Cause-specific mortality in COPD subpopulations: a cohort study of 339 647 people in England

Background Identifying correlates of cause-specific mortality in patients with chronic obstructive pulmonary disease (COPD) may aid the targeting of therapies to reduce mortality. We determined factors associated with causes of death in a primary care COPD population. Methods Clinical Practice Research Datalink Aurum was linked to Hospital Episode Statistics and death certificate data. People with COPD alive between 1 January 2010 and 1 January 2020 were included. Patient characteristics were defined before the start of follow-up: (a) frequency and severity of exacerbations; (b) emphysema or chronic bronchitis; (c) Global Obstructive Lung Disease (GOLD) groups A–D; and (d) airflow limitation. We used Cox Proportional Hazards regression and competing risks to investigate the association between patient characteristics and risk of all-cause, COPD and cardiovascular (CV) mortality. Results 339 647 people with COPD were included of which 97 882 died during follow-up (25.7% COPD related and 23.3% CV related). Airflow limitation, GOLD group, exacerbation frequency and severity, and COPD phenotype were associated with all-cause mortality. Exacerbations, both increased frequency and severity, were associated with COPD-related mortality (≥2 exacerbations vs none adjusted HR: 1.64, 1.57–1.71; 1 severe vs none adjusted HR: 2.17, 2.04–2.31, respectively). Patients in GOLD groups B–D had a higher risk of COPD and CV mortality compared with GOLD group A (GOLD group D vs group A, adjusted HR for COPD mortality: 4.57, 4.23–4.93 and adjusted HR for CV mortality: 1.53, 1.41–1.65). Increasing airflow limitation was also associated with both COPD and CV mortality (GOLD 4 vs 1, adjusted HR: 12.63, 11.82–13.51 and adjusted HR: 1.75, 1.60–1.91, respectively). Conclusion Poorer airflow limitation, worse functional status and exacerbations had substantial associations with risk of all-cause mortality. Differing results for CV and COPD-related mortality suggests interventions to prevent mortality may need to target particular characteristics or time points in the disease course.