重症慢性呼吸道疾病合并侵袭性肺曲霉病的临床特点

Clinical features of invasive pulmonary aspergillosis in critically ill patients with chronic respiratory diseases

目的总结重症慢性呼吸道疾病（CRD）合并侵袭性肺曲霉病（IPA）的临床特点，为早期诊断和治疗提供依据。方法分析2004年10月至2007年2月在北京朝阳医院呼吸科重症监护室（RICU）住院的149例痰或BALF分离出曲霉的CRD患者资料。以SPSS10．0统计软件进行数据处理，所有计量资料以均数±标准差表示，计数资料以例数表示。计量资料采用t检验，计数资料采用χ^2检验。结果149例CRD患者中共收集16例IPA病例（COPD1 1例，COPD合并支气管哮喘4例，支气管扩张症1例），其中3例确诊，10例临床诊断，3例拟诊。12例在人RICU前使用过大量糖皮质激素，15例使用广谱抗生素。15例临床表现为严重气道痉挛，9例行无创通气失败，14例因严重呼吸衰竭而需有创机械通气。12例X线胸片可见明显渗出影。外周血白细胞及中性粒细胞比例在疾病后期迅速增高；早期气管镜检查可见气道黏膜充血、水肿、糜烂，气道痉挛，痰液黏稠，后期气道黏膜可出现伪膜；早期真菌病原学检查阳性率低（2／12），后期阳性率高（10／12）；早期治疗的患者存活率高（4／4），晚期治疗效果差（11／12），由呼吸衰竭迅速进展为多脏器衰竭是最主要的死亡原因。结论CRD合并IPA并不少见，预后差。根据临床特点进行早期诊断及经验性治疗可改善患者的预后。

Objective To describe the clinical features of invasive pulmonary aspergillosis （IPA） in critically ill patients with chronic respiratory diseases （CRD） and to estimate its value for early diagnosis and treatment. Methods Retrospective study of critically ill CRD patients with positive Aspergillus from sputum or bronchial alveolar lavage fluid in a respiratory ICU of a teaching hospital. Results There were 149 CRD patients admitted between October 2004 and February 2007. Among these patients, 16 cases of IPA （ 11 COPD ,4 COPD with asthma, 1 bronchiectasis ） were collected. Three cases fulfilled the criteria of proven IPA, 10 of probable and 3 of possible IPA. Corticosteroids and multiple broad-spectrum antibiotics had been administered to 12 and 15 patients respectively. Fifteen patients experienced worsening of bronchospasm leading to acute respiratory failure. Nine patients failed to improve on noninvasive ventilation, and 14 patients required invasive ventilation. Twelve patients had infiltrates on chest X-ray. Before the appearance of infiltrates, bronchoscopy showed tracheobronchial inflammatory changes with severe bronchospasm. With the rapid progression of infiltrates, bronchial pseudomembrane was observed, with increased white blood cell count and exacerbated radiology findings. The rate of positive isolation of Aspergillus from airway samples during early stage was lower than late stage （2/12 vs 10/12 ）. Early treatment was started before the appearance of infiltrates in 4 patients, all of whom survived. Although antifungal treatment was started when IPA was suspected after the appearance of infiltrates, 11 of 12 patients died in septic shock or multiple-organ failure. Conclusions IPA occurring in critically ill CRD patients is not rare and has a poor prognosis. Early diagnosis and empirical antifungal treatment based on certain clinical features may improve the outcome.