Skip to main content
SpringerLink
Log in

Acute Respiratory Distress Syndrome: Therapeutics, Pathobiology, and Prognosis

  • Chapter
  • First Online:
Chronic Lung Diseases

  • 1161 Accesses

Abstract

Acute respiratory distress syndrome (ARDS) is a critical syndrome consisting of acute respiratory failure, which is characterized by injury to the alveolar capillary barrier that leads to the influx of protein-rich fluid infiltrates into alveolar spaces and subsequent devastating lung fibrosis. This deadly respiratory condition can be caused by various pulmonary (e.g., pneumonia, aspiration) or non-pulmonary (e.g., sepsis, pancreatitis, trauma) injuries, leading to the development of nonhydrostatic pulmonary edema. Despite various seminal events in the understanding of molecular mechanisms underpinning the ARDS, the armamentarium of therapies aimed at the underlying pathology remains limited and highly ineffective. ARDS has an enormous mortality rate of approximately 40%. Till today, ARDS management remains mostly supportive with lung-protective mechanical ventilation. Here, we deduce the recent advances in the understanding of the biology of the disease, the diagnosis, and the treatment of ARDS. Moreover, this review also provides a historical background and highlights areas of future perspectives in therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ware LB, Matthay MA (2000) The acute respiratory distress syndrome. N Engl J Med 342:1334–1349

    PubMed  CAS  Google Scholar 

  2. Alessandri F, Pugliese F, Ranieri VM (2018) The role of rescue therapies in the treatment of severe ARDS. Respir Care 63:92–101

    PubMed  Google Scholar 

  3. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE (1967) Acute respiratory distress in adults. Lancet 2:319–323

    PubMed  CAS  Google Scholar 

  4. Roy GB, Lorraine BW, Yves B, Michael AM (2001) Treatment of ARDS. Chest 120:1347–1367

    Google Scholar 

  5. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD et al (2012) Acute respiratory distress syndrome: the Berlin Definition. JAMA 307:2526–2533

    Google Scholar 

  6. Heidemann SM, Nair A, Bulut Y, Sapru A (2017) Pathophysiology and management of acute respiratory distress syndrome in children. Pediatr Clin North Am 64:1017–1037

    PubMed  Google Scholar 

  7. Sapru A, Flori H, Quasney MW et al (2015) Pathobiology of acute respiratory distress syndrome. Pediatr Crit Care Med 16:S6–S22

    PubMed  Google Scholar 

  8. Katz R (1987) Adult respiratory distress syndrome in children. Clin Chest Med 8:635–639

    PubMed  CAS  Google Scholar 

  9. Sherrill DL, Camilli A, Lebowitz MD (1989) On the temporal relationships between lung function and somatic growth. Am Rev Respir Dis 140:638–644

    PubMed  CAS  Google Scholar 

  10. Wang X, Dockery DW, Wypij D et al (1993) Pulmonary function between 6 and 18 years of age. Pediatr Pulmonol 15:75–88

    PubMed  Google Scholar 

  11. Nanchal RS, Truwit JD (2018) Recent advances in understanding and treating acute respiratory distress syndrome. F1000Res 7:F1000 Faculty Rev-1322

    PubMed  PubMed Central  Google Scholar 

  12. Villar J, Sulemanji D, Kacmarek RM (2014) The acute respiratory distress syndrome: incidence and mortality, has it changed? Curr Opin Crit Care 20:3–9

    PubMed  Google Scholar 

  13. Wang T, Gross C, Desai AA et al (2017) Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets. Am J Physiol Lung Cell Mol Physiol 312:L452–L476

    PubMed  Google Scholar 

  14. Fan E, Brodie D, Slutsky AS (2018) Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA 319:698–710

    PubMed  Google Scholar 

  15. Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, Adhikari NKJ, Amato MBP, Branson R, Brower RG et al (2017) An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 195:1253–1263

    PubMed  Google Scholar 

  16. Rubenfeld GD, Caldwell E, Peabody E et al (2005) Incidence and outcomes of acute lung injury. N Engl J Med 353:1685–1693

    PubMed  CAS  Google Scholar 

  17. Park J, Pabon M, Choi AMK et al (2017) Plasma surfactant protein-D as a diagnostic biomarker for acute respiratory distress syndrome: validation in US and Korean cohorts. BMC Pulm Med 17:204

    PubMed  PubMed Central  Google Scholar 

  18. Terpstra ML, Aman J, van Nieuw Amerongen GP, Groeneveld AB (2014) Plasma biomarkers for acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med 42:691–700

    PubMed  CAS  Google Scholar 

  19. Hermans C, Bernard A (1999) Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med 159:646–678

    PubMed  CAS  Google Scholar 

  20. Flori H, Glidden D, Rutherford G et al (2005) Pediatric acute lung injury: prospective evaluation of risk factors associated with mortality. Am J Respir Crit Care Med 171:995–1001

