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.

No abstract

Traditional approaches to understanding metabolomics in mental illness have focused on investigating a single disorder or comparisons between diagnoses, but a growing body of evidence suggests substantial mechanistic overlap in mental disorders that could be reflected by the metabolome. In this study, we investigated associations between global plasma metabolites and abnormal scores on the depression, anxiety, and phobic anxiety subscales of the Brief Symptom Inventory (BSI) among 405 older males who participated in the Normative Aging Study (NAS). Our analysis revealed overlapping and distinct metabolites associated with each mental health dimension subscale and four metabolites belonging to xenobiotic, carbohydrate, and amino acid classes that were consistently associated across all three symptom dimension subscales. Furthermore, three of these four metabolites demonstrated a higher degree of alteration in men who reported poor scores in all three dimensions compared to men with poor scores in only one, suggesting the potential for shared underlying biology but a differing degree of perturbation when depression and anxiety symptoms co-occur. Our findings implicate pathways of interest relevant to the overlap of mental health conditions in aging veterans and could represent clinically translatable targets underlying poor mental health in this high-risk population.

The application of large-scale metabolomic profiling 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 identified and independently replicated seventeen steroid metabolites that were significantly 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 confirmed in a four-year ICS clinical trial. Cortisol levels extracted from electronic medical records confirmed 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 modifications and improving overall patient care.