The Role of Infections in BOS

  • Robin K. AveryEmail author
Part of the Respiratory Medicine book series (RM, volume 8)


Background: Infectious agents, particularly cytomegalovirus (CMV), have long been considered to be potential triggers for BOS, although the exact magnitude of the role of infections and the mechanisms thereof remain an area of active research. Methods: This chapter will review previous literature and newer results concerning the possible roles of CMV, other herpesviruses, community-acquired respiratory viruses, bacteria (including Pseudomonas, other gram-negative, gram-positive, and atypical organisms), and fungi, including colonization as well as invasive infection. Results: The text reviews and evaluates the body of literature supporting a role for these infectious agents as risk factors for BOS and time to BOS. Changing patterns of infection over time are taken into account, and studies that have shown an association between BOS (or lack thereof) and CMV are reviewed. Strategies for prevention or early treatment of infections are discussed as potential means of preserving allograft function long term. Immunizations, stringent infection-control practices, and antimicrobial treatment including newer therapies will be discussed. Conclusion: In addition to the classic literature that has focused on CMV, an expanding spectrum of infectious organisms has been implicated as possible risk factors for BOS. Increasing knowledge of the impact of long-term antiviral suppression, prophylaxis, and outcomes of early therapy will help guide future recipient management.


Infection Cytomegalovirus Bacterial Pseudomonas Gram-positive Gram-negative Fungal Prophylaxis 


  1. 1.
    Soghikian MV, Valentine VG, Berry GJ, Patel HR, Robbins RC, Theodore J. Impact of ganciclovir prophylaxis on heart-lung and lung transplant recipients. J Heart Lung Transplant. 1996;15(9):881–7.PubMedGoogle Scholar
  2. 2.
    Zeevi A, Morel P, Spichty K, Dauber J, Yousem S, Williams P, et al. Clinical significance of CMV-specific T helper responses in lung transplant recipients. Hum Immunol. 1998;59(12):768–75.PubMedCrossRefGoogle Scholar
  3. 3.
    Bando K, Paradis IL, Komatsu K, Konishi H, Matsushima M, Keena RJ, et al. Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation. J Thorac Cardiovasc Surg. 1995;109(1):49–57; discussion 57–9.Google Scholar
  4. 4.
    Kroshus TJ, Kshettry VR, Savik K, John R, Hertz MI, Bolman 3rd RM. Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation. J Thorac Cardiovasc Surg. 1997;114(2):195–202.PubMedCrossRefGoogle Scholar
  5. 5.
    Cerrina J, Le Roy LF, Herve PH, Parquin F, Harari S, Chapelier A, et al. Role of CMV pneumonia in the development of obliterative bronchiolitis in heart-lung and double-lung transplant recipients. Transpl Int. 1992;5 Suppl 1:S242–5.PubMedGoogle Scholar
  6. 6.
    Heng D, Sharples LD, McNeil K, Stewart S, Wreghitt T, Wallwork J. Bronchiolitis obliterans syndrome: incidence, natural history, prognosis, and risk factors. J Heart Lung Transplant. 1998;17(12):1255–63.PubMedGoogle Scholar
  7. 7.
    Keenan RJ, Lega ME, Dummer JS, Paradis IL, Dauber JH, Rabinowich H, et al. Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation. Transplantation. 1991;51(2):433–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Tikkanen JM, Kallio EA, Bruggeman CA, Koskinen PK, Lemstrom KB. Prevention of cytomegalovirus infection-enhanced experimental obliterative bronchiolitis by antiviral prophylaxis or immunosuppression in rat tracheal allografts. Am J Respir Crit Care Med. 2001;164(4):672–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Wiebe K, Fraund S, Steinmuller C, Steinhoff G. Rat cytomegalovirus and Listeria monocytogenes infection enhance chronic rejection after allogenic rat lung transplantation. Transpl Int. 2005;18(10):1166–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Weseslindtner L, Nachbagauer R, Kundi M, Jaksch P, Kerschner H, Simon B, et al. Human cytomegalovirus infection in lung transplant recipients triggers a CXCL-10 response. Am J Transplant. 2011;11(3):542–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Uhlin M, Mattsson J, Maeurer M. Update on viral infections in lung transplantation. Curr Opin Pulm Med. 2012;18(3):264–70.PubMedCrossRefGoogle Scholar
  12. 12.
