael E; Ställberg, Björn; Lisspers, Karin; Sundh, Josefin; van der Molen, Thys; Tsiligianni, Ioanna

2016-01-01

Suitable tools for assessing the severity of chronic obstructive pulmonary disease (COPD) include multi-component indices and the global initiative for chronic obstructive lung disease (GOLD) categories. The aim of this study was to evaluate the dyspnoea, obstruction, smoking, exacerbation (DOSE) and the age, dyspnoea, obstruction (ADO) indices and GOLD categories as measures of current health status and future outcomes in COPD patients. This was an observational cohort study comprising 5,114 primary care COPD patients across three databases from UK, Sweden and Holland. The associations of DOSE and ADO indices with (i) health status using the Clinical COPD Questionnaire (CCQ) and St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment test (CAT) and with (ii) current and future exacerbations, admissions and mortality were assessed in GOLD categories and DOSE and ADO indices. DOSE and ADO indices were significant predictors of future exacerbations: incident rate ratio was 1.52 (95% confidence intervals 1.46–1.57) for DOSE, 1.16 (1.12–1.20) for ADO index and 1.50 (1.33–1.68) and 1.23 (1.10–1.39), respectively, for hospitalisations. Negative binomial regression showed that the DOSE index was a better predictor of future admissions than were its component items. The hazard ratios for mortality were generally higher for ADO index groups than for DOSE index groups. The GOLD categories produced widely differing assessments for future exacerbation risk or for hospitalisation depending on the methods used to calculate them. None of the assessment systems were excellent at predicting future risk in COPD; the DOSE index appears better than the ADO index for predicting many outcomes, but not mortality. The GOLD categories predict future risk inconsistently. The DOSE index and the GOLD categories using exacerbation frequency may be used to identify those at high risk for exacerbations and admissions. PMID:27053297

Multi-component assessment of chronic obstructive pulmonary disease: an evaluation of the ADO and DOSE indices and the global obstructive lung disease categories in international primary care data sets.

PubMed

Jones, Rupert C; Price, David; Chavannes, Niels H; Lee, Amanda J; Hyland, Michael E; Ställberg, Björn; Lisspers, Karin; Sundh, Josefin; van der Molen, Thys; Tsiligianni, Ioanna

2016-04-07

Suitable tools for assessing the severity of chronic obstructive pulmonary disease (COPD) include multi-component indices and the global initiative for chronic obstructive lung disease (GOLD) categories. The aim of this study was to evaluate the dyspnoea, obstruction, smoking, exacerbation (DOSE) and the age, dyspnoea, obstruction (ADO) indices and GOLD categories as measures of current health status and future outcomes in COPD patients. This was an observational cohort study comprising 5,114 primary care COPD patients across three databases from UK, Sweden and Holland. The associations of DOSE and ADO indices with (i) health status using the Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ) and COPD Assessment test (CAT) and with (ii) current and future exacerbations, admissions and mortality were assessed in GOLD categories and DOSE and ADO indices. DOSE and ADO indices were significant predictors of future exacerbations: incident rate ratio was 1.52 (95% confidence intervals 1.46-1.57) for DOSE, 1.16 (1.12-1.20) for ADO index and 1.50 (1.33-1.68) and 1.23 (1.10-1.39), respectively, for hospitalisations. Negative binomial regression showed that the DOSE index was a better predictor of future admissions than were its component items. The hazard ratios for mortality were generally higher for ADO index groups than for DOSE index groups. The GOLD categories produced widely differing assessments for future exacerbation risk or for hospitalisation depending on the methods used to calculate them. None of the assessment systems were excellent at predicting future risk in COPD; the DOSE index appears better than the ADO index for predicting many outcomes, but not mortality. The GOLD categories predict future risk inconsistently. The DOSE index and the GOLD categories using exacerbation frequency may be used to identify those at high risk for exacerbations and admissions.

Ethanol extract of the tuber of Alisma orientale reduces the pathologic features in a chronic obstructive pulmonary disease mouse model.

PubMed

Kim, Kyun Ha; Song, Hyuk-Hwan; Ahn, Kyung-Seop; Oh, Sei-Ryang; Sadikot, Ruxana T; Joo, Myungsoo

2016-07-21

The tuber of Alismataceae Alisma orientale Juzepzuk has been prescribed as a remedy for treating the diseases associated with body fluid dysfunction such as edema and inflammatory lung diseases. Chronic obstructive pulmonary disease (COPD) is a debilitating, inflammatory lung disease without effective treatment. Along with persistent inflammation, autophagy has been recently reported to contribute to COPD. Here, by employing a murine model, we examined whether the tuber of the plant is effective against COPD MATERIALS AND METHODS: The ethanol extract of the tuber of A. orientale Juzepzuk (EEAO) was fingerprinted by HPLC. For the establishment of COPD lung, mice received single intratracheal (i.t.) spraying of elastase and LPS per week for 2 weeks. After approximated to the dose prescribed typically to patients, EEAO was administered to the lung 2h after each LPS treatment. Morphometric analyses, semi-quantitative RT-PCR, and western blot were performed to evaluate the effects of EEAO on emphysema, inflammation, and autophagy in mouse lungs. The effect of EEAO on autophagy was also assessed by western blot at the cellular level with murine macrophages and human lung epithelial cells. When receiving i.t. elastase and LPS for 2 weeks, mice developed emphysema and inflammation in the lung. EEAO treatment, however, significantly reduced emphysema and inflammatory cell infiltration to the lung with concomitant decrease of the production of pro-inflammatory cytokines including TNF-α, IL-6, and TGF-β, signature cytokines of COPD. Unlike control mice, the lungs of the COPD mice expressed LC3-II, a biomarker for autophagy formation, which was decreased by EEAO treatment. EEAO also lowered the expression of LC3-II in murine macrophage, RAW 264.7, and human lung epithelial cell, BEAS-2B, which was associated with EEAO activating mTOR. EEAO relieved COPD pathologic features in a mouse model, which was associated with suppression of lung inflammation, emphysema, and autophagy. Our results suggest an effectiveness of the tuber of A. orientale in chronic inflammatory lung diseases such as COPD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2016-01-01

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

The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

PubMed

Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

2018-01-09

Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota.

Diesel exhaust particles induce the over expression of tumor necrosis factor-alpha (TNF-alpha) gene in alvelor machrophage and failed to induce apoptosis through activation of nuclear factor-kappaB (NF-kappaB)

EPA Science Inventory

Exposure to particulate matter (PM2.5-10), including diesel exhaust particles (DEP) has been reported to induce lung injury and exacerbation of asthma and chronic obstructive pulmonary disease. Alveolar macrophages play a major role in the lung's response to inhaled particles and...

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology.

PubMed

Bodas, Manish; Vij, Neeraj

2017-05-04

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.

PubMed

Ramadan, Wijdan H; Kabbara, Wissam K; El Khoury, Ghada M; Al Assir, Sarah A

2015-01-01

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations.

PubMed

Washko, George R; Fan, Vincent S; Ramsey, Scott D; Mohsenifar, Zab; Martinez, Fernando; Make, Barry J; Sciurba, Frank C; Criner, Gerald J; Minai, Omar; Decamp, Malcolm M; Reilly, John J

2008-01-15

Lung volume reduction surgery (LVRS) has been demonstrated to provide a functional and mortality benefit to a select group of subjects with chronic obstructive pulmonary disease (COPD). The effect of LVRS on COPD exacerbations has not been as extensively studied, and whether improvement in postoperative lung function alters the risk of disease exacerbations is not known. To examine the effect, and mechanism of potential benefit, of LVRS on COPD exacerbations by comparing the medical and surgical cohorts of the National Emphysema Treatment Trial (NETT). A COPD exacerbation was defined using Centers for Medicare and Medicaid Services data and International Classification of Diseases, Ninth Revision, discharge diagnosis. There was no difference in exacerbation rate or time to first exacerbation between the medical and surgical cohorts during the year before study randomization (P = 0.58 and 0.85, respectively). Postrandomization, the surgical cohort experienced an approximate 30% reduction in exacerbation frequency (P = 0.0005). This effect was greatest in those subjects with the largest postoperative improvement in FEV(1) (P = 0.04) when controlling for changes in other spirometric measures of lung function, lung capacities, and room air arterial blood gas tensions. Finally, LVRS increased the time to first exacerbation in both those subjects with and those without a prior history of exacerbations (P = 0.0002 and P < 0.0001, respectively). LVRS reduces the frequency of COPD exacerbations and increases the time to first exacerbation. One explanation for this benefit may be the postoperative improvement in lung function.

Prone position improves lung mechanical behavior and enhances gas exchange efficiency in mechanically ventilated chronic obstructive pulmonary disease patients.

PubMed

Mentzelopoulos, Spyros D; Zakynthinos, Spyros G; Roussos, Charris; Tzoufi, Maria J; Michalopoulos, Argyris S

2003-06-01

Pronation might favorably affect respiratory system (rs) mechanics and function in volume-controlled, mode-ventilated chronic obstructive pulmonary disease (COPD) patients. We studied 10 COPD patients, initially positioned supine (baseline supine [supine(BAS)]) and then randomly and consecutively changed to protocol supine (supine(PROT)), semirecumbent, and prone positions. Rs mechanics and inspiratory work (W(I)) were assessed at baseline (0.6 L) (all postures) and sigh (1.2 L) (supine(BAS) excluded) tidal volume (V(T)) with rapid airway occlusion during constant-flow inflation. Hemodynamics and gas exchange were assessed in all postures. There were no complications. Prone positioning resulted in (a) increased dynamic-static chest wall (cw) elastance (at both V(Ts)) and improved oxygenation versus supine(BAS), supine(PROT), and semirecumbent, (b) decreased additional lung (L) resistance-elastance versus supine(PROT) and semirecumbent at sigh V(T), (c) decreased L-static elastance (at both V(Ts)) and improved CO(2) elimination versus supine(BAS) and supine(PROT), and (d) improved oxygenation versus all other postures. Semirecumbent positioning increased mainly additional cw-resistance versus supine(BAS) and supine(PROT) at baseline. V(T) W(I)-sub-component changes were consistent with changes in rs, cw, and L mechanical properties. Total rs-W(I) and hemodynamics were unaffected by posture change. After pronation, five patients were repositioned supine (supine(POSTPRO)). In supine(POSTPRO), static rs-L elastance were lower, and oxygenation was still improved versus supine(BAS). Pronation of mechanically ventilated COPD patients exhibits applicability and effectiveness and improves oxygenation and sigh-L mechanics versus semirecumbent ("gold standard") positioning. By assessing respiratory mechanics, inspiratory work, hemodynamics, and gas exchange, we showed that prone positioning of mechanically ventilated chronic obstructed pulmonary disease patients improves oxygenation and lung mechanics during sigh versus semirecumbent positioning. Furthermore, certain pronation-related benefits versus preprone-supine positioning (reduced lung elastance and improved oxygenation) are maintained in the postprone supine position.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-10-10

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

“Sentinel” Circulating Tumor Cells Allow Early Diagnosis of Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease

PubMed Central

Ilie, Marius; Hofman, Véronique; Long-Mira, Elodie; Selva, Eric; Vignaud, Jean-Michel; Padovani, Bernard; Mouroux, Jérôme; Marquette, Charles-Hugo; Hofman, Paul

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. Migration of circulating tumor cells (CTCs) into the blood stream is an early event that occurs during carcinogenesis. We aimed to examine the presence of CTCs in complement to CT-scan in COPD patients without clinically detectable lung cancer as a first step to identify a new marker for early lung cancer diagnosis. The presence of CTCs was examined by an ISET filtration-enrichment technique, for 245 subjects without cancer, including 168 (68.6%) COPD patients, and 77 subjects without COPD (31.4%), including 42 control smokers and 35 non-smoking healthy individuals. CTCs were identified by cytomorphological analysis and characterized by studying their expression of epithelial and mesenchymal markers. COPD patients were monitored annually by low-dose spiral CT. CTCs were detected in 3% of COPD patients (5 out of 168 patients). The annual surveillance of the CTC-positive COPD patients by CT-scan screening detected lung nodules 1 to 4 years after CTC detection, leading to prompt surgical resection and histopathological diagnosis of early-stage lung cancer. Follow-up of the 5 patients by CT-scan and ISET 12 month after surgery showed no tumor recurrence. CTCs detected in COPD patients had a heterogeneous expression of epithelial and mesenchymal markers, which was similar to the corresponding lung tumor phenotype. No CTCs were detected in control smoking and non-smoking healthy individuals. CTCs can be detected in patients with COPD without clinically detectable lung cancer. Monitoring “sentinel” CTC-positive COPD patients may allow early diagnosis of lung cancer. PMID:25360587

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

PubMed

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

2018-01-01

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

Sing Your Lungs Out—a community singing group for chronic obstructive pulmonary disease: a 1-year pilot study

PubMed Central

McNaughton, Amanda; Weatherall, Mark; Williams, Mathew; McNaughton, Harry; Aldington, Sarah; Williams, Gayle; Beasley, Richard

2017-01-01

Objective Singing group participation may benefit patients with chronic obstructive pulmonary disease (COPD). Previous studies are limited by small numbers of participants and short duration of generally hospital-based singing group intervention. This study examines the feasibility of long-term participation in a community singing group for patients with COPD who had completed pulmonary rehabilitation (PR). Methods This was a feasibility cohort study. Patients with COPD who had completed PR and were enrolled in a weekly community exercise group were recruited to a new community-based singing group which met weekly for over 1 year. Measurements at baseline, 4 months and 1 year comprised comprehensive pulmonary function tests including lung volumes, 6 min walk test (6MWT), Clinical COPD Questionnaire (CCQ), Hospital Anxiety and Depression Scale (HADS) and hospital admission days for acute exacerbation of COPD (AECOPD) for 1 year before and after the first singing group session. Findings There were 28 participants with chronic lung disease recruited from 140 people approached. Five withdrew in the first month. 21 participants meeting Global Initiative for Chronic Obstructive Lung Disease criteria for COPD completed 4-month and 18 completed 1-year assessments. The mean attendance was 85%. For the prespecified primary outcome measure, total HADS score, difference between baseline and 12 months was −0.9, 95% CI −3.0 to 1.2, p=0.37. Of the secondary measures, a significant reduction was observed for HADS anxiety score after 1 year of −0.9 (95% CI −1.8 to −0.1) points, p=0.038 and an increase in the 6MWT at 1 year, of 65 (95% CI 35 to 99) m compared with baseline p<0.001. Conclusions Our findings support the feasibility of long-term participation in a community singing group for adults with COPD who have completed PR and are enrolled in a weekly community exercise group and provide evidence of improved exercise capacity and a reduction in anxiety. Trial registration number ACTRN12615000736549; Results. PMID:28119393

[Severity classification of chronic obstructive pulmonary disease based on deep learning].

PubMed

Ying, Jun; Yang, Ceyuan; Li, Quanzheng; Xue, Wanguo; Li, Tanshi; Cao, Wenzhe

2017-12-01

In this paper, a deep learning method has been raised to build an automatic classification algorithm of severity of chronic obstructive pulmonary disease. Large sample clinical data as input feature were analyzed for their weights in classification. Through feature selection, model training, parameter optimization and model testing, a classification prediction model based on deep belief network was built to predict severity classification criteria raised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We get accuracy over 90% in prediction for two different standardized versions of severity criteria raised in 2007 and 2011 respectively. Moreover, we also got the contribution ranking of different input features through analyzing the model coefficient matrix and confirmed that there was a certain degree of agreement between the more contributive input features and the clinical diagnostic knowledge. The validity of the deep belief network model was proved by this result. This study provides an effective solution for the application of deep learning method in automatic diagnostic decision making.

Assessment of lung function in a large cohort of patients with acromegaly.

PubMed

Störmann, Sylvère; Gutt, Bodo; Roemmler-Zehrer, Josefine; Bidlingmaier, Martin; Huber, Rudolf M; Schopohl, Jochen; Angstwurm, Matthias W

2017-07-01

Acromegaly is associated with increased mortality due to respiratory disease. To date, lung function in patients with acromegaly has only been assessed in small studies, with contradicting results. We assessed lung function parameters in a large cohort of patients with acromegaly. Lung function of acromegaly patients was prospectively assessed using spirometry, blood gas analysis and body plethysmography. Biochemical indicators of acromegaly were assessed through measurement of growth hormone and IGF-I levels. This study was performed at the endocrinology outpatient clinic of a tertiary referral center in Germany. We prospectively tested lung function of 109 acromegaly patients (53 male, 56 female; aged 24-82 years; 80 with active acromegaly) without severe acute or chronic pulmonary disease. We compared lung volume, air flow, airway resistance and blood gases to normative data. Acromegaly patients had greater lung volumes (maximal vital capacity, intra-thoracic gas volume and residual volume: P  < 0.001, total lung capacity: P  = 0.006) and showed signs of small airway obstruction (reduced maximum expiratory flow when 75% of the forced vital capacity (FVC) has been exhaled: P  < 0.001, lesser peak expiratory flow: P  = 0.01). There was no significant difference between active and inactive acromegaly. Female patients had significantly altered lung function in terms of subclinical airway obstruction. In our cross-sectional analysis of lung function in 109 patients with acromegaly, lung volumes were increased compared to healthy controls. Additionally, female patients showed signs of subclinical airway obstruction. There was no difference between patients with active acromegaly compared with patients biochemically in remission. © 2017 European Society of Endocrinology.

Lung disease and coal mining: what pulmonologists need to know.

PubMed

Go, Leonard H T; Krefft, Silpa D; Cohen, Robert A; Rose, Cecile S

2016-03-01

Coal mine workers are at risk for a range of chronic respiratory diseases including coal workers' pneumoconiosis, diffuse dust-related fibrosis, and chronic obstructive pulmonary disease. The purpose of this review is to describe coal mining processes and associated exposures to inform the diagnostic evaluation of miners with respiratory symptoms. Although rates of coal workers' pneumoconiosis declined after regulations were enacted in the 1970s, more recent data shows a reversal in this downward trend. Rapidly progressive pneumoconiosis with progressive massive fibrosis (complicated coal workers' pneumoconiosis) is being observed with increased frequency in United States coal miners, with histologic findings of silicosis and mixed-dust pneumoconiosis. There is increasing evidence of decline in lung function in individuals with pneumoconiosis. Multiple recent cohort studies suggest increased risk of lung cancer in coal miners. A detailed understanding of coal mining methods and processes allows clinicians to better evaluate and confirm chronic lung diseases caused by inhalational hazards in the mine atmosphere.

Quality Improvement Initiatives to Optimize the Management of Chronic Obstructive Pulmonary Disease in Patients With Lung Cancer.

PubMed

Digby, Geneviève C; Robinson, Andrew

2017-11-01

Patients with lung cancer (LC) frequently have chronic obstructive pulmonary disease (COPD), the optimization of which improves outcomes. A 2014 Queen's University Hospitals audit demonstrated that COPD was underdiagnosed and undertreated in outpatients with LC. We sought to improve the diagnosis and management of COPD in this population. We implemented change using a Define/Measure/Analyze/Improve/Control (DMAIC) improvement cycle. Data were obtained by chart review from the Cancer Care Ontario database and e-Patient System for patients with newly diagnosed LC, including patient characteristics, pulmonary function test (PFT) data, and bronchodilator therapies. Improvement cycle 1 included engaging stakeholders and prioritizing COPD management by respirologists in the Lung Diagnostic Assessment Program. Improvement cycle 2 included physician restructuring and developing a standard work protocol. Data were analyzed monthly and presented on statistical process control P-charts, which assessed differences over time. The χ 2 and McNemar tests assessed for significance between independent and dependent groups, respectively. A total of 477 patients were studied (165 patients at baseline, 166 patients in cycle 1, and 127 patients in cycle 2). There was no change in PFT completion over time, although respirology-managed patients were significantly more likely to undergo a PFT than patients who were not managed by respirology (56.7% v 96.1%; P < .00001). The proportion of respirology-managed patients with LC with airflow obstruction receiving inhaled bronchodilator significantly increased (baseline, 46.3%; cycle 1, 51.0%; and cycle 2, 74.3%). By cycle 2, patients with airflow obstruction were more likely to receive a long-acting bronchodilator if managed by respirology (74.3% v 44.8%; P = .0009). COPD is underdiagnosed and undertreated in outpatients with LC. A DMAIC quality improvement strategy emphasizing COPD treatment during LC evaluation in the Lung Diagnostic Assessment Program significantly improved COPD management.

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

PubMed

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

2017-07-01

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

DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease

PubMed Central

Birch, Jodie; Anderson, Rhys K.; Correia-Melo, Clara; Jurk, Diana; Hewitt, Graeme; Marques, Francisco Madeira; Green, Nicola J.; Moisey, Elizabeth; Birrell, Mark A.; Belvisi, Maria G.; Black, Fiona; Taylor, John J.; Fisher, Andrew J.; De Soyza, Anthony

2015-01-01

Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the first line of defense in the lungs and are important to COPD pathogenesis. However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood. We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure. We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro. We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected. With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure. Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema. We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8. We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD. PMID:26386121

Low prevalence of obstructive lung disease in a suburban population of Malaysia: A BOLD collaborative study.

PubMed

Loh, Li Cher; Rashid, Abdul; Sholehah, Siti; Gnatiuc, Louisa; Patel, Jaymini H; Burney, Peter

2016-08-01

As a Burden of Obstructive Lung Disease (BOLD) collaboration, we studied the prevalence of chronic obstructive pulmonary disease (COPD) and its associated risk factors in a suburban population in Malaysia. Nonhospitalized men or women of age ≥ 40 years from a Penang district were recruited by stratified simple random sampling. Participants completed detailed questionnaires on respiratory symptoms and exposure to COPD risk factors. Prebronchodilator and post-bronchodilator spirometry conducted was standardized across all international BOLD sites in device and data quality control. Of the 1218 individuals recruited for the study, 663 (340 men and 323 women) had complete questionnaire data and acceptable post-bronchodilator spirometry. The estimated population prevalence of Global Initiative for Chronic Obstructive Lung Disease (GOLD) ≥ stage I was 6.5% or 3.4% based on either fixed forced expiratory volume in 1 s/forced vital capacity ratio of <0.7 or National Health and Nutritional Examination Survey-derived lower limit of normal ratio while the prevalence of GOLD ≥ stage II was either 4.6% or 3.1%, respectively. Multivariate logistic regression analysis showed independent association between all stages of COPD with cigarette smoking pack years (adjusted odds ratio per 10-year increase: 1.73; 95% confidence interval: 1.09-2.75), use of biomass fuel for cooking (1.61; 1.10-2.36) and exposure to dusty job (1.50; 1.09-2.06). This study represented the first robust population-based epidemiology data on COPD for Malaysia. Compared with other sites globally, our estimated population prevalence was relatively low. In addition to cigarette smoking, use of biomass fuel and exposure to dusty job represented significant risk to the development of COPD. © 2016 Asian Pacific Society of Respirology.

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

PubMed

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

2014-08-20

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

Sing Your Lungs Out: a qualitative study of a community singing group for people with chronic obstructive pulmonary disease (COPD)

PubMed Central

McNaughton, Amanda; Aldington, Sarah; Williams, Gayle; Levack, William M M

2016-01-01

Objective To explore the ways in which participation in a community singing group contributed to the health and well-being of patients with chronic obstructive pulmonary disease (COPD). Design Qualitative description, based on transcripts from individual interviews and a focus group meeting with people with COPD participating in the singing group, regarding their experience. Setting Urban community, Wellington, New Zealand. Participants 23 people (13 women and 10 men), 51–91 years with COPD (21) or interstitial lung disease (2). Results The weekly singing group was a well-attended activity, with self-reported benefits to health and well-being. 4 key themes were identified: being in the ‘right space’, connection, purpose and growth, and participation in a meaningful physical activity. Conclusions This study helps us to better understand how participation in a community singing group can benefit the health and well-being of patients with COPD. Trial registration number ACTRN12615000736549; Results. PMID:27650768

Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation.

PubMed

Chuchalin, Alexander G; Khaltaev, Nikolai; Antonov, Nikolay S; Galkin, Dmitry V; Manakov, Leonid G; Antonini, Paola; Murphy, Michael; Solodovnikov, Alexander G; Bousquet, Jean; Pereira, Marcelo H S; Demko, Irina V

2014-01-01

Estimation suggests that at least 4 million people die, annually, as a result of chronic respiratory disease (CRD). The Global Alliance against Chronic Respiratory Diseases (GARD) was formed following a mandate from the World Health Assembly to address this serious and growing health problem. To investigate the prevalence of CRD in Russian symptomatic patients and to evaluate the frequency of major risk factors for CRD in Russia. A cross-sectional, population-based epidemiological study using the GARD questionnaire on adults from 12 regions of the Russian Federation. Common respiratory symptoms and risk factors were recorded. Spirometry was performed in respondents with suspected CRD. Allergic rhinitis (AR) and chronic bronchitis (CB) were defined by the presence of related symptoms according to the Allergic Rhinitis and its Impact on Asthma and the Global Initiative for Obstructive Lung Disease guidelines; asthma was defined based on disease symptoms; chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume per 1 second/forced vital capacity ratio <0.7 in symptomatic patients, following the Global Initiative for Obstructive Lung Disease guidelines. The number of questionnaires completed was 7,164 (mean age 43.4 years; 57.2% female). The prevalence of asthma symptoms was 25.7%, AR 18.2%, and CB 8.6%. Based on patient self-reported diagnosis, 6.9% had asthma, 6.5% AR, and 22.2% CB. The prevalence of COPD based on spirometry in patients with respiratory symptoms was estimated as 21.8%. The prevalence of respiratory diseases and risk factors was high in Russia when compared to available data. For bronchial asthma and AR, the prevalence for related symptoms was higher than self-reported previous diagnosis.

Lack of Correlation Between Pulmonary and Systemic Inflammation Markers in Patients with Chronic Obstructive Pulmonary Disease: A Simultaneous, Two-Compartmental Analysis.

PubMed

Núñez, Belen; Sauleda, Jaume; Garcia-Aymerich, Judith; Noguera, Aina; Monsó, Eduard; Gómez, Federico; Barreiro, Esther; Marín, Alicia; Antó, Josep Maria; Agusti, Alvar

2016-07-01

The origin of systemic inflammation in chronic obstructive pulmonary disease (COPD) patients remains to be defined, but one of the most widely accepted hypothesis is the 'spill over' of inflammatory mediators from the lung to the circulation. To evaluate the relationship between pulmonary and systemic inflammation in COPD quantifying several inflammatory markers in sputum and serum determined simultaneously. Correlations between various inflammatory variables (TNF-α, IL6, IL8) in sputum and serum were evaluated in 133 patients from the PAC-COPD cohort study. A secondary objective was the evaluation of relationships between inflammatory variables and lung function. Inflammatory markers were clearly higher in sputum than in serum. No significant correlation was found (absolute value, r=0.03-0.24) between inflammatory markers in blood and in sputum. There were no significant associations identified between those markers and lung function variables, such as FEV1, DLCO and PaO2 neither. We found no correlation between pulmonary and systemic inflammation in patients with stable COPD, suggesting different pathogenic mechanisms. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

Serum PARC/CCL-18 Concentrations and Health Outcomes in Chronic Obstructive Pulmonary Disease

PubMed Central

Sin, Don D.; Miller, Bruce E.; Duvoix, Annelyse; Man, S. F. Paul; Zhang, Xuekui; Silverman, Edwin K.; Connett, John E.; Anthonisen, Nicholas A.; Wise, Robert A.; Tashkin, Donald; Celli, Bartolome R.; Edwards, Lisa D.; Locantore, Nicholas; MacNee, William; Tal-Singer, Ruth; Lomas, David A.

2011-01-01

Rationale: There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. Objectives: To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. Methods: PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. Measurements and Main Results: Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. Conclusions: Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID:21216880

Anesthetic considerations in the patients of chronic obstructive pulmonary disease undergoing laparoscopic surgeries

PubMed Central

Khetarpal, Ranjana; Bali, Kusum; Chatrath, Veena; Bansal, Divya

2016-01-01

The aim of this study was to review the various anesthetic options which can be considered for laparoscopic surgeries in the patients with the chronic obstructive pulmonary disease. The literature search was performed in the Google, PubMed, and Medscape using key words “analgesia, anesthesia, general, laparoscopy, lung diseases, obstructive.” More than thirty-five free full articles and books published from the year 1994 to 2014 were retrieved and studied. Retrospective data observed from various studies and case reports showed regional anesthesia (RA) to be valid and safer option in the patients who are not good candidates of general anesthesia like patients having obstructive pulmonary diseases. It showed better postoperative patient outcome with respect to safety, efficacy, postoperative pulmonary complications, and analgesia. So depending upon disease severity RA in various forms such as spinal anesthesia, paravertebral block, continuous epidural anesthesia, combined spinal epidural anesthesia (CSEA), and CSEA with bi-level positive airway pressure should be considered. PMID:26957682

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study

PubMed Central

Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A.; Austin, John H. M.; Bluemke, David A.; Carr, James; Choi, Jiwoong; Goldstein, Thomas A.; Gomes, Antoinette S.; Hoffman, Eric A.; Kawut, Steven M.; Lima, Joao; Michos, Erin D.; Post, Wendy S.; Po, Ming Jack; Prince, Martin R.; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M.; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M.

2015-01-01

Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature. PMID:26067761

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

PubMed

Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A; Austin, John H M; Bluemke, David A; Carr, James; Choi, Jiwoong; Goldstein, Thomas A; Gomes, Antoinette S; Hoffman, Eric A; Kawut, Steven M; Lima, Joao; Michos, Erin D; Post, Wendy S; Po, Ming Jack; Prince, Martin R; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M; Barr, R Graham

2015-09-01

Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

[Transport of mucoid mucus in healthy individuals and patients with chronic obstructive pulmonary disease and bronchiectasis].

PubMed

Lima Afonso, J; Tambascio, J; Dutra de Souza, H C; Jardim, J R; Baddini Martinez, J A; Gastaldi, A C

2013-01-01

To characterise and compare the in vitro transport properties of respiratory mucoid secretion in individuals with no lung disease and in stable patients with chronic obstructive pulmonary disease (COPD) and bronchiectasis. Samples of mucus were collected, from 21 volunteers presenting no lung disease who had undergone surgery, from 10 patients presenting chronic COPD, and from 16 patients with bronchiectasis. Mucociliary transport (MCT), transport by cough (SCM), and contact angle (CAM) were evaluated. MCT was found to be greater in healthy individuals (1.0±0.19) than in COPD (0.91±0.17) and bronchiectasis (0.76±0.23) patients (p<0.05), whereas SCM was greater in COPD patients (16.31±7.35 cm) than in patients with bronchiectasis (12.16±6.64 cm) and healthy individuals (10.50±25.8 cm) (p<0.05). No significant differences were observed between the groups regarding CAM. Mucus from healthy individuals allows better mucociliary transport compared to that from patients with lung diseases. However, the mucus from COPD patients allows a better transport by coughing, demonstrating that these individuals have adapted to a defence mechanism compared to patients with bronchiectasis, who have impairment in their ciliary and cough transport mechanisms. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Pulmonary hypertension in chronic obstructive pulmonary disease and interstitial lung diseases.

PubMed

Weitzenblum, Emmanuel; Chaouat, Ari; Canuet, Matthieu; Kessler, Romain

2009-08-01

Pulmonary hypertension (PH) is a common complication of chronic respiratory diseases and particularly of chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD). Owing to its frequency COPD is by far the most common cause of PH. It is generally a mild to moderate PH, pulmonary artery mean pressure (PAP) usually ranging between 20 and 25 mm Hg, but PH may worsen during exercise, sleep, and particularly during exacerbations of the disease. These acute increases in PAP may lead to the development of right heart failure. A small proportion of COPD patients may present "disproportionate" PH defined by a resting PAP >35 to 40 mm Hg. The prognosis is particularly poor in these patients. PH is relatively frequent in advanced ILD and particularly in idiopathic pulmonary fibrosis. As in COPD the diagnosis is suggested by Doppler echocardiography, but the confirmation still requires right heart catheterization. As in COPD, functional (alveolar hypoxia) and morphological factors (vascular remodeling, destruction of the pulmonary parenchyma) explain the elevation of pulmonary vascular resistance that leads to PH. Also as in COPD PH is most often mild to moderate. In ILD the presence of PH predicts a poor prognosis. The treatment of PH relies on long-term oxygen therapy. "New" vasodilator drugs have rarely been used in COPD and ILD patients exhibiting severe PH. In advanced ILD the presence of PH is a supplemental argument for considering lung transplantation.

Mast cells in airway diseases and interstitial lung disease.

PubMed

Cruse, Glenn; Bradding, Peter

2016-05-05

Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. Published by Elsevier B.V.

Dual-energy micro-CT imaging of pulmonary airway obstruction: correlation with micro-SPECT

NASA Astrophysics Data System (ADS)

Badea, C. T.; Befera, N.; Clark, D.; Qi, Y.; Johnson, G. A.

2014-03-01

To match recent clinical dual energy (DE) CT studies focusing on the lung, similar developments for DE micro-CT of the rodent lung are required. Our group has been actively engaged in designing pulmonary gating techniques for micro- CT, and has also introduced the first DE micro-CT imaging method of the rodent lung. The aim of this study was to assess the feasibility of DE micro-CT imaging for the evaluation of airway obstruction in mice, and to compare the method with micro single photon emission computed tomography (micro-SPECT) using technetium-99m labeled macroaggregated albumin (99mTc-MAA). The results suggest that the induced pulmonary airway obstruction causes either atelectasis, or air-trapping similar to asthma or chronic bronchitis. Atelectasis could only be detected at early time points in DE micro-CT images, and is associated with a large increase in blood fraction and decrease in air fraction. Air trapping had an opposite effect with larger air fraction and decreased blood fraction shown by DE micro-CT. The decrease in perfusion to the hypoventilated lung (hypoxic vasoconstriction) is also seen in micro-SPECT. The proposed DE micro-CT technique for imaging localized airway obstruction performed well in our evaluation, and provides a higher resolution compared to micro-SPECT. Both DE micro-CT and micro-SPECT provide critical, quantitative lung biomarkers for image-based anatomical and functional information in the small animal. The methods are readily linked to clinical methods allowing direct comparison of preclinical and clinical results.

Diagnostic management of chronic obstructive pulmonary disease.

PubMed

Broekhuizen, B D L; Sachs, A P E; Hoes, A W; Verheij, T J M; Moons, K G M

2012-01-01

Detection of early chronic obstructive pulmonary disease (COPD) in patients presenting with respiratory symptoms is recommended; however, diagnosing COPD is difficult because a single gold standard is not available. The aim of this article is to review and interpret the existing evidence, theories and consensus on the individual parts of the diagnostic work-up for COPD. Relevant articles are discussed under the subheadings: history taking, physical examination, spirometry and additional lung function assessment. Wheezing, cough, phlegm and breathlessness on exertion are suggestive signs for COPD. The diagnostic value of the physical examination is limited, except for auscultated pulmonary wheezing or reduced breath sounds, increasing the probability of COPD. Spirometric airflow obstruction after bronchodilation, defined as a lowered ratio of the forced volume in one second to the forced vital capacity (FEV1/FVC ratio), is a prerequisite, but can only confirm COPD in combination with suggestive symptoms. Different thresholds are being recommended to define low FEV1/FVC, including a fixed threshold, and one varying with gender and age; however, the way physicians interpret these thresholds in their assessment is not well known. Body plethysmography allows a more complete assessment of pulmonary function, providing results on the total lung capacity and the residual volume and is indicated when conventional spirometry results are inconclusive. Chest radiography has no diagnostic value for COPD but is useful to exclude alternative diagnoses such as heart failure or lung cancer. Extensive history taking is of key importance in diagnosing COPD.

"You get old, you get breathless, and you die": chronic obstructive pulmonary disease in Barnsley, UK.

PubMed

Small, Nell; Gardiner, Clare; Barnes, Sarah; Gott, Merryn; Halpin, David; Payne, Sheila; Seamark, David

2012-11-01

We report patients, family members and health professionals' experiences of Chronic Obstructive Pulmonary Disease (COPD) in Barnsley, northern England. A widespread belief that having "bad lungs" is part of normal ageing shapes everyday experience in this former mining town. People with COPD, and their families, link its cause to the areas industrial past and are sceptical of a medical orthodoxy that attributes cause to smoking. They doubt doctors' objectivity. Encouraging uptake of care, promoting smoking cessation, and developing care planning would be enhanced by engaging with the significance of place in the social narrative of health evident in this town. Copyright © 2012 Elsevier Ltd. All rights reserved.

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

PubMed Central

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

2017-01-01

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI). PMID:28335527

[Bronchopulmonary diseases features in miners of Kolsky Transpolar area].

PubMed

Siurin, S A; Nikanov, A N

2009-01-01

Miners engaged into open-cast and underground extraction of copper-nickel ores in Kolsky Transpolar area have chronic bronchitis as a main nosologic entity among chronic bronchopulmonary diseases (19.1% of the workers). Considerably lower (4.0% of the workers) occurrence concerns chronic obstructive lung disease and bronchial asthma, both developed before the occupational involvement (1.3% of the workers). Complex of occupational and nonoccupational risk factors is connected mostly with smoking that increases COLD/CB risk 10.7-15.8-fold.

Awareness of risk factors among persons at risk for lung cancer, chronic obstructive pulmonary disease and sleep apnea: A Canadian population-based study

PubMed Central

Walker, Shannon L; Saltman, David L; Colucci, Rosemary; Martin, Lesli

2010-01-01

OBJECTIVE To assess awareness among persons at risk for lung cancer, chronic obstructive pulmonary disease (COPD) and sleep apnea regarding symptoms and risk factors of the disease, and their attitudes regarding the disease and toward those who are affected. METHODS A quantitative hybrid telephone and Internet survey of a representative population of Canadian adults at risk for at least one of the three diseases was conducted. To measure the awareness and attitudes of First Nations, Inuit and Métis people to these diseases, a proportionate number were also surveyed. RESULTS A total of 3626 individuals were contacted. Of these, 3036 (84%) were eligible to participate. Of those at risk for lung cancer and COPD, 65% and 69%, respectively, were due to tobacco smoke exposure. Among those at risk, 72% believed that they were informed about lung cancer compared with 36% for COPD and 56% for sleep apnea. Most respondents were knowledgeable about the common symptoms of lung cancer, COPD and sleep apnea, but were less aware of the impact lifestyle choices could have on the development of these disorders and the availability of treatment. Most of the participants (77%) believed that smoking was an addiction rather than a habit (19%). There were no significant differences in the awareness of risk factors, symptoms and attitudes toward all three lung diseases between First Nations, Inuit and Métis people and the general population. CONCLUSIONS Canadians are reasonably aware of risk factors and symptoms for lung cancer and sleep apnea. However, there is poor awareness of COPD as a disease entity. There is a lack of appreciation for the impact lifestyle choices and changes can have on lung diseases. PMID:21165351

Awareness of risk factors among persons at risk for lung cancer, chronic obstructive pulmonary disease and sleep apnea: a Canadian population-based study.

PubMed

Walker, Shannon L; Saltman, David L; Colucci, Rosemary; Martin, Leslie

2010-01-01

To assess awareness among persons at risk for lung cancer, chronic obstructive pulmonary disease (COPD) and sleep apnea regarding symptoms and risk factors of the disease, and their attitudes regarding the disease and toward those who are affected. A quantitative hybrid telephone and Internet survey of a representative population of Canadian adults at risk for at least one of the three diseases was conducted. To measure the awareness and attitudes of First Nations, Inuit and Métis people to these diseases, a proportionate number were also surveyed.  A total of 3626 individuals were contacted. Of these, 3036 (84%) were eligible to participate. Of those at risk for lung cancer and COPD, 65% and 69%, respectively, were due to tobacco smoke exposure. Among those at risk, 72% believed that they were informed about lung cancer compared with 36% for COPD and 56% for sleep apnea. Most respondents were knowledgeable about the common symptoms of lung cancer, COPD and sleep apnea, but were less aware of the impact lifestyle choices could have on the development of these disorders and the availability of treatment. Most of the participants (77%) believed that smoking was an addiction rather than a habit (19%). There were no significant differences in the awareness of risk factors, symptoms and attitudes toward all three lung diseases between First Nations, Inuit and Métis people and the general population. Canadians are reasonably aware of risk factors and symptoms for lung cancer and sleep apnea. However, there is poor awareness of COPD as a disease entity. There is a lack of appreciation for the impact lifestyle choices and changes can have on lung diseases.