    PubMed  Google Scholar 

  21. Yehya N, Servaes S, Thomas NJ (2015) Characterizing degree of lung injury in pediatric acute respiratory distress syndrome. Crit Care Med 43:937–946

    PubMed  Google Scholar 

  22. Zimmerman JJ, Akhtar SR, Caldwell E et al (2009) Incidence and outcomes of pediatric acute lung injury. Pediatrics 124:87–95

    PubMed  Google Scholar 

  23. Cheifetz IM (2016) Year in review 2015: pediatric ARDS. Respir Care 61:980–985

    PubMed  Google Scholar 

  24. Spadaro S, Park M, Turrini C et al (2019) Biomarkers for Acute Respiratory Distress syndrome and prospects for personalised medicine. J Inflamm (Lond) 16:1

    Google Scholar 

  25. Yanagi S, Tsubouchi H, Miura A, Matsumoto N, Nakazato M (2015) Breakdown of epithelial barrier integrity and overdrive activation of alveolar epithelial cells in the pathogenesis of acute respiratory distress syndrome and lung fibrosis. Biomed Res Int 2015:573210

    PubMed  PubMed Central  Google Scholar 

  26. Bachofen M, Weibel ER (1977) Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis 116:589–615

    PubMed  CAS  Google Scholar 

  27. Ware LB, Eisner MD, Thompson BT et al (2004) Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury. Am J Respir Crit Care Med 170:766–772

    PubMed  Google Scholar 

  28. Orfanos SE, Armaganidis A, Glynos C et al (2000) Pulmonary capillary endothelium bound angiotensin-converting enzyme activity in acute lung injury. Circulation 102:2011–2018

    PubMed  CAS  Google Scholar 

  29. Parsons PE, Eisner MD, Thompson BT et al (2005) Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 33:1–2

    PubMed  CAS  Google Scholar 

  30. Aggarwal NR, King LS, D’Alessio FR (2014) Diverse macrophage populations mediate acute lung inflammation and resolution. Am J Physiol Lung Cell Mol Physiol 306:L709–L725

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Caudrillier A, Kessenbrock K, Gilliss BM et al (2012) Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest 122:2661–2671

    PubMed  PubMed Central  CAS  Google Scholar 

  32. Fan E, Needham DM, Stewart TE (2005) Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 294:2889–2896

    PubMed  CAS  Google Scholar 

  33. Anderson ID, Fearon KC, Grant IS (1996) Laparotomy for abdominal sepsis in the critically ill. Br J Surg 83:535–539

    PubMed  CAS  Google Scholar 

  34. Sinanan M, Maier RV, Carrico CJ (1984) Laparotomy for intraabdominal sepsis in patients in an ICUs. Arch Surg 119:652–658

    PubMed  CAS  Google Scholar 

  35. Doyle RL, Szaflarski N, Modin GW et al (1995) Identification of patients with acute lung injury: predictors of mortality. Am J Respir Crit Care Med 152:1818–1824

    PubMed  CAS  Google Scholar 

  36. Brower RG, Ware LB, Berthiaume Y, Matthay MA (2001) Treatment of ARDS. Chest 120:1347–1367

    PubMed  CAS  Google Scholar 

  37. Falke KJ, Pontoppidan H, Kumar A et al (1972) Ventilation with end-expiratory pressure in acute lung disease. J Clin Invest 51:2315–2323

    PubMed  PubMed Central  CAS  Google Scholar 

  38. Lamy M, Fallat RJ, Koeniger E et al (1976) Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome. Am Rev Respir Dis 114:267–284

    PubMed  CAS  Google Scholar 

  39. Royston BD, Webster NR, Nunn JF (1990) Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen. J Appl Physiol 69:1532–1537

    PubMed  CAS  Google Scholar 

  40. Fracica PJ, Knapp MJ, Piantadosi CA, Takeda K, Fulkerson WJ, Coleman RE, Wolfe WG, Crapo JD (1991) Responses of baboons to prolonged hyperoxia: physiology and qualitative pathology. J Appl Physiol 71:2352–2362

    PubMed  CAS  Google Scholar 

  41. Royer F, Martin DJ, Benchetrit G, Grimbert FA (1988) Increase in pulmonary capillary permeability in dogs exposed to 100% O2. J Appl Physiol 65:1140–1146

    PubMed  CAS  Google Scholar 

  42. Fox RB, Hoidal JR, Brown DM, Repine JE (1981) Pulmonary inflammation due to oxygen toxicity: involvement of chemotactic factors and polymorphonuclear leukocytes. Am Rev Respir Dis 123:521–523

    PubMed  CAS  Google Scholar 

  43. Shank JC, Latshaw RF (1980) Adult respiratory distress syndrome. Am Fam Physician 21:107–114

    PubMed  CAS  Google Scholar 

  44. Falke KJ, Pontoppidan H, Kumar A, Leith DE, Geffin B, Laver MB (1972) Ventilation with end-expiratory pressure in acute lung disease. J Clin Invest 51:2315–2323

