Semin Respir Crit Care Med 2013; 34(04): 475-486
DOI: 10.1055/s-0033-1351122
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Viral Pathogens and Acute Lung Injury: Investigations Inspired by the SARS Epidemic and the 2009 H1N1 Influenza Pandemic

Carolyn M. Hendrickson
1   Division of Pulmonary and Critical Care Medicine, Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, California
,
Michael A. Matthay
1   Division of Pulmonary and Critical Care Medicine, Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, California
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
11. August 2013 (online)

Abstract

Acute viral pneumonia is an important cause of acute lung injury (ALI), although not enough is known about the exact incidence of viral infection in ALI. Polymerase chain reaction-based assays, direct fluorescent antigen (DFA) assays, and viral cultures can detect viruses in samples from the human respiratory tract, but the presence of the virus does not prove it to be a pathogen, nor does it give information regarding the interaction of viruses with the host immune response and bacterial flora of the respiratory tract. The severe acute respiratory syndrome (SARS) epidemic and the 2009 H1N1 influenza pandemic provided a better understanding of how viral pathogens mediate lung injury. Although the viruses initially infect the respiratory epithelium, the relative role of epithelial damage and endothelial dysfunction has not been well defined. The inflammatory host immune response to H1N1 infection is a major contributor to lung injury. The SARS coronavirus causes lung injury and inflammation in part through actions on the nonclassical renin angiotensin pathway. The lessons learned from the pandemic outbreaks of SARS coronavirus and H1N1 capture key principles of virally mediated ALI. There are pathogen-specific pathways underlying virally mediated ALI that converge onto a common end pathway resulting in diffuse alveolar damage. In terms of therapy, lung protective ventilation is the cornerstone of supportive care. There is little evidence that corticosteroids are beneficial, and they might be harmful. Future therapeutic strategies may be targeted to specific pathogens, the pathogenetic pathways in the host immune response, or enhancing repair and regeneration of tissue damage.

 
  • References

  • 1 Rubenfeld GD, Caldwell E, Peabody E , et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005; 353 (16) 1685-1693
  • 2 Esposito S, Daleno C, Prunotto G , et al. Impact of viral infections in children with community-acquired pneumonia: results of a study of 17 respiratory viruses. Influenza Other Respi Viruses 2013; 7 (1) 18-26
  • 3 Limaye AP, Boeckh M. CMV in critically ill patients: pathogen or bystander?. Rev Med Virol 2010; 20 (6) 372-379
  • 4 Chiche L, Forel JM, Papazian L. The role of viruses in nosocomial pneumonia. Curr Opin Infect Dis 2011; 24 (2) 152-156
  • 5 Ksiazek TG, Erdman D, Goldsmith CS , et al; SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003; 348 (20) 1953-1966
  • 6 Peiris JS, Lai ST, Poon LL , et al; SARS study group. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 2003; 361 (9366) 1319-1325
  • 7 Booth CM, Matukas LM, Tomlinson GA , et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 2003; 289 (21) 2801-2809
  • 8 Donnelly CA, Ghani AC, Leung GM , et al. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet 2003; 361 (9371) 1761-1766
  • 9 Leung GM, Hedley AJ, Ho LM , et al. The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients. Ann Intern Med 2004; 141 (9) 662-673
  • 10 Smits SL, de Lang A, van den Brand JM , et al. Exacerbated innate host response to SARS-CoV in aged non-human primates. PLoS Pathog 2010; 6 (2) e1000756
  • 11 Ding Y, Wang H, Shen H , et al. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol 2003; 200 (3) 282-289
