Tobacco Smoking is Associated with Combined Pulmonary Fibrosis and Emphysema and Worse Outcomes in Interstitial Lung Disease.

BACKGROUND

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared to non-smokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality.

METHODS

We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD) and mortality in patients stratified by tobacco smoking status (ever-versus-never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four non-tertiary medical centers. Data was analyzed by two-sided t-tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusing capacity (DLCO), ILD subtype, antifibrotic therapy, and hospital center.

RESULTS

Of 1163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (PF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than non-smokers(P<0.01). Time to LFD in smokers was shorter(19.7±20 months vs. 24.8±29 months;P=0.038] and survival time was decreased [10.75(10.08-11.50) years vs. 20(18.67-21.25) years; adjusted mortality HR=1.50, 95%CI 1.17-1.92;P<0.0001] compared to non-smokers. Smokers had 12% greater odds of death for every additional ten-pack-years of smoking(P<0.0001). Mortality outcomes remained consistent in the non-tertiary cohort (HR=1.51, 95%CI=1.03-2.23;P=0.036).

CONCLUSIONS

Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.