Reactive protein clearance and its correlation with airway hyperreactivity in patients with acute bronchitis

XU Wei, CHENG Jixia, LI Jie, ZHANG Hua

Journal of Jinan University Natural Science & Medicine Edition ›› 2024, Vol. 45 ›› Issue (5) : 502-511.

PDF(1064 KB)
Fig/Tab
Advanced Search
更多内容请点击
PDF(1064 KB)
Journal of Jinan University Natural Science & Medicine Edition ›› 2024, Vol. 45 ›› Issue (5) : 502-511. DOI: 10.11778/j.jdxb.20240038
Research on clinical medicine

Reactive protein clearance and its correlation with airway hyperreactivity in patients with acute bronchitis

Author information +
History +

Abstract

Objective: To explore the correlation between C-reactive protein clearance rate (CRPc) and airway hyperresponsiveness (AHR) in acute bronchitis patients, in order to provide a reference for clinical diagnosis of AHR degree in acute bronchitis patients. Methods: A total of 182 patients with acute bronchitis admitted to Luzhou Hospital of Traditional Chinese Medicine from June 2020 to June 2023 were selected as the study objects, and were divided into group A: mild (n=67), group B: moderate (n=59), and group C: severe (n=56) according to the different degrees of AHR. The method of 1∶1 orientation matching was used to adjust the balance of patient data. All patients underwent lung examination, fasting blood was collected in the morning, and serum indexes of patients were detected by enzyme-linked immunosorbent assay. CRP level and CRPc were detected within 24 h and after admission and 3, 5, and 7 d after treatment. Multivariate Logistic regression analysis was conducted to analyze the correlation between CRPc and AHR degree, analyze the clinical factors affecting AHR degree, construct the corresponding prediction model and evaluate. Results: After 1∶1 orientation matching, 47 patients with mild, moderate and severe AHR with no statistical difference in various indicators before treatment were obtained. After treatment, the levels of FEV1/FVC, MVV, interferon-γ (IFN-γ), IL-10 and PD20FEV1 in the 3 groups were increased, while the levels of CRP, YKL-39 and LTE4 were decreased, indicating a significant improvement effect. In addition, the levels of FEV1/FVC, MVV, IFN-γ, IL-10 and PD20FEV1 in group A were higher than those in the other two groups, while the levels of CRP, YKL-39 and LTE4 were lower than those in the other two groups, and the improvement effect was better. The CRPc of group A, B and C after 7 d of treatment were (70.66±14.85)%, (60.55±15.52)% and (48.24±14.47)%, respectively, and the CRPc of group A were significantly higher than those of the other two groups. Multivariate Logistic regression analysis showed that CRPc-3 (OR=0.85, 95%CI: 0.69-0.87), CRPc-5 (OR=0.92, 95%CI: 0.77-0.95) and CRPc-7 (OR=0.96, 95%CI: 0.89-0.98) were correlated with the degree of AHR in patients. YKL-39 and LTE4 are risk factors (OR>1) for developing severe AHR, while CRPc-3, CRPc-5, CRPc-7, IFN-γ and PD20FEV1 are protective factors (OR<1) for developing severe AHR. All 7 factors have high predictive value for the risk of developing severe AHR, but the combined detection has the highest predictive value. A model built by combining the above 7 factors: Logit(P)=-2.036-0.449 (CRPc-3)-0.507(CRPc-5)-0.114(CRPc-7)-0.464(IFN-γ)+0.449(LTE4)+0.622(YKL-39)-0.200(PD20FEV1). When P=0.90, the Yoden index is the highest and the prediction effect is the best with prediction accuracy 83.10%, sensitivity 93.71%, and specificity 78.52%. Conclusion: Patients with mild AHR had higher CRPc than those with moderate and severe AHR, CRPc-3, CRPc-5 and CRPc-7 were correlated with the degree of AHR.

Key words

acute bronchitis / C-reactive protein / C-reactive protein clearance rate / airway hyperresponsiveness

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations
XU Wei , CHENG Jixia , LI Jie , ZHANG Hua. Reactive protein clearance and its correlation with airway hyperreactivity in patients with acute bronchitis. Journal of Jinan University Natural Science & Medicine Edition. 2024, 45(5): 502-511 https://doi.org/10.11778/j.jdxb.20240038
开放科学标识码（OSID）
急性支气管炎主要是指患者在各种因素影响下出现的支气管黏膜急性炎症[1],多发生于气温骤变或寒冷季节,发病机制比较复杂,患者发病后主要表现为发热、咽痛、咳痰、肺部啰音等症状[2-3]。老人和儿童为主要患病人群。患者若没有得到及时治疗,病情会加重,进而可能发展为肺炎等严重疾病,有研究显示急性支气管炎患者中有60%~70%的人会使用抗生素,这一做法增加了患者发生抗生素耐药性感染的风险[4],不利于患者的康复。
气道高反应性(airway hyperresponsiveness,AHR)是指人体在吸入少量刺激物后气道发生过度收缩反应,从而引起气道的管腔狭窄和阻力明显增加[5-6]。大多数研究报道这是由于气道炎症所导致的[7⇓-9]。当气道受到刺激后,多种炎症因子大量释放,损伤了气道上皮内神经,从而导致AHR的发生。而C反应蛋白(C-reactive protein,CRP)是一种非特异性的炎症标志物[10],对炎症反应具有调节作用。在人体受到损伤时,CRP的水平会在短时间内大幅度上升。已有研究证明,CRP是心血管疾病重要的预测因子[11],同时,CRP已经被提议作为肺部病情加重诊断和治疗的生物标志物[12],但CRP在急性支气管炎及其与AHR的相关性方面的研究较少,因此,本研究旨探讨急性支气管炎患者治疗后CRP清除率(C-reactive clearance rate,CRPc)及其与气道高反应性的相关性,以期为临床治疗提供理论指导。

