Smoking exposures and mortality risk in individuals with idiopathic pulmonary fibrosis: a UK Biobank cohort study.

Authors

Qiyun Tu, Xinyue Zhang, Yuxin Zou, Yuqing Lv, Lifeng Yan, Chenchen Hou, Lina Wang, Wenhui Sun, Haiyang Zhang, Manyi Pan, Tianyu Zhou, Baopeng Liu, Xiahui Ge, Huaqi Guo, Weining Xiong

Published in

Frontiers in public health. Volume 14. Pages 1884390. Epub Sep 16, 2026.

Abstract

Smoking and secondhand smoke (SHS) exposures are established modifiable risk factors for premature mortality, but their joint associations with recorded idiopathic pulmonary fibrosis (IPF) remain uncertain. We examined active and passive smoking exposures in relation to all-cause and cause-specific mortality and evaluated departures from additivity with recorded IPF history.
This prospective UK Biobank cohort included 270,644 participants. Exposures comprised baseline smoking status, cumulative pack-years, maternal smoking around birth, adult SHS, and a composite passive SHS indicator. Multivariable Cox models, additive and multiplicative interaction analyses, and restricted cubic spline models were used after adjustment for demographic, socioeconomic, lifestyle, and genetic covariates.
During a median follow-up of 13.8 years, 20,959 deaths occurred. Ever-recorded IPF history was associated with all-cause mortality (HR 4.255, 95% CI 3.937-4.597), and active and passive smoking measures were also associated with mortality. In the additive interaction analyses, a positive departure from additivity was observed only between maternal smoking around birth and recorded IPF in relation to respiratory mortality (RERI 16.969, 95% CI 2.935-31.002; AP 0.248, 95% CI 0.082-0.414; SI 1.337, 95% CI 1.068-1.673). Corresponding positive RERI estimates were observed in analyses restricted to White participants, among participants with complete covariate data, and after excluding deaths occurring within the first 2 years of follow-up. The confidence intervals for the other RERI estimates in the primary analysis included zero. Dose-response associations were nonlinear among participants without recorded IPF and approximately linear among those with recorded IPF, although estimates in the latter group were less precise.
Active and passive smoking measures and ever-recorded IPF history were associated with mortality in this cohort. Evidence for positive additive interaction was confined to maternal smoking around birth and respiratory mortality and should be interpreted as hypothesis-generating. The observational findings do not establish causal or biological synergy and require replication in independent cohorts.

PMID:
42819413
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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