呼吸性 MUC5B 失衡与严重社区获得性肺炎有关。
Respiratory MUC5B disproportion is involved in severe community-acquired pneumonia.
机构信息
Department of Emergency, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Rd, Nanjing, 210029, People's Republic of China.
Department of Emergency, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 98 Nantong West Rd, Yangzhou, 225001, People's Republic of China.
出版信息
BMC Pulm Med. 2022 Mar 15;22(1):90. doi: 10.1186/s12890-022-01870-x.
BACKGROUND
Mucus production is a process involved in the pathogenesis of Community-acquired pneumonia (CAP). The study is to determine Mucin 5B (MUC5B) protein concentration and its proportion in the bronchoalveolar lavage fluid (BALF) of CAP patients and evaluate its value to help assess disease severity.
METHODS
A total of 118 patients were enrolled in this cross-sectional study, including 45 with severe CAP (SCAP) and 73 with non-severe CAP (NSCAP). MUC5B concentration in BALF were determined by immunoblotting analysis. Total protein concentration of BALF was detected by Pierce BCA kit. Cytokines IL6, IL10, IFNγ, IL13, and IL17 in BALF were measured using commercial enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was applied to evaluate the relationships between MUC5B concentration or MUC5B/total protein ratio and the CURB-65 score, as well as cytokines. Logistic regression analysis was used to identify the independent factors associated with severe CAP. Receiver operating characteristic (ROC) curve was used to evaluate the assessment value of MUC5B/total protein ratio and other indexes for CAP severity.
RESULTS
MUC5B concentration in the BALF of NSCAP group was higher than that in SCAP group [NSCAP 13.56 µg/ml (IQR 5.92-25.79) vs. SCAP 8.20 µg/ml (IQR 4.97-14.03), p = 0.011]. The total protein concentration in the BALF of NSCAP group was lower than that in SCAP group [NSCAP 0.38 mg/ml (IQR 0.15-1.10) vs. SCAP 0.68 mg/ml (IQR 0.46-1.69), p = 0.002]. The MUC5B/total protein ratio was remarkably higher in NSCAP group than that in SCAP groups [NSCAP 3.66% (IQR 1.50-5.56%) vs. SCAP 1.38% (IQR 0.73-1.76%), p < 0.001]. MUC5B/total protein ratio was negatively correlated with total protein concentration (r = - 0.576, p < 0.001), IL6 (r = - 0.312, p = 0.001), IL10 (r = - 0.228, p = 0.013), IL13 (r = - 0.183, p = 0.048), IL17 (r = - 0.282, p = 0.002) and CURB-65 score (r = - 0.239, p = 0.009). Logistic regression identified that MUC5B/total protein ratio, IL6 level and CURB-65 score as independent variables related to CAP severity. ROC curve demonstrated best assessment value of MUC5B/total protein ratio for SCAP (AUC 0.803, p < 0.001), with a sensitivity of 88.9% and a specificity of 64.4%.
CONCLUSIONS
Respiratory MUC5B disproportion is related to CAP severity. MUC5B/total protein ratio may serve as an assessment marker and a potential therapeutic target for severe CAP.
背景
黏液产生是社区获得性肺炎（CAP）发病机制的一个过程。本研究旨在确定黏液素 5B（MUC5B）蛋白在 CAP 患者支气管肺泡灌洗液（BALF）中的浓度及其比例，并评估其对帮助评估疾病严重程度的价值。
方法
本研究共纳入 118 例患者，其中 45 例为重症 CAP（SCAP），73 例为非重症 CAP（NSCAP）。采用免疫印迹分析测定 BALF 中 MUC5B 浓度。采用 Pierce BCA 试剂盒测定 BALF 中总蛋白浓度。采用商业酶联免疫吸附试验（ELISA）测定 BALF 中细胞因子 IL6、IL10、IFNγ、IL13 和 IL17。采用 Spearman 相关分析评估 MUC5B 浓度或 MUC5B/总蛋白比值与 CURB-65 评分以及细胞因子之间的关系。采用 logistic 回归分析识别与重症 CAP 相关的独立因素。采用受试者工作特征（ROC）曲线评估 MUC5B/总蛋白比值和其他指标对 CAP 严重程度的评估价值。
结果
NSCAP 组 BALF 中 MUC5B 浓度高于 SCAP 组[NSCAP 13.56µg/ml（IQR 5.92-25.79）比 SCAP 8.20µg/ml（IQR 4.97-14.03），p=0.011]。NSCAP 组 BALF 中总蛋白浓度低于 SCAP 组[NSCAP 0.38mg/ml（IQR 0.15-1.10）比 SCAP 0.68mg/ml（IQR 0.46-1.69），p=0.002]。NSCAP 组 MUC5B/总蛋白比值明显高于 SCAP 组[NSCAP 3.66%（IQR 1.50-5.56%）比 SCAP 1.38%（IQR 0.73-1.76%），p<0.001]。MUC5B/总蛋白比值与总蛋白浓度呈负相关（r=-0.576，p<0.001），与 IL6（r=-0.312，p=0.001）、IL10（r=-0.228，p=0.013）、IL13（r=-0.183，p=0.048）、IL17（r=-0.282，p=0.002）和 CURB-65 评分呈负相关（r=-0.239，p=0.009）。Logistic 回归分析确定 MUC5B/总蛋白比值、IL6 水平和 CURB-65 评分是与 CAP 严重程度相关的独立变量。ROC 曲线显示 MUC5B/总蛋白比值对 SCAP 的评估价值最佳（AUC 0.803，p<0.001），其灵敏度为 88.9%，特异性为 64.4%。
结论
呼吸 MUC5B 比例失调与 CAP 严重程度有关。MUC5B/总蛋白比值可能作为评估重症 CAP 的标志物和潜在治疗靶点。
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