151
Views
0
CrossRef citations to date
0
Altmetric
Review

Anti-inflammatory therapies for acute respiratory distress syndrome

, , , , , , & show all
Pages 1143-1155 | Received 17 Sep 2023, Accepted 22 Nov 2023, Published online: 27 Nov 2023

References

  • 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(7):727–759. doi: 10.1007/s00134-023-07050-7
  • Villar J, Szakmany T, Grasselli G, et al. Redefining ARDS: a paradigm shift. Crit Care. 2023;27(1):416. doi: 10.1186/s13054-023-04699-w
  • 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
  • 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
  • Silva PL, Pelosi P, Rocco PRM. Personalized pharmacological therapy for ARDS: a light at the end of the tunnel. Expert Opin Investig Drugs. 2020;29(1):49–61. doi: 10.1080/13543784.2020.1699531
  • Rocco PR, Zin WA. Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome Are Different. Curr Opin Crit Care. 2005;11(1):10–17. doi: 10.1097/00075198-200502000-00003
  • Horie S, McNicholas B, Rezoagli E, et al. Emerging pharmacological therapies for ARDS: COVID-19 and beyond. Intensive care Med. 2020;46(12):2265–2283. doi: 10.1007/s00134-020-06141-z
  • Beitler JR, Thompson BT, Baron RM, et al. Advancing precision medicine for acute respiratory distress syndrome. Lancet Respir Med. 2022;10(1):107–120. doi: 10.1016/S2213-2600(21)00157-0
  • Bos LDJ, Artigas A, Constantin J-M, et al. Precision medicine in acute respiratory distress syndrome: workshop report and recommendations for future research. Eur Respir Rev. 2021;30(159):200317. doi: 10.1183/16000617.0317-2020
  • Ware LB, Matthay MA, Mebazaa A. Designing an ARDS trial for 2020 and beyond: focus on enrichment strategies. Intensive care Med. 2020;46(12):2153–2156. doi: 10.1007/s00134-020-06232-x
  • Battaglini D, Al-Husinat L, Normando AG, et al. Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes. Respir Res. 2022;23(1):318. doi: 10.1186/s12931-022-02233-0
  • Calfee CS, Delucchi K, Parsons PE, et al. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2(8):611–620. doi: 10.1016/S2213-2600(14)70097-9
  • 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
  • Famous KR, Delucchi K, Ware LB, et al. Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy. Am J Respir Crit Care Med. 2017;195(3):331–338. doi: 10.1164/rccm.201603-0645OC
  • Sinha P, Furfaro D, Cummings MJ, et al. Latent class analysis reveals COVID-19–related acute respiratory distress syndrome subgroups with differential responses to Corticosteroids. Am J Respir Crit Care Med. 2021;204(11):1274–1285. doi: 10.1164/rccm.202105-1302OC
  • Coppola S, Pozzi T, Gurgitano M, et al. Radiological pattern in ARDS patients: partitioned respiratory mechanics, gas exchange and Lung Recruitability. Ann Intensive Care. 2021;11(1):78. doi: 10.1186/s13613-021-00870-0
  • Pozzi T, Fratti I, Tomarchio E, et al. Early time-course of respiratory mechanics, mechanical power and gas exchange in ARDS patients. J Crit Care. 2024;79:154444. doi: 10.1016/j.jcrc.2023.154444
  • Pelosi P, Ball L, Barbas CSV, et al. Personalized mechanical ventilation in acute respiratory distress syndrome. Crit Care. 2021;25(1):250. doi: 10.1186/s13054-021-03686-3
  • Rizzo AN, Aggarwal NR, Thompson BT, et al. Advancing precision medicine for the diagnosis and treatment of acute respiratory distress syndrome. J Clin Med. 2023;12(4):1563. doi: 10.3390/jcm12041563
  • Wildi K, Livingstone S, Palmieri C, et al. The discovery of biological subphenotypes in ARDS: a novel approach to targeted medicine? J Intensive Care. 2021;9(1):14. doi: 10.1186/s40560-021-00528-w
