Semin Respir Crit Care Med 2021; 42(03): 392-410
DOI: 10.1055/s-0041-1729175
Review Article

Chronic Lung Allograft Dysfunction: Evolving Concepts and Therapies

Olawale Amubieya
1   Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
,
Allison Ramsey
1   Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
,
Ariss DerHovanessian
1   Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
,
Gregory A. Fishbein
2   Department of Pathology, The David Geffen School of Medicine at UCLA, Los Angeles, California
,
Joseph P. Lynch III
1   Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
,
John A. Belperio
1   Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
,
S. Samuel Weigt
1   Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
› Author Affiliations

Abstract

The primary factor that limits long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care. Our understanding of CLAD continues to evolve. Consensus definitions of CLAD and the major CLAD phenotypes were recently updated and clarified, but it remains to be seen whether the current definitions will lead to advances in management or impact care. Understanding the potential differences in pathogenesis for each CLAD phenotype may lead to novel therapeutic strategies, including precision medicine. Recognition of CLAD risk factors may lead to earlier interventions to mitigate risk, or to avoid risk factors all together, to prevent the development of CLAD. Unfortunately, currently available therapies for CLAD are usually not effective. However, novel therapeutics aimed at both prevention and treatment are currently under investigation. We provide an overview of the updates to CLAD-related terminology, clinical phenotypes and their diagnosis, natural history, pathogenesis, and potential strategies to treat and prevent CLAD.



Publication History

Article published online:
24 May 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Chambers DC, Cherikh WS, Harhay MO. et al; International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-Sixth Adult Lung and Heart-Lung Transplantation Report-2019; focus theme: donor and recipient size match. J Heart Lung Transplant 2019; 38 (10) 1042-1055
  • 2 Grossman RF, Frost A, Zamel N. et al; The Toronto Lung Transplant Group. Results of single-lung transplantation for bilateral pulmonary fibrosis. N Engl J Med 1990; 322 (11) 727-733
  • 3 Colvin M, Smith JM, Skeans MA. et al. OPTN/SRTR 2015 annual data report: heart. Am J Transplant 2017; 17 (Suppl. 01) 286-356
  • 4 Hart A, Smith JM, Skeans MA. et al. OPTN/SRTR 2015 annual data report: kidney. Am J Transplant 2017; 17 (Suppl. 01) 21-116
  • 5 Kim WR, Lake JR, Smith JM. et al. OPTN/SRTR 2015 annual data report: liver. Am J Transplant 2017; 17 (Suppl. 01) 174-251
  • 6 Knoop C, Estenne M. Acute and chronic rejection after lung transplantation. Semin Respir Crit Care Med 2006; 27 (05) 521-533
  • 7 Vermeulen KM, Groen H, van der Bij W, Erasmus ME, Koëter GH, TenVergert EM. The effect of bronchiolitis obliterans syndrome on health related quality of life. Clin Transplant 2004; 18 (04) 377-383
  • 8 van den Berg JW, van Enckevort PJ, TenVergert EM, Postma DS, van der Bij W, Koëter GH. Bronchiolitis obliterans syndrome and additional costs of lung transplantation. Chest 2000; 118 (06) 1648-1652
  • 9 Reitz BA, Wallwork JL, Hunt SA. et al. Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease. N Engl J Med 1982; 306 (10) 557-564
  • 10 Toronto Lung Transplant G. Toronto Lung Transplant Group. Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med 1986; 314 (18) 1140-1145
  • 11 Burke CM, Theodore J, Dawkins KD. et al. Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation. Chest 1984; 86 (06) 824-829
  • 12 Yousem SA, Burke CM, Billingham ME. Pathologic pulmonary alterations in long-term human heart-lung transplantation. Hum Pathol 1985; 16 (09) 911-923
  • 13 Griffith BP, Paradis IL, Zeevi A. et al. Immunologically mediated disease of the airways after pulmonary transplantation. Ann Surg 1988; 208 (03) 371-378
  • 14 Estenne M, Ketelbant P, Primo G, Yernault JC. Human heart-lung transplantation: physiologic aspects of the denervated lung and post-transplant obliterative bronchiolitis. Am Rev Respir Dis 1987; 135 (04) 976-978
  • 15 Burke CM, Theodore J, Baldwin JC. et al. Twenty-eight cases of human heart-lung transplantation. Lancet 1986; 1 (8480): 517-519
  • 16 Coalson JJ, Kastl DG, Whalen MH, Greenfield LG. Allografted lungs in matched dogs with induced pulmonary hypertension. Am J Pathol 1974; 74 (03) 533-550
  • 17 Veith FJ, Sinha SB, Blümcke S. et al. Nature and evolution of lung allograft rejection with and without immunosuppression. J Thorac Cardiovasc Surg 1972; 63 (04) 509-520
  • 18 Baker RR, Sabanayagam P, Zarins CK. et al. Functional and morphologic changes after lung allografting in baboons. Surg Gynecol Obstet 1973; 137 (04) 650-654
  • 19 Byers III JM, Sabanayagam P, Baker RR, Hutchins GM. Pathologic changes in baboon lung allografts. Comparison of two immunosuppression regimes. Ann Surg 1973; 178 (06) 754-760
  • 20 Joseph WL, Morton DL. Morphologic alterations in the transplanted primate lung. Surg Gynecol Obstet 1971; 133 (05) 821-825
  • 21 Harjula A, Baldwin JC, Tazelaar HD, Jamieson SW, Reitz BA, Shumway NE. Minimal lung pathology in long-term primate survivors of heart-lung transplantation. Transplantation 1987; 44 (06) 852-854
  • 22 Tazelaar HD, Prop J, Nieuwenhuis P, Billingham ME, Wildevuur CR. Obliterative bronchiolitis in the transplanted rat lung. Transplant Proc 1987; 19 (1, Pt 2): 1052
  • 23 Prop J, Wildevuur CR, Nieuwenhuis P. Lung allograft rejection in the rat. III. Corresponding morphological rejection phases in various rat strain combinations. Transplantation 1985; 40 (02) 132-136
  • 24 Romaniuk A, Prop J, Petersen AH, Nieuwenhuis P, Wildevuur CR. Increased expression of class II major histocompatibility complex antigens in untreated and cyclosporine-treated rat lung allografts. J Heart Transplant 1986; 5 (06) 455-460
  • 25 Romaniuk A, Prop J, Petersen AH, Wildevuur CR, Nieuwenhuis P. Expression of class II major histocompatibility complex antigens by bronchial epithelium in rat lung allografts. Transplantation 1987; 44 (02) 209-214
  • 26 Tazelaar HD, Prop J, Nieuwenhuis P, Billingham ME, Wildevuur CR. Airway pathology in the transplanted rat lung. Transplantation 1988; 45 (05) 864-869
  • 27 Berry GJ, Brunt EM, Chamberlain D. et al; The International Society for Heart Transplantation. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Lung Rejection Study Group. J Heart Transplant 1990; 9 (06) 593-601
  • 28 Cooper JD, Billingham M, Egan T. et al; International Society for Heart and Lung Transplantation. A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. J Heart Lung Transplant 1993; 12 (05) 713-716
  • 29 Yousem SA, Berry GJ, Cagle PT. et al. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group. J Heart Lung Transplant 1996; 15 (1, Pt 1): 1-15
