Horita Nobuyuki, Akahane Makiko, Okada Yukinori, Kobayashi Yosuke, Arai Takahiko, Amano Izuki, Takezawa Tomoko, To Masako, To Yasuo
Department of Allergy and Respiratory Medicine, The Fraternity Memorial Hospital, Japan.
Intern Med. 2011;50(3):189-95. doi: 10.2169/internalmedicine.50.4327. Epub 2011 Feb 1.
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) occurs during the chronic progressive course of idiopathic pulmonary fibrosis. Mortality is estimated to be >70%, because no effective treatment has been established. We evaluated the effectiveness of combination therapy of tacrolimus and methylprednisolone for AE-IPF.
Patients of AE-IPF treated with methylprednisolone pulse therapy with or without tacrolimus (targeting 20 ng/mL) during the period between January 2001 and April 2010 were retrospectively reviewed. The primary endpoints were survival rate and duration. We also observed lactate dehydrogenase levels, partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio), KL-6, occurrence of re-exacerbation, and computed tomography score.
Fifteen Japanese patients [tacrolimus group aged 74.2±6.0 years old (n=5), non-tacrolimus group aged 75.1±12.8 years old (n=10)] were identified. Pre-treatment clinical parameters were not significantly different between the two groups. Four of 5 tacrolimus group patients and 1 of 10 non-tacrolimus group patients survived (p<0.05). The median survival durations were >92 days (tacrolimus group) and 38 days (non-tacrolimus group) (p<0.05). Lactate dehydrogenase levels and the P/F ratio were also significantly favorable in the tacrolimus group. KL-6 and CT score were not significantly different in both groups. Four re-acute exacerbations were observed only in the non-tacrolimus group.
Combined tacrolimus and methylprednisolone pulse therapy mitigates AE-IPF, prevents re-acute exacerbation, and contributes to a better prognosis.
特发性肺纤维化急性加重（AE-IPF）发生于特发性肺纤维化的慢性进展过程中。由于尚未确立有效的治疗方法，据估计死亡率>70%。我们评估了他克莫司与甲泼尼龙联合治疗AE-IPF的有效性。
回顾性分析2001年1月至2010年4月期间接受甲泼尼龙冲击治疗且联合或不联合他克莫司（目标浓度20 ng/mL）的AE-IPF患者。主要终点为生存率和生存时间。我们还观察了乳酸脱氢酶水平、动脉血氧分压/吸入氧分数比（P/F比）、KL-6、再次加重的发生情况以及计算机断层扫描评分。
确定了15例日本患者[他克莫司组74.2±6.0岁（n = 5），非他克莫司组75.1±12.8岁（n = 10）]。两组治疗前的临床参数无显著差异。他克莫司组5例患者中有4例存活，非他克莫司组10例患者中有1例存活（p<0.05）。中位生存时间分别为>92天（他克莫司组）和38天（非他克莫司组）（p<0.05）。他克莫司组的乳酸脱氢酶水平和P/F比也明显更优。两组的KL-6和CT评分无显著差异。仅在非他克莫司组观察到4次再次急性加重。
他克莫司与甲泼尼龙联合冲击治疗可减轻AE-IPF，预防再次急性加重，并有助于改善预后。