  • Sinha P, Meyer NJ, Calfee CS. Biological phenotyping in sepsis and acute respiratory distress syndrome. Annu Rev Med. 2023;74(1):457–471. doi: 10.1146/annurev-med-043021-014005
  • Marik PE, Meduri GU, Rocco PRM, et al. Glucocorticoid Treatment in Acute Lung Injury and Acute Respiratory Distress Syndrome. Crit Care Clin. 2011;27(3):589–607. doi: 10.1016/j.ccc.2011.05.007
  • 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(1):122. doi: 10.1186/s13054-021-03546-0
  • Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids — New mechanisms for old drugs. N Engl J Med. 2005;353(16):1711–1723. doi: 10.1056/NEJMra050541
  • Barnes PJ. How Corticosteroids Control Inflammation: Quintiles Prize Lecture 2005: Corticosteroids and Inflammation. Br J Pharmacol. 2006;148(3):245–254. doi: 10.1038/sj.bjp.0706736
  • Meduri GU, Golden E, Freire AX, et al. Methylprednisolone infusion in early severe ARDS. Chest. 2007;131(4):954–963. doi: 10.1378/chest.06-2100
  • Bernard GR, Luce JM, Sprung CL, et al. High-dose Corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med. 1987;317(25):1565–1570. doi: 10.1056/NEJM198712173172504
  • Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of Corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006;354(16):1671–1684. doi: 10.1056/NEJMoa051693
  • 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
  • Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015;163(7):519–528. doi: 10.7326/M15-0715
  • Arabi YM, Chrousos GP, Meduri GU. The Ten reasons why Corticosteroid therapy reduces mortality in severe COVID-19. Intensive care Med. 2020;46(11):2067–2070. doi: 10.1007/s00134-020-06223-y
  • The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704. doi: 10.1056/NEJMoa2021436
  • The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, et al. Association between administration of systemic Corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. 2020;324(13):1330. doi: 10.1001/jama.2020.17023
  • Lewis SR, Pritchard MW, Thomas CM, et al. Pharmacological agents for adults with acute respiratory distress syndrome. Cochrane Database Syst Rev. 2019. doi: 10.1002/14651858.CD004477.pub3
  • Robba C, Battaglini D, Ball L, et al. Ten Things you need to know about Intensive Care unit management of mechanically ventilated patients with COVID-19. Expert Rev Respir Med. 2021;15(10):1293–1302. doi: 10.1080/17476348.2021.1906226
  • Sinha P, Delucchi KL, McAuley DF, et al. Development and validation of parsimonious algorithms to classify acute respiratory distress syndrome phenotypes: a secondary analysis of randomised controlled trials. Lancet Respir Med. 2020;8(3):247–257. doi: 10.1016/S2213-2600(19)30369-8
  • 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
  • Martin-Loeches I, Nagavci B, Torres A. Final Approval for Corticosteroids in Severe CAP? For Sure, in Septic Shock. Crit Care. 2023;27(1):342. doi: 10.1186/s13054-023-04613-4
  • Sekheri M, Rizo-Téllez SA, Othman A, et al. Interferon-β regulates proresolving lipids to promote the resolution of acute airway inflammation. Proc Natl Acad Sci. 2022;119(31):e2201146119. doi: 10.1073/pnas.2201146119
  • 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
  • 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: a randomized clinical trial. JAMA. 2020;323(8):725. doi: 10.1001/jama.2019.22525
  • 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. PLoS One. 2019;14(9):e0222313. doi: 10.1371/journal.pone.0222313