  • 30 Stewart S, Fishbein MC, Snell GI. et al. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant 2007; 26 (12) 1229-1242
  • 31 Estenne M, Maurer JR, Boehler A. et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant 2002; 21 (03) 297-310
  • 32 Meyer KC, Raghu G, Verleden GM. et al; ISHLT/ATS/ERS BOS Task Force Committee, ISHLT/ATS/ERS BOS Task Force Committee. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J 2014; 44 (06) 1479-1503
  • 33 Bando K, Paradis IL, Similo S. et al. Obliterative bronchiolitis after lung and heart-lung transplantation. An analysis of risk factors and management. J Thorac Cardiovasc Surg 1995; 110 (01) 4-13 , discussion 13–14
  • 34 Keller CA, Cagle PT, Brown RW, Noon G, Frost AE. Bronchiolitis obliterans in recipients of single, double, and heart-lung transplantation. Chest 1995; 107 (04) 973-980
  • 35 Girgis RE, Tu I, Berry GJ. et al. Risk factors for the development of obliterative bronchiolitis after lung transplantation. J Heart Lung Transplant 1996; 15 (12) 1200-1208
  • 36 Kroshus TJ, Kshettry VR, Savik K, John R, Hertz MI, Bolman III RM. Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation. J Thorac Cardiovasc Surg 1997; 114 (02) 195-202
  • 37 Husain AN, Siddiqui MT, Holmes EW. et al. Analysis of risk factors for the development of bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 1999; 159 (03) 829-833
  • 38 Clelland C, Higenbottam T, Otulana B. et al. Histologic prognostic indicators for the lung allografts of heart-lung transplants. J Heart Transplant 1990; 9 (3, Pt 1): 177-185, discussion 185–186
  • 39 El-Gamel A, Sim E, Hasleton P. et al. Transforming growth factor beta (TGF-beta) and obliterative bronchiolitis following pulmonary transplantation. J Heart Lung Transplant 1999; 18 (09) 828-837
  • 40 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 (09) 1033-1040
  • 41 Ross DJ, Marchevsky A, Kramer M, Kass RM. “Refractoriness” of airflow obstruction associated with isolated lymphocytic bronchiolitis/bronchitis in pulmonary allografts. J Heart Lung Transplant 1997; 16 (08) 832-838
  • 42 Konen E, Weisbrod GL, Pakhale S, Chung T, Paul NS, Hutcheon MA. Fibrosis of the upper lobes: a newly identified late-onset complication after lung transplantation?. AJR Am J Roentgenol 2003; 181 (06) 1539-1543
  • 43 Pakhale SS, Hadjiliadis D, Howell DN. et al. Upper lobe fibrosis: a novel manifestation of chronic allograft dysfunction in lung transplantation. J Heart Lung Transplant 2005; 24 (09) 1260-1268
  • 44 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) 1159-1164
  • 45 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 (07) 735-742
  • 46 Verleden GM, Vos R, Verleden SE. et al. Survival determinants in lung transplant patients with chronic allograft dysfunction. Transplantation 2011; 92 (06) 703-708
  • 47 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 (02) 127-133
  • 48 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 (02) 159-166
  • 49 DerHovanessian A, Todd JL, Zhang A. et al. Validation and refinement of chronic lung allograft dysfunction phenotypes in bilateral and single lung recipients. Ann Am Thorac Soc 2016; 13 (05) 627-635
  • 50 Paraskeva M, McLean C, Ellis S. et al. Acute fibrinoid organizing pneumonia after lung transplantation. Am J Respir Crit Care Med 2013; 187 (12) 1360-1368
  • 51 Glanville AR. Bronchoscopic monitoring after lung transplantation. Semin Respir Crit Care Med 2010; 31 (02) 208-221
  • 52 Glanville AR, Verleden GM, Todd JL. et al. Chronic lung allograft dysfunction: definition and update of restrictive allograft syndrome—a consensus report from the Pulmonary Council of the ISHLT. J Heart Lung Transplant 2019; 38 (05) 483-492
  • 53 Verleden GM, Glanville AR, Lease ED. et al. Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment—a consensus report from the Pulmonary Council of the ISHLT. J Heart Lung Transplant 2019; 38 (05) 493-503
  • 54 Nathan SD, Barnett SD, Wohlrab J, Burton N. Bronchiolitis obliterans syndrome: utility of the new guidelines in single lung transplant recipients. J Heart Lung Transplant 2003; 22 (04) 427-432
  • 55 Lama VN, Murray S, Mumford JA. et al. Prognostic value of bronchiolitis obliterans syndrome stage 0-p in single-lung transplant recipients. Am J Respir Crit Care Med 2005; 172 (03) 379-383
  • 56 Hachem RR, Chakinala MM, Yusen RD. et al. The predictive value of bronchiolitis obliterans syndrome stage 0-p. Am J Respir Crit Care Med 2004; 169 (04) 468-472
  • 57 Collins J. Imaging of the chest after lung transplantation. J Thorac Imaging 2002; 17 (02) 102-112
  • 58 Miller Jr WT, Kotloff RM, Blumenthal NP, Aronchick JM, Gefter WB, Miller WT. Utility of high resolution computed tomography in predicting bronchiolitis obliterans syndrome following lung transplantation: preliminary findings. J Thorac Imaging 2001; 16 (02) 76-80
  • 59 Konen E, Gutierrez C, Chaparro C. et al. Bronchiolitis obliterans syndrome in lung transplant recipients: can thin-section CT findings predict disease before its clinical appearance?. Radiology 2004; 231 (02) 467-473
  • 60 Berstad AE, Aaløkken TM, Kolbenstvedt A, Bjørtuft O. Performance of long-term CT monitoring in diagnosing bronchiolitis obliterans after lung transplantation. Eur J Radiol 2006; 58 (01) 124-131
  • 61 Kramer MR, Stoehr C, Whang JL. et al. The diagnosis of obliterative bronchiolitis after heart-lung and lung transplantation: low yield of transbronchial lung biopsy. J Heart Lung Transplant 1993; 12 (04) 675-681
  • 62 Pomerance A, Madden B, Burke MM, Yacoub MH. Transbronchial biopsy in heart and lung transplantation: clinicopathologic correlations. J Heart Lung Transplant 1995; 14 (04) 761-773
  • 63 Chamberlain D, Maurer J, Chaparro C, Idolor L. Evaluation of transbronchial lung biopsy specimens in the diagnosis of bronchiolitis obliterans after lung transplantation. J Heart Lung Transplant 1994; 13 (06) 963-971
  • 64 Suhling H, Dettmer S, Greer M. et al. Phenotyping chronic lung allograft dysfunction using body plethysmography and computed tomography. Am J Transplant 2016; 16 (11) 3163-3170
  • 65 Suwara MI, Vanaudenaerde BM, Verleden SE. et al. Mechanistic differences between phenotypes of chronic lung allograft dysfunction after lung transplantation. Transpl Int 2014; 27 (08) 857-867
  • 66 Dettmer S, Shin HO, Vogel-Claussen J. et al. CT at onset of chronic lung allograft dysfunction in lung transplant patients predicts development of the restrictive phenotype and survival. Eur J Radiol 2017; 94: 78-84
  • 67 Kneidinger N, Milger K, Janitza S. et al. Lung volumes predict survival in patients with chronic lung allograft dysfunction. Eur Respir J 2017; 49 (04) 49
  • 68 Billingham ME. Pathology of the transplanted heart and lung. Cardiovasc Clin 1990; 20 (02) 71-85
  • 69 Ofek E, Sato M, Saito T. et al. Restrictive allograft syndrome post lung transplantation is characterized by pleuroparenchymal fibroelastosis. Mod Pathol 2013; 26 (03) 350-356
