Tobacco smoking and risk for pulmonary fibrosis: A prospective cohort study in UK Biobank.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with unknown etiology. A limited number of small studies showed an effect of tobacco smoking on risk for IPF, but second-hand smoking has not been examined.Are smoking-related exposures associated with risk for IPF, and is there any interaction between them?We designed a prospective cohort study in UK Biobank, including 437,453 non-related men and women of white ethnic background (aged 40 to 69 at baseline). We assessed the effect of tobacco smoking-related exposures on risk for IPF using Cox regression adjusted for age, sex, Townsend deprivation index, and home area population density. We also examined for potential additive and multiplicative interaction between these exposures. Multiple imputation with chained equations was used to deal with missing data.We identified 802 incident IPF cases. We showed an association between smoking status (HR, 2.12; 95% CI, 1.81-2.47), maternal smoking (HR, 1.38; 95% CI, 1.18-1.62) and smoking in household (HR, 1.26; 95% CI, 1.02-1.57) with risk for IPF in the multivariable model. In ever smokers, a dose-response relationship was observed between pack-years of smoking and risk of IPF (HR per 1 pack-year increase, 1.013; 95% CI, 1.009-1.016). Furthermore, an additive and multiplicative interaction was observed between maternal smoking and smoking status with a relative excess risk due to interaction of 1.00 (95% CI, 0.45-1.54) and a ratio of HR of 1.50 (95% CI, 1.05-2.14).Active and passive tobacco smoking have an independent detrimental effect on risk of IPF and work synergistically. Also, intensity of smoking presents a dose-response association with IPF, strengthening the hypothesis for a potentially causal association.

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Authors: Vanesa Bellou, Lazaros Belbasis, Evangelos Evangelou