  • Xu J, Yang J, Chen J, et al. Vitamin D Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Regulation of the Renin-Angiotensin System. Mol Med Rep. 2017;16(5):7432–7438. doi: 10.3892/mmr.2017.7546
  • Shi Y-Y, Liu T-J, Fu J-H, et al. Vitamin D/VDR signaling attenuates lipopolysaccharide-induced acute lung injury by maintaining the integrity of the pulmonary epithelial barrier. Mol Med Rep. 2016;13(2):1186–1194. doi: 10.3892/mmr.2015.4685
  • Kong J, Zhu X, Shi Y, et al. VDR attenuates acute lung injury by blocking ang-2-tie-2 pathway and Renin-Angiotensin System. Mol Endocrinol. 2013;27(12):2116–2125. doi: 10.1210/me.2013-1146
  • Zheng S, Yang J, Hu X, et al. Vitamin D attenuates lung injury via stimulating epithelial repair, reducing epithelial cell apoptosis and inhibits TGF-β induced epithelial to Mesenchymal transition. Biochem Pharmacol. 2020;177:113955. doi: 10.1016/j.bcp.2020.113955
  • 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–e1135. doi: 10.1097/CCM.0000000000003405
  • The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early high-dose Vitamin D 3 for critically ill, Vitamin D–deficient patients. N Engl J Med. 2019;381(26):2529–2540. doi: 10.1056/NEJMoa1911124
  • Wei Y, Wang Z, Su L, et al. Platelet count mediates the contribution of a genetic variant in LRRC 16A to ARDS risk. Chest. 2015;147(3):607–617. doi: 10.1378/chest.14-1246
  • Toner P, Boyle AJ, McNamee JJ, et al. Aspirin as a treatment for ARDS. Chest. 2022;161(5):1275–1284. doi: 10.1016/j.chest.2021.11.006
  • Mezidi M, Guérin C. Aspirin for Prevention of acute respiratory distress syndrome (ARDS): Let’s not throw the baby with the water! Ann Transl Med. 2016;4(19):376–376. doi: 10.21037/atm.2016.07.28
  • Tung Y-T, Wei C-H, Yen C-C, et al. Aspirin attenuates hyperoxia-induced acute respiratory distress syndrome (ARDS) by suppressing pulmonary inflammation via the NF-κB signaling pathway. Front Pharmacol. 2022;12:793107. doi: 10.3389/fphar.2021.793107
  • Kor DJ, Carter RE, Park PK, et al. Effect of Aspirin on development of ARDS in at-risk patients presenting to the emergency department: the LIPS-A randomized clinical trial. JAMA. 2016;315(22):2406. doi: 10.1001/jama.2016.6330
  • Chakraborty N, Muzaffar SN, Siddiqui SS. Aspirin cannot stop multiple pathophysiologic pathways of ARDS. Chest. 2022;161(6):e391–e392. doi: 10.1016/j.chest.2022.01.072
  • Azh N, Barzkar F, Motamed‐Gorji N, et al. Nonsteroidal anti‐inflammatory drugs in acute viral respiratory tract infections: an updated systematic review. Pharmacol Res Perspect. 2022;10(2). doi: 10.1002/prp2.925
  • Sweeney RM, McAuley DF. Do nonventilatory strategies for acute lung injury and ARDS work? In Evidence-based practice of critical care. Elsevier; 2010. p. 73–81. doi: 10.1016/B978-1-4160-5476-4.00012-2
  • Bernard GR, Wheeler AP, Russell JA, et al. The effects of ibuprofen on the physiology and survival of patients with sepsis. N Engl J Med. 1997;336(13):912–918. doi: 10.1056/NEJM199703273361303
  • Teafatiller T, Agrawal S, De Robles G, et al. Vitamin C enhances antiviral functions of lung epithelial cells. Biomolecules. 2021;11(8):1148. doi: 10.3390/biom11081148
  • 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
  • Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov. 2005;4(12):977–987. doi: 10.1038/nrd1901
  • 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(1):196. doi: 10.1186/s12890-019-0968-6
  • 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(10):3190–3198. doi: 10.26355/eurrev_201805_15080
  • 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(5):620–626. doi: 10.1164/rccm.201003-0423OC
