摘要目的 探讨程序性死亡蛋白-1及其配体(PD-1/PD-L1)抑制剂致免疫相关肺炎的高危因素、临床表现、影像学特征、诊断、治疗和预后.方法 回顾性分析军事科学院附属医院收治的1例晚期食管癌患者使用PD-1抑制剂Pembrolizumab所致免疫相关肺炎的临床资料并对相关文献进行复习.以“PD-1 inhibitor、PD-L1 inhibitor、Pembrolizumab、Nivolumab、Atezolizumab”联合“Pneumonitis”为检索词检索Medline数据库,检索时间截止到2017年3月31日.结果 患者男,60岁,食管癌术后,局部辅助放、化疗后复发,给予多疗程化疗病情仍进展,给予Pembrolizumab(3 mg/kg,静脉注射,每3周1次)治疗6个周期后,患者出现发热,咳嗽、气短,症状进行性加重.胸部CT显示:双肺弥漫磨玻璃、渗出实变影伴右侧胸腔积液.病理示细胞性间质性肺炎.给予足量激素治疗后症状控制,CT提示病变吸收,激素快速减停以及减量中,2次肺炎复发,恢复足量激素病情可再度控制,目前激素维持治疗,原发病维持稳定.在Medline数据库中共检索到14篇文献共88例免疫相关肺炎病例,加上本例,共89例.PD-1/PD-L1抑制剂所致免疫相关肺炎,男、女均可发病;中位年龄67岁;以1～2级多见,最常见临床表现为气短、咳嗽、发热及其他免疫相关损伤,约20％患者可无任何症状;最常见影像学表现为磨玻璃影、网格状影、实变及小叶中心型结节;最常见病理类型为机化性肺炎;治疗方面可予足量激素治疗后缓慢规律减量,重症患者可联合免疫抑制剂;预后较好,大部分患者能完全缓解,少部分死于疾病进展或治疗过程中合并的感染.结论 需要提高对PD-1/PD-L1抑制剂所致免疫相关肺炎的认识,及早发现,及时处理,预后相对良好.

abstractsObjective To investigate the risk factors,clinical manifestations,radiological features,diagnosis,treatment and prognosis of immune-related pneumonitis caused by programmed death-1 (PD-1)/ PD-L1 inhibitors.Methods The clinical data of immune-related pneumonitis caused by PD-1 inhibitor Pembrolizumab in a patient with advanced esophageal carcinoma admitted to the 307th Hospital of Chinese People's Liberation Army was retrospectively analyzed and the related literatures were reviewed.We searched Medline database using the keywords "PD-1 inhibitor","PD-L1 inhibitor","Pembrolizumab","Nivolumab","Atezolizumab" combined with "Pneumonitis" by Mar 31,2017.Results The patient was a 60-year-old male presented with progression disease after surgery,local radiation and couples of chemotherapy for his esophageal carcinoma.Then pembrolizumab,a kind of PD-l inhibitors,was given intravenously every 3 weeks with the average dosage 3 mg per kg.After six cycles of pembrolizumab,the patient began to have fever,cough and dyspnea,which aggravated gradually.Chest CT showed diffuse ground glass opacity,exudation and consolidation in both lungs and little pleural effusion in the right side.Cellular interstitial pneumonitis was confirmed by pathological examination.The patient's symptoms were alleviated after enough steroids and chest CT showed pulmonary infiltration was also absorbed.But the pneumonitis reoccurred twice after stopping or tapering steroids quickly and could also be controlled by using steroids again.Now the patient was still given steroids treatment and the primary esophageal cancer remained stable.14 articles were retrieved and 88 cases of immune-related pneumonitis caused by PD-1/PD-L1 inhibitors were reported.Among these 89 cases with immune-related pneumonitis,both male and female could attack and the median age was 67 years old.Most cases were grade 1 or 2.The common clinical manifestations were dyspnea,cough,fever and other immune-related damages.And about 20％ patients had no symptoms.Ground glass opacities,reticular opacities,consolidation and centrilobular nodules were the common radiological features.The commonest histologic pattern of pneumonitis associated with anti-PD-1/PD-L1 therapy on lung biopsy was organizing pneumonia.Adequate steroid and tapering slowly is the standard treatment.Immunosuppressive agents could be added in some serious cases.The prognosis was relatively good.Most patients were alleviated but few patients died of progression disease or infections during treatment.Conclusions Immune-related pneumonitis associated with PD-I/PD-L1 inhibitor should be aware of;early detection,early treatment,and the prognosis could be better.