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

Abstract

Background: Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce.

Methods: Post-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.

Results: In 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.

Conclusion: The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival.

Trial registration: NCT00563381; Study identifier: BI 205.389.

Figure 1

Multivariate model for time to first COPD exacerbation (all) and effect of covariates. Time to first COPD exacerbation was analysed using multivariate Cox regression with stepwise model selection. Potential covariates originally also included 'smoking status’ with categories 'non-current smoker’; 'current smoker’ and 'concomitant diagnoses at baseline’ with categories '0, 1 and > 1’ but turned out to be non-significant for the significance level chosen. ^a≥ 1 exacerbation versus no exacerbation. ^bOverall p-value based on Wald’s χ² test for optimal model. ^cIncludes 23 GOLD category 1 patients. BMI = body mass index; CI = confidence interval; COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease; ICS = inhaled corticosteroids.

Figure 2

Exacerbation frequency and severity of airflow limitation (GOLD category). GOLD category 2 includes 23 patients with GOLD category 1. GOLD = Global Initiative for Chronic Obstructive Lung Disease.

Figure 3

Frequency distribution of patients with exacerbations by number of (A) exacerbations and (B) severe exacerbations.

Figure 4

Incidence rates of all-cause mortality in patients with no exacerbations, patients ≥ 1 moderate exacerbation, and patients experiencing ≥ 1 severe exacerbation while on study treatment.