Skip to main content

Advertisement

Log in

Chronic lung allograft dysfunction

  • Review Article
  • Published:
Indian Journal of Thoracic and Cardiovascular Surgery Aims and scope Submit manuscript
  • 5 Altmetric

Abstract

Lung transplantation remains the only cure for selected patients with advanced irreversible lung diseases. More than 4000 lung transplants are performed worldwide annually. In the last two decades, significant advances have been made in this arena, the most impactful being a modest but improved survival of the recipients. Unfortunately majority of recipients still succumb to chronic lung allograft dysfunction (CLAD), and it remains the most common cause of death after the first year of transplantation. Below is a concise review of the current definition of CLAD, including the various phenotypes, and a brief discussion of the tools available for its diagnosis and management.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Chambers DC, Cherikh WS, Harhay MO, et al. 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;38:1042–55.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Meyer KC, Raghu G, Verleden GM, et al. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014;44:1479–503.

    Article  PubMed  Google Scholar 

  3. Cooper JD, Billingham M, Egan T, 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;12:713–6.

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  Google Scholar 

  6. Verleden SE, Ruttens D, Vandermeulen E, et al. Restrictive chronic lung allograft dysfunction: where are we now? J Heart Lung Transplant. 2015;34:625–30.

  7. 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;38:493–503.

    Article  PubMed  Google Scholar 

  8. Suhling H, Dettmer S, Greer M, et al. Phenotyping chronic lung allograft dysfunction using body plethysmography and computed tomography. Am J Transplant. 2016;16:3163–70.

    Article  CAS  PubMed  Google Scholar 

  9. Levy L, Huszti E, Renaud-Picard B, et al. Risk assessment of chronic lung allograft dysfunction phenotypes: validation and proposed refinement of the 2019 International Society for Heart and Lung Transplantation classification system. J Heart Lung Transplant. 2020;39:761–70.

    Article  PubMed  Google Scholar 

  10. 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;12:745–52.

    Article  CAS  PubMed  Google Scholar 

  11. 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;13:919–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Palmer SM Jr, Henshaw NG, Howell DN, Miller SE, Davis RD, Tapson VF. Community respiratory viral infection in adult lung transplant recipients. Chest. 1998;113:944–50.

    Article  PubMed  Google Scholar 

  13. Hadjiliadis D, Duane Davis R, Steele MP, et al. Gastroesophageal reflux disease in lung transplant recipients. Clin Transplant. 2003;17:363–8.

    Article  PubMed  Google Scholar 

  14. Whitson BA, Prekker ME, Herrington CS, et al. Primary graft dysfunction and long-term pulmonary function after lung transplantation. J Heart Lung Transplant. 2007;26:1004–11.

    Article  PubMed  Google Scholar 

  15. Huang HJ, Yusen RD, Meyers BF, et al. Late primary graft dysfunction after lung transplantation and bronchiolitis obliterans syndrome. Am J Transplant. 2008;8:2454–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Verleden SE, Ruttens D, Vandermeulen E, et al. Elevated bronchoalveolar lavage eosinophilia correlates with poor outcome after lung transplantation. Transplantation. 2014;97:83–9.

    Article  PubMed  Google Scholar 

  17. Lee ES, Gotway MB, Reddy GP, Golden JA, Keith FM, Webb WR. Early bronchiolitis obliterans following lung transplantation: accuracy of expiratory thin-section CT for diagnosis. Radiology. 2000;216:472–7.

    Article  CAS  PubMed  Google Scholar 

  18. Leung AN, Fisher K, Valentine V, et al. Bronchiolitis obliterans after lung transplantation: detection using expiratory HRCT. Chest. 1998;113:365–70.

    Article  CAS  PubMed  Google Scholar 

  19. Verleden SE, de Jong PA, Ruttens D, et al. Functional and computed tomographic evolution and survival of restrictive allograft syndrome after lung transplantation. J Heart Lung Transplant. 2014;33:270–7.

    Article  PubMed  Google Scholar 

  20. Neurohr C, Huppmann P, Samweber B, et al. Prognostic value of bronchoalveolar lavage neutrophilia in stable lung transplant recipients. J Heart Lung Transplant. 2009;28:468–74.

    Article  PubMed  Google Scholar 

  21. Vandermeulen E, Verleden SE, Ruttens D, et al. BAL neutrophilia in azithromycin-treated lung transplant recipients: clinical significance. Transpl Immunol. 2015;33:37–44.

    Article  CAS  PubMed  Google Scholar 

  22. Ofek E, Sato M, Saito T, et al. Restrictive allograft syndrome post lung transplantation is characterized by pleuroparenchymal fibroelastosis. Mod Pathol. 2013;26:350–6.

    Article  CAS  PubMed  Google Scholar 

  23. Verleden SE, Todd JL, Sato M, et al. Impact of CLAD phenotype on survival after lung retransplantation: a multicenter study. Am J Transplant. 2015;15:2223–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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:e1910297.

    PubMed  Google Scholar 

  25. Cantu E 3rd, Appel JZ 3rd, 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;78:1142–51.

    Article  PubMed  Google Scholar 

  26. Li H, Zhou Y, Fan F, et al. Effect of azithromycin on patients with diffuse panbronchiolitis: retrospective study of 51 cases. Intern Med. 2011;50:1663–9.

