{
  "abstract": "Purpose Subphenotype classifiers for acute respiratory distress syndrome (ARDS) dichotomise patients into hyperinflammatory versus hypoinflammatory subgroups. These models demonstrated prognostic and predictive values but were developed primarily in Caucasian populations. Generalisability of these models in Asian patients, who experience worse clinical outcomes, has not been established. We aimed to profile host responses in Asian patients with ARDS and evaluate the generalisability of established classifiers in this understudied population compared with a Caucasian cohort.Methods We prospectively enrolled patients with ARDS from medical intensive care units in Beijing, China, and Pittsburgh, Pennsylvania, USA. In the Beijing cohort, 37 protein biomarkers were measured, with 10 overlapping biomarkers measured in the Pittsburgh cohort. Six established subphenotype models were assessed for generalisability and intermodel agreement. Sensitivity analyses, including latent class analysis, were conducted to explore biological heterogeneity within Asians.Results Between 2011 and 2020, a total of 356 patients with ARDS (83% meeting the Berlin Definition; the rest on high-flow nasal cannula (HFNC) meeting the New Global Definition) were enrolled across Beijing (97% Han Asian) and Pittsburgh (90% Caucasian) sites, with comparable baseline hypoxaemia severity but disparate outcome. While the proportion of hyperinflammatory versus hypoinflammatory subphenotypes was predicted to be overall similar across different cohorts per each model, we observed poor intermodel agreement. We observed heightened inflammation in Berlin patients with ARDS compared with HFNC-ARDS within our Asian cohort.Conclusion Established subphenotype classifiers demonstrated similar distribution of subphenotypes in Asian patients with ARDS. However, poor intermodel agreement highlights the need for further investigation into model variability with models coming closer to bedside implementation.Trial registration number NCT02975908.",
  "authors": [
    {
      "affiliations": [
        "Tsinghua Medicine, Tsinghua University, Beijing, China",
        "Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA",
        "Department of Pulmonary and Critical Care Medicine, Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China",
        "National Center for Respiratory Medicine",
        "National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China"
      ],
      "name": "Haopu Yang"
    },
    {
      "affiliations": [
        "Department of Pulmonary and Critical Care Medicine, Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China",
        "National Center for Respiratory Medicine",
        "National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China"
      ],
      "name": "Jingen Xia"
    },
    {
      "affiliations": [
        "Department of Pulmonary and Critical Care Medicine, Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China",
        "National Center for Respiratory Medicine",
        "National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China"
      ],
      "name": "Xu Huang"
    },
    {
      "affiliations": [
        "Department of Pulmonary and Critical Care Medicine, Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China",
        "National Center for Respiratory Medicine",
        "National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China"
      ],
      "name": "Yu Bai"
    },
    {
      "affiliations": [
        "Department of Pulmonary and Critical Care Medicine, Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China",
        "National Center for Respiratory Medicine",
        "National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China"
      ],
      "name": "Dan Jin"
    },
    {
      "affiliations": [
        "Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Seyed Mehdi Nouraie"
    },
    {
      "affiliations": [
        "Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Bryan J McVerry"
    },
    {
      "affiliations": [
        "Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Alison Morris"
    },
    {
      "affiliations": [
        "Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Georgios D Kitsios"
    },
    {
      "affiliations": [
        "Department of Pulmonary and Critical Care Medicine, Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China",
        "National Center for Respiratory Medicine",
        "National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China"
      ],
      "name": "Chen Wang"
    },
    {
      "affiliations": [
        "Department of Pulmonary and Critical Care Medicine, Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China",
        "National Center for Respiratory Medicine",
        "National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China"
      ],
      "name": "Qingyuan Zhan"
    }
  ],
  "title": "Generalisability of ARDS biological subphenotype models in Asians: an international, multicentre, prospective biomarker study",
  "uid": "9f6b70eb-87c1-502a-8669-9f20b1569aa3"
}