    Weigt SS, Elashoff RM, Keane MP, Strieter RM, Gomperts BN, Xue YY, et al. Altered levels of CC chemokines during pulmonary CMV predict BOS and mortality post-lung transplantation. Am J Transplant. 2008;8(7):1512–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Mitsani D, Nguyen MH, Girnita DM, Spichty K, Kwak EJ, Silveira FP, et al. A polymorphism linked to elevated levels of interferon-gamma is associated with an increased risk of cytomegalovirus disease among Caucasian lung transplant recipients at a single center. J Heart Lung Transplant. 2011;30(5):523–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Bauer CC, Jaksch P, Aberle SW, Haber H, Lang G, Klepetko W, et al. Relationship between cytomegalovirus DNA load in epithelial lining fluid and plasma of lung transplant recipients and analysis of coinfection with Epstein-Barr virus and human herpesvirus 6 in the lung compartment. J Clin Microbiol. 2007;45(2):324–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Tamm M, Aboyoun CL, Chhajed PN, Rainer S, Malouf MA, Glanville AR. Treated cytomegalovirus pneumonia is not associated with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2004;170(10):1120–3.PubMedCrossRefGoogle Scholar
  16. 16.
    Snyder LD, Finlen-Copeland CA, Turbyfill WJ, Howell D, Willner DA, Palmer SM. Cytomegalovirus pneumonitis is a risk for bronchiolitis obliterans syndrome in lung transplantation. Am J Respir Crit Care Med. 2010;181(12):1391–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Valentine VG, Gupta MR, Walker Jr JE, Seoane L, Bonvillain RW, Lombard GA, et al. Effect of etiology and timing of respiratory tract infections on development of bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2009;28(2):163–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Valentine VG, Weill D, Gupta MR, Raper B, Laplace SG, Lombard GA, et al. Ganciclovir for cytomegalovirus: a call for indefinite prophylaxis in lung transplantation. J Heart Lung Transplant. 2008;27(8):875–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Valentine VG, Bonvillain RW, Gupta MR, Lombard GA, LaPlace SG, Dhillon GS, et al. Infections in lung allograft recipients: ganciclovir era. J Heart Lung Transplant. 2008;27(5):528–35.PubMedCrossRefGoogle Scholar
  20. 20.
    Palmer SM, Limaye AP, Banks M, Gallup D, Chapman J, Lawrence EC, et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial. Ann Intern Med. 2010;152(12):761–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Finlen Copeland CA, Davis WA, Snyder LD, Banks M, Avery R, Davis RD, et al. Long-term efficacy and safety of 12 months of valganciclovir prophylaxis compared with 3 months after lung transplantation: a single-center, long-term follow-up analysis from a randomized, controlled cytomegalovirus prevention trial. J Heart Lung Transplant. 2011;30(9):990–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Humar A, Michaels M. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant. 2006;6(2):262–74.PubMedCrossRefGoogle Scholar
  23. 23.
    Humar A, Snydman D. Cytomegalovirus in solid organ transplant recipients. Am J Transplant. 2009;9 Suppl 4:S78–86.PubMedCrossRefGoogle Scholar
  24. 24.
    Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Snydman DR, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation. 2010;89(7):779–95.PubMedCrossRefGoogle Scholar
  25. 25.
    Westall GP, Michaelides A, Williams TJ, Snell GI, Kotsimbos TC. Human cytomegalovirus load in plasma and bronchoalveolar lavage fluid: a longitudinal study of lung transplant recipients. J Infect Dis. 2004;190(6):1076–83.PubMedCrossRefGoogle Scholar
  26. 26.
    Tu W, Potena L, Stepick-Biek P, Liu L, Dionis KY, Luikart H, et al. T-cell immunity to subclinical cytomegalovirus infection reduces cardiac allograft disease. Circulation. 2006;114(15):1608–15.PubMedCrossRefGoogle Scholar
  27. 27.
    Potena L, Holweg CT, Vana ML, Bashyam L, Rajamani J, McCormick AL, et al. Frequent occult infection with cytomegalovirus in cardiac transplant recipients despite antiviral prophylaxis. J Clin Microbiol. 2007;45(6):1804–10.PubMedCrossRefGoogle Scholar
  28. 28.
