{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:56:06Z","timestamp":1790765766316,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Lung-protective ventilation in acute respiratory distress syndrome (ARDS) is guided by whole-lung measures, although the same acceptable breath may stabilize regions undergoing repeated alveolar collapse and expansion (RACE) while overdistending tissue already open. Fatigue-Aware Alveolar Stress and Strain Tracking (FAAST) is a clinician-in-the-loop framework designed to make this regional tradeoff observable. Methods: We first constructed a deterministic, twenty-compartment, phenotype-conditioned model from published observations of acute lung injury. With FAAST excluded, the test lung was evaluated controller-blind against nine prespecified correspondence targets under conventional ventilation and frozen after all nine were met. FAAST was then applied in four experiments examining alternative ventilator strategies, regional observability, a recruitment\u2013overdistension crossover, and the interaction between recruitment and tidal-volume reduction. Results: Before FAAST analysis, the frozen phenotype model met all nine prespecified correspondence targets. FAAST analysis then showed that globally acceptable pressures could coexist with suprathreshold regional loading, while a summed-dose controller obscured opposing regional states. At 96 h, median modeled structural-compliance loss was 61.4% at positive end-expiratory pressure (PEEP) 8 cm H2O, 40.7% with the FAAST crossover at mean PEEP 13.5 cm H2O, and 39.3% at fixed PEEP 15. In a fresh virtual cohort, the crossover remained favorable to PEEP 8 in every matched case. Tidal-volume reduction lowered loss by 1.2 points at practice PEEP and 5.9 points after recruitment, with a 4.4-point interaction. No strategy eliminated regional injury. Conclusions: Within this model, global protection did not ensure regional protection. Compartmental analysis preserved information lost through aggregation and generated hypotheses for matching the complete ventilator pattern to lung state. These model-conditional findings do not establish clinical efficacy or a validated PEEP target; external waveform, imaging, physiologic, and outcome validation is required before clinical use.<\/jats:p>","DOI":"10.3390\/jcm15197545","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:54Z","timestamp":1790614254000},"page":"7545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Global Protective Ventilator Settings Are Not Regional Protection: A Compartment-Resolved Framework for Personalizing Mechanical Ventilation in Acute Respiratory Distress Syndrome"],"prefix":"10.3390","volume":"15","author":[{"given":"Michael S.","family":"Champagne","sequence":"first","affiliation":[{"name":"VentGuard Analytics, LLC, Webster, TX 77598, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Acute Respiratory Distress Syndrome Network, Brower, R.G., Matthay, M.A., Morris, A., Schoenfeld, D., Thompson, B.T., and Wheeler, A. (2000). Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N. Engl. J. Med., 342, 1301\u20131308.","DOI":"10.1056\/NEJM200005043421801"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann, H.P., Wheeler, A.P., Bernard, G.R., Thompson, B.T., Hayden, D., deBoisblanc, B., Connors, A.F., Hite, R.D., and Harabin, A.L. (2006). Comparison of two fluid-management strategies in acute lung injury. N. Engl. J. Med., 354, 2564\u20132575.","DOI":"10.1056\/NEJMoa062200"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/CCM.0000000000003499","article-title":"Declining mortality in patients with acute respiratory distress syndrome: An analysis of the Acute Respiratory Distress Syndrome Network trials","volume":"47","author":"Zhang","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1513\/AnnalsATS.201512-841OC","article-title":"Mortality trends of acute respiratory distress syndrome in the United States from 1999 to 2013","volume":"13","author":"Cochi","year":"2016","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1056\/NEJMsa1410639","article-title":"Driving pressure and survival in the acute respiratory distress syndrome","volume":"372","author":"Amato","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1007\/s00134-018-5375-6","article-title":"Mechanical power of ventilation is associated with mortality in critically ill patients: An analysis of patients in two observational cohorts","volume":"44","author":"Deliberato","year":"2018","journal-title":"Intensive Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s00134-016-4505-2","article-title":"Ventilator-related causes of lung injury: The mechanical power","volume":"42","author":"Gattinoni","year":"2016","journal-title":"Intensive Care. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2419374122","DOI":"10.1073\/pnas.2419374122","article-title":"Mechanical ventilation energy analysis: Recruitment focuses injurious power in the ventilated lung","volume":"122","author":"Gaver","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1097\/00003246-200105000-00036","article-title":"Altered alveolar mechanics in the acutely injured lung","volume":"29","author":"Schiller","year":"2001","journal-title":"Crit. Care Med."},{"key":"ref_11","unstructured":"Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators, Cavalcanti, A.B., Suzumura, \u00c9.A., Laranjeira, L.N., de Moraes Paisani, D., Damiani, L.P., Guimar\u00e3es, H.P., Romano, E.R., de Moraes Regenga, M., and Taniguchi, L.N.T. (2017). Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs. low PEEP on mortality in patients with acute respiratory distress syndrome: A randomized clinical trial. JAMA, 318, 1335\u20131345."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Brower, R.G., Lanken, P.N., MacIntyre, N., Matthay, M.A., Morris, A., Ancukiewicz, M., Schoenfeld, D., and Thompson, B.T. (2004). Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N. Engl. J. Med., 351, 327\u2013336.","DOI":"10.1056\/NEJMoa032193"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1007\/s00134-005-2627-z","article-title":"The concept of \u201cbaby lung\u201d","volume":"31","author":"Gattinoni","year":"2005","journal-title":"Intensive Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dushianthan, A., Grocott, M.P.W., Murugan, G.S., Wilkinson, T.M.A., and Postle, A.D. (2023). Pulmonary Surfactant in Adult ARDS: Current Perspectives and Future Directions. Diagnostics, 13.","DOI":"10.3390\/diagnostics13182964"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1186\/s13054-017-1905-9","article-title":"Regional physiology of ARDS","volume":"21","author":"Gattinoni","year":"2017","journal-title":"Crit. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1164\/rccm.200607-915OC","article-title":"Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome","volume":"175","author":"Terragni","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1164\/rccm.202005-2046OC","article-title":"LUNG SAFE Investigators and the ESICM Trials Group. Compliance phenotypes in early acute respiratory distress syndrome before the COVID-19 pandemic","volume":"202","author":"Panwar","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_18","unstructured":"Champagne, M.S. (2026). Fatigue-Aware Alveolar Stress and Strain Tracking: A Theoretical Biomechanics Framework for Regional Stress-Strain Dose Accumulation in Ventilator-Induced Lung Injury. Front. Bioeng. Biotechnol., in press."},{"key":"ref_19","unstructured":"Champagne, M.S. (2026). FAAST-2 Regional Lung Intelligence: Frozen Reproducibility Release v1.0.0, Zenodo."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40635-017-0121-x","article-title":"Personalizing mechanical ventilation according to physiologic parameters to stabilize alveoli and minimize ventilator induced lung injury (VILI)","volume":"5","author":"Nieman","year":"2017","journal-title":"Intensive Care Med. Exp."},{"key":"ref_21","first-page":"e7376","article-title":"Different characteristics of ventilator application between tracheostomy- and noninvasive positive pressure ventilation patients with amyotrophic lateral sclerosis","volume":"96","author":"Park","year":"2017","journal-title":"Medicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1056\/NEJMoa052052","article-title":"Lung recruitment in patients with the acute respiratory distress syndrome","volume":"354","author":"Gattinoni","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1007\/s00134-011-2388-9","article-title":"Time to generate ventilator-induced lung injury among mammals with healthy lungs: A unifying hypothesis","volume":"37","author":"Caironi","year":"2011","journal-title":"Intensive Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yamaguchi, E., Yao, J., Aymond, A., Chrisey, D.B., Nieman, G.F., Bates, J.H.T., and Gaver, D.P. (2022). Electric Cell-Substrate Impedance Sensing (ECIS) as a platform for evaluating barrier-function susceptibility and damage from pulmonary atelectrauma. Biosensors, 12.","DOI":"10.3390\/bios12060390"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1097\/CCM.0b013e31827417a6","article-title":"Lung stress and strain during mechanical ventilation: Any difference between statics and dynamics?","volume":"41","author":"Protti","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0021-9290(99)00092-5","article-title":"Analysis of stress distribution in the alveolar septa of normal and simulated emphysematic lungs","volume":"32","author":"Gefen","year":"1999","journal-title":"J. Biomech."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8783","DOI":"10.1038\/s41598-019-45343-4","article-title":"The role of three-dimensionality and alveolar pressure in the distribution and amplification of alveolar stresses","volume":"9","author":"Hurtado","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/TA.0b013e31825c7a82","article-title":"Early stabilizing alveolar ventilation prevents acute respiratory distress syndrome: A novel timing-based ventilatory intervention to avert lung injury","volume":"73","author":"Roy","year":"2012","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1001\/jama.282.1.54","article-title":"Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: A randomized controlled trial","volume":"282","author":"Ranieri","year":"1999","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1056\/NEJMra1208707","article-title":"Ventilator-induced lung injury","volume":"369","author":"Slutsky","year":"2013","journal-title":"N. Engl. J. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7545\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:54:41Z","timestamp":1790762081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":30,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["jcm15197545"],"URL":"https:\/\/doi.org\/10.3390\/jcm15197545","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]}}}