1 材料与方法

1.1 研究对象

选取泸州市中医院2020年6月到2023年6月收治的182例急性支气管炎患者作为参与者。通过查询医院的电子病历收集患者的一般资料。
AHR程度评估标准[13]:患者体内FEV1下降20%激发剂累计含量(provocation dosage when FEV1 is reduced by 20%, PD20FEV1)组胺在0.9~3.2 μmoL时判定为轻度;当含量在0.1~0.8 μmoL时判定为中度;当含量小于0.1 μmoL时判定为重度AHR。根据AHR严重程度不同,将患者分为A组:轻度(n=67)、B组:中度(n=59)、C组:重度(n=56),倾向性评分匹配调整均衡性,共成功匹配到47对。
纳入标准:①符合急性气管-支气管炎基层诊疗指南(2018年)[14];②因急性上呼吸道感染导致气管高反应性;③无肺部相关基础性疾病;④病程小于5 d,且病情可控。
排除标准:①患有肺癌或其他恶性肿瘤疾病;②合并有下呼吸道感染疾病;③合并心脑血管疾病;④由于长期吸烟(烟龄>5年)使气道对冷空气、烟雾等刺激的敏感性增加,从而导致的气道反应性增高。
患者均已签署知情同意书,本研究通过泸州市中医院伦理委员会审核批准(审批号:20220319011)。

1.2 研究方法

1.2.1 试剂与仪器

便捷式肺功能仪(海益联医学仪器发展有限公司,Pony FX);ECP ELISA检测试剂盒(上海心语生物科技有限公司,XYU-H01419);LTE4 ELISA试剂盒(上海通蔚实业有限公司,TW-E4368);多功能酶标仪(美谷分子仪器有限公司,Spectra Max i3x)。

1.2.2 治疗方法

3组患者均接受了常规的西药治疗方案,该方案涵盖了多个针对性的治疗措施,包括止咳平喘、化痰及必要的吸氧等。具体方案如下:将0.5 g左氧氟沙星与250 mL生理盐水混合后进行静脉滴注,每日进行一次。此外,将30 mg的氨溴索注射液与100 mL生理盐水混合后进行静脉滴注,每日一次,疗程一周。

1.2.3 肺功能检测

采用便捷式肺功能仪对所有患者进行肺部检查,记录患者治疗前1 d和治疗7 d后的用力肺活量(forced vital capacity, FVC)、每分钟最大通气量(maximum voluntary ventilation, MVV)、1 s用力呼气容积(forced expiratory volume in the first second, FEV1)、一秒率(FEV1/FVC)及最大呼气中期流速(maximal mid-expiratory flow curve, MMF)。

1.2.4 血液指标检测

采集患者入院24 h内及治疗后7 d的清晨空腹血,采用ELISA试验检测患者低密度脂蛋白胆固醇(low density lipoprotein-cholesterol, LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol, HDL-C)、血红蛋白(haemoglobin, Hb)、白细胞(white blood cells, WBC)、白细胞介素-6(interleukin-6, IL-6)、白细胞介素-10(interleukin-10, IL-10)、γ-干扰素(interferon-γ, IFN-γ)、人软骨糖蛋白39(human cartilage glycoprotein 39, YKL-39)的含量。
分别于患者入院24 h内及治疗后第3、5及7天采集清晨空腹血,采用免疫透射比浊法检测患者CRP水平。CRP-n表示患者第n 天的CRP水平,如CRP-1表示患者入院24 h内的CRP水平;CRPc-n=(CRP-1-CRP-n)/CRP-1。CRPc-n表示患者第n天的CRP清除率,CRPc-3,CRPc-5,CRPc-7分别第3,5,7天的CRPc。

1.2.5 AHR指标的检测

主要包括嗜酸性粒细胞阳离子蛋白(eosinophil cationic protein, ECP)、白三烯E4(leukotriene E4, LTE4)、PD20FEV1。
采集患者痰液及新鲜尿液,分别使用ECP和LTE4的ELISA试剂盒,检测患者痰液中的ECP水平和尿液中的LTE4水平。
PD20FEV1水平通过胺激发试验检测,以乙酰甲胆碱为激发剂,胺激发结束后常规吸入沙丁胺醇,叮嘱患者平静放松呼吸。

1.3 统计学分析

采用SPSS 22.0进行数据分析,计量资料用平均值±标准差表示,组间比较行F检验,计数资料以频数(百分率)表示,组间比较行 χ2检验。多因素 Logistic 回归分析探讨CRP水平与AHR程度的相关性,并以影响患者气道高反应性程度的因素,构建预测模型。P<0.05为差异或相关性具有统计学意义。

2 结果

2.1 倾向性匹配结果

利用倾向性评分匹配法进行1:1匹配,共匹配成功47对。由表1可得,匹配前3组患者在性别、年龄、BMI、饮酒史、糖尿病、冠心病方面的差异具有统计学意义(P<0.05),匹配后组间一般资料差异均无统计学意义(P>0.05),匹配效果较好,匹配前后直方图,见图1。
Table 1 Comparison of baseline data before and after disposition matching in patients with different degrees of AHR n(%)