  • 12 Hwang DM, Chamberlain DW, Poutanen SM, Low DE, Asa SL, Butany J. Pulmonary pathology of severe acute respiratory syndrome in Toronto. Mod Pathol 2005; 18 (1) 1-10
  • 13 Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med 2006; 3 (9) e343
  • 14 Li W, Moore MJ, Vasilieva N , et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426 (6965) 450-454
  • 15 Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203 (2) 631-637
  • 16 Lau YL, Peiris JS. Pathogenesis of severe acute respiratory syndrome. Curr Opin Immunol 2005; 17 (4) 404-410
  • 17 He L, Ding Y, Zhang Q , et al. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol 2006; 210 (3) 288-297
  • 18 Imai Y, Kuba K, Rao S , et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005; 436 (7047) 112-116
  • 19 Rey-Parra GJ, Vadivel A, Coltan L , et al. Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury. J Mol Med (Berl) 2012; 90 (6) 637-647
  • 20 Hagiwara S, Iwasaka H, Hidaka S, Hasegawa A, Koga H, Noguchi T. Antagonist of the type-1 ANG II receptor prevents against LPS-induced septic shock in rats. Intensive Care Med 2009; 35 (8) 1471-1478
  • 21 Wösten-van Asperen RM, Lutter R, Specht PA , et al. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist. J Pathol 2011; 225 (4) 618-627
  • 22 Treml B, Neu N, Kleinsasser A , et al. Recombinant angiotensin-converting enzyme 2 improves pulmonary blood flow and oxygenation in lipopolysaccharide-induced lung injury in piglets. Crit Care Med 2010; 38 (2) 596-601
  • 23 Kong SL, Chui P, Lim B, Salto-Tellez M. Elucidating the molecular physiopathology of acute respiratory distress syndrome in severe acute respiratory syndrome patients. Virus Res 2009; 145 (2) 260-269
  • 24 Smits SL, van den Brand JM, de Lang A , et al. Distinct severe acute respiratory syndrome coronavirus-induced acute lung injury pathways in two different nonhuman primate species. J Virol 2011; 85 (9) 4234-4245
  • 25 Kharofa J, Cohen EP, Tomic R, Xiang Q, Gore E. Decreased risk of radiation pneumonitis with incidental concurrent use of angiotensin-converting enzyme inhibitors and thoracic radiation therapy. Int J Radiat Oncol Biol Phys 2012; 84 (1) 238-243
  • 26 Maeda N, Uede T. Swine-origin influenza-virus-induced acute lung injury: novel or classical pathogenesis?. World J Biol Chem 2010; 1 (5) 85-94
  • 27 Dawood FS, Jain S, Finelli L , et al; Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; 360 (25) 2605-2615
  • 28 Hui DS, Lee N, Chan PK. Clinical management of pandemic 2009 influenza A(H1N1) infection. Chest 2010; 137 (4) 916-925
  • 29 Maines TR, Jayaraman A, Belser JA , et al. Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science 2009; 325 (5939) 484-487
  • 30 Munster VJ, de Wit E, van den Brand JM , et al. Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 2009; 325 (5939) 481-483
  • 31 Itoh Y, Shinya K, Kiso M , et al. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 2009; 460 (7258) 1021-1025
  • 32 Shrestha SS, Swerdlow DL, Borse RH , et al. Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010). Clin Infect Dis 2011; 52 (Suppl. 01) S75-S82
  • 33 Louie JK, Acosta M, Jamieson DJ, Honein MA, California Pandemic Working G. California Pandemic (H1N1) Working Group. Severe 2009 H1N1 influenza in pregnant and postpartum women in California. N Engl J Med 2010; 362 (1) 27-35
  • 34 Centers for Disease Control and Prevention (CDC). Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - United States, May-August 2009. MMWR Morb Mortal Wkly Rep 2009; 58 (38) 1071-1074
  • 35 Jamieson DJ, Honein MA, Rasmussen SA , et al; Novel Influenza A (H1N1) Pregnancy Working Group. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009; 374 (9688) 451-458
  • 36 Jain S, Kamimoto L, Bramley AM , et al; 2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation Team. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009; 361 (20) 1935-1944
