Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease

TLDR

Although exacerbations are key events in COPD, our understanding of their frequency, determinants, and effects remains incomplete. The study tested whether a frequent‑exacerbation phenotype of COPD exists independent of disease severity by analyzing 2,138 patients in the ECLIPSE cohort. Exacerbations were defined as events that prompted antibiotic or corticosteroid prescription or hospitalization. Over three years, exacerbation rates increased with COPD severity (0.85, 1.34, 2.00 per person for stages 2–4), 22–47 % of patients had frequent exacerbations, a history of prior exacerbations was the strongest predictor, and the phenotype was stable, associated with GERD/heartburn, poorer quality of life, and higher white‑cell counts, highlighting the need for targeted prevention. Funded by GlaxoSmithKline (ClinicalTrials.gov NCT00292552).

Abstract

Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity.We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years.Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count.Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)