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.
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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
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
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
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
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
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
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
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
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
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
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
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
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