基于威布尔数学模型的毛细支气管炎患儿复发性喘息风险分析

N. Tokarchuk, O. Ocheredko, A. Overchuk
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To analyze the risk factors for recurrent wheezing in children with bronchiolitis, considering allergic history, the influence of external factors (passive smoking, place of residence), levels of VCAM-1, ECP, EDN in the blood serum.Material and Methods. This article is a part of the research work of the Department of Paediatrics No. 1 of Vinnytsia National Medical University named after M.I. Pyrohov on the topic \"Optimization of diagnosis and treatment of somatic pathology in children\", state registration No. 0115U007075.A clinical examination of 67 infants was carried out. The main group consisted of 34 children with bronchiolitis without a complicated allergic history. The comparison group consisted of 33 children with bronchiolitis who had a burdened allergic history. The average age of the children in the main group was 8.4±1.6 months, and 6.2±1.4 months in the comparison group. 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It was established that the research does not contradict the basic bioethical norms and meets the principles of compliance with the basic provisions of the GCP (1996), the Council of Europe Convention on Human Rights and Biomedicine (04.04.1997), WMA Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (1964-2008) and Order of the Ministry of Health of Ukraine No. 690 of 23.09.2009 (as amended by Order of the Ministry of Health of Ukraine No. 523 of 12.07.2012). All patients were informed about the purpose and possible consequences of the research procedures. All patients signed an informed written consent to participate in the study prior to the procedure.Results of the study. The risks of recurrent wheezing in children with bronchiolitis according to the Weibull model were allergic history ( β=1,996) mixed feeding, and to an even greater extent artificial feeding ( β=7,832 and β=8,337). High serum levels of ECP β=5,03, EDN β=0,182 and VCAM-1 β=0,0254 are reliable markers of increased risk of recurrent wheezing in children with bronchiolitis. Living in rural areas ( β=-5,8) significantly reduces the risk of recurrent wheezing in children with bronchiolitis compared to children living in urban areas β=0.0162).Conclusions. 1. The levels of VCAM-1, ECP and EDN in the blood serum were recognized as reliable markers for the prognosis of recurrent vesicitis in children with bronchiolitis. The level of EDN ≤ 7 ng/ml in the blood serum is a prognostic marker for the risk of recurrent wheezing in children with bronchiolitis.2. The hypothesis that artificial feeding in children with bronchiolitis with a complicated allergic history confirms and significantly increases the risk of recurrent vesicitis in children with bronchiolitis. 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引用次数: 0