表1 不同程度AHR患者倾向性匹配前后基线资料比较

变量 匹配前 匹配后
A组(n=67) B组(n=59) C组(n=56) F/χ2值 P值 A组(n=47) B组(n=47) C组(n=47) F/χ2值 P值
性别 6.930 0.031 1.533 0.465
男 42(62.69) 26(44.07) 23(41.07) 27(57.45) 24(51.06) 21(44.68)
女 25(37.31) 33(55.93) 33(58.93) 20(42.55) 23(48.94) 26(55.32)
年龄/岁 63.71±5.26 66.98±5.47 60.95±4.47 6.650 0.034 66.81±2.37 65.92±3.05 66.89±2.68 1.511 0.134
BMI/(kg·m-2) 7.706 0.021 1.079 0.583
≥25 27(40.30) 38(64.41) 26(46.43) 23(48.94) 25(53.19) 20(42.55)
<25 40(59.70) 21(35.59) 30(53.57) 24(51.06) 22(46.81) 27(57.45)
吸烟史 6.003 0.050 1.640 0.440
有 30(44.78) 29(49.15) 37(66.07) 25(53.19) 27(57.45) 31(65.96)
无 37(55.22) 30(50.85) 19(33.93) 22(46.81) 20(42.55) 16(34.04)
饮酒史 6.772 0.034 2.130 0.345
有 43(64.18) 25(42.37) 34(60.71) 26(55.32) 23(48.94) 30(63.83)
无 24(35.82) 34(57.63) 22(39.29) 21(44.68) 24(51.06) 17(36.17)
高血压 4.866 0.088 3.465 0.177
有 28(41.79) 33(55.93) 34(60.71) 20(42.55) 24(51.06) 29(61.70)
无 39(58.21) 26(44.07) 22(39.29) 27(57.45) 23(48.94) 18(38.30)
糖尿病 6.119 0.047 2.440 0.295
有 25(37.31) 35(59.32) 26(46.43) 20(42.55) 27(57.45) 21(44.68)
无 42(62.69) 24(40.68) 30(53.57) 27(57.45) 20(42.55) 26(55.32)
冠心病 6.823 0.033 2.485 0.289
有 20(29.85) 30(50.85) 27(48.21) 16(34.04) 22(46.81) 23(48.94)
无 47(70.15) 29(49.15) 29(51.79) 31(65.96) 25(53.19) 24(51.06)
Figure 1 The distribution of predisposition score was matched with the covering kernel density histogram

图1 匹配前后倾向性评分分布与覆盖核密度直方图

Full size|PPT slide

2.2 治疗前后各指标比较结果

由表2可知,3组患者除PD20FEV1有显著差异外,其他指标治疗前差异无统计学意义(P>0.05),治疗后3组患者FEV1/FVC、MVV、IFN-γ、IL-10和PD20FEV1水平升高,CRP、YKL-39、LTE4水平降低,且A组患者FEV1/FVC、MVV、IFN-γ、IL-10和PD20FEV1水平高于其他2组,CRP、YKL-39和LTE4水平低于其他2组,3组之间的差异具有统计学意义(P<0.05)。
Table 2 Comparison of all indexes before treatment and 7 days after treatment n(%)

表2 患者治疗前及治疗7 d后各指标比较

变量 治疗前 治疗后
A组(n=47) B组(n=47) C组(n=47) F/χ2值 P值 A组(n=47) B组(n=47) C组(n=47) F/χ2值 P值
收缩压<90 mmHg 10(21.28) 12(25.53) 15(31.91) 1.392 0.498 7(14.89) 8(17.02) 10(21.28) 0.681 0.712
FVC/L 2.77±0.12 2.41±0.13 2.53±0.15 1.759 0.415 3.85±0.20 3.42±0.11 3.20±0.14 4.452 0.108
MMF/(L·s-1) 3.71±1.02 3.86±1.10 4.01±1.06 1.419 0.492 2.75±0.09 3.14±1.03 3.32±1.11 3.711 0.156
FEV1/L 1.21±0.25 1.14±0.23 1.19±0.26 2.821 0.244 2.06±0.10 1.85±0.18 1.74±0.20 3.081 0.214
(FEV1/FVC)/% 49.87±3.12 48.65±3.57 47.13±3.64 1.079 0.583 57.69±3.66 55.28±3.251) 52.87±3.301)2) 6.806 0.033
MVV/L 72.30±11.23 72.06±10.47 71.68±10.02 1.196 0.550 90.67±13.54 84.55±12.621) 80.24±12.031)2) 8.294 0.016
cLDL-C/(mmol·L-1) 2.68±0.11 2.71±0.20 2.75±0.13 2.238 0.327 2.42±0.12 2.30±0.24 2.40±0.18 5.476 0.065
cHDL-C/(mmol·L-1) 1.15±0.10 1.13±0.08 1.11±0.09 1.192 0.551 1.33±0.15 1.31±0.12 1.27±0.10 2.564 0.278
ρHb/(g·L-1) 129.65±14.06 130.70±13.81 132.17±14.50 2.161 0.339 110.80±9.01 116.32±9.16 121.65±10.02 4.470 0.107
ρCRP/(mg·L-1) 21.30±1.03 21.95±1.11 22.68±1.14 1.662 0.436 6.25±0.32 8.66±0.411) 11.74±0.531)2) 13.742 0.001
WBC/(×109·L-1) 19.58±2.51 20.17±2.30 19.86±2.25 1.874 0.392 9.02±0.39 9.97±0.22 10.74±0.41 2.170 0.338
ρIFN-γ/(ng·L-1) 56.74±1.63 56.09±1.39 55.58±1.55 1.706 0.426 85.13±2.68 78.51±2.801) 74.74±2.121)2) 12.113 0.002
ρYKL-39/(ng·L-1) 63.59±2.83 62.87±3.05 61.68±2.94 2.293 0.318 22.13±1.62 25.24±1.361) 27.95±1.561)2) 7.400 0.025
ρIL-6/(pg·mL-1) 89.54±13.56 91.52±14.30 92.31±13.72 4.352 0.114 62.43±12.11 63.64±11.82 65.59±13.26 1.294 0.524
ρIL-10/(μg·mL-1) 323.54±58.63 321.67±59.41 319.55±58.72 5.304 0.071 810.47±98.51 754.28±90.201) 712.63±92.331)2) 7.638 0.022
ρECP/(ng·mL-1) 87.51±20.36 88.50±17.38 89.42±19.87 3.065 0.216 33.62±6.54 38.59±6.91 42.08±6.05 3.581 0.167
ρLTE4/(pg·mL-1) 820.36±58.65 823.58±60.74 825.66±61.28 4.470 0.107 268.47±49.62 325.84±53.181) 357.14±52.011)2) 7.818 0.020
PD20FEV1/μmoL 1.34±0.04 0.68±0.06 0.07±0.10 5.812 0.042 2.01±0.12 0.74±0.171) 0.09±0.151)2) 6.593 0.037
1)与A组比较,P<0.05;2)与B组比较,P<0.05。
1)Compared with group A, P<0.05; 2)Compared with group B, P<0.05.

