An update on the pharmacological management of acute respiratory distress syndrome

References

• Battaglini D, Fazzini B, Silva PL, et al. Challenges in ARDS definition, management, and identification of effective personalized therapies. J Clin Med. 2023;12(4):1381. doi: 10.3390/jcm12041381
   PubMed Web of Science ®Google Scholar
• Villar J, Slutsky AS. The incidence of the adult respiratory distress syndrome. Am Rev Respir Dis. 1989;140(3):814–816. doi: 10.1164/ajrccm/140.3.814
   PubMedGoogle Scholar
• Luhr OR, Antonsen K, Karlsson M, et al. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and iceland. Am J Respir Crit Care Med. 1999;159:1849–1861. doi: 10.1164/ajrccm.159.6.9808136
   PubMed Web of Science ®Google Scholar
• Ferguson ND, Frutos-Vivar F, Esteban A. Mortality rates in patients with ARDS: what should be the reference standard? Intensive care med. New York (NY): Springer New York; 2003. p. 231–242.
   Google Scholar
• Villar J, González-Martin JM, Añón JM, et al. Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe acute respiratory distress syndrome. Sci Rep. 2023;13:1543. doi: 10.1038/s41598-023-28824-5
   PubMed Web of Science ®Google Scholar
• Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788. doi: 10.1001/jama.2016.0291
   PubMed Web of Science ®Google Scholar
• Battaglini D, Robba C, Pelosi P, et al. Treatment for acute respiratory distress syndrome in adults: a narrative review of phase 2 and 3 trials. Expert Opin Emerg Drugs. 2022;27(2):187–209. doi: 10.1080/14728214.2022.2105833
   PubMed Web of Science ®Google Scholar
• Grasselli G, Calfee CS, Camporota L, et al. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies. Intensive Care Med. 2023;49:727–759. doi: 10.1007/s00134-023-07050-7
   PubMed Web of Science ®Google Scholar
• Qadir N, Sahetya S, Munshi L, et al. An update on management of adult patients with acute respiratory distress syndrome: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2024;209:24–36. doi: 10.1164/rccm.202311-2011ST
   PubMed Web of Science ®Google Scholar
• Battaglini D, Robba C, Ball L, et al. Emerging therapies for COVID-19 pneumonia. Expert Opin Investig Drugs. 2020;29(7):633–637. doi: 10.1080/13543784.2020.1771694
   PubMed Web of Science ®Google Scholar
• Silva PL, Scharffenberg M, Rocco PRM. Understanding the mechanisms of ventilator-induced lung injury using animal models. Intensive Care Med Exp. 2023;11(1):82. doi: 10.1186/s40635-023-00569-5
   PubMed Web of Science ®Google Scholar
• Bos LDJ, Ware LB. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. The Lancet. 2022;400:1145–1156. doi: 10.1016/S0140-6736(22)01485-4
   PubMed Web of Science ®Google Scholar
• Silva PL, Ball L, Rocco PRM, et al. Physiological and pathophysiological consequences of mechanical ventilation. Semin Respir Crit Care Med. 2022;43:321–334. doi: 10.1055/s-0042-1744447
   PubMed Web of Science ®Google Scholar
• Thille AW, Esteban A, Fernández-Segoviano P, et al. Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: a prospective cohort study of clinical autopsies. Lancet Respir Med. 2013;1(5):395–401. doi: 10.1016/S2213-2600(13)70053-5
   PubMed Web of Science ®Google Scholar
• Spadaro S, Park M, Turrini C, et al. Biomarkers for acute respiratory distress syndrome and prospects for personalised medicine. J Inflamm. 2019;16:1. doi: 10.1186/s12950-018-0202-y
   Google Scholar
• Battaglini D, Iavarone IG, Al-Husinat L, et al. Anti-inflammatory therapies for acute respiratory distress syndrome. Expert Opin Investig Drugs. 2023;32(12):1143–1155. doi: 10.1080/13543784.2023.2288080
   PubMed Web of Science ®Google Scholar
• Lin P, Zhao Y, Li X, et al. Decreased mortality in acute respiratory distress syndrome patients treated with corticosteroids: an updated meta-analysis of randomized clinical trials with trial sequential analysis. Crit Care. 2021;25:122. doi: 10.1186/s13054-021-03546-0
   PubMed Web of Science ®Google Scholar
• Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8(3):267–276. doi: 10.1016/S2213-2600(19)30417-5
   PubMed Web of Science ®Google Scholar
• Battaglini D, Cruz F, Robba C, et al. Failed clinical trials on COVID-19 acute respiratory distress syndrome in hospitalized patients: common oversights and streamlining the development of clinically effective therapeutics. Expert Opin Investig Drugs. 2022;31(10):995–1015. doi: 10.1080/13543784.2022.2120801
   PubMed Web of Science ®Google Scholar
• Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically Ill PAtients (Part I): society of crit care med (SCCM) and European society of intensive care medicine (ESICM) 2017. Crit Care Med. 2017;45(12):2078–2088. doi: 10.1097/CCM.0000000000002737
   PubMed Web of Science ®Google Scholar
• Lewis SR, Pritchard MW, Thomas CM, et al. Pharmacological agents for adults with acute respiratory distress syndrome. Cochrane Database Of Systematic Rev. 2019;7:CD004477. doi: 10.1002/14651858.CD004477.pub3
   PubMedGoogle Scholar
• Chaudhuri D, Nei AM, Rochwerg B, et al. Focused update: guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. Crit Care Med. 2024;52(5):e219–33. doi: 10.1097/CCM.0000000000006172
   PubMed Web of Science ®Google Scholar
• Feng Y. Efficacy of statin therapy in patients with acute respiratory distress syndrome/acute lung injury: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2018;22:3190–3198. doi: 10.26355/eurrev_201805_15080
   PubMed Web of Science ®Google Scholar
• Craig TR, Duffy MJ, Shyamsundar M, et al. A randomized clinical trial of hydroxymethylglutaryl– coenzyme a reductase inhibition for acute lung injury (The HARP study). Am J Respir Crit Care Med. 2011;183:620–626. doi: 10.1164/rccm.201003-0423OC
   PubMed Web of Science ®Google Scholar
• McAuley DF, Laffey JG, O’Kane CM, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371(18):1695–1703. doi: 10.1056/NEJMoa1403285
   PubMed Web of Science ®Google Scholar
• Calfee CS, Delucchi KL, Sinha P, et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018;6(9):691–698. doi: 10.1016/S2213-2600(18)30177-2
   PubMed Web of Science ®Google Scholar
• Truwit J, Bernard G, Steingrub J, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370:2191–2200.
   PubMed Web of Science ®Google Scholar
• Sinha P, Delucchi KL, Thompson BT, et al. Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study. Intensive Care Med. 2018;44:1859–1869. doi: 10.1007/s00134-018-5378-3
   PubMed Web of Science ®Google Scholar
• Pienkos SM, Moore AR, Guan J, et al. Effect of total cholesterol and statin therapy on mortality in ARDS patients: a secondary analysis of the SAILS and HARP-2 trials. Crit Care. 2023;27:126. doi: 10.1186/s13054-023-04387-9
   PubMed Web of Science ®Google Scholar
• Moore AR, Pienkos SM, Sinha P, et al. Elevated plasma interleukin-18 identifies high-risk acute respiratory distress syndrome patients not distinguished by prior latent class analyses using traditional inflammatory cytokines: a retrospective analysis of two randomized clinical trials. Crit Care Med. 2023;51(12):e269–74. doi: 10.1097/CCM.0000000000006028
   PubMed Web of Science ®Google Scholar
• Boyle AJ, Ferris P, Bradbury I, et al. Baseline plasma IL-18 may predict simvastatin treatment response in patients with ARDS: a secondary analysis of the HARP-2 randomised clinical trial. Crit Care. 2022;26:164. doi: 10.1186/s13054-022-04025-w
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhu Z, Jiao W, et al. Ulinastatin treatment for acute respiratory distress syndrome in China: a meta-analysis of randomized controlled trials. BMC Pulm Med. 2019;19:196. doi: 10.1186/s12890-019-0968-6
   PubMed Web of Science ®Google Scholar
• Bellingan G, Maksimow M, Howell DC, et al. The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study. Lancet Respir Med. 2014;2(2):98–107. doi: 10.1016/S2213-2600(13)70259-5
   PubMed Web of Science ®Google Scholar
• Ranieri VM, Pettilä V, Karvonen MK, et al. Effect of intravenous interferon β-1a on death and days free from mechanical ventilation among patients with moderate to severe acute respiratory distress syndrome. JAMA. 2020;323:725. doi: 10.1001/jama.2019.22525
   PubMed Web of Science ®Google Scholar
• Mammen MJ, Aryal K, Alhazzani W, et al. Interferon beta-1a for patients with moderate to severe acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials. Pol Arch Intern Med. 2020;130:287–296. doi: 10.20452/pamw.15279
   PubMedGoogle Scholar
• Fisher SA, Rahimzadeh M, Brierley C, et al. The role of vitamin D in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory disease or in healthy volunteers: a systematic review. Gorman S, editor. PLoS One. 2019;14(9):e0222313. doi: 10.1371/journal.pone.0222313
   PubMed Web of Science ®Google Scholar
• Ginde A, Brower R, Caterino J, et al. Early high-dose vitamin d 3 for critically Ill, vitamin D–deficient patients. N Engl J Med. 2019;381:2529–2540.
