High genetic risk for idiopathic pulmonary fibrosis (IPF) and an unfavorable lifestyle are significantly associated with increased risk for IPF, particularly when combined, according to study findings published in CHEST.
Investigators sought to examine the relationship between lifestyle factors and the risk for developing IPF. They also sought to determine the extent to which genetic susceptibility to IPF modified the effect of lifestyle on IPF risk.
This prospective cohort study used data from more than half a million participants (37-73 years of age) in the UK Biobank recruited from 22 centers across the UK since 2006. After exclusions for incomplete genetic data, missing lifestyle variables (self-reported), secondary pulmonary fibrosis diseases (self-reported), or history of IPF at baseline, 407,615 participants (mean [SD] age, 56.17 [8.09] years; 53.21% women) were included in the final analyses and followed-up through IPF diagnosis or death, or through December 2020 (median follow-up, 11.98 years). The researchers restricted analyses to individuals of European descent and participants with at least 6 years’ residence at their current address.
Investigators constructed a polygenic risk score (PRS) for each participant as well as a lifestyle score, then classified participants into categories based on genetic risk level (high, medium, or low) and lifestyle (favorable, intermediate, or unfavorable). Overall, the researchers found 1248 incident cases of IPF (incidence density about 25.80/100,000 person-years). Participants with IPF were more likely to be White Europeans, male, older, with higher prevalence of pre-existing diseases and lower educational background. Participants with IPF were more inclined to an unfavorable lifestyle (unhealthy dietary habits, excessive alcohol consumed over time, smoking, lack of regular physical activity).
Investigators found that intermediate lifestyle (hazard ratio [HR] compared with favorable lifestyle, 1.38; 95% CI, 1.22-1.57) and unfavorable lifestyle (HR vs favorable lifestyle, 2.27; 95% CI, 1.85-2.79) were significantly associated with increased risk of IPF. Participants with unfavorable lifestyle combined with high genetic risk vs those with favorable lifestyle and low genetic risk faced the highest IPF risk (HR, 7.80; 95% CI, 5.48-11.09). The interaction of unfavorable lifestyle and high genetic risk accounted for approximately 32.7% (95% CI, 11.3%-54.1%) of IPF risk.
When stratified by age only and using favorable lifestyle as the reference group, analyses showed that unfavorable and intermediate lifestyle were associated with incident IPF risk across age groups (no interaction between age and lifestyle; P for interaction >.05). When stratified by age only and using low genetic risk as the reference group, analyses showed no interaction between age and genetic risk (P for interaction >.05).
Cox regression model analyses identified specific lifestyle variables positively associated with increased risk of IPF, including unhealthy fruit and vegetable intake, unhealthy oily fish intake, processed meat intake, unhealthy TV viewing duration, irregular physical activity, and current smoking; red meat, sleep time, and alcohol were not linked with increased risk for IPF. Unfavorable lifestyle in the sex- and age-adjusted model (HR, 2.82; 95% CI, 2.31-3.45) and intermediate lifestyle (HR, 1.54; 95% CI, 1.35-1.75) were significantly associated with increased risk of IPF vs favorable lifestyle (P for trend <.001).
Investigators found the adjusted risk for incident IPF was 127.1% (95% CI, 85.2%-178.5%) higher in participants with unfavorable lifestyle vs favorable lifestyle and that the risk for incident IPF 38.4% higher (95% CI, 21.8%-57.4%) among those with intermediate lifestyle vs favorable lifestyle. Notably, these risk calculations were adjusted for hyperlipidemia, diabetes, hypertension, employment status, body mass index, ethnicity, and education, and were not affected by the additional adjustment for air pollutants.
Significant study limitations include response bias in self-reported questionnaires and lack of generalizability beyond White Europeans.
“Exposure to unfavorable lifestyle significantly increased the risk of IPF, particularly in those with high genetic risk,” the investigators concluded, adding that those with high genetic risk for IPF should be encouraged to adhere to a healthy lifestyle.
Ma Y, Cui F, Li D, et al. Lifestyle, genetic susceptibility, and the risk of idiopathic pulmonary fibrosis: a large prospective cohort study. Chest. Published online April 12, 2023. doi:10.1016/j.chest.2023.04.008