Exacerbation Burden in COPD and Occurrence of Mortality in a Cohort of Italian Patients: Results of the Gulp Study.

Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up. Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period. Setting: Ten Italian academic secondary- and tertiary-care centers. Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited. Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality. Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors. Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.