  • 70 Sato M, Hwang DM, Ohmori-Matsuda K. et al. Revisiting the pathologic finding of diffuse alveolar damage after lung transplantation. J Heart Lung Transplant 2012; 31 (04) 354-363
  • 71 Shino MY, Weigt SS, Li N. 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 (09) 1117-1125
  • 72 Verleden SE, Gottlieb J, Dubbeldam A. et al. “White-out” after lung transplantation: a multicenter cohort description of late acute graft failure. Am J Transplant 2017; 17 (07) 1905-1911
  • 73 Lama VN, Murray S, Lonigro RJ. et al. Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients. Am J Respir Crit Care Med 2007; 175 (11) 1192-1198
  • 74 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 (06) 658-666
  • 75 Finlen Copeland CA, Snyder LD, Zaas DW, Turbyfill WJ, Davis WA, Palmer SM. Survival after bronchiolitis obliterans syndrome among bilateral lung transplant recipients. Am J Respir Crit Care Med 2010; 182 (06) 784-789
  • 76 Sato M, Ohmori-Matsuda K, Saito T. et al. Time-dependent changes in the risk of death in pure bronchiolitis obliterans syndrome (BOS). J Heart Lung Transplant 2013; 32 (05) 484-491
  • 77 Verleden SE, Todd JL, Sato M. et al. Impact of CLAD phenotype on survival after lung retransplantation: a multicenter study. Am J Transplant 2015; 15 (08) 2223-2230
  • 78 Billings JL, Hertz MI, Savik K, Wendt CH. Respiratory viruses and chronic rejection in lung transplant recipients. J Heart Lung Transplant 2002; 21 (05) 559-566
  • 79 Botha P, Archer L, Anderson RL. et al. Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation 2008; 85 (05) 771-774
  • 80 Khalifah AP, Hachem RR, Chakinala MM. et al. Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death. Am J Respir Crit Care Med 2004; 170 (02) 181-187
  • 81 Ruttmann E, Geltner C, Bucher B. et al. Combined CMV prophylaxis improves outcome and reduces the risk for bronchiolitis obliterans syndrome (BOS) after lung transplantation. Transplantation 2006; 81 (10) 1415-1420
  • 82 Weigt SS, Derhovanessian A, Liao E. et al. CXCR3 chemokine ligands during respiratory viral infections predict lung allograft dysfunction. Am J Transplant 2012; 12 (02) 477-484
  • 83 Weigt SS, Elashoff RM, Huang C. et al. Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome. Am J Transplant 2009; 9 (08) 1903-1911
  • 84 Weigt SS, Elashoff RM, Keane MP. et al. Altered levels of CC chemokines during pulmonary CMV predict BOS and mortality post-lung transplantation. Am J Transplant 2008; 8 (07) 1512-1522
  • 85 Blondeau K, Mertens V, Vanaudenaerde BA. et al. Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection. Eur Respir J 2008; 31 (04) 707-713
  • 86 D'Ovidio F, Mura M, Tsang M. et al. Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation. J Thorac Cardiovasc Surg 2005; 129 (05) 1144-1152
  • 87 Nawrot TS, Vos R, Jacobs L. et al. The impact of traffic air pollution on bronchiolitis obliterans syndrome and mortality after lung transplantation. Thorax 2011; 66 (09) 748-754
  • 88 Verleden SE, Scheers H, Nawrot TS. et al. Lymphocytic bronchiolitis after lung transplantation is associated with daily changes in air pollution. Am J Transplant 2012; 12 (07) 1831-1838
  • 89 Sumpter TL, Wilkes DS. Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection. Am J Physiol Lung Cell Mol Physiol 2004; 286 (06) L1129-L1139
  • 90 Wilkes DS, Heidler KM, Yasufuku K. et al. Cell-mediated immunity to collagen V in lung transplant recipients: correlation with collagen V release into BAL fluid. J Heart Lung Transplant 2001; 20 (02) 167
  • 91 Shino MY, Weigt SS, Li N. et al. Impact of allograft injury time of onset on the development of chronic lung allograft dysfunction after lung transplantation. Am J Transplant 2017; 17 (05) 1294-1303
  • 92 Shino MY, Weigt SS, Li N. et al. The prognostic importance of bronchoalveolar lavage fluid CXCL9 during minimal acute rejection on the risk of chronic lung allograft dysfunction. Am J Transplant 2018; 18 (01) 136-144
  • 93 Shino MY, Weigt SS, Li N. et al. The prognostic importance of CXCR3 chemokine during organizing pneumonia on the risk of chronic lung allograft dysfunction after lung transplantation. PLoS One 2017; 12 (07) e0180281
  • 94 Verleden SE, Ruttens D, Vandermeulen E. et al. Bronchiolitis obliterans syndrome and restrictive allograft syndrome: do risk factors differ?. Transplantation 2013; 95 (09) 1167-1172
  • 95 Qin S, Rottman JB, Myers P. et al. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 1998; 101 (04) 746-754
  • 96 Belperio JA, Keane MP, Burdick MD. et al. Role of CXCL9/CXCR3 chemokine biology during pathogenesis of acute lung allograft rejection. J Immunol 2003; 171 (09) 4844-4852
  • 97 Belperio JA, Keane MP, Burdick MD. et al. Critical role for CXCR3 chemokine biology in the pathogenesis of bronchiolitis obliterans syndrome. J Immunol 2002; 169 (02) 1037-1049
  • 98 Shino MY, DerHovanessian A, Sayah DM. et al. The impact of allograft CXCL9 during respiratory infection on the risk of chronic lung allograft dysfunction. OBM Transplant 2018; 2 (04) 2
  • 99 Zhu J, Paul WE. CD4 T cells: fates, functions, and faults. Blood 2008; 112 (05) 1557-1569
  • 100 Hodge S, Holmes M, Banerjee B. et al. Posttransplant bronchiolitis obliterans syndrome is associated with bronchial epithelial to mesenchymal transition. Am J Transplant 2009; 9 (04) 727-733
  • 101 Iacono A, Dauber J, Keenan R. et al. Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine. Transplantation 1997; 64 (02) 263-269
  • 102 Lu KC, Jaramillo A, Lecha RL. et al. Interleukin-6 and interferon-gamma gene polymorphisms in the development of bronchiolitis obliterans syndrome after lung transplantation. Transplantation 2002; 74 (09) 1297-1302
  • 103 Meloni F, Vitulo P, Cascina A. et al. Bronchoalveolar lavage cytokine profile in a cohort of lung transplant recipients: a predictive role of interleukin-12 with respect to onset of bronchiolitis obliterans syndrome. J Heart Lung Transplant 2004; 23 (09) 1053-1060
  • 104 Moudgil A, Bagga A, Toyoda M, Nicolaidou E, Jordan SC, Ross D. Expression of gamma-IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients. Clin Transplant 1999; 13 (02) 201-207
  • 105 Neuringer IP, Walsh SP, Mannon RB, Gabriel S, Aris RM. Enhanced T cell cytokine gene expression in mouse airway obliterative bronchiolitis. Transplantation 2000; 69 (03) 399-405
  • 106 Räisänen-Sokolowski A, Glysing-Jensen T, Russell ME. Leukocyte-suppressing influences of interleukin (IL)-10 in cardiac allografts: insights from IL-10 knockout mice. Am J Pathol 1998; 153 (05) 1491-1500
  • 107 Belperio JA, Burdick MD, Keane MP. et al. The role of the CC chemokine, RANTES, in acute lung allograft rejection. J Immunol 2000; 165 (01) 461-472
  • 108 Iasella CJ, Hoji A, Popescu I. et al. Type-1 immunity and endogenous immune regulators predominate in the airway transcriptome during chronic lung allograft dysfunction. Am J Transplant 2020; (epub online ahead of print) DOI: 10.1111/ajt.16360.
