{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:33Z","timestamp":1787028573819,"version":"build-2736575974"},"reference-count":80,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Publication Fund of Heidelberg University Hospital, Heidelberg, Germany"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute hypoxemic respiratory failure is a critical challenge in intensive care. A substantial proportion of patients present with asymmetric acute lung injury (ALI), complicating management due to heterogeneous lung involvement. While lung-protective mechanical ventilation represents the standard of care, the optimal approach to positive end-expiratory pressure (PEEP) titration remains unclear. This study investigated the effects of transpulmonary pressure (TPP)-guided PEEP titration vs. a fixed PEEP strategy in a porcine model of unilateral ALI. A total of 14 pigs underwent ALI induction via unilateral surfactant depletion and were randomized to receive either a fixed PEEP of 5 cmH2O or a PEEP targeting a slightly positive TPP at end-expiration. Over six hours, respiratory mechanics, high-resolution computed tomography (HRCT), histological lung injury scores (LIS), and plasma protein biomarkers were assessed. TPP-guided PEEP titration significantly lowered driving pressure and improved compliance compared to fixed low PEEP, suggesting more homogeneous tidal volume distribution. HRCT revealed less collateral injury in the initially non-injured lung in the TPP-guided group. However, histopathological LIS did not differ between groups. Exploratory cytokine profiling showed systemic inflammatory activation\u2014including pro- and anti-inflammatory responses\u2014only in the TPP-guided group. These findings indicate that TPP-guided PEEP titration may optimize ventilation by balancing alveolar recruitment and overdistension in asymmetric ALI, with clear effects on physiological and imaging parameters, but without parallel effects on cytokine responses. Further research is needed to assess its long-term impact and clinical relevance.<\/jats:p>","DOI":"10.3390\/ijms26209985","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:20:12Z","timestamp":1760973612000},"page":"9985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimizing Positive End-Expiratory Pressure in Asymmetric Acute Lung Injury in a Porcine Model: The Role of Transpulmonary Pressure"],"prefix":"10.3390","volume":"26","author":[{"given":"Claudine H.","family":"Mutschler","sequence":"first","affiliation":[{"name":"Medical Faculty, Department of Anesthesiology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6110-2713","authenticated-orcid":false,"given":"Benjamin","family":"Seybold","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Anesthesiology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Aschauer","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Anesthesiology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Englert","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"},{"name":"Medical Faculty, Institute of Pathology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleo-Aron","family":"Weis","sequence":"additional","affiliation":[{"name":"Medical Faculty, Institute of Pathology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Poth","sequence":"additional","affiliation":[{"name":"Center for Model System and Comparative Pathology (CMCP), Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Defne","family":"Cetiner","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"},{"name":"Medical Faculty, Department of Diagnostic and Interventional Radiology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark O.","family":"Wielp\u00fctz","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"},{"name":"Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, University of Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea","family":"Kehr","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Molecular and Translational Cardiology, University Heidelberg, 69117 Heidelberg, Germany"},{"name":"Internal Medicine III, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Anesthesiology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Kalenka","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Anesthesiology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"},{"name":"District Hospital Bergstrasse, 69646 Heppenheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-2783","authenticated-orcid":false,"given":"Mascha O.","family":"Fiedler-Kalenka","sequence":"additional","affiliation":[{"name":"Medical Faculty, Department of Anesthesiology, University Heidelberg, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"2003317","DOI":"10.1183\/13993003.03317-2020","article-title":"Outcome of acute hypoxaemic respiratory failure: Insights from the LUNG SAFE Study","volume":"57","author":"Pham","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_3","first-page":"2526","article-title":"Acute respiratory distress syndrome: The Berlin Definition","volume":"307","author":"Force","year":"2012","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1001\/jama.2017.21907","article-title":"Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment","volume":"319","author":"Fan","year":"2018","journal-title":"JAMA"},{"key":"ref_5","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."