What does this research mean for the field?

A smoking cessation intervention provides a sustained mortality benefit over 32.5 years in female patients with COPD, but not in male patients. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

May 20, 2026

A16-07 Sex Differences in Mortality Benefits of a Smoking Cessation Intervention in COPD: 32.5 Year Follow-up From the Lung Health Study

Key Points

This research aims to assess long-term mortality benefits of a smoking cessation intervention in COPD, specifically examining sex differences.
Randomized clinical trial design with follow-up to 32.5 years
Vital status obtained from the US National Death Index for 5,279 participants
Cox-proportional hazards models used to analyze mortality effects stratified by sex and other factors
Females in the smoking cessation group showed lower mortality (HR 0.87, 95% CI 0.77 to 0.98) compared to usual care.
No significant mortality effect was found in males (HR 1.01, 95% CI 0.92 to 1.10).
Significant interaction by sex (interaction p-value 0.05) indicated different outcomes between genders.

Abstract

Abstract Rationale The Lung Health Study was a randomized clinical trial of a smoking cessation intervention compared to usual care in individuals with expiratory airflow obstruction on spirometry and minimal symptoms. Participants were enrolled between 1986 and 1988. At 14.5 years of follow-up, the smoking cessation intervention reduced mortality (HR 0.85, 95% CI 0.73 to 0.98), but that benefit did not meet statistical significance at 32.5 years of follow-up (HR 0.95, 95% CI 0.89 to 1.02). We hypothesized that the beneficial effect of the smoking cessation intervention on mortality may persist in some subgroups of participants through 32.5-years of follow-up. Methods We obtained vital status for participants at US sites (9 of the 10 clinical trial sites) from the US National Death Index (last follow-up 12/31/2019). Cox-proportional hazards models were used to compare the effect of the smoking cessation intervention with usual care on all-cause mortality in subgroups stratified by sex, baseline age tertiles, forced expiratory volume in 1-second (FEV1) percent predicted tertiles, and cigarettes per day. Analyses were performed on an intention-to-treat basis. Interactions were tested using hierarchically related proportional hazards models. Results At baseline, the 5,279 participants included in this analysis had a mean (SD) age of 48.5 (6.8) years, FEV1 percent predicted of 75.0 (8.8), and smoked 31.7 (12.9) cigarettes per day. Females made up 37.1% of the sample. There was a significant sex interaction (interaction p-value 0.05), where females assigned to the smoking cessation intervention had lower mortality than those assigned to usual care (HR 0.87, 95% CI 0.77 to 0.98), but there was no effect in males (1.01, 95% CI 0.92 to 1.10). There were no significant interactions by age, lung function or smoking intensity (Figure). Conclusion The beneficial effects of a smoking cessation intervention have persisted over more than three decades of follow-up in females, but not in males. Reasons for this sex difference are not clear, but future analyses could explore whether these differences are explained by differences in smoking cessation success rates or by biological differences in nicotine metabolism and susceptibility to adverse effects of smoking. This abstract is funded by: None

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