Sex differences in chronic obstructive pulmonary disease evaluated using optical coherence tomography

NASA Astrophysics Data System (ADS)

Kirby, Miranda; Zhang, Wei; Laratta, Peter K.; Sin, Don D.; Lam, Stephen; Coxson, Harvey O.

2014-03-01

Although there are more women than men dying of chronic obstructive pulmonary disease (COPD) in the United States and elsewhere, we still do not have a clear understanding of the differences in the pathophysiology of airflow obstruction between the sexes. Optical coherence tomography (OCT) is an emerging imaging technology that has the capability of imaging small bronchioles with resolution approaching histology. Therefore, our objective was to compare OCT-derived airway wall measurements between males and females matched for lung size and in anatomically matched small airways. Subjects 50-80 yrs were enrolled in the British Columbia Lung Health Study and underwent OCT and spirometry. OCT was performed using a 1.5mm diameter probe/sheath in anatomically matched airways for males and females; the right lower lobe (RB8 or RB9) or left lower lobe (LB8 or LB9) during end-expiration. OCT airway wall area (Aaw) was obtained by manual segmentation. For males and females there was no significant difference in OCT Aaw (p=0.12). Spearman correlation coefficients indicated that the forced expiratory volume in 1 second (FEV1) and Aaw were significantly correlated for males (r=-0.78, p=0.004) but not for females (r=-0.20, p=0.49) matched for lung size. These novel OCT findings demonstrate that while there were no overall sex differences in airway wall thickness, the relationship between lung function and airway wall thickness was correlated only in men. Therefore, factors other than airway remodeling may be driving COPD pathogenesis in women and OCT may provide important information for investigating airway remodeling and its relationship with COPD progression.

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

PubMed

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

2013-04-01

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

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

PubMed Central

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

2011-01-01

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

Association between childhood asthma and chronic obstructive pulmonary disease in later life.

PubMed

Hirayama, Fumi; Lee, Andy H

2015-03-01

Persistent chronic inflammation and impaired lung growth due to asthma in childhood may have long-term impact on pulmonary function and increase susceptibility to chronic obstructive pulmonary disease (COPD) in later life. To investigate whether childhood asthma is associated with adult lung function and the risk of developing COPD among Japanese older adults, a case-control study was conducted in central Japan. A total of 300 patients with COPD aged 50 to 75 years were referred by respiratory physicians, while 400 controls were recruited from the community. All participants underwent spirometric measurements of lung function. Information on childhood asthma, demographic characteristics, and lifestyle characteristics was obtained by face-to-face interview using a structured questionnaire. The prevalence of childhood asthma was higher (P = .015) among the cases (6.3%) than among the control group (2.4%). Childhood asthma was significantly associated with the risk of COPD (adjusted odds ratio 3.32, 95% confidence interval 1.05-10.45). Participants with childhood asthma had lower (P = .010) forced expiratory volume in 1 second (mean 1.63 L, standard deviation [SD] 0.64 L) than those without (mean 2.04 L, SD 0.75 L). However, the adjusted lung function difference did not attain statistical significance after controlling for confounding variables such as age and cumulative smoking exposure. The epidemiological evidence suggested a positive association between childhood asthma and COPD in later life. Further study of the effect of adequate childhood asthma treatment on future risk of COPD should be undertaken. © 2012 APJPH.

Stem cell treatment for chronic lung diseases.

PubMed

Tzouvelekis, Argyris; Ntolios, Paschalis; Bouros, Demosthenes

2013-01-01

Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will not only help to relieve patient symptoms but will also affect the natural course of the respective disease. Regenerative medicine represents a promising option with several fruitful therapeutic applications in patients suffering from chronic lung diseases. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administered stem cells within chronically injured lung as well as the mechanisms regulating the activation of resident progenitor cells. On the other hand, salient data arising from few 'brave' pilot investigations of the safety of stem cell treatment in chronic lung diseases seem promising. The main scope of this review article is to summarize the current state of knowledge regarding the application status of stem cell treatment in chronic lung diseases, address important safety and efficacy issues and present future challenges and perspectives. In this review, we argue in favor of large multicenter clinical trials setting realistic goals to assess treatment efficacy. We propose the use of biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn. Copyright © 2013 S. Karger AG, Basel.

Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

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

Yao Hongwei; Rahman, Irfan, E-mail: irfan_rahman@urmc.rochester.edu

Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-{kappa}B), autophagy and unfolded protein response leading to chronic lung inflammatorymore » response. Cigarette smoke also activates canonical/alternative NF-{kappa}B pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD.« less

Positron emission tomography-based evidence of low-amplitude respiratory motion in patients with chronic obstructive pulmonary disease.

PubMed

Daouk, Joël; Bailly, Pascal; Kamimura, Mitsuhiro; Sacksick, David; Jounieaux, Vincent; Meyer, Marc-Etienne

2015-05-01

Chronic obstructive pulmonary disease (COPD) is characterized by low vital capacity and tidal volume, which translate into smaller respiratory motions. We sought to demonstrate the limited respiratory motion in COPD by comparing respiratory-gated and free-breathing positron emission tomography (PET) images of lung nodules ("CT-based" and "Ungated" images) in patients with and without COPD. We studied 74 lung lesions (37 malignant) in 60 patients (23 patients with COPD; 37 without). An Ungated PET examination was followed by a CT-based acquisition. Maximum standard uptake value (SUVmax) for each lesion on PET images was measured. On CT images, we checked for the presence of emphysema and pleural adhesions or indentations associated with the nodules. Lastly, we used univariate and then multivariate analyses to determine the lung function parameters possibly affecting respiratory motion in patients with and without COPD. The mean "CT-based" vs. "Ungated" difference in SUVmax was 0.3 and 0.6 for patients with and without COPD, respectively. Statistical analysis revealed that lesion site, hyperinflation and pleural indentation were independently associated with a difference in SUVmax. PET lung lesion images in patients with COPD are barely influenced by respiratory motion. Thoracic hyperinflation in patients with COPD was found to be independently associated with an effect of respiratory motion on PET images. Moreover, pleural indentation limits the respiratory motion of lung nodules, regardless of the presence or absence of COPD.

Difference in airflow obstruction between Hispanic and non-Hispanic White female smokers.

PubMed

Sood, Akshay; Stidley, Christine A; Picchi, Maria A; Celedón, Juan C; Gilliland, Frank; Crowell, Richard E; Belinsky, Steven A; Tesfaigzi, Yohannes

2008-10-01

Smoking-related respiratory diseases are a major cause of morbidity and mortality. However, the relationship between smoking and respiratory disease has not been well-studied among ethnic minorities in general and among women in particular. The objective of this cross-sectional study was to evaluate the risk of airflow obstruction and to assess lung function among Hispanic and non-Hispanic White (NHW) female smokers in a New Mexico cohort. Participants completed a questionnaire detailing smoking history and underwent spirometry testing. Outcomes studied included airflow obstruction, selected lung function parameters, and chronic mucus hyper-secretion. Chi square, logistic, and linear regression techniques were utilized. Of the 1,433 eligible women participants, 248 (17.3%) were Hispanic; and 319 had airflow obstruction (22.3%). Hispanic smokers were more likely to be current smokers, and report lower pack-years of smoking, compared to NHW smokers (p < 0.05 for all analyses). Further, Hispanic smokers were at a reduced risk of airflow obstruction compared to NHW smokers, with an O.R. of 0.51, 95% C.I. 0.34, 0.78 (p = 0.002) after adjustment for age, BMI, pack-years and duration of smoking, and current smoking status. Following adjustment for covariates, Hispanic smokers also had a higher mean absolute and percent predicted post-bronchodilator FEV(1)/FVC ratio, as well as higher mean percent predicted FEV(1) (p < 0.05 for all analyses). Hispanic female smokers in this New Mexico-based cohort had lower risk of airflow obstruction and better lung function than NHW female smokers. Further, smoking history did not completely explain these associations.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis.

PubMed

Lowry, Kathryn P; Gazelle, G Scott; Gilmore, Michael E; Johanson, Colden; Munshi, Vidit; Choi, Sung Eun; Tramontano, Angela C; Kong, Chung Yin; McMahon, Pamela M

2015-05-15

Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30-pack-year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack-year thresholds. We used a previously validated simulation model to compare the health benefits of lung cancer screening in current and former smokers ages 55-80 with ≥30 pack-years with hypothetical programs using lower pack-year thresholds for individuals with COPD (≥20, ≥10, and ≥1 pack-years). Calibration targets for COPD prevalence and associated lung cancer risk were derived using the Framingham Offspring Study limited data set. We performed sensitivity analyses to evaluate the stability of results across different rates of adherence to screening, increased competing mortality risk from COPD, and increased surgical ineligibility in individuals with COPD. The primary outcome was projected life expectancy. Programs using lower pack-year thresholds for individuals with COPD yielded the highest life expectancy gains for a given number of screens. Highest life expectancy was achieved when lowering the pack-year threshold to ≥1 pack-year for individuals with COPD, which dominated all other screening strategies. These results were stable across different adherence rates to screening and increases in competing mortality risk for COPD and surgical ineligibility. Current and former smokers with COPD may disproportionately benefit from lung cancer screening. A lower pack-year threshold for screening eligibility may benefit this high-risk patient population. © 2015 American Cancer Society.

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

PubMed Central

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

2009-01-01

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

The impact of combined pulmonary fibrosis and chronic obstructive pulmonary disease on long-term survival after lung cancer surgery.

PubMed

Sekine, Yasuo; Sakairi, Yuichi; Yoshino, Mitsuru; Koh, Eitetsu; Hata, Atsushi; Suzuki, Hidemi; Yoshino, Ichiro

2014-06-01

The purpose of this study was to determine the impact of pulmonary fibrosis (PF) on postoperative complications and on long-term survival after surgical resection in lung cancer patients with chronic obstructive pulmonary disease (COPD). A retrospective chart review was conducted of 380 patients with COPD who had undergone pulmonary resection for lung cancer at the University Hospital between 1990 and 2005. The definition of COPD was a preoperative forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of less than 70%; PF was defined as obvious bilateral fibrous change in the lower lung fields, confirmed by computed tomography. PF was present in 41 patients (10.8%) with COPD; the remaining 339 patients (89.2%) did not have PF. The preoperative FVC/FEV1 was significantly lower in the group of patients with PF than in the group without (p < 0.05). Acute lung injury and home oxygen therapy were significantly more common in the PF group; however, the 30-day mortality was similar between the groups. The cumulative survival at 3 and 5 years was 53.6 and 36.9%, respectively, in the PF group and 71.4 and 66.1%, respectively, in the non-PF group (p = 0.0009). Increased age, decreased body mass index, advanced pathologic stage, and the existence of PF were identified as independent risk factors for decreased survival. PF is a risk factor for decreased survival after surgical treatment in lung cancer patients with COPD. Georg Thieme Verlag KG Stuttgart · New York.

[The results of the evaluation of 208 patients referred in the first 4 years to a lung transplantation program. The Lung Transplantation Group of Hospital Vall d'Hebron].

PubMed

Morell, F; Román, A; Bravo, C; Nicolau, F; Martí, S

1996-01-01

Retrospective analysis of the patients referred for possible lung transplants between 1990 and 1994. Between 1990 and 1994 the Lung Transplant Program at Hospital Vall d'Hebron received 208 referrals from all over Spain. The cases most often involved a combination of bronchiectasia and cystic fibrosis (29%), chronic obstructive pulmonary disease (25%) and pulmonary fibrosis (16.5%). Internationally established guidelines for lung transplantation were used to screen the cases and the results have been analyzed retrospectively. After first evaluating the report sent by the patient's pneumonologist, 100 patients (49%) were considered candidates for further hospital study. Of the 100, 53 (25%) were finally placed on an active waiting list. Twenty-seven (12.9%) of the 53 received transplants, 6 died while waiting, and the others remained on the waiting list on 31 December 1994. Mortality among the rejected patients between the first visit until the end of the study, excluding those who were not yet classified as serious cases and those who were terminally ill, was 36/123 (29%). Actuarial survival rates at 12 and 24 months for transplanted patients were 64 and 49%, respectively. After following the currently accepted screening methods, one in 4 patients referred for possible lung transplantation was finally given a place on the active waiting list. The series studied here is noteworthy for the relatively low number of patients with chronic obstructive pulmonary disease in comparison with other programs, although we expect the number to increase in the coming years.

Identifying possible asthma-COPD overlap syndrome in patients with a new diagnosis of COPD in primary care.

PubMed

Baarnes, Camilla Boslev; Kjeldgaard, Peter; Nielsen, Mia; Miravitlles, Marc; Ulrik, Charlotte Suppli

2017-01-05

The asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) remains poorly characterised. Our aim was to describe an algorithm for identifying possible ACOS in adults with newly diagnosed COPD in primary care. General practitioners (n=241) consecutively recruited subjects ⩾35 years, with tobacco exposure, at least one respiratory symptom and no previous diagnosis of obstructive lung disease. Possible ACOS was defined as chronic airflow obstruction, i.e., post-bronchodilator (BD) forced expiratory volume 1/forced vital capacity (FEV 1 /FVC) ratio<0.70, combined with wheeze (ACOS wheeze) and/or significant BD reversibility (ACOS BD reversibility). Of 3,875 (50% females, mean age 57 years) subjects screened, 700 (18.1%) were diagnosed with COPD, i.e., symptom(s), tobacco exposure and chronic airflow obstruction. Indications for ACOS were found in 264 (38%) of the COPD patients. The prevalence of ACOS wheeze and ACOS BD reversibility was 27% (n=190) and 16% (n=113), respectively (P<0.001), and only 6% (n=39) of the COPD patients fulfilled both criteria for ACOS. Patients with any ACOS were younger (P=0.04), had more dyspnoea (P<0.001), lower FEV 1 %pred (67% vs. 74%; P<0.001) and lower FEV 1 /FVC ratio (P=0.001) compared with COPD-only patients. Comparing subjects fulfilling both criteria for ACOS with those fulfilling criteria for ACOS wheeze only (n=151) and those fulfilling criteria for ACOS BD reversibility only (n=74) revealed no significant differences. Irrespective of the applied ACOS definition, no significant difference in life-time tobacco exposure was found between ACOS- and COPD-only patients. In subjects with a new diagnosis of COPD, the prevalence of ACOS is high. When screening for COPD in general practice among patients with no previous diagnosis of obstructive lung disease, patients with possible ACOS may be identified by self-reported wheeze and/or BD reversibility.

Determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease: The DOC study.

PubMed

Ronaldson, Sarah J; Dyson, Lisa; Clark, Laura; Hewitt, Catherine E; Torgerson, David J; Cooper, Brendan G; Kearney, Matt; Laughey, William; Raghunath, Raghu; Steele, Lisa; Rhodes, Rebecca; Adamson, Joy

2018-06-01

Early identification of chronic obstructive pulmonary disease (COPD) results in patients receiving appropriate management for their condition at an earlier stage in their disease. The determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease (DOC) study was a case-finding study to enhance early identification of COPD in primary care, which evaluated the diagnostic accuracy of a series of simple lung function tests and symptom-based case-finding questionnaires. Current smokers aged 35 or more were invited to undertake a series of case-finding tools, which comprised lung function tests (specifically, spirometry, microspirometry, peak flow meter, and WheezoMeter) and several case-finding questionnaires. The effectiveness of these tests, individually or in combination, to identify small airways obstruction was evaluated against the gold standard of spirometry, with the quality of spirometry tests assessed by independent overreaders. The study was conducted with general practices in the Yorkshire and Humberside area, in the UK. Six hundred eighty-one individuals met the inclusion criteria, with 444 participants completing their study appointments. A total of 216 (49%) with good-quality spirometry readings were included in the analysis. The most effective case-finding tools were found to be the peak flow meter alone, the peak flow meter plus WheezoMeter, and microspirometry alone. In addition to the main analysis, where the severity of airflow obstruction was based on fixed ratios and percent of predicted values, sensitivity analyses were conducted by using lower limit of normal values. This research informs the choice of test for COPD identification; case-finding by use of the peak flow meter or microspirometer could be used routinely in primary care for suspected COPD patients. Only those testing positive to these tests would move on to full spirometry, thereby reducing unnecessary spirometric testing. © 2018 John Wiley & Sons, Ltd.

Six-minute-walk distance and accelerometry predict outcomes in chronic obstructive pulmonary disease independent of Global Initiative for Chronic Obstructive Lung Disease 2011 Group.

PubMed

Durheim, Michael T; Smith, Patrick J; Babyak, Michael A; Mabe, Stephanie K; Martinu, Tereza; Welty-Wolf, Karen E; Emery, Charles F; Palmer, Scott M; Blumenthal, James A

2015-03-01

The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P=0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P=0.002). Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD.

Redefining Cut-Points for High Symptom Burden of the Global Initiative for Chronic Obstructive Lung Disease Classification in 18,577 Patients With Chronic Obstructive Pulmonary Disease.

PubMed

Smid, Dionne E; Franssen, Frits M E; Gonik, Maria; Miravitlles, Marc; Casanova, Ciro; Cosio, Borja G; de Lucas-Ramos, Pilar; Marin, Jose M; Martinez, Cristina; Mir, Isabel; Soriano, Joan B; de Torres, Juan P; Agusti, Alvar; Atalay, Nart B; Billington, Julia; Boutou, Afroditi K; Brighenti-Zogg, Stefanie; Chaplin, Emma; Coster, Samantha; Dodd, James W; Dürr, Selina; Fernandez-Villar, Alberto; Groenen, Miriam T J; Guimarães, Miguel; Hejduk, Karel; Higgins, Victoria; Hopkinson, Nicholas S; Horita, Nobuyuki; Houben-Wilke, Sarah; Janssen, Daisy J A; Jehn, Melissa; Joerres, Rudolf; Karch, Annika; Kelly, Julia L; Kim, Yu-Il; Kimura, Hiroshi; Koblizek, Vladimir; Kocks, Janwillem H; Kon, Samantha S C; Kwon, Namhee; Ladeira, Inês; Lee, Sang-Do; Leuppi, Joerg D; Locantore, Nicholas; Lopez-Campos, José L; D-C Man, William; Maricic, Lana; Mendoza, Laura; Miedinger, David; Mihaltan, Florin; Minami, Seigo; van der Molen, Thys; Murrells, Trevor J; Nakken, Nienke; Nishijima, Yu; Norman, Ian J; Novotna, Barbora; O'Donnell, Denis E; Ogata, Yoshitaka; Pereira, Eanes D; Piercy, James; Price, David; Pothirat, Chaicharn; Raghavan, Natya; Ringbaek, Thomas; Sajkov, Dimitar; Sigari, Naseh; Singh, Sally; Small, Mark; da Silva, Guilherme F; Tanner, Rebecca J; Tsiligianni, Ioanna G; Tulek, Baykal; Tzanakis, Nikolaos; Vanfleteren, Lowie E G W; Watz, Henrik; Webb, Katherine A; Wouters, Emiel F M; Xie, Guogang G; Yoshikawa, Masanori; Spruit, Martijn A

2017-12-01

Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Experimental determination of the respiratory tract deposition of diesel combustion particles in patients with chronic obstructive pulmonary disease

PubMed Central

2012-01-01

Background Air pollution, mainly from combustion, is one of the leading global health risk factors. A susceptible group is the more than 200 million people worldwide suffering from chronic obstructive pulmonary disease (COPD). There are few data on lung deposition of airborne particles in patients with COPD and none for combustion particles. Objectives To determine respiratory tract deposition of diesel combustion particles in patients with COPD during spontaneous breathing. Methods Ten COPD patients and seven healthy subjects inhaled diesel exhaust particles generated during idling and transient driving in an exposure chamber. The respiratory tract deposition of the particles was measured in the size range 10–500 nm during spontaneous breathing. Results The deposited dose rate increased with increasing severity of the disease. However, the deposition probability of the ultrafine combustion particles (< 100 nm) was decreased in COPD patients. The deposition probability was associated with both breathing parameters and lung function, but could be predicted only based on lung function. Conclusions The higher deposited dose rate of inhaled air pollution particles in COPD patients may be one of the factors contributing to their increased vulnerability. The strong correlations between lung function and particle deposition, especially in the size range of 20–30 nm, suggest that altered particle deposition could be used as an indicator respiratory disease. PMID:22839109

The Role of Innate and Adaptive Immune Cells in the Immunopathogenesis of Chronic Obstructive Pulmonary Disease.

PubMed

Nurwidya, Fariz; Damayanti, Triya; Yunus, Faisal

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic and progressive inflammatory disease of the airways and lungs that results in limitations of continuous airflow and is caused by exposure to noxious gasses and particles. A major cause of morbidity and mortality in adults, COPD is a complex disease pathologically mediated by many inflammatory pathways. Macrophages, neutrophils, dendritic cells, and CD8+ T-lymphocytes are the key inflammatory cells involved in COPD. Recently, the non-coding small RNA, micro-RNA, have also been intensively investigated and evidence suggest that it plays a role in the pathogenesis of COPD. Here, we discuss the accumulated evidence that has since revealed the role of each inflammatory cell and their involvement in the immunopathogenesis of COPD. Mechanisms of steroid resistance in COPD will also be briefly discussed.

Public spirometry for primary prevention of COPD.

PubMed

Zirlik, Sabine; Wich, Christina; Frieser, Markus; Hildner, Kai; Kleye, Christin; Neurath, Markus F; Fuchs, Florian S

2014-02-01

The most effective action for primary prevention of chronic obstructive lung disease is smoking cessation early enough. In secondary prevention, smokers with airway obstruction were more likely to quit smoking. The aim of this study was to evaluate the impact of a public spirometry on smoking habits in terms of primary prevention. Spirometry with its medical analysis was offered to visitors of a local public event called 'Lange Nacht der Wissenschaften' ('Long night of sciences'). The impact of results on smoking habits was evaluated in all smokers with an anonymized questionnaire afterwards. Two hundred fifty-seven people with the median age of 30 years (interquartile range 22-46) were examined. Out of 44 current smokers (17.1%), only two individuals showed a prebronchodilator FEV1/forced vital capacity-value <0.7. Fourteen smokers stated to have an increased motivation to quit smoking whereas 28 smokers declared that their motivation to quit smoking was independent of spirometry result. These smokers were significantly younger (median age 28 vs. 40 years, P = 0.025) without differences in spirometry results or smoking habits. In an unselected population with a high amount of younger adults, normal spirometry did not show a short-term benefit for primary prevention of chronic obstructive lung disease in terms of increasing motivation to quit smoking. © 2013 John Wiley & Sons, Ltd.

An Update on the Global Initiative for Chronic Obstructive Lung Disease 2017 Guidelines With a Focus on Classification and Management of Stable COPD.

PubMed

Burkes, Robert M; Donohue, James F

2018-06-01

The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines offer important changes to the assessment and management of stable COPD of importance to practitioners, respiratory therapists, pharmacists, and nurses who care for patients with COPD. Therapies are now chosen based on the burden of symptoms and the history of COPD exacerbations, and inhaler regimens are modifiable based on continual clinical reassessment. Although identifying the degree of airway obstruction remains important for informing the clinical status of the patient with COPD, FEV 1 is no longer used to direct the therapeutic approach. Therapies and modes of inhaled medication delivery for each GOLD grouping have been modified and reflect the need for reevaluation of patient symptoms and COPD exacerbation history as an indicator to add or withdraw therapies. As the knowledge of this important disease continues to expand, exacerbation and symptom prevention in patients with stable COPD will remain as an important target of COPD therapies and research. Novel drug combinations and delivery devices are sure to positively affect the practitioner's approach to patients with stable COPD. The new 2017 GOLD guidelines represent a step toward personalized care of the patient with COPD. Copyright © 2018 by Daedalus Enterprises.

Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial–American College of Radiology Imaging Network Cohort

PubMed Central

Hopkins, Raewyn J.; Duan, Fenghai; Chiles, Caroline; Greco, Erin M.; Gamble, Greg D.; Aberle, Denise

2017-01-01

Rationale: Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk. Objectives: We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1–4. Methods: In the National Lung Screening Trial–ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group). Measurements and Main Results: Compared with those with no airflow limitation, where lung cancer incidence was 3.78/1,000 person years, incidence rates increased in a simple linear relationship: GOLD 1 (6.27/1,000 person yr); GOLD 2 (7.86/1,000 person yr); GOLD 3 (10.71/1,000 person yr); and GOLD 4 (13.25/1,000 person yr). All relationships were significant versus the reference group at a P value of 0.0001 or less. Conclusions: In a large prospective study of high-risk cigarette smokers, we report a strong linear relationship between increasing severity of airflow limitation and risk of lung cancer. PMID:28076701

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

PubMed

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

2014-09-01

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

Pulmonary tumorlets with surrounding fibrous tissue--suspected carcinoma: case report and review of the literature.

PubMed

Alerić, Ivan; Mosler, Domagoj; Seiwerth, Sven; Polić, Ines Mlinarević; Mosler, Elvira Lazić

2014-06-01

Pulmonary tumorlets are small, often multiple nodular proliferations of pulmonary neuroendocrine cells. They are common incidental findings in chronic inflammatory pulmonary diseases. They can also be found in normal lung parenchyma and as one part of the continuum known as diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. In many cases, they are incidental histologic findings of no importance or clinical consequences, or they can be associated with a very slow progression of either obstructive or mixed obstructive/restrictive impairment with good prognosis. Only rarely, they metastasize to an adjacent lymph node or produce ectopic neuroendocrine products. When found during diagnostic examination, they represent a doubt to be a malignant tumor until proven otherwise, which is often impossible without biopsy or surgical removal of the adjacent lung lobe. Hereby, we present a patient with a persistent nodular lung structure after being treated for nonspecific symptoms, cough with non purulent sputum and pain among the scapulae, for a period of one month. He had otherwise normal clinical and laboratory findings, except for a mild mixed obstructive/restrictive pattern of impairment that was shown by lung spirometry. After 8 months, he underwent lobectomy of the medial lobe of the lung with partial lymphadenectomy, since the diagnostic methods applied could not define the nature of lung nodular infiltration. Histologic examination showed a few tumorlets surrounded by the fibrous tissue with a very dense lymphocyte infiltration. We present a review of the literature and emphasize the necessity to include tumorlets with adjacent fibrosis as part of the differential diagnosis of a solitary nodular lung structure.

Signs of Gas Trapping in Normal Lung Density Regions in Smokers.

PubMed

Bodduluri, Sandeep; Reinhardt, Joseph M; Hoffman, Eric A; Newell, John D; Nath, Hrudaya; Dransfield, Mark T; Bhatt, Surya P

2017-12-01

A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known. To identify subthreshold structural disease in normal-appearing lung regions in smokers. We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity. The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV 1 (adjusted β = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted β = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted β = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted β = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV 1 change at follow-up (adjusted β = -3.013; 95% CI, -4.478 to -1.548; P = 0.001). Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

[Potential of antiinflammatory therapy in patients with chronic obstructive lung disease].

PubMed

Fedorova, T A; Ekkert, N V; Chernekhovskaia, N E; Roĭtman, A P; Makarova, O V; Zhidkova, N V

2005-01-01

The aim of the study was to investigate the effects of erespal (fenspirid) on the clinical manifestations and parameters of inflammation in patients with chronic obstructive lung disease (COLD). The two stages of the study included 3-weak treatment during exacerbation periods and a 3-month outpatient follow-up during clinical remission periods. Erespal was administered twice a day in a total dose of 160 mg/day. The study included evaluation of clinical symptoms, respiratory function, bronchoscopic data, laboratory indices of inflammation, antioxydative status, life quality (LQ), as well as cytological and cytochemical analysis of induced sputum (IS). During exacerbation periods of COLD the researchers observed early and noticeable antitussive and mucolytic action of erespal, which were associated with lessening of bronchial obstruction and inflammation, significant fall of C-reactive protein level, cytosis in IS, proportion of neutrophiles (p < 0.01), elevation of lysosomal cation proteins in neutrophiles (p < 0.01), increase of total oxidant serum level (in 46.2% of the patients vs. 26.3% of the patients in the conventional therapy group). Long term (3 months) treatment with erespal led to further positive dynamics of clinical and laboratory indices of inflammation, and improved the results of cytological and cytochemical study of IS. The results of the study demonstrate that inclusion of erespal in complex therapy of COLD increases efficacy of treatment, due to its anti-inflammatory action during the periods of exacerbation and relative remission, prevents augmenting of bronchial obstruction, and improves patients' LQ.

Ultrasonographic assessment of the diaphragm in chronic obstructive pulmonary disease patients: relationships with pulmonary function and the influence of body composition - a pilot study.

PubMed

Smargiassi, Andrea; Inchingolo, Riccardo; Tagliaboschi, Linda; Di Marco Berardino, Alessandro; Valente, Salvatore; Corbo, Giuseppe Maria

2014-01-01

Skeletal muscle weakness with loss of fat-free mass (FFM) is one of the main systemic effects of chronic obstructive pulmonary disease (COPD). The diaphragm is also involved, leading to disadvantageous conditions and poor contractile capacities. We measured the thickness of the diaphragm (TD) by ultrasonography to evaluate the relationships between echographic measurements, parameters of respiratory function and body composition data. Thirty-two patients (23 males) underwent (1) pulmonary function tests, (2) echographic assessment of TD in the zone of apposition at various lung volumes, i.e. TD at residual volume (TDRV), TD at functional residual capacity (TDFRC) and TD at total lung capacity (TDTLC), and (3) bioelectrical body impedance analysis. The BMI and the BODE (BMI-Obstruction-Dyspnea-Exercise) index values were reported. TDRV, TDFRC and TDTLC measured 3.3, 3.6 and 6 mm, respectively, with good intraobserver reproducibility (0.97, 0.97 and 0.96, respectively). All the TDs were found to be related to FFM, with the relationship being greater for TDFRC (r(2) = 0.39 and p = 0.0002). With regard to lung volumes, inspiratory capacity (IC) was found to be closely related to TDTLC (r(2) = 0.42 and p = 0.0001). The difference between TDTLC and TDRV, as a thickening value (TDTLCRV), was closely related to FVC (r(2) = 0.34 and p = 0.0004) and to air-trapping indices (RV/TLC, FRC/TLC and IC/TLC): the degree of lung hyperinflation was greater and the TDTLCRV was less. Finally, we found a progressive reduction of both thicknesses and thickenings as the severity of IC/TLC increased, with a significant p value for the trend in both analyses (p = 0.02). Ultrasonographic assessment of the diaphragm could be a useful tool for studying disease progression in COPD patients, in terms of lung hyperinflation and the loss of FFM. © 2014 S. Karger AG, Basel.

Automated segmentation of the lungs from high resolution CT images for quantitative study of chronic obstructive pulmonary diseases

NASA Astrophysics Data System (ADS)

Garg, Ishita; Karwoski, Ronald A.; Camp, Jon J.; Bartholmai, Brian J.; Robb, Richard A.

2005-04-01

Chronic obstructive pulmonary diseases (COPD) are debilitating conditions of the lung and are the fourth leading cause of death in the United States. Early diagnosis is critical for timely intervention and effective treatment. The ability to quantify particular imaging features of specific pathology and accurately assess progression or response to treatment with current imaging tools is relatively poor. The goal of this project was to develop automated segmentation techniques that would be clinically useful as computer assisted diagnostic tools for COPD. The lungs were segmented using an optimized segmentation threshold and the trachea was segmented using a fixed threshold characteristic of air. The segmented images were smoothed by a morphological close operation using spherical elements of different sizes. The results were compared to other segmentation approaches using an optimized threshold to segment the trachea. Comparison of the segmentation results from 10 datasets showed that the method of trachea segmentation using a fixed air threshold followed by morphological closing with spherical element of size 23x23x5 yielded the best results. Inclusion of greater number of pulmonary vessels in the lung volume is important for the development of computer assisted diagnostic tools because the physiological changes of COPD can result in quantifiable anatomic changes in pulmonary vessels. Using a fixed threshold to segment the trachea removed airways from the lungs to a better extent as compared to using an optimized threshold. Preliminary measurements gathered from patient"s CT scans suggest that segmented images can be used for accurate analysis of total lung volume and volumes of regional lung parenchyma. Additionally, reproducible segmentation allows for quantification of specific pathologic features, such as lower intensity pixels, which are characteristic of abnormal air spaces in diseases like emphysema.

Bronchiolitis Obliterans Syndrome: The Achilles’ Heel of Lung Transplantation

PubMed Central

Weigt, S. Samuel; DerHovanessian, Ariss; Wallace, W. Dean; Lynch, Joseph P.; Belperio, John A.

2016-01-01

Lung transplantation is a therapeutic option for patients with end-stage pulmonary disorders. Unfortunately, chronic lung allograft dysfunction (CLAD), most commonly manifest as bronchiolitis obliterans syndrome (BOS), continues to be highly prevalent and is the major limitation to long-term survival. The pathogenesis of BOS is complex and involves alloimmune and nonalloimmune pathways. Clinically, BOS manifests as airway obstruction and dyspnea that are classically progressive and ultimately fatal; however, the course is highly variable, and distinguishable phenotypes may exist. There are few controlled studies assessing treatment efficacy, but only a minority of patients respond to current treatment modalities. Ultimately, preventive strategies may prove more effective at prolonging survival after lung transplantation, but their remains considerable debate and little data regarding the best strategies to prevent BOS. A better understanding of the risk factors and their relationship to the pathological mechanisms of chronic lung allograft rejection should lead to better pharmacological targets to prevent or treat this syndrome. PMID:23821508

The Lung Immune Response to Nontypeable Haemophilus influenzae (Lung Immunity to NTHi)

PubMed Central

King, Paul T.; Sharma, Roleen

2015-01-01

Haemophilus influenzae is divided into typeable or nontypeable strains based on the presence or absence of a polysaccharide capsule. The typeable strains (such as type b) are an important cause of systemic infection, whilst the nontypeable strains (designated as NTHi) are predominantly respiratory mucosal pathogens. NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract. In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease. NTHi induces a strong inflammatory response in the respiratory tract with activation of immune responses, which often fail to clear the bacteria from the lung. This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology. This review will summarise the current literature about the lung immune response to nontypeable Haemophilus influenzae, a topic that has important implications for patient management. PMID:26114124

Inflammasomes in the lung.

PubMed

Pinkerton, James W; Kim, Richard Y; Robertson, Avril A B; Hirota, Jeremy A; Wood, Lisa G; Knight, Darryl A; Cooper, Matthew A; O'Neill, Luke A J; Horvat, Jay C; Hansbro, Philip M

2017-06-01

Innate immune responses act as first line defences upon exposure to potentially noxious stimuli. The innate immune system has evolved numerous intracellular and extracellular receptors that undertake surveillance for potentially damaging particulates. Inflammasomes are intracellular innate immune multiprotein complexes that form and are activated following interaction with these stimuli. Inflammasome activation leads to the cleavage of pro-IL-1β and release of the pro-inflammatory cytokine, IL-1β, which initiates acute phase pro-inflammatory responses, and other responses are also involved (IL-18, pyroptosis). However, excessive activation of inflammasomes can result in chronic inflammation, which has been implicated in a range of chronic inflammatory diseases. The airways are constantly exposed to a wide variety of stimuli. Inflammasome activation and downstream responses clears these stimuli. However, excessive activation may drive the pathogenesis of chronic respiratory diseases such as severe asthma and chronic obstructive pulmonary disease. Thus, there is currently intense interest in the role of inflammasomes in chronic inflammatory lung diseases and in their potential for therapeutic targeting. Here we review the known associations between inflammasome-mediated responses and the development and exacerbation of chronic lung diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Advances in the Evaluation of Respiratory Pathophysiology during Exercise in Chronic Lung Diseases

PubMed Central

O'Donnell, Denis E.; Elbehairy, Amany F.; Berton, Danilo C.; Domnik, Nicolle J.; Neder, J. Alberto

2017-01-01

Dyspnea and exercise limitation are among the most common symptoms experienced by patients with various chronic lung diseases and are linked to poor quality of life. Our understanding of the source and nature of perceived respiratory discomfort and exercise intolerance in chronic lung diseases has increased substantially in recent years. These new mechanistic insights are the primary focus of the current review. Cardiopulmonary exercise testing (CPET) provides a unique opportunity to objectively evaluate the ability of the respiratory system to respond to imposed incremental physiological stress. In addition to measuring aerobic capacity and quantifying an individual's cardiac and ventilatory reserves, we have expanded the role of CPET to include evaluation of symptom intensity, together with a simple “non-invasive” assessment of relevant ventilatory control parameters and dynamic respiratory mechanics during standardized incremental tests to tolerance. This review explores the application of the new advances in the clinical evaluation of the pathophysiology of exercise intolerance in chronic obstructive pulmonary disease (COPD), chronic asthma, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). We hope to demonstrate how this novel approach to CPET interpretation, which includes a quantification of activity-related dyspnea and evaluation of its underlying mechanisms, enhances our ability to meaningfully intervene to improve quality of life in these pathologically-distinct conditions. PMID:28275353

Role of bronchodilation and pattern of breathing in increasing tidal expiratory flow with progressive induced hypercapnia in chronic obstructive pulmonary disease.

PubMed

Finucane, Kevin E; Singh, Bhajan

2018-01-01

Hypercapnia (HC) in vitro relaxes airway smooth muscle; in vivo, it increases respiratory effort, tidal expiratory flows (V̇ exp ), and, by decreasing inspiratory duration (Ti), increases elastic recoil pressure (Pel) via lung viscoelasticity; however, its effect on airway resistance is uncertain. We examined the contributions of bronchodilation, Ti, and expiratory effort to increasing V̇ exp with progressive HC in 10 subjects with chronic obstructive pulmonary disease (COPD): mean forced expiratory volume in 1 s (FEV 1 ) 53% predicted. Lung volumes (Vl), V̇ exp , esophageal pressure (Pes), Ti, and end-tidal Pco 2 ([Formula: see text]) were measured during six tidal breaths followed by an inspiratory capacity (IC), breathing air, and at three levels of HC. V̇ exp and V̇ with submaximal forced vital capacities breathing air (V̇ sFVC ) were compared. Pulmonary resistance ( Rl) was measured from the Pes-V̇ relationship. V̇ exp and Pes at end-expiratory lung volume (EELV) + 0.3 tidal volume [V̇ (0.3Vt) and Pes (0.3Vt) , respectively], Ti, and Rl correlated with [Formula: see text] ( P < 0.001 for all) and were independent of tiotropium. [Formula: see text], Ti, and Pes (0.3Vt) predicted the increasing V̇ (0.3Vt) /V̇ sFVC(0.3Vt) [multiple regression analysis (MRA): P = 0.001, 0.004, and 0.025, respectively]. At [Formula: see text] ≥ 50 Torr, V̇ (0.3Vt) /V̇ sFVC(0.3Vt) exceeded unity in 30 of 36 measurements and was predicted by [Formula: see text] and Pes (0.3Vt) (MRA: P = 0.02 and 0.025, respectively). Rl decreased at [Formula: see text] 45 Torr ( P < 0.05) and did not change with further HC. IC and Vl (0.3Vt) did not change with HC. We conclude that in COPD HC increases V̇ exp due to bronchodilation, increased Pel secondary to decreasing Ti, and increased expiratory effort, all promoting lung emptying and a stable EELV. NEW & NOTEWORTHY The response of airways to intrapulmonary hypercapnia (HC) is uncertain. In chronic obstructive pulmonary disease (COPD), progressive HC increases tidal expiratory flows by inducing bronchodilation and via an increased rate of inspiration and lung viscoelasticity, a probable increase in lung elastic recoil pressure, both changes increasing expiratory flows, promoting lung emptying and a stable end-expiratory volume. Bronchodilation with HC occurred despite optimal standard bronchodilator therapy, suggesting that in COPD further bronchodilation is possible.

