CHEST critical care · 2026
Characterization and 3-Year Survival of Clinical Subtypes and Host Response Phenotypes of Acute Respiratory Failure Requiring Mechanical Ventilation.
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Kitsios Georgios D, Bain William G, Evankovich John W, Prendergast Niall, Hensley Matthew, Suber Tomeka, Inman Kyle, Schaefer Caitlin, Saul Melissa, Chen Xiaoping, Haque Menaal, Lee Janet, Rizzo Alicia, Qin Shulin, Zhang Yingze, Morris Alison, Cruz Charles Dela, Nouraie Seyed Mehdi, McVerry Bryan J, Shah Faraaz A
Аннотация
BACKGROUND: Acute 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 METHODS: Prospective 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.
RESULTS: Patients 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 (P < .01 for all). Plasma inflammatory biomarkers were highest in patients with ARDS and ARFA, with hyperinflammatory subphenotype prevalence ranging from 0% (AoCHRF) to 30.1% (ARFA). Three-year survival ranged from 10.5% (AEILD) to 67.0% (airway control): 37.7% (other or multifactorial), 48.1% (AoCHRF), 56.9% (CHF), 53.2% (ARFA), and 51.3% (ARDS). Hyperinflammatory subphenotype classification predicted lower survival (42.9% vs 54.9%; P < .01), predominantly in patients with ARDS and ARFA, whereas patients with other subtypes showed minimal subphenotype-associated survival differences.
INTERPRETATION: Our 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.
RESEARCH QUESTION: How do ARF subtypes differ in clinical, physiologic, and biological characteristics and in long-term survival?
STUDY DESIGN AND METHODS: Prospective 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.
RESULTS: Patients 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 (P < .01 for all). Plasma inflammatory biomarkers were highest in patients with ARDS and ARFA, with hyperinflammatory subphenotype prevalence ranging from 0% (AoCHRF) to 30.1% (ARFA). Three-year survival ranged from 10.5% (AEILD) to 67.0% (airway control): 37.7% (other or multifactorial), 48.1% (AoCHRF), 56.9% (CHF), 53.2% (ARFA), and 51.3% (ARDS). Hyperinflammatory subphenotype classification predicted lower survival (42.9% vs 54.9%; P < .01), predominantly in patients with ARDS and ARFA, whereas patients with other subtypes showed minimal subphenotype-associated survival differences.
INTERPRETATION: Our 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.