Lung Cancer in interstitial lung disease: a matched case-control and cohort analysis

Background Lung cancer is significantly more common in patients with idiopathic pulmonary fibrosis (IPF) than the general population. Whether this risk extends to other fibrotic interstitial lung diseases (ILDs) including hypersensitivity pneumonitis (HP) and connective-tissue disease ILD (CTD-ILD), remains uncertain. We aimed to characterise lung cancer prevalence and incidence across ILDs. Methods We conducted matched case-control and cohort analyses using the Optimum Patient Care Research Database. Adults with incident ILD were matched up to 1:4 to controls by age, sex, and practice. Pre-existing lung cancer was examined using conditional logistic regression. Lung cancer incidence rates were analysed using Fine–Gray competing-risk models. Analyses were conducted overall and by ILD subtype. Findings We evaluated 15 777 people with ILD (10 030 IPF, 4347 CTD-ILD, 1400 HP) and 62 417 controls. Prevalence of lung cancer at index date was 1.3% in ILD versus 0.4% in controls (OR 2.68; 95%CI 2.21–3.23). During follow-up (median 3.0 years, IQR 1.3–5.4), 540 (3.5%) ILD cases and 790 (1.3%) controls developed lung cancer. The incidence rate was 963.43 in ILD versus 367.57 in controls per 100 000 person-years with sub-distributional hazard ratio (sHR) of 1.93 (95%CI 1.72–2.17). Lung cancer risk was elevated in cases with IPF (sHR 2.36, 95%CI 2.08–2.69) and CTD-ILD (sHR 1.78, 95%CI 1.48–2.14) but not HP. Findings were consistent in never-smokers. Interpretation A strong relationship between ILD and lung cancer exists, with increased risk in CTD-ILD and IPF compared to the general population. Findings of this study support consideration of targeted lung-cancer surveillance within ILD management paradigms.