Lung Function Affected by a Single COPD Exacerbation

September 4, 2012 (Vienna, Austria) — Changes in the parameters of lung function before and after just 1 exacerbation of chronic obstructive pulmonary disease (COPD) underscore the impact of such exacerbations on lung function decline.

According to data reported here at the European Respiratory Society 2012 Annual Congress, a single exacerbation causes significant lung damage and directs the rate of lung decline in the progression of COPD because of damage to lung capacity.

COPD exacerbations are associated with high mortality, and the average patient with COPD is likely to experience 1 to 3 exacerbations a year. Although frequent COPD exacerbations are linked to a rapid decline in lung function and disease progression toward emphysema, few data exist on how much a single exacerbation affects the rate of decline. Furthermore, whether exacerbations are a cause or an effect of disease progression is a matter of debate.

According to lead author David M. Halpin, MD, FRCP, from the Department of Respiratory Medicine at the Royal Devon and Exeter Hospital in Exeter, United Kingdom, "it is not known whether frequent exacerbations cause an increased rate of decline in lung capacity due to permanent damage or if an increased rate of decline leads to more frequent exacerbations."

To determine the annual rate of decline in lung capacity, a retrospective analysis of data from the 4-year Understanding the Potential Long-Term Impacts on Function With Tiotropium (UPLIFT) trial was performed. The decline was assessed by comparing measurements of pre- and postbronchodilator forced expiratory volume in 1 s (FEV₁) and of forced vital capacity (FVC) before and after the first COPD exacerbation, which was defined as an increase in or the new onset of more than 1 respiratory symptom lasting 3 or more days that required treatment with antibiotics or systemic corticosteroids.

To examine the impact of a single episode, only patients with 3 or more pulmonary function tests before and after the exacerbation and with no further exacerbations during the study period were eligible.

Dr. Halpin noted that because of this stringent patient selection, results might not be indicative of the rate of decline in the overall COPD population.

The mean age of the study population (n = 462) was 64 years, and 78% of patients were male.

The mean annual rate of decline was determined using linear regression. The data demonstrated a significant decline in lung function after just 1 exacerbation.

Overall, a significant increase in the rates of decline before and after an exacerbation were seen in pre- and postbronchodilator FEV₁.

The mean prebronchodilator FEV₁was –27.5 mL/year (range, –101.1 to 49.5 mL/year); after the exacerbation, this increased to –48.7 mL/year (range, –134.1 to 22.2 mL/year; P = .0006). The mean postbronchodilator FEV₁was –27.8 mL/year (range, –97.0 to 41.7 mL/year); after the exacerbation, this increased to –59.0 mL/year (range, –132.7 to 15.7 mL/year; P = .0002).

Similar increases in the rates of decline were seen with prebronchodilator and postbronchodilator FVC, which showed trends toward a decline in lung function after the exacerbation (P = .0403 and P = .0775, respectively).

Conway Wong, CMDHB, from the Department of Respiratory Medicine at Middlemore Hospital in Auckland, New Zealand, told Medscape Medical News that "this study confirms the importance of the occurrence of a single exacerbation. The ECLIPSE [Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints] study showed that a history of exacerbation is the best predictor of a future exacerbation. The UPLIFT study shows that each exacerbation may have deleterious effects on lung function."

The UPLIFT authors explain that "when the rate of decline in lung function is measured for 1 to 2 years postexacerbation, the data suggest that a single exacerbation can lead to a significant rate of decrease in function in patients with moderate to severe COPD."

Dr. Halpin added that "these data suggest that episodes drive the course of the disease, rather than resulting from progressive disease."

Dr. Halpin reports receiving honoraria from Admirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Internune, MSD, Novartis, Nycomed, and Pfizer. Dr. Wong has disclosed no relevant financial relationships.

European Respiratory Society (ERS) 2012 Annual Congress: Abstract 194OC. Presented September 2, 2012.