  • 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
  • Truwit JD, Bernard GR, Steingrub J, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191–2200. doi: 10.1056/NEJMoa1401520
  • 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(1):126. doi: 10.1186/s13054-023-04387-9
  • 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 Cell Mol Physiol. 2020;318(4):L801–L812. doi: 10.1152/ajplung.00108.2019
  • Lomas-Neira J, Monaghan SF, Huang X, et al. Novel role for PD-1: PD-L1 as mediator of pulmonary vascular endothelial cell functions in pathogenesis of indirect ARDS in mice. Front Immunol. 2018;9:3030. doi: 10.3389/fimmu.2018.03030
  • Xu J, Wang J, Wang X, et al. Soluble PD-L1 improved direct ARDS by reducing monocyte-derived macrophages. Cell Death Dis. 2020;11(10):934. doi: 10.1038/s41419-020-03139-9
  • 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(5):691–693. doi: 10.1038/s41416-020-0930-7
  • Christian MD, Poutanen SM, Loutfy MR, et al. Severe Acute Respiratory Syndrome. Clin Infect Dis. 2004;38(10):1420–1427. doi: 10.1086/420743
  • Lee JS, Shin E-C. The type I interferon response in COVID-19: implications for treatment. Nat Rev Immunol. 2020;20(10):585–586. doi: 10.1038/s41577-020-00429-3
  • Ishii M, Yamaguchi Y, Isumi K, et al. Transgenic mice overexpressing Vitamin D receptor (VDR) show anti-inflammatory effects in lung tissues. Inflammation. 2017;40(6):2012–2019. doi: 10.1007/s10753-017-0641-2
  • Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;i6583. doi: 10.1136/bmj.i6583
  • Ul Afshan F, Nissar B, Chowdri NA, et al. Relevance of Vitamin D3 in COVID-19 infection. Gene Rep. 2021;24:101270. doi: 10.1016/j.genrep.2021.101270
  • Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R. Vitamin D Receptor Stimulation to Reduce Acute Respiratory Distress Syndrome (ARDS) in Patients with Coronavirus SARS-CoV-2 Infections. J Steroid Biochem Mol Biol. 2020;202:105719. doi: 10.1016/j.jsbmb.2020.105719
  • Notz Q, Herrmann J, Schlesinger T, et al. Vitamin D deficiency in critically ill COVID-19 ARDS patients. Clin Nutr. 2022;41(12):3089–3095. doi: 10.1016/j.clnu.2021.03.001
  • De Niet S, Trémège M, Coffiner M, et al. Positive effects of Vitamin D supplementation in patients hospitalized for COVID-19: a randomized, double-blind, placebo-controlled trial. Nutrients. 2022;14(15):3048. doi: 10.3390/nu14153048
  • Annweiler C, Beaudenon M, Gautier J, et al. High-dose versus standard-dose Vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): a multicenter, open-label, randomized controlled superiority trial. PLOS Med. 2022;19(5):e1003999. doi: 10.1371/journal.pmed.1003999
  • Cannata-Andía JB, Díaz-Sottolano A, Fernández P, et al. A single-oral bolus of 100,000 IU of Cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D—a Randomised Multicentre International clinical trial. BMC Med. 2022;20(1):83. doi: 10.1186/s12916-022-02290-8
  • Lefrançais E, Ortiz-Muñoz G, Caudrillier A, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature. 2017;544(7648):105–109. doi: 10.1038/nature21706
  • Asaduzzaman M, Lavasani S, Rahman M, et al. Platelets support pulmonary recruitment of neutrophils in abdominal sepsis*. Crit Care Med. 2009;37(4):1389–1396. doi: 10.1097/CCM.0b013e31819ceb71
  • Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest. 2006;116(12):3211–3219. doi: 10.1172/JCI29499
  • Boyle AJ, Di Gangi S, Hamid UI, et al. Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced Intensive Care unit mortality: a prospective analysis. Crit Care. 2015;19(1):109. doi: 10.1186/s13054-015-0846-4
