Immunosuppression: Have We Learnt Anything?

Ramsey R. Hachem, MD


Semin Respir Crit Care Med. 2018;39(2):172-180. 

In This Article

Abstract and Introduction


Outcomes after lung transplantation remain disappointing because there is a high incidence of chronic lung allograft dysfunction (CLAD), which typically follows a progressive clinical course and often results in allograft failure and death. Chronic rejection is considered the predominant cause of CLAD. Thus, optimal immunosuppression has been viewed as having the potential to prevent CLAD and improve survival after lung transplantation. Numerous clinical trials have been conducted investigating the efficacy and safety of various immunosuppressive agents. Many studies have been small and single-center clinical trials but some have been international and multicenter trials enrolling more than 300 patients. This review focuses on clinical trials of immunosuppression conducted in lung transplantation and points out strengths and limitations of the various studies. Ultimately, the findings of these clinical trials explain the current state of practice in lung transplantation and identify gaps in knowledge that require additional study. Finally, there is an ongoing need for carefully designed and conducted clinical trials to improve clinical practice and outcomes after lung transplantation.


Lung transplantation is the ultimate treatment for patients with end-stage lung disease. However, outcomes after transplantation remain disappointing, and the median survival in the latest International Society for Heart and Lung Transplantation (ISHLT) Registry Report was 5.8 years.[1] Graft failure and infections are the leading causes of death in the first year after transplantation, but bronchiolitis obliterans syndrome (BOS) and late graft failure are the primary causes of death beyond the first year after transplantation accounting for 40 to 50% of deaths.[1] In the Registry Report, late graft failure is undoubtedly a form of chronic lung allograft dysfunction (CLAD). Furthermore, the median survival after the diagnosis of CLAD is approximately 2.5 years, and recipients who develop CLAD have worse quality of life compared with those who do not.[2–4] Thus, CLAD has emerged as the primary obstacle to better long-term outcomes after lung transplantation. Although the pathogenesis of CLAD has yet to be elucidated, clinical risk factors have been identified. These include acute cellular rejection, lymphocytic bronchiolitis, antibody-mediated rejection, the development of donor-specific antibodies to mismatched donor-recipient human leukocyte antigens (HLA), primary graft dysfunction, community-acquired respiratory viral infections, and gastroesophageal reflux disease.[5–18] As various forms of rejection have consistently been strong risk factors for CLAD, the lung transplant community has focused on immunosuppressive therapy to prevent or delay the onset of CLAD with the hope of improving survival and quality of life. This article will review the literature of clinical trials examining the efficacy and safety of induction and maintenance immunosuppression after lung transplantation.