[Living with advanced chronic obstructive pulmonary disease: The impact of dyspnoea on patients and caregivers].

PubMed

Costa, Xavier; Gómez-Batiste, Xavier; Pla, Margarida; Martínez-Muñoz, Marisa; Blay, Carles; Vila, Laura

2016-12-01

To understand the experiences of patients and caregivers living with advanced chronic obstructive pulmonary disease, the impact of their symptoms and care needs arising from a functional, emotional, and social context. Qualitative study. Phenomenological perspective. Data were collected during 2013-2015. Primary, secondary and intermediate care. Osona (Barcelona). The study included 10 Primary Care patients with advanced chronic obstructive pulmonary disease, their respective 10 caregivers, and 19 primary care professionals, as well as 2 lung specialists, 2 palliative care professionals involved in their care, and one clinical psychologist. Theoretical sampling. Semi-structured and in-depth interviews with patients, caregivers, and professionals (47 interviews). The emergent topics identified in patients and caregivers interviews refer to dyspnoea, the predominant symptom without effective treatment and with a major impact on patients and caregivers lives. A symptom with great functional, emotional and social repercussions to which they need to adapt in order to survive. Beyond pharmacological measures to control respiratory symptoms, proper care of patients with chronic obstructive pulmonary disease, requires understanding of suffering, the losses and limitations that it causes in their lives and those of their caregivers. A palliative, holistic and closer approach to their real experiences, together with an empowerment to adapt to debilitating symptoms, could contribute to a better life in the end-stages of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

The emerging role of myeloid-derived suppressor cells in lung diseases.

PubMed

Kolahian, Saeed; Öz, Hasan Halit; Zhou, Benyuan; Griessinger, Christoph M; Rieber, Nikolaus; Hartl, Dominik

2016-03-01

Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterised by their potential to control T-cell responses and to dampen inflammation. While the role of MDSCs in cancer has been studied in depth, our understanding of their relevance for infectious and inflammatory disease conditions has just begun to evolve. Recent studies highlight an emerging and complex role for MDSCs in pulmonary diseases. In this review, we discuss the potential contribution of MDSCs as biomarkers and therapeutic targets in lung diseases, particularly lung cancer, tuberculosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis. Copyright ©ERS 2016.

[Chronic Obstructive Pulmonary Disease (COPD) - Rational Diagnostics and Therapy].

PubMed

Burkhardt, R; Pankow, W

2016-08-01

In general chronic obstructive pulmonary disease (COPD) can be diagnosed in family practice from history and spirometry. Inconclusive spirometry findings have to be assessed further by techniques available in a pulmonologist's office. Further testing is done for differential diagnostic reasons and for prognostic appraisal. Successful smoking cessation importantly alters the natural downhill course of the disease. Patient education and rehabilitative interventions (e. g. participation in lung sport groups) help to improve life quality. Medical therapies with bronchospasmolytics applied by inhalation as monotherapies, free and fixed combinations have symptomatic benefit. Considering the increase of pneumonia risk from inhaled corticosteroids their use should be restricted to patients with a straightforward indication, e. g. coexisting asthma. © Georg Thieme Verlag KG Stuttgart · New York.

Phytoceuticals: the new 'physic garden' for asthma and chronic obstructive pulmonary disease.

PubMed

Grandhi, Sumalatha; Donnelly, Louise E; Rogers, Duncan F

2007-10-01

Phytoceuticals (non-nutritional but beneficial plant chemicals) merit investigation as pharmacotherapy for asthma and chronic obstructive pulmonary disease (COPD). Although asthma is mostly treated adequately, COPD is not. Thus, there is a need for new drugs with improved therapeutic benefit, especially in COPD. Recent interest in herbal remedies has redirected attention towards plants as sources of improved treatments for lung disease. Phytoceuticals from a variety of plants and plant products, including butterbur, English ivy, apples, chocolate, green tea and red wine, demonstrate broad-spectrum pharmacotherapeutic activities that could be exploited in the clinic. Well-designed clinical trials are required to determine whether these beneficial activities are reproduced in patients, with the prospect that phytoceuticals are the new physic garden for asthma and COPD.

Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

PubMed

Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

2015-03-01

Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.

PubMed

Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J

2016-05-01

Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

A systematic review of quality and cost-effectiveness derived from Markov models evaluating smoking cessation interventions in patients with chronic obstructive pulmonary disease.

PubMed

Kirsch, Florian

2015-04-01

Smoking cessation is the only strategy that has shown a lasting reduction in the decline of lung function in patients with chronic obstructive pulmonary disease. This study aims to evaluate the cost-effectiveness of smoking cessation interventions in patients with chronic obstructive pulmonary disease, to assess the quality of the Markov models and to estimate the consequences of model structure and input data on cost-effectiveness. A systematic literature search was conducted in PubMed, Embase, BusinessSourceComplete and Econlit on June 11, 2014. Data were extracted, and costs were inflated. Model quality was evaluated by a quality appraisal, and results were interpreted. Ten studies met the inclusion criteria. The results varied widely from cost savings to additional costs of €17,004 per quality adjusted life year. The models scored best in the category structure, followed by data and consistency. The quality of the models seems to rise over time, and regarding the results there is no economic reason to refuse the reimbursement of any smoking cessation intervention.

Role of the fixed combination of fluticasone and salmeterol in adult Chinese patients with asthma and COPD

PubMed Central

Gao, Jinming; Pleasants, Roy A

2015-01-01

Chronic obstructive pulmonary disease (COPD) and asthma are common airway disorders characterized by chronic airway inflammation and airflow obstruction, and are a leading cause of morbidity and mortality in the People’s Republic of China. These two diseases pose a high economic burden on the family and the whole of society. Despite evidence-based Global Initiative for Chronic Obstructive Lung Disease and Global Initiative for Asthma guidelines being available for the diagnosis and management of COPD and asthma, many of these patients are not properly diagnosed or managed in the People’s Republic of China. The value of combination therapy with inhaled corticosteroids and long-acting β2-agonists has been established in the management of asthma and COPD globally. Combinations of inhaled corticosteroids and long-acting β2-agonists such as fluticasone and salmeterol, have been shown to be effective for improving symptoms, health status, and reducing exacerbations in both diseases. In this review, we discuss the efficacy and safety of this combination therapy from key studies, particularly in the People’s Republic of China. PMID:25926729

Protective effect of fenspiride on the bronchi in rats with chronic obstructive pulmonary disease.

PubMed

Kuzubova, N A; Lebedeva, E S; Fedin, A N; Dvorakovskaya, I V; Titova, O N

2013-06-01

We studied the effect of a non-steroidal anti-inflammatory drug fenspiride on contractive activity of bronchial smooth muscles on the model of chronic obstructive pulmonary disease of rats induced by 60-day exposure to nitrogen dioxide. The administration of fenspiride during the acute stage of the disease (day 15) abolished the constricting effect of the pollutant on the bronchial smooth muscles. Dilatation effect of fenspiride in a low dose (0.15 mg/kg) was mediated by its interaction with nerve endings of bronchial capsaicin-sensitive nerve C-fibers. The interaction of drug with receptors of C-fibers prevented neurogenic inflammation, which was confirmed by the absence of structural changes in the lungs typical of this pathology. The broncholytic effect of fenspiride in a high dose (15 mg/kg) was mediated by not only afferent pathways, but also its direct relaxing action on smooth muscle cells. The observed anti-inflammatory and bronchodilatation effect of fenspiride in very low doses can be used for prevention of chronic obstructive pulmonary disease in risk-group patients contacting with aggressive environmental factors.

Level of daily physical activity in chronic obstructive pulmonary disease (COPD) patients according to GOLD classification.

PubMed

Rodó-Pin, Anna; Balañá, Ana; Molina, Lluís; Gea, Joaquim; Rodríguez, Diego A

2017-02-09

The Global Initiative for Chronic Obstructive Lung Disease (GOLD guideline) for patients with chronic obstructive pulmonary disease does not adequately reflect the impact of the disease because does not take into account daily physical activity (DPA). Forty eight patients (12 in each GOLD group) were prospectively recruited. DPA was evaluated by accelerometer. Patients were classified into 3 levels of activity (very inactive, sedentary, active). No significant differences in levels of physical activity among GOLD groups (P=.361) were observed. The percentages of very inactive patients were 33% in group A, 42% in group B, 42% in group C and 59% in group D. In addition, high percentage of sedentary patients were observed through 4 groups, in group A (50%), B and C (42%, each), and group D (41%). COPD patients has very low levels of physical activity at all stages of GOLD classification even those defined as low impact (such as GOLD A). Is necessary to detect patients at risk who might benefit from specific interventions. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Histopathological Analogies in Chronic Pulmonary Lesions between Cattle and Humans: Basis for an Alternative Animal Model

PubMed Central

Ramírez-Romero, Rafael; Nevárez-Garza, Alicia M.; Rodríguez-Tovar, Luis E.; Wong-González, Alfredo; Ledezma-Torres, Rogelio A.; Hernández-Vidal, Gustavo

2012-01-01

Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP) and chronic obstructive pulmonary disease (COPD) in human beings, calves are proposed as an alternative animal model. PMID:22629176

Health-hazard evaluation report HETA 88-391-2156, Morton Salt Company, Weeks Island, Louisiana

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

Ferguson, R.P.; Knutti, E.B.

1991-11-01

In response to a request from the International Chemical Workers Union, project director, an evaluation was undertaken of possible hazardous working conditions at the Morton Salt Company (SIC-1479), Weeks Island, Louisiana. At Weeks Island the salt was mined from large domes, circular in shape and from a few hundred yards to a mile across. The only detectable overexposures in the mining operation were to coal-tar pitch volatiles. None of the 20 personal breathing zone and area air samples collected in the mill were above detectable limits for asbestos (1332214). The prevalences of chronic cough and chronic phlegm reported were statisticallymore » different, exceeding those reported by a group of nonexposed blue collar workers. Chronic symptoms were reported by underground workers in all smoking categories, but only by those surface workers who also smoked. There were more complaints about eye irritation and tearing of the eyes in the underground workers, consistent with diesel byproduct exposure. Four workers were identified through pulmonary function test results with mild obstructive lung disease and one with moderate obstructive lung disease. Three workers with mild restriction of lung volume were noted. None of the 61 chest films taken read positively for pneumoconiosis. The authors conclude that overexposures to coal-tar pitch volatiles existed at the time of the survey. The authors recommend measures for reducing occupational exposures to workplace contaminants. A follow up medical questionnaire survey should be conducted.« less

[Prevalence of tobacco smoking among phthisio-pulmonological inpatients].

PubMed

Ugriumov, A I

2001-01-01

A questionnaire survey of 222 phthisiopulmonological inpatients has indicated that 21.7 of the males and 4.05% of the females are smokers. Among clinical and morphological forms of tuberculosis, fibrocavernous tuberculosis is prevalent in smokers. Tuberculoma and post tuberculous fibrosis of varying severity are common in never smokers. Smokers are at high risk for lung cancer and at less risk for sarcoidosis with the equal incidence of chronic obstructive lung disease. The paper states that hospital physicians pay little attention to smoking among their patients.

Quantitative computed tomography of pulmonary emphysema and ventricular function in chronic obstructive pulmonary disease patients with pulmonary hypertension.

PubMed

Huang, Yu-Sen; Hsu, Hsao-Hsun; Chen, Jo-Yu; Tai, Mei-Hwa; Jaw, Fu-Shan; Chang, Yeun-Chung

2014-01-01

This study strived to evaluate the relationship between degree of pulmonary emphysema and cardiac ventricular function in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) using electrocardiographic-gated multidetector computed tomography (CT). Lung transplantation candidates with the diagnosis of COPD and PH were chosen for the study population, and a total of 15 patients were included. The extent of emphysema is defined as the percentage of voxels below -910 Hounsfield units in the lung windows in whole lung CT without intravenous contrast. Heart function parameters were measured by electrocardiographic-gated CT angiography. Linear regression analysis was conducted to examine the associations between percent emphysema and heart function indicators. Significant correlations were found between percent emphysema and right ventricular (RV) measurements, including RV end-diastolic volume (R(2) = 0.340, p = 0.023), RV stroke volume (R(2) = 0.406, p = 0.011), and RV cardiac output (R(2) = 0.382, p = 0.014); the correlations between percent emphysema and left ventricular function indicators were not observed. The study revealed that percent emphysema is correlated with RV dysfunction among COPD patients with PH. Based on our findings, percent emphysema can be considered for use as an indicator to predict the severity of right ventricular dysfunction among COPD patients.

Digging through the Obstruction: Insight into the Epithelial Cell Response to Respiratory Virus Infection in Patients with Cystic Fibrosis.

PubMed

Hendricks, Matthew R; Bomberger, Jennifer M

2016-05-01

Respiratory virus infections are common but generally self-limiting infections in healthy individuals. Although early clinical studies reported low detection rates, the development of molecular diagnostic techniques by PCR has led to an increased recognition that respiratory virus infections are associated with morbidity and acute exacerbations of chronic lung diseases, such as cystic fibrosis (CF). The airway epithelium is the first barrier encountered by respiratory viruses following inhalation and the primary site of respiratory viral replication. Here, we describe how the airway epithelial response to respiratory viral infections contributes to disease progression in patients with CF and other chronic lung diseases, including the role respiratory viral infections play in bacterial acquisition in the CF patient lung. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Stage 1 development of a patient-reported experience measure (PREM) for chronic obstructive pulmonary disease (COPD).

PubMed

Walker, Susan; Andrew, Sharon; Hodson, Matthew; Roberts, C Michael

2017-07-24

The study aimed to explore patients' experience of living with chronic obstructive pulmonary disease and their perspective of their community healthcare for chronic obstructive pulmonary disease to extract affective responses in order to develop potential items for a patient-reported experience measure for chronic obstructive pulmonary disease. Qualitative face-face interviews were conducted, in the community, with 64 patients with chronic obstructive pulmonary disease recruited from General Practices and Breathe-Easy community groups in the Outer North East, East and City areas of London and Essex, UK. A two phase analysis of the qualitative data was conducted to identify themes arising from patients' description of living with chronic obstructive pulmonary disease and their perceptions of their community healthcare and subsequently the affective responses underlying the themes raised by patients, which gave emotional colour to the themes, bringing the thematic analysis closer to the subjective patient experience. Five themes were identified from the interview data: 'Journey to diagnosis'; 'Smoking'; 'Usual care'; 'My everyday life'; and 'Exacerbations'. Twenty-one affective responses were identified and categorised as either 'negative', 'positive' or 'bivalent'. 'Frustration', a negative affective response was prevalent in four themes. 'Gratitude', 'hope' and 'happiness/enjoyment' were among the more positive responses more prevalent across several themes. By conducting a novel two-way analysis (thematic and affective) it was possible to identify themes and affective responses that were aligned to those themes. This enabled the development of 38 chronic obstructive pulmonary disease-specific experience items to take forward for further testing including item reduction and validity and reliability in the next stage of the patient-reported experience measure development. GIVING IMPORTANCE TO PATIENTS' EMOTIONS: An exploration of patient perceptions of living with chronic lung disease will help develop a new patient reported experience scale. Healthcare services are aiming to provide effective patient-centered care for those with chronic obstructive pulmonary disease (COPD). Such care strategies require structured, validated patient feedback scales to facilitate accurate communication between patients, carers and healthcare professionals. Susan Walker at Anglia Ruskin University in Chelmsford, UK, and co-workers analyzed qualitative data from interviews with 64 COPD patients in London and Essex regarding their emotions and perceptions of living with COPD, with the aim of creating a patient reported experience measure, or PREM. Initial results identified five themes-including 'journey to diagnosis' and 'everyday life'-and twenty-one affective responses, ranging from negative to positive. The team will take these results forward for further validation.

Sing Your Lungs Out-a community singing group for chronic obstructive pulmonary disease: a 1-year pilot study.

PubMed

McNaughton, Amanda; Weatherall, Mark; Williams, Mathew; McNaughton, Harry; Aldington, Sarah; Williams, Gayle; Beasley, Richard

2017-01-24

Singing group participation may benefit patients with chronic obstructive pulmonary disease (COPD). Previous studies are limited by small numbers of participants and short duration of generally hospital-based singing group intervention. This study examines the feasibility of long-term participation in a community singing group for patients with COPD who had completed pulmonary rehabilitation (PR). This was a feasibility cohort study. Patients with COPD who had completed PR and were enrolled in a weekly community exercise group were recruited to a new community-based singing group which met weekly for over 1 year. Measurements at baseline, 4 months and 1 year comprised comprehensive pulmonary function tests including lung volumes, 6 min walk test (6MWT), Clinical COPD Questionnaire (CCQ), Hospital Anxiety and Depression Scale (HADS) and hospital admission days for acute exacerbation of COPD (AECOPD) for 1 year before and after the first singing group session. There were 28 participants with chronic lung disease recruited from 140 people approached. Five withdrew in the first month. 21 participants meeting Global Initiative for Chronic Obstructive Lung Disease criteria for COPD completed 4-month and 18 completed 1-year assessments. The mean attendance was 85%. For the prespecified primary outcome measure, total HADS score, difference between baseline and 12 months was -0.9, 95% CI -3.0 to 1.2, p=0.37. Of the secondary measures, a significant reduction was observed for HADS anxiety score after 1 year of -0.9 (95% CI -1.8 to -0.1) points, p=0.038 and an increase in the 6MWT at 1 year, of 65 (95% CI 35 to 99) m compared with baseline p<0.001. Our findings support the feasibility of long-term participation in a community singing group for adults with COPD who have completed PR and are enrolled in a weekly community exercise group and provide evidence of improved exercise capacity and a reduction in anxiety. ACTRN12615000736549; Results. 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/.

Dysregulated Functions of Lung Macrophage Populations in COPD.

PubMed

Kapellos, Theodore S; Bassler, Kevin; Aschenbrenner, Anna C; Fujii, Wataru; Schultze, Joachim L

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD.

Dysregulated Functions of Lung Macrophage Populations in COPD

PubMed Central

Bassler, Kevin; Aschenbrenner, Anna C.

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. PMID:29670919

Pulmonary effects of inhaled concentrated fine particles (PM2.5) in somkers and patients with chronic obstructive lung disease

EPA Science Inventory

Although numerous field and epidemiological studies of particulate matter (PM) have strongly suggested that patients with COPD and smokers may be susceptible to fine particles (PM2.5), very little is known about the health effects on such sub-populations. In a randomized double...

Lung epithelial stem cells and their niches: Fgf10 takes center stage.

PubMed

Volckaert, Thomas; De Langhe, Stijn

2014-01-01

Throughout life adult animals crucially depend on stem cell populations to maintain and repair their tissues to ensure life-long organ function. Stem cells are characterized by their capacity to extensively self-renew and give rise to one or more differentiated cell types. These powerful stem cell properties are key to meet the changing demand for tissue replacement during normal lung homeostasis and regeneration after lung injury. Great strides have been made over the last few years to identify and characterize lung epithelial stem cells as well as their lineage relationships. Unfortunately, knowledge on what regulates the behavior and fate specification of lung epithelial stem cells is still limited, but involves communication with their microenvironment or niche, a local tissue environment that hosts and influences the behaviors or characteristics of stem cells and that comprises other cell types and extracellular matrix. As such, an intimate and dynamic epithelial-mesenchymal cross-talk, which is also essential during lung development, is required for normal homeostasis and to mount an appropriate regenerative response after lung injury. Fibroblast growth factor 10 (Fgf10) signaling in particular seems to be a well-conserved signaling pathway governing epithelial-mesenchymal interactions during lung development as well as between different adult lung epithelial stem cells and their niches. On the other hand, disruption of these reciprocal interactions leads to a dysfunctional epithelial stem cell-niche unit, which may culminate in chronic lung diseases such as chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF).

Associations between Ambient Particulate Matter and Nitrogen Dioxide and Chronic Obstructive Pulmonary Diseases in Adults and Effect Modification by Demographic and Lifestyle Factors

PubMed Central

Leem, Jong Han; Kim, Hwan Cheol

2018-01-01

This study was undertaken to investigate the associations between chronic exposure to particulate matter of medium aerodynamic diameter ≤10 or ≤2.5 µm (PM10 or PM2.5) and nitrogen dioxide (NO2) levels and lung function and to examine a possible change in these relationships by demographic and lifestyle factors. Chronic obstructive pulmonary disease (COPD) was defined using the Global Initiative for COPD criteria (forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <70%). Associations of lung function and COPD with PM10 or PM2.5 or NO2 were examined using linear and logistic regression analyses among 1264 Korean adults. The highest tertiles of PM2.5 (≥37.1 μg/m3) and NO2 (≥53.8 μg/m3) exposure were significantly associated with COPD (highest versus lowest tertile of PM2.5: adjusted odds ratio (OR) = 1.79, 95% CI: 1.02–3.13; highest versus lowest tertile of NO2: adjusted OR = 1.83, 95% CI: 1.04–3.21). A 10 μg/m3 increase in PM10 concentration was associated with a 1.85 L (95% CI –3.65 to –0.05) decrease in FEV1 and a 1.73 L (95% CI –3.35 to –0.12) decrease in FVC, with the strongest negative association among older people and those with less education. Reduced lung function was associated with PM2.5 exposure in subjects with no physical activity. This study provides evidence that exposure to ambient air pollution has adverse effects on lung function in adults. PMID:29463050

Respiratory symptoms, lung function decrement and chronic obstructive pulmonary disease in pre-menopausal Indian women exposed to biomass smoke.

PubMed

Mukherjee, Sayali; Roychoudhury, Sanghita; Siddique, Shabana; Banerjee, Madhuchanda; Bhattacharya, Purba; Lahiri, Twisha; Ray, Manas Ranjan

2014-12-01

The impact of chronic exposure to smoke from biomass burning on respiratory health has been examined. Six-hundred and eighty-one non-smoking women (median age 35 years) from eastern India who cook exclusively with biomass (wood, dung and crop residues) and 438 age-matched women from similar neighborhood who cook with liquefied petroleum gas (LPG) were examined. Pulmonary function test was done by spirometry. The concentrations of particulate matter having diameter of < 10 µm (PM10) and < 2.5 µm (PM2.5) in indoor air was measured by real-time aerosol monitor. Compared with LPG users, biomass users had greater prevalence of upper (50.9 versus 28.5%) and lower respiratory symptoms (71.8 versus 30.8%) and dyspnea (58.4 versus 19.9%). They showed reduction in all parameters measured by spirometer especially in mid-expiratory volume. PM10 and PM2.5 concentration in biomass using kitchen were 2-3-times more than LPG-using kitchen, and the decline in spirometry values was positively associated PM10 and PM2.5 levels in indoor air after controlling education, family income and kitchen location as potential confounders. Overall, 29.7% of biomass users and 16.4% of LPG users had deficient lung function, and restrictive type of deficiency was predominant. Chronic obstructive pulmonary disease (COPD) was diagnosed in 4.6% of biomass and 0.9% of LPG users. Women who predominantly used dung cake and did not possess separate kitchen had poorer lung function. Cumulative exposure to biomass smoke causes lung function decrement and facilitates COPD development even in non-smoking and relatively young pre-menopausal women.

Emerging therapies for the treatment of skeletal muscle wasting in chronic obstructive pulmonary disease.

PubMed

Passey, Samantha L; Hansen, Michelle J; Bozinovski, Steven; McDonald, Christine F; Holland, Anne E; Vlahos, Ross

2016-10-01

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that constitutes a major global health burden. A significant proportion of patients experience skeletal muscle wasting and loss of strength as a comorbidity of their COPD, a condition that severely impacts on their quality of life and survival. At present, the lung pathology is considered to be largely irreversible; however, the inherent adaptability of muscle tissue offers therapeutic opportunities to tackle muscle wasting and potentially reverse or delay the progression of this aspect of the disease, to improve patients' quality of life. Muscle wasting in COPD is complex, with contributions from a number of factors including inflammatory cytokines, oxidative stress, growth and anabolic hormones, nutritional status, and physical activity. In this review, we discuss current and emerging therapeutic approaches to treat muscle wasting in COPD, including a number of pharmacological therapies that are in development for muscle atrophy in other pathological states that could be of relevance for treating muscle wasting in COPD patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Role of Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

PubMed Central

Vlahos, Ross; Bozinovski, Steven

2014-01-01

Alveolar macrophages (AMs) represent a unique leukocyte population that responds to airborne irritants and microbes. This distinct microenvironment coordinates the maturation of long-lived AMs, which originate from fetal blood monocytes and self-renew through mechanisms dependent on GM-CSF and CSF-1 signaling. Peripheral blood monocytes can also replenish lung macrophages; however, this appears to occur in a stimuli specific manner. In addition to mounting an appropriate immune response during infection and injury, AMs actively coordinate the resolution of inflammation through efferocytosis of apoptotic cells. Any perturbation of this process can lead to deleterious responses. In chronic obstructive pulmonary disease (COPD), there is an accumulation of airway macrophages that do not conform to the classic M1/M2 dichotomy. There is also a skewed transcriptome profile that favors expression of wound-healing M2 markers, which is reflective of a deficiency to resolve inflammation. Endogenous mediators that can promote an imbalance in inhibitory M1 vs. healing M2 macrophages are discussed, as they are the plausible mechanisms underlying why AMs fail to effectively resolve inflammation and restore normal lung homeostasis in COPD. PMID:25309536

Sing Your Lungs Out: a qualitative study of a community singing group for people with chronic obstructive pulmonary disease (COPD).

PubMed

McNaughton, Amanda; Aldington, Sarah; Williams, Gayle; Levack, William M M

2016-09-20

To explore the ways in which participation in a community singing group contributed to the health and well-being of patients with chronic obstructive pulmonary disease (COPD). Qualitative description, based on transcripts from individual interviews and a focus group meeting with people with COPD participating in the singing group, regarding their experience. Urban community, Wellington, New Zealand. 23 people (13 women and 10 men), 51-91 years with COPD (21) or interstitial lung disease (2). The weekly singing group was a well-attended activity, with self-reported benefits to health and well-being. 4 key themes were identified: being in the 'right space', connection, purpose and growth, and participation in a meaningful physical activity. This study helps us to better understand how participation in a community singing group can benefit the health and well-being of patients with COPD. ACTRN12615000736549; Results. 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/

Impact of micro-environmental changes on respiratory tract infections with intracellular bacteria.

PubMed

Shima, Kensuke; Coopmeiners, Jonas; Graspeuntner, Simon; Dalhoff, Klaus; Rupp, Jan

2016-11-01

Community-acquired pneumonia is caused by intra- and extracellular bacteria, with some of these bacteria also being linked to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. Chlamydia pneumoniae is an obligate intracellular pathogen that is highly sensitive to micro-environmental conditions controlling both pathogen growth and host immune responses. The availability of nutrients, as well as changes in oxygen, pH and interferon-γ levels, have been shown to directly influence the chlamydial life cycle and clearance. Although the lung has been traditionally regarded as a sterile environment, sequencing approaches have enabled the identification of a large number of bacteria in healthy and diseased lungs. The influence of the lung microbiota on respiratory infections has not been extensively studied so far and data on chlamydial infections are currently unavailable. In the present study, we speculate on how lung microbiota might interfere with acute and chronic infections by focusing exemplarily on the obligate intracellular C. pneumoniae. Furthermore, we consider changes in the gut microbiota as an additional player in the control of lung infections, especially in view the increasing evidence suggesting the involvement of the gut microbiota in various immunological processes throughout the human body. © 2016 Federation of European Biochemical Societies.

Glycerol particle cigarettes: a less harmful option for chronic smokers.

PubMed Central

Sutherland, G; Russell, M A; Stapleton, J A; Feyerabend, C

1993-01-01

In 20 smokers who switched to a new type of virtually tar free cigarette for three days, average nicotine intake was reduced by 44%, carbon monoxide intake increased by 19%, while estimated tar intake was reduced by about 90%. Such cigarettes pose substantially less risk of cancer and chronic obstructive lung disease than conventional cigarettes, and their acceptability and safety could be improved by increasing nicotine yield, reducing carbon monoxide yield, and improving the flavour. PMID:8511737

Effects of periodontal treatment on lung function and exacerbation frequency in patients with chronic obstructive pulmonary disease and chronic periodontitis: a 2-year pilot randomized controlled trial.

PubMed

Zhou, Xuan; Han, Jing; Liu, Zhiqiang; Song, Yiqing; Wang, Zuomin; Sun, Zheng

2014-06-01

To evaluate the direct effects of periodontal therapy in Chronic Obstructive Pulmonary Disease (COPD) patients with chronic periodontitis (CP). In a pilot randomized controlled trial, 60 COPD patients with CP were randomly assigned to receive scaling and root planing (SRP) treatment, supragingival scaling treatment, or oral hygiene instructions only with no periodontal treatment. We evaluated their periodontal indexes, respiratory function, and COPD exacerbations at baseline, 6 months, 1, and 2 years. Compared with the control group, measurements of periodontal indexes were significantly improved in patients in two treatment groups at 6-month, 1-year, and 2-year follow-up (all p < 0.05). Overall, the means of forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) and FEV1 were significantly higher in the two therapy groups compared with the control group during the follow-up (p < 0.05). In addition, the frequencies of COPD exacerbation were significantly lower in the two therapy groups than in the control group at 2-year follow-up (p < 0.05). Our preliminary results from this pilot trial suggest that periodontal therapy in COPD patients with CP may improve lung function and decrease the frequency of COPD exacerbation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The connection between chronic obstructive pulmonary disease symptoms and hyperinflation and its impact on exercise and function.

PubMed

Cooper, Christopher B

2006-10-01

Forced expiratory volume in 1 second (FEV1) has served as an important diagnostic measurement of chronic obstructive pulmonary disease (COPD) but has not been found to correlate with patient-centered outcomes such as exercise tolerance, dyspnea, or health-related quality of life. It has not helped us understand why some patients with severe FEV1 impairment have better exercise tolerance compared with others with similar FEV1 values. Hyperinflation, or air trapping caused by expiratory flow limitation, causes operational lung volumes to increase and even approach the total lung capacity (TLC) during exercise. Some study findings suggest that a dyspnea limit is reached when the end-inspiratory lung volume encroaches within approximately 500 mL of TLC. The resulting limitation in daily physical activity establishes a cycle of decline that includes physical deconditioning (elevated blood lactic acid levels at lower levels of exercise) and worsening dyspnea. Hyperinflation is reduced by long-acting bronchodilators that reduce airways resistance. The deflation of the lungs, in turn, results in an increased inspiratory capacity. For example, the once-daily anticholinergic bronchodilator tiotropium increases inspiratory capacity, 6-minute walk distance, and cycle exercise endurance time, and it decreases isotime fatigue or dyspnea. Pulmonary rehabilitation and oxygen therapy both reduce ventilatory requirements and improve breathing efficiency, thereby reducing hyperinflation and improving exertional dyspnea. Thus, hyperinflation is directly associated with patient-centered outcomes such as dyspnea and exercise limitation. Furthermore, therapeutic interventions--including pharmacotherapy and lung volume--reduction surgery--that reduce hyperinflation improve these outcomes.

Induction of mesenchymal cell phenotypes in lung epithelial cells by adenovirus E1A.

PubMed

Behzad, A R; Morimoto, K; Gosselink, J; Green, J; Hogg, J C; Hayashi, S

2006-12-01

Epithelial-mesenchymal transformation is now recognised as an important feature of tissue remodelling. The present report concerns the role of adenovirus infection in inducing this transformation in an animal model of chronic obstructive pulmonary disease. Guinea pig primary peripheral lung epithelial cells (PLECs) transfected with adenovirus E1A (E1A-PLECs) were compared to guinea pig normal lung fibroblasts (NLFs) transfected with E1A (E1A-NLFs). These cells were characterised by PCR, immunocytochemistry, electron microscopy, and Western and Northern blot analyses. Electrophoretic mobility shift assays were performed in order to examine nuclear factor (NF)-kappaB and activator protein (AP)-1 binding activities. E1A-PLECs and E1A-NLFs positive for E1A DNA, mRNA and protein expressed cytokeratin and vimentin but not smooth muscle alpha-actin. Both exhibited cuboidal morphology and junctional complexes, but did not contain lamellar bodies or express surfactant protein A, B or C mRNAs. These two cell types differed, however, in their NF-kappaB and AP-1 binding after lipopolysaccharide stimulation, possibly due to differences in the expression of the subunits that comprise these transcriptional complexes. E1A transfection results in the transformation of peripheral lung epithelial cells and normal lung fibroblasts to a phenotype intermediate between that of the two primary cells. It is postulated that this intermediate phenotype may play a major role in the remodelling of the airways in chronic obstructive pulmonary disease associated with persistence of adenovirus E1A DNA.

Notch signaling in lung diseases: focus on Notch1 and Notch3

PubMed Central

Zong, Dandan; Ouyang, Ruoyun; Li, Jinhua; Chen, Yan; Chen, Ping

2016-01-01

Notch signaling is an evolutionarily conserved cell–cell communication mechanism that plays a key role in lung homeostasis, injury and repair. The loss of regulation of Notch signaling, especially Notch1 and Notch3, has recently been linked to the pathogenesis of important lung diseases, in particular, chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, pulmonary arterial hypertension (PAH), lung cancer and lung lesions in some congenital diseases. This review focuses on recent advances related to the mechanisms and the consequences of aberrant or absent Notch1/3 activity in the initiation and progression of lung diseases. Our increasing understanding of this signaling pathway offers great hope that manipulating Notch signaling may represent a promising alternative complementary therapeutic strategy in the future. PMID:27378579

Individualized prediction of lung-function decline in chronic obstructive pulmonary disease

PubMed Central

Zafari, Zafar; Sin, Don D.; Postma, Dirkje S.; Löfdahl, Claes-Göran; Vonk, Judith; Bryan, Stirling; Lam, Stephen; Tammemagi, C. Martin; Khakban, Rahman; Man, S.F. Paul; Tashkin, Donald; Wise, Robert A.; Connett, John E.; McManus, Bruce; Ng, Raymond; Hollander, Zsuszanna; Sadatsafavi, Mohsen

2016-01-01

Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being −124 to −15 mL/yr for smokers and −83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD. Trial registration: Lung Health Study — ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study — ClinicalTrials.gov, no. NCT00751660 PMID:27486205

Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

PubMed

Åhrman, Emma; Hallgren, Oskar; Malmström, Lars; Hedström, Ulf; Malmström, Anders; Bjermer, Leif; Zhou, Xiao-Hong; Westergren-Thorsson, Gunilla; Malmström, Johan

2018-03-01

Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes, with specific focus on the matrisome, using data-independent acquisition and targeted data analysis (SWATH-MS). Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition, we show important quantitative and qualitative effects of the solubility of matrisome proteins. COPD was characterized by a disease-specific increase in ECM regulators, metalloproteinase inhibitor 3 (TIMP3) and matrix metalloproteinase 28 (MMP-28), whereas for IPF, impairment in cell adhesion proteins, such as collagen VI and laminins, was most prominent. For both diseases, we identified increased levels of proteins involved in the regulation of endopeptidase activity, with several proteins belonging to the serpin family. The established human lung quantitative proteome inventory and the construction of a tissue-specific protein assay library provides a resource for future quantitative proteomic analyses of human lung tissues. We present a sequential tissue extraction strategy to determine changes in extractability of matrisome proteins in end-stage COPD and IPF compared to healthy control tissue. Extensive quantitative analysis of the proteome changes of the disease states revealed altered solubility of matrisome proteins involved in ECM regulators and cell-ECM communication. The results highlight disease-specific remodeling mechanisms associated with COPD and IPF. Copyright © 2018 Elsevier B.V. All rights reserved.

Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases.

PubMed

Vij, Neeraj; Min, Taehong; Bodas, Manish; Gorde, Aakruti; Roy, Indrajit

2016-11-01

The success of drug delivery to target airway cell(s) remains a significant challenge due to the limited ability of nanoparticle (NP) systems to circumvent protective airway-defense mechanisms. The size, density, surface and physical-chemical properties of nanoparticles are the key features that determine their ability to navigate across the airway-barrier. We evaluated here the efficacy of a PEGylated immuno-conjugated PLGA-nanoparticle (PINP) to overcome this challenge and selectively deliver drug to specific inflammatory cells (neutrophils). We first characterized the size, shape, surface-properties and neutrophil targeting using dynamic laser scattering, transmission electron microscopy and flow cytometry. Next, we assessed the efficacy of neutrophil-targeted PINPs in transporting through the airway followed by specific binding and release of drug to neutrophils. Finally, our results demonstrate the efficacy of PINP mediated non-steroidal anti-inflammatory drug-(ibuprofen) delivery to neutrophils in murine models of obstructive lung diseases, based on its ability to control neutrophilic-inflammation and resulting lung disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of chronic obstructive pulmonary disease and hemorrhoids

PubMed Central

Lin, Lih-Hwa; Siu, Justin Ji-Yuen; Liao, Po-Chi; Chiang, Jen-Huai; Chou, Pei-Chi; Chen, Huey-Yi; Ho, Tsung-Jung; Tsai, Ming-Yen; Chen, Yung-Hsiang; Chen, Wen-Chi

2017-01-01

Abstract According to traditional Chinese medicine (TCM) theory, a specific physiological and pathological relationship exists between the lungs and the large intestine. The aim of this study is to delineate the association of chronic obstructive pulmonary disease (COPD) and hemorrhoids in order to verify the “interior–exterior” relationship between the lungs and the large intestine. A retrospective cohort study is conceived from the National Health Insurance Research Database, Taiwan. The 2 samples (COPD cohort and non-COPD cohort) were selected from the 2000 to 2003 beneficiaries of the NHI, representing patients age 20 and older in Taiwan, with the follow-up ending on December 31, 2011. The COPD cohort (n = 51,506) includes every patient newly diagnosed as having Chronic Obstructive Pulmonary Disease (COPD, ICD-9-CM: 490–492, 494, 496), who have made at least 2 confirmed visits to the hospital/clinic. The non-COPD cohort (n = 103,012) includes patients without COPD and is selected via a 1:2 (COPD: non-COPD) matching by age group (per 5 years), gender, and index date (diagnosis date of COPD for the COPD cohort). Compared with non-COPD cohorts, patients with COPD have a higher likelihood of having hemorrhoids and the age-, gender- and comorbidies-adjusted hazard ratio (HR) for hemorrhoids is 1.56 (95% confidence intervals [CI]:1.50–1.62). The adjusted HR of hemorrhoids for females is 0.79 (95% CI: 0.77–0.83), which is significantly less than that for males. The elderly groups, 40 to 59 years and aged 60 or above, have higher adjusted HRs than younger age groups (20–39 years), 1.19 (95% CI: 1.14–1.26), and 1.18 (95% CI: 1.12–1.24), respectively. Patients with COPD may have a higher likelihood to have hemorrhoids in this retrospective cohort study. This study verifies the fundamental theorem of TCM that there is a definite pathogenic association between the lungs and large intestine. PMID:28272246

Association of chronic obstructive pulmonary disease and hemorrhoids: A nationwide cohort study.

