Rodríguez-Moreno A, Ridao N, García-Ledesma P, Calvo N, Pérez-Flores I, Marques M, Barrientos A, Sánchez-Fructuoso A I
Department of Nephrology, Hospital Clínico San Carlos, Madrid, Spain.
Transplant Proc. 2009 Jul-Aug;41(6):2163-5. doi: 10.1016/j.transproceed.2009.06.003.
Mammalian target of rapamycin (mTOR) inhibitors induce pneumonitis, an unusual but potentially fatal side effect of this drug group. We retrospectively collected the cases of pneumonitis induced by sirolimus or everolimus among 1471 adult cadaveric renal transplant recipients who were grafted at our institution from 1980-2008. Due to chronic transplant dysfunction or tumor, 205 patients were switched from calcineurin inhibitors to sirolimus (n = 88) or to everolimus (n = 117). Six patients (2.9%) developed pneumonitis: 1 was associated with sirolimus and 5 with everolimus (5 males and 1 female; median age, 60 years [range, 47-73 years]). Median times from conversion to pneumonitis onset were 34 days in 4 patients (range, 24-46 days) and 491 days in 2 subjects (range, 454-528 days). The mean drug trough level at presentation was 8.2 microg/L (range, 5.5-13.8 microg/L). The most common symptoms were dry cough (n = 6), fever (n = 5), and dyspnea (n = 4). Imaging tests revealed lower lobe involvement in all patients. Bronchoalveolar lavage performed in 4 patients showed lymphocytic alveolitis. All patients completely recovered after drug withdrawal. Five patients received steroids, 5 were switched to a calcineurin inhibitor, and 1 was switched to the other mTOR inhibitor. In conclusion, mTOR inhibitor-associated pneumonitis is a rare disease. Sirolimus did not cause more cases of pneumonitis than everolimus. Pneumonitis development was not dependent upon the drug blood level. Lower lobe involvement and lymphocytic alveolitis were usually present. Discontinuation of the mTOR inhibitor with steroid prescription resulted in adequate outcomes. A change to the other mTOR inhibitor should be contemplated if patient circumstances require this type of immunosuppression.
雷帕霉素哺乳动物靶点（mTOR）抑制剂可引发肺炎，这是该类药物一种不常见但可能致命的副作用。我们回顾性收集了1980年至2008年在我院接受移植的1471例成年尸体肾移植受者中由西罗莫司或依维莫司诱发肺炎的病例。由于慢性移植功能障碍或肿瘤，205例患者从钙调神经磷酸酶抑制剂转换为西罗莫司（n = 88）或依维莫司（n = 117）。6例患者（2.9%）发生肺炎：1例与西罗莫司有关，5例与依维莫司有关（5例男性和1例女性；中位年龄60岁[范围47 - 73岁]）。从转换用药到肺炎发作的中位时间，4例患者为34天（范围24 - 46天），2例患者为491天（范围454 - 528天）。出现症状时的平均药物谷浓度为8.2μg/L（范围5.5 - 13.8μg/L）。最常见的症状为干咳（n = 6）、发热（n = 5）和呼吸困难（n = 4）。影像学检查显示所有患者下叶均受累。4例患者进行的支气管肺泡灌洗显示淋巴细胞性肺泡炎。所有患者停药后均完全康复。5例患者接受了类固醇治疗，5例转换为钙调神经磷酸酶抑制剂，1例转换为另一种mTOR抑制剂。总之，mTOR抑制剂相关肺炎是一种罕见疾病。西罗莫司引发肺炎的病例数并不比依维莫司多。肺炎的发生不依赖于药物血药浓度。通常存在下叶受累和淋巴细胞性肺泡炎。停用mTOR抑制剂并开具类固醇可取得良好疗效。如果患者情况需要这种类型的免疫抑制，应考虑换用另一种mTOR抑制剂。