   PubMed Web of Science ®Google Scholar
• Parekh D, Dancer RCA, Scott A, et al. Vitamin D to prevent lung injury following esophagectomy—a randomized, placebo-controlled trial*. Crit Care Med. 2018;46(12):e1128–35. doi: 10.1097/CCM.0000000000003405
   PubMed Web of Science ®Google Scholar
• Jolliffe DA, Camargo CA, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021;9(5):276–292. doi: 10.1016/S2213-8587(21)00051-6
   PubMed Web of Science ®Google Scholar
• Quraishi SA, Bhan I, Matthay MA, et al. Vitamin D status and clinical outcomes in acute respiratory distress syndrome: a secondary analysis from the assessment of low tidal volume and elevated end-expiratory volume to obviate lung injury (ALVEOLI) trial. J Intensive Care Med. 2022;37:793–802. doi: 10.1177/08850666211028139
   PubMed Web of Science ®Google Scholar
• Kor DJ, Carter RE, Park PK, et al. Effect of aspirin on development of ARDS in At-risk patients presenting to the emergency department. JAMA. 2016;315:2406. doi: 10.1001/jama.2016.6330
   PubMed Web of Science ®Google Scholar
• Toner P, Boyle AJ, McNamee JJ, et al. Aspirin as a treatment for ARDS. Chest. 2022;161:1275–1284. doi: 10.1016/j.chest.2021.11.006
   PubMed Web of Science ®Google Scholar
• Bernard GR, Wheeler AP, Russell JA, et al. The effects of ibuprofen on the physiology and survival of patients with sepsis. The ibuprofen in sepsis study group. N Engl J Med. 1997;336:912–918. doi: 10.1056/NEJM199703273361303
   PubMed Web of Science ®Google Scholar
• Teafatiller T, Agrawal S, De Robles G, et al. Vitamin C enhances antiviral functions of lung epithelial cells. Biomolecules. 2021;11:1148. doi: 10.3390/biom11081148
   PubMed Web of Science ®Google Scholar
• Fowler AA, Truwit JD, Hite RD, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure. JAMA. 2019;322:1261. doi: 10.1001/jama.2019.11825
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ding S, Li C, et al. Effects of N-acetylcysteine treatment in acute respiratory distress syndrome: a meta-analysis. Exp Ther Med. 2017;14(4):2863–2868. doi: 10.3892/etm.2017.4891
   PubMed Web of Science ®Google Scholar
• Moradi M, Mojtahedzadeh M, Mandegari A, et al. The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine. Respir Med. 2009;103(3):434–441. doi: 10.1016/j.rmed.2008.09.013
   PubMed Web of Science ®Google Scholar
• Ortolani O, Conti A, De Gaudio AR, et al. Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome. Shock. 2000;13(1):14–18. doi: 10.1097/00024382-200013010-00003
   PubMed Web of Science ®Google Scholar
• Domenighetti G, Suter PM, Schaller M-D, et al. Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study. J Crit Care. 1997;12(4):177–182. doi: 10.1016/S0883-9441(97)90029-0
   PubMed Web of Science ®Google Scholar
• Bernard GR, Wheeler AP, Arons MM, et al. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. Chest. 1997;112:164–172. doi: 10.1378/chest.112.1.164
   PubMed Web of Science ®Google Scholar
• Christie JD, Vaslef S, Chang PK, et al. A randomized dose-escalation study of the safety and anti-inflammatory activity of the p38 mitogen-activated protein kinase inhibitor dilmapimod in severe trauma subjects at risk for acute respiratory distress syndrome. Crit Care Med. 2015;43(9):1859–1869. doi: 10.1097/CCM.0000000000001132
   PubMed Web of Science ®Google Scholar