    Gorzer I, Kerschner H, Jaksch P, Bauer C, Seebacher G, Klepetko W, et al. Virus load dynamics of individual CMV-genotypes in lung transplant recipients with mixed-genotype infections. J Med Virol. 2008;80(8):1405–14.PubMedCrossRefGoogle Scholar
  29. 29.
    Ljungman P, Singh N. Human herpesvirus-6 infection in solid organ and stem cell transplant recipients. J Clin Virol. 2006;37 Suppl 1:S87–91.PubMedCrossRefGoogle Scholar
  30. 30.
    Cone RW, Hackman RC, Huang ML, Bowden RA, Meyers JD, Metcalf M, et al. Human herpesvirus 6 in lung tissue from patients with pneumonitis after bone marrow transplantation. N Engl J Med. 1993;329(3):156–61.PubMedCrossRefGoogle Scholar
  31. 31.
    Neurohr C, Huppmann P, Leuchte H, Schwaiblmair M, Bittmann I, Jaeger G, et al. Human herpesvirus 6 in bronchalveolar lavage fluid after lung transplantation: a risk factor for bronchiolitis obliterans syndrome? Am J Transplant. 2005;5(12):2982–91.PubMedCrossRefGoogle Scholar
  32. 32.
    Ross DJ, Chan RC, Kubak B, Ardehali A, Laks H, Nichols WS. Bronchiolitis obliterans with organizing pneumonia: possible association with human herpes virus-7 infection after lung transplantation. J Heart Lung Transplant. 2001;20(2):171.PubMedCrossRefGoogle Scholar
  33. 33.
    Engelmann I, Welte T, Fuhner T, Simon AR, Mattner F, Hoy L, et al. Detection of Epstein-Barr virus DNA in peripheral blood is associated with the development of bronchiolitis obliterans syndrome after lung transplantation. J Clin Virol. 2009;45(1):47–53.PubMedCrossRefGoogle Scholar
  34. 34.
    Krams SM, Martinez OM. Epstein-Barr virus, rapamycin, and host immune responses. Curr Opin Organ Transplant. 2008;13(6):563–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Manuel O, Kumar D, Moussa G, Chen MH, Pilewski J, McCurry KR, et al. Lack of association between beta-herpesvirus infection and bronchiolitis obliterans syndrome in lung transplant recipients in the era of antiviral prophylaxis. Transplantation. 2009;87(5):719–25.PubMedCrossRefGoogle Scholar
  36. 36.
    Kaiser L, Aubert JD, Pache JC, Deffernez C, Rochat T, Garbino J, et al. Chronic rhinoviral infection in lung transplant recipients. Am J Respir Crit Care Med. 2006;174(12):1392–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Weigt SS, Derhovanessian A, Liao E, Hu S, Gregson AL, Kubak BM, et al. CXCR3 chemokine ligands during respiratory viral infections predict lung allograft dysfunction. Am J Transplant. 2012;12(2):477–84.PubMedCrossRefGoogle Scholar
  38. 38.
    Kumar D, Erdman D, Keshavjee S, Peret T, Tellier R, Hadjiliadis D, et al. Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Am J Transplant. 2005;5(8):2031–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Kumar D, Husain S, Chen MH, Moussa G, Himsworth D, Manuel O, et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation. 2010;89(8):1028–33.PubMedCrossRefGoogle Scholar
  40. 40.
    Gottlieb J, Schulz TF, Welte T, Fuehner T, Dierich M, Simon AR, et al. Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study. Transplantation. 2009;87(10):1530–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Khalifah AP, Hachem RR, Chakinala MM, Schechtman KB, Patterson GA, Schuster DP, et al. Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death. Am J Respir Crit Care Med. 2004;170(2):181–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Vilchez RA, Dauber J, McCurry K, Iacono A, Kusne S. Parainfluenza virus infection in adult lung transplant recipients: an emergent clinical syndrome with implications on allograft function. Am J Transplant. 2003;3(2):116–20.PubMedCrossRefGoogle Scholar
  43. 43.
