Lung Function Trajectories Leading to Chronic Obstructive Pulmonary Disease as Predictors of Exacerbations and Mortality

Rationale: Chronic obstructive pulmonary disease (COPD) can develop not only through a lung function trajectory dominated by an accelerated decline of FEV1 from normal maximally attained FEV1 in early adulthood (normal maximally attained FEV1 trajectory) but also through a trajectory with FEV1 below normal in early adulthood (low maximally attained FEV1 trajectory).Objectives: To test whether the long-term risk of exacerbations and mortality differs between these two subtypes of COPD.Methods: The cohort included 1,170 young adults enrolled in the Copenhagen City Heart Study during the 1970s and 1980s. In 2001-2003, which served as the baseline for the present analyses, 79 participants had developed COPD through normal maximally attained FEV1 trajectory, 65 had developed COPD through low maximally attained FEV1 trajectory, and 1,026 did not have COPD.Measurements and Main Results: From 2001 until 2018, we observed 139 severe exacerbations of COPD and 215 deaths, of which 55 were due to nonmalignant respiratory disease. In Cox models, there was no difference with regard to risk of severe exacerbations between the two trajectories, but individuals with normal maximally attained FEV1 had an increased risk of nonmalignant respiratory disease mortality (using inverse probability of censoring weighting with adjusted hazard ratio [HR], 6.20; 95% confidence interval [CI], 2.09-18.37; P = 0.001) and all-cause mortality (adjusted HR, 1.93; 95% CI, 1.14-3.26; P = 0.01) compared with individuals with low maximally attained FEV1.Conclusions: COPD developed through normal maximally attained FEV1 trajectory is associated with an increased risk of respiratory and all-cause mortality compared with COPD developed through low maximally attained FEV1 trajectory.