PubMed

Lin, Lih-Hwa; Siu, Justin Ji-Yuen; Liao, Po-Chi; Chiang, Jen-Huai; Chou, Pei-Chi; Chen, Huey-Yi; Ho, Tsung-Jung; Tsai, Ming-Yen; Chen, Yung-Hsiang; Chen, Wen-Chi

2017-03-01

According to traditional Chinese medicine (TCM) theory, a specific physiological and pathological relationship exists between the lungs and the large intestine. The aim of this study is to delineate the association of chronic obstructive pulmonary disease (COPD) and hemorrhoids in order to verify the "interior-exterior" relationship between the lungs and the large intestine. A retrospective cohort study is conceived from the National Health Insurance Research Database, Taiwan. The 2 samples (COPD cohort and non-COPD cohort) were selected from the 2000 to 2003 beneficiaries of the NHI, representing patients age 20 and older in Taiwan, with the follow-up ending on December 31, 2011. The COPD cohort (n = 51,506) includes every patient newly diagnosed as having Chronic Obstructive Pulmonary Disease (COPD, ICD-9-CM: 490-492, 494, 496), who have made at least 2 confirmed visits to the hospital/clinic. The non-COPD cohort (n = 103,012) includes patients without COPD and is selected via a 1:2 (COPD: non-COPD) matching by age group (per 5 years), gender, and index date (diagnosis date of COPD for the COPD cohort). Compared with non-COPD cohorts, patients with COPD have a higher likelihood of having hemorrhoids and the age-, gender- and comorbidies-adjusted hazard ratio (HR) for hemorrhoids is 1.56 (95% confidence intervals [CI]:1.50-1.62). The adjusted HR of hemorrhoids for females is 0.79 (95% CI: 0.77-0.83), which is significantly less than that for males. The elderly groups, 40 to 59 years and aged 60 or above, have higher adjusted HRs than younger age groups (20-39 years), 1.19 (95% CI: 1.14-1.26), and 1.18 (95% CI: 1.12-1.24), respectively. Patients with COPD may have a higher likelihood to have hemorrhoids in this retrospective cohort study. This study verifies the fundamental theorem of TCM that there is a definite pathogenic association between the lungs and large intestine.

Classification of Airflow Limitation Based on z-Score Underestimates Mortality in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Tejero, Elena; Prats, Eva; Casitas, Raquel; Galera, Raúl; Pardo, Paloma; Gavilán, Adelaida; Martínez-Cerón, Elisabet; Cubillos-Zapata, Carolina; Del Peso, Luis; García-Río, Francisco

2017-08-01

Global Lung Function Initiative recommends reporting lung function measures as z-score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. To evaluate the prognostic capacity of the AL classifications based on z-score or percentage predicted of FEV 1 in patients with chronic obstructive pulmonary disease (COPD). A cohort of 2,614 patients with COPD recruited outside the hospital setting was examined after a mean (± SD) of 57 ± 13 months of follow-up, totaling 10,322 person-years. All-cause mortality was analyzed, evaluating the predictive capacity of several AL staging systems. Based on Global Initiative for Chronic Obstructive Lung Disease guidelines, 461 patients (17.6%) had mild, 1,452 (55.5%) moderate, 590 (22.6%) severe, and 111 (4.2%) very severe AL. According to z-score classification, 66.3% of patients remained with the same severity, whereas 23.7% worsened and 10.0% improved. Unlike other staging systems, patients with severe AL according to z-score had higher mortality than those with very severe AL (increase of risk by 5.2 and 3.9 times compared with mild AL, respectively). The predictive capacity for 5-year survival was slightly higher for FEV 1 expressed as percentage of predicted than as z-score (area under the curve: 0.714-0.760 vs. 0.649-0.708, respectively). A severity-dependent relationship between AL grades by z-score and mortality was only detected in patients younger than age 60 years. In patients with COPD, the AL classification based on z-score predicts worse mortality than those based on percentage of predicted. It is possible that the z-score underestimates AL severity in patients older than 60 years of age with severe functional impairment.

Meaning of living with severe chronic obstructive lung disease: a qualitative study

PubMed Central

Marx, Gabriella; Nasse, Maximilian; Stanze, Henrikje; Boakye, Sonja Owusu; Nauck, Friedemann; Schneider, Nils

2016-01-01

Objectives To explore what it means for patients to live with chronic obstructive pulmonary disease (COPD) as an incurable and constantly progressing disease. Design Qualitative longitudinal study using narrative and semistructured interviews. This paper presents findings of the initial interviews. Analysis using grounded theory. Setting Lung care clinics and community care in Lower Saxony, Germany. Participants 17 patients with advanced-stage COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) III/IV). Findings Analysis shows that these patients have difficulties accepting their life situation and feel at the mercy of the disease, which could be identified as a core-experienced phenomenon. Over a long period of time, patients have only a vague feeling of being ill, caused by uncertain knowledge, slow progress and doubtful attribution of clinical symptoms of the disease (causal conditions). As an action strategy, patients try to maintain daily routines for as long as possible after diagnosis. Both effective standard and rescue medication, which helps to reduce breathlessness and other symptoms, and the feeling of being faced with one's own responsibility (intervening conditions) support this strategy, whereby patients' own responsibility is too painful to acknowledge. As a consequence, patients try to deny the threat to life for a long period of time. Frequently, they need to experience facing their own limits, often in the form of an acute crisis, to realise their health situation. The experience of the illness is contextualised by a continuous increase in limited mobility and social isolation. Conclusion In order to help patients to improve disease awareness, to accept their life situation and to improve their reduced quality of life, patients may benefit from the early integration of palliative care (PC), considering its multiprofessional patient-centred and team-centred approach. Psychological support and volunteer work, which are relevant aspects of PC, should be appropriate to address psychosocial needs. More research is needed to evaluate how patients could benefit from early PC. PMID:27932338

Hand grip strength and chronic obstructive pulmonary disease in Korea: an analysis in KNHANES VI.

PubMed

Lee, Su Hwan; Kim, Soo Jung; Han, Yeji; Ryu, Yon Ju; Lee, Jin Hwa; Chang, Jung Hyun

2017-01-01

Muscle mass is known to be associated with mortality in elderly adults. Because hand grip strength (HGS) is known as a simple assessment tool for muscular strength, many researchers have studied the association between HGS and disease. However, empirical evidence for the relationship between chronic obstructive pulmonary disease (COPD) and HGS is still controversial. The aim of this study was to evaluate the association between COPD and HGS, using Korean population data. This was a population-based cross-sectional study. Data were obtained from the sixth Korean National Health and Nutrition Examination Survey, which was conducted from 2013 to 2015. To reduce the effects of HGS-related factors and potential confounding factors, propensity score matching was used to match subjects with and without COPD. Among 14,930 subjects, 832 were enrolled in each group (non-COPD and COPD) after propensity score matching. COPD subjects did not have lower HGS than non-COPD subjects (non-COPD vs COPD, male, 38.0±7.0 vs 38.9±7.0 kg, P =0.044, female, 23.8±4.6 vs 24.2±4.9 kg, P =0.342). Lung function was classified by Global Initiative for Chronic Obstructive Lung Disease stages and was not significantly associated with HGS. For male COPD subjects, there was a significant correlation between HGS and the EuroQol Five-Dimension Questionnaire (EQ5D) utility score index, which is an indicator of quality of life that adjusts for age and body mass index ( r =0.201, P <0.001). The correlation was absent for female subjects ( r =0.098, P =0.170). COPD subjects did not have lower HGS than non-COPD subjects. HGS did not associate with lung function. However, the HGS of male COPD subjects was positively associated with EQ5D utility score index, an indicator of quality of life. HGS may be helpful as an additional method to the evaluation of quality of life in male COPD patients.

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

Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?

PubMed Central

Gehlen, Heidrun

2016-01-01

Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is commonly used to evaluate the severity of local inflammation in the lung. Other mediators of inflammation, like interleukins involved in the chemotaxis of neutrophils, have been studied. Chronic obstructive pneumopathies lead to remodeling of bronchial walls and lung parenchyma, ultimately causing fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important proteolytic enzymes during remodeling in human medicine and increasing evidence exists for the horse as well. A systemic involvement has been shown for severe equine asthma by increased acute phase proteins like serum amyloid A and haptoglobin in peripheral blood during exacerbation. Studies focusing on these and further possible inflammatory markers for chronic respiratory disease in the horse are discussed in this review of the literature. PMID:28053371

Aspergillus sensitisation in bidi smokers with and without chronic obstructive lung disease.

PubMed

Agarwal, Ritesh; Bhogal, Sumita; Choudhary, Hansraj; Aggarwal, Ashutosh N; Sehgal, Inderpaul S; Dhooria, Sahajal; Behera, Digambar; Chakrabarti, Arunaloke

2017-06-01

Recent studies have described fungal sensitisation in patients with chronic obstructive pulmonary disease (COPD). However, no study has evaluated fungal sensitisation specifically in bidi smokers. Herein, we evaluate the prevalence of Aspergillus sensitisation in bidi smokers. Bidi smokers with and without COPD underwent chest radiography, spirometry, Aspergillus skin test, A. fumigatus precipitins, A. fumigatus-specific IgE and total IgE. Aspergillus sensitisation was defined as the presence of either immediate cutaneous hyperreactivity to Aspergillus antigen or raised A. fumigatus-specific IgE level >0.35 kUA/L. Bidis were obtained from a subset of cases and controls and cultured for the growth of any fungus. Two hundred subjects with COPD and 72 chronic bidi smokers without COPD were included in the study (258 men; mean age, 56.8 years). Aspergillus sensitisation was found to be significantly higher in bidi smokers without COPD (27.8%) compared to the COPD cases (16%). Age, COPD, lung function, severity of smoking and current smoking were not associated with Aspergillus sensitisation, on a multivariate logistic regression analysis. We found a high prevalence of Aspergillus sensitisation in bidi-smoking subjects. More studies are required to confirm the findings of our study. © 2017 Blackwell Verlag GmbH.

Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study.

PubMed

Hadchouel, Alice; Marchand-Martin, Laetitia; Franco-Montoya, Marie-Laure; Peaudecerf, Laetitia; Ancel, Pierre-Yves; Delacourt, Christophe

2015-01-01

Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25-75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease.

Up-regulation of Pim-3 in Chronic Obstructive Pulmonary Disease (COPD) patients and its potential therapeutic role in COPD rat modeling.

PubMed

Yang, Cheng; Li, Li; Guo, Junhua; Zhang, Weiqiang; Zhu, Wenbiao; Rao, Xinhui; Huang, Wenjie

2017-04-01

Pim-3 belongs to the PIM kinase family and plays an important role in promoting inflammation, which is essential in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Immunohistochemistry (IHC), western blot, and RT-PCR analyses were performed to assess the expression of Pim-3 in both COPD and healthy lung tissue samples. SMA (Smooth Muscle Actin) and Cyclin D1 expression were detected by IHC. We also constructed animal models for the control, COPD, and Pim-3 inhibition groups, in order to analyze the effects of Pim-3 inhibition on COPD, and the role of Pim-3 in the p38 pathway. Compared with normal lung tissue, Pim-3 mRNA and protein were up-regulated in COPD tissue. Expression of Cyclin D1 and SMA were also up-regulated in the COPD group. In the animal model experiment, we found that suppression of Pim-3 decreased Pim-3, Cyclin D1, and SMA expression, as well as ameliorated lung damage in COPD patients. The inhibition of Pim-3 also resulted in the suppression of the p38 pathway. Our study suggests that up-regulation of Pim-3 successfully accelerated COPD development, and aggravated lung damage. The molecular mechanism of Pim-3 in COPD might be related to the p38 pathway, and is correlated with Cyclin D1 and SMA expression. Copyright © 2017 Elsevier GmbH. All rights reserved.

Ventilation inhomogeneity in obstructive lung diseases measured by electrical impedance tomography: a simulation study.

PubMed

Schullcke, B; Krueger-Ziolek, S; Gong, B; Jörres, R A; Mueller-Lisse, U; Moeller, K

2017-10-10

Electrical impedance tomography (EIT) has mostly been used in the Intensive Care Unit (ICU) to monitor ventilation distribution but is also promising for the diagnosis in spontaneously breathing patients with obstructive lung diseases. Beside tomographic images, several numerical measures have been proposed to quantitatively assess the lung state. In this study two common measures, the 'Global Inhomogeneity Index' and the 'Coefficient of Variation' were compared regarding their capability to reflect the severity of lung obstruction. A three-dimensional simulation model was used to simulate obstructed lungs, whereby images were reconstructed on a two-dimensional domain. Simulations revealed that minor obstructions are not adequately recognized in the reconstructed images and that obstruction above and below the electrode plane may result in misleading values of inhomogeneity measures. EIT measurements on several electrode planes are necessary to apply these measures in patients with obstructive lung diseases in a promising manner.

Pulmonary arterial hypertension and cor pulmonale associated with chronic domestic woodsmoke inhalation

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

Sandoval, J.; Salas, J.; Martinez-Guerra, M.L.

1993-01-01

We describe the clinical, radiologic, functional, and pulmonary hemodynamic characteristics of a group of 30 nonsmoking patients with a lung disease that may be related to intense, long-standing indoor wood-smoke exposure. The endoscopic and some of the pathologic findings are also presented. Intense and prolonged wood-smoke inhalation may produce a chronic pulmonary disease that is similar in many aspects to other forms of inorganic dust-exposure interstitial lung disease. It affects mostly country women in their 60s, and severe dyspnea and cough are the outstanding complaints. The chest roentgenograms show a diffuse, bilateral, reticulonodular pattern, combined with normalized or hyperinflated lungs,more » as well as indirect signs of pulmonary arterial hypertension (PAH). On the pulmonary function test the patients show a mixed restrictive-obstructive pattern with severe hypoxemia and variable degrees of hypercapnia. Endoscopic findings are those of acute and chronic bronchitis and intense anthracotic staining of the airways appears to be quite characteristic. Fibrous and inflammatory focal thickening of the alveolar septa as well as diffuse parenchymal anthracotic deposits are the most prominent pathologic findings, although inflammatory changes of the bronchial epithelium are also present. The patients had severe PAH in which, as in other chronic lung diseases, chronic alveolar hypoxia may play the main pathogenetic role. However, PAH in wood-smoke inhalation-associated lung disease (WSIALD) appears to be more severe than in other forms of interstitial lung disease and tobacco-related COPD. The patients we studied are a selected group and they may represent one end of the spectrum of the WSIALD.« less

Unemployment in chronic airflow obstruction around the world: results from the BOLD study.

PubMed

Grønseth, Rune; Erdal, Marta; Tan, Wan C; Obaseki, Daniel O; Amaral, Andre F S; Gislason, Thorarinn; Juvekar, Sanjay K; Koul, Parvaiz A; Studnicka, Michael; Salvi, Sundeep; Burney, Peter; Buist, A Sonia; Vollmer, William M; Johannessen, Ane

2017-09-01

We aimed to examine associations between chronic airflow obstruction (CAO) and unemployment across the world.Cross-sectional data from 26 sites in the Burden of Obstructive Lung Disease (BOLD) study were used to analyse effects of CAO on unemployment. Odds ratios for unemployment in subjects aged 40-65 years were estimated using a multilevel mixed-effects generalised linear model with study site as random effect. Site-by-site heterogeneity was assessed using individual participant data meta-analyses.Out of 18 710 participants, 11.3% had CAO. The ratio of unemployed subjects with CAO divided by subjects without CAO showed large site discrepancies, although these were no longer significant after adjusting for age, sex, smoking and education. The site-adjusted odds ratio (95% CI) for unemployment was 1.79 (1.41-2.27) for CAO cases, decreasing to 1.43 (1.14-1.79) after adjusting for sociodemographic factors, comorbidities and forced vital capacity. Of other covariates that were associated with unemployment, age and education were important risk factors in high-income sites (4.02 (3.53-4.57) and 3.86 (2.80-5.30), respectively), while female sex was important in low- to middle-income sites (3.23 (2.66-3.91)).In the global BOLD study, CAO was associated with increased levels of unemployment, even after adjusting for sociodemographic factors, comorbidities and lung function. Copyright ©ERS 2017.

[Chronic pulmonary diseases: point of view of partners and their assessments with regard to the effects of lung sports].

PubMed

Nell, C; Kehr, K; Hildebrandt, O; Sohrabi, K; Cassel, W; Greulich, T; Koehler, K-I; Koehler, U

2011-12-01

Chronic diseases of the respiratory organs have, besides restrictions of lung function, also physical, mental and social consequences. The chronic disease impacts negatively not only the patient's own quality of life but also that of his/her partner and/or relative. As treatment modalities, besides drug therapy, above all outpatient rehabilitation measures have proved to be effective. In this pilot study we sought answers to three questions: (i) How is the quality of life of the patient's partner and/or relative influenced by the disease? How does the partner/relative assess the effect of the disease on the chronically ill patient? How does the partner/relative assess the effect of lung sports on the chronically ill patient? A specially conceived questionnaire was given to the partners/relatives of 25 patients with chronic pulmonary diseases. The patients, 23 with chronic obstructive pulmonary disease and 2 with pulmonary fibrosis, have been participating in lung sports once a week for more than three years. The average age of the patients was 67 years. The patients' illness also negatively influenced the quality of life of the partner to a considerable extent. The impact of the patients' pulmonary disease on the healthy partner was assessed as being rather moderate. Restrictions of social life were essentially influenced by the amount of assistance required by the pulmonary patient. The therapeutic effects of lung sports on the well-being of the patient were aways considered to be positive by the respective partner/relatives. A chronic pulmonary illness also has a negative influence on the partner/relative's quality of life. The necessity for extensive assistance in daily life is accompanied by a considerable negative impact on the partner's quality of life. According to the opinion of the partner/relative, lung sports have positive effects in all of the chronically ill patient's fields of life. © Georg Thieme Verlag KG Stuttgart · New York.

Variability of spirometry in chronic obstructive pulmonary disease: results from two clinical trials.

PubMed

Herpel, Laura B; Kanner, Richard E; Lee, Shing M; Fessler, Henry E; Sciurba, Frank C; Connett, John E; Wise, Robert A

2006-05-15

Our goal is to determine short-term intraindividual biologic and measurement variability in spirometry of patients with a wide range of stable chronic obstructive pulmonary disease severity, using datasets from the National Emphysema Treatment Trial (NETT) and the Lung Health Study (LHS). This may be applied to determine criteria that can be used to assess a clinically meaningful change in spirometry. A total of 5,886 participants from the LHS and 1,215 participants from the NETT performed prebronchodilator spirometry during two baseline sessions. We analyzed varying criteria for absolute and percent change of FEV(1) and FVC to determine which criterion was met by 90% of the participants. The mean +/- SD FEV(1) for the initial session was 2.64 +/- 0.60 L (75.1 +/- 8.8% predicted) for the LHS and 0.68 +/- 0.22 L (23.7 +/- 6.5% predicted) for the NETT. The mean +/- SD number of days between test sessions was 24.9 +/- 17.1 for the LHS and 85.7 +/- 21.7 for the NETT. As the degree of obstruction increased, the intersession percent difference of FEV(1) increased. However, the absolute difference between tests remained relatively constant despite the severity of obstruction (0.106 +/- 0.10 L). Over 90% of participants had an intersession FEV(1) difference of less than 225 ml irrespective of the severity of obstruction. Absolute changes in FEV(1) rather than percent change should be used to determine whether patients with chronic obstructive pulmonary disease have improved or worsened between test sessions.

Mindfulness-Based Symptom and Stress Management Apps for Adults With Chronic Lung Disease: Systematic Search in App Stores

PubMed Central

2018-01-01

Background Up to 70% of lung cancer survivors are affected by chronic obstructive pulmonary disease (COPD), a common, debilitating, comorbid disease. Lung cancer and COPD are both characterized by symptoms such as breathlessness, fatigue, and psychological distress. These distressing chronic symptoms are exacerbated by stress and detract from an individual’s quality of life. Objective The aim of this study was to identify and evaluate evidence-based, commercially available apps for promoting mindfulness-based strategies among adults with a COPD or lung cancer history (ie, chronic lung disease). Methods For this review, an interdisciplinary research team used 19 keyword combinations in the search engines of Google and iOS app stores in May 2017. Evaluations were conducted on the apps’ (1) content, (2) usability heuristics, (3) grade-level readability, and (4) cultural sensitivity. Results The search resulted in 768 apps (508 in iOS and 260 in Google stores). A total of 9 apps met the inclusion criteria and received further evaluation. Only 1 app had below an eighth-grade reading level; the ninth one did not have enough text to calculate a readability score. None of the 9 apps met the cultural sensitivity evaluation criteria. Conclusions This systematic review identified critical design flaws that may affect the ease of using the apps in this study. Few mobile apps promote mindfulness-based strategies among adults with chronic lung disease (ie, COPD or lung cancer or both), but those that exist, overall, do not meet the latest scientific evidence. Recommendations include more stringent regulation of health-related apps, use of evidence-based frameworks and participatory design processes, following evidence-based usability practices, use of culturally sensitive language and images, and ensuring that content is written in plain language. PMID:29764800

Innovations in health information technologies for chronic pulmonary diseases.

PubMed

Himes, Blanca E; Weitzman, Elissa R

2016-04-05

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic obstructive lung disorders in the US that affect over 49 million people. There is no cure for asthma or COPD, but clinical guidelines exist for controlling symptoms that are successful in most patients that adhere to their treatment plan. Health information technologies (HITs) are revolutionizing healthcare by becoming mainstream tools to assist patients in self-monitoring and decision-making, and subsequently, driving a shift toward a care model increasingly centered on personal adoption and use of digital and web-based tools. While the number of chronic pulmonary disease HITs is rapidly increasing, most have not been validated as clinically effective tools for the management of disease. Online communities for asthma and COPD patients are becoming sources of empowerment and support, as well as facilitators of patient-centered research efforts. In addition to empowering patients and facilitating disease self-management, HITs offer promise to aid researchers in identifying chronic pulmonary disease endotypes and personalized treatments based on patient-specific profiles that integrate symptom occurrence and medication usage with environmental and genomic data.

Automated assessment of aortic and main pulmonary arterial diameters using model-based blood vessel segmentation for predicting chronic thromboembolic pulmonary hypertension in low-dose CT lung screening

NASA Astrophysics Data System (ADS)

Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Sugiura, Toshihiko; Tanabe, Nobuhiro; Kusumoto, Masahiko; Eguchi, Kenji; Kaneko, Masahiro

2018-02-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of the pulmonary vasculature by residual organized thrombi. A morphological abnormality inside mediastinum of CTEPH patient is enlargement of pulmonary artery. This paper presents an automated assessment of aortic and main pulmonary arterial diameters for predicting CTEPH in low-dose CT lung screening. The distinctive feature of our method is to segment aorta and main pulmonary artery using both of prior probability and vascular direction which were estimated from mediastinal vascular region using principal curvatures of four-dimensional hyper surface. The method was applied to two datasets, 64 lowdose CT scans of lung cancer screening and 19 normal-dose CT scans of CTEPH patients through the training phase with 121 low-dose CT scans. This paper demonstrates effectiveness of our method for predicting CTEPH in low-dose CT screening.

Cardiovascular function in pulmonary emphysema.

PubMed

Visca, Dina; Aiello, Marina; Chetta, Alfredo

2013-01-01

Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function.

Respiratory system. Part 2: Gaseous exchange.

PubMed

McLafferty, Ella; Johnstone, Carolyn; Hendry, Charles; Farley, Alistair

This article, which isthe last in the life sciences series and the second of two articles on the respiratory system, describes gaseous exchange in the lungs, transport of oxygen and carbon dioxide, and internal and external respiration. The article concludes with a brief consideration of two conditions that affect gas exchange and transport: carbon monoxide poisoning and chronic obstructive pulmonary disease.

Pulmonary function response in smokers and patients with chronic obstructive lung diseae (COPD) following exposure to concentrated fine (PM2.5) particles

EPA Science Inventory

Population-based studies strongly suggest that smokers and patients with COPD may be susceptible to particulate matter (PM). The reported associations were stronger with fine than coarse PM .These findings, however, have not been supported by laboratory or clinical data. We stu...

Airflow obstruction was associated with elevation of brachial-ankle pulse wave velocity but not ankle-brachial index in aged patients with chronic obstructive pulmonary disease.

PubMed

Chen, Rui; He, Wanbing; Zhang, Kun; Zheng, Houzhen; Lin, Lin; Nie, Ruqiong; Wang, Jingfeng; Huang, Hui

2015-09-01

Both brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) are important predictors for cardiovascular disease (CVD). Patients with chronic obstructive pulmonary disease (COPD) are at high risk of CVD. But the association between airflow obstruction and baPWV or ABI was still unclear. The study was aimed to investigate the influencing factors on arterial stiffness in aged COPD patients. 67 aged patients with COPD and 67 age- and sex-matched controls without COPD were enrolled in this study. COPD patients were grouped into four groups according to the Global Initiative for Chronic Obstructive Lung Disease Guidelines (GOLD). Both baPWV and ABI were evaluated. Spirometry indices, blood pressure, smoking history and related laboratory parameters were also collected. Comparing with controls, all COPD patients had significantly higher baPWV (1933 ± 355 cm/s versus 1515 ± 256 cm/s, P < 0.001) but not ABI (P = 0.196). And baPWV values were significantly highest at GOLD stage 4. Forced expiratory volume in 1 s (FEV1) was the most significant factor influencing baPWV, after adjusting for age, systolic blood pressure and other traditional cardiovascular risk factors (β = -0.463, P = 0.014). Arterial stiffness was serious in aged patients with COPD. Spirometry index FEV1 was a possible important predictor for the severity of arterial stiffness of COPD patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Importance of indoor dust biological ultrafine particles in the pathogenesis of chronic inflammatory lung diseases

PubMed Central

Kim, Yoon-Keun; Kang, Tae Soo; Kim, You-Young

2017-01-01

The role of infectious agents in the etiology of inflammatory diseases once believed to be non-infectious is increasingly being recognized. Many bacterial components in the indoor dust can evoke inflammatory lung diseases. Bacteria secrete nanometer-sized vesicles into the extracellular milieu, so-called extracellular vesicles (EV). which are pathophysiologically related to inflammatory diseases. Microbiota compositions in the indoor dust revealed the presence of both Gram-negative and Gram-positive bacteria. Escherichia coli is a model organism of Gram-negative Enterobacteriaceae. The repeated inhalation of E. coli-derived EVs caused neutrophilic inflammation and emphysema in a dose-dependent manner. The emphysema induced by E. coli-derived EVs was partially eliminated by the absence of Interferon-gamma or interleukin-17, suggesting that Th1 and/or Th17 cell responses are important in the emphysema development. Meanwhile, the repeated inhalation of Staphylococcus aureus-derived EVs did not induce emphysema, although they induced neutrophilic inflammation in the lung. In terms of microbial EV compositions in the indoor dust, genera Pseudomonas, Acinetobacter, Enterobacter, and Staphylococcus were dominant. As for the clinical significance of sensitization to EVs in the indoor dust, EV sensitization was closely associated with asthma, chronic obstructive pulmonary disorder (COPD), and lung cancer. These data indicate that biological ultrafine particles in the indoor dust, which are mainly composed of microbial EVs, are important in the pathogenesis of chronic lung diseases associated with neutrophilic inflammation. Taken together, microbial EVs in the indoor dust are an important diagnostic and therapeutic target for the control of chronic lung diseases, such as asthma, COPD, and lung cancer. PMID:29161804

Importance of indoor dust biological ultrafine particles in the pathogenesis of chronic inflammatory lung diseases.

PubMed

Yang, Jinho; Kim, Yoon-Keun; Kang, Tae Soo; Jee, Young-Koo; Kim, You-Young

2017-01-01

The role of infectious agents in the etiology of inflammatory diseases once believed to be non-infectious is increasingly being recognized. Many bacterial components in the indoor dust can evoke inflammatory lung diseases. Bacteria secrete nanometer-sized vesicles into the extracellular milieu, so-called extracellular vesicles (EV). which are pathophysiologically related to inflammatory diseases. Microbiota compositions in the indoor dust revealed the presence of both Gram-negative and Gram-positive bacteria. Escherichia coli is a model organism of Gram-negative Enterobacteriaceae. The repeated inhalation of E. coli-derived EVs caused neutrophilic inflammation and emphysema in a dose-dependent manner. The emphysema induced by E. coli-derived EVs was partially eliminated by the absence of Interferon-gamma or interleukin-17, suggesting that Th1 and/or Th17 cell responses are important in the emphysema development. Meanwhile, the repeated inhalation of Staphylococcus aureus-derived EVs did not induce emphysema, although they induced neutrophilic inflammation in the lung. In terms of microbial EV compositions in the indoor dust, genera Pseudomonas, Acinetobacter, Enterobacter, and Staphylococcus were dominant. As for the clinical significance of sensitization to EVs in the indoor dust, EV sensitization was closely associated with asthma, chronic obstructive pulmonary disorder (COPD), and lung cancer. These data indicate that biological ultrafine particles in the indoor dust, which are mainly composed of microbial EVs, are important in the pathogenesis of chronic lung diseases associated with neutrophilic inflammation. Taken together, microbial EVs in the indoor dust are an important diagnostic and therapeutic target for the control of chronic lung diseases, such as asthma, COPD, and lung cancer.

Domestic solid fuel combustion in an adult population in Nigeria: A cross sectional analysis of association with respiratory symptoms, quality of life and lung function.

PubMed

Obaseki, Daniel O; Awopeju, Olayemi F; Awokola, Babatunde I; Adeniyi, Bamidele O; Adefuye, Bolanle O; Ozoh, Obianuju B; Isiguzo, Godsent C; Amusa, Ganiyu A; Adewole, Olufemi O; Erhabor, Gregory E

2017-09-01

We examined the association of respiratory symptoms, health status, and lung function with the use of solid fuel (wood, charcoal, coal or crop residue) for cooking or heating in a predominantly non-smoking population. Using the protocol of the Burden of Obstructive Lung Diseases (BOLD) initiative, we collected representative population data using questionnaires and spirometry tests. We categorized solid fuel use into 'never user', 'ex user' and 'current user' based on responses to the survey. We developed regression models to evaluate the relation between use of solid fuel and the prevalence of respiratory symptoms, quality of life and lung function adjusting for confounding variables. Out of 1147 respondents with complete information on domestic fuel type, 33% were 'never-users', 19% were 'ex-users' while 48% reported current use of solid fuel for domestic cooking and/or indoor heating. Compared with never-users, current solid fuel users were more likely to report cough (OR: 1.7, 95% CI: 1.0, 2.9), cough or phlegm (OR: 1.6, 95% CI: 1.0, 2.5) and the association was stronger among women (OR: 3.0, 95% CI: 1.3, 7.1 and OR: 2.3, 95% CI: 1.1, 5.2, respectively). Current solid fuel users also had lower mental health status (coefficient: ?1.5, 95% CI: ?2.8, - 0.2) compared with the group of never-users. Current or previous domestic use of solid fuels for cooking or heating was not associated with higher prevalence of chronic airflow obstruction (FEV 1 /FVC < LLN). Using solid fuel for domestic cooking or heating was associated with a higher risk of cough or phlegm and a lower mental quality of life. However we found no significant effect in the prevalence of chronic airflow obstruction in Ife, Nigeria. Copyright © 2017. Published by Elsevier Ltd.

Lung Infarction Following Pulmonary Embolism: A Comparative Study on Clinical Conditions and CT Findings to Identify Predisposing Factors.

PubMed

Kirchner, J; Obermann, A; Stückradt, S; Tüshaus, C; Goltz, J; Liermann, D; Kickuth, R

2015-06-01

The aim of this study was to identify factors predisposing to lung infarction in patients with pulmonary embolism (PE). We performed a retrospective analysis on 154 patients with the final diagnosis of PE being examined between January 2009 and December 2012 by means of a Toshiba Aquilion 64 CT scanner. The severity of clinical symptoms was defined by means of a clinical index with 4 classes. The pulmonary clot load was quantified using a modified severity index of PE as proposed by Miller. We correlated several potential predictors of pulmonary infarction such as demographic data, pulmonary clot burden, distance of total vascular obstruction and pleura, the presence of cardiac congestion, signs of chronic bronchitis or emphysema with the occurrence of pulmonary infarction. Computed tomography revealed 78 areas of pulmonary infarction in 45/154 (29.2 %) patients. The presence of infarction was significantly higher in the right lung than in the left lung (p < 0.001). We found no correlation between pulmonary infarction and the presence of accompanying malignant diseases (r = -0.069), signs of chronic bronchitis (r = -0.109), cardiac congestion (r = -0.076), the quantified clot burden score (r = 0.176), and the severity of symptoms (r = -0.024). Only a very weak negative correlation between the presence of infarction and age (r = -0.199) was seen. However, we could demonstrate a moderate negative correlation between the distance of total vascular occlusion and the occurrence of infarction (r = -0.504). Neither cardiac congestion nor the degree of pulmonary vascular obstruction are main factors predisposing to pulmonary infarction in patients with PE. It seems that a peripheral total vascular obstruction more often results in infarction than even massive central clot burden. © Georg Thieme Verlag KG Stuttgart · New York.

Substance deposition assessment in obstructed pulmonary system through numerical characterization of airflow and inhaled particles attributes.

PubMed

Lalas, Antonios; Nousias, Stavros; Kikidis, Dimitrios; Lalos, Aris; Arvanitis, Gerasimos; Sougles, Christos; Moustakas, Konstantinos; Votis, Konstantinos; Verbanck, Sylvia; Usmani, Omar; Tzovaras, Dimitrios

2017-12-20

Chronic obstructive pulmonary disease (COPD) and asthma are considered as the two most widespread obstructive lung diseases, whereas they affect more than 500 million people worldwide. Unfortunately, the requirement for detailed geometric models of the lungs in combination with the increased computational resources needed for the simulation of the breathing did not allow great progress to be made in the past for the better understanding of inflammatory diseases of the airways through detailed modelling approaches. In this context, computational fluid dynamics (CFD) simulations accompanied by fluid particle tracing (FPT) analysis of the inhaled ambient particles are deemed critical for lung function assessment. Also they enable the understanding of particle depositions on the airways of patients, since these accumulations may affect or lead to inflammations. In this direction, the current study conducts an initial investigation for the better comprehension of particle deposition within the lungs. More specifically, accurate models of the airways obstructions that relate to pulmonary disease are developed and a thorough assessment of the airflow behavior together with identification of the effects of inhaled particle properties, such as size and density, is conducted. Our approach presents a first step towards an effective personalization of pulmonary treatment in regards to the geometric characteristics of the lungs and the in depth understanding of airflows within the airways. A geometry processing technique involving contraction algorithms is established and used to employ the different respiratory arrangements associated with lung related diseases that exhibit airways obstructions. Apart from the normal lung case, two categories of obstructed cases are examined, i.e. models with obstructions in both lungs and models with narrowings in the right lung only. Precise assumptions regarding airflow and deposition fraction (DF) over various sections of the lungs are drawn by simulating these distinct incidents through the finite volume method (FVM) and particularly the CFD and FPT algorithms. Moreover, a detailed parametric analysis clarifies the effects of the particles size and density in terms of regional deposition upon several parts of the pulmonary system. In this manner, the deposition pattern of various substances can be assessed. For the specific case of the unobstructed lung model most particles are detected on the right lung (48.56% of total, when the air flowrate is 12.6 L/min), a fact that is also true when obstructions arise symmetrically in both lungs (51.45% of total, when the air flowrate is 6.06 L/min and obstructions occur after the second generation). In contrast, when narrowings are developed on the right lung only, most particles are pushed on the left section (68.22% of total, when the air flowrate is 11.2 L/min) indicating that inhaled medication is generally deposited away from the areas of inflammation. This observation is useful when designing medical treatment of lung diseases. Furthermore, particles with diameters from 1 μm to 10 μm are shown to be mainly deposited on the lower airways, whereas particles with diameters of 20 μm and 30 μm are mostly accumulated in the upper airways. As a result, the current analysis indicates increased DF levels in the upper airways when the particle diameter is enlarged. Additionally, when the particles density increases from 1000 Kg/m 3 to 2000 Kg/m 3 , the DF is enhanced on every generation and for all cases investigated herein. The results obtained by our simulations provide an accurate and quantitative estimation of all important parameters involved in lung modeling. The treatment of respiratory diseases with inhaled medical substances can be advanced by the clinical use of accurate CFD and FPT simulations and specifically by evaluating the deposition of inhaled particles in a regional oriented perspective in regards to different particle sizes and particle densities. Since a drug with specific characteristics (i.e. particle size and density) exhibits maximum deposition on particular lung areas, the current study provides initial indications to a qualified physician for proper selection of medication.

Effects of a helium/oxygen mixture on individuals' lung function and metabolic cost during submaximal exercise for participants with obstructive lung diseases.

PubMed

Häussermann, Sabine; Schulze, Anja; Katz, Ira M; Martin, Andrew R; Herpich, Christiane; Hunger, Theresa; Texereau, Joëlle

2015-01-01

Helium/oxygen therapies have been studied as a means to reduce the symptoms of obstructive lung diseases with inconclusive results in clinical trials. To better understand this variability in results, an exploratory physiological study was performed comparing the effects of helium/oxygen mixture (78%/22%) to that of medical air. The gas mixtures were administered to healthy, asthmatic, and chronic obstructive pulmonary disease (COPD) participants, both moderate and severe (6 participants in each disease group, a total of 30); at rest and during submaximal cycling exercise with equivalent work rates. Measurements of ventilatory parameters, forced spirometry, and ergospirometry were obtained. There was no statistical difference in ventilatory and cardiac responses to breathing helium/oxygen during submaximal exercise. For asthmatics, but not for the COPD participants, there was a statistically significant benefit in reduced metabolic cost, determined through measurement of oxygen uptake, for the same exercise work rate. However, the individual data show that there were a mixture of responders and nonresponders to helium/oxygen in all of the groups. The inconsistent response to helium/oxygen between individuals is perhaps the key drawback to the more effective and widespread use of helium/oxygen to increase exercise capacity and for other therapeutic applications.

In Vitro Microfluidic Models of Mucus-Like Obstructions in Small Airways

NASA Astrophysics Data System (ADS)

Mulligan, Molly K.; Grotberg, James B.; Sznitman, Josué

2012-11-01

Liquid plugs can form in the lungs as a result of a host of different diseases, including cystic fibrosis and chronic obstructive pulmonary disease. The existence of such fluid obstructions have been found as far down in the bronchiole tree as the sixteenth generation, where bronchiole openings have diameters on the order of a hundred to a few hundred microns. Understanding the propagation of liquid plugs within the bifurcating branches of bronchiole airways is important because their presence in the lungs, and their rupture and break-up, can cause injury to the epithelial cells lining the airway walls as a result of high wall shear stresses. In particular, liquid plug rupture and break-up frequently occurs at airway bifurcations. Until present, however, experimental studies of liquid plugs have generally been restricted to Newtonian fluids that do not reflect the actual pseudoplastic properties of lung mucus. The present work attempts to uncover the propagation, rupture and break-up of mucus-like liquid plugs in the lower generations of the airway tree using microfluidic models. Our approach allows the dynamics of mucus-like plug break-up to be studied in real-time, in a one-to-one in vitro model, as a function of mucus rheology and bronchial tree geometry.

Airway hyperresponsiveness in chronic obstructive pulmonary disease: A marker of asthma-chronic obstructive pulmonary disease overlap syndrome?