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1056\/NEJMoa1214103","article-title":"Prone positioning in severe acute respiratory distress syndrome","volume":"368","author":"Guerin","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1056\/NEJM199802053380602","article-title":"Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome","volume":"338","author":"Amato","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_8","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_9","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_10","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1097\/ALN.0b013e318297d487","article-title":"Unilateral acid aspiration augments the effects of ventilator lung injury in the contralateral lung","volume":"119","author":"Amigoni","year":"2013","journal-title":"Anesthesiology"},{"key":"ref_11","first-page":"CD009098","article-title":"High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome","volume":"3","author":"Villarejo","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1164\/rccm.202108-1972OC","article-title":"Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis","volume":"205","author":"Dianti","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1007\/s00134-022-06698-x","article-title":"In search of the Holy Grail: Identifying the best PEEP in ventilated patients","volume":"48","author":"Gattinoni","year":"2022","journal-title":"Intensive Care Med."},{"key":"ref_14","first-page":"351","article-title":"Lung recruitment in unilateral lung disease","volume":"68","author":"Blanch","year":"2002","journal-title":"Minerva Anestesiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S0140-6736(21)00439-6","article-title":"Acute respiratory distress syndrome","volume":"398","author":"Meyer","year":"2021","journal-title":"Lancet"},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40635-020-00350-y","article-title":"Comparison of direct and indirect models of early induced acute lung injury","volume":"8","author":"Chimenti","year":"2020","journal-title":"Intensive Care Med. Exp"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1165\/rcmb.2021-0531ST","article-title":"Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report","volume":"66","author":"Kulkarni","year":"2022","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1164\/rccm.202005-1556OC","article-title":"Role of Positive End-Expiratory Pressure and Regional Transpulmonary Pressure in Asymmetrical Lung Injury","volume":"203","author":"Bastia","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1165\/rcmb.2009-0210ST","article-title":"An official American Thoracic Society workshop report: Features and measurements of experimental acute lung injury in animals","volume":"44","author":"Downey","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"The UniProt Consortium (2021). UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res., 49, D480\u2013D489.","DOI":"10.1093\/nar\/gkaa1100"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s40635-023-00569-5","article-title":"Understanding the mechanisms of ventilator-induced lung injury using animal models","volume":"11","author":"Silva","year":"2023","journal-title":"Intensive Care Med. Exp."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S643","DOI":"10.33549\/physiolres.933539","article-title":"A novel experimental model of acute respiratory distress syndrome in pig","volume":"65","author":"Otahal","year":"2016","journal-title":"Physiol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1186\/s12967-022-03753-5","article-title":"Unilateral acute lung injury in pig: A promising animal model","volume":"20","author":"Geilen","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"L510","DOI":"10.1152\/ajplung.00524.2019","article-title":"Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury","volume":"318","author":"Stenlo","year":"2020","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0272-5231(05)70158-1","article-title":"Pulmonary pathology of acute respiratory distress syndrome","volume":"21","author":"Tomashefski","year":"2000","journal-title":"Clin. Chest Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2119\/molmed.2010.00138","article-title":"Contribution of neutrophils to acute lung injury","volume":"17","author":"Grommes","year":"2011","journal-title":"Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1007\/s00134-015-4046-0","article-title":"Acute respiratory distress syndrome in patients with and without diffuse alveolar damage: An autopsy study","volume":"41","author":"Lorente","year":"2015","journal-title":"Intensive Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1148\/radiology.216.2.r00jl05531","article-title":"Hyperoxia-induced diffuse alveolar damage in pigs: Correlation between thin-section CT and histopathologic findings","volume":"216","author":"Ichikado","year":"2000","journal-title":"Radiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13613-016-0208-7","article-title":"Associations between positive end-expiratory pressure and outcome of patients without ARDS at onset of ventilation: A systematic review and meta-analysis of randomized controlled trials","volume":"6","author":"Filho","year":"2016","journal-title":"Ann. Intensive Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1164\/rccm.202402-0326ED","article-title":"Alveolar Collapse as a Threat to Mechanically Ventilated Lungs","volume":"209","author":"Spinelli","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s43856-024-00449-3","article-title":"Pathophysiological profile of non-ventilated lung injury in healthy female pigs undergoing mechanical ventilation","volume":"4","author":"Spinelli","year":"2024","journal-title":"Commun. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jointm.2021.01.003","article-title":"Ten golden rules for individualized mechanical ventilation in acute respiratory distress syndrome","volume":"1","author":"Battaglini","year":"2021","journal-title":"J. Intensive Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00134-024-07351-5","article-title":"Assessing lung recruitability: Does it help with PEEP settings?","volume":"50","author":"Gattinoni","year":"2024","journal-title":"Intensive Care Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1164\/rccm.201702-0388LE","article-title":"Airway Closure in Acute Respiratory Distress Syndrome: An Underestimated and Misinterpreted Phenomenon","volume":"197","author":"Chen","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00134-023-07050-7","article-title":"ESICM guidelines on acute respiratory distress syndrome: Definition, phenotyping and respiratory support strategies","volume":"49","author":"Grasselli","year":"2023","journal-title":"Intensive Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1001\/jama.2019.0555","article-title":"Effect of Titrating Positive End-Expiratory Pressure (PEEP) with an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients with Acute Respiratory Distress Syndrome: A Randomized Clinical Trial","volume":"321","author":"Beitler","year":"2019","journal-title":"JAMA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1164\/rccm.202009-3539OC","article-title":"Effect of Esophageal Pressure-guided Positive End-Expiratory Pressure on Survival from Acute Respiratory Distress Syndrome: A Risk-based and Mechanistic Reanalysis of the EPVent-2 Trial","volume":"204","author":"Sarge","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_41","unstructured":"Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial Investigators (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_42","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10877-019-00267-2","article-title":"Effect of transpulmonary pressure-guided positive end-expiratory pressure titration on lung injury in pigs with acute respiratory distress syndrome","volume":"34","author":"Wu","year":"2020","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1097\/ALN.0000000000000373","article-title":"Compressive forces and computed tomography-derived positive end-expiratory pressure in acute respiratory distress syndrome","volume":"121","author":"Cressoni","year":"2014","journal-title":"Anesthesiology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/TA.0000000000000900","article-title":"How much esophageal pressure-guided end-expiratory transpulmonary pressure is sufficient to maintain lung recruitment in lavage-induced lung injury?","volume":"80","author":"Huang","year":"2016","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1164\/rccm.202310-1895OC","article-title":"Limiting Overdistention or Collapse When Mechanically Ventilating Injured Lungs: A Randomized Study in a Porcine Model","volume":"209","author":"Sousa","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s13054-024-04950-y","article-title":"Transpulmonary pressure monitoring in critically ill patients: Pros and cons","volume":"28","author":"Ball","year":"2024","journal-title":"Crit. Care"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1007\/s00134-016-4400-x","article-title":"Esophageal and transpulmonary pressure in the clinical setting: Meaning, usefulness and perspectives","volume":"42","author":"Mauri","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s13054-016-1446-7","article-title":"Airway driving pressure and lung stress in ARDS patients","volume":"20","author":"Chiumello","year":"2016","journal-title":"Crit. Care"},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1148\/radiol.2373041515","article-title":"Prediction of prognosis for acute respiratory distress syndrome with thin-section CT: Validation in 44 cases","volume":"238","author":"Ichikado","year":"2006","journal-title":"Radiology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e000545","DOI":"10.1136\/bmjopen-2011-000545","article-title":"Fibroproliferative changes on high-resolution CT in the acute respiratory distress syndrome predict mortality and ventilator dependency: A prospective observational cohort study","volume":"2","author":"Ichikado","year":"2012","journal-title":"BMJ Open"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S2213-2600(19)30138-9","article-title":"Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): A multicentre, single-blind, randomised controlled trial","volume":"7","author":"Constantin","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1164\/ajrccm.164.9.2103121","article-title":"What has computed tomography taught us about the acute respiratory distress syndrome?","volume":"164","author":"Gattinoni","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S2213-2600(13)70053-5","article-title":"Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: A prospective cohort study of clinical autopsies","volume":"1","author":"Thille","year":"2013","journal-title":"Lancet Respir. Med"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1164\/rccm.202101-0122OC","article-title":"Addition of 5% CO2 to Inspiratory Gas Prevents Lung Injury in an Experimental Model of Pulmonary Artery Ligation","volume":"204","author":"Marongiu","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Haase, J., Buchloh, D.C., Hammermuller, S., Salz, P., Mrongowius, J., Carvalho, N.C., Beda, A., Rau, A., Starke, H., and Spieth, P.M. (2019). Mechanical Ventilation Strategies Targeting Different Magnitudes of Collapse and Tidal Recruitment in Porcine Acid Aspiration-Induced Lung Injury. J. Clin. Med., 8.","DOI":"10.3390\/jcm8081250"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1007\/s00134-006-0117-6","article-title":"PEEP has beneficial effects on inflammation in the injured and no deleterious effects on the noninjured lung after unilateral lung acid instillation","volume":"32","author":"Schreiber","year":"2006","journal-title":"Intensive Care Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Fiedler, M.O., Deutsch, B.L., Simeliunas, E., Diktanaite, D., Harms, A., Brune, M., Uhle, F., Weigand, M., Brenner, T., and Kalenka, A. (2020). Effect of moderate elevated intra-abdominal pressure on lung mechanics and histological lung injury at different positive end-expiratory pressures. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0230830"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1164\/rccm.201805-0869OC","article-title":"Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation","volume":"199","author":"Araos","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_60","first-page":"382","article-title":"Cytokines and biotrauma in ventilator-induced lung injury: A critical review of the literature","volume":"63","author":"Halbertsma","year":"2005","journal-title":"Neth. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20241076","DOI":"10.1515\/med-2024-1076","article-title":"Progress in cytokine research for ARDS: A comprehensive review","volume":"19","author":"Zhou","year":"2024","journal-title":"Open Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1152\/japplphysiol.01089.2007","article-title":"Spatial and temporal heterogeneity of ventilator-associated lung injury after surfactant depletion","volume":"104","author":"Otto","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.4103\/0366-6999.226840","article-title":"Molecular Mechanisms of Ventilator-Induced Lung Injury","volume":"131","author":"Chen","year":"2018","journal-title":"Chin. Med. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e854","DOI":"10.1097\/CCM.0000000000001721","article-title":"Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome","volume":"44","author":"Guldner","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/CCM.0b013e3182a264ed","article-title":"Compartmentalization of lung injury--atelectasis versus overstretch","volume":"42","author":"Cereda","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1097\/CCM.0b013e31829a822a","article-title":"Volutrauma, but not atelectrauma, induces systemic cytokine production by lung-marginated monocytes","volume":"42","author":"Wakabayashi","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3501373","DOI":"10.1155\/2016\/3501373","article-title":"A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome","volume":"2016","author":"Blondonnet","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12931-025-03137-5","article-title":"Pathophysiological mechanisms of ARDS: A narrative review from molecular to organ-level perspectives","volume":"26","author":"Zhou","year":"2025","journal-title":"Respir. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/0300985811402846","article-title":"Swine as models in biomedical research and toxicology testing","volume":"49","author":"Swindle","year":"2012","journal-title":"Vet. Pathol."},{"key":"ref_70","first-page":"788","article-title":"A simple method for assessing the validity of the esophageal balloon technique","volume":"126","author":"Baydur","year":"1982","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1164\/rccm.2106157","article-title":"Acute interstitial pneumonia: Comparison of high-resolution computed tomography findings between survivors and nonsurvivors","volume":"165","author":"Ichikado","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"333","DOI":"10.2214\/ajr.168.2.9016201","article-title":"Acute interstitial pneumonia: High-resolution CT findings correlated with pathology","volume":"168","author":"Ichikado","year":"1997","journal-title":"Am. J. Roentgenol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1074\/mcp.M900419-MCP200","article-title":"Dual-color proteomic profiling of complex samples with a microarray of 810 cancer-related antibodies","volume":"9","author":"Schroder","year":"2010","journal-title":"Mol. Cell. Proteom."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"D687","DOI":"10.1093\/nar\/gkab1028","article-title":"The reactome pathway knowledgebase 2022","volume":"50","author":"Gillespie","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"D613","DOI":"10.1093\/nar\/gkaa1024","article-title":"WikiPathways: Connecting communities","volume":"49","author":"Martens","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Seybold, B., Deutsch, A.M., Deutsch, B.L., Simeliunas, E., Weigand, M.A., Fiedler-Kalenka, M.O., and Kalenka, A. (2024). Differential Effects of Intra-Abdominal Hypertension and ARDS on Respiratory Mechanics in a Porcine Model. Medicina, 60.","DOI":"10.3390\/medicina60060843"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s43856-023-00283-z","article-title":"Discovery and systematic assessment of early biomarkers that predict progression to severe COVID-19 disease","volume":"3","author":"Hufnagel","year":"2023","journal-title":"Commun. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Sill, M., Schroder, C., Hoheisel, J.D., Benner, A., and Zucknick, M. (2010). Assessment and optimisation of normalisation methods for dual-colour antibody microarrays. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-556"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/9985\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:11:53Z","timestamp":1761019913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/9985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":80,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26209985"],"URL":"https:\/\/doi.org\/10.3390\/ijms26209985","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]}}}