Chest
Special FeaturesClinical Epidemiology of COPD: Insights From 10 Years of the COPDGene Study
Section snippets
Genetic Findings in COPDGene
Identifying genetic determinants of COPD has been a major goal of the COPDGene study since its inception. Most genetic studies in COPDGene thus far have been based on genome-wide panels of hundreds of thousands of common genetic variants (known as single nucleotide polymorphisms), which have been tested in genome-wide association studies (GWAS) with the presence/absence of COPD and with multiple COPD-related phenotypes, including imaging features, clinical characteristics, COPD subtypes, and
Chronic Bronchitis
The importance of CB is frequently overlooked, particularly among patients with milder disease and those without airflow obstruction. CB is present in about one-quarter of the COPDGene participants with COPD and is associated with heightened exacerbation risk, worse health status, more dyspnea, and reduced 6-min walk distance compared with those without CB.6, 7, 8 In COPDGene, historical exacerbation rates were nearly twice as high in those with CB as in those without CB. St. George’s
Asthma/COPD Overlap
The heterogeneity of COPD and new therapies for asthma have resulted in a renewed interest in ACO. This patient population has been difficult to study because such patients are often excluded from both COPD and asthma studies. In COPDGene, the major inclusion criterion was a history of cigarette smoking, and subjects with a history of asthma were not excluded nor were they targeted for inclusion.1
Hardin et al12 identified 915 subjects with a COPD spirometric Global Initiative for Chronic
Impact of Sex, Race, and Age
Data from COPDGene describe the important sex and racial differences in the phenotypic expression of COPD. These differences translate into higher risk of disease severity, particularly in women. For example, patients with severe COPD (FEV1 < 50% predicted) diagnosed at an early age (< 55 years) revealed female predominance (66%) and association with maternal smoking and maternal COPD (Fig 1).16 It was also noted that the airways of female subjects who smoke exhibit higher wall area percentage
COPD Exacerbations
COPDGene used subject self-report to identify exacerbations in the 12 months prior to enrollment.1 Subsequent exacerbations during longitudinal follow-up were assessed by using automated telephone calls every 3 to 6 months.27 COPDGene evaluated exacerbations in relation to demographic characteristics, radiographic abnormalities, lung function, and biomarkers.
Although a previous study reported that exacerbations are associated with accelerated lung function decline, this study included subjects
Comorbidities
The extensive collection of data regarding comorbidities and medication exposure during the recruitment phase of COPDGene and the longitudinal design served as an ideal platform for evaluating the impact of coexisting diseases on patients with COPD and different degrees of severity. A self-reported list of current medications was obtained and comorbid conditions were ascertained based on subject recall of a physician diagnosis except for obesity, which was based on BMI and imaging.1
A study
Implications for Disease Classification and Treatment
The GOLD statement currently categorizes COPD based on lung function, the history of exacerbations, and respiratory symptoms.46 Although this classification has been widely accepted, evidence suggests that there are many different phenotypes of COPD beyond these three patient characteristics. COPDGene has provided further insights regarding the risk of specific outcomes (Fig 5). Some predictors are nonmodifiable, such as age, race, and sex, and the presence of CB and ACO. Others may be
Limitations
COPDGene has several limitations that deserve mention. First, several of the variables, such as previous exacerbations and comorbid conditions, were based on self-report and may be subject to recall bias or physician misdiagnosis; particularly in the setting of asthma, the diagnosis can be subject to misclassification. Second, the study is limited by the loss of some subjects during the follow-up time. This loss is common in longitudinal observational studies but may bias the estimations caused
Future Directions and Research Needs
COPDGene is ongoing, and phase III, recently funded by the NHLBI, will invite subjects to return for a third visit 10 years following their initial enrollment. The longitudinal evaluation of this richly characterized cohort will continue to provide additional information regarding the natural history of the disease and implications of subject characteristics on various outcomes. Because the subjects were assessed in a multidimensional fashion, demographic characteristics, symptom scores,
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: D. J. M. reports consulting fees for GlaxoSmithKline, Sunovion, Sanofi/Regeneron, AstraZeneca, and Novartis. A. A. reports consultancy for Boehringer Ingelheim, AstraZeneca, Novartis, and Sunovion. S. P. B. is supported by the National Institutes of Health (NIH) [K23HL133438] and has received research grants from AstraZeneca and ProterixBio. R. P. B. reports consulting fees for Boehringer Ingelheim,
References (46)
- et al.