PubMed

Tkacova, Ruzena; Dai, Darlene L Y; Vonk, Judith M; Leung, Janice M; Hiemstra, Pieter S; van den Berge, Maarten; Kunz, Lisette; Hollander, Zsuzsanna; Tashkin, Donald; Wise, Robert; Connett, John; Ng, Raymond; McManus, Bruce; Paul Man, S F; Postma, Dirkje S; Sin, Don D

2016-12-01

The impact of airway hyperreactivity (AHR) on respiratory mortality and systemic inflammation among patients with chronic obstructive pulmonary disease (COPD) is largely unknown. We used data from 2 large studies to determine the relationship between AHR and FEV 1 decline, respiratory mortality, and systemic inflammation. We sought to determine the relationship of AHR with FEV 1 decline, respiratory mortality, and systemic inflammatory burden in patients with COPD in the Lung Health Study (LHS) and the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study. The LHS enrolled current smokers with mild-to-moderate COPD (n = 5887), and the GLUCOLD study enrolled former and current smokers with moderate-to-severe COPD (n = 51). For the primary analysis, we defined AHR by a methacholine provocation concentration of 4 mg/mL or less, which led to a 20% reduction in FEV 1 (PC 20 ). The primary outcomes were FEV 1 decline, respiratory mortality, and biomarkers of systemic inflammation. Approximately 24% of LHS participants had AHR. Compared with patients without AHR, patients with AHR had a 2-fold increased risk of respiratory mortality (hazard ratio, 2.38; 95% CI, 1.38-4.11; P = .002) and experienced an accelerated FEV 1 decline by 13.2 mL/y in the LHS (P = .007) and by 12.4 mL/y in the much smaller GLUCOLD study (P = .079). Patients with AHR had generally reduced burden of systemic inflammatory biomarkers than did those without AHR. AHR is common in patients with mild-to-moderate COPD, affecting 1 in 4 patients and identifies a distinct subset of patients who have increased risk of disease progression and mortality. AHR may represent a spectrum of the asthma-COPD overlap phenotype that urgently requires disease modification. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

Sundar, Isaac K.; Hwang, Jae-Woong; Wu, Shaoping

Research highlights: {yields} Vitamin D deficiency is linked to accelerated decline in lung function. {yields} Levels of vitamin D receptor (VDR) are decreased in lungs of patients with COPD. {yields} VDR knock-out mouse showed increased lung inflammation and emphysema. {yields} This was associated with decline in lung function and increased MMPs. {yields} VDR knock-out mouse model is useful for studying the mechanisms of lung diseases. -- Abstract: Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. Themore » level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR{sup -/-}) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-{kappa}B) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.« less

COPD, emphysema and the onset of lung cancer. A systematic review.

PubMed

Mouronte-Roibás, Cecilia; Leiro-Fernández, Virginia; Fernández-Villar, Alberto; Botana-Rial, Maribel; Ramos-Hernández, Cristina; Ruano-Ravina, Alberto

2016-11-28

Chronic Obstructive Pulmonary Disease (COPD) and emphysema have been described as possible risk factors for lung cancer. We aim to assess the relationship between COPD, emphysema and the onset of lung cancer. We have developed a systematic review of the published literature in order to systematically analyze the scientific evidence available on this association, applying predefined inclusion and exclusion criteria. 11 Studies were included. Both COPD and emphysema seem to increase the risk of developing lung cancer, being this risk higher for smokers with heavier tobacco consumption. These results emphasize the need for physicians to perform spirometries in current and former smokers and lung image tests when needed in order to identify COPD and emphysema and thus select patients at higher risk of developing lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Airway disease phenotypes in animal models of cystic fibrosis.

PubMed

McCarron, Alexandra; Donnelley, Martin; Parsons, David

2018-04-02

In humans, cystic fibrosis (CF) lung disease is characterised by chronic infection, inflammation, airway remodelling, and mucus obstruction. A lack of pulmonary manifestations in CF mouse models has hindered investigations of airway disease pathogenesis, as well as the development and testing of potential therapeutics. However, recently generated CF animal models including rat, ferret and pig models demonstrate a range of well characterised lung disease phenotypes with varying degrees of severity. This review discusses the airway phenotypes of currently available CF animal models and presents potential applications of each model in airway-related CF research.

Smart watch-based coaching with tiotropium and olodaterol ameliorates physical activity in patients with chronic obstructive pulmonary disease

PubMed Central

Hataji, Osamu; Nishii, Yoichi; Ito, Kentaro; Sakaguchi, Tadashi; Saiki, Haruko; Suzuki, Yuta; D'Alessandro-Gabazza, Corina; Fujimoto, Hajime; Kobayashi, Tetsu; Gabazza, Esteban C.; Taguchi, Osamu

2017-01-01

Combined therapy with tiotropium and olodaterol notably improves parameters of lung function and quality of life in patients with chronic obstructive pulmonary disease (COPD) compared to mono-components; however, its effect on physical activity is unknown. The present study evaluated whether combination therapy affects daily physical performance in patients with COPD under a smart watch-based encouragement program. This was a non-blinded clinical trial with no randomization or placebo control. A total of 20 patients with COPD were enrolled in the present study. The patients carried an accelerometer for 4 weeks; they received no therapy during the first 2 weeks but they were treated with combined tiotropium and olodaterol under a smart watch-based encouragement program for the last 2 weeks. The pulmonary function test, COPD assessment test, 6-min walk distance and parameters of physical activity were significantly improved (P<0.05) by combination therapy under smart watch-based coaching compared with values prior to treatment. To the best of our knowledge, the present study for the first time provides evidence that smart watch-based coaching in combination with tiotropium and olodaterol may improve daily physical activity in chronic obstructive pulmonary disease. PMID:29104624

Respiratory Muscle Strength in Patients With Chronic Obstructive Pulmonary Disease.

PubMed

Kim, Nam-Sik; Seo, Jeong-Hwan; Ko, Myoung-Hwan; Park, Sung-Hee; Kang, Seong-Woong; Won, Yu Hui

2017-08-01

To compare the respiratory muscle strength between patients with stable and acutely exacerbated (AE) chronic obstructive pulmonary disease (COPD) at various stages. A retrospective medical record review was conducted on patients with COPD from March 2014 to May 2016. Patients were subdivided into COPD stages 1-4 according to the Global Initiative for Chronic Obstructive Lung Disease guidelines: mild, moderate, severe, and very severe. A rehabilitation physician reviewed their medical records and initial assessment, including spirometry, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), COPD Assessment Test, and modified Medical Research Council scale. We then compared the initial parameters in patients with a stable condition and those at AE status. The AE group (n=94) had significantly lower MIP (AE, 55.93±20.57; stable, 67.88±24.96; p=0.006) and MIP% (AE, 82.82±27.92; stable, 96.64±30.46; p=0.015) than the stable patient group (n=36). MIP, but not MEP, was proportional to disease severity in patients with AE and stable COPD. The strength of the inspiratory muscles may better reflect severity of disease when compared to that of expiratory muscles.

Is It Time to Change the Definition of Acute Exacerbation of Chronic Obstructive Pulmornary Disease? What Do We Need to Add?

PubMed

Montes de Oca, Maria; Laucho-Contreras, Maria Eugenia

2018-06-14

Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) are associated with increased mortality, rate of hospitalization, use of healthcare resources, and have a negative impact on disease progression, quality of life and lung function of patients with chronic obstructive pulmonary disease (COPD). There is an imperative need to homogenize the definition of AECOPD because the incidence of exacerbations has a significant influence or implication on treatment decision making, particularly in pharmacotherapy and could impact the outcome or change the statistical significance of a therapeutic intervention in clinical trials. In this review, using PubMed searches, we have analyzed the weaknesses and strengths of the different used AECOPD definitions (symptom-based, healthcare-based definition or the combinations of both), as well as the findings of the studies that have assessed the relationship of different biomarkers with the diagnosis, etiology and differential diagnosis of AECOPD and the progress towards the development of a more precise definition of COPD exacerbation. Finally, we have proposed a simple definition of AECOPD, which must be validated in future clinical trials to define its accuracy and usefulness in daily practice.

Smart watch-based coaching with tiotropium and olodaterol ameliorates physical activity in patients with chronic obstructive pulmonary disease.

PubMed

Hataji, Osamu; Nishii, Yoichi; Ito, Kentaro; Sakaguchi, Tadashi; Saiki, Haruko; Suzuki, Yuta; D'Alessandro-Gabazza, Corina; Fujimoto, Hajime; Kobayashi, Tetsu; Gabazza, Esteban C; Taguchi, Osamu

2017-11-01

Combined therapy with tiotropium and olodaterol notably improves parameters of lung function and quality of life in patients with chronic obstructive pulmonary disease (COPD) compared to mono-components; however, its effect on physical activity is unknown. The present study evaluated whether combination therapy affects daily physical performance in patients with COPD under a smart watch-based encouragement program. This was a non-blinded clinical trial with no randomization or placebo control. A total of 20 patients with COPD were enrolled in the present study. The patients carried an accelerometer for 4 weeks; they received no therapy during the first 2 weeks but they were treated with combined tiotropium and olodaterol under a smart watch-based encouragement program for the last 2 weeks. The pulmonary function test, COPD assessment test, 6-min walk distance and parameters of physical activity were significantly improved (P<0.05) by combination therapy under smart watch-based coaching compared with values prior to treatment. To the best of our knowledge, the present study for the first time provides evidence that smart watch-based coaching in combination with tiotropium and olodaterol may improve daily physical activity in chronic obstructive pulmonary disease.

Six-Minute-Walk Distance and Accelerometry Predict Outcomes in Chronic Obstructive Pulmonary Disease Independent of Global Initiative for Chronic Obstructive Lung Disease 2011 Group

PubMed Central

Smith, Patrick J.; Babyak, Michael A.; Mabe, Stephanie K.; Martinu, Tereza; Welty-Wolf, Karen E.; Emery, Charles F.; Palmer, Scott M.; Blumenthal, James A.

2015-01-01

Rationale: The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. Objectives: To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Methods: Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Measurements and Main Results: Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P = 0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P = 0.002). Conclusions: Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD. PMID:25568929

Peak flow meter with a questionnaire and mini-spirometer to help detect asthma and COPD in real-life clinical practice: a cross-sectional study.

PubMed

Thorat, Yogesh T; Salvi, Sundeep S; Kodgule, Rahul R

2017-05-09

Peak flow meter with questionnaire and mini-spirometer are considered as alternative tools to spirometry for screening of asthma and chronic obstructive pulmonary disease. However, the accuracy of these tools together, in clinical settings for disease diagnosis, has not been studied. Two hundred consecutive patients with respiratory complaints answered a short symptom questionnaire and performed peak expiratory flow measurements, standard spirometry with Koko spirometer and mini-spirometry (COPD-6). Spirometry was repeated after bronchodilation. Physician made a final diagnosis of asthma, chronic obstructive pulmonary disease and others. One eighty nine patients (78 females) with age 51 ± 17 years with asthma (115), chronic obstructive pulmonary disease (33) and others (41) completed the study. "Breathlessness > 6months" and "cough > 6months" were important symptoms to detect obstructive airways disease. "Asymptomatic period > 2 weeks" had the best sensitivity (Sn) and specificity (Sp) to differentiate asthma and chronic obstructive pulmonary disease. A peak expiratory flow of < 80% predicted was the best cut-off to detect airflow limitation (Sn 90%, Sp 50%). Respiratory symptoms with PEF < 80% predicted, had Sn 84 and Sp 93% to detect OAD. COPD-6 device under-estimated FEV 1 by 13 mL (95% CI: -212, 185). At a cut-off of 0.75, the FEV 1 /FEV 6 had the best accuracy (Sn 80%, Sp 86%) to detect airflow limitation. Peak flow meter with few symptom questions can be effectively used in clinical practice for objective detection of asthma and chronic obstructive pulmonary disease, in the absence of good quality spirometry. Mini-spirometers are useful in detection of obstructive airways diseases but FEV 1 measured is inaccurate. DIFFERENTIATING CONDITIONS IN POORLY-EQUIPPED SETTINGS: A simple questionnaire and peak flow meter measurements can help doctors differentiate between asthma and chronic lung disease. In clinical settings where access to specialist equipment and knowledge is limited, it can be challenging for doctors to tell the difference between asthma and chronic obstructive pulmonary disease (COPD). To determine a viable alternative method for differentiating between these diseases, Rahul Kodgule and colleagues at the Chest Research Foundation in Pune, India, trialed a simplified version of two existing symptom questionnaires, combined with peak flow meter measurements. They assessed 189 patients using this method, and found it aided diagnosis with high sensitivity and specificity. Breathlessness, cough and wheeze were the minimal symptoms required for COPD diagnosis, while the length of asymptomatic periods was most helpful in distinguishing asthma from COPD.

Occupation and three-year incidence of respiratory symptoms and lung function decline: the ARIC Study.

PubMed

Mirabelli, Maria C; London, Stephanie J; Charles, Luenda E; Pompeii, Lisa A; Wagenknecht, Lynne E

2012-03-20

Specific occupations are associated with adverse respiratory health. Inhalation exposures encountered in these jobs may place workers at risk of new-onset respiratory disease. We analyzed data from 8,967 participants from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal cohort study. Participants included in this analysis were free of chronic cough and phlegm, wheezing, asthma, chronic bronchitis, emphysema, and other chronic lung conditions at the baseline examination, when they were aged 45-64 years. Using data collected in the baseline and first follow-up examination, we evaluated associations between occupation and the three-year incidence of cough, phlegm, wheezing, and airway obstruction and changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured by spirometry. All associations were adjusted for age, cigarettes per day, race, smoking status, and study center. During the approximately three-year follow-up, the percentage of participants developing chronic cough was 3%; chronic phlegm, 3%; wheezing, 3%; and airway obstruction, defined as FEV1 < lower limit of normal (LLN) and FEV1/FVC < LLN, 2%. The average annual declines in FEV1 and FVC were 56 mL and 66 mL, respectively, among men and 40 mL and 52 mL, respectively, among women. Relative to a referent category of managerial and administrative support occupations, elevated risks of new-onset chronic cough and chronic phlegm were observed for mechanics and repairers (chronic cough: RR: 1.81, 95% CI: 1.02, 3.21; chronic phlegm: RR: 2.10, 95% CI: 1.23, 3.57) and cleaning and building service workers (chronic cough: RR: 1.85, 95% CI: 1.01, 3.37; chronic phlegm: RR: 2.28, 95% CI: 1.27, 4.08). Despite the elevated risk of new-onset symptoms, employment in cleaning and building services was associated with attenuated lung function decline, particularly among men, who averaged annual declines in FEV1 and FVC of 14 mL and 23 mL, respectively, less than the declines observed in the referent population. Employment in mechanic and repair jobs and cleaning and building service occupations are associated with increased incidence of respiratory symptoms. Specific occupations affect the respiratory health of adults without pre-existing respiratory health symptoms and conditions, though long-term health consequences of inhalation exposures in these jobs remain largely unexplored.

Occupation and three-year incidence of respiratory symptoms and lung function decline: the ARIC Study

PubMed Central

2012-01-01

Background Specific occupations are associated with adverse respiratory health. Inhalation exposures encountered in these jobs may place workers at risk of new-onset respiratory disease. Methods We analyzed data from 8,967 participants from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal cohort study. Participants included in this analysis were free of chronic cough and phlegm, wheezing, asthma, chronic bronchitis, emphysema, and other chronic lung conditions at the baseline examination, when they were aged 45-64 years. Using data collected in the baseline and first follow-up examination, we evaluated associations between occupation and the three-year incidence of cough, phlegm, wheezing, and airway obstruction and changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured by spirometry. All associations were adjusted for age, cigarettes per day, race, smoking status, and study center. Results During the approximately three-year follow-up, the percentage of participants developing chronic cough was 3%; chronic phlegm, 3%; wheezing, 3%; and airway obstruction, defined as FEV1 < lower limit of normal (LLN) and FEV1/FVC < LLN, 2%. The average annual declines in FEV1 and FVC were 56 mL and 66 mL, respectively, among men and 40 mL and 52 mL, respectively, among women. Relative to a referent category of managerial and administrative support occupations, elevated risks of new-onset chronic cough and chronic phlegm were observed for mechanics and repairers (chronic cough: RR: 1.81, 95% CI: 1.02, 3.21; chronic phlegm: RR: 2.10, 95% CI: 1.23, 3.57) and cleaning and building service workers (chronic cough: RR: 1.85, 95% CI: 1.01, 3.37; chronic phlegm: RR: 2.28, 95% CI: 1.27, 4.08). Despite the elevated risk of new-onset symptoms, employment in cleaning and building services was associated with attenuated lung function decline, particularly among men, who averaged annual declines in FEV1 and FVC of 14 mL and 23 mL, respectively, less than the declines observed in the referent population. Conclusions Employment in mechanic and repair jobs and cleaning and building service occupations are associated with increased incidence of respiratory symptoms. Specific occupations affect the respiratory health of adults without pre-existing respiratory health symptoms and conditions, though long-term health consequences of inhalation exposures in these jobs remain largely unexplored. PMID:22433119

Low-Level Laser Therapy Reduces Lung Inflammation in an Experimental Model of Chronic Obstructive Pulmonary Disease Involving P2X7 Receptor.

PubMed

da Cunha Moraes, Gabriel; Vitoretti, Luana Beatriz; de Brito, Auriléia Aparecida; Alves, Cintia Estefano; de Oliveira, Nicole Cristine Rigonato; Dos Santos Dias, Alana; Matos, Yves Silva Teles; Oliveira-Junior, Manoel Carneiro; Oliveira, Luis Vicente Franco; da Palma, Renata Kelly; Candeo, Larissa Carbonera; Lino-Dos-Santos-Franco, Adriana; Horliana, Anna Carolina Ratto Tempestine; Gimenes Júnior, João Antonio; Aimbire, Flavio; Vieira, Rodolfo Paula; Ligeiro-de-Oliveira, Ana Paula

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible airflow limitation, airway inflammation and remodeling, and enlargement of alveolar spaces. COPD is in the top five leading causes of deaths worldwide and presents a high economic cost. However, there are some preventive measures to lower the risk of developing COPD. Low-level laser therapy (LLLT) is a new effective therapy, with very low cost and no side effects. So, our objective was to investigate if LLLT reduces pulmonary alterations in an experimental model of COPD. C57BL/6 mice were submitted to cigarette smoke for 75 days (2x/day). After 60 days to smoke exposure, the treated group was submitted to LLLT (diode laser, 660 nm, 30 mW, and 3 J/cm 2 ) for 15 days and euthanized for morphologic and functional analysis of the lungs. Our results showed that LLLT significantly reduced the number of inflammatory cells and the proinflammatory cytokine secretion such as IL-1 β , IL-6, and TNF- α in bronchoalveolar lavage fluid (BALF). We also observed that LLLT decreased collagen deposition as well as the expression of purinergic P2X7 receptor. On the other hand, LLLT increased the IL-10 release. Thus, LLLT can be pointed as a promising therapeutic approach for lung inflammatory diseases as COPD.

Prevention and management of lung cancer in China.

PubMed

Hong, Qun-Ying; Wu, Guo-Ming; Qian, Gui-Sheng; Hu, Cheng-Ping; Zhou, Jian-Ying; Chen, Liang-An; Li, Wei-Min; Li, Shi-Yue; Wang, Kai; Wang, Qi; Zhang, Xiao-Ju; Li, Jing; Gong, Xin; Bai, Chun-Xue

2015-09-01

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer. © 2015 American Cancer Society.

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

PubMed Central

Sundar, Isaac K.; Ahmad, Tanveer; Yao, Hongwei; Hwang, Jae-woong; Gerloff, Janice; Lawrence, B. Paige; Sellix, Michael T.; Rahman, Irfan

2015-01-01

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations. PMID:25923474

Lung function, respiratory symptoms and venous thromboembolism risk: the Atherosclerosis Risk in Communities Study.

PubMed

Kubota, Y; London, S J; Cushman, M; Chamberlain, A M; Rosamond, W D; Heckbert, S R; Zakai, N; Folsom, A R

2016-12-01

Essentials The association of lung function with venous thromboembolism (VTE) is unclear. Chronic obstructive pulmonary disease (COPD) patterns were associated with a higher risk of VTE. Symptoms were also associated with a higher risk of VTE, but a restrictive pattern was not. COPD may increase the risk of VTE and respiratory symptoms may be a novel risk marker for VTE. Background The evidence for the association between chronic obstructive pulmonary disease (COPD) and venous thromboembolism (VTE) is limited. There is no study investigating the association between restrictive lung disease (RLD) and respiratory symptoms with VTE. Objectives To investigate prospectively the association of lung function and respiratory symptoms with VTE. Patients/Methods In 1987-1989, we assessed lung function by using spirometry, and obtained information on respiratory symptoms (cough, phlegm, and dyspnea) in 14 654 participants aged 45-64 years, without a history of VTE or anticoagulant use, and followed them through 2011. Participants were classified into four mutually exclusive groups: 'COPD' (forced expiratory volume in 1 s [FEV 1 ]/forced vital capacity [FVC] below the lower limit of normal [LLN]), 'RLD' (FEV 1 /FVC ≥ LLN and FVC < LLN), 'respiratory symptoms with normal spirometic results' (without RLD or COPD), and 'normal' (without respiratory symptoms, RLD, or COPD). Results We documented 639 VTEs (238 unprovoked and 401 provoked VTEs). After adjustment for VTE risk factors, VTE risk was increased for individuals with either respiratory symptoms with normal spirometric results (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12-1.73) or COPD (HR 1.33, 95% CI 1.07-1.67) but not for those with RLD (HR 1.15, 95% CI 0.82-1.60). These elevated risks of VTE were derived from both unprovoked and provoked VTE. Moreover, FEV 1 and FEV 1 /FVC showed dose-response relationships with VTE. COPD was more strongly associated with pulmonary embolism than with deep vein thrombosis. Conclusions Obstructive spirometric patterns were associated with an increased risk of VTE, suggesting that COPD may increase the risk of VTE. Respiratory symptoms may represent a novel risk marker for VTE. © 2016 International Society on Thrombosis and Haemostasis.

Survival after Lung Volume Reduction in Chronic Obstructive Pulmonary Disease

PubMed Central

Hogg, James C.; Chu, Fanny S. F.; Tan, Wan C.; Sin, Don D.; Patel, Sanjay A.; Pare, Peter D.; Martinez, Fernando J.; Rogers, Robert M.; Make, Barry J.; Criner, Gerard J.; Cherniack, Reuben M.; Sharafkhaneh, Amir; Luketich, James D.; Coxson, Harvey O.; Elliott, W. Mark; Sciurba, Frank C.

2007-01-01

Rationale: COPD is associated with reduced life expectancy. Objectives: To determine the association between small airway pathology and long-term survival after lung volume reduction in chronic obstructive pulmonary disease (COPD) and the effect of corticosteroids on this pathology. Methods: Patients with severe (GOLD-3) and very severe (GOLD-4) COPD (n = 101) were studied after lung volume reduction surgery. Respiratory symptoms, quality of life, pulmonary function, exercise tolerance, chest radiology, and corticosteroid treatment status were assessed preoperatively. The severity of luminal occlusion, wall thickening, and the presence of small airways containing lymphoid follicles were determined in resected lung tissue. Kaplan-Meier survival analysis and Cox proportional hazards models were used to determine the relationship between survival and small airway pathology. The effect of corticosteroids on this pathology was assessed by comparing treated and untreated groups. Measurements and Main Results: The quartile of subjects with the greatest luminal occlusion, adjusted for covariates, died earlier than subjects who had the least occlusion (hazard ratio, 3.28; 95% confidence interval, 1.55–6.92; P = 0.002). There was a trend toward a reduction in the number of airways containing lymphoid follicles (P = 0.051) in those receiving corticosteroids, with a statistically significant difference between the control and oral ± inhaled corticosteroid–treated groups (P = 0.019). However, corticosteroid treatment had no effect on airway wall thickening or luminal occlusion. Conclusions: Occlusion of the small airways by inflammatory exudates containing mucus is associated with early death in patients with severe emphysema treated by lung volume reduction surgery. Corticosteroid treatment dampens the host immune response in these airways by reducing lymphoid follicles without changing wall thickening and luminal occlusion. PMID:17556723

Association of lung function and chronic obstructive pulmonary disease with American Heart Association's Life's Simple 7 cardiovascular health metrics.

PubMed

Fan, Wenjun; Lee, Hwa; Lee, Angela; Kieu, Chi; Wong, Nathan D

2017-10-01

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U.S. There is a strong association between COPD and cardiovascular (CV) disease; however, the relation between COPD and CV health factors is not well defined. We examined the relation between lung function and CV health factors defined by American Heart Association's (AHA) Life's Simple 7 (LS7). We studied 6352 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) 2009-2012. Analysis of variance was used to compare mean FEV1% of predicted across levels of each LS7 metric and population attributable risk was calculated based on COPD prevalence. We also conducted linear regression and logistic regression analyses to determine the association between lung function, COPD and LS7 score. Overall 19.9% of subjects were defined as having COPD. Subjects in the highest categories of the LS7 metrics had the highest mean values of FEV1% of predicted (p < 0.0001 except for total cholesterol). Current smoking and hypertension had a population attributed risk of 21.8% and 21.1% of COPD, respectively. Compared to subjects with 0 ideal health factors, the gender and ethnicity-adjusted odds (95% CI) for COPD were 0.45 (0.22-0.93), 0.22 (0.11-0.43) for those with 4 and 5-7 factors, but adjustment for age attenuated this relation. LS7 score is associated with lung function as well as the odds of COPD that is largely explained by age. Studies are needed to show if promotion of CV health will preserve healthy lung function. Copyright © 2017 Elsevier Ltd. All rights reserved.

"I Can Breathe Again!" Patients' Self-Management Strategies for Episodic Breathlessness in Advanced Disease, Derived From Qualitative Interviews.

PubMed

Simon, Steffen T; Weingärtner, Vera; Higginson, Irene J; Benalia, Hamid; Gysels, Marjolein; Murtagh, Fliss E M; Spicer, James; Linde, Philipp; Voltz, Raymond; Bausewein, Claudia

2016-08-01

Episodic breathlessness causes additional distress to breathless patients with advanced disease, but management is still insufficient and there is a lack of knowledge on effective coping strategies. The aim was to explore patients' self-management strategies for episodic breathlessness. In-depth interviews with patients suffering from episodic breathlessness as a result of chronic heart failure, chronic obstructive pulmonary disease, lung cancer, or motor neuron disease were conducted. Interviews were transcribed verbatim and analyzed guided by the analytic hierarchy of Framework analysis. A total of 51 participants were interviewed (15 chronic heart failure, 14 chronic obstructive pulmonary disease, 13 lung cancer, and nine motor neuron disease; age, mean [SD], 68 [12], 41% women, median Karnofsky index 60%). They described six main strategies for coping with episodes of breathlessness: reduction of physical exertion, cognitive and psychological strategies, breathing techniques and positions, air and oxygen, drugs and medical devices, and environmental and other strategies. Some strategies were used in an opposing way, e.g., concentrating on the breathing vs. distraction from any thoughts of breathlessness or laying down flat vs. standing up and raising hands. Patients used a number of different strategies to cope with episodic breathlessness, adding more detailed understanding of existing strategies for breathlessness. The findings, therefore, may provide a valuable aid for health care providers, affected patients, and their relatives. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Comorbidity in chronic obstructive pulmonary disease. Related to disease severity?

PubMed

Echave-Sustaeta, Jose M; Comeche Casanova, Lorena; Cosio, Borja G; Soler-Cataluña, Juan Jose; Garcia-Lujan, Ricardo; Ribera, Xavier

2014-01-01

Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients. This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients. In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists. The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected. The Charlson comorbidity score was calculated. Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%. Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage. COPD patients attended to in internal medicine departments show high scores of comorbidity. However, GOLD stage was not an independent predictor of comorbidity.

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability

PubMed Central

Zago, Michela; Sheridan, Jared A.; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H.; Hamid, Qutayba

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients. PMID:28749959

Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability.

PubMed

Zago, Michela; Sheridan, Jared A; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H; Hamid, Qutayba; Baglole, Carolyn J

2017-01-01

Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients.

Dysregulation of Antiviral Function of CD8(+) T Cells in the Chronic Obstructive Pulmonary Disease Lung. Role of the PD-1-PD-L1 Axis.

PubMed

McKendry, Richard T; Spalluto, C Mirella; Burke, Hannah; Nicholas, Ben; Cellura, Doriana; Al-Shamkhani, Aymen; Staples, Karl J; Wilkinson, Tom M A

2016-03-15

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to respiratory viral infections that cause exacerbations. The mechanisms underlying this susceptibility are not understood. Effectors of the adaptive immune response-CD8(+) T cells that clear viral infections-are present in increased numbers in the lungs of patients with COPD, but they fail to protect against infection and may contribute to the immunopathology of the disease. CD8(+) function and signaling through the programmed cell death protein (PD)-1 exhaustion pathway were investigated as a potential key mechanism of viral exacerbation of the COPD lung. Tissue from control subjects and patients with COPD undergoing lung resection was infected with live influenza virus ex vivo. Viral infection and expression of lung cell markers were analyzed using flow cytometry. The proportion of lung CD8(+) T cells expressing PD-1 was greater in COPD (mean, 16.2%) than in controls (4.4%, P = 0.029). Only epithelial cells and macrophages were infected with influenza, and there was no difference in the proportion of infected cells between controls and COPD. Infection up-regulated T-cell PD-1 expression in control and COPD samples. Concurrently, influenza significantly up-regulated the marker of cytotoxic degranulation (CD107a) on CD8(+) T cells (P = 0.03) from control subjects but not on those from patients with COPD. Virus-induced expression of the ligand PD-L1 was decreased on COPD macrophages (P = 0.04) with a corresponding increase in IFN-γ release from infected COPD explants compared with controls (P = 0.04). This study has established a signal of cytotoxic immune dysfunction and aberrant immune regulation in the COPD lung that may explain both the susceptibility to viral infection and the excessive inflammation associated with exacerbations.

Dysregulation of Antiviral Function of CD8+ T Cells in the Chronic Obstructive Pulmonary Disease Lung. Role of the PD-1–PD-L1 Axis

PubMed Central

McKendry, Richard T.; Spalluto, C. Mirella; Burke, Hannah; Nicholas, Ben; Cellura, Doriana; Al-Shamkhani, Aymen; Staples, Karl J.

2016-01-01

Rationale: Patients with chronic obstructive pulmonary disease (COPD) are susceptible to respiratory viral infections that cause exacerbations. The mechanisms underlying this susceptibility are not understood. Effectors of the adaptive immune response—CD8+ T cells that clear viral infections—are present in increased numbers in the lungs of patients with COPD, but they fail to protect against infection and may contribute to the immunopathology of the disease. Objectives: CD8+ function and signaling through the programmed cell death protein (PD)-1 exhaustion pathway were investigated as a potential key mechanism of viral exacerbation of the COPD lung. Methods: Tissue from control subjects and patients with COPD undergoing lung resection was infected with live influenza virus ex vivo. Viral infection and expression of lung cell markers were analyzed using flow cytometry. Measurements and Main Results: The proportion of lung CD8+ T cells expressing PD-1 was greater in COPD (mean, 16.2%) than in controls (4.4%, P = 0.029). Only epithelial cells and macrophages were infected with influenza, and there was no difference in the proportion of infected cells between controls and COPD. Infection up-regulated T-cell PD-1 expression in control and COPD samples. Concurrently, influenza significantly up-regulated the marker of cytotoxic degranulation (CD107a) on CD8+ T cells (P = 0.03) from control subjects but not on those from patients with COPD. Virus-induced expression of the ligand PD-L1 was decreased on COPD macrophages (P = 0.04) with a corresponding increase in IFN-γ release from infected COPD explants compared with controls (P = 0.04). Conclusions: This study has established a signal of cytotoxic immune dysfunction and aberrant immune regulation in the COPD lung that may explain both the susceptibility to viral infection and the excessive inflammation associated with exacerbations. PMID:26517304

Exposing a deadly alliance: novel insights into the biological links between COPD and lung cancer.

PubMed

Vermaelen, K; Brusselle, G

2013-10-01

Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide and is expected to become the third leading cause of death in 2020. COPD is characterized by progressive airflow limitation, due to a combination of chronic inflammation and remodeling of the small airways (bronchiolitis) and loss of elastic recoil caused by destruction of the alveolar walls (emphysema). Lung cancer is the most important cause of cancer-related death in the world. (Cigarette) smoking is the principal culprit causing both COPD and lung cancer; in addition, exposure to environmental tobacco smoke, biomass fuel smoke, coal smoke and outdoor air pollution have also been associated with an increased incidence of both diseases. Importantly, smokers with COPD--defined as either not fully reversible airflow limitation or emphysema--have a two- to four-fold increased risk to develop lung cancer. In this review, we highlight several of the genetic, epigenetic and inflammatory mechanisms, which link COPD and carcinogenesis in the lungs. Elucidating the biological pathways and networks, which underlie the increased susceptibility of lung cancer in patients with COPD, has important implications for screening, prevention, diagnosis and treatment of these two devastating pulmonary diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

[The importance of lung volumes in the investigation of heavy smokers].

PubMed

Ben Saad, H; Ben Amor, L; Ben Mdalla, S; Ghannouchi, I; Ben Essghair, M; Sfaxi, R; Garrouche, A; Rouatbi, N; Rouatbi, S

2014-01-01

Lung hyperinflation (LH) has become a major concern in the management of chronic obstructive pulmonary disease (COPD). To evaluate the role of lung volumes in the positive diagnosis of COPD and in the assessment of airway obstruction reversibility. Three hundred and sixty-six male smokers over the age of 35 with more than 40 pack-years exposure were included in the study. Plethysmographic data were determined before/after taking a bronchodilator (BBD, ABD). Applied definitions: airflow obstruction: BBD FEV1/FVC<0.70. LH: BBD residual volume (RV)>upper limit of normal. Expressions of reversibility: Δvariable=(ABD-BBD) values; Δinit%=Δvariable/BBD value and Δref%=Δvariable/reference value. A 12%init and a 0.2L increase in either FEV1 or FVC or a 10%ref or - 300 mL decrease in RV were considered as clinically significant. Over the 85 smokers without airflow obstruction, 68% had LH. In the hyperinflated group (n=314), and compared to changes in FEV1 and FVC, these RV changes detected more respondents (54% for FEV1 and FVC vs. 65% for RV, P=0.002). This was not the case for the group free from LH (n=52) (23% for FEV1 and FVC vs. 35% for RV, P=0.09). In the 58 hyperinflated groups free from airflow obstruction, and compared to changes in FEV1 and FVC, changes in RV detected more respondents (24% for FEV1 and FVC vs. 71% for RV, P=0.0001). In heavy smokers, it seems essential to include LH as a criterion for a positive diagnosis of COPD and of reversibility evaluation. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Regulation of pulmonary inflammation by mesenchymal cells.

PubMed

Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael

2014-12-01

Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue remodelling, but also have an important role in pulmonary inflammation. This review will describe the immunomodulatory functions of pulmonary mesenchymal cells, such as airway smooth muscle (ASM) cells and lung fibroblasts, in chronic respiratory disease. An important theme of the review is that pulmonary mesenchymal cells not only respond to inflammatory mediators, but also produce their own mediators, whether pro-inflammatory or pro-resolving, which influence the quantity and quality of the lung immune response. The notion that defective pro-inflammatory or pro-resolving signalling in these cells potentially contributes to disease progression is also discussed. Finally, the concept of specifically targeting pulmonary mesenchymal cell immunomodulatory function to improve therapeutic control of chronic respiratory disease is considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria.

PubMed

Agrawal, Anurag; Mabalirajan, Ulaganathan

2016-01-15

Altered bioenergetics with increased mitochondrial reactive oxygen species production and degradation of epithelial function are key aspects of pathogenesis in asthma and chronic obstructive pulmonary disease (COPD). This motif is not unique to obstructive airway disease, reported in related airway diseases such as bronchopulmonary dysplasia and parenchymal diseases such as pulmonary fibrosis. Similarly, mitochondrial dysfunction in vascular endothelium or skeletal muscles contributes to the development of pulmonary hypertension and systemic manifestations of lung disease. In experimental models of COPD or asthma, the use of mitochondria-targeted antioxidants, such as MitoQ, has substantially improved mitochondrial health and restored respiratory function. Modulation of noncoding RNA or protein regulators of mitochondrial biogenesis, dynamics, or degradation has been found to be effective in models of fibrosis, emphysema, asthma, and pulmonary hypertension. Transfer of healthy mitochondria to epithelial cells has been associated with remarkable therapeutic efficacy in models of acute lung injury and asthma. Together, these form a 3R model--repair, reprogramming, and replacement--for mitochondria-targeted therapies in lung disease. This review highlights the key role of mitochondrial function in lung health and disease, with a focus on asthma and COPD, and provides an overview of mitochondria-targeted strategies for rejuvenating cellular respiration and optimizing respiratory function in lung diseases. Copyright © 2016 the American Physiological Society.

Prevalence of chronic obstructive pulmonary disease in asymptomatic smokers

PubMed Central

Sansores, Raúl H; Velázquez-Uncal, Mónica; Pérez-Bautista, Oliver; Villalba-Caloca, Jaime; Falfán-Valencia, Ramcés; Ramírez-Venegas, Alejandra

2015-01-01

Background Physicians do not routinely recommend smokers to undergo spirometry unless they are symptomatic. Objective To test the hypothesis that there are a significant number of asymptomatic smokers with chronic obstructive pulmonary disease (COPD), we estimated the prevalence of COPD in a group of asymptomatic smokers. Methods Two thousand nine hundred and sixty-one smokers with a cumulative consumption history of at least 10 pack-years, either smokers with symptoms or smokers without symptoms (WOS) were invited to perform a spirometry and complete a symptom questionnaire. Results Six hundred and thirty-seven (21.5%) smokers had no symptoms, whereas 2,324 (78.5%) had at least one symptom. The prevalence of COPD in subjects WOS was 1.5% when considering the whole group of smokers (45/2,961) and 7% when considering only the group WOS (45/637). From 329 smokers with COPD, 13.7% were WOS. Subjects WOS were younger, had better lung function and lower cumulative consumption of cigarettes, estimated as both cigarettes per day and pack-years. According to severity of airflow limitation, 69% vs 87% of subjects were classified as Global Initiative for Chronic Obstructive Lung Disease stages I–II in the WOS and smokers with symptoms groups, respectively (P<0.001). A multivariate analysis showed that forced expiratory volume in 1 second (mL) was the only predictive factor for COPD in asymptomatic smokers. Conclusion Prevalence of COPD in asymptomatic smokers is 1.5%. This number of asymptomatic smokers may be excluded from the benefit of an “early” intervention, not just pharmacological but also from smoking cessation counseling. The higher forced expiratory volume in 1 second may contribute to prevent early diagnosis. PMID:26586941

Prevalence of chronic obstructive pulmonary disease in asymptomatic smokers.

PubMed

Sansores, Raúl H; Velázquez-Uncal, Mónica; Pérez-Bautista, Oliver; Villalba-Caloca, Jaime; Falfán-Valencia, Ramcés; Ramírez-Venegas, Alejandra

2015-01-01

Physicians do not routinely recommend smokers to undergo spirometry unless they are symptomatic. To test the hypothesis that there are a significant number of asymptomatic smokers with chronic obstructive pulmonary disease (COPD), we estimated the prevalence of COPD in a group of asymptomatic smokers. Two thousand nine hundred and sixty-one smokers with a cumulative consumption history of at least 10 pack-years, either smokers with symptoms or smokers without symptoms (WOS) were invited to perform a spirometry and complete a symptom questionnaire. Six hundred and thirty-seven (21.5%) smokers had no symptoms, whereas 2,324 (78.5%) had at least one symptom. The prevalence of COPD in subjects WOS was 1.5% when considering the whole group of smokers (45/2,961) and 7% when considering only the group WOS (45/637). From 329 smokers with COPD, 13.7% were WOS. Subjects WOS were younger, had better lung function and lower cumulative consumption of cigarettes, estimated as both cigarettes per day and pack-years. According to severity of airflow limitation, 69% vs 87% of subjects were classified as Global Initiative for Chronic Obstructive Lung Disease stages I-II in the WOS and smokers with symptoms groups, respectively (P<0.001). A multivariate analysis showed that forced expiratory volume in 1 second (mL) was the only predictive factor for COPD in asymptomatic smokers. Prevalence of COPD in asymptomatic smokers is 1.5%. This number of asymptomatic smokers may be excluded from the benefit of an "early" intervention, not just pharmacological but also from smoking cessation counseling. The higher forced expiratory volume in 1 second may contribute to prevent early diagnosis.

