Risk Of COPD Research Articles

S4 Occupational asthma; is this the cause of excess respiratory symptoms and COPD described in bitumen exposed workers?

IntroductionEpidemiological studies suggest increased risk of asthma and COPD in asphalt exposed workers.1 Bitumen is used in this industry. In this case we describe occupational asthma caused by bitumen exposure...

Espirometría como método de cribado y de intervención antitabaco en fumadores de alto riesgo en atención primaria

ObjectiveTo show the effectiveness of screening in the detection of new cases of COPD in smokers of high-risk, and to describe the characteristics associated with COPD, as well as determine the predisposition to quit. DesignA cross-sectional and multicentre study. LocationBasic Primary Care Centres representing different rural and urban areas of Lleida. ParticipantsA total of 497 active smokers without COPD from 40 to 70 years selected from the database Primary Care Database (e-CAP). InterventionSpirometry was performed on all patients. The spirometry results were reported and brief counselling was given on quitting smoking and the readiness to stop smoking was determined. VariablesAge, gender, height, weight, smoking, respiratory symptoms and physical activity. ResultsThe majority of patients (65.4%) were men, age 51± 7.6 years. They smoked an average of 32 packs/year; 40.4% performed moderate activity and 27.4% referred to some respiratory symptoms. Of the 25% who had an obstructive or mixed pattern, 75.8% of the cases had a moderate level of severity. A decision to quit was made by 38.8%.In the multivariate analysis, gender, age 50 to 59 years and a smoking index>40 were associated with COPD. Moderate or intense physical activity decreased the risk of COPD. ConclusionsTo perform spirometry in high-risk smokers, to show the spirometry results and give brief anti-smoking counselling, enables not previously diagnosed cases of COPD to be detected. It also helps to determine the readiness to stop smoking and to establish individualised treatment and follow-up plans.

Prevalence of chronic obstructive pulmonary disease in rural women of Tamilnadu: implications for refining disease burden assessments attributable to household biomass combustion

BackgroundChronic obstructive11This paper was orally presented in the Annual conference International Society of Environmental Epidemiology held in Pasadena in 2008. pulmonary disease (COPD) is the 13th leading cause of burden of disease worldwide and is expected to become 5th by 2020. Biomass fuel combustion significantly contributes to COPD, although smoking is recognized as the most important risk factor. Rural women in developing countries bear the largest share of this burden resulting from chronic exposures to biomass fuel smoke. Although there is considerable strength of evidence for the association between COPD and biomass smoke exposure, limited information is available on the background prevalence of COPD in these populations.ObjectiveThis study was conducted to estimate the prevalence of COPD and its associated factors among non-smoking rural women in Tiruvallur district of Tamilnadu in Southern India.DesignThis cross-sectional study was conducted among 900 non-smoking women aged above 30 years, from 45 rural villages of Tiruvallur district of Tamilnadu in Southern India in the period between January and May 2007. COPD assessments were done using a combination of clinical examination and spirometry. Logistic regression analysis was performed to examine the association between COPD and use of biomass for cooking. R software was used for statistical analysis.ResultsThe overall prevalence of COPD in this study was found to be 2.44% (95% CI: 1.43–3.45). COPD prevalence was higher in biomass fuel users than the clean fuel users 2.5 vs. 2%, (OR: 1.24; 95% CI: 0.36–6.64) and it was two times higher (3%) in women who spend >2 hours/day in the kitchen involved in cooking. Use of solid fuel was associated with higher risk for COPD, although no statistically significant results were obtained in this study.ConclusionThe estimates generated in this study will contribute significantly to the growing database of available information on COPD prevalence in rural women. Moreover, with concomitant indoor air pollution measurements, it may be possible to increase the resolution of the association between biomass use and COPD prevalence and refine available attributable burden of disease estimates.

Cross-sectional survey of respiratory symptoms and exposures in Scottish health service cleaners

ObjectivesHealth service cleaners play a key role in safeguarding patients' health. Limited research has been done on cleaners' workplace exposures and respiratory health. This study assessed the risk of asthma...

Lifetime risk of COPD: what will the future bring?

Lifetime risk of COPD: what will the future bring?

