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

Discovering the biological basis of progression in chronic obstructive pulmonary disease (COPD), especially of rapid decline (RD) in FEV1, is essential to develop precision therapies. First, to define baseline characteristic of RD (≥100 mL/year), relative to those who were stable-to-improved (S/I) or with intermediate decline (D)-categories based on spirometric data from the Framingham Offspring Cohort. Second, to examine these categories as predictors of longitudinal COPD outcomes, adjusting for baseline characteristics. Among ever-smoking SPIROMICS participants with ≥2 spirometric measurements over 8 years, we fit slopes of postbronchodilator FEV1 change by linear regression. 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. In this heavy smoking cohort (≥20 pack-years), there were 747 S/I (40%) and 336 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, RD: 32%, 37%, 43%; P<0.001); 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. 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.