• Yang S, Dumitrescu TP. Population pharmacokinetics and pharmacodynamics modelling of dilmapimod in severe trauma subjects at risk for acute respiratory distress syndrome. Drugs R D. 2017;17:145–158. doi: 10.1007/s40268-016-0161-9
   PubMed Web of Science ®Google Scholar
• Proudfoot A, Bayliffe A, O’Kane CM, et al. Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury. Thorax. 2018;73:723–730. doi: 10.1136/thoraxjnl-2017-210305
   PubMed Web of Science ®Google Scholar
• Horie S, McNicholas B, Rezoagli E, et al. Emerging pharmacological therapies for ARDS: COVID-19 and beyond. Intensive Care Med. 2020;46:2265–2283. doi: 10.1007/s00134-020-06141-z
   PubMed Web of Science ®Google Scholar
• Fredenburgh LE, Perrella MA, Barragan-Bradford D, et al. A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS. JCI Insight. 2018;3(23):3. doi: 10.1172/jci.insight.124039
   Web of Science ®Google Scholar
• Xu S, Yang Q, Bai J, et al. Blockade of endothelial, but not epithelial, cell expression of PD-L1 following severe shock attenuates the development of indirect acute lung injury in mice. Am J Physiol-Lung Cellular And Mol Physiol. 2020;318:L801–12. doi: 10.1152/ajplung.00108.2019
   PubMed Web of Science ®Google Scholar
• Xu J, Wang J, Wang X, et al. Soluble PD-L1 improved direct ARDS by reducing monocyte-derived macrophages. Cell Death Dis. 2020;11:934. doi: 10.1038/s41419-020-03139-9
   PubMed Web of Science ®Google Scholar
• Pickles OJ, Lee LYW, Starkey T, et al. Immune checkpoint blockade: releasing the breaks or a protective barrier to COVID-19 severe acute respiratory syndrome? Br J Cancer. 2020;123:691–693. doi: 10.1038/s41416-020-0930-7
   PubMed Web of Science ®Google Scholar
• Mei SHJ, Haitsma JJ, Dos Santos CC, et al. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med. 2010;182:1047–1057. doi: 10.1164/rccm.201001-0010OC
   PubMed Web of Science ®Google Scholar
• Guerra AD, Cantu DA, Vecchi JT, et al. Mesenchymal stromal/stem cell and minocycline-loaded hydrogels inhibit the growth of staphylococcus aureus that evades immunomodulation of blood-derived leukocytes. Aaps J. 2015;17:620–630. doi: 10.1208/s12248-015-9728-6
   PubMed Web of Science ®Google Scholar
• Lopes-Pacheco M, Rocco PRM. Functional enhancement strategies to potentiate the therapeutic properties of mesenchymal stromal cells for respiratory diseases. Front Pharmacol. 2023;14:1067422. doi: 10.3389/fphar.2023.1067422
   PubMed Web of Science ®Google Scholar
• dos Santos CC, Lopes-Pacheco M, English K, et al. The MSC-EV-microRNAome: a perspective on therapeutic mechanisms of action in sepsis and ARDS. Cells. 2024;13:122. doi: 10.3390/cells13020122
   PubMed Web of Science ®Google Scholar
• Zheng G, Huang L, Tong H, et al. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study. Respir Res. 2014;15:39. doi: 10.1186/1465-9921-15-39
   PubMed Web of Science ®Google Scholar
• Wick KD, Leligdowicz A, Zhuo H, et al. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS. JCI Insight. 2021;6:e1488983. doi: 10.1172/jci.insight.148983
   Web of Science ®Google Scholar
• Matthay MA, Calfee CS, Zhuo H, et al. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med. 2019;7(2):154–162. doi: 10.1016/S2213-2600(18)30418-1
   PubMed Web of Science ®Google Scholar
• Gorman E, Shankar-Hari M, Hopkins P, et al. Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: a phase 1 trial. EClinicalMedicine. 2021;41:101167. doi: 10.1016/j.eclinm.2021.101167
