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Current and prospective treatments of obliterative bronchiolitis

Sixteen years after its first description, obliterative bronchiolitis (OB) remains the dominant cause of morbidity and mortality in long-term survivors of lung transplantation. Current preventative and therapeutic strategies focus on risk factor identification and management. Acute pulmonary allograft rejection has been identified as the major risk factor for the development of OB, but to date, only one adequately powered multicenter, randomized trial has been initiated to investigate the role of alternative immunosuppressive agents in preventing OB. A further two trials are planned to commence in the latter half of 2000. When mature data from these three trials are available, the respective roles of mycophenolate mofetil, tacrolimus and rapamycin should be clarified. Similarly, only one multicenter, international, randomized placebo–controlled trial for the prevention of OB in high-risk patients and one randomized study into the efficacy of therapy for established bronchiolitis obliterans syndrome have commenced. Both of these studies employ RAD (rapamycin derivative, Novartis Pharmaceuticals, Basel, Switzerland). Single-center studies have examined the utility of tacrolimus-mycophenolate-methotrexate-cyclophosphamide-cytolytic therapy with muromonab-CD3 (OKT3) or antithymocyte globulin (ATG), photopheresis, plasmapheresis, and total lymphoid irradiation. The multiplicity of agents tried underscores their lack of universal efficacy, and speaks strongly in favor of adequately powered trials to guide management. Retransplantation remains the only cure for established, severe OB.