The chronic bronchitic phenotype of COPD: an analysis of the COPDGene study
Chest
(2011) - et al.
The clinical impact of non-obstructive chronic bronchitis in current and former smokers
Respir Med
(2014) - et al.
Asthma is a risk factor for respiratory exacerbations without increased rate of lung function decline: five-year follow-up in adult smokers from the COPDGene study
Chest
(2018) - et al.
Prediction of acute respiratory disease in current and former smokers with and without COPD
Chest
(2014) - et al.
Racial differences in quality of life in patients with COPD
Chest
(2011) - et al.
examining the effects of age on health outcomes of chronic obstructive pulmonary disease: results from the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study and evaluation of chronic obstructive pulmonary disease longitudinally to identify predictive surrogate endpoints cohorts
J Am Med Dir Assoc
(2017) - et al.
Obesity is associated with increased morbidity in moderate to severe COPD
Chest
(2017) - et al.
Genetic epidemiology of COPD (COPDGene) study design
COPD
(2010) - et al.
Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE)
Eur Respir J
(2008) - et al.
Design of the subpopulations and intermediate outcomes in COPD study (SPIROMICS)
Thorax
(2014)
Opportunities and challenges in the genetics of COPD 2010: an International COPD Genetics Conference report
COPD
Alpha-1 antitrypsin PiMZ genotype is associated with chronic obstructive pulmonary disease in two racial groups
Ann Am Thorac Soc
Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study
Respir Res
Persistent and newly developed chronic bronchitis are associated with worse outcomes in chronic obstructive pulmonary disease
Ann Am Thorac Soc
Epidemiology standardization project (American Thoracic Society)
Am Rev Respir Dis
Comparison between an alternative and the classic definition of chronic bronchitis in COPDGene
Ann Am Thorac Soc
The clinical features of the overlap between COPD and asthma
Respir Res
The clinical and genetic features of COPD-asthma overlap syndrome
Eur Respir J
Analysis of asthma-chronic obstructive pulmonary disease overlap syndrome defined on the basis of bronchodilator response and degree of emphysema
Ann Am Thorac Soc
Early-onset chronic obstructive pulmonary disease is associated with female sex, maternal factors, and African American race in the COPDGene study
Am J Respir Crit Care Med
Gender differences of airway dimensions in anatomically matched sites on CT in smokers
COPD
Risk factors for COPD exacerbations in inhaled medication users: the COPDGene study biannual longitudinal follow-up prospective cohort
BMC Pulm Med
Gender differences in COPD: are women more susceptible to smoking effects than men?
Thorax
Cited by (59)
A Commentary on Multi-omics Data Integration in Systems Vaccinology
2024, Journal of Molecular BiologyLung repair and regeneration: Advanced models and insights into human disease
2024, Cell Stem CellEpigenetic hallmarks in pulmonary fibrosis: New advances and perspectives
2023, Cellular SignallingTobacco Use and Tobacco Dependence Management
2023, Clinics in Chest MedicineAssociation Among Chronic Obstructive Pulmonary Disease Severity, Exacerbation Risk, and Anxiety and Depression Symptoms in the SPIROMICS Cohort
2023, Journal of the Academy of Consultation-Liaison PsychiatryCitation Excerpt :High symptom burden and elevated exacerbation risk may have a synergistic effect contributing to the increased odds of anxiety and depression in group D. COPDGene, another cohort study that enrolled smokers with and without COPD, has been publishing findings on COPD phenotypes and susceptibility genes since 2009.34 In a 2019 cross-sectional analysis of the COPDGene cohort, Iyer et al. analyzed 5331 subjects to determine the prevalence of anxiety and depressive symptoms among the GOLD groups and the characteristics associated with psychiatric symptoms in unmedicated subjects.18
Intravenous Iron Replacement Improves Exercise Tolerance in COPD: A Single-Blind Randomized Trial
2022, Archivos de BronconeumologiaCitation Excerpt :Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality worldwide.1,2 COPD is associated with various comorbidities such as cardiovascular disease, cachexia, osteoporosis, metabolic syndrome, depression, pulmonary hypertension, lung cancer, and anaemia.1–3 These comorbidities influence mortality and hospitalizations independently, so should be treated appropriately.2,4
FUNDING/SUPPORT: This research was supported by the National Heart, Lung, and Blood Institute [Grants U01 HL089897 and U01 HL089856]. The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee composed of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Sunovion.