  • Wang Y, Zhong M, Wang Z, et al. The preventive effect of antiplatelet therapy in acute respiratory distress syndrome: a meta-analysis. Crit Care. 2018;22(1):60. doi: 10.1186/s13054-018-1988-y
  • Panka BA, De Grooth H-J, Spoelstra-de Man AME, et al. Prevention or treatment of ards with Aspirin: a review of preclinical models and meta-analysis of clinical studies. Shock. 2017;47(1):13–21. doi: 10.1097/SHK.0000000000000745
  • 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: the CITRIS-ALI randomized clinical trial. JAMA. 2019;322(13):1261. doi: 10.1001/jama.2019.11825
  • Matthay MA, Arabi YM, Siegel ER, et al. Phenotypes and personalized medicine in the acute respiratory distress syndrome. Intensive care Med. 2020;46(12):2136–2152. doi: 10.1007/s00134-020-06296-9
  • Zhu C, Xie J, Zhao Z, et al. PD-L1 maintains neutrophil Extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury. Front Immunol. 2022;13:949217. doi: 10.3389/fimmu.2022.949217
  • Robba C, Battaglini D, Pelosi P, et al. Multiple Organ Dysfunction in SARS-CoV-2: MODS-CoV-2. Expert Rev Respir Med. 2020;14(9):865–868. doi: 10.1080/17476348.2020.1778470
  • Sabbatino F, Conti V, Franci G, et al. PD-L1 dysregulation in COVID-19 patients. Front Immunol. 2021;12:695242. doi: 10.3389/fimmu.2021.695242
  • Dabrowska S, Andrzejewska A, Janowski M, et al. Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cells and Extracellular Vesicles: Therapeutic Outlook for Inflammatory and Degenerative Diseases. Front Immunol. 2021;11:591065. doi: 10.3389/fimmu.2020.591065
  • 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(1):31. doi: 10.1186/s13054-022-04287-4
  • Byrnes D, Masterson CH, Artigas A, et al. Mesenchymal Stem/Stromal cells therapy for sepsis and acute respiratory distress syndrome. Semin Respir Crit Care Med. 2021;42(1):020–039. doi: 10.1055/s-0040-1713422
  • Lopes-Pacheco M, Robba C, Rocco PRM, et al. Current understanding of the therapeutic benefits of Mesenchymal Stem cells in acute respiratory distress syndrome. Cell Biol Toxicol. 2020;36(1):83–102. doi: 10.1007/s10565-019-09493-5
  • Laffey JG, Matthay MA. F ifty Y ears of R esearch in ARDS.Cell-based therapy for acute respiratory distress syndrome. Biology and potential therapeutic value. Am J Respir Crit Care Med. 2017;196(3):266–273. doi: 10.1164/rccm.201701-0107CP
  • Devaney J, Horie S, Masterson C, et al. Human Mesenchymal stromal cells decrease the severity of acute lung injury induced by E. Coli in the rat. Thorax. 2015;70(7):625–635. doi: 10.1136/thoraxjnl-2015-206813
  • 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(8):1047–1057. doi: 10.1164/rccm.201001-0010OC
  • 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(3):620–630. doi: 10.1208/s12248-015-9728-6
  • Carla A, Pereira B, Boukail H, et al. Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis. Respir Res. 2020;21(1):81. doi: 10.1186/s12931-020-01337-9
  • Alcayaga-Miranda F, Dutra Silva J, Parada N, et al. Safety and efficacy of clinical-grade, cryopreserved menstrual blood Mesenchymal stromal cells in experimental acute respiratory distress syndrome. Front Cell Dev Biol. 2023;11:1031331. doi: 10.3389/fcell.2023.1031331
  • 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
  • Khoury M, Cuenca J, Cruz FF, et al. Current status of cell-based therapies for respiratory virus infections: applicability to COVID-19. Eur Respir J. 2020;55(6):2000858. doi: 10.1183/13993003.00858-2020
