Characteristics Associated with Lung Function Trajectories: An Analysis of the SPIROMICS Cohort

Rationale: Discovering the biological basis of progression in chronic obstructive pulmonary disease (COPD), especially of rapid decline (RD) in forced expiratory volume in 1 second, is essential to the development of precision therapies. Objectives: First, we sought to define baseline characteristics of RD (>100 ml/yr), relative to participants with stable-to-improved (S/I) status or with intermediate decline (D)—categories based on spirometric data from the Framingham Offspring cohort. Second, we sought to examine these categories as predictors of longitudinal COPD outcomes, adjusting for baseline characteristics. Methods: Among ever-smoking participants in the Subpopulations and Intermediate Outcomes in COPD Study (or, SPIROMICS) with two or more spirometric measurements over 8 years, we used linear regression to fit slopes of postbronchodilator change in forced expiratory volume in 1 second. We used ordinal regression, testing baseline characteristics as predictors of lung function change categories (S/I, D, and RD) and used those categories to assess associated clinical outcomes. Results: In this heavy-smoking cohort (>20 pack-years), the status of 747 participants was S/I (40%), and that of 336 participants was RD (18%). In adjusted models of baseline factors associated with trajectories of decline, steeper decline was associated with better initial lung function (all P < 0.001) and greater likelihood of baseline bronchodilator responsiveness (S/I, D, and RD: 32%, 37%, and 43%, respectively; P < 0.001); there was no association between RD and race, ethnicity, socioeconomic status, medical history, or respiratory medication use. Regarding clinical endpoints, RD was associated with greater symptom burden, worse health-related quality of life, and increased mortality, but not exacerbation frequency. Conclusions: Categorical definitions of S/I and RD highlight bronchodilator responsiveness and smoking as risks for adverse outcomes, including death. Contrasting these disease trajectories will support the future identification of the biological bases of COPD progression.