Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.
Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.
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DOI：
10.1371/journal.pone.0062917
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Laguna TA
中科院分区：
文献类型：
--
作者：
Zemanick ET;Harris JK;Wagner BD;Robertson CE;Sagel SD;Stevens MJ;Accurso FJ;Laguna TA
肺部病情加重（PEx）通常与气道感染和炎症相关，是囊性纤维化（CF）发病的主要原因。分子微生物学方法可从 PEx 期间采集的 CF 气道样本中检测复杂的微生物群。 CF PEx 期间气道微生物群、炎症和肺功能之间的关系尚不清楚。确定接受 PEx 治疗的 CF 受试者气道微生物群、炎症和肺功能之间的关系。在PEx治疗的早期（0-3天）和晚期（>7天）期间，收集CF受试者的咳出的痰液和血液并进行肺功能测试。通过培养、16S rRNA 扩增子焦磷酸测序以及总细菌和特定细菌的定量 PCR 来分析痰液。痰IL-8和中性粒细胞弹性蛋白酶（NE）；并测量循环C反应蛋白（CRP）。从 21 名 CF 受试者中采集了 37 份痰样本。在治疗早期，较低的多样性与假单胞菌的高相对丰度 (RA) (r = −0.67，p<0.001)、预测的 FEV1% 降低 (r = 0.49，p = 0.03) 和 CRP 增加 (r = −0.58，p = 0.01) 相关。与假单胞菌相反，专性和兼性厌氧菌属与较少的炎症和较高的 FEV1 相关。通过治疗，qPCR 检测结果显示，RA 假单胞菌和铜绿假单胞菌数量有所减少，而厌氧菌属的反应则表现出明显的变异性。与假单胞菌或葡萄球菌相比，普雷沃菌的 RA 变化与 FEV1 对治疗反应的变异性更大相关。与早期恶化时的假单胞菌相比，通过测序从痰中鉴定出的厌氧菌与较少的炎症和较高的肺功能相关。 CF PEx 治疗会导致厌氧菌属发生不同的变化，这表明需要进行更大规模的研究，特别是针对没有传统 CF 病原体的患者。
Pulmonary exacerbations (PEx), frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF). Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood. To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx. Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0–3d.) and late treatment (>7d.) for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE); and circulating C-reactive protein (CRP) were measured. Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA) of Pseudomonas (r = −0.67, p<0.001), decreased FEV1% predicted (r = 0.49, p = 0.03) and increased CRP (r = −0.58, p = 0.01). In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV1. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV1 response to treatment than Pseudomonas or Staphylococcus. Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.