Photo Credit: Evgeniya Pavlova

The following is a summary of “Plasma pharmacometabolomics of inhaled corticosteroid-related adrenal suppression in asthma,” published in the March 2025 issue of Journal of Allergy and Clinical Immunology by Tran et al. 

Inhaled corticosteroids (ICS) treat asthma but may cause adrenal insufficiency at higher doses. Identifying at-risk patients can improve treatment. 

Researchers conducted a retrospective study identifying metabolite signatures and pathways linked to ICS-related adrenal insufficiency in asthma.  

They integrated global metabolomics with medical records in 2 asthma cohorts. In 711 patients (Pharmacogenomics of Adrenal Suppression with Inhaled Corticosteroids (PhASIC) cohort), 1,397 metabolites were analyzed, and 810 were selected. Plasma cortisol served as a biomarker, with linear regression assessing metabolite associations, adjusting for confounders. Findings were validated in 575 ICS users, with pathway and network analyses conducted. 

The results showed 12 of 810 metabolites were linked to adrenal insufficiency after multiple comparison correction. In the validation cohort, three replicated, including 2 steroid metabolites (tetrahydrocortisol glucuronide, tetrahydrocortisol glucuronide (5)) and homocitrulline. Pathway analyses identified disruptions in steroid, bile acid, urea cycle, and long-chain polyunsaturated fatty acid metabolism. 

Investigators identified specific metabolites in steroid and non-steroid pathways associated with adrenal insufficiency from ICS use. 

Source: jacionline.org/article/S0091-6749(25)00274-X/full