    Article  CAS  PubMed  Google Scholar 

  27. Crosbie PAJ, Woodhead MA. Long-term macrolide therapy in chronic inflammatory airway diseases. Eur Respir J. 2009;33:171–81.

    Article  CAS  PubMed  Google Scholar 

  28. Ruttens D, Verleden SE, Vandermeulen E, et al. Prophylactic azithromycin therapy after lung transplantation: post hoc analysis of a randomized controlled trial. Am J Transplant. 2016;16:254–61.

    Article  CAS  PubMed  Google Scholar 

  29. 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;70:442–50.

    Article  PubMed  Google Scholar 

  30. Verleden GM, Verleden SE, Vos R, et al. Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a pilot study. Transpl Int. 2011;24:651–6.

    Article  PubMed  Google Scholar 

  31. Vos R, Eynde RV, Ruttens D, et al. Montelukast in chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant. 2019;38:516–27.

    Article  PubMed  Google Scholar 

  32. Ruttens D, Verleden SE, Demeyer H, et al. Montelukast for bronchiolitis obliterans syndrome after lung transplantation: A randomized controlled trial. PLoS One. 2018;13:e0193564.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. January SE, Fester KA, Bain KB, et al. Rabbit antithymocyte globulin for the treatment of chronic lung allograft dysfunction. Clin Transplant. 2019;33:e13708.

    Article  PubMed  Google Scholar 

  34. Pecoraro Y, Carillo C, Diso D, et al. Efficacy of extracorporeal photopheresis in patients with bronchiolitis obliterans syndrome after lung transplantation. Transplant Proc. 2017;49:695–8.

    Article  CAS  PubMed  Google Scholar 

  35. Verleden GM, Lievens Y, Dupont LJ, et al. Efficacy of total lymphoid irradiation in azithromycin nonresponsive chronic allograft rejection after lung transplantation. Transplant Proc. 2009;41:1816–20.

    Article  CAS  PubMed  Google Scholar 

  36. Fisher AJ, Rutherford RM, Bozzino J, Parry G, Dark JH, Corris PA. The safety and efficacy of total lymphoid irradiation in progressive bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2005;5:537–43.

    Article  PubMed  Google Scholar 

  37. Veit T, Leuschner G, Sisic A, et al. Pirfenidone exerts beneficial effects in patients with IPF undergoing single lung transplantation. Am J Transplant. 2019;19:2358–65.

    Article  CAS  PubMed  Google Scholar 

  38. Suhling H, Bollmann B, Gottlieb J. Nintedanib in restrictive chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transplant. 2016;35:939–40.

    Article  PubMed  Google Scholar 

  39. 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;103:2645–53.

    Article  PubMed  Google Scholar 

  40. Philippot Q, Debray M-P, Bun R, et al. Use of CT-SCAN score and volume measures to early identify restrictive allograft syndrome in single lung transplant recipients. J Heart Lung Transplant. 2020;39:125–33.

    Article  PubMed  Google Scholar 

  41. Verleden SE, Gheysens O, Goffin KE, et al. Role of 18F-FDG PET/CT in restrictive allograft syndrome after lung transplantation. Transplantation. 2019;103:823–31.

    Article  CAS  PubMed  Google Scholar 

  42. Golocheikine AS, Saini D, Ramachandran S, Trulock EP, Patterson A, Mohanakumar T. Soluble CD30 levels as a diagnostic marker for bronchiolitis obliterans syndrome following human lung transplantation. Transpl Immunol. 2008;18:260–3.

    Article  CAS  PubMed  Google Scholar 

  43. Agbor-Enoh S, Chan JL, Singh A, et al. Circulating cell-free DNA as a biomarker of tissue injury: assessment in a cardiac xenotransplantation model. J Heart Lung Transplant. 2018;37:967–75.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Neujahr DC, Perez SD, Mohammed A, et al. Cumulative exposure to gamma interferon-dependent chemokines CXCL9 and CXCL10 correlates with worse outcome after lung transplant. Am J Transplant. 2012;12:438–46.

    Article  CAS  PubMed  Google Scholar 

  45. Yang JYC, Verleden SE, Zarinsefat A, et al. Cell-Free DNA and CXCL10 derived from bronchoalveolar lavage predict lung transplant survival. J Clin Med. 2019;8:241. https://doi.org/10.3390/jcm8020241.

    Article  CAS  PubMed Central  Google Scholar 

  46. 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:e0180281.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Aramini B, Kim C, Diangelo S, et al. Donor surfactant protein D (SP-D) polymorphisms are associated with lung transplant outcome. Am J Transplant. 2013;13:2130–6.

    Article  CAS  PubMed  Google Scholar 

  48. D’Ovidio F, Kaneda H, Chaparro C, et al. Pilot study exploring lung allograft surfactant protein A (SP-A) expression in association with lung transplant outcome. Am J Transplant. 2013;13:2722–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anupam Kumar.

Ethics declarations

Ethics approval

Not applicable being a review article.

Informed consent

Not applicable.

Research involving human participants and/or animals

Not applicable as per institutional ethical committee as the scientific information presented in paper does not fall into category of clinical trial or usage of experimental modalities.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, A., Garcha, P.S. Chronic lung allograft dysfunction. Indian J Thorac Cardiovasc Surg 38 (Suppl 2), 318–325 (2022). https://doi.org/10.1007/s12055-021-01228-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12055-021-01228-8

Keywords

Navigation