  • 109 Zhai Y, Ghobrial RM, Busuttil RW, Kupiec-Weglinski JW. Th1 and Th2 cytokines in organ transplantation: paradigm lost?. Crit Rev Immunol 1999; 19 (02) 155-172
  • 110 Keane MP, Gomperts BN, Weigt S. et al. IL-13 is pivotal in the fibro-obliterative process of bronchiolitis obliterans syndrome. J Immunol 2007; 178 (01) 511-519
  • 111 Lama VN, Harada H, Badri LN. et al. Obligatory role for interleukin-13 in obstructive lesion development in airway allografts. Am J Pathol 2006; 169 (01) 47-60
  • 112 Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 2000; 404 (6776): 407-411
  • 113 Belperio JA, Keane MP, Burdick MD. et al. Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis obliterans syndrome. J Clin Invest 2001; 108 (04) 547-556
  • 114 Pain M, Royer PJ, Loy J. et al; COLT Consortium. T cells promote bronchial epithelial cell secretion of matrix metalloproteinase-9 via a C-C chemokine receptor type 2 pathway: implications for chronic lung allograft dysfunction. Am J Transplant 2017; 17 (06) 1502-1514
  • 115 Palchevskiy V, Xue YY, Kern R. et al. CCR4 expression on host T cells is a driver for alloreactive responses and lung rejection. JCI Insight 2019; 5: 5
  • 116 Vanaudenaerde BM, De Vleeschauwer SI, Vos R. et al. The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant 2008; 8 (09) 1911-1920
  • 117 Nakagiri T, Inoue M, Morii E. et al. Local IL-17 production and a decrease in peripheral blood regulatory T cells in an animal model of bronchiolitis obliterans. Transplantation 2010; 89 (11) 1312-1319
  • 118 Fan L, Benson HL, Vittal R. et al. Neutralizing IL-17 prevents obliterative bronchiolitis in murine orthotopic lung transplantation. Am J Transplant 2011; 11 (05) 911-922
  • 119 Yamada Y, Vandermeulen E, Heigl T. et al. The role of recipient derived interleukin-17A in a murine orthotopic lung transplant model of restrictive chronic lung allograft dysfunction. Transpl Immunol 2016; 39: 10-17
  • 120 Chanut-Delalande H, Fichard A, Bernocco S, Garrone R, Hulmes DJ, Ruggiero F. Control of heterotypic fibril formation by collagen V is determined by chain stoichiometry. J Biol Chem 2001; 276 (26) 24352-24359
  • 121 Iwata T, Chiyo M, Yoshida S. et al. Lung transplant ischemia reperfusion injury: metalloprotease inhibition down-regulates exposure of type V collagen, growth-related oncogene-induced neutrophil chemotaxis, and tumor necrosis factor-alpha expression. Transplantation 2008; 85 (03) 417-426
  • 122 Hachem RR, Yusen RD, Meyers BF. et al. Anti-human leukocyte antigen antibodies and preemptive antibody-directed therapy after lung transplantation. J Heart Lung Transplant 2010; 29 (09) 973-980
  • 123 Haque MA, Mizobuchi T, Yasufuku K. et al. Evidence for immune responses to a self-antigen in lung transplantation: role of type V collagen-specific T cells in the pathogenesis of lung allograft rejection. J Immunol 2002; 169 (03) 1542-1549
  • 124 Bharat A, Fields RC, Trulock EP, Patterson GA, Mohanakumar T. Induction of IL-10 suppressors in lung transplant patients by CD4+25+ regulatory T cells through CTLA-4 signaling. J Immunol 2006; 177 (08) 5631-5638
  • 125 Fukami N, Ramachandran S, Saini D. et al. Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of chronic rejection. J Immunol 2009; 182 (01) 309-318
  • 126 Burlingham WJ, Love RB, Jankowska-Gan E. et al. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest 2007; 117 (11) 3498-3506
  • 127 Bhorade SM, Chen H, Molinero L. 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 (05) 540-546
  • 128 Gregson AL, Hoji A, Palchevskiy V. et al. Protection against bronchiolitis obliterans syndrome is associated with allograft CCR7+ CD45RA- T regulatory cells. PLoS One 2010; 5 (06) e11354
  • 129 Salman J, Ius F, Knoefel AK. et al. Association of higher CD4+ CD25high CD127low, FoxP3+, and IL-2+ T cell frequencies early after lung transplantation with less chronic lung allograft dysfunction at two years. Am J Transplant 2017; 17 (06) 1637-1648
  • 130 Piloni D, Morosini M, Magni S. et al. Analysis of long term CD4+CD25highCD127 T-reg cells kinetics in peripheral blood of lung transplant recipients. BMC Pulm Med 2017; 17 (01) 102
  • 131 Le Moine A, Goldman M, Abramowicz D. Multiple pathways to allograft rejection. Transplantation 2002; 73 (09) 1373-1381
  • 132 Morrell MR, Pilewski JM, Gries CJ. et al. De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation. J Heart Lung Transplant 2014; 33 (12) 1288-1294
  • 133 Safavi S, Robinson DR, Soresi S, Carby M, Smith JD. De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 2014; 33 (12) 1273-1281
  • 134 Snyder LD, Wang Z, Chen DF. et al. Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients. Chest 2013; 144 (01) 226-233
  • 135 Le Pavec J, Suberbielle C, Lamrani L. et al. De-novo donor-specific anti-HLA antibodies 30 days after lung transplantation are associated with a worse outcome. J Heart Lung Transplant 2016; 35 (09) 1067-1077
  • 136 Tikkanen JM, Singer LG, Kim SJ. et al. De novo DQ donor-specific antibodies are associated with chronic lung allograft dysfunction after lung transplantation. Am J Respir Crit Care Med 2016; 194 (05) 596-606
  • 137 Vandermeulen E, Verleden SE, Bellon H. et al. Humoral immunity in phenotypes of chronic lung allograft dysfunction: a broncho-alveolar lavage fluid analysis. Transpl Immunol 2016; 38: 27-32
  • 138 Brugière O, Suberbielle C, Thabut G. et al. Lung transplantation in patients with pretransplantation donor-specific antibodies detected by Luminex assay. Transplantation 2013; 95 (05) 761-765
  • 139 Hadjiliadis D, Chaparro C, Reinsmoen NL. et al. Pre-transplant panel reactive antibody in lung transplant recipients is associated with significantly worse post-transplant survival in a multicenter study. J Heart Lung Transplant 2005; 24 (7, Suppl): S249-S254
  • 140 Kim M, Townsend KR, Wood IG. et al. Impact of pretransplant anti-HLA antibodies on outcomes in lung transplant candidates. Am J Respir Crit Care Med 2014; 189 (10) 1234-1239
  • 141 Bosanquet JP, Witt CA, Bemiss BC. et al. The impact of pre-transplant allosensitization on outcomes after lung transplantation. J Heart Lung Transplant 2015; 34 (11) 1415-1422
