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

Abstract

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.

Keywords: chronic obstructive pulmonary disease (COPD); exacerbations; mortality; trajectories.

Figure 1.

Outline of the study. Participants were assigned into one of three FEV₁ trajectories of interest: no chronic obstructive pulmonary disease (COPD), COPD developed through low maximally attained FEV₁ trajectory, and COPD developed through normal maximally attained FEV₁ trajectory based on information from the 1976–1978 or 1981–1983 examination. After the baseline 2001–2003 examination, individuals were followed for 17 years with regard to risk of severe exacerbations of COPD, respiratory disease mortality, and all-cause mortality.

Figure 2.

Maintenance medication for chronic obstructive pulmonary disease (COPD) and severe exacerbations of COPD. (A and B) Inverse Kaplan-Meier curves with inverse probability of censoring weighting (IPCW) for maintenance medication for COPD (in subjects not receiving maintenance medication at baseline) and severe exacerbations of COPD for the three trajectories. (C) Cox proportional hazards regression analysis weighted by IPCW and adjusted for age and sex. Additional adjustment was made for FEV₁% predicted value when comparing the two COPD trajectories. CI = confidence interval.

Figure 3.

Respiratory disease mortality and all-cause mortality. (A and B) Inverse Kaplan-Meier curves for respiratory disease mortality with inverse probability of censoring weighting (IPCW) and all-cause mortality without IPCW for the three trajectories. (C) Cox proportional hazards regression analysis with IPCW (respiratory disease mortality) and without IPCW (all-cause mortality), both adjusted for age and sex. Additional adjustment was made for FEV₁% predicted value when comparing the two chronic obstructive pulmonary disease trajectories. CI = confidence interval; COPD = chronic obstructive pulmonary disease.