Skip to main content
SpringerLink
Log in

Lung Allograft Dysfunction (LAD) and Bronchiolitis Obliterans Syndrome

  • Chapter
  • First Online:
Book cover Lung Transplantation

  • 851 Accesses

Abstract

Lung transplantation is currently considered as an ultimate lifesaving treatment for selected patients suffering from end-stage pulmonary disease. Long-term survival, however, is hampered by chronic rejection, the major manifestation of chronic lung allograft dysfunction (CLAD). Various phenotypes of CLAD exist including the classical bronchiolitis obliterans syndrome (BOS) and the recently described restrictive allograft syndrome (RAS). BOS is considered to be a chronic rejection and defined as a persistent and obstructive pulmonary function defect (in the absence of any other cause) and histopathologically identified as small airway plugging or obliteration termed obliterative bronchiolitis (OB). RAS patients develop also a persistent decline in FEV1 of at least 20%, but a restrictive rather than obstructive pulmonary function defect (defined as a concomitant decline in total lung capacity of at least 10%) and demonstrate persistent interstitial and ground-glass opacities on chest computed tomographic (CT) scan. Patients with RAS have a much worse prognosis after diagnosis. This book chapter will discuss the different chronic rejection phenotypes, their etiology, diagnosis, prognosis, risk factors, mechanisms, and treatment modalities.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Sayegh MH, Carpenter CB. Transplantation 50 years later—progress, challenges, and promises. N Engl J Med. 2004;351(26):2761–6.

    Article  CAS  PubMed  Google Scholar 

  2. Goldfarb SB, Levvey BJ, Edwards LB, Dipchand AI, Kucheryavaya AY, Lund LH, et al. The Registry of the International Society for Heart and Lung Transplantation: nineteenth pediatric lung and heart-lung transplantation report-2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transplant. 2016;35(10):1196–205.

    Article  PubMed  Google Scholar 

  3. Cooper JD, Billingham M, Egan T, Hertz MI, Higenbottam T, Lynch J, et al. A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 1993;12(5):713–6.

    PubMed  CAS  Google Scholar 

  4. Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002;21(3):297–310.

    Article  PubMed  Google Scholar 

  5. Verleden GM, Vos R, Vanaudenaerde B, Dupont L, Yserbyt J, Van Raemdonck D, et al. Current views on chronic rejection after lung transplantation. Transpl Int. 2015;28(10):1131–9.

    Article  PubMed  Google Scholar 

  6. Verleden GM, Raghu G, Meyer KC, Glanville AR, Corris P. A new classification system for chronic lung allograft dysfunction. J Heart Lung Transplant. 2014;33(2):127–33.

    Article  PubMed  Google Scholar 

  7. Glanville AR. Bronchoscopic monitoring after lung transplantation. Semin Respir Crit Care Med. 2010;31(2):208–21.

    Article  PubMed  Google Scholar 

  8. Derom F, Barbier F, Ringoir S, Versieck J, Rolly G, Berzsenyi G, et al. Ten-month survival after lung homotransplantation in man. J Thorac Cardiovasc Surg. 1971;61(6):835–46.

    PubMed  CAS  Google Scholar 

  9. Owen J, Punt J, Stranford S. Kuby immunology. 7th ed. New York: WH Freeman; 2013.

    Google Scholar 

  10. Verleden SE, Sacreas A, Vos R, Vanaudenaerde BM, Verleden GM. Advances in understanding bronchiolitis obliterans after lung transplantation. Chest. 2016;150(1):219–25.

    Article  PubMed  Google Scholar 

  11. Sato M, Waddell TK, Wagnetz U, Roberts HC, Hwang DM, Haroon A, et al. Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction. J Heart Lung Transplant. 2011;30(7):735–42.

    Article  PubMed  Google Scholar 

  12. Woodrow JP, Shlobin OA, Barnett SD, Burton N, Nathan SD. Comparison of bronchiolitis obliterans syndrome to other forms of chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant. 2010;29(10):1159–64.

