Chronic Lung Allograft Dysfunction: Phenotypes and the Future

  • Daniel C. Chambers


Chronic lung allograft dysfunction (CLAD, an umbrella term which encompasses two subtypes—restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS)) remains the major barrier to long-term survival after lung transplantation. CLAD affects approximately 10% of patients each year and has proven a particularly difficult problem to address, with no major improvements in survival for 3 decades. In this chapter, current diagnostic and management paradigms are discussed, as are preventative approaches. Finally, a more optimistic outlook for patients developing CLAD in coming years, based on a better understanding of pathogenesis, is outlined.


Chronic lung allograft dysfunction Restrictive allograft syndrome Bronchiolitis obliterans syndrome Lung transplant Fibrosis Rejection 


  1. 1.
    Chambers DC, Yusen RD, Cherikh WS, et al. The Registry of the International Society for Heart and Lung Transplantation: thirty-fourth adult lung and heart-lung transplantation report-2017; focus theme: allograft ischemic time. J Heart Lung Transplant. 2017;36:1047–59.CrossRefPubMedGoogle Scholar
  2. 2.
    Sato M, Waddell TK, Wagnetz U, et al. Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction. J Heart Lung Transplant. 2011;30:735–42.CrossRefPubMedGoogle Scholar
  3. 3.
    Todd JL, Jain R, Pavlisko EN, 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;189:159–66.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hachem RR, Tiriveedhi V, Patterson GA, Aloush A, Trulock EP, Mohanakumar T. Antibodies to K-alpha 1 tubulin and collagen V are associated with chronic rejection after lung transplantation. Am J Transplant. 2012;12:2164–71.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    DerHovanessian A, Weigt SS, Palchevskiy V, et al. The role of TGF-beta in the association between primary graft dysfunction and bronchiolitis obliterans syndrome. Am J Transplant. 2016;16:640–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Cao P, Aoki Y, Badri L, et al. Autocrine lysophosphatidic acid signaling activates beta-catenin and promotes lung allograft fibrosis. J Clin Invest. 2017;127:1517–30.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    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;177:1033–40.CrossRefPubMedGoogle Scholar
  8. 8.
    Gallagher HM, Sarwar G, Tse T, et al. Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival. J Heart Lung Transplant. 2015;34:1442–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Vanaudenaerde BM, Meyts I, Vos R, et al. A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy. Eur Respir J. 2008;32:832–43.CrossRefPubMedGoogle Scholar
  10. 10.
    Benden C, Haughton M, Leonard S, Huber LC. Therapy options for chronic lung allograft dysfunction-bronchiolitis obliterans syndrome following first-line immunosuppressive strategies: a systematic review. J Heart Lung Transplant. 2017;36:921–33.CrossRefPubMedGoogle Scholar
  11. 11.
    King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–92.CrossRefPubMedGoogle Scholar
  12. 12.
    Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82.CrossRefPubMedGoogle Scholar
  13. 13.
    Chambers DC, Enever D, Lawrence S, et al. Mesenchymal stromal cell therapy for chronic lung allograft dysfunction: results of a first-in-man study. Stem Cells Transl Med. 2017;6:1152–7.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Qld Lung Transplant ServiceThe Prince Charles HospitalBrisbaneAustralia
  2. 2.Faculty of MedicineThe University of QueenslandBrisbaneAustralia

Personalised recommendations