    Liu M, Mallory GB, Schecter MG, Worley S, Arrigain S, Robertson J, et al. Long-term impact of respiratory viral infection after pediatric lung transplantation. Pediatr Transplant. 2010;14(3):431–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Liu M, Worley S, Arrigain S, Aurora P, Ballmann M, Boyer D, et al. Respiratory viral infections within one year after pediatric lung transplant. Transpl Infect Dis. 2009;11(4):304–12.PubMedCrossRefGoogle Scholar
  45. 45.
    Milstone AP, Brumble LM, Barnes J, Estes W, Loyd JE, Pierson 3rd RN, et al. A single-season prospective study of respiratory viral infections in lung transplant recipients. Eur Respir J. 2006;28(1):131–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Soccal PM, Aubert JD, Bridevaux PO, Garbino J, Thomas Y, Rochat T, et al. Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients. Clin Infect Dis. 2010;51(2):163–70.PubMedCrossRefGoogle Scholar
  47. 47.
    Vu DL, Bridevaux PO, Aubert JD, Soccal PM, Kaiser L. Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies. Am J Transplant. 2011;11(5):1071–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Speich R, van der Bij W. Epidemiology and management of infections after lung transplantation. Clin Infect Dis. 2001;33 Suppl 1:S58–65.PubMedCrossRefGoogle Scholar
  49. 49.
    Girgis RE, Tu I, Berry GJ, Reichenspurner H, Valentine VG, Conte JV, et al. Risk factors for the development of obliterative bronchiolitis after lung transplantation. J Heart Lung Transplant. 1996;15(12):1200–8.PubMedGoogle Scholar
  50. 50.
    Vos R, Vanaudenaerde BM, De Vleeschauwer SI, Van Raemdonck DE, Dupont LJ, Verleden GM. De novo or persistent pseudomonal airway colonization after lung transplantation: importance for bronchiolitis obliterans syndrome? Transplantation 2008;86(4):624–5; author reply 635–6.Google Scholar
  51. 51.
    Flume PA, Egan TM, Paradowski LJ, Detterbeck FC, Thompson JT, Yankaskas JR. Infectious complications of lung transplantation. Impact of cystic fibrosis. Am J Respir Crit Care Med. 1994;149(6):1601–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Nunley DR, Grgurich W, Iacono AT, Yousem S, Ohori NP, Keenan RJ, et al. Allograft colonization and infections with pseudomonas in cystic fibrosis lung transplant recipients. Chest. 1998;113(5):1235–43.PubMedCrossRefGoogle Scholar
  53. 53.
    Botha P, Archer L, Anderson RL, Lordan J, Dark JH, Corris PA, et al. Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation. 2008;85(5):771–4.PubMedCrossRefGoogle Scholar
  54. 54.
    Gottlieb J, Mattner F, Weissbrodt H, Dierich M, Fuehner T, Strueber M, et al. Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis. Respir Med. 2009;103(5):743–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Gupta MR, Valentine VG, Walker Jr JE, Lombard GA, LaPlace SG, Seoane L, et al. Clinical spectrum of gram-positive infections in lung transplantation. Transpl Infect Dis. 2009;11(5):424–31.PubMedCrossRefGoogle Scholar
  56. 56.
    Huang HC, Weigt SS, Derhovanessian A, Palchevskiy V, Ardehali A, Saggar R, et al. Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality. J Heart Lung Transplant. 2011;30(7):790–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis. 1998;27(5):1266–77.PubMedCrossRefGoogle Scholar
  58. 58.
    Charpin JM, Stern M, Lebrun G, Aubin P, Grenet D, Israel-Biet D. Increased endothelin-1 associated with bacterial infection in lung transplant recipients. Transplantation. 2001;71(12):1840–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Borthwick LA, Sunny SS, Oliphant V, Perry J, Brodlie M, Johnson GE, et al. Pseudomonas aeruginosa accentuates epithelial-to-mesenchymal transition in the airway. Eur Respir J. 2011;37(5):1237–47.PubMedCrossRefGoogle Scholar
  60. 60.