2.3 CRP清除率比较结果

3组患者经过治疗后,CRP水平较治疗前均显著下降(图2),差异具有统计学意义(P<0.05)。由表3和图2可知,3组患者在治疗后,CRP水平呈现逐渐降低的趋势,CRPc呈现升高的趋势,且第3、5和7天时,A组患者CRP水平小于其他2组,CRPc大于其他2组,3组之间的差异具有统计学意义(P<0.05),治疗7 d后,3组患者CRPc分别为70.66%、60.55%和48.24%,A组患者CRPc显著高于其他2组。
Table 3 Comparison of CRPc in different groups %

表3 组间CRPc比较

分组 n CRPc-1 CRPc-3 CRPc-5 CRPc-7 F值 P值
A组 47 - 34.23±8.13 50.28±9.40 70.66±14.85 125.346 <0.001
B组 47 - 25.42±6.281) 43.78±10.511) 60.55±15.521) 111.337 <0.001
C组 47 - 19.36±6.861)2) 29.98±9.391)2) 48.24±14.471)2) 87.305 <0.001
F值 51.661 52.797 26.500
P值 <0.001 <0.001 <0.001
1)表示与A组比较,P<0.05;2)表示与B组比较,P<0.05。
1)Compared with group A, P<0.05; 2) Compared with group B, P<0.05.
Figure 2 Comparison of CRP level in all groups before and after treatment

图2 治疗前后各组患者CRP水平比较

2)P<0.01; 3)P<0.001。

Full size|PPT slide

2.4 AHR程度与不同时期CRP清除率的相关性分析结果

将患者不同时间点CRPc逐层划分(Q1~Q5),逐步排除存在共线性的混杂因素,校正FEV1/FVC、MVV、IFN-γ、YKL-39、IL-10、LTE4和PD20FEV1。
由表4可知,在未校正模型中,CRPc-3、CRPc-5和CRPc-7与患者AHR程度显著相关(P<0.001)。将除CRP外的其他因素作为控制变量来进行调整:模型1=调整FEV1/FVC、MVV和PC20FEV1;模型2=在模型1的基础上调整IFN-γ、YKL-39、IL-10和LTE4。调整后CRPc-3、CRPc-5和CRPc-7仍是预测AHR程度的保护因素,CRPc越高,患者AHR程度越轻,两者存在相关性。CRPc-3:(OR=0.85,95%CI: 0.69~0.87)、CRPc-5:(OR=0.92,95%CI:0.77~0.95)、CRPc-7:(OR=0.96,95%CI:0.89~0.98),趋势性检验存在统计学意义(P<0.001)。
Table 4 Correlation between the degree of AHR and CRPc at different periods

表4 AHR程度与不同时期CRPc的相关性

组别 CRPc-3 CRPc-5 CRPc-7
OR值(95%CI) P值 OR值(95%CI) P值 OR值(95%CI) P值
未校正模型
A组 0.88(0.50,0.99) 0.001 0.89(0.58,0.92) 0.001 0.91(0.56,0.95) <0.001
B组 0.87(0.52,0.90) 0.001 0.62(0.50,0.76) 0.001 0.89(0.52,0.93) 0.001
C组 0.90(0.52,0.97) 0.001 0.87(0.48,0.90) <0.001 0.91(0.58,0.95) <0.001
模型1
A组 0.78(0.65,0.83) 0.001 0.80(0.33,0.91) 0.001 0.91(0.78,0.93) <0.001
B组 0.73(0.56,0.86) 0.001 0.82(0.41,0.94) 0.001 0.93(0.70,0.96) 0.001
C组 0.79(0.58,0.85) 0.001 0.84(0.81,0.93) 0.001 0.92(0.85,0.97) 0.001
模型2
A组 0.83(0.62,0.88) 0.001 0.86(0.67,0.99) 0.001 0.95(0.82,0.97) <0.001
B组 0.93(0.63,0.96) 0.001 0.90(0.67,0.94) <0.001 0.94(0.73,0.96) <0.001
C组 0.85(0.69,0.87) 0.001 0.92(0.77,0.95) <0.001 0.96(0.89,0.98) <0.001

