痰中抗菌肽 SLPI 和 β 防御素-1 与 FEV 呈负相关。
Antimicrobial Peptides SLPI and Beta Defensin-1 in Sputum are Negatively Correlated with FEV.
机构信息
Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
出版信息
Int J Chron Obstruct Pulmon Dis. 2021 May 28;16:1437-1447. doi: 10.2147/COPD.S301622. eCollection 2021.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) and asthma have heterogeneous inflammation with inhaled corticosteroids (ICS) as a mainstay of treatment. There is increased prevalence of non-typeable (NTHi) persistence in airways of patients with neutrophilic airway inflammation, potentially due to suppressed host defence after corticosteroid treatment. Antimicrobial peptides (AMPs) have antimicrobial activity against pathogens and immunomodulatory effects. We investigated whether AMPs associate with NTHi presence in COPD and asthma, and whether ICS alter this.
METHODS
Secretory leukocyte protease inhibitor (SLPI), osteopontin, elafin and beta defensin-1 were measured in sputum supernatants from healthy donors (n=9), asthmatics (n=21) and patients with COPD (n=14). Elafin and beta defensin-1 were measured in a primary human bronchial epithelial cells (HBECs) from healthy and COPD donors infected with NTHi and pre-treated with fluticasone propionate (FP) and budesonide (BUD). Internalised NTHi was quantified by qPCR.
RESULTS
Sputum SLPI was negatively correlated with FEV1 (p<0.001, r=-0.610), FEV1% predicted (p<0.001, r=-0.583) and FEV1/FVC (p=0.001, r=-0.528). Sputum beta defensin-1 was negatively associated with FEV1 (p<0.001***r=-0.594). SLPI and beta defensin-1 levels in sputum were higher in the healthy controls and COPD group compared to the asthma group (p=0.001 and p=0.014) and (p<0.001 and p=0.007, respectively). ICS use was associated with higher sputum osteopontin compared to those with no ICS use. NTHi infection of COPD HBECs produced higher levels of beta defensin-1 compared to healthy donors (mean (SD) release: 45.1pg/mL (7.3) vs 21.2pg/mL (7.3) respectively, p=0.014). Elafin release from HBECs from COPD donors did not change following NTHi infection; however, elafin from healthy donors was significantly reduced (%mean reduction: 23.7%, 95% confidence intervals (CI) of reduction: 5.3-38.4%, p<0.01).
CONCLUSION
Sputum SLPI and beta defensin-1 may be markers to identify those patients with declining lung function. ICS use was associated with higher sputum osteopontin compared to those with no ICS use.
背景
慢性阻塞性肺疾病（COPD）和哮喘具有异质性炎症，吸入皮质类固醇（ICS）是其主要治疗方法。气道中存在非定型（NTHi）持续性感染的患者中性粒细胞性气道炎症增加，这可能是由于皮质类固醇治疗后宿主防御功能受到抑制。抗菌肽（AMPs）对病原体具有抗菌活性和免疫调节作用。我们研究了 AMPs 是否与 COPD 和哮喘患者的 NTHi 存在相关，以及 ICS 是否会改变这种情况。
方法
在健康供体（n=9）、哮喘患者（n=21）和 COPD 患者（n=14）的痰上清液中测量分泌白细胞蛋白酶抑制剂（SLPI）、骨桥蛋白、Elafin 和β-防御素-1。在来自健康和 COPD 供体的原代人支气管上皮细胞（HBEC）中测量 Elafin 和β-防御素-1，这些细胞感染了 NTHi，并预先用氟替卡松丙酸酯（FP）和布地奈德（BUD）处理。通过 qPCR 定量内化的 NTHi。
结果
痰 SLPI 与 FEV1 呈负相关（p<0.001，r=-0.610），与 FEV1%预测呈负相关（p<0.001，r=-0.583），与 FEV1/FVC 呈负相关（p=0.001，r=-0.528）。痰中β-防御素-1与 FEV1 呈负相关（p<0.001***r=-0.594）。与哮喘组相比，健康对照组和 COPD 组的痰 SLPI 和β-防御素-1水平更高（p=0.001 和 p=0.014）和（p<0.001 和 p=0.007，分别）。与未使用 ICS 的患者相比，使用 ICS 的患者痰中骨桥蛋白水平更高。COPD HBEC 感染 NTHi 后β-防御素-1水平高于健康供体（平均（SD）释放：45.1pg/mL（7.3）比 21.2pg/mL（7.3），p=0.014）。COPD 供体 HBEC 感染 NTHi 后 Elafin 释放没有变化；然而，来自健康供体的 Elafin 显著减少（%平均减少：23.7%，95%置信区间（CI）减少：5.3-38.4%，p<0.01）。
结论
痰 SLPI 和β-防御素-1可能是识别肺功能下降患者的标志物。与未使用 ICS 的患者相比，使用 ICS 的患者痰中骨桥蛋白水平更高。
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