[Epidemiological and socio-medical problems assoicated with respiratory disorders in Switzerland (author's transl)].

PubMed

Keller, R; Bohn, W

1978-09-01

Disorders of the respiratory tract account for about 13 percent of overall mortality in Switzerland, for about 50 percent of all hospital admissions and for about 7 percent of the nursing days. Cases of obstructive respiratory disease, pneumonia and carcinoma of the lung predominate. Morbidity regarding newly discovered cases of tuberculos is still 0.5 percent and 40 percent of the population are still positive reactors. BCG vaccination of newborns and of all tuberculin-negative schoolchildren is the approved prophylactic procedure. Periodic mass radiography of adults on a voluntary basis, aimed at the early diagnosis of pulmonary disorders, shows an incidence of 0.4/1 000 and of 0.3/1 000 for new cases of tuberculosis and lung cancer respectively. Cases of chronic obstructive respiratory disease who require hospitalization for above-average length and are frequently on sick leave present special sociomedical problems.

Lung volumes identify an at-risk group in persons with prolonged secondhand tobacco smoke exposure but without overt airflow obstruction.

PubMed

Arjomandi, Mehrdad; Zeng, Siyang; Geerts, Jeroen; Stiner, Rachel K; Bos, Bruce; van Koeverden, Ian; Keene, Jason; Elicker, Brett; Blanc, Paul D; Gold, Warren M

2018-01-01

Exposure to secondhand smoke (SHS) is associated with occult obstructive lung disease as evident by abnormal airflow indices representing small airway disease despite having preserved spirometry (normal forced expiratory volume in 1 s-to-forced vital capacity ratio, FEV 1 /FVC). The significance of lung volumes that reflect air trapping in the presence of preserved spirometry is unclear. To investigate whether lung volumes representing air trapping could determine susceptibility to respiratory morbidity in people with SHS exposure but without spirometric chronic obstructive pulmonary disease, we examined a cohort of 256 subjects with prolonged occupational SHS exposure and preserved spirometry. We elicited symptom prevalence by structured questionnaires, examined functional capacity (maximum oxygen uptake, VO 2max ) by exercise testing, and estimated associations of those outcomes with air trapping (plethysmography-measured residual volume-to-total lung capacity ratio, RV/TLC), and progressive air trapping with exertion (increase in fraction of tidal breathing that is flow limited on expiration during exercise (per cent of expiratory flow limitation, %EFL)). RV/TLC was within the predicted normal limits, but was highly variable spanning 22%±13% and 16%±8% across the increments of FEV 1 /FVC and FEV 1 , respectively. Respiratory complaints were prevalent (50.4%) with the most common symptom being ≥2 episodes of cough per year (44.5%). Higher RV/TLC was associated with higher OR of reporting respiratory symptoms (n=256; r 2 =0.03; p=0.011) and lower VO 2max (n=179; r 2 =0.47; p=0.013), and %EFL was negatively associated with VO 2max (n=32; r 2 =0.40; p=0.017). In those at risk for obstruction due to SHS exposure but with preserved spirometry, higher RV/TLC identifies a subgroup with increased respiratory symptoms and lower exercise capacity.

Identifying the heterogeneity of COPD by V/P SPECT: a new tool for improving the diagnosis of parenchymal defects and grading the severity of small airways disease.

PubMed

Bajc, M; Chen, Y; Wang, J; Li, X Y; Shen, W M; Wang, C Z; Huang, H; Lindqvist, A; He, X Y

2017-01-01

Airway obstruction and possible concomitant pulmonary diseases in COPD cannot be identified conventionally with any single diagnostic tool. We aimed to diagnose and grade COPD severity and identify pulmonary comorbidities associated with COPD with ventilation/perfusion single-photon emission computed tomography (V/P SPECT) using Technegas as the functional ventilation imaging agent. 94 COPD patients (aged 43-86 years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-IV) were examined with V/P SPECT and spirometry. Ventilation and perfusion defects were analyzed blindly according to the European guidelines. Penetration grade of Technegas in V SPECT measured the degree of obstructive small airways disease. Total preserved lung function and penetration grade of Technegas in V SPECT were assessed by V/P SPECT and compared to GOLD stages and spirometry. Signs of small airway obstruction in the ventilation SPECT images were found in 92 patients. Emphysema was identified in 81 patients. Two patients had no signs of COPD, but both of them had a pulmonary embolism, and in one of them we also suspected a lung tumor. The penetration grade of Technegas in V SPECT and total preserved lung function correlated significantly to GOLD stages ( r =0.63 and -0.60, respectively, P <0.0001). V/P SPECT identified pulmonary embolism in 30 patients (32%). A pattern typical for heart failure was present in 26 patients (28%). Parenchymal changes typical for pneumonia or lung tumor were present in several cases. V/P SPECT, using Technegas as the functional ventilation imaging agent, is a new tool to diagnose COPD and to grade its severity. Additionally, it revealed heterogeneity of COPD caused by pulmonary comorbidities. The characteristics of these comorbidities suggest their significant impact in clarifying symptoms, and also their influence on the prognosis.

Differences in medication adherence are associated with beliefs about medicines in asthma and COPD.

PubMed

Brandstetter, Susanne; Finger, Tamara; Fischer, Wiebke; Brandl, Magdalena; Böhmer, Merle; Pfeifer, Michael; Apfelbacher, Christian

2017-01-01

Adherence to medication is crucial for achieving treatment control in chronic obstructive lung diseases. This study refers to the "necessity-concerns framework" and examines the associations between beliefs about medicines and self-reported medication adherence in people with chronic obstructive lung disease. 402 patients (196 with asthma, 206 with COPD) participated in the study and completed a questionnaire comprising the "Beliefs about Medicines-Questionnaire" (BMQ) and the "Medication Adherence Report Scale" (MARS). Multivariable logistic regression analyses with the BMQ-subscales as explanatory and the dichotomized MARS-score as dependent variable were computed for the asthma and the COPD sample, respectively, and adjusted for potentially confounding variables. 19% of asthma patients and 34% of COPD patients were completely adherent to their prescribed medication. While specific beliefs about the necessity of medicines were positively associated with medication adherence both in patients with asthma and with COPD, general beliefs about harm and overuse of medicines by doctors were negatively associated with medication adherence only among patients with asthma. The findings of this study suggest that patients' specific beliefs about the necessity of medicines represent an important modifiable target for improving patient-doctor consultations when prescribing medicines.

Evidence of Biomass Smoke Exposure as a Causative Factor for the Development of COPD

PubMed Central

Capistrano, Sarah J.; van Reyk, David

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive disease of the lungs characterised by chronic inflammation, obstruction of airways, and destruction of the parenchyma (emphysema). These changes gradually impair lung function and prevent normal breathing. In 2002, COPD was the fifth leading cause of death, and is estimated by the World Health Organisation (WHO) to become the third by 2020. Cigarette smokers are thought to be the most at risk of developing COPD. However, recent studies have shown that people with life-long exposure to biomass smoke are also at high risk of developing COPD. Most common in developing countries, biomass fuels such as wood and coal are used for cooking and heating indoors on a daily basis. Women and children have the highest amounts of exposures and are therefore more likely to develop the disease. Despite epidemiological studies providing evidence of the causative relationship between biomass smoke and COPD, there are still limited mechanistic studies on how biomass smoke causes, and contributes to the progression of COPD. This review will focus upon why biomass fuels are used, and their relationship to COPD. It will also suggest methodological approaches to model biomass exposure in vitro and in vivo. PMID:29194400

Biomass smoke as a risk factor for chronic obstructive pulmonary disease: effects on innate immunity.

PubMed

Olloquequi, Jordi; Silva O, Rafael

2016-07-01

Chronic obstructive pulmonary disease (COPD), a major cause of mortality and morbidity worldwide, is considered an archetypical disease of innate immunity, where inhaled particles and gases trigger an inflammatory response, favoring tissue proliferation in small airways and tissue destruction in lung parenchyma, in addition to the recruitment of immune cells to these compartments. Although cigarette smoking is still considered the main risk factor for developing COPD, the trend of proposing biomass smoke (BS) exposure as a principal risk factor is gaining importance, as around 3 billion people worldwide are exposed to this pollutant daily. A considerable amount of evidence has shown the potential of BS as an enhancer of lung inflammation. However, an impairment of some innate immune responses after BS exposure has also been described. Regarding the mechanisms by which biomass smoke alters the innate immune responses, three main classes of cell surface receptors-the TLRs, the scavenger receptors and the transient receptor potential channels-have shown the ability to transduce signals initiated after BS exposure. This article is an updated and comprehensive review of the immunomodulatory effects described after the interaction of BS components with these receptors. © The Author(s) 2016.

[The Relationship of Serum Leptin Level and Metabolism in Elderly People with Stable Chronic Obstructive Pulmonary Disease].

PubMed

Yang, Lu; Zhang, Xue-mei; Hu, Xiu-ying; Zhang, Yan-ling

2016-01-01

To investigate the correlation of serum leptin and to energy consumption and metabolization in the patients with chronic obstructive pulmonary disease (COPD). We included 92 outpatients with stable COPD in West China Hospital of Sichuan University as trail group (COPD group) and 80 healthy elderly people in community as control group. All patients and healthy control received the measurements of body mass index (BMI), fat mass, resting energy expenditure (REE), lung function, serum leptin and tumor necrosis factor-α (TNF-α). The concentrations of serum leptin, BMI and lung function were lower in COPD group than those in control group (P < 0.01). The concentrations of serum leptin between two groups were not difference after the adjusted results of BMI and fat mass.. There was no difference of REE and TNF-α concentrations in these two groups. The serum leptin had positive correlation with BMI and fat mass, but there were no correlation between of TNF-α and serum leptin. In elderly people with stable COPD, the decline on the serum leptin is related to the decrease of BMI and fat mass, but barely related to the level of TNF-α.

Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients.

PubMed

Husain, Shahid; Kwak, Eun Jeong; Obman, Asia; Wagener, Marilyn M; Kusne, Shimon; Stout, Janet E; McCurry, Kenneth R; Singh, Nina

2004-05-01

The clinical utility of Platelia trade mark Aspergillus galactomannan antigen for the early diagnosis of invasive aspergillosis was prospectively assessed in 70 consecutive lung transplant recipients. Sera were collected twice weekly and tested for galactomannan. Invasive aspergillosis was documented in 17.1% (12/70) of the patients. Using the generalized estimating equation model, at the cutoff value of >or= 0.5, the sensitivity of the test was 30%, specificity 93% with positive and negative likelihood ratios of 4.2 and 0.75, respectively. Increasing the cutoff value to >or= 0.66 yielded a sensitivity of 30%, specificity of 95%, and positive and negative likelihood ratios of 5.5 and 0.74. A total of 14 patients had false-positive tests, including nine who had cystic fibrosis or chronic obstructive pulmonary disease. False-positive tests occurred within 3 days of transplantation in 43% (6/14) of the patients, and within 7 days in 64% (9/14). Thus, the test demonstrated excellent specificity, but a low sensitivity for the diagnosis of aspergillosis in this patient population. Patients with cystic fibrosis or chronic obstructive pulmonary disease may transiently have a positive test in the early post-transplant period.

Is exercise important in chronic obstructive pulmonary disease?

PubMed

Make, Barry; Casaburi, Richard

2007-09-01

Chronic obstructive pulmonary disease impairs the ability of patients to perform maximal physical exercise, particularly in patients with severe lung disease. However, differing perceptions of the meaning and importance of exercise to patients and caregivers is likely to impair patient-physician communication about current medical status and outcomes of therapeutic interventions. Other outcomes of importance to patients including actual performance of functional activity during daily life and health-related quality of life may also be affected by impaired exercise capacity. However, the relationships between exercise, activity, and quality of life are inconsistent. Thus, measurement of physiologic and patient-centered outcomes may provide the best approach to assessing responses to therapeutic interventions. These concepts were explored in a conference sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. and Pfizer Inc and reviewed in the articles generated from the symposium in this issue of COPD.

The use of health status questionnaires in the management of chronic obstructive pulmonary disease patients in clinical practice.

PubMed

van der Molen, Thys; Diamant, Zuzana; Kocks, Jan Willem H; Tsiligianni, Ioanna G

2014-08-01

Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone. Both questionnaires are designed to provide the clinician information enabling a more personalized disease approach and subsequent management. Although both Clinical COPD Questionnaire and COPD Assessment Test have good discriminate properties, their use as prognostic markers of severity and their ability to modify disease management has not yet been fully established. New studies are needed to further determine their value on several disease outcomes.

[Lung transplantation].

PubMed

Santillán-Doherty, Patricio; Jasso-Victoria, Rogelio; Olmos-Zúñiga, Raúl; Sotres-Vega, Avelina; Argote-Greene, Luis Marcelo; Escalante-Tattersfield, Tomás; Villalba-Caloca, Jaime

2005-01-01

Lung transplantation (LT) has evolved to become an important alternative in the management of patients with end-stage pulmonary disease and chronic respiratory failure. The beginnings of this technique can be traced back to the experiments of Carrel and Guthrie over a hundred years ago. However, it was not until 1963 when the first clinical experience was performed by Hardy. Clinical success did not arrive until the 1980's thanks to the works of the Toronto Lung Transplant Group. Well established criteria have been described in order to consider a patient as a potential candidate to receive a lung. Several diseases are capable of causing terminal lung damage and in general they can be classified according to their origin as obstructive (COPD, emphysema), restrictive (fibrosis), chronic infectious (cystic fibrosis, bronquiectasis), and vascular (primary pulmonary hypertension). The most frequent diagnosis is COPD. Clinically relevant modes of LT include the implant of one lung (single LT), or both lungs (bilateral sequential LT). Transplantation of the cardiopulmonary block is reserved for special situations and lobar transplantation is still considered experimental. Donor condition is essential to the success of LT. The potential donor patient frequently suffers deterioration in lung function due to edema formation or infection and both complications restrict lung's using for transplantation. Lung preservation is also limited to a short period of time which rarely exceeds 6 hours in spite of specially-designed preservative solutions such as the low potassium dextran. Outcome after LT shows current one-year survival between 65-70% with reduction to 40-45% after five years. Mortality within the first year is usually related to primary graft failure and infection. Long-term survival depends on controlling infectious problems due to immunosuppression as well as the development of bronchilitis obliterans as a manifestation of chronic rejection. LT is a therapeutic modality reserved for selected patients with chronic respiratory failure due to end-stage lung disease.

The measurement of lung volumes using body plethysmography and helium dilution methods in COPD patients: a correlation and diagnosis analysis.

PubMed

Tang, Yongjiang; Zhang, Mingke; Feng, Yulin; Liang, Binmiao

2016-11-23

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by persistent airflow limitation. Moreover, lung hyperinflation evaluated by lung volumes is also the key pathophysiologic process during COPD progression. Nevertheless, there is still no preferred method to evaluate lung volumes. For this study, we recruited 170 patients with stable COPD to assess lung volumes stratified by airflow limitation severity. Lung volumes including residual volume (RV) and total lung capacity (TLC) were determined by both body plethysmography and helium dilution methods. The discrepancies between these two methods were recorded as ΔRV%pred, ΔTLC%pred, and ΔRV/TLC. We found that ΔRV%pred, ΔTLC%pred, and ΔRV/TLC increased significantly with the severity of COPD. The differences of lung capacity between these two methods were negatively correlated with FEV 1 %pred, and diffusing capacity for carbon monoxide (D L CO%pred). Moreover, the receiver operating characteristic (ROC) for ΔTLC%pred to distinguish severe COPD from non-severe COPD had an area under curve (AUC) of 0.886. The differences of lung volume parameters measured by body plethysmography and helium dilution methods were associated with airflow limitation and can effectively differentiate COPD severity, which may be a supportive method to assess the lung function of stable COPD patients.

Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers.

PubMed

Castaldi, Peter J; San José Estépar, Raúl; Mendoza, Carlos S; Hersh, Craig P; Laird, Nan; Crapo, James D; Lynch, David A; Silverman, Edwin K; Washko, George R

2013-11-01

Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Compared with percentage of low-attenuation area less than -950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.

The relationship between perioperative administration of inhaled corticosteroid and postoperative respiratory complications after pulmonary resection for non-small-cell lung cancer in patients with chronic obstructive pulmonary disease.

PubMed

Yamanashi, Keiji; Marumo, Satoshi; Shoji, Tsuyoshi; Fukui, Takamasa; Sumitomo, Ryota; Otake, Yosuke; Sakuramoto, Minoru; Fukui, Motonari; Huang, Cheng-Long

2015-12-01

Inhaled corticosteroid (ICS) treatment has been shown to increase the risk of respiratory complications in patients with stable chronic obstructive pulmonary disease (COPD). However, the effects of perioperative ICS treatment on postoperative respiratory complications after lung cancer surgery have not been elucidated. The aim of this study was to investigate whether perioperative ICS treatment would increase the risk of postoperative respiratory complications after lung cancer surgery in patients with COPD. We retrospectively analyzed 174 consecutive COPD patients with non-small-cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between January 2007 and December 2014. Subjects were grouped based on whether or not they were administered perioperative ICS treatment. Postoperative cardiopulmonary complications were compared between the groups. There were no statistically significant differences in the incidence of postoperative respiratory complications (P = 0.573) between the perioperative ICS treatment group (n = 16) and the control group (n = 158). Perioperative ICS treatment was not significantly associated with postoperative respiratory complications in the univariate or multivariate analysis (odds ratio [OR] = 0.553, 95% confidence interval [CI] = 0.069-4.452, P = 0.578; OR = 0.635, 95% CI = 0.065-6.158, P = 0.695, respectively). Kaplan-Meier analysis showed that there were no statistically significant differences in the postoperative respiratory complications-free durations between the groups (P = 0.566), even after propensity score matching (P = 0.551). There was no relationship between perioperative ICS administration and the incidences of postoperative respiratory complications after surgical resection for NSCLC in COPD patients.

Efficacy of tiotropium/olodaterol on lung volume, exercise capacity, and physical activity

PubMed Central

Ichinose, Masakazu; Minakata, Yoshiaki; Motegi, Takashi; Ueki, Jun; Gon, Yasuhiro; Seki, Tetsuo; Anzai, Tatsuhiko; Nakamura, Shuhei; Hirata, Kazuto

2018-01-01

Purpose This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD. Patients and methods A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II–IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa. The primary endpoint was inspiratory capacity (IC) at peak post-dose. Results Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p<0.0001). Forced expiratory volume in 1 s (difference: 105 mL; 95% CI: 88, 123), forced vital capacity (difference: 163 mL; 95% CI: 130, 197), and slow vital capacity (difference: 134 mL; 95% CI: 91, 176) improved with tiotropium/olodaterol (all p<0.0001). Adjusted mean 6-min walk distance was similar between treatments in the overall population but was significantly increased with tiotropium/olodaterol in the subgroup with Global Initiative for Chronic Obstructive Lung Disease stage III/IV at baseline (difference: 18.1 m; 95% CI: 2.3, 33.9; p=0.0254). In a post hoc analysis, tiotropium/olodaterol improved the values for ≥2.0 metabolic equivalents (difference: 5.0 min; 95% CI: 0.4, 9.7; p=0.0337). Conclusion Tiotropium/olodaterol significantly improved IC compared with tiotropium and potentially enhanced the exercise capacity in COPD patients. A slight improvement in physical activity of relatively more than moderate intensity was also seen with tiotropium/olodaterol. PMID:29750027

16S rDNA-based metagenomic analysis of dental plaque and lung bacteria in patients with severe acute exacerbations of chronic obstructive pulmonary disease.

PubMed

Tan, L; Wang, H; Li, C; Pan, Y

2014-12-01

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are leading causes of mortality in hospital intensive care units. We sought to determine whether dental plaque biofilms might harbor pathogenic bacteria that can eventually cause lung infections in patients with severe AE-COPD. Paired samples of subgingival plaque biofilm and tracheal aspirate were collected from 53 patients with severe AE-COPD. Total bacterial DNA was extracted from each sample individually for polymerase chain reaction amplification and/or generation of bacterial 16S rDNA sequences and cDNA libraries. We used a metagenomic approach, based on bacterial 16S rDNA sequences, to compare the distribution of species present in dental plaque and lung. Analysis of 1060 sequences (20 clones per patient) revealed a wide range of aerobic, anaerobic, pathogenic, opportunistic, novel and uncultivable bacterial species. Species indistinguishable between the paired subgingival plaque and tracheal aspirate samples (97-100% similarity in 16S rDNA sequence) were dental plaque pathogens (Aggregatibacter actinomycetemcomitans, Capnocytophaga sputigena, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and lung pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Streptococcus pneumoniae). Real-time polymerase chain reaction of 16S rDNA indicated lower levels of Pseudomonas aeruginosa and Porphyromonas gingivalis colonizing the dental plaques compared with the paired tracheal aspirate samples. These results support the hypothesis that dental bacteria may contribute to the pathology of severe AE-COPD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence and underdiagnosis of airway obstruction among middle-aged adults in northern France: The ELISABET study 2011-2013.

PubMed

Quach, Alexandre; Giovannelli, Jonathan; Chérot-Kornobis, Natalie; Ciuchete, Alina; Clément, Guillaume; Matran, Régis; Amouyel, Philippe; Edmé, Jean-Louis; Dauchet, Luc

2015-12-01

Airway obstruction (AO), mainly due to chronic obstructive pulmonary disease (COPD) in adults, is a major cause of mortality and poor quality of life. However, few data are available for France. This study was designed to calculate the prevalence AO among middle-aged adults in northern France, explore the associated risk factors and evaluate the underdiagnosis. The Enquête Littoral Souffle Air Biologie Environnement (ELISABET) was a cross-sectional study of a representative sample of 3276 adults aged from 40 to 64 in two urban areas in northern France (Lille and Dunkirk). Participants filled out a questionnaire and performed spirometry testing, without a reversibility test. The age-standardized estimated prevalence [95% confidence interval] of AO was 16.0% [13.9; 17.9] in Lille and 13.7% [11.7; 15.7] in Dunkirk with the Global initiative for chronic Obstructive Lung Disease (GOLD) definition and 10.8% [9.2; 12.5] and 9.5% [7.9; 11.2] respectively with the lower limit of normal calculated with the Global Lung Initiative (GLI) 2012 equations. AO was associated with age, male gender, tobacco consumption and low body mass index. The underdiagnosis rate was greater than 70%. Previously undiagnosed participants with AO displayed more respiratory symptoms compared with participants without AO and less than participants with previously diagnosed AO. The prevalence of AO in northern France ranged from 9.5 to 16.0%, depending on the centre and definition used. The high underdiagnosis rate observed here suggests that greater efforts should be made to identify individuals presenting with the symptoms and/or risk factors associated with AO. Copyright © 2015 Elsevier Ltd. All rights reserved.

Artificial intelligence in diagnosis of obstructive lung disease: current status and future potential.

PubMed

Das, Nilakash; Topalovic, Marko; Janssens, Wim

2018-03-01

The application of artificial intelligence in the diagnosis of obstructive lung diseases is an exciting phenomenon. Artificial intelligence algorithms work by finding patterns in data obtained from diagnostic tests, which can be used to predict clinical outcomes or to detect obstructive phenotypes. The purpose of this review is to describe the latest trends and to discuss the future potential of artificial intelligence in the diagnosis of obstructive lung diseases. Machine learning has been successfully used in automated interpretation of pulmonary function tests for differential diagnosis of obstructive lung diseases. Deep learning models such as convolutional neural network are state-of-the art for obstructive pattern recognition in computed tomography. Machine learning has also been applied in other diagnostic approaches such as forced oscillation test, breath analysis, lung sound analysis and telemedicine with promising results in small-scale studies. Overall, the application of artificial intelligence has produced encouraging results in the diagnosis of obstructive lung diseases. However, large-scale studies are still required to validate current findings and to boost its adoption by the medical community.

MTOR Suppresses Cigarette Smoke-Induced Epithelial Cell Death and Airway Inflammation in Chronic Obstructive Pulmonary Disease.

PubMed

Wang, Yong; Liu, Juan; Zhou, Jie-Sen; Huang, Hua-Qiong; Li, Zhou-Yang; Xu, Xu-Chen; Lai, Tian-Wen; Hu, Yue; Zhou, Hong-Bin; Chen, Hai-Pin; Ying, Song-Min; Li, Wen; Shen, Hua-Hao; Chen, Zhi-Hua

2018-04-15

Airway epithelial cell death and inflammation are pathological features of chronic obstructive pulmonary disease (COPD). Mechanistic target of rapamycin (MTOR) is involved in inflammation and multiple cellular processes, e.g., autophagy and apoptosis, but little is known about its function in COPD pathogenesis. In this article, we illustrate how MTOR regulates cigarette smoke (CS)-induced cell death, airway inflammation, and emphysema. Expression of MTOR was significantly decreased and its suppressive signaling protein, tuberous sclerosis 2 (TSC2), was increased in the airway epithelium of human COPD and in mouse lungs with chronic CS exposure. In human bronchial epithelial cells, CS extract (CSE) activated TSC2, inhibited MTOR, and induced autophagy. The TSC2-MTOR axis orchestrated CSE-induced autophagy, apoptosis, and necroptosis in human bronchial epithelial cells; all of which cooperatively regulated CSE-induced inflammatory cytokines IL-6 and IL-8 through the NF-κB pathway. Mice with a specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly augmented airway inflammation and airspace enlargement in response to CS exposure, accompanied with enhanced levels of autophagy, apoptosis, and necroptosis in the lungs. Taken together, these data demonstrate that MTOR suppresses CS-induced inflammation and emphysema-likely through modulation of autophagy, apoptosis, and necroptosis-and thus suggest that activation of MTOR may represent a novel therapeutic strategy for COPD. Copyright © 2018 by The American Association of Immunologists, Inc.

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

PubMed

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

2015-11-01

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

Enteral nutrition in the chronic obstructive pulmonary disease (COPD) patient.

PubMed

DeBellis, Heather F; Fetterman, James W

2012-12-01

Chronic obstructive pulmonary disease (COPD) is a progressive, chronic disease, in which malnutrition can have an undesirable effect. Therefore, the patient's nutritional status is critical for optimizing outcomes in COPD. The initial nutrition assessment is focused on identifying calorically compromised COPD patients in order to provide them with appropriate nutrition. Nutritional intervention consists of oral supplementation and enteral nutrition to prevent weight loss and muscle mass depletion. Evaluation of nutritional status should include past medical history (medications, lung function, and exercise tolerance) and dietary history (patient's dietary habits, food choices, meal patterns, food allergy information, and malabsorption issues), in addition to physiological stress, visceral proteins, weight, fat-free mass, and body mass index. The current medical literature conflicts regarding the appropriate type of formulation to select for nutritional intervention, especially regarding the amount of calories from fat to provide COPD patients. This review article focuses on the enteral product formulations currently available, and how they are most appropriately utilized in patients with COPD.

[The effects of air pollution and climate change on pulmonary diseases].

PubMed

Rohde, G

2008-04-01

From as early as 1930 there has been evidence for effects on health of air pollution. Ozone, particulates and nitrogen dioxide are the most important pollutants today. The acute increase in air pollution leads to a significant raise in morbidity and mortality. Hospital admissions of patients with chronic obstructive pulmonary disease (COPD) or asthma are more frequent during these periods. Chronic exposure to pollution causes bronchitis, accelerated decline of lung function and impaired maturing of the lungs. Ozone and a residence in proximity to major roads seem to play a role in the development of asthma. A further important environmental factor is climate change, which has an impact on air pollution but also on distribution and quality of aero-allergens and the dissemination and transmission of respiratory pathogens.

When obesity and chronic obstructive pulmonary disease collide. Physiological and clinical consequences.

PubMed

O'Donnell, Denis E; Ciavaglia, Casey E; Neder, J Alberto

2014-05-01

In many parts of the world, the prevalence of both chronic obstructive pulmonary disease (COPD) and obesity is increasing at an alarming rate. Such patients tend to have greater respiratory symptoms, more severe restriction of daily activities, poorer health-related quality of life, and greater health care use than their nonobese counterparts. Physiologically, increasing weight gain is associated with lung volume reduction effects in both health and disease, and this should be considered when interpreting common pulmonary function tests where lung volume is the denominator, such as FEV1/FVC and the ratio of diffusing capacity of carbon monoxide to alveolar volume, or indeed when evaluating the physiological consequences of emphysema in obese individuals. Contrary to expectation, the presence of mild to moderate obesity in COPD appears to have little deleterious effect on respiratory mechanics and muscle function, exertional dyspnea, and peak symptom-limited oxygen uptake during cardiopulmonary exercise testing. Thus, in evaluating obese patients with COPD reporting activity restriction, additional nonpulmonary factors, such as increased metabolic loading, cardiocirculatory impairment, and musculoskeletal abnormalities, should be considered. Care should be taken to recognize the presence of obstructive sleep apnea in obese patients with COPD, as effective treatment of the former condition likely conveys an important survival advantage. Finally, morbid obesity in COPD presents significant challenges to effective management, given the combined effects of erosion of the ventilatory reserve and serious metabolic and cardiovascular comorbidities that collectively predispose to an increased risk of death from respiratory failure.

Computerized tomographic quantification of chronic obstructive pulmonary disease as the principal determinant of frontal P vector.

PubMed

Chhabra, Lovely; Sareen, Pooja; Gandagule, Amit; Spodick, David

2012-04-01

Verticalization of the P-wave axis is characteristic of chronic obstructive pulmonary disease (COPD). We studied the correlation of P-wave axis and computerized tomographically quantified emphysema in patients with COPD/emphysema. Individual correlation of P-wave axis with different structural types of emphysema was also studied. High-resolution computerized tomographic scans of 23 patients >45 years old with known COPD were reviewed to assess the type and extent of emphysema using computerized tomographic densitometric parameters. Electrocardiograms were then independently reviewed and the P-wave axis was calculated in customary fashion. Degree of the P vector (DOPV) and radiographic percent emphysematous area (RPEA) were compared for statistical correlation. The P vector and RPEA were also directly compared to the forced expiratory volume at 1 second. RPEA and the P vector had a significant positive correlation in all patients (r = +0.77, p <0.0001) but correlation was very strong in patients with predominant lower lobe emphysema (r = +0.89, p <0.001). Forced expiratory volume at 1 second and the P vector had almost a linear inverse correlation in predominantly lower lobe emphysema (r = -0.92, p <0.001). DOPV positively correlated with radiographically quantified emphysema. DOPV and RPEA were strong predictors of qualitative lung function in patients with predominantly lower lobe emphysema. In conclusion, a combination of high DOPV and predominantly lower lobe emphysema indicates severe obstructive lung dysfunction in patients with COPD. Copyright © 2012 Elsevier Inc. All rights reserved.

Diaphragmatic mobility: relationship with lung function, respiratory muscle strength, dyspnea, and physical activity in daily life in patients with COPD.

PubMed

Rocha, Flávia Roberta; Brüggemann, Ana Karla Vieira; Francisco, Davi de Souza; Medeiros, Caroline Semprebom de; Rosal, Danielle; Paulin, Elaine

2017-01-01

To evaluate diaphragmatic mobility in relation to lung function, respiratory muscle strength, dyspnea, and physical activity in daily life (PADL) in patients with COPD. We included 25 patients with COPD, classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria, and 25 healthy individuals. For all of the participants, the following were evaluated: anthropometric variables, spirometric parameters, respiratory muscle strength, diaphragmatic mobility (by X-ray), PADL, and the perception of dyspnea. In the COPD group, diaphragmatic mobility was found to correlate with lung function variables, inspiratory muscle strength, and the perception of dyspnea, whereas it did not correlate with expiratory muscle strength or PADL. In patients with COPD, diaphragmatic mobility seems to be associated with airway obstruction and lung hyperinflation, as well as with ventilatory capacity and the perception of dyspnea, although not with PADL. Avaliar a relação da mobilidade diafragmática com a função pulmonar, força muscular respiratória, dispneia e atividade física de vida diária (AFVD) em pacientes com DPOC. Foram avaliados 25 pacientes com diagnóstico de DPOC, classificados de acordo com critérios da Global Initiative for Chronic Obstructive Lung Disease, e 25 indivíduos saudáveis. Todos foram submetidos às seguintes avaliações: mensuração antropométrica, espirometria, força muscular respiratória, mobilidade diafragmática (por radiografia), AFVD e percepção de dispneia. No grupo DPOC, houve correlações da mobilidade diafragmática com variáveis de função pulmonar, força muscular inspiratória e percepção de dispneia. Não houve correlações da mobilidade diafragmática com força muscular expiratória e AFVD. A mobilidade diafragmática parece estar associada tanto com a obstrução das vias aéreas quanto com a hiperinsuflação pulmonar em pacientes com DPOC, assim como com a capacidade ventilatória e percepção de dispneia, mas não com AFVD.

Clinical, radiological, and physiological differences between obliterative bronchiolitis and problematic severe asthma in adolescents and young adults: the early origins of the overlap syndrome?

PubMed

Bandeira, Teresa; Negreiro, Filipa; Ferreira, Rosário; Salgueiro, Marisa; Lobo, Luísa; Aguiar, Pedro; Trindade, J C

2011-06-01

Few reports have compared chronic obstructive lung diseases (OLDs) starting in childhood. To describe functional, radiological, and biological features of obliterative bronchiolitis (OB) and further discriminate to problematic severe asthma (PSA) or to diagnose a group with overlapping features. Patients with OB showed a greater degree of obstructive lung defect and higher hyperinflation (P < 0.001). The most frequent high-resolution computed tomography (HRCT) features (increased lung volume, inspiratory decreased attenuation, mosaic pattern, and expiratory air trapping) showed significantly greater scores in OB patients. Patients with PSA have shown a higher frequency of atopy (P < 0.05). ROC curve analysis demonstrated discriminative power for the LF variables, HRCT findings and for atopy between diagnoses. Further analysis released five final variables more accurate for the identification of a third diagnostic group (FVC%t, post-bronchodilator ΔFEV(1) in ml, HRCT mosaic pattern, SPT, and D. pteronyssinus-specific IgE). We found that OB and PSA possess identifiable characteristic features but overlapping values may turn them undistinguishable. Copyright © 2011 Wiley-Liss, Inc.

Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach.

PubMed

Kelsen, Steven G; Duan, Xunbao; Ji, Rong; Perez, Oscar; Liu, Chunli; Merali, Salim

2008-05-01

Cigarette smoking, which exposes the lung to high concentrations of reactive oxidant species (ROS) is the major risk factor for chronic obstructive pulmonary disease (COPD). Recent studies indicate that ROS interfere with protein folding in the endoplasmic reticulum and elicit a compensatory response termed the "unfolded protein response" (UPR). The importance of the UPR lies in its ability to alter expression of a variety of genes involved in antioxidant defense, inflammation, energy metabolism, protein synthesis, apoptosis, and cell cycle regulation. The present study used comparative proteomic technology to test the hypothesis that chronic cigarette smoking induces a UPR in the human lung. Studies were performed on lung tissue samples obtained from three groups of human subjects: nonsmokers, chronic cigarette smokers, and ex-smokers. Proteomes of lung samples from chronic cigarette smokers demonstrated 26 differentially expressed proteins (20 were up-regulated, 5 were down-regulated, and 1 was detected only in the smoking group) compared with nonsmokers. Several UPR proteins were up-regulated in smokers compared with nonsmokers and ex-smokers, including the chaperones, glucose-regulated protein 78 (GRP78) and calreticulin; a foldase, protein disulfide isomerase (PDI); and enzymes involved in antioxidant defense. In cultured human airway epithelial cells, GRP78 and the UPR-regulated basic leucine zipper, transcription factors, ATF4 and Nrf2, which enhance expression of important anti-oxidant genes, increased rapidly (< 24 h) with cigarette smoke extract. These data indicate that cigarette smoke induces a UPR response in the human lung that is rapid in onset, concentration dependent, and at least partially reversible with smoking cessation. We speculate that activation of a UPR by cigarette smoke may protect the lung from oxidant injury and the development of COPD.

Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series.

PubMed

O'Brien, Catherine E; Anderson, Paula J; Stowe, Cindy D

2010-03-01

To describe the use of lubiprostone for constipation in 3 adults with cystic fibrosis (CF). This case series describes the use of lubiprostone for the treatment of constipation in 3 adults with CF (mean +/- SD length of therapy 17.3 +/- 1.5 mo). All 3 patients were prescribed lubiprostone 24 microg twice daily after hospitalization for treatment of intestinal obstruction. Patient 1 continues on chronic polyethylene glycol (PEG) 3350 and lubiprostone and has not had a recurrence of obstruction. Patient 2 requires aggressive chronic therapy with PEG 3350, lubiprostone, and methylnaltrexone. She has had 1 recurrence of obstruction. Patient 3 continues with lubiprostone taken several times per week with good control of constipation and no recurrence of obstruction to date. The adverse effect profile has been tolerable in all 3 patients. CF is caused by a genetic mutation resulting in a dysfunctional or absent CF transmembrane conductance regulator that normally functions as a chloride channel. This results in viscous secretions in multiple organ systems including the lungs and intestinal tract. Accumulation of viscous intestinal contents contributes to constipation, which is common among adults with CF and can sometimes lead to intestinal obstruction. Lubiprostone is indicated for chronic constipation and works by activating type 2 chloride channels (ClC-2) in the intestinal tract. Because it utilizes an alternate chloride channel, lubiprostone may be especially effective for constipation in patients with CF. Lubiprostone provides an additional option for the treatment of constipation in adults with CF. Its use in the CF population deserves further study.

[Chronic hypoxia and cardiovascular risk : Clinical significance of different forms of hypoxia].

PubMed

Koehler, U; Hildebrandt, O; Krönig, J; Grimm, W; Otto, J; Hildebrandt, W; Kinscherf, R

2018-06-01

It is of fundamental importance to differentiate whether chronic hypoxia occurs intermittently or persistently. While chronic intermittent hypoxia (CIH) is found typically in patients with obstructive sleep apnea (OAS), chronic persistent hypoxia (CPH) is typically diagnosed in patients with chronic lung disease. Cardiovascular risk is markedly increased in patients with CIH compared to patients with CPH. The frequent change between oxygen desaturation and reoxygenation in patients with CIH is associated with increased hypoxic stress, increased systemic inflammation, and enhanced adrenergic activation followed by endothelial dysfunction and increased arteriosclerosis. The pathophysiologic consequences of CPH are less well understood. The relationship between CPH and the development of pulmonary hypertension, pulmonary heart disease as well as polycythemia has been established.

A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study.

PubMed

Sonoda, Nao; Morimoto, Akiko; Tatsumi, Yukako; Asayama, Kei; Ohkubo, Takayoshi; Izawa, Satoshi; Ohno, Yuko

2018-05-01

To assess the impact of diabetes on restrictive and obstructive lung function impairment. This 5-year prospective study included 7524 participants aged 40-69years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥7.0mmol/l (126mg/dl), HbA1c≥6.5% (48mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) <80% predicted and forced expiratory volume in 1s (FEV 1 ) to FVC ratio (FEV 1 /FVC) <0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014. During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04-2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72-1.21)]. Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment. Copyright © 2017. Published by Elsevier Inc.

Lung and Heart Sounds Analysis: State-of-the-Art and Future Trends.

PubMed

Padilla-Ortiz, Ana L; Ibarra, David

2018-01-01

Lung sounds, which include all sounds that are produced during the mechanism of respiration, may be classified into normal breath sounds and adventitious sounds. Normal breath sounds occur when no respiratory problems exist, whereas adventitious lung sounds (wheeze, rhonchi, crackle, etc.) are usually associated with certain pulmonary pathologies. Heart and lung sounds that are heard using a stethoscope are the result of mechanical interactions that indicate operation of cardiac and respiratory systems, respectively. In this article, we review the research conducted during the last six years on lung and heart sounds, instrumentation and data sources (sensors and databases), technological advances, and perspectives in processing and data analysis. Our review suggests that chronic obstructive pulmonary disease (COPD) and asthma are the most common respiratory diseases reported on in the literature; related diseases that are less analyzed include chronic bronchitis, idiopathic pulmonary fibrosis, congestive heart failure, and parenchymal pathology. Some new findings regarding the methodologies associated with advances in the electronic stethoscope have been presented for the auscultatory heart sound signaling process, including analysis and clarification of resulting sounds to create a diagnosis based on a quantifiable medical assessment. The availability of automatic interpretation of high precision of heart and lung sounds opens interesting possibilities for cardiovascular diagnosis as well as potential for intelligent diagnosis of heart and lung diseases.

