Risk Factors for Chronic Obstructive Pulmonary Disease Exacerbations among Individuals without a History of Recent Exacerbations: A COPDGene Analysis

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are detrimental events in the natural history of COPD, but the risk factors associated with future exacerbations in the absence of a history of recent exacerbations are not fully understood. Objectives: To identify risk factors for COPD exacerbations among participants in the Genetic Epidemiology of COPD Study (COPDGene) without a history of exacerbation in the previous year. Methods: We identified participants with a smoking history enrolled in COPDGene who had COPD (defined as forced expiratory volume in 1 second [FEV₁]/forced vital capacity < 0.70), no exacerbation in the year before their second study site visit, and who completed at least one longitudinal follow-up questionnaire in the following 36 months. We used univariable and multivariable zero-inflated negative binomial regression models to identify risk factors associated with increased rates of exacerbation. Each risk factor's regression coefficient (β) was rounded to the nearest 0.25 and incorporated into a graduated risk score. Results: Among the 1,528 participants with a smoking history and COPD enrolled in COPDGene without exacerbation in the year before their second study site visit, 508 participants (33.2%) had at least one moderate or severe exacerbation in the 36 months studied. Gastroesophageal reflux disease, chronic bronchitis, high symptom burden (as measured by Modified Medical Research Council Dyspnea Scale and COPD Assessment Test), and lower FEV₁% predicted were associated with an increased risk of exacerbation. Each 1-point increase in our graduated risk score was associated with a 25-30% increase in exacerbation rate in the 36 months studied. Conclusions: In patients with COPD without a recent history of exacerbations, gastroesophageal reflux disease, chronic bronchitis, high symptom burden, and lower lung function are associated with increased risk of future exacerbation using a simple risk score that can be used in clinical practice.