Prediction of the pathogens that are the cause of pneumonia by the battlefield hypothesis.

Prediction of the pathogens that are the cause of pneumonia by the battlefield hypothesis.
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DOI:
10.1371/journal.pone.0024474
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Hagiwara K
Hagiwara K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hirama T;Yamaguchi T;Miyazawa H;Tanaka T;Hashikita G;Kishi E;Tachi Y;Takahashi S;Kodama K;Egashira H;Yokote A;Kobayashi K;Nagata M;Ishii T;Nemoto M;Tanaka M;Fukunaga K;Morita S;Kanazawa M;Hagiwara K

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共生微生物是肺炎的常见原因。然而,在气道中检测到这些微生物并不意味着它们是致病病原体;它们可能仅仅作为定植者存在。在高达50%的肺炎病例中,致病病原体仍未被识别,从而阻碍了靶向治疗。在推测肺部微生物在肺炎中的作用时,我们提出了战场假说。在“肺炎战场”中,生物体与人体的细胞数量比可能是生物体致病作用的指标。使用痰液样本的实时PCR反应,我们检验了该假设是否预测了4种代表性微生物的细菌学临床试验结果:肺炎链球菌、流感嗜血杆菌、假单胞菌属、和卡他莫拉菌。使用224份痰液样本,为每种微生物设定微生物与人细胞数比的临界值,高于该临界值时,怀疑微生物的致病作用。然后在一项包含153个样本的前瞻性研究中检验了临界值的有效性;将样本分为3组,每组包含93%、7%和0%的肺炎样本,其中肺炎链球菌的致病作用已被临床试验所证实。流感嗜血杆菌、假单胞菌属、卡他莫拉菌为0%,卡他莫拉菌为0%。战场假说使得对PCR结果的合理解释成为可能,并预测了肺炎,其中临床试验表明了微生物的致病作用。基于战场假说的PCR反应可能有助于促进肺炎的靶向治疗。本报告中描述的前瞻性观察研究在启动前已在大学医院医学信息网络(UMIN)注册中心注册,UMIN是国际医学期刊编辑委员会(ICMJE)批准的注册中心。UMIN注册编号为UMIN 000001118:一项研究HIRA-TAN系统临界值有效性的前瞻性研究(2008年4月9日)。
Commensal organisms are frequent causes of pneumonia. However, the detection of these organisms in the airway does not mean that they are the causative pathogens; they may exist merely as colonizers. In up to 50% cases of pneumonia, the causative pathogens remain unidentified, thereby hampering targeting therapies. In speculating on the role of a commensal organism in pneumonia, we devised the battlefield hypothesis. In the “pneumonia battlefield,” the organism-to-human cell number ratio may be an index for the pathogenic role of the organism. Using real-time PCR reactions for sputum samples, we tested whether the hypothesis predicts the results of bacteriological clinical tests for 4 representative commensal organisms: Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis. The cutoff value for the organism-to-human cell number ratio, above which the pathogenic role of the organism was suspected, was set up for each organism using 224 sputum samples. The validity of the cutoff value was then tested in a prospective study that included 153 samples; the samples were classified into 3 groups, and each group contained 93%, 7%, and 0% of the samples from pneumonia, in which the pathogenic role of Streptococcus pneumoniae was suggested by the clinical tests. The results for Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis were 100%, 0%, and 0%, respectively. The battlefield hypothesis enabled legitimate interpretation of the PCR results and predicted pneumonia in which the pathogenic role of the organism was suggested by the clinical test. The PCR reactions based on the battlefield hypothesis may help to promote targeted therapies for pneumonia. The prospective observatory study described in the current report had been registered to the University Hospital Medical Information Network (UMIN) registry before its initiation, where the UMIN is a registry approved by the International Committee of Medical Journal Editors (ICMJE). The UMIN registry number was UMIN000001118: A prospective study for the investigation of the validity of cutoff values established for the HIRA-TAN system (April 9, 2008).
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