  • 142 Maruyama T, Jaramillo A, Narayanan K, Higuchi T, Mohanakumar T. Induction of obliterative airway disease by anti-HLA class I antibodies. Am J Transplant 2005; 5 (09) 2126-2134
  • 143 Levine DJ, Glanville AR, Aboyoun C. 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 (04) 397-406
  • 144 Berry GJ, Burke MM, Andersen C. et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2013; 32 (12) 1147-1162
  • 145 Haas M, Sis B, Racusen LC. et al; Banff Meeting Report Writing Committee. Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014; 14 (02) 272-283
  • 146 Glanville AR. Antibody-mediated rejection in lung transplantation: myth or reality?. J Heart Lung Transplant 2010; 29 (04) 395-400
  • 147 Westall GP, Snell GI. Antibody-mediated rejection in lung transplantation: fable, spin, or fact?. Transplantation 2014; 98 (09) 927-930
  • 148 Goers TA, Ramachandran S, Aloush A, Trulock E, Patterson GA, Mohanakumar T. De novo production of K-alpha1 tubulin-specific antibodies: role in chronic lung allograft rejection. J Immunol 2008; 180 (07) 4487-4494
  • 149 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 (08) 2164-2171
  • 150 Saini D, Weber J, Ramachandran S. et al. Alloimmunity-induced autoimmunity as a potential mechanism in the pathogenesis of chronic rejection of human lung allografts. J Heart Lung Transplant 2011; 30 (06) 624-631
  • 151 Bharat A, Mohanakumar T. Immune responses to tissue-restricted nonmajor histocompatibility complex antigens in allograft rejection. J Immunol Res 2017; 2017: 6312514
  • 152 Chiu S, Fernandez R, Subramanian V. et al. Lung injury combined with loss of regulatory T cells leads to de novo lung-restricted autoimmunity. J Immunol 2016; 197 (01) 51-57
  • 153 Adachi E, Hopkinson I, Hayashi T. Basement-membrane stromal relationships: interactions between collagen fibrils and the lamina densa. Int Rev Cytol 1997; 173: 73-156
  • 154 Yasufuku K, Heidler KM, Woods KA. et al. Prevention of bronchiolitis obliterans in rat lung allografts by type V collagen-induced oral tolerance. Transplantation 2002; 73 (04) 500-505
  • 155 Tiriveedhi V, Angaswamy N, Brand D. et al. A shift in the collagen V antigenic epitope leads to T helper phenotype switch and immune response to self-antigen leading to chronic lung allograft rejection. Clin Exp Immunol 2012; 167 (01) 158-168
  • 156 Zaffiri L, Shah RJ, Stearman RS. et al. Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. Transpl Immunol 2019; 56: 101224
  • 157 Bharat A, Saini D, Steward N. et al. Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection. Ann Thorac Surg 2010; 90 (04) 1094-1101
  • 158 Andrade CF, Waddell TK, Keshavjee S, Liu M. Innate immunity and organ transplantation: the potential role of toll-like receptors. Am J Transplant 2005; 5 (05) 969-975
  • 159 Chen L, Wang T, Zhou P. et al. TLR engagement prevents transplantation tolerance. Am J Transplant 2006; 6 (10) 2282-2291
  • 160 Porrett PM, Yuan X, LaRosa DF. et al. Mechanisms underlying blockade of allograft acceptance by TLR ligands. J Immunol 2008; 181 (03) 1692-1699
  • 161 Todd JL, Wang X, Sugimoto S. 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 (05) 556-566
  • 162 Palmer SM, Burch LH, Trindade AJ. et al. Innate immunity influences long-term outcomes after human lung transplant. Am J Respir Crit Care Med 2005; 171 (07) 780-785
  • 163 Kastelijn EA, van Moorsel CH, Rijkers GT. et al. Polymorphisms in innate immunity genes associated with development of bronchiolitis obliterans after lung transplantation. J Heart Lung Transplant 2010; 29 (06) 665-671
  • 164 Palmer SM, Klimecki W, Yu L. et al. Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. Am J Transplant 2007; 7 (03) 693-699
  • 165 Saito T, Liu M, Binnie M. et al. Distinct expression patterns of alveolar “alarmins” in subtypes of chronic lung allograft dysfunction. Am J Transplant 2014; 14 (06) 1425-1432
  • 166 Whyte RI, Rossi SJ, Mulligan MS. et al. Mycophenolate mofetil for obliterative bronchiolitis syndrome after lung transplantation. Ann Thorac Surg 1997; 64 (04) 945-948
  • 167 Speich R, Schneider S, Hofer M. et al. Mycophenolate mofetil reduces alveolar inflammation, acute rejection and graft loss due to bronchiolitis obliterans syndrome after lung transplantation. Pulm Pharmacol Ther 2010; 23 (05) 445-449
  • 168 Sarahrudi K, Carretta A, Wisser W. et al. The value of switching from cyclosporine to tacrolimus in the treatment of refractory acute rejection and obliterative bronchiolitis after lung transplantation. Transpl Int 2002; 15 (01) 24-28
  • 169 Cairn J, Yek T, Banner NR, Khaghani A, Hodson ME, Yacoub M. Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome. J Heart Lung Transplant 2003; 22 (01) 50-57
  • 170 Borro J, Bravo C, Solé A. et al. Conversion from cyclosporine to tacrolimus stabilizes the course of lung function in lung transplant recipients with bronchiolitis obliterans syndrome. Transplant Proc 2007; 39 (07) 2416-2419
  • 171 Cahill BC, Somerville KT, Crompton JA. et al. Early experience with sirolimus in lung transplant recipients with chronic allograft rejection. J Heart Lung Transplant 2003; 22 (02) 169-176
  • 172 January SE, Fester KA, Bain KB. et al. Rabbit antithymocyte globulin for the treatment of chronic lung allograft dysfunction. Clin Transplant 2019; 33 (10) e13708
  • 173 Izhakian S, Wasser WG, Fox BD, Vainshelboim B, Reznik JE, Kramer MR. Effectiveness of rabbit antithymocyte globulin in chronic lung allograft dysfunction. Transplant Proc 2016; 48 (06) 2152-2156
  • 174 Kesten S, Rajagopalan N, Maurer J. Cytolytic therapy for the treatment of bronchiolitis obliterans syndrome following lung transplantation. Transplantation 1996; 61 (03) 427-430
  • 175 Snell GI, Esmore DS, Williams TJ. Cytolytic therapy for the bronchiolitis obliterans syndrome complicating lung transplantation. Chest 1996; 109 (04) 874-878
  • 176 Date H, Lynch JP, Sundaresan S, Patterson GA, Trulock EP. The impact of cytolytic therapy on bronchiolitis obliterans syndrome. J Heart Lung Transplant 1998; 17 (09) 869-875