    Vos R, Blondeau K, Vanaudenaerde BM, Mertens V, Van Raemdonck DE, Sifrim D, et al. Airway colonization and gastric aspiration after lung transplantation: do birds of a feather flock together? J Heart Lung Transplant. 2008;27(8):843–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Glanville AR, Gencay M, Tamm M, Chhajed P, Plit M, Hopkins P, et al. Chlamydia pneumoniae infection after lung transplantation. J Heart Lung Transplant. 2005;24(2):131–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Kotsimbos TC, Snell GI, Levvey B, Spelman DW, Fuller AJ, Wesselingh SL, et al. Chlamydia pneumoniae serology in donors and recipients and the risk of bronchiolitis obliterans syndrome after lung transplantation. Transplantation. 2005;79(3):269–75.PubMedCrossRefGoogle Scholar
  63. 63.
    Husain S, Kahane S, Friedman MG, Paterson DL, Studer S, McCurry KR, et al. Simkania negevensis in bronchoalveolar lavage of lung transplant recipients: a possible association with acute rejection. Transplantation. 2007;83(2):138–43.PubMedCrossRefGoogle Scholar
  64. 64.
    Gunderson CC, Gupta MR, Lopez F, Lombard GA, LaPlace SG, Taylor DE, et al. Clostridium difficile colitis in lung transplantation. Transpl Infect Dis. 2008;10(4):245–51.PubMedCrossRefGoogle Scholar
  65. 65.
    Nunley DR, Ohori P, Grgurich WF, Iacono AT, Williams PA, Keenan RJ, et al. Pulmonary aspergillosis in cystic fibrosis lung transplant recipients. Chest. 1998;114(5):1321–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Weigt SS, Elashoff RM, Huang C, Ardehali A, Gregson AL, Kubak B, et al. Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome. Am J Transplant. 2009;9(8):1903–11.PubMedCrossRefGoogle Scholar
  67. 67.
    Liu M, Worley S, Mallory Jr GB, Arrigain S, Robertson J, Schecter MG, et al. Fungal infections in pediatric lung transplant recipients: colonization and invasive disease. J Heart Lung Transplant. 2009;28(11):1226–30.PubMedCrossRefGoogle Scholar
  68. 68.
    Danziger-Isakov LA, Worley S, Arrigain S, Aurora P, Ballmann M, Boyer D, et al. Increased mortality after pulmonary fungal infection within the first year after pediatric lung transplantation. J Heart Lung Transplant. 2008;27(6):655–61.PubMedCrossRefGoogle Scholar
  69. 69.
    Husain S, Zaldonis D, Kusne S, Kwak EJ, Paterson DL, McCurry KR. Variation in antifungal prophylaxis strategies in lung transplantation. Transpl Infect Dis. 2006;8(4):213–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Neoh CF, Snell GI, Kotsimbos T, Levvey B, Morrissey CO, Slavin MA, et al. Antifungal prophylaxis in lung transplantation—a world-wide survey. Am J Transplant. 2011;11(2):361–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Drew RH, Dodds Ashley E, Benjamin Jr DK, Duane Davis R, Palmer SM, Perfect JR. Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation. 2004;77(2):232–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Husain S, Capitano B, Corcoran T, Studer SM, Crespo M, Johnson B, et al. Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients. Transplantation. 2010;90(11):1215–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Griffiths PD, Stanton A, McCarrell E, Smith C, Osman M, Harber M, et al. Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial. Lancet. 2011;377(9773):1256–63.PubMedCrossRefGoogle Scholar
  74. 74.
    Kumar D, Blumberg EA, Danziger-Isakov L, Kotton CN, Halasa NB, Ison MG, et al. Influenza vaccination in the organ transplant recipient: review and summary recommendations. Am J Transplant. 2011;11(10):2020–30.PubMedCrossRefGoogle Scholar
  75. 75.
    Kumar D, Michaels MG, Morris MI, Green M, Avery RK, Liu C, et al. Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. Lancet Infect Dis. 2010;10(8):521–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Hynicka LM, Ensor CR. Prophylaxis and treatment of respiratory syncytial virus in adult immunocompromised patients. Ann Pharmacother. 2012;46(4):558–66.PubMedCrossRefGoogle Scholar
  77. 77.
    Fuehner T, Dierich M, Duesberg C, DeWall C, Welte T, Haverich A, et al. Single-centre experience with oral ribavirin in lung transplant recipients with paramyxovirus infections. Antivir Ther. 2011;16(5):733–40.PubMedCrossRefGoogle Scholar
  78. 78.
