Seo Sachiko, Renaud Christian, Kuypers Jane M, Chiu Charles Y, Huang Meei-Li, Samayoa Erik, Xie Hu, Yu Guixia, Fisher Cynthia E, Gooley Ted A, Miller Steven, Hackman Robert C, Myerson David, Sedlak Ruth H, Kim Yae-Jean, Fukuda Takahiro, Fredricks David N, Madtes David K, Jerome Keith R, Boeckh Michael
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
Department of Microbiology and Immunology, University of Montreal, Montreal, Canada;
Blood. 2015 Jun 11;125(24):3789-97. doi: 10.1182/blood-2014-12-617035. Epub 2015 Apr 27.
Newer diagnostic methods may link more idiopathic pneumonia syndrome (IPS) cases to an infectious agent. Bronchoalveolar lavage (BAL) samples from 69 hematopoietic cell transplant (HCT) recipients with IPS diagnosed between 1992 and 2006 were tested for 28 pathogens (3 bacteria and 25 viruses) by quantitative polymerase chain reaction and for Aspergillus by galactomannan assay. Research BALs from 21 asymptomatic HCT patients served as controls. Among 69 HCT patients with IPS, 39 (56.5%) had a pathogen detected. The most frequent pathogens were human herpesvirus-6 (HHV-6) (N = 20 [29%]) followed by human rhinovirus (HRV), cytomegalovirus (CMV), and Aspergillus (N = 8 [12%] in each). HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P = .03). Mortality in patients with only pathogens of "uncertain" significance in lung was similar to that in patients with pathogens of "established" significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia.
更新的诊断方法可能会将更多特发性肺炎综合征（IPS）病例与感染源联系起来。对1992年至2006年间诊断为IPS的69例造血细胞移植（HCT）受者的支气管肺泡灌洗（BAL）样本进行检测，通过定量聚合酶链反应检测28种病原体（3种细菌和25种病毒），并通过半乳甘露聚糖测定法检测曲霉菌。来自21例无症状HCT患者的研究性BAL样本作为对照。在69例患有IPS的HCT患者中，39例（56.5%）检测到病原体。最常见的病原体是人类疱疹病毒6型（HHV-6）（n = 20 [29%]），其次是人类鼻病毒（HRV）、巨细胞病毒（CMV）和曲霉菌（各n = 8 [12%]）。对照组中很少检测到HHV-6和HRV，而CMV和曲霉菌偶尔检测到且病原体载量较低。有病原体的患者第100天生存率比没有病原体的患者差（风险比，1.88；P = 0.03）。肺部仅存在“意义不确定”病原体的患者死亡率与存在“已明确”意义病原体的患者相似。宏基因组下一代测序未发现其他重要病原体。我们的研究表明，约一半的IPS患者BAL中检测到病原体，病原体检测与死亡率增加相关。因此，扩大感染检测范围可显著提高特发性肺炎的诊断准确性。
