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RATIONALE The respective effects of PEEP and pressure support delivered through the helmet interface in hypoxemic patients need to be better understood. OBJECTIVES To assess the respective effects of helmet pressure support (NIV) and continuous positive-airway pressure (CPAP) compared to high-flow nasal oxygen (HFNO) on effort to breathe, lung inflation and gas exchange in hypoxemic patients (PaO2/FiO2≤200). METHODS Fifteen patients underwent 1-hour phases (constant FiO2) of HFNO (60 L/min), helmet NIV (PEEP=14 cmH2O, pressure support=12 cmH2O) and CPAP (PEEP=14 cmH2O) in randomized sequence. MEASUREMENTS Inspiratory esophageal (ΔPES) and transpulmonary pressure (ΔPL) swings were used as surrogates for inspiratory effort and lung distension, respectively. Tidal volume (VT) and end-expiratory lung volume were assessed with electrical impedance tomography. MAIN RESULTS ΔPES was lower during NIV vs. CPAP and HFNO (5[3-9] cmH2O vs. 13[10-19] vs. 10[8-13], p=0.001 and p=0.01). ΔPL was not statistically different between treatments. PaO2/FiO2 ratio was significantly higher during NIV and CPAP vs. HFNO (166[136-215] and 175[158-281] vs. 120[107-149], p=0.002 and p=0.001). NIV and CPAP similarly increased VT vs. HFNO (mean change: 70%[95%CI: 17-122], p=0.02; 93% [95%CI: 30-155], p=0.002) and end-expiratory lung volume (mean change: 198%[95%CI: 67-330], p=0.001; 263%[95%CI: 121-407], p=0.001), mostly due to increased aeration/ventilation in dorsal lung regions. During HFNO, 14/15 patients had pendelluft involving>10% of VT: pendelluft was mitigated by CPAP and further by NIV. CONCLUSIONS Compared to HFNO, helmet NIV, but not CPAP, reduced ΔPES. CPAP and NIV similarly increased oxygenation, end-expiratory lung volume and VT, without affecting ΔPL. NIV, and to a lesser extent, CPAP, mitigated pendelluft. Clinical trial registration available at www. CLINICALTRIALS gov, ID: NCT04241861.