KEYSTONE, COLO. – Chronic bronchitis and gender might provide more clinically meaningful clues to phenotyping patients with chronic obstructive pulmonary disease than does lung function, recent findings from the COPDGene study suggest.
"There are a lot of important features of COPD that we don’t capture by FEV1 [forced expiratory volume in 1 second], and we need additional clinical features and radiographic information so we can tailor our therapies even more in the future," COPDGene investigator Dr. Barry J. Make said at a meeting on allergy and respiratory diseases.
Researchers with the ongoing COPD genetic epidemiology study used the ATS (American Thoracic Society) questionnaire to identify chronic bronchitis in 1,061 patients with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 2-4 COPD. In all, 290 patients had chronic bronchitis, defined as cough and sputum for at least 3 months/year for at least 2 consecutive years, and 771 did not have chronic bronchitis.
The researchers found that chronic bronchitis is a predictor of future COPD exacerbations, said Dr. Make, codirector of the COPD program and medical director of respiratory care services at Denver’s National Jewish Health, which sponsored the meeting. The chronic bronchitis–positive group had 1.21 exacerbations/patient per year, compared with 0.63 exacerbations/patient per year in the chronic bronchitis–negative group (P less than .027). In addition, more patients in the chronic bronchitis–positive group reported severe exacerbations (26.6% vs. 20%; P = .024).
"We’re concerned about exacerbations, because if you’re hospitalized with an exacerbation of COPD, your mortality within the first year after you get out of the hospital is 20%," he said.
COPD patients with chronic bronchitis were younger, smoked more, were more often current smokers, and had more wheezing and nocturnal awakenings caused by cough and dyspnea. Dr. Make pointed out that the ATS questionnaire is validated to check for cough and sputum, but also emphasized the importance of using CT in assessing patients with COPD.
Notably, patients who have chronic bronchitis have thicker airways on chest CT, compared with the chronic bronchitis–negative group, as indicated by a higher mean segmental wall area percentage (63.2% vs. 62.6%; P = .013). Their percent gas trapping and lung emphysema were similar (Chest 2011;140:626-33).
A second COPDGene study in 1,002 COPD patients reported that each 1-mm increase in bronchial wall thickness on quantitative CT is associated with a 1.84-fold increase in annual COPD exacerbations after multivariate analysis that adjusted for lung function, Dr. Make said. The analysis also found that for patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in annual exacerbation rate (Radiology 2011;261:274-82).
Thus, COPD patients with chronic bronchitis and emphysema have more exacerbations, and "from CT exam, we can predict a patient’s future exacerbations," he said.
Dr. Make pointed out that a history of chronic bronchitis and at least one COPD exacerbation requiring systemic corticosteroids and/or hospitalization were among the inclusion criteria for two pivotal trials that led to the 2011 approval of the phosphodiesterase-4 inhibitor roflumilast (Daliresp). Pooled data from the multicenter trials demonstrated a significant 17% reduction with roflumilast in the rate of moderate or severe exacerbations per patient per year among adult outpatients with COPD (Lancet 2009;374:685-94).
"Here we have personalized medicine that has made it to the FDA [U.S. Food and Drug Administration], but in order to determine if this medication might be right for your patients, you need to collect the right information," he said.
Gender Differences
Women with COPD are known to have more exacerbations than men, to have lower lung function than men with the same cigarette exposure, and to have more symptoms than men with the same lung function. In addition, more women die of COPD, compared with men. Yet, data are limited regarding gender differences in lung anatomy that might explain this troubling paradox, at least in part. Dr. Make highlighted a recent study that identified gender differences in airway dimensions in 1,021 male and 1,026 female smokers in the COPDGene cohort (COPD 2011;8:285-92).
Multidetector CT scans of the chest revealed that in all airways measured, women smokers had higher wall area percentage but smaller luminal area, internal diameter, and airway wall thickness than did male smokers. Gender remained one of the most significant predictors for these differences on multivariate analysis, even after researchers adjusted for age, body size, and other confounders.
"So maybe we should look at women differently than men – think about why they’re different and how to treat them or prevent the disease differently," said Dr. Make, who coauthored the study.