Risk and outcome of interstitial lung disease in inflammatory bowel disease: Evidence from a Danish Nationwide Population-Based Cohort Study
Abstract
Background: Extra-intestinal manifestations of inflammatory bowel disease (IBD) are well-recognized, but the long-term risk of developing interstitial lung disease (ILD) in IBD and its impact on mortality remain poorly understood. We aimed to assess the risk of ILD in patients with IBD and the subsequent effect on survival. Methods: This nationwide cohort study (1978-2022) utilized the Danish National Patient Registry, including 53 591 patients with IBD and 267 955 age- and sex-matched controls. Adjusted hazard ratios (aHRs) were estimated using Cox regression, adjusted for age, sex, education, and Charlson Comorbidity Index (CCI). Cumulative incidence was assessed via the Aalen–Johansen estimator. Mortality in patients with comorbid IBD-ILD was analyzed using Cox regression and Kaplan-Meier curves. Results: The 45-year cumulative incidence of ILD was 2.1% for IBD versus 0.9% for controls (P < .001), and aHR was 2.1 (95% CI, 1.8-2.4). Furthermore, the aHR was 3.0 (95% CI, 2.2-4.1) in patients with frequent IBD-related hospitalizations compared to matched controls. The 5-year mortality in concomitant IBD and ILD was 29.3% (95% CI, 23.3-35.3) compared to 11.9% (95% CI, 9.8-14.0) for matched patients with only IBD. Male sex and higher CCI were independent risk factors for both ILD and mortality (all P < .001). Conclusion: IBD is associated with a two-fold increase in ILD risk. Risk factors may include old age, longstanding disease, male sex, and comorbidity. Comorbid IBD-ILD increases mortality substantially compared to only IBD, highlighting the need for clinical awareness and early detection to improve outcomes.
Plain Language Summary
Inflammatory bowel disease (IBD) — which includes Crohn's disease and ulcerative colitis — is primarily known as a gut condition, but it can also affect other organs. Interstitial lung disease (ILD) is a serious condition where lung tissue becomes scarred and inflamed over time, making breathing progressively harder. In this nationwide Danish study spanning over four decades, we investigated how much more likely IBD patients are to develop ILD, and what happens to their survival if they do. We followed 53,591 IBD patients and nearly 270,000 matched controls from 1978 to 2022. Over a 45-year period, 2.1% of IBD patients developed ILD compared to 0.9% of controls — representing a more than two-fold increased risk. Patients with frequent IBD-related hospitalisations had a three-fold increased risk. When IBD and ILD occurred together, five-year mortality was 29% — more than double the 12% seen in IBD patients without ILD. Male sex, older age, and greater overall illness burden were independent risk factors for both developing ILD and dying from it. Our findings show that IBD carries a significant and underappreciated risk of serious lung disease. Clinicians caring for IBD patients — particularly older men with severe or longstanding disease — should maintain awareness of respiratory symptoms and consider early investigation for ILD, as prompt detection may improve survival.