    Article  PubMed  Google Scholar 

  13. Suhling H, Dettmer S, Rademacher J, Greer M, Mark G, Shin H-O, et al. Spirometric obstructive lung function pattern early after lung transplantation. Transplantation. 2012;93(2):230–5.

    Article  PubMed  Google Scholar 

  14. Verleden SE, Vasilescu DM, Willems S, Ruttens D, Vos R, Vandermeulen E, et al. The site and nature of airway obstruction after lung transplantation. Am J Respir Crit Care Med. 2014;189(3):292–300.

    Article  PubMed  Google Scholar 

  15. Galbán CJ, Han MK, Boes JL, Chughtai KA, Meyer CR, Johnson TD, et al. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression. Nat Med. 2012;18(11):1711–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Verleden SE, Vos R, Vandermeulen E, Ruttens D, Bellon H, Heigl T, et al. Parametric response mapping of bronchiolitis obliterans syndrome progression after lung transplantation. Am J Transplant. 2016;16(11):3262–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Renne J, Lauermann P, Hinrichs JB, Schönfeld C, Sorrentino S, Gutberlet M, et al. Chronic lung allograft dysfunction: oxygen-enhanced T1-mapping MR imaging of the lung. Radiology. 2015;276(1):266–73.

    Article  PubMed  Google Scholar 

  18. Verleden SE, de Jong PA, Ruttens D, Vandermeulen E, van Raemdonck DE, Verschakelen J, et al. Functional and computed tomographic evolution and survival of restrictive allograft syndrome after lung transplantation. J Heart Lung Transplant. 2014;33(3):270–7.

    Article  PubMed  Google Scholar 

  19. Sato M. Chronic lung allograft dysfunction after lung transplantation: the moving target. Gen Thorac Cardiovasc Surg. 2013;61(2):67–78.

    Article  PubMed  Google Scholar 

  20. Verleden SE, Ruttens D, Vandermeulen E, Bellon H, Dubbeldam A, De Wever W, et al. Predictors of survival in restrictive chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant. 2016;35(9):1078–84.

    Article  PubMed  Google Scholar 

  21. Paraskeva M, McLean C, Ellis S, Bailey M, Williams T, Levvey B, et al. Acute fibrinoid organizing pneumonia after lung transplantation. Am J Respir Crit Care Med. 2013;187(12):1360–8.

    Article  PubMed  Google Scholar 

  22. Corris PA, Christie JD. Update in transplantation 2007. Am J Respir Crit Care Med. 2008;177(10):1062–7.

    Article  PubMed  Google Scholar 

  23. Neurohr C, Huppmann P, Samweber B, Leuschner S, Zimmermann G, Leuchte H, et al. Prognostic value of bronchoalveolar lavage neutrophilia in stable lung transplant recipients. J Heart Lung Transplant. 2009;28(5):468–74.

    Article  PubMed  Google Scholar 

  24. Davis WA, Finlen Copeland CA, Todd JL, Snyder LD, Martissa JA, Palmer SM. Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation. Am J Transplant. 2012;12(3):745–52.

    Article  CAS  PubMed  Google Scholar 

  25. Glanville AR, Aboyoun CL, Havryk A, Plit M, Rainer S, Malouf MA. Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation. Am J Respir Crit Care Med. 2008;177(9):1033–40.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. Hachem RR, Tiriveedhi V, Patterson GA, Aloush A, Trulock EP, Mohanakumar T. Antibodies to K-α 1 tubulin and collagen V are associated with chronic rejection after lung transplantation. Am J Transplant. 2012;12(8):2164–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nawrot TS, Vos R, Jacobs L, Verleden SE, Wauters S, Mertens V, et al. The impact of traffic air pollution on bronchiolitis obliterans syndrome and mortality after lung transplantation. Thorax. 2011;66(9):748–54.

    Article  PubMed  Google Scholar 

  30. Bhinder S, Chen H, Sato M, Copes R, Evans GJ, Chow C-W, et al. Air pollution and the development of posttransplant chronic lung allograft dysfunction. Am J Transplant. 2014;14(12):2749–57.

    Article  CAS  PubMed  Google Scholar 

  31. Sharples LD, McNeil K, Stewart S, Wallwork J. Risk factors for bronchiolitis obliterans: a systematic review of recent publications. J Heart Lung Transplant. 2002;21(2):271–81.