Diagnosis and management of chronic lung disease in deployed military personnel.

PubMed

Morris, Michael J; Lucero, Pedro F; Zanders, Thomas B; Zacher, Lisa L

2013-08-01

Military personnel are a unique group of individuals referred to the pulmonary physician for evaluation. Despite accession standards that limit entrance into the military for individuals with various pre-existing lung diseases, the most common disorders found in the general population such as asthma and chronic obstructive pulmonary disease remain frequently diagnosed. Military personnel generally tend to be a more physically fit population who are required to exercise on a regular basis and as such may have earlier presentations of disease than their civilian counterparts. Exertional dyspnea is a common complaint; establishing a diagnosis may be challenging given the subtle nature of symptoms and lack of specificity with pulmonary function testing. The conflicts over the past 10 years in Iraq and Afghanistan have also given rise to new challenges for deployed military. Various respiratory hazards in the deployed environment include suspended geologic dusts, burn pits, vehicle exhaust emissions, industrial air pollution, and isolated exposure incidents and may give rise to both acute respiratory symptoms and chronic lung disease. In the evaluation of deployed military personnel, establishing the presence of actual pulmonary disease and the relationship of existing disease to deployment is an ongoing issue to both military and civilian physicians. This paper reviews the current evidence for chronic lung disease in the deployed military population and addresses any differences in diagnosis and management.

Protective effects of grape seed and skin extract against high-fat-diet-induced lipotoxicity in rat lung.

PubMed

El Ayed, Mohamed; Kadri, Safwen; Smine, Selima; Elkahoui, Salem; Limam, Ferid; Aouani, Ezzedine

2017-09-13

Obesity is a public health problem characterized by increased fat accumulation in different tissues. Obesity is directly linked to breathing problems and medical complications with lung, including obstructive sleep apnea syndrome, obesity hypoventilation syndrome, chronic obstructive pulmonary disease, asthma….In the present work, we aimed to investigate the effect of high fat diet (HFD) on lung lipotoxicity, oxidative stress, fatty acid composition and proportions in lung and implication in asthma development. The likely protection provided by grape seed extract (GSSE) was also investigated. In order to assess HFD effect on lung and GSSE protection we used a rat model. We analyzed the lipid plasma profile, lung peroxidation and antioxidant activities (SOD, CAT and POD). We also analyzed transition metals (Ca2+, Mg2+, Zn2+ and iron) and lung free fatty acids using gas chromatography coupled to mass spectrometry (GC-MS). HFD induced lipid profile imbalance increasing cholesterol and VLDL-C. HFD also induced an oxidative stress assessed by elevated MDA level and the drop of antioxidant activities such as SOD, CAT and POD. Moreover, HFD induced mineral disturbances by decreasing magnesium level and increasing Calcium and iron levels. HFD induced also disturbances in lung fatty acid composition by increasing oleic, stearic and arachidonic acids. Interestingly, GSSE alleviated all these deleterious effects of HFD treatment. As a whole, GSSE had a significant preventive effect against HFD-induced obesity, and hence may be used as an anti-obesity agent, and a benefic agent with potential applications against damages in lung tissue.

[Influence of smoking and industrial air pollutants on respiratory health of nickel industry workers].

PubMed

Shilov, V V; Siurin, S A

2015-01-01

Studies covered respiratory health of 1530 workers of nickel industry, among which were 796 (52.0%) smokers. Findings are that tobacco smoke combined with nickel industry hazards cause potentized negative effects in respiratory organs, with earlier and more frequent chronic bronchitis. For isolated influence of these factors, chronic bronchitis risk is higher from exposure to tobacco smoke vs. occupational hazards (OR = 2.48; DI 1.49-4.13). Chronic obstructive lung disease development in nickel industry workers is caused by smoking. Industrial air pollutants appeared to have no potentizing effect on COLD formation, as well as on toxic pneumosclerosis formation.

Development of a simple binary response questionnaire to identify airflow obstruction in a smoking population in Argentina.

PubMed

Bergna, Miguel A; García, Gabriel R; Alchapar, Ramon; Altieri, Hector; Casas, Juan C Figueroa; Larrateguy, Luis; Nannini, Luis J; Pascansky, Daniel; Grabre, Pedro; Zabert, Gustavo; Miravitlles, Marc

2015-06-01

The CODE questionnaire (COPD detection questionnaire), a simple, binary response scale (yes/no), screening questionnaire, was developed for the identification of patients with chronic obstructive pulmonary disease (COPD). We conducted a survey of 468 subjects with a smoking history in 10 public hospitals in Argentina. Patients with a previous diagnosis of COPD, asthma and other respiratory illness were excluded. Items that measured conceptual domains in terms of characteristics of symptoms, smoking history and demographics data were considered. 96 (20.5%) subjects had a diagnosis of COPD according to the 2010 Global Initiative for Chronic Obstructive Lung Disease strategy document. The variables selected for the final questionnaire were based on univariate and multivariate analyses and clinical criteria. Finally, we selected the presence or absence of six variables (age ≥50 years, smoking history ≥30 pack-years, male sex, chronic cough, chronic phlegm and dyspnoea). Of patients without any of these six variables (0 points), none had COPD. The ability of the CODE questionnaire to discriminate between subjects with and without COPD was good (the area under the receiver operating characteristic curve was 0.75). Higher scores were associated with a greater probability of COPD. The CODE questionnaire is a brief, accurate questionnaire that can identify smoking individuals likely to have COPD. Copyright ©ERS 2015.

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

PubMed

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

2016-07-15

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

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

PubMed

Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; de Oliveira, Ana Paula Ligeiro

2015-01-01

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke–Induced COPD in C57BL/6 mice

PubMed Central

Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; Ligeiro de Oliveira, Ana Paula

2015-01-01

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J—660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

IREB2, CHRNA5, CHRNA3, FAM13A & hedgehog interacting protein genes polymorphisms & risk of chronic obstructive pulmonary disease in Tatar population from Russia.

PubMed

Korytina, Gulnaz Faritovna; Akhmadishina, Leysan Zinurovna; Viktorova, Elena Vitalievna; Kochetova, Olga Vladimirovna; Viktorova, Tatyana Victorovna

2016-12-01

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system affecting primarily distal respiratory pathways and lung parenchyma. This study was aimed at investigating the association of COPD with IREB2, CHRNA5, CHRNA3, FAM13A and hedgehog interacting protein (HHIP) genes in a Tatar population from Russia. Six single nucleotide polymorphisms (SNPs) (rs13180, rs16969968, rs1051730, rs6495309, rs7671167, rs13118928) were genotyped by the real-time polymerase chain reaction in this study (511 COPD patients and 508 controls). Logistic regression was used to detect the association of SNPs and haplotypes of linked loci in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and pack-years. The rs13180 (IREB2), rs16969968 (CHRNA5) and rs1051730 (CHRNA3) were significantly associated with COPD in additive model [Padj =0.00001, odds ratio (OR)=0.64; Padj =0.0001, OR=1.41 and Padj =0.0001, OR=1.47]. The C-G haplotype by rs13180 and rs1051730 was a protective factor for COPD in our population (Padj =0.0005, OR=0.61). These results were confirmed only in smokers. The rs16969968 and rs1051730 were associated with decrease of forced expiratory volume in 1 sec % predicted (Padj =0.005 and Padj =0.0019). Our study showed the association of rs13180, rs16969968 and rs1051730 with COPD and lung function in Tatar population from Russia. Further studies need to be done in other ethnic populations.

Wine, spirits and the lung: good, bad or indifferent?

PubMed

Kamholz, Stephan L

2006-01-01

The putative cardiovascular risks and benefits of the ingestion of wine and alcohol-containing spirits have been well publicized; however, less attention has been focused upon the health effects of wine and spirits consumption on the respiratory system. This paper will highlight epidemiologic, clinical and experimental data on the effects of wine and distilled spirits [and the chemical components thereof] on lung function, chronic obstructive pulmonary disease progression, lung cancer risk, risk of developing acute respiratory distress syndrome, high altitude pulmonary edema and wine [sulfite] associated asthma. Several studies have demonstrated a positive [beneficial] effect of light-to-moderate wine consumption on pulmonary function, while chronic ingestion of distilled spirits may have either no effect, or a negative effect. Studies in Scandinavia, Europe and South America have suggested a possible protective effect of wine ingestion against lung cancer, especially adenocarcinoma. Resveratrol [3,5,4'-trihydroxystilbene] a polyphenolic compound found in red wine, has anti-oxidant, anti-inflammatory and estrogen agonist effects and may be responsible for some of the health benefits of wine. The spectrum of potentially beneficial clinical effects of resveratrol and other wine-derived compounds is discussed.

Persistent Pneumocystis colonization leads to the development of chronic obstructive pulmonary disease (COPD) in a non-human primate model of AIDS

PubMed Central

Shipley, Timothy W.; Kling, Heather M.; Morris, Alison; Patil, Sangita; Kristoff, Jan; Guyach, Siobhan E.; Murphy, Jessica M.; Shao, Xiuping; Sciurba, Frank C.; Rogers, Robert M.; Richards, Thomas; Thompson, Paul; Montelaro, Ronald C.; Coxson, Harvey O.; Hogg, James C.; Norris, Karen A.

2010-01-01

HIV-infected patients are at increased risk for development of pulmonary complications, including chronic obstructive pulmonary disease (COPD). Inflammation associated with sub-clinical infection has been postulated to promote COPD. Persistence of Pneumocystis (Pc) is associated with HIV and COPD, although a causal relationship has not been established. We used a simian/human immunodeficiency virus (SHIV) model of HIV infection to study pulmonary effects of Pc colonization. SHIV-infected/Pc-colonized monkeys developed progressive obstructive pulmonary disease characterized by increased emphysematous tissue and bronchial-associated lymphoid tissue. Elevated Th2 cytokines and pro-inflammatory mediators in bronchoalveolar lavage fluid coincided with Pc colonization and pulmonary function decline. These results support the concept that an infectious agent contributes to development of HIV-associated lung disease and suggests that Pc colonization may be a risk factor for the development of HIV-associated COPD. Furthermore, this model allows examination of early host responses important to disease progression thus identifying potential therapeutic targets for COPD. PMID:20533880

Clinical and Radiographic Predictors of GOLD–Unclassified Smokers in the COPDGene Study

PubMed Central

Hokanson, John E.; Murphy, James R.; Regan, Elizabeth A.; Make, Barry J.; Lynch, David A.; Crapo, James D.; Silverman, Edwin K.

2011-01-01

Rationale: A significant proportion of smokers have lung function impairment characterized by a reduced FEV1 with a preserved FEV1/FVC ratio. These smokers are a poorly characterized group due to their systematic exclusion from chronic obstructive pulmonary disease (COPD) studies. Objectives: To characterize the clinical, functional, and radiographic features of Global Initiative for Chronic Obstructive Lung Disease (GOLD)-Unclassified (FEV1/FVC ≥ 0.7 and FEV1 < 80% predicted) and lower limits of normal (LLN)-unclassified (FEV1/FVC ≥ LLN and FEV1 < LLN) subjects compared to smokers with normal lung function and subjects with COPD. Methods: Data from the first 2,500 subjects enrolled in the COPDGene study were analyzed. All subjects had 10 or more pack-years of smoking and were between the ages of 45 and 80 years. Multivariate regression models were constructed to determine the clinical and radiological variables associated with GOLD-Unclassified (GOLD-U) and LLN-Unclassified status. Separate multivariate regressions were performed in the subgroups of subjects with complete radiologic measurement variables available. Measurements and Main Results: GOLD-U smokers account for 9% of smokers in COPDGene and have increased body mass index (BMI), a disproportionately reduced total lung capacity, and a higher proportion of nonwhite subjects and subjects with diabetes. GOLD-U subjects exhibit increased airway wall thickness compared to smoking control subjects and decreased gas trapping and bronchodilator responsiveness compared to subjects with COPD. When LLN criteria were used to define the “unclassified” group, African American subjects were no longer overrepresented. Both GOLD-U and LLN-Unclassified subjects demonstrated a wide range of lung function impairment, BMI, and percentage of total lung emphysema. Conclusions: Subjects with reduced FEV1 and a preserved FEV1/FVC ratio are a heterogeneous group with significant symptoms and functional limitation who likely have a variety of underlying etiologies beyond increased BMI. Clinical trial registered with www.clinicaltrials.gov (NCT000608764). PMID:21493737

Risk factors for pulmonary arterial hypertension in patients with tuberculosis-destroyed lungs and their clinical characteristics compared with patients with chronic obstructive pulmonary disease.

PubMed

Jo, Yong Suk; Park, Ju-Hee; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

2017-01-01

There are limited data on pulmonary arterial hypertension (PAH) in patients with tuberculosis-destroyed lung (TDL), a sequela of pulmonary tuberculosis. We identified the risk factors for PAH and their effects on acute exacerbation and mortality in patients with TDL, as well as the clinical differences in patients with chronic obstructive pulmonary disease (COPD) and PAH. A retrospective cohort study was conducted from 2010 through 2015 in a municipal referral hospital in South Korea. PAH was defined when echocardiographic pulmonary arterial pressure (PAP) was >40 mmHg. The clinical features and course of TDL patients with or without PAH were evaluated and differences between patients with COPD and PAH were analyzed. Among the 195 patients with TDL, echocardiographic data were available in 53 patients, and their mean PAP was 50.72±23.99 mmHg. The PAH group (n=37) had a smaller lung volume (forced vital capacity % predicted, 51.55% vs 72.37%, P <0.001) and more extensively destroyed lungs (3.27 lobes vs 2 lobes, P <0.001) than those in the non-PAH group (n=16). A higher PAP was significantly correlated with a higher frequency of acute exacerbation ( r =0.32, P =0.02). Multivariate analyses did not reveal any significant risk factors contributing to PAH in patients with TDL. Compared to COPD patients with PAH, TDL patients with PAH have smaller lung volume but a less severe airflow limitation. Tricuspid regurgitation and a D-shaped left ventricle during diastole were more frequently observed in TDL patients. The risk of exacerbation was not different between patients with PAH in COPD and TDL. PAH in patients with TDL was associated with severity of lung destruction but risk of exacerbation and mortality did not significantly differ between patients with PAH and without PAH.

Refining Susceptibility Loci of Chronic Obstructive Pulmonary Disease with Lung eqtls

PubMed Central

Lamontagne, Maxime; Couture, Christian; Postma, Dirkje S.; Timens, Wim; Sin, Don D.; Paré, Peter D.; Hogg, James C.; Nickle, David; Laviolette, Michel; Bossé, Yohan

2013-01-01

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality worldwide. Recent genome-wide association studies (GWAS) have identified robust susceptibility loci associated with COPD. However, the mechanisms mediating the risk conferred by these loci remain to be found. The goal of this study was to identify causal genes/variants within susceptibility loci associated with COPD. In the discovery cohort, genome-wide gene expression profiles of 500 non-tumor lung specimens were obtained from patients undergoing lung surgery. Blood-DNA from the same patients were genotyped for 1,2 million SNPs. Following genotyping and gene expression quality control filters, 409 samples were analyzed. Lung expression quantitative trait loci (eQTLs) were identified and overlaid onto three COPD susceptibility loci derived from GWAS; 4q31 (HHIP), 4q22 (FAM13A), and 19q13 (RAB4B, EGLN2, MIA, CYP2A6). Significant eQTLs were replicated in two independent datasets (n = 363 and 339). SNPs previously associated with COPD and lung function on 4q31 (rs1828591, rs13118928) were associated with the mRNA expression of HHIP. An association between mRNA expression level of FAM13A and SNP rs2045517 was detected at 4q22, but did not reach statistical significance. At 19q13, significant eQTLs were detected with EGLN2. In summary, this study supports HHIP, FAM13A, and EGLN2 as the most likely causal COPD genes on 4q31, 4q22, and 19q13, respectively. Strong lung eQTL SNPs identified in this study will need to be tested for association with COPD in case-control studies. Further functional studies will also be needed to understand the role of genes regulated by disease-related variants in COPD. PMID:23936167

Hospital care following emergency admission: a critical incident case study of the experiences of patients with advanced lung cancer and Chronic Obstructive Pulmonary Disease.

PubMed

Bailey, Cara; Hewison, Alistair; Karasouli, Eleni; Staniszewska, Sophie; Munday, Daniel

2016-08-01

To explore the experiences of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and lung cancer, their carers and healthcare professionals following emergency admission to acute care hospital. Emergency admissions of people with lung cancer and COPD have increased and there is global concern about the number of patients who die in hospital. The experience of patients with advanced lung cancer and COPD admitted to hospital as an emergency when nearing the end of life has not previously been investigated. Qualitative critical incident case study. Semistructured interviews were conducted with 39 patients (15 with COPD and 24 with lung cancer), 20 informal carers and 50 healthcare professionals, exploring patients' experiences of emergency hospital admission. Interviews took place after admission and following discharge. Participants nominated relatives and healthcare professionals for interview. Data were analysed thematically. Patients were satisfied with their 'emergency' care but not the care they received once their initial symptoms had been stabilised. The poorer quality care they experienced was characterised by a lack of attention to their fundamental needs, lack of involvement of the family, poor communication about care plans and a lack of continuity between primary and secondary care. A conceptual model of 'spectacular' and 'subtacular' trajectories of care was used to relate the findings to the wider context of health care provision. The complex nature of illness for patients with advanced respiratory disease makes emergency hospital admissions likely. Whilst patients (with COPD and lung cancer) were satisfied with care in the acute 'spectacular' phase of their admission, more attention needs to be given to the continuing care needs of patients in the 'subtacular' phase. This is the first study to explore the patient experience of acute care following an emergency admission and identifies where there is potential for care to be improved. © 2016 John Wiley & Sons Ltd.

Risk factors for the development of chronic pulmonary aspergillosis in patients with nontuberculous mycobacterial lung disease

PubMed Central

Hwang, Na Young; Park, Hye Yun; Jeon, Kyeongman; Kang, Eun-Suk

2017-01-01

Nontuberculous mycobacterial lung disease (NTM-LD) is increasingly recognized as an important predisposing condition for the development of chronic pulmonary aspergillosis (CPA), but there are limited data on the risk factors for CPA development in NTM-LD patients. We reviewed the medical records of 566 patients who, at the time of diagnosis of NTM-LD, did not have CPA and who received ≥12 months of treatment for NTM-LD between January 2010 and June 2015. Of these patients, 41 (7.2%) developed CPA (NTM-CPA group), whereas the remaining 525 patients did not develop CPA (NTM group). The median time to the development of CPA was 18.0 months from treatment initiation for NTM-LD. The NTM-CPA group was older and had significantly higher proportions of males, current smokers, and patients with a low body mass index (<18.5 kg/m2), when compared to the NTM group. Moreover, the NTM-CPA group was more likely to have a history of tuberculosis and chronic obstructive lung disease and to have used inhaled or systemic steroids. In the NTM-CPA group, more than 40% of patients had Mycobacterium abscessus complex (MABC) as the cause of NTM-LD, and the fibrocavitary form of NTM-LD was the most common; both associations were higher than in the NTM group. Overall, 17 (3%) patients died, and the NTM-CPA group had a higher mortality rate than did the NTM group (19.5% vs. 1.7%, respectively; P<0.001). In a multivariable analysis, old age, male gender, low body mass index, chronic obstructive lung disease, systemic steroids, MABC as the etiologic organism, and the fibrocavitary form of NTM-LD remained significant predictors of development of CPA. In conclusion, CPA occurred in 7.2% of patients after initiation of treatment for NTM-LD, and some risk factors were associated with CPA development. Given the worse prognosis, early diagnosis and treatment of CPA are important in patients with NTM-LD. PMID:29190796

A lifetime Markov model for the economic evaluation of chronic obstructive pulmonary disease.

PubMed

Menn, Petra; Leidl, Reiner; Holle, Rolf

2012-09-01

Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death worldwide. It has serious health effects and causes substantial costs for society. The aim of the present paper was to develop a state-of-the-art decision-analytic model of COPD whereby the cost effectiveness of interventions in Germany can be estimated. To demonstrate the applicability of the model, a smoking cessation programme was evaluated against usual care. A seven-stage Markov model (disease stages I to IV according to the GOLD [Global Initiative for Chronic Obstructive Lung Disease] classification, states after lung-volume reduction surgery and lung transplantation, death) was developed to conduct a cost-utility analysis from the societal perspective over a time horizon of 10, 40 and 60 years. Patients entered the cohort model at the age of 45 with mild COPD. Exacerbations were classified into three levels: mild, moderate and severe. Estimation of stage-specific probabilities (for smokers and quitters), utilities and costs was based on German data where possible. Data on effectiveness of the intervention was retrieved from the literature. A discount rate of 3% was applied to costs and effects. Probabilistic sensitivity analysis was used to assess the robustness of the results. The smoking cessation programme was the dominant strategy compared with usual care, and the intervention resulted in an increase in health effects of 0.54 QALYs and a cost reduction of &U20AC;1115 per patient (year 2007 prices) after 60 years. In the probabilistic analysis, the intervention dominated in about 95% of the simulations. Sensitivity analyses showed that uncertainty primarily originated from data on disease progression and treatment cost in the early stages of disease. The model developed allows the long-term cost effectiveness of interventions to be estimated, and has been adapted to Germany. The model suggests that the smoking cessation programme evaluated was more effective than usual care as well as being cost-saving. Most patients had mild or moderate COPD, stages for which parameter uncertainty was found to be high. This raises the need to improve data on the early stages of COPD.

Meaning of living with severe chronic obstructive lung disease: a qualitative study.

PubMed

Marx, Gabriella; Nasse, Maximilian; Stanze, Henrikje; Boakye, Sonja Owusu; Nauck, Friedemann; Schneider, Nils

2016-12-08

To explore what it means for patients to live with chronic obstructive pulmonary disease (COPD) as an incurable and constantly progressing disease. Qualitative longitudinal study using narrative and semistructured interviews. This paper presents findings of the initial interviews. Analysis using grounded theory. Lung care clinics and community care in Lower Saxony, Germany. 17 patients with advanced-stage COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) III/IV). Analysis shows that these patients have difficulties accepting their life situation and feel at the mercy of the disease, which could be identified as a core-experienced phenomenon. Over a long period of time, patients have only a vague feeling of being ill, caused by uncertain knowledge, slow progress and doubtful attribution of clinical symptoms of the disease (causal conditions). As an action strategy, patients try to maintain daily routines for as long as possible after diagnosis. Both effective standard and rescue medication, which helps to reduce breathlessness and other symptoms, and the feeling of being faced with one's own responsibility (intervening conditions) support this strategy, whereby patients' own responsibility is too painful to acknowledge. As a consequence, patients try to deny the threat to life for a long period of time. Frequently, they need to experience facing their own limits, often in the form of an acute crisis, to realise their health situation. The experience of the illness is contextualised by a continuous increase in limited mobility and social isolation. In order to help patients to improve disease awareness, to accept their life situation and to improve their reduced quality of life, patients may benefit from the early integration of palliative care (PC), considering its multiprofessional patient-centred and team-centred approach. Psychological support and volunteer work, which are relevant aspects of PC, should be appropriate to address psychosocial needs. More research is needed to evaluate how patients could benefit from early PC. 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/.

Influence of vascular network design on gas transfer in lung assist device technology.

PubMed

Bassett, Erik K; Hoganson, David M; Lo, Justin H; Penson, Elliot J N; Vacanti, Joseph P

2011-01-01

Blood oxygenators are vital for the critically ill, but their use is limited to the hospital setting. A portable blood oxygenator or a lung assist device for ambulatory or long-term use would greatly benefit patients with chronic lung disease. In this work, a biomimetic blood oxygenator system was developed which consisted of a microfluidic vascular network covered by a gas permeable silicone membrane. This system was used to determine the influence of key microfluidic parameters-channel size, oxygen exposure length, and blood shear rate-on blood oxygenation and carbon dioxide removal. Total gas transfer increased linearly with flow rate, independent of channel size and oxygen exposure length. On average, CO(2) transfer was 4.3 times higher than oxygen transfer. Blood oxygen saturation was also found to depend on the flow rate per channel but in an inverse manner; oxygenation decreased and approached an asymptote as the flow rate per channel increased. These relationships can be used to optimize future biomimetic vascular networks for specific lung applications: gas transfer for carbon dioxide removal in patients with chronic obstructive pulmonary disease or oxygenation for premature infants requiring complete lung replacement therapy.

Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity.

PubMed

Koo, Hyeon-Kyoung; Hong, Yoonki; Lim, Myoung Nam; Yim, Jae-Joon; Kim, Woo Jin

2016-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity. Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses. There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant. Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients.

Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity

PubMed Central

Koo, Hyeon-Kyoung; Hong, Yoonki; Lim, Myoung Nam; Yim, Jae-Joon; Kim, Woo Jin

2016-01-01

Objective Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease–antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity. Methods Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses. Results There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant. Conclusion Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients. PMID:27313452

Mindfulness-Based Symptom and Stress Management Apps for Adults With Chronic Lung Disease: Systematic Search in App Stores.

PubMed

Owens, Otis L; Beer, Jenay M; Reyes, Ligia I; Gallerani, David G; Myhren-Bennett, Amanda R; McDonnell, Karen K

2018-05-15

Up to 70% of lung cancer survivors are affected by chronic obstructive pulmonary disease (COPD), a common, debilitating, comorbid disease. Lung cancer and COPD are both characterized by symptoms such as breathlessness, fatigue, and psychological distress. These distressing chronic symptoms are exacerbated by stress and detract from an individual's quality of life. The aim of this study was to identify and evaluate evidence-based, commercially available apps for promoting mindfulness-based strategies among adults with a COPD or lung cancer history (ie, chronic lung disease). For this review, an interdisciplinary research team used 19 keyword combinations in the search engines of Google and iOS app stores in May 2017. Evaluations were conducted on the apps' (1) content, (2) usability heuristics, (3) grade-level readability, and (4) cultural sensitivity. The search resulted in 768 apps (508 in iOS and 260 in Google stores). A total of 9 apps met the inclusion criteria and received further evaluation. Only 1 app had below an eighth-grade reading level; the ninth one did not have enough text to calculate a readability score. None of the 9 apps met the cultural sensitivity evaluation criteria. This systematic review identified critical design flaws that may affect the ease of using the apps in this study. Few mobile apps promote mindfulness-based strategies among adults with chronic lung disease (ie, COPD or lung cancer or both), but those that exist, overall, do not meet the latest scientific evidence. Recommendations include more stringent regulation of health-related apps, use of evidence-based frameworks and participatory design processes, following evidence-based usability practices, use of culturally sensitive language and images, and ensuring that content is written in plain language. ©Otis L Owens, Jenay M Beer, Ligia I Reyes, David G Gallerani, Amanda R Myhren-Bennett, Karen K McDonnell. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 15.05.2018.

Comparison between an Alternative and the Classic Definition of Chronic Bronchitis in COPDGene

PubMed Central

Crapo, James; Zhao, Huaqing; Jones, Paul W.; Silverman, Edwin K.; Comellas, Alejandro; Make, Barry J.; Criner, Gerard J.

2015-01-01

Rationale: Previous studies on chronic bronchitis (CB) have used varying definitions. Objectives: We sought to compare an alternative CB definition, using the St. George’s Respiratory Questionnaire (SGRQ), a commonly used assessment tool, with the classic definition and to investigate if it had independent or additive value. Methods: We analyzed data from 4,513 subjects from Global Initiative for Chronic Obstructive Lung Disease groups 1 to 4 in the COPDGene cohort. We compared the classic definition of CB with the SGRQ definition, defined by their answers to the questions about both cough and phlegm. We compared the Classic CB+ versus CB− groups, and the SGRQ CB+ and CB− groups. We also analyzed the cohort split into four groups: Classic CB+/SGRQ CB+, Classic CB+/SGRQ CB−, Classic CB−/SGRQ CB+, Classic CB−/SGRQ CB−. Measurements and Main Results: A total of 26.1% subjects were Classic CB+, whereas 39.9% were SGRQ CB+. When the SGRQ definition was compared with the Classic CB definition, using this as the gold standard, the SGRQ CB definition had a sensitivity and specificity of 0.87 and 0.77, respectively. The SGRQ CB+ and Classic CB+ groups were strikingly similar, with more respiratory symptoms and exacerbations, worse lung function, and greater airway wall thickness. In addition, the Classic CB+/SGRQ CB+, Classic CB+/SGRQ CB−, and Classic CB−/SGRQ CB+ groups shared similar characteristics as well. Conclusions: The SGRQ CB definition identifies more subjects with chronic cough and sputum who share a similar phenotype identified by the Classic CB definition. The addition of the SGRQ CB definition to the classic one can be used to identify more patients with chronic obstructive pulmonary disease at risk for poor outcomes. PMID:25575351

Chronic Obstructive Pulmonary Disease Assessment Test Can Predict Depression: A Prospective Multi-Center Study

PubMed Central

Lee, Young Seok; Park, Sunghoon; Oh, Yeon-Mok; Lee, Sang-Do; Park, Sung-Woo; Kim, Young Sam; In, Kwang Ho; Jung, Bock Hyun; Lee, Kwan Ho; Ra, Seung Won; Hwang, Yong Il; Park, Yong-Bum

2013-01-01

This study was conducted to investigate the association between the chronic obstructive pulmonary disease (COPD) assessment test (CAT) and depression in COPD patients. The Korean versions of the CAT and patient health questionnaire-9 (PHQ-9) were used to assess COPD symptoms and depressive disorder, respectively. In total, 803 patients with COPD were enrolled from 32 hospitals and the prevalence of depression was 23.8%. The CAT score correlated well with the PHQ-9 score (r=0.631; P<0.001) and was significantly associated with the presence of depression (β±standard error, 0.452±0.020; P<0.001). There was a tendency toward increasing severity of depression in patients with higher CAT scores. By assessment groups based on the 2011 Global Initiative for Chronic Obstructive Lung Disease guidelines, the prevalence of depression was affected more by current symptoms than by airway limitation. The area under the receiver operating characteristic curve for the CAT was 0.849 for predicting depression, and CAT scores ≥21 had the highest accuracy rate (80.6%). Among the eight CAT items, energy score showed the best correlation and highest power of discrimination. CAT scores are significantly associated with the presence of depression and have good performance for predicting depression in COPD patients. PMID:23853488

Impact of GOLD groups of chronic pulmonary obstructive disease on surgical complications.

PubMed

Kim, Hyung-Jun; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Lee, Sang-Min; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Choi, Sun Mi

2016-01-01

Chronic obstructive pulmonary disease (COPD) is associated with increased postoperative complications. Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classified COPD patients into four groups based on spirometry results and the severity of symptoms. The objective of this study was to evaluate the impact of GOLD groups on postoperative complications. We reviewed the medical records of COPD patients who underwent preoperative spirometry between April and August 2013 at a tertiary hospital in Korea. We divided the patients into GOLD groups according to the results of spirometry and self-administered questionnaires that assessed the symptom severity and exacerbation history. GOLD groups, demographic characteristics, and operative conditions were analyzed. Among a total of 405 COPD patients, 70 (17.3%) patients experienced various postoperative complications, including infection, wound, or pulmonary complications. Thoracic surgery, upper abdominal surgery, general anesthesia, large estimated blood loss during surgery, and longer anesthesia time were significant risk factors for postoperative complications. Patients in high-risk group (GOLD groups C or D) had an increased risk of postoperative complications compared to those in low-risk group (GOLD groups A or B). COPD patients in GOLD groups representing a high exacerbation risk have an increased risk of postoperative complications compared to those with low risk.

Chronic obstructive pulmonary disease: getting it right. Does optimal management of chronic obstructive pulmonary disease alter disease progression and improve survival?

PubMed

Russell, Richard E

2014-03-01

We live in a world where people live longer lives. The standardized mortality rate for many diseases is decreasing. Chronic obstructive pulmonary disease (COPD) is not following this trend. Over the last 10 years, interventions for COPD have been developed, but have any changed the prognosis or trajectory of this modern epidemic? We review the most recent and classical literature in order to answer this question. Recent analyses of data have clarified which interventions are effective in COPD and which are not. New studies have defined what is achievable with the current therapies. Only two interventions have been demonstrated to improve survival: smoking cessation and long-term oxygen therapy. Other treatments do reduce exacerbations, improve lung function and improve the patient's quality of life, but do not affect physiological disease progression or mortality. There is much work to do, not only to improve the treatments we have for this disease, but also to diagnose it early, intervene at the right time, reduce the treatment side-effects and most importantly understand the pathophysiology better. Moreover, we are duty bound to look at each patient and review what we are trying to achieve for each one through appropriate phenotyping as well as sometimes taking a more palliative approach.

Practical aspects of inhaler use in the management of chronic obstructive pulmonary disease in the primary care setting.

PubMed

Yawn, Barbara P; Colice, Gene L; Hodder, Rick

2012-01-01

Sustained bronchodilation using inhaled medications in moderate to severe chronic obstructive pulmonary disease (COPD) grades 2 and 3 (Global Initiative for Chronic Obstructive Lung Disease guidelines) has been shown to have clinical benefits on long-term symptom control and quality of life, with possible additional benefits on disease progression and longevity. Aggressive diagnosis and treatment of symptomatic COPD is an integral and pivotal part of COPD management, which usually begins with primary care physicians. The current standard of care involves the use of one or more inhaled bronchodilators, and depending on COPD severity and phenotype, inhaled corticosteroids. There is a wide range of inhaler devices available for delivery of inhaled medications, but suboptimal inhaler use is a common problem that can limit the clinical effectiveness of inhaled therapies in the real-world setting. Patients' comorbidities, other physical or mental limitations, and the level of inhaler technique instruction may limit proper inhaler use. This paper presents information that can overcome barriers to proper inhaler use, including issues in device selection, steps in correct technique for various inhaler devices, and suggestions for assessing and monitoring inhaler techniques. Ensuring proper inhaler technique can maximize drug effectiveness and aid clinical management at all grades of COPD.

Practical aspects of inhaler use in the management of chronic obstructive pulmonary disease in the primary care setting

PubMed Central

Yawn, Barbara P; Colice, Gene L; Hodder, Rick

2012-01-01

Sustained bronchodilation using inhaled medications in moderate to severe chronic obstructive pulmonary disease (COPD) grades 2 and 3 (Global Initiative for Chronic Obstructive Lung Disease guidelines) has been shown to have clinical benefits on long-term symptom control and quality of life, with possible additional benefits on disease progression and longevity. Aggressive diagnosis and treatment of symptomatic COPD is an integral and pivotal part of COPD management, which usually begins with primary care physicians. The current standard of care involves the use of one or more inhaled bronchodilators, and depending on COPD severity and phenotype, inhaled corticosteroids. There is a wide range of inhaler devices available for delivery of inhaled medications, but suboptimal inhaler use is a common problem that can limit the clinical effectiveness of inhaled therapies in the real-world setting. Patients’ comorbidities, other physical or mental limitations, and the level of inhaler technique instruction may limit proper inhaler use. This paper presents information that can overcome barriers to proper inhaler use, including issues in device selection, steps in correct technique for various inhaler devices, and suggestions for assessing and monitoring inhaler techniques. Ensuring proper inhaler technique can maximize drug effectiveness and aid clinical management at all grades of COPD. PMID:22888221

Phosphodiesterase 4 inhibitors in chronic obstructive pulmonary disease: a new approach to oral treatment

PubMed Central

Currie, Graeme P; Butler, Claire A; Anderson, Wendy J; Skinner, Chris

2008-01-01

Chronic obstructive pulmonary disease represents a major global health care burden for both primary and secondary care providers and is the most common respiratory condition necessitating hospital admission. Short-acting bronchodilators play a vital role in immediate relief of symptoms, while inhaled long-acting bronchodilators and inhaled corticosteroids are advocated for regular use in individuals with persistent symptoms and exacerbations. Theophylline is a nonspecific phosphodiesterase inhibitor and is usually reserved for patients with ongoing symptoms despite optimum inhaled bronchodilator treatment or when difficulty is encountered with inhaler devices. However, it is often not widely used mainly due to frequency of dose-related adverse effects, numerous drug interactions and narrow therapeutic index. This in turn has lead to the development of more selective phosphodiesterase inhibitors in an attempt to create a drug which patients can use with beneficial effects but without the problems associated with theophylline. Current data do indicate that phosphodiesterase 4 inhibitors confer some benefits in chronic obstructive pulmonary disease when compared to placebo in terms of lung function, quality of life and exacerbations. They are also generally well tolerated. Further studies are required to determine fully their long-term beneficial and adverse effect profiles and ultimately where they might comfortably sit in management algorithms. PMID:18341675

Inhaled corticosteroids in chronic obstructive pulmonary disease: a pro–con perspective

PubMed Central

Babu, K Suresh; Kastelik, Jack A; Morjaria, Jaymin B

2014-01-01

Current guidelines limit regular use of inhaled corticosteroids (ICS) to a specific subgroup of patients with chronic obstructive pulmonary disease (COPD) in whom the forced expiratory volume in 1 s is <60% of predicted and who have frequent exacerbations. In these patients, there is evidence that ICS reduce the frequency of exacerbations and improve lung function and quality of life. However, a review of the literature suggests that the evidence available may be interpreted to favour or contradict these observations. It becomes apparent that COPD is a heterogeneous condition. Clinicians therefore need to be aware of the heterogeneity as well as having an understanding of how ICS may be used in the context of the specific subgroups of patients with COPD. This review argues for and against the use of ICS in COPD by providing an in-depth analysis of the currently available evidence. PMID:25099256

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

PubMed

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

2011-09-01

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

Occupation and the Prevalence of Respiratory Health Symptoms and Conditions: The Atherosclerosis Risk in Communities Study

PubMed Central

Mirabelli, Maria C.; London, Stephanie J.; Charles, Luenda E.; Pompeii, Lisa A.; Wagenknecht, Lynne E.

2011-01-01

Objectives To examine associations between occupation and respiratory health in a large, population-based cohort of adults in the United States. Methods Data from 15,273 participants, aged 45-64 years, in the Atherosclerosis Risk in Communities (ARIC) study were used to examine associations of current or most recent job held with the prevalence of self-reported chronic cough, chronic bronchitis, wheeze, asthma, and measures of lung function collected by spirometry. Results Eleven percent of participants reported wheeze and 9% were classified as having airway obstruction. Compared to individuals in managerial and administrative jobs, increased prevalences of respiratory outcomes were observed among participants in selected occupations, including construction and extractive trades (wheeze: prevalence ratio [PR]: 1.92, 95% confidence interval [CI]: 1.35, 2.73; airway obstruction: PR: 1.31, 95% CI: 1.05, 1.65). Conclusions Specific occupations are associated with adverse respiratory health. PMID:22157701

Occupation and the prevalence of respiratory health symptoms and conditions: the Atherosclerosis Risk in Communities Study.