COPD in the general population: Prevalence, incidence and survival

Worldwide, COPD is a leading cause of chronic morbidity and mortality. Although its prevalence is already well documented, very few studies have measured its incidence. We therefore investigated the prevalence, incidence and lifetime risk of COPD in the general population. In a population-based study including subjects ≥ 40, with 12 months of history available in the Dutch IPCI database, we identified COPD cases by a two-step validation algorithm. Among 185,325 participants with 601,283 years of follow-up, 7308 subjects with COPD were identified, and 1713 had incident COPD. The overall IR of physician-diagnosed COPD was 2.92/1000PY (95%CI 2.78-3.06). The incidence of COPD was higher in men (3.54; 95%CI 3.33-3.77) than in women (2.34; 95%CI 2.17-2.52), and the overall baseline prevalence of COPD was 3.02% (95%CI 2.94-3.10). For people who had entered the study free of COPD at the age of 40, the risk of developing COPD within the next 40 years was 12.7% for men and 8.3% for women. In patients with very severe COPD, 26% died after 1 year of follow-up, whereas 2.8% died among the non-COPD subjects. In the general population in the Netherlands, three on 1000 subjects were diagnosed with COPD per year. The incidence increased rapidly with age and was higher in men than in women. One in eight men and one in 12 women, being COPD free at the age of 40, will develop COPD during their further life. Mortality rates differed substantially between COPD patients and non-COPD subjects of the same age, underlining the burden of this disease.

POLYMORPHISM IN INTERLEUKIN-4 GENE AND THE RISK OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN A NORTH INDIAN POPULATION : A CASE-CONTROL STUDY

The genetic variability (polymorphisms) can be a factor in COPD risk. We investigated the potential relationship between COPD and polymorphism of the interleukin 4 (IL-4 70 bp repeats) gene. In our study we observed the association between IL-4 (70 bp repeats) genotypes and COPD risk. A total of 400 subjects (200 cases and 200 controls). Using a case control design individuals were genotyped for IL- 4 using polymerase chain reaction (PCR) and restriction fragment length polymorphism techniques. The data obtained were analyzed using multiple logistic regressions by the help of SPSS ver 11.5. The OR of combined genotype of IL-4(Rp1-Rp2+Rp1) was showed 2 fold increase risk of COPD. In smokers, 5 fold significantly increased risk of COPD was observed with Rp1 genotype of IL-4. The genetic polymorphism in cytokine and IL-4 (70 bp repeats) gene may play an important role in the development of COPD.

Determinants of Spirometry Use and Accuracy of COPD Diagnosis in Primary Care

It is unclear if primary care physicians are following guidelines or using other patient characteristics and factors to determine when to perform spirometry in patients at risk for COPD. It is also unclear to what degree a diagnosis of COPD is accurately reflected by spirometry results. To examine characteristics associated with use of spirometry in primary care for patients with increased risk for COPD and to determine the accuracy of COPD diagnosis in patients with spirometry. Retrospective cohort study. A cohort that met the following criteria was identified: ≥35years of age; ≥ 2 primary care visits in internal medicine clinic in 2007; at least one respiratory or smoking cessation medication, or diagnosis of COPD or shortness of breath or dyspnea in 2007. Medical records of all primary care physician visits prior to the time of inclusion in 2007 were reviewed. Data on patient demographics, co-morbidities, respiratory medication use, presence of symptoms, history of tobacco use, and pulmonary function tests were extracted. A total 1052 patients were identified. Dyspnea on exertion (Adjusted odds ratio (AOR) 1.52 [95% CI 1.06-2.18]) and chronic cough (AOR 1.71 [1.07-2.72]) were the only chronic symptoms associated with use of spirometry. Current (AOR 1.54 [0.99-2.40]) or past smoking (AOR 1.09 [0.72-1.65]) status were not associated with use of spirometry. Of the 159 patients with a diagnosis of COPD, 93 (58.5%) met GOLD criteria and 81(50.9%) met lower limit of normal (LLN) criteria for COPD. Clinicians use spirometry more often among patients with symptoms suggestive of COPD but not more often among patients with current or past tobacco use. For patients who had a spirometry and a diagnosis of COPD, primary care physicians were accurate in their diagnosis only half of the time.