    Article  PubMed  Google Scholar 

  32. 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.

    Article  PubMed  Google Scholar 

  33. Vos R, Vanaudenaerde BM, Geudens N, Dupont LJ, Van Raemdonck DE, Verleden GM. Pseudomonal airway colonisation: risk factor for bronchiolitis obliterans syndrome after lung transplantation? Eur Respir J. 2008;31(5):1037–45.

    Article  CAS  PubMed  Google Scholar 

  34. D’Ovidio F, Mura M, Ridsdale R, Takahashi H, Waddell TK, Hutcheon M, et al. The effect of reflux and bile acid aspiration on the lung allograft and its surfactant and innate immunity molecules SP-A and SP-D. Am J Transplant. 2006;6(8):1930–8.

    Article  CAS  PubMed  Google Scholar 

  35. Vos R, Vanaudenaerde BM, De Vleeschauwer SI, Willems-Widyastuti A, Scheers H, Van Raemdonck DE, et al. Circulating and intrapulmonary C-reactive protein: a predictor of bronchiolitis obliterans syndrome and pulmonary allograft outcome. J Heart Lung Transplant. 2009;28(8):799–807.

    Article  PubMed  Google Scholar 

  36. Verleden GM, Vos R, Verleden SE, De Wever W, De Vleeschauwer SI, Willems-Widyastuti A, et al. Survival determinants in lung transplant patients with chronic allograft dysfunction. Transplantation. 2011;92(6):703–8.

    Article  PubMed  Google Scholar 

  37. Todd JL, Jain R, Pavlisko EN, Finlen Copeland CA, Reynolds JM, Snyder LD, et al. Impact of forced vital capacity loss on survival after the onset of chronic lung allograft dysfunction. Am J Respir Crit Care Med. 2014;189(2):159–66.

    PubMed  PubMed Central  Google Scholar 

  38. Verleden SE, Ruttens D, Vandermeulen E, Vaneylen A, Dupont LJ, Van Raemdonck DE, et al. Bronchiolitis obliterans syndrome and restrictive allograft syndrome: do risk factors differ? Transplantation. 2013;95(9):1167–72.

    Article  PubMed  Google Scholar 

  39. Verleden SE, Ruttens D, Vandermeulen E, van Raemdonck DE, Vanaudenaerde BM, Verleden GM, et al. Elevated bronchoalveolar lavage eosinophilia correlates with poor outcome after lung transplantation. Transplantation. 2014;97(1):83–9.

    Article  PubMed  Google Scholar 

  40. Verleden SE, Ruttens D, Vos R, Vandermeulen E, Moelants E, Mortier A, et al. Differential cytokine, chemokine and growth factor expression in phenotypes of chronic lung allograft dysfunction. Transplantation. 2015;99(1):86–93.

    Article  CAS  PubMed  Google Scholar 

  41. Shino MY, Weigt SS, Li N, Palchevskiy V, Derhovanessian A, Saggar R, et al. CXCR3 ligands are associated with the continuum of diffuse alveolar damage to chronic lung allograft dysfunction. Am J Respir Crit Care Med. 2013;188(9):1117–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Saito T, Liu M, Binnie M, Sato M, Hwang D, Azad S, et al. Distinct expression patterns of alveolar “alarmins” in subtypes of chronic lung allograft dysfunction. Am J Transplant. 2014;14(6):1425–32.

    Article  CAS  PubMed  Google Scholar 

  43. Vandermeulen E, Verleden SE, Bellon H, Ruttens D, Lammertyn E, Claes S, et al. Humoral immunity in phenotypes of chronic lung allograft dysfunction: a broncho-alveolar lavage fluid analysis. Transpl Immunol. 2016;38:27–32.

    Article  CAS  PubMed  Google Scholar 

  44. Kelly FL, Kennedy VE, Jain R, Sindhwani NS, Finlen Copeland CA, Snyder LD, et al. Epithelial clara cell injury occurs in bronchiolitis obliterans syndrome after human lung transplantation. Am J Transplant. 2012;12(11):3076–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gilpin SE, Lung KC, Sato M, Singer LG, Keshavjee S, Waddell TK. Altered progenitor cell and cytokine profiles in bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2012;31(2):222–8.

