ArticleCHEST critical care2026
Characterization and 3-Year Survival of Clinical Subtypes and Host Response Phenotypes of Acute Respiratory Failure Requiring Mechanical Ventilation.
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20 authors.
Georgios D KitsiosDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
William G BainDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
John W EvankovichDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Niall PrendergastDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Matthew HensleyDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Tomeka SuberDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Kyle InmanDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Caitlin SchaeferDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Melissa SaulDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Xiaoping ChenDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Menaal HaqueDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Janet LeeDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Alicia RizzoDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Shulin QinDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Yingze ZhangDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Alison MorrisDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Charles Dela CruzDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Seyed Mehdi NouraieDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Bryan J McVerryDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Faraaz A ShahDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., C. S., M. S., X. C., A. R., S. Q., Y. Z., C. D. C., S. M. N., B. J. M., and F. A. S.), Department of Medicine, the Acute Lung Injury and Infection Center of Excellence (G. D. K., W. G. B., J. W. E., N. P., M. H., T. S., K. I., A. R., C. D. C., S. M. N., B. J. M., and F. A. S.), University of Pittsburgh; the Veterans Affairs Pittsburgh Healthcare System (W. G. C., B. J. M., and F. A. S.), Pittsburgh, PA; the George Washington University (M. H.), Washington, DC; the Washington University School of Medicine (J. L.), St. Louis, MO; and the Rutgers Robert Wood Johnson Medical School (A. M.), New Brunswick, NJ. B. J. M. and F. A. S. contributed equally to this manuscript.
Funding
Regulation of Cardiolin Byosynthesis in Epithelial InjuryP01HL114453 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2014 to 2023
$21.3MPrecision Medicine Approach to Glucocortisteroids in SepsisR01GM141081 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ANGUS, DEREK C, YENDE, SACHIN · 2021 to 2024
$2.6MAirspace Candida Colonization and Lung Injury (AirCCoLIN)R01HL176668 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Georgios Kitsios · 2025 to 2026
$1.4MImproving Characterization of Individualized Treatment Effects in Critical IllnessR35GM160146 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Faraaz Ali Shah · 2025 to 2026
$875kPrecision Medicine for Nutrition in EDENR21HL168070 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHAH, FARAAZ ALI · 2023 to 2024
$239kMicrobial Determinants of Acute Respiratory Distress Syndrome Severity (MiDAS)R03HL162655 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KITSIOS, GEORGIOS · 2022 to 2023
$159kNHLBI NIH HHS P01 HL114453NHLBI NIH HHS R01 HL176668NHLBI NIH HHS R03 HL162655NHLBI NIH HHS R21 HL168070NIGMS NIH HHS R01 GM141081NIGMS NIH HHS R35 GM160146
Abstract
backgroundAcute respiratory failure (ARF) requiring invasive mechanical ventilation affects approximately 1.5 million adults in the United States annually. Whereas ARDS is well characterized, non-ARDS ARF-comprising most patients who are mechanically ventilated-lacks systematic characterization of clinical features, biological profiles, and long-term outcomes. RESEARCH QUESTION: How do ARF subtypes differ in clinical, physiologic, and biological characteristics and in long-term survival? STUDY DESIGN AND
methodsProspective cohort study of 826 mechanically ventilated adults enrolled at a single academic center from 2011 through 2024. Patients were classified systematically into 7 predefined ARF subtypes using consensus methodology. We compared physiologic features, biological subphenotypes, and 3-year survival.
resultsPatients were classified as having ARDS (36.1%), being at risk for ARDS (ARFA; 34.1%), having airway control (10.7%), having other or multifactorial features (7.4%), having congestive heart failure (CHF; 6.2%), having acute-on-chronic hypercapnic respiratory failure (AoCHRF; 3.3%), and having acute exacerbation of interstitial lung disease (AEILD; 2.3%). Subtypes differed significantly in gas exchange (hypoxemia and ventilatory ratio), respiratory mechanics (normalized elastance), and radiographic severity (
interpretationOur results show that patients who are mechanically ventilated with ARF demonstrate marked heterogeneity in physiologic features, biology, and long-term outcomes. Overall, fewer than one-half of patients survived to 3 years, but survival varied markedly across clinical subtypes beyond traditional ARDS categorization. Clinical subtype classification identifies distinct populations with divergent long-term prognoses, providing information complementary to biological subphenotyping. These findings provide quantitative outcome data to support prognostic counseling and to establish a reproducible framework for clinical research in ARF resulting from heterogeneous causes.
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acute respiratory failureARDSprecision medicinepredictionsubphenotype
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