中国HIV阴性宿主肺隐球菌病前瞻性多中心临床研究

A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China

目的了解我国呼吸学科肺隐球菌病的诊疗现状,完善对HIV阴性肺隐球菌病临床特征的认识。方法采用前瞻性、多中心、开放性队列研究设计,通过涂片培养、抗原检测及组织病理学检查等病原学诊断方法,在22家参研单位呼吸科普通病房和呼吸重症监护室筛检肺隐球菌病,连续纳入研究期间收治的所有HIV阴性肺隐球菌病病例,采集并分析主要临床资料。结果共入选肺隐球菌病患者457例,其中播散性感染占3.28%(15/457),病死率0.88%(4/457),主要的诊断依据为组织标本病理检查的阳性结果(74.40%,340/457)和隐球菌抗原检测的阳性结果(37.64%,172/457)。肺隐球菌病占同时期呼吸科住院患者总人数的2.04‰(457/223 748),华南地区、华东地区该比例最高;70.24%(321/457)的患者不合并任何基础疾病,87.75%(401/457)的患者无已知免疫缺陷;咳嗽、咳痰为最常见的临床症状,25.16%(115/457)的患者无任何临床症状和体征。在影像表现方面,肺内多发病变多于孤立病变,胸膜下病变多于肺门周围或内中带病变,形态上则以直径1~5 cm的中等大小结节和直径3 mm~1 cm的小结节最为常见。血清隐球菌抗原的敏感率为71.99%(203/282), 抗原阳性患者在基础免疫状态、临床症状、影像学表现以及感染类型等方面均有别于抗原阴性患者。免疫缺陷患者在临床症状和体征、感染相关炎症指标水平、影像学特点、血清隐球菌抗原阳性率以及预后等方面有别于非免疫缺陷患者。结论我国HIV阴性肺隐球菌病多数无合并基础疾病或免疫缺陷,总体预后良好,但临床类型多样,临床表现和影像表现复杂多变,早期诊断难度较大。

Objective To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China.Methods A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals.The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture,antigen detection and histopathology were enrolled in the study.The clinical data of enrolled patients were collected and analyzed.Results A total of 457 cases of pulmonary cryptococcosis were enrolled,among which 3.28%(15/457)were disseminated infections.The case fatality rate was 0.88%(4/457).The majority of the cases were diagnosed by histopathological examinations(74.40%,340/457)and cryptococcus antigen detection(37.64%,172/457).Patients with pulmonary cryptococcosis accounted for 2.04‰(457/223748)of the total hospitalized patients in the Department of Respiratory Diseases during the same period,and the ratio was the highest in south and east China.Meanwhile,70.24%(321/457)of the patients had no underlying diseases,while 87.75%(401/457)were found to have immunocompetent status.Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis.However,25.16%(115/457)of the patients had no clinical symptom or physical signs.In terms of imaging features on pulmonary CT,multiple pulmonary lesions were more common than isolated lesions,and there were more subpleural lesions than perihilar or medial lesions.Morphologically,most of the lesions were middle-sized nodules(1-5 cm)or small-sized nodules(3 mm to 1 cm).The sensitivity of serum cryptococcus antigen test was 71.99%(203/282).Moreover,antigen-positive patients differed from antigen-negative patients in terms of basic immune status,clinical symptoms,imaging features and infection types.Meanwhile,immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms,physical signs,infection-related inflammation indicator levels,imaging features,serum cryptococcus antigen positive rate and prognosis.Conclusions The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status,and the overrall prognosis was favorable.However,early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.