Examining Web Equivalence and Risk Factor Sensitivity of the COPD Population Screener

Objectives The primary aim was to assess the equivalence of an Internet-based chronic obstructive pulmonary disease–population screener (COPD-PS) relative to a validated paper-and-pencil version. A secondary aim was to compare groups based on known COPD risk factors, such as smoking status and gender. Methods Using an online panel survey organization, participants were randomized to internet or paper-and-pencil assessment where they completed the COPD-PS and other study forms. A subset of respondents also completed a test-retest reliability assessment. Finally, several thousand additional online respondents completed the COPD-PS for risk factor analyses. Results A total of 1006 adults completed the randomized study (N = 504 online, N = 502 by mail). There were no differences between the arms in mean COPD-PS scores (mean difference: 0.12; 95% confidence interval: −0.14–+0.37; P = 0.365). In the web arm, 106/504 (21.0%) exceeded the screening cut-off compared to 101/502 (20.1%) in the paper-administration arm (difference in proportions: 0.9%; 95% confidence interval: −4.1%–+5.9%; P = 0.720). Subgroup analyses on a separate cohort of 3001 adults demonstrated hypothesized differences between groups defined by smoking status, presence of COPD, and shortness of breath. Conclusion The methods of administration that were evaluated in this study (internet vs. paper and pencil) resulted in no significant differences in COPD-PS mean scores. Furthermore, the predictive utility of the COPD-PS was not different between methods of administration, even after accounting for age and smoking status.

Increased platelet activation in patients with stable and acute exacerbation of COPD

RationaleChronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and cardiovascular disease. Interaction between inflammatory cells and activated platelets is important in the pathogenesis of atherothrombosis and may contribute...

Abstract LB-449: The relationship between CHRNA5 gene polymorphism and the strength of nicotine addiction in lung cancer, COPD and healthy smokers

Abstract Introduction. A rare variant of chromosomal region 15q25.1, marked by rs16969968 (substitution 1354G>A or D398N in CHRNA5 gene), was found to be associated with increased lung cancer risk and nicotine dependence appearance. We attempted to confirm the relationship between polymorphism of gene for nicotine acetylocholine receptor A subunit 5 (CHRNA5) and stage of nicotine dependence measured by the result of Fagerström test and cotinine level in serum in lung cancer, COPD and healthy smokers. Methods. Polymorphism of CHRNA5 gene was analised using PCR-RFLP method in the group of 97 lung cancer patients, 99 COPD patients and 98 healthy volunteers. The Fagerström Test for Nicotine Dependence was used as a standard instrument for assessing the intensity of this physical addiction. Cotinine serum level was measured using ELISA method. Results. In all analyzed subjects, the frequency of AA, AG and GG genotypes were 11%, 47% and 42%, respectively. The polymorphism of CHRNA5 gene does not have a significant influence on the elevated risk of lung cancer and COPD. The presence of GG genotype decreased the risk of strength of nicotine addiction (HR=0.238, 95%CI:[0.066–0.857], p<0.05). We observed that allele A was presented more frequently in the subjects with high level of nicotine dependence and in the subjects with early (<25 years) onset of addiction (p<0.05). Moreover, cotinine serum level significantly correlated with results of Fagerström test (p<0.001). The carriers of allele A expressed significantly higher level of serum cotinine when compared with the carriers of GG genotype (p=0.05). Conclusion. In the presented abstract we report for the first time the relationship between the polymorphism of CHRNA5 gene and the strength of nicotine addiction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-449. doi:10.1158/1538-7445.AM2011-LB-449

COPD in Never Smokers: Results From the Population-Based Burden of Obstructive Lung Disease Study

Background:Never smokers comprise a substantial proportion of patients with COPD. Their characteristics and possible risk factors in this population are not yet well defined.Methods:We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study. Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines. In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.Results:Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD. Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD. This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio. Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.Conclusion:This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD. Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers.

Ocena Stanu Odżywienia u Chorych na Przewlekłą Obturacyjną Chorobę Płuc (POChP) Oraz Wpływ Diety na Ryzyko jej Wystąpienia

It is estimated that in patients with COPD malnutrition affects 10-15% of patients with mild to moderate stage of disease and 50% of patients with advanced stage of disease. Available studies indicate that weight loss and muscle mass loss are negative prognostic indicators, therefore early diagnosis of malnutrition seems to be a key measure in the treatment of COPD. In the article the authors discuss and compare the most commonly used methods to assess nutritional status and provide information on the impact of diet on risk of COPD in the future. Nutritional status of patients with COPD is difficult to assess. To date, no published standards are available. Reliable and accurate assessment of nutritional status is essential for planning further care and may contribute to the improvement of nutritional status and contribute positively to the course of the disease.