   PubMedGoogle Scholar
• Gorman EA, Rynne J, Gardiner HJ, et al. Repair of acute respiratory distress syndrome in COVID-19 by stromal cells (REALIST-COVID trial): a multicenter, randomized, controlled clinical trial. Am J Respir Crit Care Med. 2023;208:256–269. doi: 10.1164/rccm.202302-0297OC
   PubMedGoogle Scholar
• Wang F, Li Y, Wang B, et al. The safety and efficacy of mesenchymal stromal cells in ARDS: a meta-analysis of randomized controlled trials. Crit Care. 2023;27:31. doi: 10.1186/s13054-022-04287-4
   PubMed Web of Science ®Google Scholar
• Bellingan G, Jacono F, Bannard-Smith J, et al. Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial. Intensive Care Med. 2022;48:36–44. doi: 10.1007/s00134-021-06570-4
   PubMed Web of Science ®Google Scholar
• Ichikado K, Kotani T, Kondoh Y, et al. Clinical efficacy and safety of multipotent adult progenitor cells (invimestrocel) for acute respiratory distress syndrome (ARDS) caused by pneumonia: a randomized, open-label, standard therapy–controlled, phase 2 multicenter study (ONE-BRIDGE). Stem Cell Res Ther. 2023;14:217. doi: 10.1186/s13287-023-03451-z
   PubMed Web of Science ®Google Scholar
• Schevitz RW, Bach NJ, Carlson DG, et al. Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2. Nat Struct Mol Biol. 1995;2:458–465. doi: 10.1038/nsb0695-458
   Google Scholar
• Hite RD, Seeds MC, Jacinto RB, et al. Lysophospholipid and fatty acid inhibition of pulmonary surfactant: non-enzymatic models of phospholipase A2 surfactant hydrolysis. Biochim et Biophys Acta (BBA) - Biomembr. 2005;1720:14–21. doi: 10.1016/j.bbamem.2005.10.014
   PubMed Web of Science ®Google Scholar
• Attalah HL, Wu Y, Alaoui-El-Azher M, et al. Induction of type-IIA secretory phospholipase A2 in animal models of acute lung injury. Eur Respir J. 2003;21(6):1040–1045. doi: 10.1183/09031936.03.00093002
   PubMed Web of Science ®Google Scholar
• Demoule A, Decailliot F, Jonson B, et al. Relationship between pressure-volume curve and markers for collagen turn-over in early acute respiratory distress syndrome. Intensive Care Med. 2006;32:413–420. doi: 10.1007/s00134-005-0043-z
   PubMed Web of Science ®Google Scholar
• Touqui L, Arbibe L. A role for phospholipase A2 in ARDS pathogenesis. Mol Med Today. 1999;5(6):244–249. doi: 10.1016/S1357-4310(99)01470-7
   PubMedGoogle Scholar
• Kim DK, Fukuda T, Thompson BT, et al. Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome. Am J Physiol-Lung Cellular And Mol Physiol. 1995;269:L109–18. doi: 10.1152/ajplung.1995.269.1.L109
   PubMed Web of Science ®Google Scholar
• Nakos G, Kitsiouli E, Hatzidaki E, et al. Phospholipases A2 and platelet-activating-factor acetylhydrolase in patients with acute respiratory distress syndrome*. Crit Care Med. 2005;33(4):772–779. doi: 10.1097/01.CCM.0000158519.80090.74
   PubMed Web of Science ®Google Scholar
• De Luca D, Minucci A, Cogo P, et al. Secretory phospholipase A2 pathway during pediatric acute respiratory distress syndrome: a preliminary study. Pediatr Crit Care Med. 2011;12:e20–4. doi: 10.1097/PCC.0b013e3181dbe95e
   PubMed Web of Science ®Google Scholar
• Hite RD, Chakrabarti A, N MV, et al. Inhibition of phospholipase-mediated phoshatidylglycerol depletion and replacement of surfactant improve surfactant function in a murine ARDS model. Am J Respir Crit Care Med. 2016:193:A4420.