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Harrison WD, Raizen M, Ghignone M, Girling L, Slykerman LJ, Prewitt RM (1983) Treatment of canine low pressure pulmonary edema: nitroprusside versus hydralazine. Am Rev Respir Dis 128:857–861

    PubMed  CAS  Google Scholar 

  46. Bone RC, Slotman G, Maunder R, Silverman H, Hyers TM, Kerstein MD, Ursprung JJ (1989) Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome: Prostaglandin E1 Study Group. Chest 96:114–119

    PubMed  CAS  Google Scholar 

  47. Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM (1991) Inhaled nitric oxide: a selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 83:2038–2047

    PubMed  CAS  Google Scholar 

  48. Fratacci MD, Frostell CG, Chen TY, Wain JC Jr, Robinson DR, Zapol WM (1991) Inhaled nitric oxide: a selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. Anesthesiology 75:990–999

    PubMed  CAS  Google Scholar 

  49. Shah NS, Nakayama DK, Jacob TD (1994) Efficacy of inhaled nitric oxide in a porcine model of adult respiratory distress syndrome. Arch Surg 129:158–164

    PubMed  CAS  Google Scholar 

  50. Rossaint R, Falke KJ, López F, Slama K, Pison U, Zapol WM (1993) Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 328:399–405

    PubMed  CAS  Google Scholar 

  51. Rayees S, Joshi JC, Tauseef M, Anwar M, Baweja S, Rochford I, Joshi B, Hollenberg MD, Reddy SP, Mehta D (2019) PAR2-mediated cAMP generation suppresses TRPV4-dependent Ca2+ signaling in alveolar macrophages to resolve TLR4-induced inflammation. Cell Rep 27:793–805

    PubMed  PubMed Central  CAS  Google Scholar 

  52. Sutherland KR, Maunder RJ, Milberg JA, Allen DL, Hudson LD (1995) Pulmonary infection during the acute respiratory distress syndrome. Am J Respir Crit Care Med 152:550–556

    PubMed  CAS  Google Scholar 

  53. Meduri GU, Wunderink RG, Leeper KV Jr, Jones CB, Tolley E, Mayhall G (1994) Causes of fever and pulmonary densities in patients with clinical manifestations of ventilator-associated pneumonia. Chest 106:221–235

    PubMed  CAS  Google Scholar 

  54. Seidenfeld JJ, Bell RC, Harris GD, Johanson WG Jr (1986) Incidence, site, and outcome of infections in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 134:12–16

    PubMed  CAS  Google Scholar 

  55. American Thoracic Society (1995) Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventative strategies; a consensus statement. Am J Respir Crit Care Med 153:1711–1725

    Google Scholar 

  56. Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M (2006) National Heart L. Blood institute acute respiratory distress syndrome clinical trials N: efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 354:1671–1684

    PubMed  CAS  Google Scholar 

  57. McNicholas BA, Rooney GM, Laffey JG (2018) Lessons to learn from epidemiologic studies in ARDS. Curr Opin Crit Care 24:41–48

    PubMed  Google Scholar 

  58. Rezoagli E, Fumagalli R, Bellani G (2017) Definition and epidemiology of acute respiratory distress syndrome. Ann Transl Med 5:282

    PubMed  PubMed Central  Google Scholar 

  59. Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, Network NA (2014) Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med 2:611–620

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Center for Lung and Vascular Biology, University of Illinois at Chicago, Chicago, IL, USA

    Vigneshwaran Vellingiri

  2. Department of Experimental Pathology and Medicine, Mayo Clinic, Rochester, MN, USA

    Prabhu Thirusangu

  3. Department of Biochemistry, Govt. Medical College Srinagar, Srinagar, India

    Inshah Din

Authors
  1. Vigneshwaran Vellingiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prabhu Thirusangu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Inshah Din
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vigneshwaran Vellingiri .

Editor information

Editors and Affiliations

  1. Department of Pharmacology, University of Illinois at Chicago, Illinois, IL, USA

    Sheikh Rayees

  2. Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India

    Inshah Din

  3. Toxicology, CSIR-IIM, Jammu, Jammu and Kashmir, India

    Gurdarshan Singh

  4. Cancer Pharmacology, CSIR-IIM, Jammu, Jammu and Kashmir, India

    Fayaz A Malik

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vellingiri, V., Thirusangu, P., Din, I. (2020). Acute Respiratory Distress Syndrome: Therapeutics, Pathobiology, and Prognosis. In: Rayees, S., Din, I., Singh, G., Malik, F. (eds) Chronic Lung Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-15-3734-9_7

Download citation

Publish with us

Policies and ethics

Search

Navigation