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 FEV1, is essential to develop precision therapies.

Objectives: 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.

Methods: 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.

Measurements and main results: 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.

Conclusion: 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.