重症哮喘患者血清MIP-1α和IL-13水平动态变化及其预后评估价值

doi:10.13481/j.1671-587x.20190635

摘要/Abstract

摘要： 目的：分析重症哮喘患者血清巨噬细胞炎症蛋白1α（MIP-1α）和白细胞介素13（IL-13）水平的动态变化，评估其判断患者短期预后的临床价值。方法：102例哮喘患者按病情严重程度分为重症哮喘组（42例重症哮喘患者）和轻症哮喘组（60例轻中度哮喘患者），选择同时期健康体检者50人作为对照组。随访1年后根据是否发生未控制哮喘发作将重症哮喘组分为控制亚组与再发亚组。在治疗前与治疗后第1、3、7天分别测定3组研究对象血清IL-13、MIP-1α、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）水平，记录3组研究对象用力肺活量（FVC）、第1秒用力呼气容积（FEV1）、FEV1/FVC、最大呼气中段流量（MMEF）和呼气峰流速（PEF）等肺功能指标，采用Pearson相关分析评估治疗第7天重症哮喘患者血清IL-13、MIP-1α与FEV1、MMEF及PEF的相关性，比较重症哮喘组中控制亚组与再发亚组患者治疗第7天时血清IL-13及MIP-1α水平，应用多元Logistic回归分析上述各临床指标与患者随访1年再发率的相关性，绘制受试者工作特征（ROC）曲线评估患者血清IL-13和MIP-1α水平对重症哮喘患者再发作的判断价值。结果：随治疗时间延长，重症哮喘组和轻症哮喘组患者血清IL-6、IL-13、TNF-α和MIP-1α水平逐渐降低（P<0.05），而FEV1、FEV1/FVC、MMEF和PEF逐渐增加（P<0.05）；同一时间点重症哮喘组患者血清IL-6、IL-13、TNF-α和MIP-1α水平高于轻症哮喘组（P<0.05）和对照组（P<0.05），而重症哮喘组患者FEV1、FEV1/FVC、MMEF和PEF低于轻症哮喘组（P<0.05）和对照组（P<0.05）。Pearson相关分析，重症哮喘患者血清IL-13及MIP-1α与FEV1、MMEF及PEF呈负相关关系（P<0.05）。随访1年，重症哮喘组控制亚组患者血清IL-13及MIP-1α水平低于再发亚组（P<0.01）。多元Logistic回归分析，治疗前后重症哮喘患者血清IL-13及MIP-1α水平差值为再发作危险性因素（OR=2.867，P=0.023； OR=2.135，P=0.033）。结论：重症哮喘患者治疗过程中血清IL-13和MIP-1α水平降低程度能较好评估患者的肺功能及随访1年后再发作情况。

关键词: 重症哮喘, 白细胞介素13, 巨噬细胞炎症蛋白1α, 预后, 受试者工作特征曲线

Abstract: Objective: To analyze the dynamic changes of serum levels of macrophage inflammatory protein-1α (MIP-1α) and interleukin-13 (IL-13) of the patients with severe asthma, and to evaluate their clinical values in judgment of the short-term prognosis in the patients with severe asthma. Methods: A total of 102 patients with asthma were divided into severe asthma group (42 cases of severe asthma) and mild asthma group (60 cases of mild and moderate asthma)according to the degree of asthma; a total of 50 contemporaneous healthy examinees were selected as control group. After follow-up for one year, the patients in severe asthma group were divided into preservation sub-group and recurrence sub-group.The serum levels of MIP-1α, IL-13, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) of the subjects in three groups were detected before therapy and on the 1st, 3rd,and 7th days after therapy respectively; the pulmonary indexes including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, maximum mid-expiratory flow (MMEF) and peak expiratory flow (PEF) of the subjects in three groups were also detected and compared. The correlations between the serum levels of MIP-1α and IL-13 on the 7th day after therapy and FEV1, MMEF and PEF were confirmed by Pearson linear correlation analysis. The serum levels of IL-13 and MIP-1α of the patients in severe ashma group on the 7th day after therapy were compared between preservation sub-group and recurrence sub-group, the relationships between the clinical indexes mentioned above and the recurrence rate of the patients after 1-year follow-up were confirmed by multivariate Logistic analysis,and the diagnostic values of the serum levels of MIP-1α and IL-13 in the recurrence of the patients with severe asthma were analyzed by receiver operating characteristic (ROC) curves. Results: With the prolongation of therapy time, the serum levels of -6, IL-13, TNF-α, and MIP-1α of the patients in severe asthma group and mild asthma group were decreased (P<0.05), and FEV1, FEV1/FVC, MMEF and PEF of the patients were increased (P<0.05). At the same time point, the serum levels of IL-6, IL-13, TNF-α, and MIP-1α of the patients in severe asthma group were higher than those in mild asthma group(P<0.05) and control group(P<0.05); FEV1, FEV1/FVC, MMEF, and PEF of the patients in severe asthma group were lower than those in mild asthma group(P<0.05) and control group (P<0.05). The Pearson linear correlation analysis results showed that there were negative correlations between serum MIP-1α, IL-13 and FEV1, MMEF, PEF (P<0.05). After 1-year follow-up, the serum levels of IL-13 and MIP-1α in the patients in preservation sub-group in severe asthma group were lower than those in recurrence sub-group (P<0.05). The multivariate Logistic analysis results showed that the differences of serum levels of MIP-1α and IL-13 were the independent risk factors of the recurrence of severe asthma (OR=2.135, P=0.033; OR=2.867, P=0.023). Conclusion: The decreasing degree of the serum levels of MIP-1α and IL-13 can assess the pulmonary function and the recurrence of the patients with severe asthma after 1-year follow-up.

