Inhaled corticosteroid increased the risk of adrenal insufficiency in patients with chronic airway diseases: a nationwide population-based study

Inhaled corticosteroids (ICS) are commonly used for airway disease, but concerns about adrenal insufficiency (AI) have arisen. This retrospective observational study investigated the link between ICS use and AI risk using data from the National Health Insurance Service-National Sample Cohort, analyzing 66,631 patients with COPD (Korean Standard Classification of Diseases [KCD] codes J42-J44) or asthma (KCD codes J45-J46). ICS use, daily dosage, and AI cases (hospitalization or ≥ 2 outpatient visits with KCD code E27) were identified via diagnostic codes. Cox proportional hazard survival analysis and inverse probability of treatment weighting (IPTW) addressed baseline differences between ICS and non-ICS users. In total 66,631 patients, the mean age was 57.3 years, 42.6% were male, and 42.2% had a Charlson comorbidity index (CCI) of 2 or higher. Among the patients, 15.5% used ICS, with a mean daily dose of 404.2 µg/day. The incidence of AI was higher in ICS users (1.69 per 1000) than in non-users (0.54 per 1000). ICS use independently increased AI risk (HR: 3.06, 95% CI: 1.82-5.14, p < 0.001). Each 100 µg/day increase in ICS was associated with a 3% increase in AI incidence (HR: 1.03, 95% CI: 1.02-1.04, p < 0.001). Quartile analysis indicated a significant AI risk increase across all ICS dosage quartiles compared with non-users. Subgroup analysis showed consistent associations with age, sex, and smoking, with stronger links in systemic steroid users (HR: 3.54, 95% CI: 2.10-5.96, p < 0.001) and those with higher CCI (HR: 2.61, 95% CI: 1.64-4.12, p < 0.001). ICS may use increases AI risk in chronic airway disease patients, particularly among systemic steroid users and those with higher CCI. Close monitoring of high-risk patients is advised, and further research is needed to clarify mechanisms and optimize safe ICS use.