免疫检查点抑制剂相关肺炎22例临床特征分析

Clinical characteristics of immune checkpoint inhibitor⁃related pneumonitis in a 22⁃case series

目的:探讨免疫检查点抑制剂相关性肺炎(CIP)的临床特点、影像学、实验室检查及治疗策略。方法:回顾性分析我院22例CIP的诊治过程,记录患者用药史、临床表现、实验室检查、胸部CT表现和治疗及预后情况。结果:22例患者中男性14例,女性8例,年龄(57.09±12.52)岁。合并肺部基础疾病史的有3(13.6%)例。有吸烟史6(27.3%)例。22例发病前均使用了程序性死亡受体1(PD⁃1)抑制剂治疗,但仅2(9.1%)例为单药PD⁃1治疗,其余合并放疗或化疗或靶向药物治疗。主要症状:干咳11(50%)例、咳嗽咳痰5(22.7%)例、乏力8(36.4%)例、发热7(31.8%)例、呼吸困难7(31.8%)例、胸痛1(4.5%)例。实验室检查中白细胞总数(7.9±6.2)∗10^(9)/L,淋巴细胞绝对值下降比例高17(77.3%),常伴有轻中重度贫血18(81.9%)例及血小板下降10(45.5%)例。合并低蛋白血症比例高达94.7%(18/19)。18例患者中分别有9(50%)例、8(44.4%)例合并肌酸激酶及乳酸脱氢酶升高。胸部CT最常见的是双肺弥漫性磨玻璃影10(45.5%)例及网格状间质性肺炎9(41.0%)例的改变。13(59.1%)例患者静脉滴注全身糖皮质激素(1-2 mg/kg·d),3(13.6%)例需要机械辅助通气。17(77.3%)例治疗后好转,2例病情进展,2例死亡,其中1例为再次重启免疫治疗。1例放弃治疗。结论:CIP临床表现缺乏特异性,主要症状为咳嗽、呼吸困难、乏力。胸部CT表现多样,以多发弥漫性磨玻璃影及间质性改变常见,治疗以糖皮质激素为主,预后差,发生CIP后再次重启免疫治疗死亡率高。

Objective:To investigate the clinical characteristics,imaging findings,laboratory testing and treatment strategies of immune checkpoint inhibitor⁃related pneumonitis(CIP).Methods:The diagnosis and treatment process of 22 CIP patients admitted to our hospital were retrospectively analyzed.The patients’medication history,clinical manifestations,laboratory testing,chest CT manifestations,treatment and prognosis were recorded.Results:Among the 22 patients,there were 14 males and 8 females,with a mean age of(57.09±12.52)years old.Three patients(13.6%)had a history of underlying pulmonary diseases,and 6(27.3%)had smoking history.Twenty⁃two patients were treated with programmed death receptor⁃1(PD⁃1)inhibitor before onset of CIP,but only 2(9.1%)were treated with PD⁃1 alone,and the rest were treated with PD⁃1 plus radiotherapy/chemotherapy or targeted therapy.The clinical manifestations were non⁃productive cough(n=11,50%),productive cough(n=5,22.7%),fatigue(n=8,36.4%),fever(n=7,31.8%),dyspnea(n=7,31.8%)and chest pain(n=1,4.5%).In the laboratory testing,the total number of white blood cells were(7.9±6.2)∗10^(9)/L;there was a high proportion of cases with declined absolute value of lymphocytes(n=17,77.3%);comorbidity with varying severity of anemia(n=18,81.9%)and thrombocytopenia(n=10,45.5%);comorbidity with hypoproteinemia was found in as high as 94.7%(18/19)of all patients.Among the 18 patients,9(50%)and 8(44.4%)were complicated with elevated creatine kinase and lactate dehydrogenase,respectively.The most common chest CT findings were bilateral diffuse ground⁃glass opacity in 10(45.5%)cases and grid⁃like interstitial pneumonia in 9(41.0%)cases.Thirteen(59.1%)patients received intravenous infusion of systemic glucocorticoids(1-2 mg/kg·d),and 3(13.6%)required mechanically assisted ventilation.Seventeen(77.3%)patients showed improvement after treatment,2 showed disease progression,2 died(including 1 on repeat immunotherapy after CIP),and 1 abandoned treatment.Conclusion:The clinical manifestations of CIP lack specificity,and are largely presented by cough,dyspnea and fatigue.Chest CT may show diverse findings which frequently include multiple diffuse ground⁃glass opacities and interstitial changes.The treatment relies heavily on glucocorticoid therapy but with poor prognosis.The mortality remains high with repeat immunotherapy after onset of CIP.