Seminars in respiratory and critical care medicine
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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.
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Semin Respir Crit Care Med · Jun 2013
ReviewLung transplantation for cystic fibrosis and bronchiectasis.
Lung transplantation has become an excellent treatment option for patients with cystic fibrosis (CF) and bronchiectasis with very advanced lung disease. Despite the challenges that the CF patients present, survival is more favorable than that seen in patients with chronic obstructive pulmonary disease and pulmonary fibrosis. Although those CF and bronchiectasis patients with severe respiratory disease are often infected with organisms that display in vitro resistance to the commonly used antibiotics, they usually have successful outcomes with transplantation, which are reported to be the same as in those patients with less resistant bacteria. ⋯ Efforts to increase the donor pool, such as low tidal volume ventilation, are effective in allowing a greater percentage of offered organs to be accepted. Perhaps the most encouraging development, however, is that of ex vivo lung perfusion. This permits not only the ability to measure the function of the lungs, something of great value for lungs from donors with circulatory death (donation after cardiac death), but also the potential to introduce lung repair and convert a nonusable lung to one that can be safely used for transplantation.