   Web of Science ®Google Scholar
• De Luca D, Minucci A, Piastra M, et al. Ex vivo effect of varespladib on secretory phospholipase A2 alveolar activity in infants with ARDS. Rota R, editor. PLOS ONE. 2012;7:e47066.
   PubMed Web of Science ®Google Scholar
• Bassford CR, Thickett DR, Perkins GD. The rise and fall of β-agonists in the treatment of ARDS. Crit Care. 2012;16:208. doi: 10.1186/cc11221
   PubMed Web of Science ®Google Scholar
• Gates S, Perkins G, Lamb S, et al. Beta-agonist lung injury TrIal-2 (BALTI-2): a multicentre, randomised, double-blind, placebo-controlled trial and economic evaluation of intravenous infusion of salbutamol versus placebo in patients with acute respiratory distress syndrome. Health Technol Assess (Rockv). 2013;17(38):1–87. doi: 10.3310/hta17380
   Web of Science ®Google Scholar
• Festic E, Carr GE, Cartin-Ceba R, et al. Randomized clinical trial of a combination of an inhaled corticosteroid and beta agonist in patients at risk of developing the acute respiratory distress syndrome. Crit Care Med. 2017;45(5):798–805. doi: 10.1097/CCM.0000000000002284
   PubMed Web of Science ®Google Scholar
• Shyamsundar M, McAuley DF, Ingram RJ, et al. Keratinocyte growth factor promotes epithelial survival and resolution in a human model of lung injury. Am J Respir Crit Care Med. 2014;189:1520–1529. doi: 10.1164/rccm.201310-1892OC
   PubMed Web of Science ®Google Scholar
• McAuley DF, Cross LM, Hamid U, et al. Keratinocyte growth factor for the treatment of the acute respiratory distress syndrome (KARE): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Respir Med. 2017;5(6):484–491. doi: 10.1016/S2213-2600(17)30171-6
   PubMed Web of Science ®Google Scholar
• Paine R, Standiford TJ, Dechert RE, et al. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med. 2012;40(1):90–97. doi: 10.1097/CCM.0b013e31822d7bf0
   PubMed Web of Science ®Google Scholar
• Frossard JL, Saluja AK, Mach N, et al. In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury. Am J Physiol-Lung Cellular And Mol Physiol. 2002;283:L541–8. doi: 10.1152/ajplung.00413.2001
   PubMed Web of Science ®Google Scholar
• Schmid B, Kredel M, Ullrich R, et al. Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS—a randomized, placebo-controlled, double-blind trial. Trials. 2021;22:643. doi: 10.1186/s13063-021-05588-9
   PubMed Web of Science ®Google Scholar
• Petty TL, Silvers GW, Paul GW, et al. Abnormalities in lung elastic properties and surfactant function in adult respiratory distress syndrome. Chest. 1979;75:571–574. doi: 10.1378/chest.75.5.571
   PubMed Web of Science ®Google Scholar
• Dushianthan A, Grocott MPW, Murugan GS, et al. Pulmonary surfactant in adult ARDS: current perspectives and future directions. Diagnostics. 2023;13:2964. doi: 10.3390/diagnostics13182964
   Web of Science ®Google Scholar
• Meng S-S, Chang W, Lu Z-H, et al. Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome: a meta-analysis of randomized controlled trials. BMC Pulm Med. 2019;19:9. doi: 10.1186/s12890-018-0761-y
   PubMed Web of Science ®Google Scholar
• Miyazaki Y, Inoue T, Kyi M, et al. Effects of a neutrophil elastase inhibitor (ONO-5046) on acute pulmonary injury induced by tumor necrosis factor alpha (TNF α) and activated neutrophils in isolated perfused rabbit lungs. Am J Respir Crit Care Med. 1998;157:89–94. doi: 10.1164/ajrccm.157.1.9612021
   PubMed Web of Science ®Google Scholar
• Kadoi Y, Hinohara H, Kunimoto F, et al. Pilot study of the effects of ONO-5046 in patients with acute respiratory distress syndrome. Anesth Analg. 2004;99(3):872–877. doi: 10.1213/01.ANE.0000129996.22368.85
   PubMed Web of Science ®Google Scholar
• Zeiher BG, Artigas A, Vincent J-L, et al. Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study. Crit Care Med. 2004;32(8):1695–1702. doi: 10.1097/01.CCM.0000133332.48386.85
   PubMed Web of Science ®Google Scholar
• Endo S, Sato N, Yaegashi Y, et al. Sivelestat sodium hydrate improves septic acute lung injury by reducing alveolar dysfunction. Res Commun Mol Pathol Pharmacol. 2006;119:53–65.