  • 37 Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S , et al; INER Working Group on Influenza. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009; 361 (7) 680-689
  • 38 Webb SA, Pettilä V, Seppelt I , et al; ANZIC Influenza Investigators. Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 2009; 361 (20) 1925-1934
  • 39 Kumar A, Zarychanski R, Pinto R , et al; Canadian Critical Care Trials Group H1N1 Collaborative. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 2009; 302 (17) 1872-1879
  • 40 Estenssoro E, Ríos FG, Apezteguía C , et al; Registry of the Argentinian Society of Intensive Care SATI. Pandemic 2009 influenza A in Argentina: a study of 337 patients on mechanical ventilation. Am J Respir Crit Care Med 2010; 182 (1) 41-48
  • 41 Konter J, Baez E, Summer RS. Obesity: “Priming” the lung for injury. Pulm Pharmacol Ther 2012;
  • 42 Stapleton RD, Dixon AE, Parsons PE, Ware LB, Suratt BT, Network NARDS. NHLBI Acute Respiratory Distress Syndrome Network. The association between BMI and plasma cytokine levels in patients with acute lung injury. Chest 2010; 138 (3) 568-577
  • 43 Kordonowy LL, Burg E, Lenox CC , et al. Obesity is associated with neutrophil dysfunction and attenuation of murine acute lung injury. Am J Respir Cell Mol Biol 2012; 47 (1) 120-127
  • 44 Quispe-Laime AM, Bracco JD, Barberio PA , et al. H1N1 influenza A virus-associated acute lung injury: response to combination oseltamivir and prolonged corticosteroid treatment. Intensive Care Med 2010; 36 (1) 33-41
  • 45 Lee N, Allen Chan KC, Hui DS , et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol 2004; 31 (4) 304-309
  • 46 Wang H, Ding Y, Li X, Yang L, Zhang W, Kang W. Fatal aspergillosis in a patient with SARS who was treated with corticosteroids. N Engl J Med 2003; 349 (5) 507-508
  • 47 Yap FH, Gomersall CD, Fung KS , et al. Increase in methicillin-resistant Staphylococcus aureus acquisition rate and change in pathogen pattern associated with an outbreak of severe acute respiratory syndrome. Clin Infect Dis 2004; 39 (4) 511-516
  • 48 Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342 (18) 1334-1349
  • 49 Wiedemann HP, Wheeler AP, Bernard GR , et al; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354 (24) 2564-2575
  • 50 Davies A, Jones D, Bailey M , et al; Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators. Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome. JAMA 2009; 302 (17) 1888-1895
  • 51 Diaz JV, Brower R, Calfee CS, Matthay MA. Therapeutic strategies for severe acute lung injury. Crit Care Med 2010; 38 (8) 1644-1650
  • 52 Bermejo-Martin JF, Ortiz de Lejarazu R, Pumarola T , et al. Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. Crit Care 2009; 13 (6) R201
  • 53 Hagau N, Slavcovici A, Gonganau DN , et al. Clinical aspects and cytokine response in severe H1N1 influenza A virus infection. Crit Care 2010; 14 (6) R203
  • 54 Mauad T, Hajjar LA, Callegari GD , et al. Lung pathology in fatal novel human influenza A (H1N1) infection. Am J Respir Crit Care Med 2010; 181 (1) 72-79
  • 55 Cheng VC, Lau YK, Lee KL , et al. Fatal co-infection with swine origin influenza virus A/H1N1 and community-acquired methicillin-resistant Staphylococcus aureus. J Infect 2009; 59 (5) 366-370
  • 56 Centers for Disease Control and Prevention (CDC). Intensive-care patients with severe novel influenza A (H1N1) virus infection - Michigan, June 2009. MMWR Morb Mortal Wkly Rep 2009; 58 (27) 749-752
  • 57 Rice TW, Rubinson L, Uyeki TM , et al; NHLBI ARDS Network. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med 2012; 40 (5) 1487-1498
  • 58 Barnard DL. Animal models for the study of influenza pathogenesis and therapy. Antiviral Res 2009; 82 (2) A110-A122
  • 59 Chan KH, Zhang AJ, To KK , et al. Wild type and mutant 2009 pandemic influenza A (H1N1) viruses cause more severe disease and higher mortality in pregnant BALB/c mice. PLoS ONE 2010; 5 (10) e13757