    Article  PubMed  Google Scholar 

  46. Andersson-Sjöland A, Erjefält JS, Bjermer L, Eriksson L, Westergren-Thorsson G. Fibrocytes are associated with vascular and parenchymal remodelling in patients with obliterative bronchiolitis. Respir Res. 2009;10:103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vanaudenaerde BM, Wuyts WA, Dupont LJ, Van Raemdonck DE, Demedts MM, Verleden GM. Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cells in vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2003;22(11):1280–3.

    Article  PubMed  Google Scholar 

  48. Murphy DM, Forrest IA, Corris PA, Johnson GE, Small T, Jones D, et al. Simvastatin attenuates release of neutrophilic and remodeling factors from primary bronchial epithelial cells derived from stable lung transplant recipients. Am J Physiol Lung Cell Mol Physiol. 2008;294(3):L592–9.

    Article  CAS  PubMed  Google Scholar 

  49. Vanaudenaerde BM, De Vleeschauwer SI, Vos R, Meyts I, Bullens DM, Reynders V, et al. The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2008;8(9):1911–20.

    Article  CAS  PubMed  Google Scholar 

  50. Subramanian V, Ramachandran S, Banan B, Bharat A, Wang X, Benshoff N, et al. Immune response to tissue-restricted self-antigens induces airway inflammation and fibrosis following murine lung transplantation. Am J Transplant. 2014;14(10):2359–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bhorade SM, Chen H, Molinero L, Liao C, Garrity ER, Vigneswaran WT, et al. Decreased percentage of CD4+FoxP3+ cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome. Transplantation. 2010;90(5):540–6.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Krustrup D, Iversen M, Martinussen T, Schultz HHL, Andersen CB. The number of FoxP3+ cells in transbronchial lung allograft biopsies does not predict bronchiolitis obliterans syndrome within the first five years after transplantation. Clin Transpl. 2015;29(3):179–84.

    Article  CAS  Google Scholar 

  53. Ruttens D, Wauters E, Kiciński M, Verleden SE, Vandermeulen E, Vos R, et al. Genetic variation in interleukin-17 receptor A is functionally associated with chronic rejection after lung transplantation. J Heart Lung Transplant. 2013;32(12):1233–40.

    Article  PubMed  Google Scholar 

  54. Verleden SE, Vos R, Vandermeulen E, Ruttens D, Vaneylen A, Dupont LJ, et al. Involvement of interleukin-17 during lymphocytic bronchiolitis in lung transplant patients. J Heart Lung Transplant. 2013;32(4):447–53.

    Article  PubMed  Google Scholar 

  55. Todd JL, Wang X, Sugimoto S, Kennedy VE, Zhang HL, Pavlisko EN, et al. Hyaluronan contributes to bronchiolitis obliterans syndrome and stimulates lung allograft rejection through activation of innate immunity. Am J Respir Crit Care Med. 2014;189(5):556–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Platzer B, Stout M, Fiebiger E. Antigen cross-presentation of immune complexes. Front Immunol. 2014;5:140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Keane MP, Gomperts BN, Weigt S, Xue YY, Burdick MD, Nakamura H, et al. IL-13 is pivotal in the fibro-obliterative process of bronchiolitis obliterans syndrome. J Immunol. 2007;178(1):511–9.

    Article  CAS  PubMed  Google Scholar 

  58. Zagai U, Lundahl J, Klominek J, Venge P, Sköld CM. Eosinophil cationic protein stimulates migration of human lung fibroblasts in vitro. Scand J Immunol. 2009;69(4):381–6.

    Article  CAS  PubMed  Google Scholar 

  59. Hügle T. Beyond allergy: the role of mast cells in fibrosis. Swiss Med Wkly. 2014;144:w13999.

    PubMed  Google Scholar 

  60. Bhatt NY, Allen JN. Update on eosinophilic lung diseases. Semin Respir Crit Care Med. 2012;33(5):555–71.

    Article  PubMed  Google Scholar 

  61. Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;20(121):156–74.