   PubMedGoogle Scholar
• Ryugo M, Sawa Y, Takano H, et al. Effect of a polymorphonuclear elastase inhibitor (sivelestat sodium) on acute lung injury after cardiopulmonary bypass: findings of a double-blind randomized study. Surg Today. 2006;36:321–326. doi: 10.1007/s00595-005-3160-y
   PubMed Web of Science ®Google Scholar
• Pu S, Wang D, Liu D, et al. Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials. BMC Pulm Med. 2017;17:148. doi: 10.1186/s12890-017-0498-z
   PubMed Web of Science ®Google Scholar
• Adhikari NKJ, Dellinger RP, Lundin S, et al. Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity. Crit Care Med. 2014;42(2):404–412. doi: 10.1097/CCM.0b013e3182a27909
   PubMed Web of Science ®Google Scholar
• Gerard L, Lecocq M, Bouzin C, et al. Increased angiotensin-converting enzyme 2 and loss of alveolar type II cells in COVID-19–related acute respiratory distress syndrome. Am J Respir Crit Care Med. 2021;204:1024–1034. doi: 10.1164/rccm.202012-4461OC
   PubMed Web of Science ®Google Scholar
• Xiao L-X, Zhu DL, Chen J, et al. Exploring the therapeutic role of early heparin administration in ARDS management: a MIMIC-IV database analysis. J Intensive Care. 2024;12:9. doi: 10.1186/s40560-024-00723-5
   PubMed Web of Science ®Google Scholar
• Dixon B, Smith RJ, Campbell DJ, et al. Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Lancet Respir Med. 2021;9(4):360–372. doi: 10.1016/S2213-2600(20)30470-7
   PubMed Web of Science ®Google Scholar
• Marini JJ, Jaber S. Dynamic predictors of VILI risk: beyond the driving pressure. Intensive Care Med. 2016;42:1597–1600. doi: 10.1007/s00134-016-4534-x
   PubMed Web of Science ®Google Scholar
• Iavarone IG, Al-Husinat L, Vélez-Páez JL, et al. Management Of neuromuscular blocking agents in critically Ill patients with lung diseases. J Clin Med. 2024;13(4):1182. doi: 10.3390/jcm13041182
   PubMed Web of Science ®Google Scholar
• Torbic H, Krishnan S, Harnegie MP, et al. Neuromuscular blocking agents for ARDS: a systematic review and meta-analysis. Respir Care. 2021;66:120–128. doi: 10.4187/respcare.07849
   PubMed Web of Science ®Google Scholar
• Yoshida T, Fujino Y, Amato MBP, et al. Fifty years of research in ARDS. Spontaneous breathing during mechanical ventilation. Risks, mechanisms, and management. Am J Respir Crit Care Med. 2017;195:985–992. doi: 10.1164/rccm.201604-0748CP
   PubMedGoogle Scholar
• Forel J-M, Roch A, Marin V, et al. Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2006;34(11):2749–2757. doi: 10.1097/01.CCM.0000239435.87433.0D
   PubMed Web of Science ®Google Scholar
• Gainnier M, Roch A, Forel J-M, et al. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2004;32(1):113–119. doi: 10.1097/01.CCM.0000104114.72614.BC
   PubMed Web of Science ®Google Scholar
• Moss M, Huang D, Brower R, et al. Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med. 2019;380:1997–2008.
   PubMed Web of Science ®Google Scholar
• Papazian L, Forel J-M, Gacouin A, et al. NeuromusculaR blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107–1116. doi: 10.1056/NEJMoa1005372
   PubMed Web of Science ®Google Scholar
• Vanhorebeek I, Latronico N, Van den Berghe G. ICU-acquired weakness. Intensive Care Med. 2020;46:637–653. doi: 10.1007/s00134-020-05944-4
   PubMed Web of Science ®Google Scholar