摘要

鉴于幼儿在毛细支气管炎后的第一年复发性喘息的频率(高达50%的病例),毛细支气管炎诊断生物学标志物的预后价值评估需要特别注意。根据现代概念,肥大细胞嗜酸性粒细胞在毛细支气管炎的发病过程中起着重要作用,其脱肉芽肿释放阳离子蛋白(嗜酸性粒细胞阳离子蛋白(ECP),嗜酸性粒细胞衍生神经毒素(EDN))和分子介质,即血管细胞粘附分子-1 (VCAM-1),它是白细胞粘附和跨内皮迁移的调节剂。这就是为什么VCAM-1、ECP和EDN被认为是评估毛细支气管炎患儿复发性喘息风险的重要预后指标。研究的目的。分析毛细支气管炎患儿反复喘息的危险因素,包括过敏史、外界因素(被动吸烟、居住地)、血清VCAM-1、ECP、EDN水平。材料和方法。本文是文尼察国立医科大学第一儿科以M.I. Pyrohov命名的“优化儿童躯体病理的诊断和治疗”课题研究工作的一部分,国家注册号为0150u007075。对67例婴儿进行了临床检查。主要组为34例无复杂过敏史的毛细支气管炎患儿。对照组包括33名有严重过敏史的毛细支气管炎患儿。主组患儿平均年龄8.4±1.6个月,对照组患儿平均年龄6.2±1.4个月。该研究的分析部分基于参数生存模型(Weibull和广义Gamma模型)。在基于Mac OS X 10.9平台,64位Intel Core i7架构的分析系统R for Mac OS X FAQ, Version 3.1.0 2014-04-10, R. app 1.64的统计软件包中对Weibull模型进行分析。这项研究得到了生物医学伦理委员会的批准,以遵守以M.I. Pyrohov命名的文尼察国立医科大学进行医学研究的道德和法律规则。经确定,这项研究不违反基本的生物伦理规范,并符合遵守《生物伦理公约》(1996年)、《欧洲委员会人权和生物医学公约》(1997年4月4日)的基本规定的原则。世界医学会关于涉及人体受试者的医学研究伦理原则的赫尔辛基宣言(1964-2008)和乌克兰卫生部2009年9月23日第690号命令(经乌克兰卫生部2012年7月12日第523号命令修正)。所有患者都被告知研究程序的目的和可能的后果。所有患者在手术前都签署了知情的书面同意书。研究结果。根据Weibull模型,毛细支气管炎患儿复发性喘息的风险分别为过敏史(β= 1996)、混合喂养和更大程度的人工喂养(β= 7832和8337)。血清ECP β=5,03, EDN β=0,182和VCAM-1 β=0,0254是毛细支气管炎患儿复发性喘息风险增加的可靠标志。与生活在城市地区的儿童相比,生活在农村地区(β=-5,8)显著降低了毛细支气管炎儿童复发性喘息的风险(β=0.0162)。1. 血清VCAM-1、ECP和EDN水平被认为是毛细支气管炎患儿复发性膀胱炎预后的可靠指标。血清EDN≤7 ng/ml可作为毛细支气管炎患儿喘息复发风险的预后指标。有复杂过敏史的毛细支气管炎患儿人工喂养的假设证实并显著增加毛细支气管炎患儿膀胱炎复发的风险。关于被动吸烟暴露在毛细支气管炎儿童复发性喘息风险显著增加中的作用的假设仅在血清中EDN水平不超过7 ng/ml的患者中得到证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ANALYSIS OF THE RISK OF RECURRENT WHEEZING IN CHILDREN WITH BRONCHIOLITIS BASED ON THE WEIBULL MATHEMATICAL MODEL
Given the frequency of recurrent wheezing (up to 50 % of cases) in young children during the first year after bronchiolitis, the assessment of the prognostic value of diagnostic biological markers of bronchiolitis requires special attention.According to modern concepts, mast cells, eosinophils, play a significant role in the pathogenesis of bronchiolitis, with degranulation of which the release of cationic proteins (eosinophilic cationic protein (ECP), eosinophil-derived neurotoxin (EDN)) and molecular mediators, namely vascular cell adhesion molecule-1 (VCAM-1), which is a regulator of leukocyte adhesion and transendothelial migration. That is why VCAM-1, ECP and EDN are discussed as important prognostic markers in assessing the risk of recurrent wheezing in children with bronchiolitis.The aim of the study. To analyze the risk factors for recurrent wheezing in children with bronchiolitis, considering allergic history, the influence of external factors (passive smoking, place of residence), levels of VCAM-1, ECP, EDN in the blood serum.Material and Methods. This article is a part of the research work of the Department of Paediatrics No. 1 of Vinnytsia National Medical University named after M.I. Pyrohov on the topic "Optimization of diagnosis and treatment of somatic pathology in children", state registration No. 0115U007075.A clinical examination of 67 infants was carried out. The main group consisted of 34 children with bronchiolitis without a complicated allergic history. The comparison group consisted of 33 children with bronchiolitis who had a burdened allergic history. The average age of the children in the main group was 8.4±1.6 months, and 6.2±1.4 months in the comparison group. The analytical component of the study was based on parametric survival models (Weibull and generalized Gamma models). The analysis of Weibull models was performed in the statistical packages of analytical system R for Mac OS X FAQ, Version 3.1.0 2014-04-10, R. app 1.64 based on the Mac OS X 10.9 platform, 64-bit Intel Core i7 architecture.The study was approved by the Commission on Biomedical Ethics for compliance with the moral and legal rules for conducting medical research at Vinnytsia National Medical University named after M.I. Pyrohov. It was established that the research does not contradict the basic bioethical norms and meets the principles of compliance with the basic provisions of the GCP (1996), the Council of Europe Convention on Human Rights and Biomedicine (04.04.1997), WMA Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (1964-2008) and Order of the Ministry of Health of Ukraine No. 690 of 23.09.2009 (as amended by Order of the Ministry of Health of Ukraine No. 523 of 12.07.2012). All patients were informed about the purpose and possible consequences of the research procedures. All patients signed an informed written consent to participate in the study prior to the procedure.Results of the study. The risks of recurrent wheezing in children with bronchiolitis according to the Weibull model were allergic history ( β=1,996) mixed feeding, and to an even greater extent artificial feeding ( β=7,832 and β=8,337). High serum levels of ECP β=5,03, EDN β=0,182 and VCAM-1 β=0,0254 are reliable markers of increased risk of recurrent wheezing in children with bronchiolitis. Living in rural areas ( β=-5,8) significantly reduces the risk of recurrent wheezing in children with bronchiolitis compared to children living in urban areas β=0.0162).Conclusions. 1. The levels of VCAM-1, ECP and EDN in the blood serum were recognized as reliable markers for the prognosis of recurrent vesicitis in children with bronchiolitis. The level of EDN ≤ 7 ng/ml in the blood serum is a prognostic marker for the risk of recurrent wheezing in children with bronchiolitis.2. The hypothesis that artificial feeding in children with bronchiolitis with a complicated allergic history confirms and significantly increases the risk of recurrent vesicitis in children with bronchiolitis. The hypothesis about the role of passive smoking exposure in a significant increase in the risk of recurrent wheezing in children with bronchiolitis was confirmed only for patients with EDN levels not exceeding 7 ng/ml in the blood serum.
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