Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma

Abstract

The application of large-scale metabolomic pro ling provides new opportunities to realize the potential of omics-based precision medicine with regard to asthma. We leveraged over 14,000 individuals from four distinct epidemiological studies. We identi ed and independently replicated seventeen steroid metabolites that were signi cantly reduced in individuals with prevalent asthma. Importantly steroid levels were reduced among all individuals with asthma regardless of medication use; however, the largest reduction was associated with inhaled corticosteroids use (ICS) that was further con rmed in a four-year ICS clinical trial. Cortisol levels extracted from electronic medical records con rmed that cortisol is reduced among asthmatics taking ICS over the entire 24-hour period, compared with all other groups.Clinical-grade adrenal suppression in asthmatics on ICS, resulting from substantial reductions in steroid metabolites, represents a larger public health problem than previously recognized. Regular cortisol testing may identify at-risk individuals, enabling personalized treatment modi cations and improving overall patient care.

Metabolomic changes related to airway inflammation, asthma pathogenesis and systemic activity following inhaled fluticasone furoate/vilanterol: a randomized controlled trial

“…For example, FF 100 µg has been previously shown to produce a 7% reduction in plasma cortisol, which although not statistically significant, is a dose-related effect [ 11 ]. Similarly, in a large metabolic profiling study by Kachroo et al [ 12 ] , a dose–effect relationship was observed with steroid metabolites including cortisol and dehydroisoandrosterone sulfate and ICS treatment. Although this reduction was primarily driven by ICS treatment, reduced steroid levels also represented a fundamental characteristic of pathophysiology of asthma [ 12 ].…”

“…Similarly, in a large metabolic profiling study by Kachroo et al [ 12 ] , a dose–effect relationship was observed with steroid metabolites including cortisol and dehydroisoandrosterone sulfate and ICS treatment. Although this reduction was primarily driven by ICS treatment, reduced steroid levels also represented a fundamental characteristic of pathophysiology of asthma [ 12 ]. It is important to note that cortisol suppression is not the same as adrenal suppression; nevertheless, reductions in steroid metabolites have been referred to as “adrenal insufficiency” by some authors [ 12 ], but this was without evidence via adrenocorticotropic hormone stimulation testing.…”

“…Although this reduction was primarily driven by ICS treatment, reduced steroid levels also represented a fundamental characteristic of pathophysiology of asthma [ 12 ]. It is important to note that cortisol suppression is not the same as adrenal suppression; nevertheless, reductions in steroid metabolites have been referred to as “adrenal insufficiency” by some authors [ 12 ], but this was without evidence via adrenocorticotropic hormone stimulation testing. Since the magnitude of the steroid metabolite reductions following low-dose ICS are generally small and hence readily reversible on discontinuation of ICS therapy, they may not be clinically significant in the majority of cases.…”

Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel Syndrome

“…Metabolomics is a comprehensive biochemical profiling technique that is used to assess systemic metabolism in a biological sample, reflecting the “net effects” of genetic, transcriptomic, proteomic, and environmental interactions [ 5 , 6 ]. The authors of a recent study performed fecal metabolomics in infants receiving PN, in which they identified 12 sphingomyelin lipids as potential biomarkers for the development of cholestasis in combination with birth anthropometry [ 7 ].…”

The Evolution of a Large Biobank at Mass General Brigham

“…The scientific dividends of the Biobank have already been substantial. For example, MGB Biobank data have been used in studies demonstrating the limitations of contemporary guidelines for managing patients at high genetic risk of coronary artery disease, to evaluate polygenetic Risk Score models for prostate cancer, and to identify extensive adrenal suppression due to inhaled coriscosteroid therapy in asthma [ 17 , 18 , 19 ]. It also provides the foundation to manage large NIH-funded research programs that require IT support that can scale and staff with large-scale recruitment and biobanking experience.…”