    Raza K, Ismailjee SB, Crespo M, Studer SM, Sanghavi S, Paterson DL, et al. Successful outcome of human metapneumovirus (hMPV) pneumonia in a lung transplant recipient treated with intravenous ribavirin. J Heart Lung Transplant. 2007;26(8):862–4.PubMedCrossRefGoogle Scholar
  79. 79.
    Glanville AR, Scott AI, Morton JM, Aboyoun CL, Plit ML, Carter IW, et al. Intravenous ribavirin is a safe and cost-effective treatment for respiratory syncytial virus infection after lung transplantation. J Heart Lung Transplant. 2005;24(12):2114–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Pelaez A, Lyon GM, Force SD, Ramirez AM, Neujahr DC, Foster M, et al. Efficacy of oral ribavirin in lung transplant patients with respiratory syncytial virus lower respiratory tract infection. J Heart Lung Transplant. 2009;28(1):67–71.PubMedCrossRefGoogle Scholar
  81. 81.
    Zamora MR, Budev M, Rolfe M, Gottlieb J, Humar A, Devincenzo J, et al. RNA interference therapy in lung transplant patients infected with respiratory syncytial virus. Am J Respir Crit Care Med. 2011;183(4):531–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Danzinger-Isakov L, Kumar D. Guidelines for vaccination of solid organ transplant candidates and recipients. Am J Transplant. 2009;9 Suppl 4:S258–62.PubMedCrossRefGoogle Scholar
  83. 83.
    Jain R, Hachem RR, Morrell MR, Trulock EP, Chakinala MM, Yusen RD, et al. Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2010;29(5):531–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Vos R, Vanaudenaerde BM, Verleden SE, Van Raemdonck DE, Dupont LJ, Verleden GM. Azithromycin in posttransplant bronchiolitis obliterans syndrome. Chest 2011;139(5):1246; author reply 1247.Google Scholar
  85. 85.
    Avery RK, Michaels MG. Strategies for safe living following solid organ transplantation. Am J Transplant. 2009;9 Suppl 4:S252–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Gordon SM, LaRosa SP, Kalmadi S, Arroliga AC, Avery RK, Truesdell-LaRosa L, et al. Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued? Clin Infect Dis. 1999;28(2):240–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Nakajima T, Palchevsky V, Perkins DL, Belperio JA, Finn PW. Lung transplantation: infection, inflammation, and the microbiome. Semin Immunopathol. 2011;33(2):135–56.PubMedCrossRefGoogle Scholar
  88. 88.
    Sharples LD, Tamm M, McNeil K, Higenbottam TW, Stewart S, Wallwork J. Development of bronchiolitis obliterans syndrome in recipients of heart-lung transplantation—early risk factors. Transplantation. 1996;61(4):560–6.PubMedCrossRefGoogle Scholar
  89. 89.
    Gutierrez CA, Chaparro C, Krajden M, Winton T, Kesten S. Cytomegalovirus viremia in lung transplant recipients receiving ganciclovir and immune globulin. Chest. 1998;113(4):924–32.PubMedCrossRefGoogle Scholar
  90. 90.
    Smith MA, Sundaresan S, Mohanakumar T, Trulock EP, Lynch JP, Phelan DL, et al. Effect of development of antibodies to HLA and cytomegalovirus mismatch on lung transplantation survival and development of bronchiolitis obliterans syndrome. J Thorac Cardiovasc Surg. 1998;116(5):812–20.PubMedCrossRefGoogle Scholar
  91. 91.
    Speich R, Thurnheer R, Gaspert A, Weder W, Boehler A. Efficacy and cost effectiveness of oral ganciclovir in the prevention of cytomegalovirus disease after lung transplantation. Transplantation. 1999;67(2):315–20.PubMedCrossRefGoogle Scholar
  92. 92.
    Schulman LL, Weinberg AD, McGregor CC, Suciu-Foca NM, Itescu S. Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation. Am J Respir Crit Care Med. 2001;163(2):437–42.PubMedCrossRefGoogle Scholar
  93. 93.
    Fiser SM, Tribble CG, Long SM, Kaza AK, Kern JA, Jones DR, et al. Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome. Ann Thorac Surg 2002;73(4):1041–7; discussion 1047–8.Google Scholar
  94. 94.