  • 177 Ensor CR, Rihtarchik LC, Morrell MR. et al. Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation. Clin Transplant 2017; 31 (04) 31
  • 178 Sithamparanathan S, Thirugnanasothy L, Morley KE. et al. Observational study of methotrexate in the treatment of bronchiolitis obliterans syndrome. Transplant Proc 2016; 48 (10) 3387-3392
  • 179 Hernández RL, Gil PU, Gallo CG, de Pablo Gafas A, Hernández MC, Alvarez MJ. Rapamycin in lung transplantation. Transplant Proc 2005; 37 (09) 3999-4000
  • 180 Gerhardt SG, McDyer JF, Girgis RE, Conte JV, Yang SC, Orens JB. Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study. Am J Respir Crit Care Med 2003; 168 (01) 121-125
  • 181 Verleden GM, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE. Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2006; 174 (05) 566-570
  • 182 Federica M, Nadia S, Monica M. et al. Clinical and immunological evaluation of 12-month azithromycin therapy in chronic lung allograft rejection. Clin Transplant 2011; 25 (04) E381-E389
  • 183 Gottlieb J, Szangolies J, Koehnlein T, Golpon H, Simon A, Welte T. Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation 2008; 85 (01) 36-41
  • 184 Vos R, Vanaudenaerde BM, Ottevaere A. et al. Long-term azithromycin therapy for bronchiolitis obliterans syndrome: divide and conquer?. J Heart Lung Transplant 2010; 29 (12) 1358-1368
  • 185 Verleden GM, Dupont LJ. Azithromycin therapy for patients with bronchiolitis obliterans syndrome after lung transplantation. Transplantation 2004; 77 (09) 1465-1467
  • 186 Jain R, Hachem RR, Morrell MR. et al. Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome. J Heart Lung Transplant 2010; 29 (05) 531-537
  • 187 Shitrit D, Bendayan D, Gidon S, Saute M, Bakal I, Kramer MR. Long-term azithromycin use for treatment of bronchiolitis obliterans syndrome in lung transplant recipients. J Heart Lung Transplant 2005; 24 (09) 1440-1443
  • 188 Porhownik NR, Batobara W, Kepron W, Unruh HW, Bshouty Z. Effect of maintenance azithromycin on established bronchiolitis obliterans syndrome in lung transplant patients. Can Respir J 2008; 15 (04) 199-202
  • 189 Kingah PL, Muma G, Soubani A. Azithromycin improves lung function in patients with post-lung transplant bronchiolitis obliterans syndrome: a meta-analysis. Clin Transplant 2014; 28 (08) 906-910
  • 190 Corris PA, Ryan VA, Small T. et al. A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation. Thorax 2015; 70 (05) 442-450
  • 191 Gan CT, Ward C, Meachery G, Lordan JL, Fisher AJ, Corris PA. Long-term effect of azithromycin in bronchiolitis obliterans syndrome. BMJ Open Respir Res 2019; 6 (01) e000465
  • 192 Verleden GM, Verleden SE, Vos R. et al. Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a pilot study. Transpl Int 2011; 24 (07) 651-656
  • 193 Vos R, Eynde RV, Ruttens D. et al; Leuven Lung Transplant Group. Montelukast in chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant 2019; 38 (05) 516-527
  • 194 Ruttens D, Verleden SE, Demeyer H. et al. Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a randomized controlled trial. PLoS One 2018; 13 (04) e0193564
  • 195 Cho A, Jantschitsch C, Knobler R. Extracorporeal photopheresis—an overview. Front Med (Lausanne) 2018; 5: 236
  • 196 Morrell MR, Despotis GJ, Lublin DM, Patterson GA, Trulock EP, Hachem RR. The efficacy of photopheresis for bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 2010; 29 (04) 424-431
  • 197 Benden C, Speich R, Hofbauer GF. et al. Extracorporeal photopheresis after lung transplantation: a 10-year single-center experience. Transplantation 2008; 86 (11) 1625-1627
  • 198 Pecoraro Y, Carillo C, Diso D. et al. Efficacy of extracorporeal photopheresis in patients with bronchiolitis obliterans syndrome after lung transplantation. Transplant Proc 2017; 49 (04) 695-698
  • 199 Jaksch P, Scheed A, Keplinger M. et al. A prospective interventional study on the use of extracorporeal photopheresis in patients with bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 2012; 31 (09) 950-957
  • 200 Del Fante C, Scudeller L, Oggionni T. et al. Long-term off-line extracorporeal photochemotherapy in patients with chronic lung allograft rejection not responsive to conventional treatment: a 10-year single-centre analysis. Respiration 2015; 90 (02) 118-128
  • 201 Greer M, Dierich M, De Wall C. et al. Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients. Am J Transplant 2013; 13 (04) 911-918
  • 202 Chionis L, Grossman BJ, Hachem R. et al. The efficacy of extracorporeal photopheresis to arrest bronchiolitis obliterans in lung allograft recipients was compared between two automated photopheresis instruments. Transfusion 2018; 58 (12) 2933-2941
  • 203 Davis Jr RD, Lau CL, Eubanks S. et al. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation. J Thorac Cardiovasc Surg 2003; 125 (03) 533-542
  • 204 Davidson JR, Franklin D, Kumar S. et al. Fundoplication to preserve allograft function after lung transplant: systematic review and meta-analysis. J Thorac Cardiovasc Surg 2020; 160 (03) 858-866
  • 205 Yusen RD, Edwards LB, Kucheryavaya AY. et al; International Society for Heart and Lung Transplantation. The registry of the International Society for Heart and Lung Transplantation: Thirty-First Adult Lung and Heart-Lung Transplant Report--2014; focus theme: retransplantation. J Heart Lung Transplant 2014; 33 (10) 1009-1024
  • 206 Brugière O, Thabut G, Castier Y. et al. Lung retransplantation for bronchiolitis obliterans syndrome: long-term follow-up in a series of 15 recipients. Chest 2003; 123 (06) 1832-1837
  • 207 Revilla-López E, Berastegui C, Sáez-Giménez B. et al. Lung retransplantation due to chronic lung allograph dysfunction: results from a Spanish Transplant Unit. [in Spanish] Arch Bronconeumol 2019; 55 (03) 134-138
  • 208 Open-Label, Extension Trial to Demonstrate the Effectiveness and Safety of L–CsA Plus Standard of Care in the Treatment of BOS in Patients Post Single or Double Lung Transplant (BOSTON-3). clinicaltrials.gov. Accessed February 17, 2021 at: https://clinicaltrials.gov/ct2/show/NCT04039347
