Acute Lung Injury: Epidemiology, Pathogenesis, and Treatment

Overview

Journal J Aerosol Med Pulm Drug Deliv

Specialties Pharmacology
Pulmonary Medicine

Date 2010 Jan 16

PMID 20073554

Citations 352

Authors

Elizabeth R Johnson

Michael A Matthay

Affiliations

Soon will be listed here.

Abstract

Acute lung injury (ALI) remains a significant source of morbidity and mortality in the critically ill patient population. Defined by a constellation of clinical criteria (acute onset of bilateral pulmonary infiltrates with hypoxemia without evidence of hydrostatic pulmonary edema), ALI has a high incidence (200,000 per year in the US) and overall mortality remains high. Pathogenesis of ALI is explained by injury to both the vascular endothelium and alveolar epithelium. Recent advances in the understanding of pathophysiology have identified several biologic markers that are associated with worse clinical outcomes. Phase III clinical trials by the NHLBI ARDS Network have resulted in improvement in survival and a reduction in the duration of mechanical ventilation with a lung-protective ventilation strategy and fluid conservative protocol. Potential areas of future treatments include nutritional strategies, statin therapy, and mesenchymal stem cells.

Citing Articles

Therapeutic role of gut microbiota in lung injury-related cognitive impairment.

Cheng Y, Hu G, Deng L, Zan Y, Chen X Front Nutr. 2025; 11:1521214.

PMID: 40017811 PMC: 11867030. DOI: 10.3389/fnut.2024.1521214.

Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers.

Meshanni J, Stevenson E, Zhang D, Sun R, Ona N, Reagan E Nat Commun. 2025; 16(1):1806.

PMID: 39984450 PMC: 11845678. DOI: 10.1038/s41467-025-56448-y.

Lung recruitment mechanics: coalescing tissue strains with organ expansion.

Shankel M, Nelson T, Quiros K, Bebawy J, Mariano C, Biddle T Respir Res. 2025; 26(1):58.

PMID: 39966833 PMC: 11834643. DOI: 10.1186/s12931-025-03118-8.

The Effect of Inhaled Ozone Therapy in Two-Hit Rat Model of Lipopolysaccharides-Induced Acute Lung Injury and Bleomycin-Induced Pulmonary Fibrosis.

Celik M, Koca M, Halici Z, Tavaci T, Halici H, Ozkaraca M Protein J. 2025; .

PMID: 39920533 DOI: 10.1007/s10930-024-10247-4.

Editorial: Model organisms in respiratory pharmacology 2023.

McCarron A, Surolia R, Ruffini L Front Pharmacol. 2025; 15:1540222.

PMID: 39872054 PMC: 11770033. DOI: 10.3389/fphar.2024.1540222.

References

Berthiaume Y, Staub N, Matthay M . Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep. J Clin Invest. 1987; 79(2):335-43. PMC: 424066. DOI: 10.1172/JCI112817. View

Calfee C, Eisner M, Parsons P, Thompson B, Conner Jr E, Matthay M . Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury. Intensive Care Med. 2008; 35(2):248-57. PMC: 2790376. DOI: 10.1007/s00134-008-1235-0. View

Matute-Bello G, Martin T . Science review: apoptosis in acute lung injury. Crit Care. 2003; 7(5):355-8. PMC: 270707. DOI: 10.1186/cc1861. View

Downey G, Dong Q, Kruger J, Dedhar S, Cherapanov V . Regulation of neutrophil activation in acute lung injury. Chest. 1999; 116(1 Suppl):46S-54S. View

Liu K, Levitt J, Zhuo H, Kallet R, Brady S, Steingrub J . Randomized clinical trial of activated protein C for the treatment of acute lung injury. Am J Respir Crit Care Med. 2008; 178(6):618-23. PMC: 2542435. DOI: 10.1164/rccm.200803-419OC. View

Hudson L, Steinberg K . Epidemiology of acute lung injury and ARDS. Chest. 1999; 116(1 Suppl):74S-82S. DOI: 10.1378/chest.116.suppl_1.74s-a. View

Reising C, Chendrasekhar A, Wall P, Paradise N, Timberlake G, Moorman D . Continuous dose furosemide as a therapeutic approach to acute respiratory distress syndrome (ARDS). J Surg Res. 1999; 82(1):56-60. DOI: 10.1006/jsre.1998.5513. View

Hernandez G, Velasco N, Wainstein C, Castillo L, Bugedo G, Maiz A . Gut mucosal atrophy after a short enteral fasting period in critically ill patients. J Crit Care. 1999; 14(2):73-7. DOI: 10.1016/s0883-9441(99)90017-5. View

. Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network. JAMA. 2000; 283(15):1995-2002. DOI: 10.1001/jama.283.15.1995. View

10.

McAuley D, Matthay M . Is there a role for beta-adrenoceptor agonists in the management of acute lung injury and the acute respiratory distress syndrome?. Treat Respir Med. 2005; 4(5):297-307. DOI: 10.2165/00151829-200504050-00001. View

11.

Seeley E, McAuley D, Eisner M, Miletin M, Matthay M, Kallet R . Predictors of mortality in acute lung injury during the era of lung protective ventilation. Thorax. 2008; 63(11):994-8. PMC: 2771451. DOI: 10.1136/thx.2007.093658. View

12.

Ware L, Conner E, Matthay M . von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury. Crit Care Med. 2002; 29(12):2325-31. DOI: 10.1097/00003246-200112000-00016. View

13.

Buchman A, Moukarzel A, Bhuta S, Belle M, Ament M, Eckhert C . Parenteral nutrition is associated with intestinal morphologic and functional changes in humans. JPEN J Parenter Enteral Nutr. 1995; 19(6):453-60. DOI: 10.1177/0148607195019006453. View

14.

Meduri G, Headley A, Golden E, J Carson S, Umberger R, Kelso T . Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1998; 280(2):159-65. DOI: 10.1001/jama.280.2.159. View

15.

Dowdy D, Eid M, Dennison C, Mendez-Tellez P, Herridge M, Guallar E . Quality of life after acute respiratory distress syndrome: a meta-analysis. Intensive Care Med. 2006; 32(8):1115-24. DOI: 10.1007/s00134-006-0217-3. View

16.

Domenighetti G, Suter P, Schaller M, Ritz R, Perret C . Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study. J Crit Care. 1998; 12(4):177-82. DOI: 10.1016/s0883-9441(97)90029-0. View

17.

Brower R, Matthay M, Morris A, Schoenfeld D, Thompson B, Wheeler A . 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. 2000; 342(18):1301-8. DOI: 10.1056/NEJM200005043421801. View

18.

Matute-Bello G, Frevert C, Liles W, Nakamura M, Ruzinski J, Ballman K . Fas/Fas ligand system mediates epithelial injury, but not pulmonary host defenses, in response to inhaled bacteria. Infect Immun. 2001; 69(9):5768-76. PMC: 98694. DOI: 10.1128/IAI.69.9.5768-5776.2001. View

19.

Wiedemann H, Wheeler A, Bernard G, Thompson B, Hayden D, deBoisblanc B . Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006; 354(24):2564-75. DOI: 10.1056/NEJMoa062200. View

20.

Liappis A, Kan V, Rochester C, Simon G . The effect of statins on mortality in patients with bacteremia. Clin Infect Dis. 2001; 33(8):1352-7. DOI: 10.1086/323334. View