Effects of smoking, depression, and anxiety on mortality in COPD patients: a prospective study.

BACKGROUND Smoking, depression, and anxiety increase the risk of death in patients with COPD, but the combined effect of these factors is unknown. We assessed the interactive effects of smoking, depression, and anxiety on mortality in patients with COPD. METHODS We collected and analyzed data from 7,787 subjects with COPD, in 14 rural communities, from May 2008 to May 2012, and used logistic regression to evaluate the interactions and relative excess risk due to interaction (RERI). We applied the attributable proportion of interaction and the synergy index to evaluate the additive interactions of the factors. RESULTS In our COPD subjects the interaction of current smoking and depression symptoms increased the death risk by 3.8-fold (odds ratio 3.78, 95% CI 2.51-5.05), with significant biological interactions (RERI 1.74, 95% CI 0.51-2.99, attributable proportion 0.48, 95% CI 0.13-0.85, synergy index 2.98, 95% CI 1.44-4.56). The biological interactions increased with increasing years or pack-years of smoking: for subjects with ≥ 30 years of smoking: RERI 1.80, 95% CI 1.05-2.75, attributable proportion 0.48, 95% CI 0.15-0.82, synergy index 2.85, 95% CI 1.75-3.96; for subjects with ≥ 40 pack-years of smoking: RERI 3.11, 95% CI 1.54-4.71, attributable proportion 0.60, 95% CI 0.31-0.91, synergy index 4.00, 95% CI 2.84-5.26. Similarly, the combined effect of current smoking and anxiety symptoms increased the death risk by 4.3-fold (odds ratio 4.27, 95% CI 95% CI 2.96-5.59), with significant biological interactions (RERI 1.51, 95% CI 0.31-2.74, attributable proportion 0.46, 95% CI 0.11-0.87, synergy index 2.89, 95% CI 1.31-4.51). The biological interactions also increased with increasing years or pack-years of smoking: for subjects with ≥ 30 years of smoking: RERI 1.41, 95% CI 0.45-2.43, attributable proportion 0.45, 95% CI 0.12-0.81, synergy index 2.88, 95% CI 1.24-5.98; for subjects with ≥ 40 pack-years of smoking: RERI 3.15, 95% CI 2.07-4.61, attributable proportion 0.55, 95% CI 0.21-0.94, synergy index 3.00, 95% CI 1.45-4.75. CONCLUSIONS Smoking, depression, and anxiety are associated with higher risk of death in patients with COPD. The risk of death, depression, and anxiety increases with increasing duration of smoking (years) and cigarette pack-years. Chinese Clinical Trials Registration ChiCTR-TRC-12001958.