  • 209 Groves S, Galazka M, Johnson B. et al. Inhaled cyclosporine and pulmonary function in lung transplant recipients. J Aerosol Med Pulm Drug Deliv 2010; 23 (01) 31-39
  • 210 Iacono AT, Corcoran TE, Griffith BP. et al. Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. Eur Respir J 2004; 23 (03) 384-390
  • 211 An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following Lung Transplantation. Accessed February 17, 2021 at: https://clinicaltrials.gov/ct2/show/NCT03978637
  • 212 Schroeder MA, Choi J, Staser K, DiPersio JF. The role of janus kinase signaling in graft-versus-host disease and graft versus leukemia. Biol Blood Marrow Transplant 2018; 24 (06) 1125-1134
  • 213 Schroeder MA, Khoury HJ, Jagasia M. et al. A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease. Blood Adv 2020; 4 (08) 1656-1669
  • 214 Zeiser R, Burchert A, Lengerke C. et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia 2015; 29 (10) 2062-2068
  • 215 Schoettler M, Duncan C, Lehmann L, Furutani E, Subramaniam M, Margossian S. Ruxolitinib is an effective steroid sparing agent in children with steroid refractory/dependent bronchiolitis obliterans syndrome after allogenic hematopoietic cell transplantation. Bone Marrow Transplant 2019; 54 (07) 1158-1160
  • 216 King Jr TE, Bradford WZ, Castro-Bernardini S. et al; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014; 370 (22) 2083-2092
  • 217 Noble PW, Albera C, Bradford WZ. et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J 2016; 47 (01) 243-253
  • 218 Richeldi L, du Bois RM, Raghu G. et al; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014; 370 (22) 2071-2082
  • 219 Distler O, Highland KB, Gahlemann M. et al; SENSCIS Trial Investigators. Nintedanib for systemic sclerosis–associated interstitial lung disease. N Engl J Med 2019; 380 (26) 2518-2528
  • 220 Flaherty KR, Wells AU, Cottin V. et al; INBUILD Trial Investigators. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 2019; 381 (18) 1718-1727
  • 221 Suhling H, Bollmann B, Gottlieb J. Nintedanib in restrictive chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant 2016; 35 (07) 939-940
  • 222 Vos R, Wuyts WA, Gheysens O. et al. Pirfenidone in restrictive allograft syndrome after lung transplantation: a case series. Am J Transplant 2018; 18 (12) 3045-3059
  • 223 Perch M, Besa V, Corris PA. et al. A European multi-center, randomized, double-blind trial of pirfenidone in bronchiolitis-obliterans-syndrome grade 1-3 in lung transplant recipients (European Trial of Pirfenidone in BOS (EPOS)). J Heart Lung Transplant 2020; 39: S12
  • 224 A Randomised Multi-center, Double-blind Trial of Nintedanib in Lung Transplant (LTx) Recipients with Bronchiolitis Obliterans Syndrome (BOS) Grade 1–2. Accessed February 17, 2021 at: https://clinicaltrials.gov/ct2/show/NCT03283007
  • 225 A European Multi-center, Randomised, Double-blind Trial of Pirfenidone in Bronchiolitis-obliterans-syndrome Grade 1–3 in Lung Transplant Recipients. Accessed February 17, 2021 at: https://clinicaltrials.gov/ct2/show/NCT02262299
  • 226 A Phase Two Randomized, Double-blinded, Placebo-controlled Study Combining Physiological, Radiographic, and Biological Biomarkers to Study the Anti-fibrotic Effect of Pirfenidone in CLAD Post Lung-transplantation. Accessed February 17, 2021 at: https://clinicaltrials.gov/ct2/show/NCT03473340
  • 227 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 (04) 1152-1157
  • 228 Keller CA, Gonwa TA, Hodge DO, Hei DJ, Centanni JM, Zubair AC. Feasibility, safety, and tolerance of mesenchymal stem cell therapy for obstructive chronic lung allograft dysfunction. Stem Cells Transl Med 2018; 7 (02) 161-167
  • 229 Phase 2 Randomised Controlled Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction (CLAD). Accessed February 17, 2021 at: https://clinicaltrials.gov/ct2/show/NCT02709343
  • 230 Chambers DC, Cherikh WS, Goldfarb SB. et al; International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth adult lung and heart-lung transplant report-2018; Focus theme: multiorgan transplantation. J Heart Lung Transplant 2018; 37 (10) 1169-1183
  • 231 Koutsokera A, Royer PJ, Antonietti JP. et al; SysCLAD Consortium. Development of a multivariate prediction model for early-onset bronchiolitis obliterans syndrome and restrictive allograft syndrome in lung transplantation. Front Med (Lausanne) 2017; 4: 109
  • 232 Newton CA, Kozlitina J, Lines JR, Kaza V, Torres F, Garcia CK. Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival. J Heart Lung Transplant 2017; 36 (08) 845-853
  • 233 Swaminathan AC, Neely ML, Frankel CW. et al. Lung transplant outcomes in patients with pulmonary fibrosis with telomere-related gene variants. Chest 2019; 156 (03) 477-485
  • 234 Chambers DC, Zuckermann A, Cherikh WS. et al; International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 37th adult lung transplantation report - 2020; focus on deceased donor characteristics. J Heart Lung Transplant 2020; 39 (10) 1016-1027
  • 235 Schultz HH, Møller CH, Zemtsovski M. et al. Donor smoking and older age increases morbidity and mortality after lung transplantation. Transplant Proc 2017; 49 (09) 2161-2168
  • 236 Chambers DC, Yusen RD, Cherikh WS. et al; International Society for Heart and Lung Transplantation. 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 (10) 1047-1059
  • 237 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 (05) 1037-1045
  • 238 De Muynck B, Van Herck A, Sacreas A. et al; Leuven Lung Transplant Group. Successful Pseudomonas aeruginosa eradication improves outcomes after lung transplantation: a retrospective cohort analysis. Eur Respir J 2020; 56 (04) 56
  • 239 Orfanos S, Gomez C, Baron S. et al. Impact of gram negative bacteria airway recolonization on the occurrence of chronic lung allograft dysfunction after lung transplantation in a population of cystic fibrosis patients. BMC Microbiol 2018; 18 (01) 88
  • 240 Weigt SS, Copeland CAF, Derhovanessian A. et al. Colonization with small conidia Aspergillus species is associated with bronchiolitis obliterans syndrome: a two-center validation study. Am J Transplant 2013; 13 (04) 919-927
