Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Trust, Southmoor Road, Manchester, M23 9QZ, UK.
Respir Res. 2020 Nov 1;21(1):289. doi: 10.1186/s12931-020-01552-4.
There is evidence that bacterial colonisation in chronic obstructive pulmonary disease (COPD) is associated with increased neutrophilic airway inflammation. This study tested the hypothesis that different bacterial phyla and species cause different inflammatory profiles in COPD patients.
Sputum was analysed by quantitative polymerase chain reaction (qPCR) to quantify bacterial load and 16S rRNA gene sequencing to identify taxonomic composition. Sputum differential cell counts (DCC) and blood DCC were obtained at baseline and 6 months. Patients were categorised into five groups based on bacterial load defined by genome copies/ml of ≥ 1 × 10, no colonisation and colonisation by Haemophilus influenzae (H. influenzae), Moraxella catarrhalis (M. catarrhalis), Streptococcus pneumoniae (S. pneumoniae), or > 1 potentially pathogenic microorganism (PPM).
We observed an increase in sputum neutrophil (%), blood neutrophil (%) and neutrophil-lymphocyte ratio (NLR) in patients colonised with H. influenzae (82.6, 67.1, and 3.29 respectively) compared to those without PPM colonisation at baseline (69.5, 63.51 and 2.56 respectively) (p < 0.05 for all analyses), with similar findings at 6 months. The bacterial load of H. influenzae and Haemophilus determined by qPCR and 16s rRNA gene sequencing respectively, and sputum neutrophil % were positively correlated between baseline and 6 months visits (p < 0.0001, 0.0150 and 0.0002 with r = 0.53, 0.33 and 0.44 respectively).
These results demonstrate a subgroup of COPD patients with persistent H. influenzae colonisation that is associated with increased airway and systemic neutrophilic airway inflammation, and less eosinophilic airway inflammation.
有证据表明，慢性阻塞性肺疾病（COPD）中的细菌定植与中性粒细胞性气道炎症增加有关。本研究检验了这样一个假设，即不同的细菌门和种属在 COPD 患者中引起不同的炎症特征。
通过定量聚合酶链反应（qPCR）分析痰标本以量化细菌负荷，并通过 16S rRNA 基因测序来鉴定分类组成。在基线和 6 个月时获得痰细胞分类计数（DCC）和血液 DCC。根据基因组拷贝数/ml 定义的细菌负荷将患者分为五组，≥1×10、无定植和定植于流感嗜血杆菌（H. influenzae）、卡他莫拉菌（M. catarrhalis）、肺炎链球菌（S. pneumoniae）或>1 种潜在致病微生物（PPM）。
与无 PPM 定植的患者相比，定植于 H. influenzae 的患者（分别为 82.6%、67.1%和 3.29%）的痰中性粒细胞（%）、血液中性粒细胞（%）和中性粒细胞-淋巴细胞比值（NLR）增加（所有分析 p<0.05），6 个月时也有类似发现。qPCR 和 16s rRNA 基因测序分别确定的 H. influenzae 细菌负荷和痰中性粒细胞%在基线和 6 个月时呈正相关（p<0.0001、0.0150 和 0.0002，r=0.53、0.33 和 0.44）。
这些结果表明，COPD 患者中有一部分持续定植于 H. influenzae，这与气道和全身中性粒细胞性气道炎症增加以及较少的嗜酸性粒细胞性气道炎症有关。
