Impact of Glucocorticoids on Interstitial Lung Disease: A Medical Information Mart for Intensive Care and Mendelian Randomization Study

BACKGROUND: Glucocorticoids are commonly used for treating interstitial lung disease (ILD); however, their causation with ILD is unclear. OBJECTIVE: To explore the correlation of glucocorticoids and 30-day ILD mortality and to analyze their causation using Mendelian randomization (MR). METHODS: ILD patients' data were extracted from the MIMIC-IV. Kaplan-Meier curves and Cox proportional hazards models assessed the relationship between glucocorticoid use and 30-day ILD mortality, including stratified analyses. The effects of different types of glucocorticoids were examined. MR analysis was conducted using Genome-Wide Association Studies data involving individuals of European ancestry to evaluate potential causal relationships between glucocorticoids, lung function parameters (FVC, FEV1, FEV1/FVC), and ILD. RESULTS: In MIMIC-IV study, ILD patients treated with glucocorticoids exhibited significantly lower survival rates within 14-30 days compared to those without treatment (log-rank P < 0.001). In ILD patients with COPD, long-acting glucocorticoids (HR = 2.400, P = 0.031) was significantly associated with an increased 30-day mortality rate. MR analyses showed a negative causative relationship between glucocorticoids and pulmonary function parameters (FVC (OR = 0.957, P < 0.001), FEV1 (OR = 0.920, P < 0.001) and FEV1/FVC (OR = 0.920, P < 0.001)), indicating that glucocorticoid use may cause a decrease in lung function parameters. A positive causal relationship with ILD (OR = 1.453, P = 0.014) suggested that glucocorticoid use may accelerate ILD progression and affect patients' prognosis. CONCLUSION: Glucocorticoid use is significantly associated with increased 30-day ILD mortality, especially for men and those with comorbid COPD. Glucocorticoids may increase the risk of ILD progression through a causal mechanism, affecting patient prognosis. Future studies should explore glucocorticoids in different ILD subtypes to develop individualized strategies.