2.5 影响患者发生重度AHR的多因素分析结果

将患者AHR程度作为因变量,以表2中显示为有差异的因素即:FEV1/FVC、MVV、CRPc-5、CRPc-7、IFN-γ、YKL-39、IL-10、LTE4和PD20FEV1作为自变量纳入Logistic 回归分析模型中。结果显示,CRPc-3、CRPc-5、CRPc-7、IFN-γ、YKL-39、LTE4和PD20FEV1是预测患者重度AHR的关键因素,其中YKL-39和LTE4是预测重度AHR的危险因素,而CRPc-3、CRPc-5、CRPc-7、IFN-γ和PD20FEV1是保护因素,见表5。
Table 5 The influence of each index on severe AHR was analyzed by multiple factors

表5 多因素分析各指标对重度AHR的影响

因素 β值 SE值 Wald值 OR值(95%CI) P值
FEV1/FVC -0.337 0.315 1.144 0.714(0.485,1.268) 0.060
MVV -0.219 0.221 0.986 0.803(0.534,1.347) 0.054
CRPc-3 -0.449 1.006 0.200 0.638(0.518,0.705) 0.043
CRPc-5 -0.507 1.583 0.103 0.602(0.563,0.735) 0.025
CRPc-7 -0.114 0.501 0.052 0.892(0.689,0.920) 0.001
IFN-γ -0.464 0.416 1.242 0.629(0.559,0.781) 0.003
YKL-39 0.622 1.023 0.370 1.863(1.420,1.953) 0.015
IL-10 -0.286 1.027 0.078 0.751(0.847,1.389) 0.051
LTE4 0.449 0.511 0.773 1.567(1.375,1.623) 0.013
PD20FEV1 -0.200 0.625 0.102 0.819(0.694,0.876) 0.035
分析该7个因素对重度AHR的预测价值,其中联合检测对重度AHR的预测价值最高(AUC=0.903),特异性高于其他各指标单独检测,其次为CRPc-7(AUC=0.871)(表6,图3)。
Table 6 Predictive value of each factor for severe AHR

表6 各因素对重度AHR的预测价值

因素 AUC值 P值 灵敏
度/%		 特异
度/%		 阳性预
测值/%		 阴性预
测值/%
CRPc-3 0.820 0.001 86.51 79.68 83.48 80.24
CRPc-5 0.843 0.001 90.15 81.39 85.60 79.93
CRPc-7 0.871 0.001 92.06 80.26 86.40 82.56
IFN-γ 0.812 0.002 80.22 79.53 78.61 83.79
YKL-39 0.750 0.005 75.40 75.82 80.54 79.42
LTE4 0.786 0.003 78.35 77.68 79.88 81.67
PD20FEV1 0.734 0.007 75.31 75.21 91.35 82.03
联合检测 0.903 <0.001 85.42 91.57 90.27 88.71
Figure 3 ROC curve of predictive value of each factor for AHR degree

图3 各因素对AHR程度预测价值的ROC曲线

Full size|PPT slide

2.6 模型构建与评价结果

根据多因素Logistic回归分析结果,构建预测患者患重度AHR的模型,P为模型预测概率,取值0~1。建立的预测模型如下:Logit(P)=-2.036-0.449(CRPc-3)-0.507(CRPc-5)-0.114(CRPc-7)-0.464(IFN-γ)+0.449(LTE4)+0.622(YKL-39)-0.200(PD20FEV1)。经计算,P=0.90时,约登指数最高,预测效果相对最好。当P大于0.90时,则认定该患者为重度AHR,预测准确度为83.10%,灵敏度为93.71%,特异度为78.52%(表7)。ROC曲线下面积为0.903,表明该预测模型诊断效能较高。同时,Hosmer-Lemeshow拟合优度检验显示出较好的拟合度,表明该模型预测概率与实际概率基本一致,具有较好的校准度(图4)。
Table 7 Prediction effect analysis of the model under different probability levels

表7 不同概率水平下模型的预测效果分析

P值 准确度/% 敏感度/% 特异度/% 假阳性率/% 假阴性率/% 约登指数
0.95 85.00 94.74 75.20 24.80 5.26 0.70
0.90 83.10 93.71 78.52 21.48 6.29 0.72
0.85 80.90 86.21 78.67 21.33 13.79 0.65
0.80 80.40 84.35 78.94 21.06 15.65 0.63
0.75 80.10 82.07 79.08 20.92 17.93 0.61
0.70 77.80 76.07 79.46 20.54 23.93 0.56
0.65 77.50 74.28 80.62 19.38 25.72 0.55
0.60 76.20 70.38 82.06 17.94 29.62 0.52
0.55 75.20 68.30 82.19 17.81 31.70 0.50
0.50 75.30 67.19 83.44 16.56 32.81 0.51
0.45 73.80 63.96 83.73 16.27 36.04 0.48
0.40 70.70 56.81 84.53 15.47 43.19 0.41
0.35 70.20 54.10 86.30 13.70 45.90 0.40
0.30 65.70 44.96 86.42 13.58 55.04 0.31
0.25 61.50 34.65 88.26 11.74 65.35 0.23
0.20 60.00 29.94 90.12 9.88 70.06 0.20
0.15 62.70 28.39 96.96 3.04 71.61 0.25
0.10 61.10 25.02 97.15 2.85 74.98 0.22
0.05 50.00 0.00 100.00 0.00 100.00 0.00
Figure 4 ROC curve and calibration curve of predictive model
A: ROC curve of the model; B: Calibration curve of the model

