Title : Interaction between age and cigarette smoking on the risk of idiopathic pulmonary fibrosis: A population-based cohort study

Background: Age and cigarette smoking are the principal non-modifiable and modifiable risk factors for idiopathic pulmonary fibrosis (IPF), respectively. Although both factors have been implicated in the development of pulmonary fibrosis, their joint contribution to IPF risk remains incompletely understood. This study examined interactions between age and cigarette smoking on both additive and multiplicative scales.

Methods: This prospective cohort study included 387,097 participants from the UK Biobank. Incident IPF was identified using ICD-10 code J84.1 through linked national health records. Age at recruitment was categorized into intervals, with participants aged 38–44 years serving as the reference group, and was additionally modeled as a continuous variable using natural splines. Smoking status was classified as never, former, or current smoking. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic, socioeconomic, lifestyle, and genetic factors. Additive interactions were assessed using the relative excess risk due to interaction (RERI) and attributable proportion (AP).

Results: During a median follow-up of 12 years, 2,054 participants developed IPF, corresponding to an incidence rate of 0.40 per 1,000 person-years. IPF incidence increased non-linearly with age, particularly after 50 years. Compared with participants aged 38–44 years, adjusted HRs exceeded 6.0 among those aged 60–64 years and 12.0 among those aged 65–69 years. Across age groups, current smokers consistently showed higher IPF risk than never smokers. The largest additive interaction was observed among current smokers aged 60–64 years (RERI = 6.92, 95% CI: 1.08–12.77; AP = 0.63, 95% CI: 0.10–1.16), indicating that 63% of the excess risk in this subgroup was attributable to the combined effect of age and smoking. A significant additive interaction was also observed among former smokers aged 60–64 years (RERI = 5.48; AP = 0.61). No statistically significant multiplicative interactions were detected.

Conclusions: IPF risk increased substantially with advancing age and was higher among individuals with a history of cigarette smoking. Positive additive interactions suggest that age and smoking jointly contribute to excess IPF risk, particularly among adults aged 60–64 years. These findings support targeted smoking prevention and cessation strategies in populations at increased risk of IPF, highlighting the importance of integrating smoking prevention and cessation efforts into strategies aimed at reducing the burden of IPF among ageing populations.

Qiyun Tu, MD, is a doctoral student in the Department of Respiratory and Critical Care Medicine at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Her research focuses on clinical epidemiology, environmental risk factors, and genetic susceptibility of chronic respiratory diseases, particularly interstitial lung diseases and idiopathic pulmonary fibrosis (IPF). She has extensive experience in large-scale population-based cohort data analysis, utilizing advanced epidemiological methods to investigate life-course environmental exposures and interactive effects on complex disease prognosis.