Differences in disease characteristics and outcomes as determined by biological sex in a large UK idiopathic pulmonary fibrosis population: analysis from the British Thoracic Society, Interstitial Lung Disease registry data

Introduction Growing evidence suggests that biological sex influences the incidence, presentation, diagnosis and outcomes of many lung diseases. Understanding these differences is the first step towards precision medicine to improve patient care. Methods In this cross-sectional study, idiopathic pulmonary fibrosis (IPF) patients enrolled in a national (UK), multicentre registry were categorised by sex and analysed for differences in demographics, pulmonary function tests, high resolution CT radiological pattern, eligibility/uptake of antifibrotics and survival. Results Of 7177 cases, 77.8% (n=5587) were male, median age 75 years (IQR 69.5–80.5) for both sexes (p=0.83). Males were more likely to have a history of smoking (males 72.9% vs females 60.5%, p24 months prior to first clinic appointment (females 40.1% vs males 36.6%, p=0.03). While more males in the cohort met eligibility criteria for antifibrotics at baseline (pirfenidone FVC 50%–80% males 54.7% vs females 47.6%, nintedanib FVC 50%–80% males 47.0% vs females 41.5%, p<0.001), a larger proportion chose not to commence antifibrotic treatment (males 47.0% vs females 29.6%, p<0.001). Female sex was associated with longer survival; for females, the 75% Kaplan-Meier survival quartile is 7.6 years (95% CI 5.51 to 9.68 years) versus 4.3 years (95% CI 3.82 to 4.78) for males (p<0.001). Male sex (HR 1.76 (95% CI 1.22 to 2.54), p=0.002), higher age (HR 1.042 (95% CI 1.02 to 1.06), p<0.001), lower baseline FVC % predicted (HR 0.98 (95% CI 0.97 to 0.98), p<0.001) and coexistent lung cancer (HR 9.3 (95% CI 2.86 to 30.24), p<0.001) were all independently associated with worse survival. Conclusion This is the first UK study to use national registry data to systematically evaluate IPF disease characteristics stratifying by biological sex and highlights distinct characteristics between groups. Future clinical trials should explicitly explore sex-specific targeted interventions and analyses to optimise future IPF patient care.