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
Macdonald et al. (Fri,) studied this question.