Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial

Kai M Beeh,Leonardo M Fabbri,Hendrik Schmidt,Susanne Stowasser,Claus F Vogelmeier,Klaus F Rabe,Thomas Glaab

doi:10.1186/1465-9921-14-116

Abstract

BackgroundData examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce.MethodsPost-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint. Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment. A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation.ResultsIn total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators. Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses. Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers. The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality.ConclusionThe frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival.Trial registrationNCT00563381; Study identifier: BI 205.389.

Highlights

Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce
Baseline covariates identified as potential predictors for exacerbation risk were age, sex, COPD severity, body mass index (BMI), inhaled corticosteroid (ICS) use at baseline, COPD duration, smoking history and the extent of antibiotic or oral corticosteroid use due to breathing problems in the previous year
The risk of a first exacerbation was higher for women compared with men; for patients with a mean baseline BMI < 20 kg/m2 compared with BMI ≥ 25 to < 30 kg/m2 (HR, 1.29; 95% Confidence interval (CI), 1.11 to 1.50) or ≥ 30 kg/m2 (HR, 1.34; 95% CI, 1.15 to 1.57); patients with ICS use at baseline versus no ICS use (HR, 1.36; 95% CI, 1.26 to 1.48); patients on ≥ 2 antibiotic courses versus < 2 antibiotic courses (HR, 1.33; 95% CI, 1.21 to 1.46); and patients on ≥ 2 systemic corticosteroid courses versus < 2 corticosteroid courses due to breathing problems in the preceding year (HR, 1.37; 95% CI, 1.22 to 1.54), respectively

Summary

Introduction

Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce. The 1-year Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) study complements and extends the few previous reports on exacerbation phenotypes This trial, being a large randomised trial using exacerbations as the primary endpoint, enables us to study more than 4400 moderate or severe exacerbations [12]. The purpose of this post-hoc analysis of the POET-COPD trial was to: determine the factors contributing to exacerbation risk; evaluate the characteristics of patients with infrequent, frequent and severe exacerbations in a large patient population; and, assess the effects of exacerbations on the incidence of hospitalisations and mortality

Methods

Results

Discussion

Conclusion