Novelli Luca, Ruggiero Roberto, De Giacomi Federica, Biffi Alice, Faverio Paola, Bilucaglia Luca, Gamberini Silvia, Messinesi Grazia, Pesci Alberto
.
Sarcoidosis Vasc Diffuse Lung Dis. 2016 Dec 23;33(4):385-391.
Acute Exacerbation (AEx) is a frequent and severe complication of Idiopathic Pulmonary Fibrosis (IPF). In the absence of consensus regarding treatment, studies evaluating the efficacy of specific therapies, such as corticosteroids and immunosuppresant agents, are needed. In this case series we evaluated the outcome in terms of survival of intravenous pulse doses of high-dose corticosteroid (methylprednisolone 1000 mg per day for 3 consecutive days) followed by montlhy cyclophosphamide administration (maximum 6 doses) in a cohort of patients with AEx-IPF referred to the Respiratory Unit, San Gerardo University Hospital, Monza, Italy, from 2009 to 2013. A total of 11 patients (7 males, median age 65 years) were enrolled. A median of five monthly pulse doses of cyclophosphamide were administered, with four patients receiving all 6 doses. Four patients died before completion. Three patients developed adverse events. Overall survival at 3 months was 73%, at 6 months 63%, at 12 months 55%, at 18 months 45% and at 2 years 27%. In-hospital mortality was 9%. Causes of death were: six respiratory failures from disease progression, one lung cancer and one breast cancer. Two patients received lung transplantation and were excluded from the Kaplan-Meier analysis. In conclusion, combined intravenous pulse doses of high-dose corticosteroid and cyclophosphamide could be a reasonable add-on therapy for AEx-IPF, considering the few side effects and safe profile. A complete and rapid diagnostic work-up associated to the proper management (e.g. support of respiratory failure with non-invasive ventilation) in the right setting, may also have a positive effect on patients' outcome.
急性加重期（AEx）是特发性肺纤维化（IPF）常见且严重的并发症。在治疗方面缺乏共识的情况下，需要开展研究评估特定疗法（如皮质类固醇和免疫抑制剂）的疗效。在本病例系列中，我们评估了2009年至2013年期间转诊至意大利蒙扎圣杰拉尔多大学医院呼吸科的一组急性加重期特发性肺纤维化（AEx-IPF）患者静脉注射大剂量皮质类固醇脉冲剂量（甲基强的松龙每天1000毫克，连续3天），随后每月给予环磷酰胺（最大6剂）后的生存结局。共纳入11例患者（7例男性，中位年龄65岁）。环磷酰胺的脉冲剂量中位数为每月5剂，4例患者接受了全部6剂。4例患者在疗程结束前死亡。3例患者出现不良事件。3个月时的总生存率为73%，6个月时为63%，12个月时为55%，18个月时为45%，2年时为27%。住院死亡率为9%。死亡原因包括：6例因疾病进展导致呼吸衰竭，1例肺癌和1例乳腺癌。2例患者接受了肺移植，被排除在Kaplan-Meier分析之外。总之，考虑到副作用较少且安全性良好，静脉注射大剂量皮质类固醇和环磷酰胺联合脉冲剂量可能是AEx-IPF合理的附加治疗方法。在合适的环境中进行完整、快速的诊断检查并进行适当管理（如使用无创通气支持呼吸衰竭），也可能对患者的预后产生积极影响。
