Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and FIO2 Ventilation Strategy in COVID-19 ARDS
Issued Date
2025-06-01
Resource Type
eISSN
29497884
Scopus ID
2-s2.0-105006506497
Journal Title
Chest Critical Care
Volume
3
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
Chest Critical Care Vol.3 No.2 (2025)
Suggested Citation
Goossen R.L., Filippini D.F.L., van Vliet R., Buiteman-Kruizinga L.A., Hollmann M.W., Myatra S.N., Neto A.S., Spronk P.E., van der Woude M.C.E., Schultz M.J., van Meenen D.M.P., Paulus F., Bos L.D.J. Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and FIO2 Ventilation Strategy in COVID-19 ARDS. Chest Critical Care Vol.3 No.2 (2025). doi:10.1016/j.chstcc.2025.100145 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110468
Title
Longitudinal Respiratory Subphenotypes and Differences in Response to Positive End-Expiratory Pressure and FIO2 Ventilation Strategy in COVID-19 ARDS
Author's Affiliation
Melbourne Medical School
Nuffield Department of Medicine
Reinier de Graaf Hospital - SSDZ
Hogeschool van Amsterdam, University of Applied Sciences
Zuyderland
Mahidol Oxford Tropical Medicine Research Unit
Medizinische Universität Wien
Monash University
Tata Memorial Hospital
Gelre Ziekenhuizen
Austin Hospital
Hospital Israelita Albert Einstein
Universiteit van Amsterdam
Nuffield Department of Medicine
Reinier de Graaf Hospital - SSDZ
Hogeschool van Amsterdam, University of Applied Sciences
Zuyderland
Mahidol Oxford Tropical Medicine Research Unit
Medizinische Universität Wien
Monash University
Tata Memorial Hospital
Gelre Ziekenhuizen
Austin Hospital
Hospital Israelita Albert Einstein
Universiteit van Amsterdam
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: In patients with ARDS, positive end-expiratory pressure (PEEP) titration remains a challenge and recommendations are not in agreement. In mechanically ventilated patients with COVID-19, subphenotypes based on different respiratory trajectories have been identified, but their heterogeneity in response to PEEP/FIO<inf>2</inf> strategy remains understudied. Research Question: Can these previously determined subphenotypes be detected early in the course of mechanical ventilation, and do these subphenotypes moderate the association between PEEP and FIO<inf>2</inf> ventilation strategy and mortality? Study Design and Methods: Retrospective analysis of invasively ventilated patients with COVID-19. Patients were categorized into 2 treatment groups: high PEEP/low FIO<inf>2</inf> strategy and low PEEP/high FIO<inf>2</inf> strategy. To replicate previously described longitudinal respiratory subphenotypes, hereafter named the low-power or high-power subphenotype, a prediction model was created. The primary outcome was the interaction between PEEP/FIO<inf>2</inf> strategy and subphenotype, with mortality as the dependent variable. Results: Of the 1,464 patients included in this analysis, 361 patients (25%) were allocated into the high PEEP/low FIO<inf>2</inf> strategy and 1,103 patients (75%) were allocated into the low PEEP/high FIO<inf>2</inf> strategy. A prediction model consisting of respiratory data of the first 2 days of invasive ventilation (area under the receiver operating characteristics curve, 0.88) assigned 908 patients (62%) to the low-power subphenotype and 556 patients (38%) to the high-power subphenotype. The high-power subphenotype was characterized by higher minute volume, mechanical power, ventilatory ratio, and driving pressure. The association between PEEP/FIO<inf>2</inf> ventilation strategy and ICU mortality was moderated by the subphenotype (P = .03), with high PEEP/low FIO<inf>2</inf> ventilation being associated with lower mortality in the low-power subphenotype (OR, 0.46; 95% CI, 0.31-0.67; P < .001) and not in the high-power subphenotype (OR, 0.85; 95% CI, 0.57-1.28; P = .44). Interpretation: In this study, high PEEP/low FIO<inf>2</inf> ventilation was associated with improved mortality only in one of the subphenotypes, suggesting that such subphenotypes influence heterogeneity of PEEP and FIO<inf>2</inf> effect and should be considered in personalized ventilation strategies. Clinical Trial Registry: ClinicalTrials.gov; No.: NCT05954351; URL: www.clinicaltrials.gov