Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma.
Stewart, Isobel D
Soeteman, Djøra I
Chu, Su H
Knihtilä, Hanna M
Wu, Ann Chen
Karlson, Elizabeth W
Wheelock, Craig E
Weiss, Scott T
Springer Science and Business Media LLC
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Kachroo, P., Stewart, I. D., Kelly, R. S., Stav, M., Mendez, K., Dahlin, A., Soeteman, D. I., et al. (2022). Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma.. Nat Med https://doi.org/10.1038/s41591-022-01714-5
The application of large-scale metabolomic profiling provides new opportunities for realizing the potential of omics-based precision medicine for asthma. By leveraging data from over 14,000 individuals in four distinct cohorts, this study identifies and independently replicates 17 steroid metabolites whose levels were significantly reduced in individuals with prevalent asthma. Although steroid levels were reduced among all asthma cases regardless of medication use, the largest reductions were associated with inhaled corticosteroid (ICS) treatment, as confirmed in a 4-year low-dose ICS clinical trial. Effects of ICS treatment on steroid levels were dose dependent; however, significant reductions also occurred with low-dose ICS treatment. Using information from electronic medical records, we found that cortisol levels were substantially reduced throughout the entire 24-hour daily period in patients with asthma who were treated with ICS compared to those who were untreated and to patients without asthma. Moreover, patients with asthma who were treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS treatment. Adrenal suppression in patients with asthma treated with ICS might, therefore, represent a larger public health problem than previously recognized. Regular cortisol monitoring of patients with asthma treated with ICS is needed to provide the optimal balance between minimizing adverse effects of adrenal suppression while capitalizing on the established benefits of ICS treatment.
Effort from PK, JALS and STW is supported by P01HL132825 from the National Heart, Lung and Blood Institute, National Institutes of Health (NIH/NHLBI), USA. IDS is funded by the Medical Research Council (MC_UU_00006/1 - Etiology and Mechanisms). Effort for RK, DIS, MC, KM, MS and JALS is supported by R01HL123915 from the NIH/NHLBI and W81XWH-17-1-0533 from the U.S.A Department of Defense. Effort for RSK is supported by K01HL146980 from the NIH/NHLBI. Effort for SHC is supported by K01HL153941 from the NIH/NHLBI. Effort for MH and JALS is supported by R01HL141826 from the NIH/NHLBI. Effort for AD is supported by K01HL130629 from the NIH/NHLBI. Effort for AD and JALS is supported by 1R01HL152244 from the NIH/NHLBI. Effort for MM and JALS is supported by R01HL155742 from the NIH/NHLBI. Effort for HK is supported by the Jane and Aatos Erkko Foundation, the Paulo Foundation, and the Pediatric Research Foundation. Effort for KLS is supported by K08HL148178 from the NIH/NHLBI. Effort for MM is supported by R01HL139634 from the NIH/NHLBI. Effort for AW is supported by K23HL151819 from the NIH/NHLBI and Thrasher Research Fund Award (15115). Effort for ACW is supported by 1R01HD085993 from the NICHD. Effort for YV is supported by K23AI130408 from the NIAID. Effort for JALS, STW, EWK is supported by the NIH U01HG008685. Effort for PZ and CEW was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (JP19K21239), the Japanese Environment Research and Technology Development Fund (No. 5-1752), the Gunma University Initiative for Advanced Research (GIAR), the Japan-Sweden Research Cooperative Program between JSPS and STINT (grant no. JPJSBP-1201854), the Swedish Heart Lung Foundation (HLF 20180290, HLF 20200693), and the Swedish Research Council (2016-02798). The EPIC-Norfolk study (https://doi.org/10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 MC-UU_12015/1 and MC_UU_00006/1) and Cancer Research UK (C864/A14136). Metabolite measurements in the EPIC-Norfolk study were supported by the MRC Cambridge Initiative in Metabolic Science (MR/L00002/1) and the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372.
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MR/N003284/1)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
External DOI: https://doi.org/10.1038/s41591-022-01714-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335809
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