{
    "abstract": "Pediatric asthma is heterogeneous, with varied clinical presentations and treatment responses. Metabolomic profiling may uncover shared and unique biological mechanisms across clinical traits that characterize pediatric asthma.\nTo characterize the varied clinical presentation of pediatric asthma by examining the metabolome's relationship with 22 clinical traits, categorized into 5 phenotypic domains: airway hyperresponsiveness (AHR), atopy, lung function (LF), blood eosinophil (B-EOS), and blood neutrophil (B-NEU).\nMetabolomic profiling was conducted on plasma samples from children in the Childhood Asthma Management Program (CAMP) (n=953) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (n=1,155) studies. We identified domain-specific and multi-domain metabolites using a fixed-effect meta-analysis of generalized linear models between metabolites and 22 clinical traits. Metabolomic Risk Scores (MRSs) were developed to summarize the metabolic processes for each domain at the patient level.\nThere were 154 unique metabolites significantly associated with at least one of 22 clinical traits (q-value<0.05). \nThis study demonstrated the power of the metabolome to capture the heterogeneity in the clinical presentation of pediatric asthma and to develop clinically relevant MRSs that inform our understanding of specific metabotypes to guide targeted treatment approaches.",
    "authors": [
        {
            "affiliation": "Brigham and Women's Hospital Channing Division of Network Medicine, Boston, Massachusetts, United States.",
            "firstname": "Kevin M",
            "initials": "KM",
            "lastname": "Mendez"
        },
        {
            "affiliation": "Brigham and Women's Hospital Channing Division of Network Medicine, Department of Systems Genetics & Genomics, Boston, Massachusetts, United States.",
            "firstname": "Priyadarshini",
            "initials": "P",
            "lastname": "Kachroo"
        },
        {
            "affiliation": "Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, United States.",
            "firstname": "Nicole",
            "initials": "N",
            "lastname": "Prince"
        },
        {
            "affiliation": "Brigham and Women's Hospital Channing Division of Network Medicine, Boston, Massachusetts, United States.",
            "firstname": "Mengna",
            "initials": "M",
            "lastname": "Huang"
        },
        {
            "affiliation": "Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, United States.",
            "firstname": "Margaret",
            "initials": "M",
            "lastname": "Cote"
        },
        {
            "affiliation": "Brigham and Women's Hospital, Channing Division of Network Mediciine, Boston, Massachusetts, United States.\nHarvard Medical School, Medicine, Boston, United States.",
            "firstname": "Su H",
            "initials": "SH",
            "lastname": "Chu"
        },
        {
            "affiliation": "Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.",
            "firstname": "Yulu",
            "initials": "Y",
            "lastname": "Chen"
        },
        {
            "affiliation": "Brigham and Women's Hospital Channing Division of Network Medicine, medicine, Boston, Massachusetts, United States.",
            "firstname": "Rinku",
            "initials": "R",
            "lastname": "Sharma"
        },
        {
            "affiliation": "Brigham and Women's Hospital, Channing Division of Network Medicine, Boston, Massachusetts, United States.",
            "firstname": "Julian",
            "initials": "J",
            "lastname": "Hecker"
        },
        {
            "affiliation": "COPSAC, Gentofte, Denmark.\nUniversity of Copenhagen Faculty of Health and Medical Sciences, Kobenhavn, Denmark.",
            "firstname": "Liang",
            "initials": "L",
            "lastname": "Chen"
        },
        {
            "affiliation": "Beth Israel Deaconess Healthcare Jamaica Plain, Cardiology, Jamaica Plain, Massachusetts, United States.",
            "firstname": "Robert",
            "initials": "R",
            "lastname": "Gerszten"
        },
        {
            "affiliation": "3Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States.",
            "firstname": "Clary",
            "initials": "C",
            "lastname": "Clish"
        },
        {
            "affiliation": "Hospital Nacional de Ninos, Pediatric Pulmonology, San Jose, Costa Rica.",
            "firstname": "Lydiana",
            "initials": "L",
            "lastname": "Avila"
        },
        {
            "affiliation": "University of Pittsburgh, Pediatric Pulmonary Medicine, Pittsburgh, Pennsylvania, United States.\nCHILDREN'S HOSPITAL OF PITTSBURGH.",
            "firstname": "Juan C",
            "initials": "JC",
            "lastname": "Celed\u00f3n"
        },
        {
            "affiliation": "Karolinska Institutet, Medical Biochemistry and Biophysics, Stockholm, Stockholm County, Sweden.",
            "firstname": "Craig E",
            "initials": "CE",
            "lastname": "Wheelock"
        },
        {
            "affiliation": "Brigham and Women's Hospital Channing Division of Network Medicine, Boston, Massachusetts, United States.\nHarvard Medical School, Boston, Massachusetts, United States.",
            "firstname": "Scott T",
            "initials": "ST",
            "lastname": "Weiss"
        },
        {
            "affiliation": "Brigham and Women's Hospital, Channing Division of Network Medicine, Boston, Massachusetts, United States.",
            "firstname": "Michael",
            "initials": "M",
            "lastname": "McGeachie"
        },
        {
            "affiliation": "Edith Cowan University, Joondalup, Australia.",
            "firstname": "David I",
            "initials": "DI",
            "lastname": "Broadhurst"
        },
        {
            "affiliation": "Brigham and Women's Hospital, Channing Division of Network Medicine, Boston, Massachusetts, United States.",
            "firstname": "Rachel S",
            "initials": "RS",
            "lastname": "Kelly"
        },
        {
            "affiliation": "Edith Cowan University, Joondalup, Australia.",
            "firstname": "Stacey N",
            "initials": "SN",
            "lastname": "Reinke"
        },
        {
            "affiliation": "Brigham and Women's Hospital Channing Division of Network Medicine, Boston, Massachusetts, United States; rejas@channing.harvard.edu.",
            "firstname": "Jessica A",
            "initials": "JA",
            "lastname": "Lasky-Su"
        }
    ],
    "conclusions": "This study demonstrated the power of the metabolome to capture the heterogeneity in the clinical presentation of pediatric asthma and to develop clinically relevant MRSs that inform our understanding of specific metabotypes to guide targeted treatment approaches.",
    "copyrights": null,
    "doi": "10.1164/rccm.202407-1382OC",
    "journal": "American journal of respiratory and critical care medicine",
    "keywords": [
        "Asthma",
        "Metabolomics",
        "Metabolomics Risk Score",
        "Metabotypes",
        "Phenotypes"
    ],
    "methods": null,
    "publication_date": "2025-02-18",
    "pubmed_id": "39965055",
    "results": null,
    "title": "Exploring the Varied Clinical Presentation of Pediatric Asthma through the Metabolome.",
    "xml": "<Element 'PubmedArticle' at 0x788503e19350>"
}