Association between the tumour necrosis factor‐α−308G/A polymorphism and chronic obstructive pulmonary disease: An update

Previous studies have suggested that the -308A allele in the tumour necrosis factor-α (TNF-α) gene promoter (rs1800629) may be a potential risk factor for COPD. However, more recent findings have been inconsistent. In the present study, a meta-analysis was performed to assess the association between the TNF-α-308G/A single nucleotide polymorphism (SNP) and the risk of COPD. Published studies were retrieved from PubMed, EMBASE and other databases. All studies assessing the association between the TNF-α-308G/A SNP and the risk of COPD were assessed. Pooled ORs with 95% CIs were calculated. In the 36 studies that met the inclusion criteria, 4975 patients and 6518 control subjects had been genotyped. The overall results showed that the association between the TNF-α-308G/A SNP and the risk of COPD was statistically significant for Asians (OR = 2.36, 95% CI: 1.84-3.02, P < 0.0001) but not for Caucasians (OR = 1.07, 95% CI: 0.91-1.25, P = 0.438). As smoking is one of the most important risk factors for COPD, a second meta-analysis that included only smokers (3018 patients and 2749 control subjects) was performed. This analysis confirmed that the association between the TNF-α-308G/A SNP and COPD was statistically significant for Asians (OR = 1.72, 95% CI: 1.14-2.61, P = 0.011) but not for Caucasians (OR = 1.16, 95% CI: 0.86-1.56, P = 0.33). This meta-analysis suggests that the TNF-α-308A genotype is associated with an increased risk of COPD in Asian but not Caucasian populations. Further studies are necessary to evaluate the relationship between TNF-α polymorphisms and the risk of COPD.

Hospitalization Rates and Survival Associated with COPD: A Nationwide Danish Cohort Study

We examined rates of first hospitalization for COPD, rates of 5-year mortality among patients hospitalized for COPD, and comparisons of mortality between COPD patients and a matched cohort free of COPD. We computed standardized rates of first COPD hospitalization. Using Cox regression, we compared 180- and 181-day to 5-year mortality among COPD patients with the comparison cohort. We used medical databases in Denmark (population 5.4million) from 1997 to 2006. We included patients 40years or older with first hospitalization for COPD (64,499) and an age- and gender-matched comparison cohort of persons without COPD hospitalization (322,495). We examined the incidence of COPD hospitalization and risks and rates of mortality in the 5years after hospitalization. Standardized rates of first hospitalization for COPD declined from 276 per 100,000 person-years in 1999 to 231 per 100,000 person-years in 2006. Within 180days of hospitalization, 16% of COPD patients and 2.4% of persons in the matched cohort died (adjusted hazard ratio=7.00, 95% CI=6.79-7.22). Between 181days and 5years, 46% of COPD patients who survived the first 180days and 19% of persons in the comparison cohort died (adjusted hazard ratio=2.91, 95% CI=2.86-2.95). COPD and comorbid diseases interacted to increase mortality in the first 180days, but not thereafter. COPD continues to be a major public health problem causing substantial mortality in the 5years after hospitalization, particularly in the first 180days and in patients with comorbid diseases.

Abstract B31: Gene-based lung cancer risk test (Respiragene), identifies high-risk smokers for early detection of lung cancer

Abstract Lung cancer results from the combined effects of smoking and genetic susceptibility. Recent studies show that between 50-90% of lung cancer cases have preexisting COPD and reduced FEV1 has been shown to be the single most important risk factor for lung cancer among smokers. Given the heritability for COPD and lung cancer is 40-75% and 15-25% respectively, it is clear genes conferring risk of COPD also underlies lung cancer susceptibility. In a study of 930 subjects, we have developed a gene-based lung cancer susceptibility model that combines genetic markers (SNPs) associated with COPD and lung cancer, with non-genetic variables (age and family history), to derive a score that helps to distinguish those smokers (and ex-smokers) at greatest risk of lung cancer. The panel includes SNPs validated in candidate and GWAS studies. In a prospective study of 1212 smokers we identified 52 new lung cancers and show their lung cancer scores are very similar to that of the original lung cancer cases (n=446). In a 2nd cross-sectional study of 606 lung cancer cases from the United Kingdom, the lung cancer score was also similarly distributed and showed similar performance in an ROC analysis. In a CT study of 25 lung cancer detected through CT screening in Spain, a similar high score was shown. Current CT screening programs for lung cancer generally target smokers over 50 years with a minimum 20 pack year history and achieve pick up rates of 1%. Using our gene-based model, where age, family history, COPD and genetic variants are combined, lung cancer detection rates maybe even higher. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B31.

Abstract B30: Susceptibility loci for lung cancer: Are COPD genes the missing link?

