Telias I.Madorno M.Pham T.Coudroy R.Mellado Artigas R.Baedorf-Kassis E.Chen C.W.Spadaro S.Chiumello D.Beitler J.Kondili E.Tiribelli N.Fredes S.Becher T.Dres M.Liu K.Terzi N.Guérin C.Mauri T.Roca O.Mancebo J.Rodriguez N.Arnal J.M.Goligher E.C.Diehl J.L.Jochmans S.Beloncle F.Rittayamai N.Mojoli F.Heunks L.de Vries H.Zhou J.X.Guervilly C.Brochard L.Mahidol University2026-05-162026-05-162026-03-01American Journal of Respiratory and Critical Care Medicine Vol.212 No.3 (2026) , 487-499https://repository.li.mahidol.ac.th/handle/123456789/116734RATIONALE: Excessive stress (distending pressure), strain (volume deformation), and drop in inspiratory alveolar pressure are proposed mechanisms for patient self-inflicted lung injury. OBJECTIVES: To dissect the influence of inspiratory effort, respiratory mechanics, and ventilation mode on lung stress, strain, and drop in inspiratory alveolar pressure and to explore their impact on oxygenation and lung compliance. METHODS: An international cohort study was conducted analyzing respiratory recordings (esophageal pressure) from patients with acute hypoxemic respiratory failure. Association between muscular pressure (Pmus), surrogates of stress (driving transalveolar pressure), strain (Vt), and inspiratory alveolar pressure relative to positive end-expiratory pressure (PEEP) were explored using mixed models, including interactions for ventilation mode, respiratory system elastance, and synchrony. Association between these and changes in oxygenation and lung compliance were explored. MEASUREMENTS AND MAIN RESULTS: Sixty patients from 15 centers represented 528 recordings (339,796 breaths). For each 1 cm H2O increase in Pmus, there were increases in driving transalveolar pressure (median [95% confidence interval (CI)], 0.28 [0.27 to 0.29] cm H2O) and Vt (median [95% CI], 0.16 [0.16 to 0.17] ml/kg of predicted body weight) and a decrease in alveolar pressure (median [95% CI], 0.25 [0.24 to 0.6] cm H2O; P < 0.001). Volume-control ventilation showed lesser increases in stress and strain surrogates than pressure-targeted modes but more drop in alveolar pressure (P < 0.001; Pmus-by-mode interaction). Breath stacking was infrequent and was associated with higher stress. Lower inspiratory alveolar pressure relative to PEEP was associated with subsequent worsening oxygenation (P = 0.04) and higher stress with worsening lung compliance (P = 0.023). CONCLUSIONS: Strong efforts are associated with high surrogates for lung stress, strain, and lower inspiratory alveolar pressure relative to PEEP, differently according to the mode of ventilation, and are associated with subsequent worsening oxygenation and lung compliance.MedicineArticleSCOPUS10.1164/rccm.202411-2155OC2-s2.0-1050382973501535497040700741