    Article  CAS  PubMed  Google Scholar 

  62. Vandermeulen E, Lammertyn E, Verleden SE, Ruttens D, Bellon H, Ricciardi M, et al. Immunological diversity in phenotypes of chronic lung allograft dysfunction: a comprehensive immunohistochemical analysis. Transpl Int. 2017;30:134–43.

    Article  CAS  PubMed  Google Scholar 

  63. Borthwick LA, Suwara MI, Carnell SC, Green NJ, Mahida R, Dixon D, et al. Pseudomonas aeruginosa induced airway epithelial injury drives fibroblast activation: a mechanism in chronic lung allograft dysfunction. Am J Transplant. 2016;16(6):1751–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Dunkelberger JR, Song W-C. Complement and its role in innate and adaptive immune responses. Cell Res. 2010;20(1):34–50.

    Article  CAS  PubMed  Google Scholar 

  65. Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S33–40.

    Article  PubMed  Google Scholar 

  66. Warrington R, Watson W, Kim HL, Antonetti FR. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol. 2011;7(1):1–8.

    Article  CAS  Google Scholar 

  67. Zeevi A. Chronic antibody-mediated rejection: new diagnostic tools—clinical significance of C4d deposition and improved detection and characterization of human leucocyte antigen antibodies. Clin Exp Immunol. 2014;178(Suppl 1):52–3.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Meyer KC, Raghu G, Verleden GM, Corris PA, Aurora P, Wilson KC, et al. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014;44(6):1479–503.

    Article  PubMed  Google Scholar 

  69. Jaramillo A, Smith MA, Phelan D, Sundaresan S, Trulock EP, Lynch JP, et al. Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation. Transplantation. 1999;67(8):1155–61.

    Article  CAS  PubMed  Google Scholar 

  70. Snyder LD, Wang Z, Chen D-F, Reinsmoen NL, Finlen-Copeland CA, Davis WA, et al. Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients. Chest. 2013;144(1):226–33.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Fukami N, Ramachandran S, Takenaka M, Weber J, Subramanian V, Mohanakumar T. An obligatory role for lung infiltrating B cells in the immunopathogenesis of obliterative airway disease induced by antibodies to MHC class I molecules. Am J Transplant. 2012;12(4):867–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Neuringer IP, Mannon RB, Coffman TM, Parsons M, Burns K, Yankaskas JR, et al. Immune cells in a mouse airway model of obliterative bronchiolitis. Am J Respir Cell Mol Biol. 1998;19(3):379–86.

    Article  CAS  PubMed  Google Scholar 

  73. Hachem RR, Yusen RD, Meyers BF, Aloush AA, Mohanakumar T, Patterson GA, et al. Anti-human leukocyte antigen antibodies and preemptive antibody-directed therapy after lung transplantation. J Heart Lung Transplant. 2010;29(9):973–80.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Jaramillo A, Smith CR, Maruyama T, Zhang L, Patterson GA, Mohanakumar T. Anti-HLA class I antibody binding to airway epithelial cells induces production of fibrogenic growth factors and apoptotic cell death: a possible mechanism for bronchiolitis obliterans syndrome. Hum Immunol. 2003;64(5):521–9.

    Article  CAS  PubMed  Google Scholar 

  75. Levine DJ, Glanville AR, Aboyoun C, Belperio J, Benden C, Berry GJ, et al. Antibody-mediated rejection of the lung: a consensus report of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2016;35(4):397–406.

    Article  PubMed  Google Scholar 

  76. Feucht HE, Felber E, Gokel MJ, Hillebrand G, Nattermann U, Brockmeyer C, et al. Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection. Clin Exp Immunol. 1991;86(3):464–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Verleden SE, Ruttens D, Vandermeulen E, Bellon H, Van Raemdonck DE, Dupont LJ, et al. Restrictive chronic lung allograft dysfunction: where are we now? J Heart Lung Transplant. 2015;34(5):625–30.