图4 预测模型的ROC曲线及校准曲线

A:模型的ROC曲线图; B:模型的校准曲线

Full size|PPT slide

3 讨论

急性支气管炎是由各种致病因素引起的一种急性炎症反应,以咳嗽为主要临床表现,同时可伴有鼻塞、流涕、全身酸痛等症状[15],是呼吸内科门诊常见病之一,如治疗不及时可能引发肺炎、心肌炎,甚至发展为慢性支气管炎,影响患者身心健康。AHR是肺部疾病的主要临床症状,是导致低氧血症、血流动力学不稳定的高危因素,也是肺部各种潜在疾病死亡率增加的风险因素[16]。
CRP具有检测方便、灵敏度高的特点,其水平与炎症反应程度及组织急性损伤程度密切相关,在机体炎症反应及损伤中起着十分重要的作用。据报道,当机体发生炎症反应时,体内CRP水平会急速上升,并且随着病情加重而呈现高表达,患者在肺炎、支气管炎及慢性阻塞性肺疾病的急性加重期血清CRP水平均明显增高,因此CRP被认为是关键炎症标志物之一,这可能是由于细菌入侵支气管炎患者后,对应组织发生明显病理改变,最终诱发病灶局部炎性反应,进而导致 CRP等多项炎性因子水平升高[17]。此外,有研究显示,FEV1的降低程度及AHR的发生频率高与体内较高水平的CRP有显著相关性[18]。本研究中,患者AHR越严重,患者体内CRP水平越高,C组患者入院后CRP水平高于其他2组,经过治疗后3组患者的炎症反应减弱,CRP水平均显著下降,3组患者的CRPc-3、CRPc-5和CRPc-7差异均具有统计学意义,且A组患者显著低于其他2组,这与CRP参与炎症反应中调节中性粒细胞有关,提示CRP参与肺部免疫反应。流行病学调查研究显示,在非过敏性哮喘患者血清中,CRP水平越高,发生AHR的概率越高。体内CRP主要是与IL-6合成,IL-6与α1抗胰蛋白酶、纤维蛋白原和结合性珠蛋白的合成有关,而α1抗胰蛋白酶与肺气体交换功能的重塑存在负相关,当患者发生急性支气管炎时,气道功能发生变化,肺功能受到影响,同时细胞膜出现损伤,使CRP的附着点暴露,由IL-6等因子将信息传递给肝脏,继而产生大量CRP[19]。
IFN-γ是由Th1辅助细胞产生的细胞因子,在细胞免疫应答中扮演着重要角色,已被证实能够抑制呼吸道疾病中的气道炎症应答[20]。本研究显示IFN-γ是重度AHR的一个保护因素。在患者血清中,IFN-γ的水平普遍较低,而C组患者的水平最低。然而,在经过治疗后,3组患者的IFN-γ水平均有显著上升,这一结果与先前的研究相吻合[21],进一步验证了药物治疗能有效提升机体内IFN-γ水平,进而抑制气道炎症反应。
在评估AHR的指标中,YKL-39、LTE4和PD20FEV1都起到了关键作用。本研究表明,YKL-39和LTE4是预测重度AHR的危险因素,而PD20FEV1则是其保护因素。经过7 d的治疗后,3组患者的PD20FEV1水平均有所上升,而YKL-39和LTE4水平则有所下降,这表明治疗有效缓解了病情,改善了AHR,促进了患者肺功能的恢复。且C组患者的YKL-39和LTE4水平明显高于A、B组,而PD20FEV1水平则显著较低,提示C组患者治疗效果相对较差。YKL-39不仅能在肿瘤细胞的生长、侵袭、血管发生等过程起作用,且对机体炎症反应的缓解也有一定的作用,患有呼吸疾病的患者体内YKL-39水平会明显上升,因此YKL-39也可以作为AHR的预测因子[22]。有研究显示气道的异常扩张与LET4介导有关,本研究中多因素分析显示LET4是重度AHR的危险因素,与文献研究相符[23]。
本研究局限性:样本量较小,未来还须增大样本量,以期提供更加精准的数据支撑。
综上所述,轻度AHR患者CRPc高于中度及重度AHR患者,患者CRPc-3、CRPc-5、CRPc-7与AHR程度存在相关性,对预测患者是否为重度AHR具有重要影响。

