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.