  • 241 Law N, Hamandi B, Fegbeutel C. et al. Lack of association of Aspergillus colonization with the development of bronchiolitis obliterans syndrome in lung transplant recipients: an international cohort study. J Heart Lung Transplant 2019; 38 (09) 963-971
  • 242 Weigt SS, Wang X, Palchevskiy V. et al. Gene expression profiling of bronchoalveolar lavage cells during Aspergillus colonization of the lung allograft. Transplantation 2018; 102 (06) 986-993
  • 243 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) 1391-1396
  • 244 Keenan RJ, Lega ME, Dummer JS. et al. Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation. Transplantation 1991; 51 (02) 433-438
  • 245 Paraskeva M, Bailey M, Levvey BJ. et al. Cytomegalovirus replication within the lung allograft is associated with bronchiolitis obliterans syndrome. Am J Transplant 2011; 11 (10) 2190-2196
  • 246 Jaamei N, Koutsokera A, Pasquier J. et al. Clinical significance of post-prophylaxis cytomegalovirus infection in lung transplant recipients. Transpl Infect Dis 2018; 20 (04) e12893
  • 247 Allyn PR, Duffy EL, Humphries RM. et al. Graft loss and CLAD-onset is hastened by viral pneumonia after lung transplantation. Transplantation 2016; 100 (11) 2424-2431
  • 248 Magnusson J, Westin J, Andersson LM. et al. Viral respiratory tract infection during the first postoperative year is a risk factor for chronic rejection after lung transplantation. Transplant Direct 2018; 4 (08) e370
  • 249 Young LR, Hadjiliadis D, Davis RD, Palmer SM. Lung transplantation exacerbates gastroesophageal reflux disease. Chest 2003; 124 (05) 1689-1693
  • 250 Cantu III E, Appel III JZ, Hartwig MG. et al. J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease. Ann Thorac Surg 2004; 78 (04) 1142-1151 , discussion 1142–1151
  • 251 Hartwig MG, Appel JZ, Davis RD. Antireflux surgery in the setting of lung transplantation: strategies for treating gastroesophageal reflux disease in a high-risk population. Thorac Surg Clin 2005; 15 (03) 417-427
  • 252 Hartwig MG, Anderson DJ, Onaitis MW. et al. Fundoplication after lung transplantation prevents the allograft dysfunction associated with reflux. Ann Thorac Surg 2011; 92 (02) 462-468 , 468–469
  • 253 Zhang CYK, Ahmed M, Huszti E. et al; CTOT-20 Investigators. Bronchoalveolar bile acid and inflammatory markers to identify high-risk lung transplant recipients with reflux and microaspiration. J Heart Lung Transplant 2020; 39 (09) 934-944
  • 254 Tangaroonsanti A, Lee AS, Crowell MD. et al. Impaired esophageal motility and clearance post-lung transplant: risk for chronic allograft failure. Clin Transl Gastroenterol 2017; 8 (06) e102
  • 255 Miele CH, Schwab K, Saggar R. et al. Lung transplant outcomes in systemic sclerosis with significant esophageal dysfunction. A comprehensive single-center experience. Ann Am Thorac Soc 2016; 13 (06) 793-802
  • 256 Hachem RR, Edwards LB, Yusen RD, Chakinala MM, Alexander Patterson G, Trulock EP. The impact of induction on survival after lung transplantation: an analysis of the International Society for Heart and Lung Transplantation Registry. Clin Transplant 2008; 22 (05) 603-608
  • 257 Hachem RR, Chakinala MM, Yusen RD. et al. A comparison of basiliximab and anti-thymocyte globulin as induction agents after lung transplantation. J Heart Lung Transplant 2005; 24 (09) 1320-1326
  • 258 Jaksch P, Ankersmit J, Scheed A. et al. Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study. Am J Transplant 2014; 14 (08) 1839-1845
  • 259 Shyu S, Dew MA, Pilewski JM. et al. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transplant 2011; 30 (07) 743-754
  • 260 Furuya Y, Jayarajan SN, Taghavi S. et al. The impact of alemtuzumab and basiliximab induction on patient survival and time to bronchiolitis obliterans syndrome in double lung transplantation recipients. Am J Transplant 2016; 16 (08) 2334-2341
  • 261 Penninga L, Møller CH, Penninga EI, Iversen M, Gluud C, Steinbrüchel DA. Antibody induction therapy for lung transplant recipients. Cochrane Database Syst Rev 2013; (11) CD008927
  • 262 Treede H, Glanville AR, Klepetko W. et al; European and Australian Investigators in Lung Transplantation. Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomized international trial in lung transplantation. J Heart Lung Transplant 2012; 31 (08) 797-804
  • 263 Hachem RR, Yusen RD, Chakinala MM. et al. A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation. J Heart Lung Transplant 2007; 26 (10) 1012-1018
  • 264 McNeil K, Glanville AR, Wahlers T. et al. Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients. Transplantation 2006; 81 (07) 998-1003
  • 265 Wijesinha M, Hirshon JM, Terrin M. et al. Survival associated with sirolimus plus tacrolimus maintenance without induction therapy compared with standard immunosuppression after lung transplant. JAMA Netw Open 2019; 2 (08) e1910297
  • 266 Ochman M, Wojarski J, Wiórek A. et al. Usefulness of the impulse oscillometry system in graft function monitoring in lung transplant recipients. Transplant Proc 2018; 50 (07) 2070-2074
  • 267 Cho E, Wu JKY, Birriel DC. et al. Airway oscillometry detects spirometric-silent episodes of acute cellular rejection. Am J Respir Crit Care Med 2020; 201 (12) 1536-1544
  • 268 Weigt SS, Wang X, Palchevskiy V. et al. Usefulness of gene expression profiling of bronchoalveolar lavage cells in acute lung allograft rejection. J Heart Lung Transplant 2019; 38 (08) 845-855
  • 269 Weigt SS, Wang X, Palchevskiy V. et al. Gene expression profiling of bronchoalveolar lavage cells preceding a clinical diagnosis of chronic lung allograft dysfunction. PLoS One 2017; 12 (01) e0169894
  • 270 Verleden SE, Ruttens D, Vandermeulen E. et al. Elevated bronchoalveolar lavage eosinophilia correlates with poor outcome after lung transplantation. Transplantation 2014; 97 (01) 83-89
  • 271 Horie M, Levy L, Houbois C. et al. Lung density analysis using quantitative chest CT for early prediction of chronic lung allograft dysfunction. Transplantation 2019; 103 (12) 2645-2653