Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Jun 2013
ReviewAcute cellular and antibody-mediated allograft rejection.
Survival post-lung transplantation remains limited to ∼ 50% at 5 years, far below survival after other solid organ transplants. Allograft rejection is a major cause of this limited survival. At least a third of lung transplant recipients experience acute rejection within 1 year posttransplantation. ⋯ Emerging data on the importance of donor-specific and non-donor-specific anti-human leukocyte antigen (anti-HLA) antibodies as well as non-HLA antibodies are presented. Larger cohorts have improved statistical analyses in recent years, leading to a clearer understanding of important topics related to ACR and AMR. Further collaborative studies and multicenter trials will be key in further advancing lung transplantation knowledge and improving outcomes in years to come.
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Semin Respir Crit Care Med · Jun 2013
Lung transplantation for interstitial lung diseases and pulmonary hypertension.
Lung transplantation (LTx) is an established therapeutic option for patients with various end-stage lung diseases. Presently the worldwide procedural frequency is ∼ 3,200 per year. Unfortunately, the shortage of donor organs leads to approximately every sixth patient in Western countries dying before a donor organ is available. ⋯ However, there are several challenges for lung transplantation. The number of lung transplantations performed is limited by the supply of donor organs, and the long-term survival rates are still inferior compared with other forms of solid organ transplantation. Nevertheless, LTx offers a survival benefit in carefully selected patients with interstitial lung diseases and pulmonary hypertension.
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Chronic obstructive pulmonary disease (COPD) represents one of the most common indications for lung transplantation, accounting for approximately one third of all procedures performed worldwide to date. Despite this extensive experience, questions remain about the appropriate timing of transplantation in the natural history of COPD, the optimal procedure to perform, and the survival benefit achieved. ⋯ Like COPD, the application of transplantation to these rare disorders also poses several questions. This article explores issues that arise when lung transplantation is utilized for treatment of both common and uncommon obstructive lung disorders.
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Lung transplantation is the ultimate treatment option for patients with end-stage lung disease. Chronic rejection, in the form of bronchiolitis obliterans syndrome, and noncytomegalovirus infections are the major causes of morbidity and mortality beyond the first year after transplantation. Most lung transplant recipients are treated lifelong with a three-drug immunosuppression regimen consisting of a calcineurin inhibitor, an antimetabolite, and low-dose corticosteroids. ⋯ Additionally, the role of mammalian target of rapamycin (mTOR) inhibitors in the treatment of lung transplant recipients and the utility of azithromycin to treat and prevent bronchiolitis obliterans syndrome are areas of active investigation. This review discusses induction and traditional maintenance immunosuppressive agents and regimens and the evidence that exists to help guide therapy. Newer research involving the use of mTOR inhibitors in place of calcineurin inhibitors or antimetabolites and azithromycin for the treatment and prevention of bronchiolitis obliterans syndrome is also explored.
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Fungal infections continue to produce morbidity and mortality in lung transplant recipients despite the widespread use of antifungal prophylaxis. There has been a decline in Candida infections but Aspergillus species predominate. Other mold pathogens including Fusarium, Scedosporium, and Zygomycetes also cause infections in lung transplant recipients. ⋯ Most lung transplant centers use either voriconazole or inhaled amphotericin preparations. However, data have emerged regarding the increased risk of squamous cell cancer in lung transplant recipients on voriconazole prophylaxis. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in a significant decrease in mortality.