Interstitial lung disease in mixed connective tissue disease: Insights from an electronic health record-based...

Pulmonary complications, including interstitial lung disease (ILD), are common and contribute to morbidity and mortality in mixed connective tissue disease (MCTD). However, risk factors for ILD in MCTD are poorly understood, which can hinder early detection of this fatal complication. The purpose of this study was to identify predictors of ILD presence in MCTD using structured electronic health record (EHR) data.

We performed a retrospective EHR-based investigation of adults with MCTD evaluated at a large urban academic medical center between 2014 and 2026. Patients were identified using an adapted Kasukawa classification algorithm. Univariable and multivariable logistic regression were used to assess associations between clinical features and ILD. Cox proportional hazards models with time-dependent ILD status were used to examine mortality. A prespecified sensitivity analysis was performed using a more restrictive cohort definition.

Among 120 patients, 61 (50.8%) had ILD. In multivariable logistic regression, pulmonary hypertension (PH) was independently associated with ILD (OR 5.10, 95% CI 1.91-13.63, p = 0.001). Age 55-74 years was independently associated with ILD (OR 7.61, 95% CI 1.74-33.33, p = 0.007). Gastroesophageal reflux disease (GERD) was associated with higher odds of ILD, although the association did not reach statistical significance after adjustment (OR 3.16, 95% CI 0.92-10.79, p = 0.067). In the survival analysis (n = 120, 11 deaths), the time-dependent hazard ratio for ILD was 2.57 (95% CI 0.74-8.94, p = 0.137); the age-adjusted HR was 2.60 (95% CI 0.75-9.03, p = 0.134).

ILD affected roughly half of patients with MCTD in this EHR-based cohort. PH and older age were independently associated with ILD, suggesting that patients with these features may warrant heightened pulmonary surveillance. Survival analyses were hypothesis-generating, with ILD associated with numerically higher mortality that did not reach statistical significance. Structured EHR methods can delineate real-world disease patterns in rare systemic autoimmune disease like MCTD. Standardized classification and routine pulmonary screening may enable earlier recognition and targeted intervention.