Abstract

Introduction: Interstitial lung disease (ILD) is a diverse spectrum of diseases resulting in scarring of lung parenchyma. Though considered rare, it is increasingly recognized in patients with inflammatory bowel disease (IBD). The pathogenesis is unclear but the changes in the lung are thought to represent the same type of inflammatory changes that occur in the bowel. The available literature on the association between IBD and ILD is largely based on case series. In this study, we sought to describe the epidemiology of ILD in patients with IBD. Methods: We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of EHR data from 27 integrated healthcare systems in the United States between 3/2017-3/2022. We identified all patients in the database with CD or UC based on Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). We compared the prevalence of ILD at least 30 days post-CD or post-UC diagnosis to a control cohort of patients without CD or UC. Results: Of the 31,699,800 patients in the database, 145,290 patients had CD and 123,800 patients had UC. Overall prevalence of ILD was higher in CD (1.89%) and UC (1.91%) compared to non-IBD patients (0.8%), with odds ratio (OR) for CD 2.38 [95% CI, 2.29-2.47, p< 0.001], and UC 2.41 [95% CI, 2.31-2.51, p< 0.001]. Odds of ILD in IBD patients tended to be higher in the cohort aged 18-65 versus age > 65, in African Americans compared to Caucasians, and was otherwise similar across gender. Among autoimmune conditions associated with ILD, IBD patients with RA and SLE had a significantly lower prevalence of ILD compared to non-IBD patients with RA or SLE. IBD patients on treatment with sulfasalazine, azathioprine, infliximab, or adalimumab tended to have lower odds of developing ILD compared to non-IBD patients on the same medications. (Table) Conclusion: In this large population-based study, we found a significantly higher prevalence of ILD in patients with CD and UC compared to patients without IBD. Interestingly, IBD patients on treatment with any of the various anti-inflammatory agents, most of which are independently associated with ILD, had lower odds of developing ILD compared to non-IBD patients on the same drugs. This data suggests that anti-inflammatory medications and IBD may be independent risk factors for development of ILD. Thus, the mechanism of lung injury in IBD patients may be unique, in which case treatment with anti-inflammatory medications may serve as a protective factor. Table 1. - Prevalence of ILD after at least 30 days post-IBD diagnosis - Above is for Crohn's Disease (CD) and below is for Ulcerative Colitis (UC) X CD Prevalence per 100,000 No CD Prevalence per 100,000 Odds Ratio 95% CI P-Value TOTAL 2750 1892 253640 804 2.38 2.29-2.47 <0.001 Adult (18-65) 1250 1225 92020 497 2.48 2.35-2.63 <0.001 Senior (65+) 1480 3583 142000 1873 1.95 1.85-2.05 <0.001 Female 1610 1827 129250 746 2.48 2.36-2.6 <0.001 Male 1140 2014 124580 888 2.29 2.16-2.43 <0.001 Caucasian 2290 2098 181110 1085 1.95 1.88-2.04 <0.001 African American 310 2391 37420 1040 2.33 2.08-2.61 <0.001 Asian 30 1685 3430 690 2.47 1.72-3.55 <0.001 Amyloidosis 20 8696 1110 6442 1.38 0.87-2.2 0.17 Systemic Sclerosis 50 16290 3850 18527 0.85 0.62-1.15 0.281 Polymyositis 30 12000 2360 13003 0.91 0.62-1.34 0.64 Rheumatoid Arthritis 510 2802 18350 4779 0.57 0.53-0.63 <0.001 Systemic Lupus Erythematosus 260 2014 6360 5332 0.37 0.32-0.41 <0.001 x x x x x x x x X UC Prevalence per 100,000 No UC Prevalence per 100,000 Odds Ratio 95% CI P-Value TOTAL 2370 1914 254000 804 2.41 2.31-2.51 <0.001 Adult (18-65) 910 1155 92360 498 2.32 2.18-2.48 <0.001 Senior (65+) 1450 3260 142010 1874 1.78 1.69-1.87 <0.001 Female 1290 1740 129570 746 2.35 2.23-2.48 <0.001 Male 1080 2191 124610 888 2.5 2.35-2.66 <0.001 Caucasian 2020 2120 181370 1086 1.97 1.89-2.06 <0.001 African American 240 2556 37500 1041 2.49 2.19-2.83 <0.001 Asian 20 1163 3440 692 1.69 1.09-2.63 <0.02 Amyloidosis 20 10526 1100 6369 1.73 1.08-2.76 0.022 Systemic Sclerosis 30 11539 3870 18590 0.57 0.39-0.84 0.004 Polymyositis 30 13636 2360 12981 1.06 0.72-1.56 0.774 Rheumatoid Arthritis 320 2362 18520 4765 0.48 0.43-0.54 <0.001 Systemic Lupus Erythematosus 110 1175 6490 5283 0.21 0.18-0.26 <0.001

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