Association of mild chronic obstructive pulmonary disease with all-cause mortality: A systematic review and meta-analysis

It is unclear whether patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 (mild) chronic obstructive pulmonary disease (COPD) have worse respiratory outcomes than individuals with normal spirometry. For this systematic review and meta-analysis, we conducted a search of PubMed, Embase, and Web of Science for all literature published up to 1 March 2023. Studies comparing mortality between mild COPD and normal spirometry were included. A random-effects model was used to estimate the combined effect size and its 95% confidence interval (CI). The primary outcome was all-cause mortality. Respiratory disease-related mortality were examined as secondary outcomes. Of 5242 titles identified, 12 publications were included. Patients with mild COPD had a higher risk of all-cause mortality than individuals with normal spirometry (pre-bronchodilator: hazard ratio HR = 1.21, 95% CI: 1.11–1.32, I2 = 47.1%; post-bronchodilator: HR = 1.19, 95% CI: 1.02–1.39, I2 = 0.0%). Funnel plots showed a symmetrical distribution of studies and did not suggest publication bias. In jackknife sensitivity analyses, the increased risk of all-cause mortality remained consistent for mild COPD. When the meta-analysis was repeated and one study was omitted each time, the HR and corresponding 95% CI were >1. Patients with mild COPD also had a higher risk of respiratory disease-related mortality (HR = 1.71, 95% CI: 1.03–2.82, I2 = 0.0%). Our results suggest that mild COPD is associated with increased all-cause mortality and respiratory disease-related mortality compared with normal spirometry. Further research is required to determine whether early intervention and treatment are beneficial in mild COPD.