作者贡献声明

徐伟:设计研究方案,采集、分析、解释数据,撰写论文;程继夏,李洁:实施研究、统计分析数据;张华:提出研究框架,对论文进行修订,指导研究。

利益冲突声明

本研究未受到企业、公司等第三方资助,不存在潜在利益冲突。

References

Publishing order | Descend order by publishing year | Descend order by cited within
[1]
滕龙飞, 陈佳丽, 周庆伟, 等. 基于网络药理学和分子对接探究三拗片治疗急性支气管炎分子作用机制[J]. 中国现代中药, 2021, 23(8):1399-1405.
TENG L F, CHEN J L, ZHOU Q W, et al. Molecular mechanism of san'ao pian in treatment of acute bronchitis based on network pharmacology and molecular docking[J]. Mod Chin Med, 2021, 23(8):1399-1405.
Cited in this article [1]
[2]
BUTT M A, PEICHER M, NGUYEN A P, et al. Antibiotic stewardship in patients with acute bronchitis: a case report of doxycycline-induced esophagitis[J]. Cureus, 2022, 14(6):e26354.
Cited in this article [1]
[3]
孙华俊, 郭玲, 相影莉. 风险筛查联合精准管理模式对发热门诊急性支气管炎留观患者康复效应、临床满意度及生活质量的影响[J]. 中国医药导报, 2023, 20(14):179-182.
SUN H J, GUO L, XIANG Y L. Effect of risk screening combined with precise management model on rehabilita-tion effectiveness, clinical satisfaction, and quality of life of patients with acute bronchitis in fever outpatient clinic[J]. China Medical Herald, 2023, 20(14):179-182.
Cited in this article [1]
[4]
TAYLOR A, ZERFAS I, LE C, et al. Treatment of acute bronchitis and its impact on return emergency department visits[J]. J Emerg Med, 2022, 63(1):10-16.
https://doi.org/10.1016/j.jemermed.2022.01.020
https://www.ncbi.nlm.nih.gov/pubmed/35933264
Cited in this article [1] Abstract
Antibiotics are not recommended in healthy, uncomplicated adults for the treatment of acute bronchitis, yet are still often prescribed. No randomized studies have examined whether prescribing antibiotics in the emergency department (ED) impacts hospital return rates.Our aim was to compare hospital return rates between those who were prescribed an antibiotic vs. those who were not prescribed an antibiotic for the treatment of acute bronchitis.A retrospective cohort study was completed evaluating patients aged 18-64 years who presented to a community teaching hospital ED with acute bronchitis between January 2017 and December 2019. The primary outcomes were 30-day ED return and hospital admissions from initial ED visit. The rates of ED return or readmitted were compared for patients prescribed an antibiotic for treatment of acute bronchitis vs. those patients who were not prescribed an antibiotic.Of the 752 patients included, 311 (41%) were prescribed antibiotics. Baseline demographics were similar between both groups. Of those prescribed an antibiotic, 26 of 311 (8.4%) returned to the hospital within 30 days compared with 33 of 441 patients (7.5%) who were not prescribed an antibiotic (odds ratio 1.13; 95% confidence interval 0.66-1.92).There was no association found between antibiotic therapy for treatment of acute bronchitis and return to the hospital.Copyright © 2022. Published by Elsevier Inc.
[5]
SPAHN J D, BRIGHTLING C E, O'BYRNE P M, et al. Effect of biologic therapies on airway hyperresponsiveness and allergic response: a systematic literature review[J]. J Asthma Allergy, 2023, 2023(16):755-774.
Cited in this article [1]
[6]
陈庆芸, 刘运禅, 石湘淋, 等. 气道高反应性637例[J]. 安徽医药, 2019, 23(9):1825-1827.
CHEN Q Y, LIU Y C, SHI X L, et al. Follow-up analysis of 637 cases of airway hyperresponsiveness[J]. Anhui Medical and Pharmaceutical Journal, 2019, 23(9):1825-1827.
Cited in this article [1]
[7]
HAMMAD H, LAMBRECHT B N. The basic immunology of asthma[J]. Cell, 2021, 184(6): 1469-1485.
https://doi.org/10.1016/j.cell.2021.02.016
https://www.ncbi.nlm.nih.gov/pubmed/33711259
Cited in this article [1] Abstract
In many asthmatics, chronic airway inflammation is driven by IL-4-, IL-5-, and IL-13-producing Th2 cells or ILC2s. Type 2 cytokines promote hallmark features of the disease such as eosinophilia, mucus hypersecretion, bronchial hyperresponsiveness (BHR), IgE production, and susceptibility to exacerbations. However, only half the asthmatics have this "type 2-high" signature, and "type 2-low" asthma is more associated with obesity, presence of neutrophils, and unresponsiveness to corticosteroids, the mainstay asthma therapy. Here, we review the underlying immunological basis of various asthma endotypes by discussing results obtained from animal studies as well as results generated in clinical studies targeting specific immune pathways.Copyright © 2021 Elsevier Inc. All rights reserved.
[8]
TEFERRA A A, VONK J M, BOEZEN H M. Longitudinal changes in airway hyperresponsiveness and COPD mortality[J]. Eur Respir J, 2020, 55(2):1901378.
Cited in this article [1]
[9]
ZHANG F F, FANG Y, YANG P, et al. Inhibition of TRPA1 reduces airway inflammation and hyperresponsiv-eness in mice with allergic rhinitis[J]. FASEB J, 2021, 35(5):e21428.
Cited in this article [1]
[10]
JI S R, ZHANG S H, CHANG Y, et al. C-reactive protein: the most familiar stranger[J]. Journal of Immunology, 2023, 210(6): 699-707.
Cited in this article [1]
[11]
LIU C, LI C. C-reactive protein and cardiovascular diseases: a synthesis of studies based on different designs[J]. Eur J Prev Cardiol, 2023, 30(15):1593-1596.
https://doi.org/10.1093/eurjpc/zwad116
https://www.ncbi.nlm.nih.gov/pubmed/37079296
Cited in this article [1]
[12]
VANDEVANTER D R, HELTSHE S L, SKALLAND M, et al. C-reactive protein (CRP) as a biomarker of pulmonary exacerbation presentation and treatment response[J]. J Cyst Fibros, 2022, 21(4):588-593.
Cited in this article [1]
[13]
朱蕾, 张静, 金美玲. 临床肺功能[M]. 2版. 北京: 人民卫生出版社, 2014:394-416.
ZHU L, ZHANG J, JIN M L. Clinical lung function[M]. 2ndEd. Beijing: People's Medical Publishing House, 2014:394-416.
Cited in this article [1]
[14]