  • Cruz FF, Weiss DJ, Rocco PRM. Prospects and progress in cell therapy for acute respiratory distress syndrome. Expert Opin Biol Ther. 2016;16(11):1353–1360. doi: 10.1080/14712598.2016.1218845
  • Zullo JA, Nadel EP, Rabadi MM, et al. The Secretome of hydrogel-coembedded endothelial progenitor cells and mesenchymal stem cells instructs macrophage polarization in endotoxemia. Stem Cells Transl Med. 2015;4(7):852–861. doi: 10.5966/sctm.2014-0111
  • Elman JS, Li M, Wang F, et al. A comparison of adipose and bone marrow-derived Mesenchymal Stromal cell secreted factors in the treatment of systemic inflammation. J Inflamm. 2014;11(1):1. doi: 10.1186/1476-9255-11-1
  • Horie S, Gonzalez H, Brady J, et al. Fresh and cryopreserved human umbilical-cord-derived Mesenchymal stromal cells attenuate injury and enhance resolution and repair following ventilation-induced lung injury. Int J Mol Sci. 2021;22(23):12842. doi: 10.3390/ijms222312842
  • Emukah C, Dittmar E, Naqvi R, et al. Mesenchymal stromal cell conditioned media for lung disease: a systematic review and meta-analysis of preclinical studies. Respir Res. 2019;20(1):239. doi: 10.1186/s12931-019-1212-x
  • Dutra Silva J, Su Y, Calfee CS, et al. Mesenchymal Stromal Cell Extracellular Vesicles Rescue Mitochondrial Dysfunction and Improve Barrier Integrity in Clinically Relevant Models of ARDS. Eur Respir J. 2021;58(1):2002978. doi: 10.1183/13993003.02978-2020
  • Cruz FF, Rocco PRM. Stem-Cell Extracellular Vesicles and Lung Repair. Stem Cell Investig. 2017;4(9):78–78. doi: 10.21037/sci.2017.09.02
  • Song Y, Dou H, Li X, et al. Exosomal miR-146a contributes to the enhanced therapeutic efficacy of interleukin-1β-primed Mesenchymal Stem cells against sepsis. Stem Cells. 2017;35(5):1208–1221. doi: 10.1002/stem.2564
  • Morrison TJ, Jackson MV, Cunningham EK, et al. Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by Extracellular vesicle mitochondrial transfer. Am J Respir Crit Care Med. 2017;196(10):1275–1286. doi: 10.1164/rccm.201701-0170OC
  • Monsel A, Zhu Y, Gennai S, et al. Therapeutic effects of human Mesenchymal Stem cell–derived microvesicles in severe pneumonia in mice. Am J Respir Crit Care Med. 2015;192(3):324–336. doi: 10.1164/rccm.201410-1765OC
  • Khatri M, Richardson LA, Meulia T. Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Influenza Virus-Induced Acute Lung Injury in a Pig Model. Stem Cell Res Ther. 2018;9(1):17. doi: 10.1186/s13287-018-0774-8
  • Su Y, Silva JD, Doherty D, et al. Mesenchymal stromal cells-derived Extracellular Vesicles reprogramme macrophages in ARDS models through the miR-181a-5p-PTEN-pSTAT5-SOCS1 axis. Thorax. 2023;78(6):617–630. doi: 10.1136/thoraxjnl-2021-218194
  • Silva JD, De Castro LL, Braga CL, et al. Mesenchymal stromal cells are more effective than their Extracellular Vesicles at reducing lung injury regardless of acute respiratory distress syndrome etiology. Stem Cells Int. 2019;2019:1–15. doi: 10.1155/2019/8262849
  • 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
  • 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
  • Wick KD, Leligdowicz A, Zhuo H, et al. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS. JCI Insight. 2021;6(12):e148983. doi: 10.1172/jci.insight.148983
  • 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(1):217. doi: 10.1186/s13287-023-03451-z
  • O’Kane CM, Matthay MA. Understanding the role of Mesenchymal stromal cells in treating COVID-19 acute respiratory distress syndrome. Am J Respir Crit Care Med. 2023;207(3):231–233. doi: 10.1164/rccm.202209-1838ED

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.