Nitrogen dioxide increases the risk of mortality in idiopathic pulmonary fibrosis

Abstract

Ambient air pollution is associated with the prognosis of idiopathic pulmonary fibrosis (IPF) patients. We aimed to identify the impacts of individual exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 mu m (PM10) and nitrogen dioxide (NO2) on IPF patients' mortality. 1114 patients (mean age 65.7 years; male 80.5%) diagnosed with IPF between 1995 and 2016 were included in this study. Individual-level long-term concentrations of PM10 and NO2 at residential addresses of patients were estimated using a national-scale exposure prediction model. The effect of PM10 and NO2 on mortality was estimated using a Cox proportional hazards model adjusted for individual-and area-level covariates. The median follow-up period was 3.8 years and 69.5% of the patients died or underwent lung transplantation. When adjusted for individual-and area-level covariates, a 10 ppb increase in NO2 concentration was associated with a 17% increase in mortality (hazard ratio (HR) 1.172, 95% CI 1.030- 1.344; p=0.016). When IPF patients were stratified by age (> 65 versus <65 years) or by sex, NO2 was a significant prognostic factor for mortality in the elderly (HR 1.331, 95% CI 1.010-1.598; p=0.010). When stratified by age and sex jointly, NO2 showed the stronger association with mortality in elderly males (HR 1.305, 95% CI 1.072-1.598; p=0.008) than in other groups. PM10 was not associated with IPF mortality in all patients and in subgroups stratified by age or sex. Our findings suggest that increased exposure to NO2 can increase the risk of mortality in patients with IPF, specifically in elderly males.