  • 60 Chen H, Wen X, To KK , et al. Quasispecies of the D225G substitution in the hemagglutinin of pandemic influenza A(H1N1) 2009 virus from patients with severe disease in Hong Kong, China. J Infect Dis 2010; 201 (10) 1517-1521
  • 61 Melidou A, Gioula G, Exindari M, Chatzidimitriou D, Diza E, Malisiovas N. Molecular and phylogenetic analysis of the haemagglutinin gene of pandemic influenza H1N1 2009 viruses associated with severe and fatal infections. Virus Res 2010; 151 (2) 192-199
  • 62 Zheng B, Chan KH, Zhang AJ , et al. D225G mutation in hemagglutinin of pandemic influenza H1N1 (2009) virus enhances virulence in mice. Exp Biol Med (Maywood) 2010; 235 (8) 981-988
  • 63 Garigliany MM, Habyarimana A, Lambrecht B , et al. Influenza A strain-dependent pathogenesis in fatal H1N1 and H5N1 subtype infections of mice. Emerg Infect Dis 2010; 16 (4) 595-603
  • 64 Crowe CR, Chen K, Pociask DA , et al. Critical role of IL-17RA in immunopathology of influenza infection. J Immunol 2009; 183 (8) 5301-5310
  • 65 Li C, Yang P, Sun Y , et al. IL-17 response mediates acute lung injury induced by the 2009 pandemic influenza A (H1N1) virus. Cell Res 2012; 22 (3) 528-538
  • 66 Chang SH, Dong C. Signaling of interleukin-17 family cytokines in immunity and inflammation. Cell Signal 2011; 23 (7) 1069-1075
  • 67 Xu S, Cao X. Interleukin-17 and its expanding biological functions. Cell Mol Immunol 2010; 7 (3) 164-174
  • 68 Peschke T, Bender A, Nain M, Gemsa D. Role of macrophage cytokines in influenza A virus infections. Immunobiology 1993; 189 (3-4) 340-355
  • 69 Perrone LA, Plowden JK, García-Sastre A, Katz JM, Tumpey TM. H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PLoS Pathog 2008; 4 (8) e1000115
  • 70 Tate MD, Pickett DL, van Rooijen N, Brooks AG, Reading PC. Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice. J Virol 2010; 84 (15) 7569-7580
  • 71 Zhang Y, Sun H, Fan L , et al. Acute respiratory distress syndrome induced by a swine 2009 H1N1 variant in mice. PLoS ONE 2012; 7 (1) e29347
  • 72 Narasaraju T, Yang E, Samy RP , et al. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol 2011; 179 (1) 199-210
  • 73 Tate MD, Brooks AG, Reading PC. The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice. Respir Res 2008; 9: 57
  • 74 Tate MD, Deng YM, Jones JE, Anderson GP, Brooks AG, Reading PC. Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol 2009; 183 (11) 7441-7450
  • 75 Zeng H, Pappas C, Belser JA , et al. Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. J Virol 2012; 86 (2) 667-678
  • 76 Gao W, Mao Q, Feng AW , et al. Inhibition of pre-B cell colony-enhancing factor attenuates inflammation and apoptosis induced by pandemic H1N1 2009 in lung endothelium. Respir Physiol Neurobiol 2011; 178 (2) 235-241
  • 77 Teijaro JR, Walsh KB, Cahalan S , et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011; 146 (6) 980-991
  • 78 Matthay MA, Liu KD. Con: corticosteroids are not indicated for treatment of acute lung injury from H1N1 viral pneumonia. Am J Respir Crit Care Med 2011; 183 (9) 1127-1128
  • 79 Liu Z, Guo Z, Wang G , et al. Evaluation of the efficacy and safety of a statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in BALB/c mice. Eur J Pharm Sci 2009; 38 (3) 215-223
  • 80 Levitt JE, Bedi H, Calfee CS, Gould MK, Matthay MA. Identification of early acute lung injury at initial evaluation in an acute care setting prior to the onset of respiratory failure. Chest 2009; 135 (4) 936-943
  • 81 Gotts JE, Matthay MA. Mesenchymal stem cells and acute lung injury. Crit Care Clin 2011; 27 (3) 719-733
  • 82 Matthay MA, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. J Clin Invest 2012; 122 (8) 2731-2740
  • 83 Yong E. Influenza: Five questions on H5N1. Nature 2012; 486 (7404) 456-458