中华医学会, 中华医学会杂志社, 中华医学会全科医学分会, 等. 急性气管-支气管炎基层诊疗指南(2018 年)[J]. 中华全科医师杂志, 2019, 18(4):314-317.
CHINESE MEDICAL ASSOCIATION, JOURNAL OF CHINESE MEDICAL ASSOCIATION, GENERAL MEDICINE BRANCH OF CHINESE MEDICAL ASSOCIATION, et al. Primary diagnosis and treatment guidelines for acute tracheobronchitis (2018)[J]. Chinese Journal of General Practitioners, 2019, 18(4):314-317.
Cited in this article [1]
[15]
LEE S W, LYU Y R, KIM S Y, et al. Efficacy and safety of GHX02 in the treatment of acute bronchitis and acute exacerbation of chronic bronchitis: a phase Ⅱ, randomized, double-blind, placebo-controlled, multicenter trial[J]. Front. Pharmacol, 2022, 2021(12):761575.
Cited in this article [1]
[16]
DUAN Q, ZHOU Y, YANG D. Endoplasmic reticulum stress in airway hyperresponsiveness[J]. Biomed Pharmacother, 2022, 149(1):112904.
Cited in this article [1]
[17]
BURGER P M, KOUDSTAALl S, MOSTERD A, et al. C-reactive protein and risk of incident heart failure in patients with cardiovascular disease[J]. J Am. Coll. Cardiol, 2023, 82(5):414-426.
Cited in this article [1]
[18]
KONY S, ZUREIKeik M, DRISS F, et al. Association of bronchial hyperresponsiveness and lung function with C-reactive protein (CRP): a population based study[J]. Thorax, 2004, 59(10):892-896.
https://www.ncbi.nlm.nih.gov/pubmed/15454657
Cited in this article [1] Abstract
C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of adverse cardiovascular events. Respiratory impairment is also associated with cardiovascular risk. Although some studies have found an inverse relationship between lung function and markers of systemic inflammation, only one study has reported a relationship between lung function and CRP levels. In contrast, little is known about the relationship between bronchial hyperresponsiveness (BHR) and systemic inflammation. The association between lung function and CRP and between BHR and CRP has been investigated.As part of the European Community Respiratory Health Survey follow up study serum CRP levels, forced expiratory volume in 1 second (FEV(1)), and BHR to methacholine (>/=20% decrease in FEV(1) to <4 mg methacholine) were measured in 259 adults aged 28-56 years free of cardiovascular disease or respiratory infection.Mean (SD) FEV(1) (adjusted for age, sex, height, and smoking status) was lower in subjects with a high CRP level (high tertile) (3.29 (0.44) l/s v 3.50 (0.44) l/s; p<0.001) and BHR was more frequent (41.9% v 24.9%; p = 0.005) than in subjects with lower CRP levels (low+middle tertiles). Similar results were obtained when the potential confounding factors were taken into account. Similar patterns of results were found in non-smokers and in non-asthmatic subjects.Increased CRP levels are strongly and independently associated with respiratory impairment and more frequent BHR. These results suggest that both respiratory impairment and BHR are associated with a systemic inflammatory process.
[19]
TSOLAKIS N, NORDVALL L, JANSON, et al. Characterization of a subgroup of non-type 2 asthma with cow's milk hypersensitivity in young subjects[J]. Clin Transl Allergy, 2019, 9(12): 1-9.
Cited in this article [1]
[20]
SIEBELER R, DE WINTHER M P J, HOEKSEMA M A. The regulatory landscape of macrophage interferon signaling in inflammation[J]. J Allergy Clin Immun, 2023, 152(2):326-337.
Cited in this article [1]
[21]
DING Y, XU F, WANG Y, et al. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway[J]. CHIN J Integr Med, 2023, 21(5):496-508.
Cited in this article [1]
[22]
TIZAOUI K, YANG J W, LEE K H, et al. The role of YKL-40 in the pathogenesis of autoimmune diseases: a comprehensive review[J]. Int J Biol Sci, 2022, 18(9): 3731.
https://doi.org/10.7150/ijbs.67587
https://www.ncbi.nlm.nih.gov/pubmed/35813465
Cited in this article [1] Abstract
YKL-40, a chitinase-3-like protein 1 (CHI3L1) or human cartilage glycoprotein 39 (HC gp-39), is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells and vascular smooth muscle cells. Its biological function is not well elucidated, but it is speculated to have some connection with inflammatory reactions and autoimmune diseases. Although having important biological roles in autoimmunity, there were only attempts to elucidate relationships of YKL-40 with a single or couple of diseases in the literature. Therefore, in order to analyze the relationship between YKL-40 and the overall diseases, we reviewed 51 articles that discussed the association of YKL-40 with rheumatoid arthritis, psoriasis, systemic lupus erythematosus, Behçet disease and inflammatory bowel disease. Several studies showed that YKL-40 could be assumed as a marker for disease diagnosis, prognosis, disease activity and severity. It is also shown to be involved in response to disease treatment. However, other studies showed controversial results particularly in the case of Behçet disease activity. Therefore, further studies are needed to elucidate the exact role of YKL-40 in autoimmunity and to investigate its potential in therapeutics.© The author(s).
[23]
HOLLENHORST M I, KRASTEVA-CHRIST G. Chemosensory cells in the respiratory tract as crucial regulators of innate immune responses[J]. J Physiol, 2023, 601(9):1555-1572.
Cited in this article [1]
PDF(1064 KB)

89

Accesses

0

Citation

Detail
Sections
Recommended
Contact us
Address: Jinan University No.601 Huangpu Dadao West,Guangzhou,China
Postal Code: 510632
Associate Editors-in-Chief Phone: 020-85227136
Editing Room Phone: 020-85227865
Visited
Total visitors:
Visitors of today:
Now online:
Copyright © Journal of Jinan University Natural Science & Medicine Edition, All Rights Reserved. 粤ICP备12087612号　

/

〈 〉