    Jackson CH, Sharples LD, McNeil K, Stewart S, Wallwork J. Acute and chronic onset of bronchiolitis obliterans syndrome (BOS): are they different entities? J Heart Lung Transplant. 2002;21(6):658–66.PubMedCrossRefGoogle Scholar
  95. 95.
    Luckraz H, Sharples L, McNeil K, Wreghitt T, Wallwork J. Cytomegalovirus antibody status of donor/recipient does not influence the incidence of bronchiolitis obliterans syndrome in lung transplantation. J Heart Lung Transplant. 2003;22(3):287–91.PubMedCrossRefGoogle Scholar
  96. 96.
    Westall GP, Michaelides A, Williams TJ, Snell GI, Kotsimbos TC. Bronchiolitis obliterans syndrome and early human cytomegalovirus DNAaemia dynamics after lung transplantation. Transplantation. 2003;75(12):2064–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Hachem RR, Chakinala MM, Yusen RD, Lynch JP, Aloush AA, Patterson GA, et al. A comparison of basiliximab and anti-thymocyte globulin as induction agents after lung transplantation. J Heart Lung Transplant. 2005;24(9):1320–6.PubMedCrossRefGoogle Scholar
  98. 98.
    Perreas KG, McNeil K, Charman S, Sharples LD, Wreghitt T, Wallwork J. Extended ganciclovir prophylaxis in lung transplantation. J Heart Lung Transplant. 2005;24(5):583–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Moffatt-Bruce SD, Karamichalis J, Robbins RC, Whyte RI, Theodore J, Reitz BA. Are heart-lung transplant recipients protected from developing bronchiolitis obliterans syndrome? Ann Thorac Surg 2006;81(1):286–91; discussion 291.Google Scholar
  100. 100.
    Ruttmann E, Geltner C, Bucher B, Ulmer H, Hofer D, Hangler HB, et al. Combined CMV prophylaxis improves outcome and reduces the risk for bronchiolitis obliterans syndrome (BOS) after lung transplantation. Transplantation. 2006;81(10):1415–20.PubMedCrossRefGoogle Scholar
  101. 101.
    Chmiel C, Speich R, Hofer M, Michel D, Mertens T, Weder W, et al. Ganciclovir/valganciclovir prophylaxis decreases cytomegalovirus-related events and bronchiolitis obliterans syndrome after lung transplantation. Clin Infect Dis. 2008;46(6):831–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Kwakkel-van Erp JM, van de Graaf EA, Paantjens AW, van Ginkel WG, Schellekens J, van Kessel DA, et al. The killer immunoglobulin-like receptor (KIR) group A haplotype is associated with bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant. 2008;27(9):995–1001.PubMedCrossRefGoogle Scholar
  103. 103.
    Solidoro P, Libertucci D, Delsedime L, Ruffini E, Bosco M, Costa C, et al. Combined cytomegalovirus prophylaxis in lung transplantation: effects on acute rejection, lymphocytic bronchitis/bronchiolitis, and herpesvirus infections. Transplant Proc. 2008;40(6):2013–4.PubMedCrossRefGoogle Scholar
  104. 104.
    Ranganathan K, Worley S, Michaels MG, Arrigan S, Aurora P, Ballmann M, et al. Cytomegalovirus immunoglobulin decreases the risk of cytomegalovirus infection but not disease after pediatric lung transplantation. J Heart Lung Transplant. 2009;28(10):1050–6.PubMedCrossRefGoogle Scholar
  105. 105.
    Paraskeva M, Bailey M, Levvey BJ, Griffiths AP, Kotsimbos TC, Williams TP, et al. Cytomegalovirus replication within the lung allograft is associated with bronchiolitis obliterans syndrome. Am J Transplant. 2011;11(10):2190–6.PubMedCrossRefGoogle Scholar
  106. 106.
    Kwakkel-van Erp JM, Paantjens AW, van Kessel DA, Grutters JC, van den Bosch JM, van de Graaf EA, et al. Mannose-binding lectin deficiency linked to cytomegalovirus (CMV) reactivation and survival in lung transplantation. Clin Exp Immunol. 2011;165(3):410–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Infectious Disease (Transplant/Oncology)Johns Hopkins HospitalBaltimoreUSA

Personalised recommendations