{
  "abstract": "Rationale: Hyperinflammatory and hypoinflammatory phenotypes previously identified in sepsis and acute respiratory distress syndrome may enable precision therapies, but their clinical relevance and translational modeling in severe pneumonia remain incompletely characterized.\n\nObjectives: To examine biomarker-defined hyperinflammatory and hypoinflammatory phenotypes in critically ill patients with pneumonia (pulmonary sepsis), test whether the biomarkers that define these phenotypes identify subgroups and outcomes in a mouse model of bacterial pneumonia, and determine whether the mouse phenotypes respond differently to therapeutic interventions.\n\nMethods: We performed latent class analysis (LCA) in a cohort of 548 ICU patients with pulmonary sepsis to identify inflammatory phenotypes and test the association of these phenotypes with clinical outcomes using validated classifier models. We developed a mouse model of pneumococcal pneumonia that recapitulated key aspects of these phenotypes and tested responses to dexamethasone and IL-6 receptor blockade.\n\nMeasurements and Main Results: Two phenotypes were identified in patients with pulmonary sepsis: a hyperinflammatory phenotype with more lung injury and increased mortality, and a hypoinflammatory phenotype with more favorable outcomes. Despite uniform pathogen exposure and baseline conditions, LCA identified 2 phenotypes in the mice with divergent trajectories (lung injury and mortality). Therapeutic benefit from anti-inflammatory interventions was observed exclusively in the more inflamed mice.\n\nConclusions: By integrating clinical data from human studies and experimental findings in a clinically relevant mouse model, this study provides a translational framework for developing phenotype-targeted therapies for critical illness, with the goal of improving patient outcomes.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "name": "Hiroki Taenaka"
    },
    {
      "name": "Bruno Evrard"
    },
    {
      "name": "Mazharul Maishan"
    },
    {
      "name": "Ruriko Watanabe"
    },
    {
      "name": "Narges Alipanah-Lechner"
    },
    {
      "name": "Sidney A Carrillo"
    },
    {
      "name": "Aartik Sarma",
      "orcid": "0000-0002-7508-7345"
    },
    {
      "name": "Natasha Spottiswoode",
      "orcid": "0000-0001-6157-3716"
    },
    {
      "name": "Kathryn M Sullivan",
      "orcid": "0000-0001-8107-8253"
    },
    {
      "name": "Melanie F Weingart"
    },
    {
      "name": "Hanjing Zhuo"
    },
    {
      "name": "Angelika Ringor"
    },
    {
      "name": "Carolyn Leroux"
    },
    {
      "name": "Olivia Chao"
    },
    {
      "name": "Chelsea Lin"
    },
    {
      "name": "Emma Schmiege"
    },
    {
      "name": "Taarini Hariharan"
    },
    {
      "name": "Liam Magee"
    },
    {
      "name": "Andrew Willmore"
    },
    {
      "name": "Suzanna Chak"
    },
    {
      "name": "Deanna Lee"
    },
    {
      "name": "Kim Bardillon"
    },
    {
      "name": "Carolyn Hendrickson"
    },
    {
      "name": "Jeffrey E Gotts"
    },
    {
      "name": "Charles R Langelier"
    },
    {
      "name": "Carolyn S Calfee"
    },
    {
      "name": "Michael A Matthay"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/06y10fpas766g.bib",
  "cited_by": 1,
  "doi": "10.1093/ajrccm/aamag402",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13721131/",
  "id": "06y10fpas766g",
  "issns": [
    "1073-449X",
    "1535-4970"
  ],
  "landing_url": "https://doi.org/10.1093/ajrccm/aamag402",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/MED00010"
    ],
    [
      "heading",
      "AcademicSubjects/MED00160"
    ],
    [
      "heading",
      "AcademicSubjects/MED00350"
    ],
    [
      "heading",
      "Original Research"
    ],
    [
      "heading",
      "Pulmonary Infections"
    ],
    [
      "openalex",
      "2713|Sepsis Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7171980964",
  "pdf_url": null,
  "pmcid": "PMC13721131",
  "pmid": "42535902",
  "published": "2026-07-31",
  "publisher": "American Thoracic Society",
  "ris": "https://research.draconitic.com/paper/06y10fpas766g.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:21:52Z",
      "native_id": "PMC13721131",
      "source": "pmc",
      "url": "https://doi.org/10.1093/ajrccm/aamag402"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Sepsis Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Inflammatory phenotypes in severe pneumonia: clinical evidence to mouse models for precision therapeutics",
  "title_text": "Inflammatory phenotypes in severe pneumonia: clinical evidence to mouse models for precision therapeutics",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:52Z",
  "url": "https://research.draconitic.com/paper/06y10fpas766g",
  "venue": "American Journal of Respiratory and Critical Care Medicine",
  "versions": []
}