PubMed

Mirabelli, Maria C; London, Stephanie J; Charles, Luenda E; Pompeii, Lisa A; Wagenknecht, Lynne E

2012-02-01

To examine associations between occupation and respiratory health in a large, population-based cohort of adults in the United States. Data from 15,273 participants, aged 45 to 64 years, in the Atherosclerosis Risk in Communities study were used to examine associations of current or most recent job held with the prevalence of self-reported chronic cough, chronic bronchitis, wheezing, asthma, and measures of lung function collected by spirometry. Eleven percent of participants reported wheezing and 9% were classified as having airway obstruction. Compared with individuals in managerial and administrative jobs, increased prevalences of respiratory outcomes were observed among participants in selected occupations, including construction and extractive trades (wheezing, prevalence ratio = 1.92, 95% confidence interval = 1.35, 2.73; airway obstruction, prevalence ratio = 1.31, 95% confidence interval = 1.05, 1.65). Specific occupations are associated with adverse respiratory health.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary.

PubMed

Vogelmeier, Claus F; Criner, Gerard J; Martinez, Fernando J; Anzueto, Antonio; Barnes, Peter J; Bourbeau, Jean; Celli, Bartolome R; Chen, Rongchang; Decramer, Marc; Fabbri, Leonardo M; Frith, Peter; Halpin, David M G; López Varela, M Victorina; Nishimura, Masaharu; Roche, Nicolas; Rodriguez-Roisin, Roberto; Sin, Don D; Singh, Dave; Stockley, Robert; Vestbo, Jørgen; Wedzicha, Jadwiga A; Agusti, Alvar

2017-03-01

This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: 1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; 2) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; 3) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; 4) nonpharmacologic therapies are comprehensively presented and; 5) the importance of comorbid conditions in managing COPD is reviewed. Copyright ©2017 the American Thoracic Society. Published with permission from the American Thoracic Society. Design and branding are copyright ©ERS 2017.

The immediate effect of soft tissue manual therapy intervention on lung function in severe chronic obstructive pulmonary disease

PubMed Central

Cruz-Montecinos, Carlos; Godoy-Olave, Diego; Contreras-Briceño, Felipe A; Gutiérrez, Paulina; Torres-Castro, Rodrigo; Miret-Venegas, Leandro; Engel, Roger M

2017-01-01

Background and objective In chronic obstructive pulmonary disease (COPD), accessory respiratory muscles are recruited as a compensatory adaptation to changes in respiratory mechanics. This results in shortening and overactivation of these and other muscles. Manual therapy is increasingly being investigated as a way to alleviate these changes. The aim of this study was to measure the immediate effect on lung function of a soft tissue manual therapy protocol (STMTP) designed to address changes in the accessory respiratory muscles and their associated structures in patients with severe COPD. Methods Twelve medically stable patients (n=12) with an existing diagnosis of severe COPD (ten: GOLD Stage III and two: GOLD Stage IV) were included. Residual volume, inspiratory capacity and oxygen saturation (SpO2) were recorded immediately before and after administration of the STMTP. A Student’s t-test was used to determine the effect of the manual therapy intervention (P<0.05). Results The mean age of the patients was 62.4 years (range 46–77). Nine were male. Residual volume decreased from 4.5 to 3.9 L (P=0.002), inspiratory capacity increased from 2.0 to 2.1 L (P=0.039) and SpO2 increased from 93% to 96% (P=0.001). Conclusion A single application of an STMTP appears to have the potential to produce immediate clinically meaningful improvements in lung function in patients with severe and very severe COPD. PMID:28260875

Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease

PubMed Central

Yang, Lei; Jiao, Xingai; Wu, Jinxiang; Zhao, Jiping; Liu, Tian; Xu, Jianfeng; Ma, Xiaohui; Cao, Liuzao; Liu, Lin; Liu, Yahui; Chi, Jingyu; Zou, Minfang; Li, Shuo; Xu, Jiawei; Dong, Liang

2018-01-01

Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensis on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy. PMID:29456676

Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease.

PubMed

Yang, Lei; Jiao, Xingai; Wu, Jinxiang; Zhao, Jiping; Liu, Tian; Xu, Jianfeng; Ma, Xiaohui; Cao, Liuzao; Liu, Lin; Liu, Yahui; Chi, Jingyu; Zou, Minfang; Li, Shuo; Xu, Jiawei; Dong, Liang

2018-03-01

Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensi s on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy.

Health-related quality of life in patients with chronic obstructive pulmonary disease in North India.

PubMed

Negi, H; Sarkar, M; Raval, A D; Pandey, K; Das, P

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a major health problem in India and constitutes an important cause of mortality and morbidity. A cross-sectional study was undertaken to assess health-related quality of life (HRQL) and its determinants in patients with COPD from India. A total of 126 patients (73.81% male) were enrolled using convenient sampling prospectively in this cross-sectional study. Eligible patients were assessed for socioeconomic status, anthropometric measures, COPD severity, dyspnea and health status using the Hindi version of St George's Respiratory Questionnaire (SGRQ). Linear regression model was used to examine the association between risk factors and HRQL score (a higher score indicating poorer HRQL), adjusting for age and sex. The mean total score for SGRQ in the patients was 52.66 ± 12.89, indicating a marked impairment of HRQL. Impairment was associated with the severity of airway obstruction, but within each Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, the variation (SD) was wide [stage I: 47.8 ± 12.3 (n = 14); stage II: 49.28 ± 11.69 (n = 47); stage III: 53.47 ± 11.69 (n = 44); stage IV: 61.75 ± 14.14 (n = 21)]. A regression analysis showed that body mass index, forced expiratory volume in 1 s (FEV 1 ), dyspnea grade, and depression were associated with poor HRQL. HRQL of COPD patients was significantly impaired across stages. Marked impairment of HRQL was found even in patients with mild disease.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

PubMed

Hecker, Louise

2018-04-01

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice.

PubMed

Gille, Thomas; Didier, Morgane; Rotenberg, Cécile; Delbrel, Eva; Marchant, Dominique; Sutton, Angela; Dard, Nicolas; Haine, Liasmine; Voituron, Nicolas; Bernaudin, Jean-François; Valeyre, Dominique; Nunes, Hilario; Besnard, Valérie; Boncoeur, Emilie; Planès, Carole

2018-01-01

Severe obstructive sleep apnea (OSA) with chronic intermittent hypoxia (IH) is common in idiopathic pulmonary fibrosis (IPF). Here, we evaluated the impact of IH on bleomycin- (BLM-) induced pulmonary fibrosis in mice. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO 2 nadir: 6%; 8 hours/day) or intermittent air (IA). In the four experimental groups, we evaluated (i) survival; (ii) alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii) lung cell apoptosis; and (iv) pulmonary fibrosis. Survival at day 21 was lower in the BLM-IH group ( p < 0.05). Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content ( p = 0.02) and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, ( p < 0.001). Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice ( p < 0.05 versus BLM-IA group). At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.

Episodes of breathlessness: types and patterns - a qualitative study exploring experiences of patients with advanced diseases.

PubMed

Simon, Steffen T; Higginson, Irene J; Benalia, Hamid; Gysels, Marjolein; Murtagh, Fliss Em; Spicer, James; Bausewein, Claudia

2013-06-01

Despite the high prevalence and impact of episodic breathlessness, information about characteristics and patterns is scarce. To explore the experience of patients with advanced disease suffering from episodic breathlessness, in order to describe types and patterns. Qualitative design using in-depth interviews with patients suffering from advanced stages of chronic heart failure, chronic obstructive pulmonary disease, lung cancer or motor neurone disease. As part of the interviews, patients were asked to draw a graph to illustrate typical patterns of breathlessness episodes. Interviews were tape-recorded, transcribed verbatim and analysed using Framework Analysis. The graphs were grouped according to their patterns. Fifty-one participants (15 chronic heart failure, 14 chronic obstructive pulmonary disease, 13 lung cancer and 9 motor neurone disease) were included (mean age 68.2 years, 30 of 51 men, mean Karnofsky 63.1, mean breathlessness intensity 3.2 of 10). Five different types of episodic breathlessness were described: triggered with normal level of breathlessness, triggered with predictable response (always related to trigger level, e.g. slight exertion causes severe breathlessness), triggered with unpredictable response (not related to trigger level), non-triggered attack-like (quick onset, often severe) and wave-like (triggered or non-triggered, gradual onset). Four patterns of episodic breathlessness could be identified based on the graphs with differences regarding onset and recovery of episodes. These did not correspond with the types of breathlessness described before. Patients with advanced disease experience clearly distinguishable types and patterns of episodic breathlessness. The understanding of these will help clinicians to tailor specific management strategies for patients who suffer from episodes of breathlessness.

Ageing and the border between health and disease.

PubMed

MacNee, William; Rabinovich, Roberto A; Choudhury, Gourab

2014-11-01

Ageing is associated with a progressive degeneration of the tissues, which has a negative impact on the structure and function of vital organs and is among the most important known risk factors for most chronic diseases. Since the proportion of the world's population aged >60 years will double in the next four decades, this will be accompanied by an increased incidence of chronic age-related diseases that will place a huge burden on healthcare resources. There is increasing evidence that many chronic inflammatory diseases represent an acceleration of the ageing process. Chronic pulmonary diseases represents an important component of the increasingly prevalent multiple chronic debilitating diseases, which are a major cause of morbidity and mortality, particularly in the elderly. The lungs age and it has been suggested that chronic obstructive pulmonary disease (COPD) is a condition of accelerated lung ageing and that ageing may provide a mechanistic link between COPD and many of its extrapulmonary effects and comorbidities. In this article we will describe the physiological changes and mechanisms of ageing, with particular focus on the pulmonary effects of ageing and how these may be relevant to the development of COPD and its major extrapulmonary manifestations. ©ERS 2014.

Pulmonary health effects of agriculture.

PubMed

Nordgren, Tara M; Bailey, Kristina L

2016-03-01

Occupational exposures in the agricultural industry are associated with numerous lung diseases, including chronic obstructive pulmonary disease, asthma, hypersensitivity pneumonitis, lung cancer, and interstitial lung diseases. Efforts are ongoing to ascertain contributing factors to these negative respiratory outcomes and improve monitoring of environmental factors leading to disease. In this review, recently published studies investigating the deleterious effects of occupational exposures in the agricultural industry are discussed. Occupational exposures to numerous agricultural environment aerosols, including pesticides, fungi, and bacteria are associated with impaired respiratory function and disease. Increases in certain farming practices, including mushroom and greenhouse farming, present new occupational exposure concerns. Improved detection methods may provide opportunities to better monitor safe exposure levels to known lung irritants. In the agricultural industry, occupational exposures to organic and inorganic aerosols lead to increased risk for lung disease among workers. Increased awareness of respiratory risks and improved monitoring of agricultural environments are necessary to limit pulmonary health risks to exposed populations.

[Oxidative stress in pathogenesis of COPD].

PubMed

Betsuyaku, Tomoko

2007-04-01

Cigarette smoke and aging are major risk factors of chronic obstructive pulmonary disease(COPD). It remains unsolved how long -term smoking with age affects the molecular responses in the lung. Respiratory tract is the major interface to the environment and is rich in glutathione, which protects lung from oxidative stress. We performed bronchoalveolar lavage for nonsmokers and smokers of various ages, who were further categorized according to the presence of emphysema on high-resolution computed tomography. We thus evaluated glutathione antioxidant system in BAL fluid. Characterization of older smokers with long-term smoking histories, contrasted with young recent smokers, may in part explain the predisposition of the lungs to destructive lung diseases. On the other hands, oxidative stress results from an imbalance in aerobic metabolism and poses a serious threat to cellular apoptosis, leading to emphysematous lung destruction. The therapeutic interference with targeted up-regulation of protective mechanisms might be critical for the success of future COPD therapies.

Inflammasome Activity in Non-Microbial Lung Inflammation

PubMed Central

Ather, Jennifer L.; Martin, Rebecca A.; Ckless, Karina; Poynter, Matthew E.

2015-01-01

The understanding of interleukin-1 (IL-1) family cytokines in inflammatory disease has rapidly developed, due in part to the discovery and characterization of inflammasomes, which are multi-subunit intracellular protein scaffolds principally enabling recognition of a myriad of cellular stimuli, leading to the activation of caspase-1 and the processing of IL-1β and IL-18. Studies continue to elucidate the role of inflammasomes in immune responses induced by both microbes and environmental factors. This review focuses on the current understanding of inflammasome activity in the lung, with particular focus on the non-microbial instigators of inflammasome activation, including inhaled antigens, oxidants, cigarette smoke, diesel exhaust particles, mineral fibers, and engineered nanomaterials, as well as exposure to trauma and pre-existing inflammatory conditions such as metabolic syndrome. Inflammasome activity in these sterile inflammatory states contribute to diseases including asthma, chronic obstructive disease, acute lung injury, ventilator-induced lung injury, pulmonary fibrosis, and lung cancer. PMID:25642415

Genetically manipulated mouse models of lung disease: potential and pitfalls

PubMed Central

Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

2012-01-01

Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

Mild chronic obstructive pulmonary disease: why spirometry is not sufficient!

PubMed

Elbehairy, Amany F; Parraga, Grace; Webb, Katherine A; Neder, J Alberto; O'Donnell, Denis E

2017-07-01

Chronic obstructive pulmonary disease (COPD) - an inflammatory disease of the airways, alveoli and lung microvasculature - is a leading cause of death worldwide. Smokers with milder airway obstruction constitute the majority of patients with this disease. Many studies have shown increased morbidity, activity-related dyspnea, exercise intolerance and mortality in such patients, compared with age-matched healthy populations. Clinical evaluation of symptomatic smokers with ostensibly mild airway obstruction poses a challenge in clinical practice as spirometry can obscure extensive heterogeneous pathophysiological impairment. Areas covered: A detailed review of the evidence for complex biological, physiological and radiological abnormalities in smokers who barely fit arbitrary spirometric criteria for COPD diagnosis. A brief discussion of the debate about current diagnostic spirometric criteria for COPD that can lead to diagnostic confusion and, in-some-instances, to inappropriate management. Finally, we provide a review of the clinical implications of these structural and functional abnormalities and try to build a solid rationale for earlier detection and effective, timely management. Expert commentary: The prevalence of mild COPD among smokers is high, yet under-diagnosis remains a major problem and there is lack of evidence-based management recommendations for this sub-population. Further tests beyond spirometry are useful in uncovering patho-physiological derangements that are clinically relevant.

The pathophysiology of bronchiectasis

PubMed Central

King, Paul T

2009-01-01

Bronchiectasis is defined by permanent and abnormal widening of the bronchi. This process occurs in the context of chronic airway infection and inflammation. It is usually diagnosed using computed tomography scanning to visualize the larger bronchi. Bronchiectasis is also characterized by mild to moderate airflow obstruction. This review will describe the pathophysiology of noncystic fibrosis bronchiectasis. Studies have demonstrated that the small airways in bronchiectasis are obstructed from an inflammatory infiltrate in the wall. As most of the bronchial tree is composed of small airways, the net effect is obstruction. The bronchial wall is typically thickened by an inflammatory infiltrate of lymphocytes and macrophages which may form lymphoid follicles. It has recently been demonstrated that patients with bronchiectasis have a progressive decline in lung function. There are a large number of etiologic risk factors associated with bronchiectasis. As there is generally a long-term retrospective history, it may be difficult to determine the exact role of such factors in the pathogenesis. Extremes of age and smoking/chronic obstructive pulmonary disease may be important considerations. There are a variety of different pathogens involved in bronchiectasis, but a common finding despite the presence of purulent sputum is failure to identify any pathogenic microorganisms. The bacterial flora appears to change with progression of disease. PMID:20037680

The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.

PubMed

Grabiec, Aleksander M; Hussell, Tracy

2016-07-01

Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called 'efferocytosis'. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections.

PULMONARY PATHOPHYSIOLOGY AND LUNG MECHANICS IN ANESTHESIOLOGY: A CASE-BASED OVERVIEW

PubMed Central

Vidal Melo, Marcos F.; Musch, Guido; Kaczka, David W.

2012-01-01

The induction and maintenance of anesthesia, surgical requirements, and patients’ unique pathophysiology all combine to create a setting in which our accumulated knowledge of respiratory physiology and lung mechanics take on immediate and central importance in patient management. In this review we will take a case-based approach to illustrate how the complex interactions between anesthesia, surgery, and patient disease impact patient care with respect to pulmonary pathophysiology and clinical decision-making. We will examine two disparate scenarios: a patient with chronic obstructive pulmonary disease undergoing a lung resection, and a patient with coronary artery disease undergoing cardiopulmonary bypass. In each example we will illustrate how important concepts in pulmonary physiology and respiratory mechanics impact clinical management decisions. PMID:23089508

Molecular Processes that Drive Cigarette Smoke–Induced Epithelial Cell Fate of the Lung

PubMed Central

Nyunoya, Toru; Mebratu, Yohannes; Contreras, Amelia; Delgado, Monica; Chand, Hitendra S.

2014-01-01

Cigarette smoke contains numerous chemical compounds, including abundant reactive oxygen/nitrogen species and aldehydes, and many other carcinogens. Long-term cigarette smoking significantly increases the risk of various lung diseases, including chronic obstructive pulmonary disease and lung cancer, and contributes to premature death. Many in vitro and in vivo studies have elucidated mechanisms involved in cigarette smoke–induced inflammation, DNA damage, and autophagy, and the subsequent cell fates, including cell death, cellular senescence, and transformation. In this Translational Review, we summarize the known pathways underlying these processes in airway epithelial cells to help reveal future challenges and describe possible directions of research that could lead to better management and treatment of these diseases. PMID:24111585

A global perspective of lung transplantation: Part 1 - Recipient selection and choice of procedure

PubMed Central

Khaghani, Asghar

Lung transplantation has grown considerably in recent years and its availability has spread to an expanding number of countries worldwide. Importantly, survival has also steadily improved, making this an increasingly viable procedure for patients with end-stage lung disease and limited life expectancy. In this first of a series of articles, recipient selection and type of transplant operation are reviewed. Pulmonary fibrotic disorders are now the most indication in the U.S., followed by chronic obstructive pulmonary disease and cystic fibrosis. Transplant centers have liberalized criteria to include older and more critically ill candidates. A careful, systematic, multi-disciplinary selection process is critical in identifying potential barriers that may increase risk and optimize long-term outcomes. PMID:29043255

Will chronic e-cigarette use cause lung disease?

PubMed

Rowell, Temperance R; Tarran, Robert

2015-12-15

Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease. Copyright © 2015 the American Physiological Society.

Will chronic e-cigarette use cause lung disease?

PubMed Central

Rowell, Temperance R.

2015-01-01

Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease. PMID:26408554

Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects.

PubMed

Busch, Robert; Hobbs, Brian D; Zhou, Jin; Castaldi, Peter J; McGeachie, Michael J; Hardin, Megan E; Hawrylkiewicz, Iwona; Sliwinski, Pawel; Yim, Jae-Joon; Kim, Woo Jin; Kim, Deog K; Agusti, Alvar; Make, Barry J; Crapo, James D; Calverley, Peter M; Donner, Claudio F; Lomas, David A; Wouters, Emiel F; Vestbo, Jørgen; Tal-Singer, Ruth; Bakke, Per; Gulsvik, Amund; Litonjua, Augusto A; Sparrow, David; Paré, Peter D; Levy, Robert D; Rennard, Stephen I; Beaty, Terri H; Hokanson, John; Silverman, Edwin K; Cho, Michael H

2017-07-01

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 × 10 -8 ) and PPP4R4/SERPINA1 (P = 1.01 × 10 -8 ) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, ∼0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

Lymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3.

PubMed

Kelsen, Steven G; Aksoy, Mark O; Georgy, Mary; Hershman, Richard; Ji, Rong; Li, Xiuxia; Hurford, Matthew; Solomides, Charalambos; Chatila, Wissam; Kim, Victor

2009-05-01

The mechanisms underlying formation of lung lymphoid follicles (LF) in chronic obstructive pulmonary disease (COPD) are unknown. The chemokine receptor CXCR3 regulates immune responses in secondary lymphoid structures elsewhere in the body and is highly expressed by Th1 lymphocytes in the airway in COPD. Because chemokine receptors control inflammatory cell homing to inflamed tissue, we reasoned that CXCR3 may contribute to LF formation in COPD. We assessed the expression of CXCR3 and its ligands (IP-10/CXCL10, Mig/CXCL9, and ITAC/CXCL11) by LF cells in never-smokers, smokers without COPD, and subjects with COPD. CXCR3, IP-10, Mig, and ITAC expression were assessed in lung sections from 46 subjects (never-smokers, smokers without COPD [S], and subjects with COPD in GOLD stages 1-4) by immunohistochemistry. CXCR3-expressing T cells (CD8+ or CD4+) and B cells (CD20+) were topographically distributed at the follicle periphery and center, respectively. The percentage of immunohistochemically identified CXCR3+ cells increased progressively while proceeding from S through GOLD 3-4 (P < 0.01 for GOLD 3-4 vs. S). Moreover, the number of CXCR3+ follicular cells correlated inversely with FEV(1) (r = 0.60). The CXCR3 ligands IP-10 and Mig were expressed by several cell types in and around the follicle, including CD68+ dendritic cells/ macrophages, airway epithelial cells, endothelial cells, and T and B cells. These results suggest that LF form in the COPD lung by recruitment and/or retention of CXCR3-expressing T and B lymphocytes, which are attracted to the region through production of CXCR3 ligands IP-10 and Mig by lung structural and follicular cells.

Lymphoid Follicle Cells in Chronic Obstructive Pulmonary Disease Overexpress the Chemokine Receptor CXCR3

PubMed Central

Kelsen, Steven G.; Aksoy, Mark O.; Georgy, Mary; Hershman, Richard; Ji, Rong; Li, XiuXia; Hurford, Matthew; Solomides, Charalambos; Chatila, Wissam; Kim, Victor

2009-01-01

Rationale: The mechanisms underlying formation of lung lymphoid follicles (LF) in chronic obstructive pulmonary disease (COPD) are unknown. The chemokine receptor CXCR3 regulates immune responses in secondary lymphoid structures elsewhere in the body and is highly expressed by Th1 lymphocytes in the airway in COPD. Because chemokine receptors control inflammatory cell homing to inflamed tissue, we reasoned that CXCR3 may contribute to LF formation in COPD. Objectives: We assessed the expression of CXCR3 and its ligands (IP-10/CXCL10, Mig/CXCL9, and ITAC/CXCL11) by LF cells in never-smokers, smokers without COPD, and subjects with COPD. Methods: CXCR3, IP-10, Mig, and ITAC expression were assessed in lung sections from 46 subjects (never-smokers, smokers without COPD [S], and subjects with COPD in GOLD stages 1–4) by immunohistochemistry. Measurements and Main Results: CXCR3-expressing T cells (CD8+ or CD4+) and B cells (CD20+) were topographically distributed at the follicle periphery and center, respectively. The percentage of immunohistochemically identified CXCR3+ cells increased progressively while proceeding from S through GOLD 3–4 (P < 0.01 for GOLD 3–4 vs. S). Moreover, the number of CXCR3+ follicular cells correlated inversely with FEV1 (r = 0.60). The CXCR3 ligands IP-10 and Mig were expressed by several cell types in and around the follicle, including CD68+ dendritic cells/ macrophages, airway epithelial cells, endothelial cells, and T and B cells. Conclusions: These results suggest that LF form in the COPD lung by recruitment and/or retention of CXCR3-expressing T and B lymphocytes, which are attracted to the region through production of CXCR3 ligands IP-10 and Mig by lung structural and follicular cells. PMID:19218194

Stage I nonsmall cell lung cancer in patients aged > or =75 years: outcomes after stereotactic radiotherapy.

PubMed

Haasbeek, Cornelis J A; Lagerwaard, Frank J; Antonisse, Marilisa E; Slotman, Ben J; Senan, Suresh

2010-01-15

The number of patients aged > or =75 years who present with a stage I nonsmall cell lung cancer (NSCLC) is increasing. Elderly patients often have significant comorbidity and may be unfit for surgery. Furthermore, surgery in the elderly is associated with increased mortality and morbidity. In this study, the authors evaluated the outcomes of stereotactic radiotherapy (SRT) in elderly patients. Since 2003, 203 tumors in 193 patients aged > or =75 years were treated using SRT (118 T1 tumors, 85 T2 tumors). The median patient age was 79 years, 80% of patients were considered medically inoperable, and 20% of patients declined surgery. The median Charlson comorbidity score was 4, and severe chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease Class III or greater) was present in 25% of patients. Risk-adapted SRT schemes were used with the same total dose of 60 grays in 3 fractions (33%), 5 fractions (50%), or 8 fractions (17% of patients), depending on the patient's risk for toxicity. SRT was well tolerated, and all but 1 patient completed treatment. Survival rates at 1 year and 3 years were 86% and 45%, respectively. Survival was correlated with performance score (P = .001) and pre-SRT lung function (P = .04). The actuarial local control rate at 3 years was 89%. Acute toxicity was uncommon, and late Radiation Therapy Oncology Group grade > or =3 toxicity was observed in <10% of patients. SRT achieved high local control rates with minimal toxicity in patients aged > or =75 years despite their significant medical comorbidities. These results indicated that more active diagnostic and therapeutic approaches are justified in elderly patients and that SRT should be considered and discussed as a curative treatment alternative.

A Dynamic Bronchial Airway Gene Expression Signature of Chronic Obstructive Pulmonary Disease and Lung Function Impairment

PubMed Central

Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Florido, Roberta; Campbell, Joshua; Liu, Gang; Xiao, Ji; Zhang, Xiaohui; Duclos, Grant; Drizik, Eduard; Si, Huiqing; Perdomo, Catalina; Dumont, Charles; Coxson, Harvey O.; Alekseyev, Yuriy O.; Sin, Don; Pare, Peter; Hogg, James C.; McWilliams, Annette; Hiemstra, Pieter S.; Sterk, Peter J.; Timens, Wim; Chang, Jeffrey T.; Sebastiani, Paola; O’Connor, George T.; Bild, Andrea H.; Postma, Dirkje S.; Lam, Stephen

2013-01-01

Rationale: Molecular phenotyping of chronic obstructive pulmonary disease (COPD) has been impeded in part by the difficulty in obtaining lung tissue samples from individuals with impaired lung function. Objectives: We sought to determine whether COPD-associated processes are reflected in gene expression profiles of bronchial airway epithelial cells obtained by bronchoscopy. Methods: Gene expression profiling of bronchial brushings obtained from 238 current and former smokers with and without COPD was performed using Affymetrix Human Gene 1.0 ST Arrays. Measurements and Main Results: We identified 98 genes whose expression levels were associated with COPD status, FEV1% predicted, and FEV1/FVC. In silico analysis identified activating transcription factor 4 (ATF4) as a potential transcriptional regulator of genes with COPD-associated airway expression, and ATF4 overexpression in airway epithelial cells in vitro recapitulates COPD-associated gene expression changes. Genes with COPD-associated expression in the bronchial airway epithelium had similarly altered expression profiles in prior studies performed on small-airway epithelium and lung parenchyma, suggesting that transcriptomic alterations in the bronchial airway epithelium reflect molecular events found at more distal sites of disease activity. Many of the airway COPD-associated gene expression changes revert toward baseline after therapy with the inhaled corticosteroid fluticasone in independent cohorts. Conclusions: Our findings demonstrate a molecular field of injury throughout the bronchial airway of active and former smokers with COPD that may be driven in part by ATF4 and is modifiable with therapy. Bronchial airway epithelium may ultimately serve as a relatively accessible tissue in which to measure biomarkers of disease activity for guiding clinical management of COPD. PMID:23471465

Serum amyloid A opposes lipoxin A₄ to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease.

PubMed

Bozinovski, Steven; Uddin, Mohib; Vlahos, Ross; Thompson, Michelle; McQualter, Jonathan L; Merritt, Anne-Sophie; Wark, Peter A B; Hutchinson, Anastasia; Irving, Louis B; Levy, Bruce D; Anderson, Gary P

2012-01-17

Chronic obstructive pulmonary disease (COPD) will soon be the third most common cause of death globally. Despite smoking cessation, neutrophilic mucosal inflammation persistently damages the airways and fails to protect from recurrent infections. This maladaptive and excess inflammation is also refractory to glucocorticosteroids (GC). Here, we identify serum amyloid A (SAA) as a candidate mediator of GC refractory inflammation in COPD. Extrahepatic SAA was detected locally in COPD bronchoalveolar lavage fluid, which correlated with IL-8 and neutrophil elastase, consistent with neutrophil recruitment and activation. Immunohistochemistry detected SAA was in close proximity to airway epithelium, and in vitro SAA triggered release of IL-8 and other proinflammatory mediators by airway epithelial cells in an ALX/FPR2 (formyl peptide receptor 2) receptor-dependent manner. Lipoxin A(4) (LXA(4)) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA(2) 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA(4). Human lung macrophages (CD68(+)) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC(50) 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA(4) but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.

Survival benefit of lung transplantation for chronic obstructive pulmonary disease in Sweden.

PubMed

Tanash, Hanan A; Riise, Gerdt C; Ekström, Magnus P; Hansson, Lennart; Piitulainen, Eeva

2014-12-01

Lung transplantation (LTx) is a therapeutic option for patients with life-threatening chronic obstructive pulmonary disease (COPD) that is refractory to conventional therapies. The survival benefit of LTx for COPD is difficult to assess. The aim of this study was to evaluate the Swedish series of LTx performed to treat COPD and to identify differences in outcome between COPD related to severe alpha-1-antitrypsin deficiency (AATD) and COPD with normal alpha-1-antitrypsin (AAT) levels. We retrospectively reviewed the data of 342 patients (128 AATD and 214 non-AATD) receiving lung transplants for end stage COPD from 1990 through 2012. The majority (71%) of patients received a single lung transplant. The median survival time after LTx for all COPD patients was 9 years (95% confidence interval [CI]: 8 to 10). Non-AATD recipients had a shorter survival time than AATD recipients, 6 years (95% CI: 5.0 to 8.8) versus 12 years (95% CI: 9.6 to 13.5, p = 0.000). Mortality was higher among non-AATD recipients after adjusting for age, pack-years of smoking, body mass index, oxygen therapy use, exercise capacity, donor age, cytomegalovirus mismatch, and transplant type (hazard ratio 1.70, 95% CI: 1.02 to 2.82). The 5-year and 10-year survival rates for the AATD recipients were 75% and 59%, respectively, compared with 60% and 31% for the non-AATD recipients. Early deaths were mainly due to cardio/cerebrovascular accidents and sepsis, and late deaths to bronchiolitis obliterans syndrome and pulmonary infections. Survival after LTx is significantly better for patients with severe AATD and end stage COPD than for the patients with COPD related to cigarette smoking. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Curative Treatment of Stage I Non-Small-Cell Lung Cancer in Patients With Severe COPD: Stereotactic Radiotherapy Outcomes and Systematic Review

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

Palma, David, E-mail: david.palma@uwo.ca; Division of Radiation Oncology, London Regional Cancer Program, London, Ontario; Lagerwaard, Frank

2012-03-01

Objectives: Patients with severe chronic obstructive pulmonary disease (COPD) have a high risk of lung cancer and of postsurgical complications. We studied outcomes after stereotactic body radiotherapy (SBRT) in patients with severe COPD, as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and performed a systematic review of the literature on outcomes after SBRT or surgery in these patients. Methods: A single-institution cohort of 176 patients with COPD GOLD III-IV and Stage I non-small-cell lung cancer (NSCLC) treated with SBRT was evaluated. A systematic review identified studies reporting outcomes after SBRT or surgery for Stage I NSCLCmore » in patients with GOLD III-IV or a predicted postoperative forced expiratory volume in 1 second (FEV1) of {<=}40%. Results: In the single-institution cohort, median follow-up was 21 months and median overall survival (OS) was 32 months. Actuarial 3-year local control was 89%, and 1- and 3-year OS were 79% and 47%, respectively. COPD severity correlated with OS (p = 0.01). The systematic review identified four other studies (two surgical, two SBRT, n = 196 patients). SBRT studies were published more recently and included older patients than surgical studies. Mean 30-day mortality was 0% post-SBRT and 10% after surgery. Local or locoregional control was high ({>=}89%) after both treatments. Post-SBRT, actuarial OS was 79-95% at 1 year and 43-70% at 3 years. Postsurgical actuarial OS was 45-86% at 1 year and 31-66% at 3 years. Conclusions: SBRT and surgery differ in risk of 30-day mortality in patients with severe COPD. Despite the negative selection of SBRT patients, survival at 1 and 3 years is comparable between the two treatments.« less

Distinct Quantitative Computed Tomography Emphysema Patterns Are Associated with Physiology and Function in Smokers

PubMed Central

San José Estépar, Raúl; Mendoza, Carlos S.; Hersh, Craig P.; Laird, Nan; Crapo, James D.; Lynch, David A.; Silverman, Edwin K.; Washko, George R.

2013-01-01

Rationale: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. Objectives: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Methods: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Measurements and Main Results: Compared with percentage of low-attenuation area less than −950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Conclusions: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures. PMID:23980521

Impact of pulmonary rehabilitation on postoperative complications in patients with lung cancer and chronic obstructive pulmonary disease.

PubMed

Saito, Hajime; Hatakeyama, Kazutoshi; Konno, Hayato; Matsunaga, Toshiki; Shimada, Yoichi; Minamiya, Yoshihiro

2017-09-01

Given the extent of the surgical indications for pulmonary lobectomy in breathless patients, preoperative care and evaluation of pulmonary function are increasingly necessary. The aim of this study was to assess the contribution of preoperative pulmonary rehabilitation (PR) for reducing the incidence of postoperative pulmonary complications in non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD). The records of 116 patients with COPD, including 51 patients who received PR, were retrospectively analyzed. Pulmonary function testing, including slow vital capacity (VC) and forced expiratory volume in one second (FEV 1 ), was obtained preoperatively, after PR, and at one and six months postoperatively. The recovery rate of postoperative pulmonary function was standardized for functional loss associated with the different resected lung volumes. Propensity score analysis generated matched pairs of 31 patients divided into PR and non-PR groups. The PR period was 18.7 ± 12.7 days in COPD patients. Preoperative pulmonary function was significantly improved after PR (VC 5.3%, FEV 1 5.5%; P < 0.05). The FEV 1 recovery rate one month after surgery was significantly better in the PR (101.6%; P < 0.001) than in the non-PR group (93.9%). In logistic regression analysis, predicted postoperative FEV 1 , predicted postoperative %FEV 1 , and PR were independent factors related to postoperative pulmonary complications after pulmonary lobectomy (odds ratio 18.9, 16.1, and 13.9, respectively; P < 0.05). PR improved the recovery rate of pulmonary function after lobectomy in the early period, and may decrease postoperative pulmonary complications. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Expression of GULP1 in bronchial epithelium is associated with the progression of emphysema in chronic obstructive pulmonary disease.

PubMed

Datta, Sayantan; Nam, Hae-Seong; Hayashi, Masamichi; Maldonado, Leonel; Goldberg, Rachel; Brait, Mariana; Sidransky, David; Illei, Peter; Baras, Alex; Vij, Neeraj; Hoque, Mohammad O

2017-03-01

GULP1 functions as a cytoplasmic adaptor protein involved in the engulfment of apoptotic cells. The aim of this study was to investigate the expression and/or promoter methylation of GULP1 in the bronchial tissue and the lung parenchyma of chronic obstructive pulmonary disease (COPD) patients and control subjects without COPD (non-smokers and smokers). Using a case-control design, we selected a group of 15 subjects with non-small cell lung carcinoma (NSCLC), 15 subjects with COPD, 9 subjects of without COPD (4 non-smokers and 5 smokers) as controls. We studied the expression of GULP1 in the bronchial tissue and the lung parenchyma by means of immunohistochemistry (IHC). To understand the mechanistic aspect of GULP1 expression in COPD and NSCLC, we performed quantitative methylation specific PCR (QMSP) in cases and controls of COPD and NSCLC. Our IHC analysis revealed that GULP1 was not expressed in pneumocytes or alveolar macrophages of COPD patients, however, GULP1 expression was detected at different levels in bronchial epithelium. GULP1 expression statistically correlated with severity of COPD-emphysema (p = 0.001, χ 2 test). GULP1 promoter methylation was not observed by QMSP assay in any of the samples thereby excluding the role of promoter methylation in differential expression of GULP1 in COPD and NSCLC. This study provides preliminary observations on the differences in GULP1 expression in different cellular components of lung tissues from COPD and control subjects. Our findings suggest a potential role for GULP1 in the pathogenesis and progression of COPD-emphysema that warrants further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin–lysoPA axis in COPD

PubMed Central

Naz, Shama; Kolmert, Johan; Yang, Mingxing; Reinke, Stacey N.; Kamleh, Muhammad Anas; Snowden, Stuart; Heyder, Tina; Levänen, Bettina; Erle, David J.; Sköld, C. Magnus; Wheelock, Åsa M.; Wheelock, Craig E.

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD. Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform. Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung. These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence. PMID:28642310

Chronic Respiratory Symptoms and Lung Function in Agricultural Workers - Influence of Exposure Duration and Smoking.

PubMed

Stoleski, Saso; Minov, Jordan; Mijakoski, Dragan; Karadzinska-Bislimovska, Jovanka

2015-03-15

Job exposure in agricultural workers often leads to respiratory impairment. To assess the influence of exposure duration and smoking on chronic respiratory symptoms and ventilatory capacity in agricultural workers. A cross-sectional study covered 75 agricultural workers, compared with an equal number of office workers matched by age, exposure duration and smoking status. Standardized questionnaire was used to obtain data on chronic respiratory symptoms, job and smoking history. Lung functional testing was performed by spirometry. The prevalence of respiratory symptoms was higher in agricultural workers, with significant difference for cough (P = 0.034), and dyspnea (P = 0.028). Chronic respiratory symptoms among agricultural workers were significantly associated with duration of exposure (P < 0.05) and daily smoking (P < 0.01), as well as with daily smoking in controls (P < 0.01). The average values of spirometric parameters in exposed workers were significantly different for MEF50 (P = 0.002), MEF75 (P = 0.000), and MEF25-75 (P = 0.049). Obstructive changes in small airways in exposed workers were strongly related to exposure duration (P < 0.05) and smoking (P < 0.01). Agricultural workers with job exposure more than 15 years had more expressed adverse respiratory symptoms and lung function decline. The results confirmed the influence of agricultural exposure and daily smoking on chronic respiratory symptoms and airflow limitation, primarily targeting the small airways.

Office-based spirometry for early detection of obstructive lung disease.

PubMed

Wallace, Laura D; Troy, Kenneth E

2006-09-01

To review the research-based evidence supporting smoking cessation as the only proven method to reduce chronic obstructive pulmonary disease (COPD) progression and to show that early detection of disease with office-based spirometry can lead to therapeutic intervention before physiologic symptoms arise. Extensive review of national and international scientific literature supplemented with drawings and algorithms. Early detection of COPD with spirometry, along with smoking cessation, and aggressive intervention can alter the insidious course of this highly preventable disease. It is imperative that nurse practitioners utilize this simple and inexpensive procedure to identify COPD in its earliest stages, so treatment can reduce individual and community disease burden, reduce morbidity and mortality, and help reduce healthcare costs. Determination of early airflow obstruction supports smoking cessation education, provides objective data for patient motivation, thereby doubling patient compliance and reducing further disease burden.

Clinical use of Heliox in asthma and COPD.

PubMed

Valli, G; Paoletti, P; Savi, D; Martolini, D; Palange, P

2007-09-01

Heliox is a low density gas mixture of helium and oxygen commonly used in deep diving (> 6 ATM). This mixture has been also used for clinical purposes, particularly in the critical care setting. Due to of its physical proprieties, Heliox breathing reduces air flow resistances within the bronchial tree; in patients with obstructive lung diseases Heliox may also reduce the work of breathing and improve pulmonary gas exchange efficiency. Beneficial effects have been documented in severe asthma attacks and in patients with chronic obstructive pulmonary disease. A reduction in WOB during mechanical ventilation and an increase in exercise endurance capacity have also been described in COPD. Heliox has been also used in the treatment of upper airways obstruction, bronchiolitis and bronchopulmonary dysplasia. Despite the encouraging results, Heliox use in routine practice remains controversial because of technical implications and high costs.