Abstract Epidemiological studies show COPD, characterized by reduced FEV1, is the most important independent risk factor for susceptibility to lung cancer. When spirometry is routinely measured, co-existing COPD is found in 50-80% of lung cancer cases compared to only 15-20% of randomly selected matched smokers. Recent GWA studies have identified a number of susceptibility loci for COPD, lung function and lung cancer. Several of these loci overlap suggesting that the gene conferring susceptibility to lung cancer might include COPD-related genes. In this case control study of Caucasian smokers matched for smoking exposure with COPD (n=458), lung cancer (N=454) and healthy smoker status (n=488) we compared the genotype frequencies of 12 loci on chromosomes 1q23, 4q22-24, 4q31, 5p15, 5q33, 6p21, 6q24 and 15q25. All subjects underwent spirometry, completed a modified ATS respiratory questionnaire and gave blood for DNA. Genotyping was done using Taqman real-time PCR (ABI 7900). We found (1) the AA genotype of CHRNA3/5 (previously associated with lung cancer) conferred susceptibility to lung cancer (OR=1.76, P=0.005) and COPD (OR-1.47, P=0.06), (2) the GG genotype of HHIP (previously associated with reduced risk of COPD) conferred protection from COPD (OR=0.59, P=0.006) and lung cancer (OR=0.70, P=0.05) and the CC genotype of FAM13A (previously associated with reduced risk of COPD) conferred protection from COPD (OR=0.71, P=0.02) and lung cancer (OR=0.64, P=0.003). These overlapping effects in lung cancer were independent of co-existing COPD. We conclude the genes conferring susceptibility to lung cancer overlap with those of COPD. Such an observation requires healthy smokers with normal lung function to be used as controls to best identify these COPD-related genes affecting the susceptibility of smokers to lung cancer. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B30.

α;1-Antitrypsin Protease Inhibitor MZ Heterozygosity Is Associated With Airflow Obstruction in Two Large Cohorts

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

COPD Screening in General Practice Using a Telephone Questionnaire

ABSTRACTChronic obstructive pulmonary disease (COPD) is a growing health problem, and an underestimated and underdiagnosed disease in primary care. The aim of this survey was to study the feasibility of detecting undiagnosed COPD patients in the general practice population with the aid of a telephone questionnaire. The study was held in 2 general practices in the Netherlands. During 2 weeks, all patients registered with these 2 practices and aged between 40 and 75 years were contacted through a call center. Persons known with a previous history or diagnosis of COPD or asthma or comorbidity were excluded from the telephone list. The telephone interview used the Respiratory Health Screening Questionnaire (DB Price, 2006). Based on the score on this instrument, respondents were classified as having a low, moderate or high risk of having COPD. Smoking behaviour and BMI were also recorded. Patients with medium and high risk for COPD were invited for spirometry, performed by 2 experienced registered nurses. The results of the telephone interview and spirometric findings were assessed by the attending GP, who established the final diagnosis. The call center reached 1032 persons, 813 of whom answered the questions. The percentage of smokers was 49.2%, with an average number of pack-years of 17.9 (SD = 17); mean BMI was 26.1. Spirometry and analysis by the GP showed that 15.7% of the medium-risk group had previously undiagnosed COPD, versus 39.6% of the high-risk group. The number of undiagnosed COPD patients in the general practice population is considerable. Case finding can focus on moderate- and high-risk groups after telephone risk assessment.

Chronic obstructive pulmonary disease in the absence of chronic bronchitis in China

COPD has a variable natural history and not all individuals follow the same course. The aim of this study was to assess the prevalence of COPD in the absence of chronic bronchitis (CB) based on a population survey in China, and to identify the determinants of CB in patients with COPD. A multi-stage cluster sampling strategy was used to survey a population from seven different provinces/cities of China. All residents over 40 years of age were interviewed using a standardized questionnaire and spirometry was measured. A post-bronchodilator FEV(1)/FVC < 70% was defined as the diagnostic criterion for COPD. All COPD patients who were screened were divided into two groups according to the presence or absence of CB. Of the population of 20,245 that was surveyed, 70% of the 1668 patients who were diagnosed with COPD reported no history of CB. The ages, BMI and comorbidities of COPD patients with or without CB were similar. Male gender, residence in a rural area, having a lower level of education, exposure to tobacco smoke or biomass fuels, poor ventilation in the kitchen and a family history of respiratory disease were all associated with a higher risk of COPD with CB. Patients without CB had less difficulty in walking and higher FEV(1)/FVC values than patients with CB, but were more likely to be underdiagnosed. The strongest predictors of CB were male gender, current smoking and severity of dyspnoea. This survey confirmed that there is a high prevalence of COPD in the absence of CB in China. It appears that CB is not essential to the diagnosis of COPD.