Key words: severe asthma, macrophage inflammatory protein-1α, interleukin-13, prognosis, receiver operating characteristic curve

中图分类号:

R562.25

吕秀云, 杨婷, 徐磊, 王立红. 重症哮喘患者血清MIP-1α和IL-13水平动态变化及其预后评估价值[J]. 吉林大学学报(医学版), 2019, 45(06): 1401-1407.

LYU Xiuyun, YANG Ting, XU Lei, WANG Lihong. Dynamic changes of MIP-1α and IL-13 levels of patients with severe asthma and their valuesin prognosis evaluation[J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1401-1407.

参考文献

[1] 金蕊,佟金平,苗姝.哮喘患者血清中巨噬细胞炎症蛋白-1的表达及其临床意义[J]. 内科急危重症杂志,2017,23(5):362-364.
[2] YANG T, LI Y, LYU Z, et al. Characteristics of proinflammatory cytokines and chemokines in airways of asthmatics: relationships with disease severity and infiltration of inflammatory cells [J]. Chin Med J (Engl), 2017, 130(17):2033-2040.
[3] MEDREK S K, PARULEKAR A D, HANANIA N A. Predictive biomarkers for asthma therapy [J]. Curr Allergy Asthma Rep, 2017,17(10):69.
[4] WU F, HUANG Y, ZHANG P, et al. Interleukin-13 peptide vaccine induces protective humoral immunity in murine asthma models [J]. Oncotarget, 2017, 9(6):6678-6690.
[5] HAMMAD MAHMOUD HAMMAD R, HAMED DHED, ELDOSOKY MAER, et al. Plasma microRNA-21, microRNA-146a and IL-13 expression in asthmatic children [J]. Innate Immun, 2018, 24(3):171-179.
[6] 中华医学会呼吸病学分会哮喘学组,中国哮喘联盟.重症哮喘诊断与处理中国专家共识[J].中华结核和呼吸杂志,2017,40(11):813-829.
[7] QUIRCE S, PHILLIPS-ANGLES E, DOMÍNGUEZ-ORTEGA J, et al. Biologics in the treatment of severe asthma [J]. Allergol Immunopathol (Madr), 2017, 45(Suppl 1):45-49.
[8] SINGH M, AGARWAL A, CHATTERJEE B, et al. Correlation of cutaneous sensitivity and cytokine response in children with asthma [J]. Lung India, 2017, 34(6):506-510.
[9] DING F, LIU B, ZOU W, et al. LPS exposure in early life protects against mucus hypersecretion in ovalbumin-induced asthma by down-regulation of the IL-13 and JAK-STAT6 pathways [J]. Cell Physiol Biochem, 2018, 46(3):1263-1274.
[10] NTONTSI P, PAPATHANASSIOU E, LOUKIDES S, et al. Targeted anti-IL-13 therapies in asthma: current data and future perspectives [J]. Expert Opin Investig Drugs, 2018, 27(2):179-186.
[11] NAKAMURA Y, SUGANO A, OHTA M, et al. Docking analysis and the possibility of prediction efficacy for an anti-IL-13 biopharmaceutical treatment with tralokinumab and lebrikizumab for bronchial asthma [J]. PLoS One, 2017, 12(11):e0188407.
[12] PARULEKAR A D, KAO C C, DIAMANT Z, et al. Targeting the interleukin-4 and interleukin-13 pathways in severe asthma: current knowledge and future needs [J]. Curr Opin Pulm Med, 2018, 24(1):50-55.
[13] BUZNEY C D, GOTTLIEB A B, ROSMARIN D. Asthma and atopic dermatitis: a review of targeted inhibition of interleukin-4 and interleukin-13 as therapy for atopic disease [J]. J Drugs Dermatol, 2016, 15(2):165-171.
[14] TSILOGIANNI Z, HILLAS G, BAKAKOS P, et al. Sputum interleukin-13 as a biomarker for the evaluation of asthma control [J]. Clin Exp Allergy, 2016, 46(7):923-931.
[15] BAVEREL P G, WHITE N, VICINI P, et al. Dose-exposure-response relationship of the investigational anti-interleukin-13 monoclonal antibody tralokinumab in patients with severe, uncontrolled asthma [J]. Clin Pharmacol Ther, 2018, 103(5): 826-835.
[16] YOSRI H, ELKASHEF W F, SAID E, et al. Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model [J]. Int Immunopharmacol, 2017, 50:305-312.
[17] KAUR M, BELL T, SALEK-ARDAKANI S, et al. Macrophage adaptation in airway inflammatory resolution [J]. Eur Respir Rev, 2015, 24(137):510-515.
[18] 肖新怀,梁小敏,苏丽芳,等.哮喘患者MIP-1α等炎症因子在血清中的表达及临床意义[J].中国医师杂志,2017,19(8):1200-1206.
[19] SUGAI K, KIMURA H, MIYAJI Y, et al. MIP-1α level in nasopharyngeal aspirates at the first wheezing episode predicts recurrent wheezing [J]. J Allergy Clin Immunol, 2016, 137(3):774-781.
[20] ROJAS-DOTOR S, SEGURA-MENDEZ NH, MIYAGUI-NAMIKAWA K, et al. Expression of resistin, CXCR3, IP-10, CCR5 and MIP-1α in obese patients with different severity of asthma [J]. Biol Res, 2013, 46(1):13-20.
[21] ISHIOKA T, YAMADA Y, KIMURA H, et al. Elevated macrophage inflammatory protein 1α and interleukin-17 production in an experimental asthma model infected with respiratory syncytial virus [J]. Int Arch Allergy Immunol, 2013, 161(Suppl 2):129-137.