    Article  PubMed  Google Scholar 

  78. Banerjee B, Musk M, Sutanto EN, Yerkovich ST, Hopkins P, Knight DA, et al. Regional differences in susceptibility of bronchial epithelium to mesenchymal transition and inhibition by the macrolide antibiotic azithromycin. PLoS One. 2012;7(12):e52309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Vos R, Vanaudenaerde BM, Verleden SE, De Vleeschauwer SI, Willems-Widyastuti A, Van Raemdonck DE, et al. A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation. Eur Respir J. 2011;37(1):164–72.

    Article  CAS  PubMed  Google Scholar 

  80. Ruttens D, Verleden SE, Vandermeulen E, Bellon H, Vanaudenaerde BM, Somers J, et al. Prophylactic azithromycin therapy after lung transplantation: post hoc analysis of a randomized controlled trial. Am J Transplant. 2016;16(1):254–61.

    Article  CAS  PubMed  Google Scholar 

  81. Baum C, Reichenspurner H, Deuse T. Bortezomib rescue therapy in a patient with recurrent antibody-mediated rejection after lung transplantation. J Heart Lung Transplant. 2013;32(12):1270–1.

    Article  PubMed  Google Scholar 

  82. Snyder LD, Gray AL, Reynolds JM, Arepally GM, Bedoya A, Hartwig MG, et al. Antibody desensitization therapy in highly sensitized lung transplant candidates. Am J Transplant. 2014;14(4):849–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Baskaran G, Tiriveedhi V, Ramachandran S, Aloush A, Grossman B, Hachem R, et al. Efficacy of extracorporeal photopheresis in clearance of antibodies to donor-specific and lung-specific antigens in lung transplant recipients. J Heart Lung Transplant. 2014;33(9):950–6.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Greer M, Dierich M, De Wall C, Suhling H, Rademacher J, Welte T, et al. Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients. Am J Transplant. 2013;13(4):911–8.

    Article  CAS  PubMed  Google Scholar 

  85. Ihle F, von Wulffen W, Neurohr C. Pirfenidone: a potential therapy for progressive lung allograft dysfunction? J Heart Lung Transplant. 2013;32(5):574–5.

    Article  PubMed  Google Scholar 

  86. King TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–92.

    Article  CAS  PubMed  Google Scholar 

  87. Vos R, Verleden SE, Ruttens D, Vandermeulen E, Yserbyt J, Dupont LJ, et al. Pirfenidone: a potential new therapy for restrictive allograft syndrome? Am J Transplant. 2013;13(11):3035–40.

    Article  CAS  PubMed  Google Scholar 

  88. Kohno M, Perch M, Andersen E, Carlsen J, Andersen CB, Iversen M. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation. Transplant Proc. 2011;43(5):1868–70.

    Article  CAS  PubMed  Google Scholar 

  89. Verleden SE, Todd JL, Sato M, Palmer SM, Martinu T, Pavlisko EN, et al. Impact of CLAD phenotype on survival after lung retransplantation: a multicenter study. Am J Transplant. 2015;15(8):2223–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium

    Bart Vanaudenaerde & Robin Vos

  2. Lung Transplant and Respiratory Intermediate Care Unit, Department of Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium

    Robin Vos

  3. Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium

    Stijn Verleden & Elly Vandermeulen

  4. Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium

    Geert Verleden

Authors
  1. Bart Vanaudenaerde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robin Vos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stijn Verleden
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elly Vandermeulen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Geert Verleden
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bart Vanaudenaerde .

Editor information

Editors and Affiliations

  1. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine University of Washington, Seattle, Washington, USA

    Ganesh Raghu

  2. Department of Internal Medicine, University of Genoa, Genoa, Italy

    Roberto G. Carbone

Rights and permissions

Reprints and permissions

Copyright information

© 2018 The Author(s)

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vanaudenaerde, B., Vos, R., Verleden, S., Vandermeulen, E., Verleden, G. (2018). Lung Allograft Dysfunction (LAD) and Bronchiolitis Obliterans Syndrome. In: Raghu, G., Carbone, R. (eds) Lung Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-91184-7_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-91184-7_16

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-91182-3

  • Online ISBN: 978-3-319-91184-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation