特异性免疫治疗儿童哮喘疗效评价及其影响因素分析
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摘要
第一部分舌下特异性免疫治疗儿童哮喘的疗效评价
目的:系统评价舌下特异性免疫治疗(SLIT)对螨变应原敏感的儿童哮喘疗效,为临床治疗和开展相关研究提供参考。
方法:以asthma AND specific immunotherapy AND mite AND control trial,哮喘和特异性免疫治疗和螨为英中文关键词,检索PubMed、EMBASE、The Cochrane Central Register of Controlled Trials (Clinical Trials),中国生物医学数据库、中国知识网、学位论文和儿童哮喘会议论文等。以文献纳入和排除标准,通过查阅文献制定效应指标的评价标准。进行文献筛选,并进行质量评价,用Revman4.2.10版进行统计分析。无法进行总合的资料进行描述性分析。
结果:共纳入了11篇文献,根据随机方法、分配隐藏、盲法和随访情况描述评分,2篇为A级,8篇为B级,1篇为C级。分析结果显示:1螨变应原SLIT治疗组与对照组比较:症状评分SMD为-1.74(95%CI-2.83~ -0.64),提示治疗组的哮喘评分较对照组明显降低。2两组用药评分的比较:SMD为-1.56(95%CI-2.95~ -0.17),提示哮喘用药评分在治疗组较对照组有显著降低。3肺功能:采用FEV1作为衡量肺功能指标,两组数据的结果分别为FEV1 SMD为0.07(95%CI-0.72~0.86)、FEV1% SMD为-0.02(95%CI-0.85~0.81),提示治疗组与对照组间的肺功能变化没有显著差别。4血清抗体的变化比较:特异性IgE总合的SMD为0.72(95%CI-0.82~2.25),提示SLIT治疗后两组的特异性IgE无显著性差别。而特异性IgG4的SMD为5.05(95%CI2.56~7.54),表明治疗结束后治疗组比对照组的特异性IgG4升高。
结论:螨变应原SLIT有助于控制螨致敏哮喘患儿症状,减少用药,通过提高特异性IgG4恢复机体正常的免疫过程,同时是一种安全的治疗方法。与对照组比较,尚没有足够的证据表明螨变应原SLIT治疗组能显著影响螨致敏哮喘患儿特异性IgE及肺功能变化。
第二部分特异性免疫治疗儿童哮喘疗效影响因素分析
目的:通过标准化尘螨特异性免疫治疗儿童哮喘的临床效果,回顾性分析影响特异性免疫治疗哮喘的预后因素。
方法:收集2007年9月至2010年2月在重庆医科大学附属儿童医院哮喘中心,进行标准化尘螨特异性免疫治疗的99名哮喘患儿,随访至特异性免疫治疗第二年结束。根据患儿临床症状缓解程度进行回顾分析,收集治疗前的肺功能、总IgE、诊断年龄等11项相关因素。用SPSS17.0统计软件进行统计检验、多因素Logistic回归分析,寻找影响特异性免疫治疗效果因素。
结果:99例患儿平均年龄为8.66±0.30岁,男女比例为74/25,其中72例临床症状缓解,而27例未明显缓解。回顾分析两组治疗前的临床资料和病史,共归纳了11项影响因素,进行统计分析。肺功能激发试验、哮喘发病年龄、合并鼻炎,与治疗效果相关,P值分别是0.008、0.001、0.043,而年龄、总IgE、病情分度、家族史、被动吸烟、过敏原、病情分度、性别、合并其他变应性疾病与治疗效果无关。多因素Logistic回归分析,哮喘发病年龄和气道高反应性P分别为0.001和0.012,是影响特异性免疫治疗疗效的独立因素。
结论:对于哮喘发病年龄小于5岁特别是小于3岁,并有明显的气道高反应性的儿童不建议进行特异性免疫治疗。
PARTⅠSystematic Review on Efficacy of Sublingual Immunotherapy for Childhood Asthma with Mite Allergen
Objective: To assess the efficacy of sublingual immunotherapy for asthma in children who are sensitive to mite and provide evidence for clinical therapy and future trial.
Method: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (Clinical Trials), CBM, CNKI were searched till November 30 2008, using the terms (asthma AND specific immunotherapy AND mite AND control trial).According to inclusion and exclusion criteria, articles were evaluated by three reviewers. Randomised controlled trials (RCTs) were assessed according to the Juni assessment .Software RevMan 4.2.10 was used to carry out statistical analysis. Analysis was performed by the method of Standardised Mean Differences (SMD) using a random-effects model. P values < 0.05 were considered statistically significant . Subgroup analyses were performed according to the type of allergen administered and the duration of treatment. The materials which can not be pooled were carried out the descriptive analysis.
Results: 11 articles which involved 722 participants identified were eligible randomised controlled trials and included。We observed symptom scores SMD = -1.74(95%CI-2.83~ -0.64)which indicated sublingual immunotherapy for children asthma with mite allergen could reduce asthma symptom scores .In term of treatment duration and the type of allergen administered, we performed subgroup analysis indicated sublingual immunotherapy with mite allergen could reduce asthma symptom scores during 4and6 months whereas increasing duration of treatment beyond 12 months does appear to increase the treatment e?ect and reduce asthma symptom scores in Dermatophagoides pteronyssinus (D.p)group. There was significantly heterogeneity, most likely due to widely differing scoring systems between studies. Medication scores SMD=-1.56(95%CI-2.95~ -0.17)suggest that medication scores was lower in treatment group than in control group. According to treatment duration and the type of allergen administered, we performed subgroup analysis indicated sublingual immunotherapy with mite allergen could reduce medication scores in Dermatophagoides pteronyssinus (D.p.) group but not in mixed allergen of D.p / D.f (Dermatophagoides farinae).We use the FEV1 to weigh the lung function. The results of change were FEV1 SMD=0.07(95%CI-0.72~0.86) and FEV1% SMD=-0.02(95%CI-0.85~0.81). There were not significant change between treatment group and control group. Antibody levels of blood serum, specific IgE in two groups of change tendencies were not significant. But the specific IgG4 change in the treatment group is higher than the control group.
Conclusion: Sublingual immunotherapy with mite allergen is helpful for reducing the child allergy asthma symptom and medication scores, restoring normal immunologic process. Increasing duration of treatment does not clearly increase efficacy. Meanwhile it is safe for children. But there are not enough evidence to indicate that the Sublingual Immunotherapy with mite allergen treatment group and the control group are different in the specificity IgE level and the lung function. Further multi-centre and large scale RCTs are still needed to be performed to evaluate the efficacy of Sublingual immunotherapy for asthma in children who are sensitive to mite. Further research is required concentrating on optimising allergen dosage and patient selection.
PARTⅡPrognosis factors in predicting clinical response to specific immunotherapy of children with asthma
Objective: By analysis of pretreatment parameters used in diagnosing asthma, serum total IgE (t-IgE) levels, onset age and bronchial hyperresponsiveness and so on, we tried to identify whether these factors can be used to predict clinical response of children with allergic asthma post treated by specific immunotherapy(SIT).
Methods: 99 children with asthma during Sep, 2007 to Feb, 2009 who had undergone 2 years of SIT administered by means of the subcutaneous immunotherapy routes were recruited in this study. All cases with or without improvement were analyzed by Logistic regression analysis for 11 related factors of clinical response to SIT. Software SPSS17.0 was used to carry on statistical analysis.
Results: The average onset age of these 99 children with asthma was 8.66±0.30 years. The proportion of boys and girls was 74/25. Good response to SIT was found in 72 cases (72%) of 99 total patients. 11factors were calculated and tested for correlation with clinical response to SIT. A significant correlation was found among asthma onset age, bronchial hyperresponsiveness, asthma with rhinitis and the clinical response to SIT. The results of Logistic regression analysis indicated that the odds ratio of asthma onset age (X1) was 3.422 (95% CI = 1.064～7.404, P = 0.001) , and the odds ratio of bronchial hyperresponsiveness (X2) was 1.341 (95% CI = 1.065～1.685, P = 0.012).
Conclusion: These results suggested that children with asthma whose onset age is younger than 5 years old, especially younger than 3 years old might not be suitable to carry on SIT. If those children are accompanied by the predominant bronchial hyperresponsiveness, they are not more suitable to take SIT.
目的:系统评价舌下特异性免疫治疗(SLIT)对螨变应原敏感的儿童哮喘疗效,为临床治疗和开展相关研究提供参考。
方法:以asthma AND specific immunotherapy AND mite AND control trial,哮喘和特异性免疫治疗和螨为英中文关键词,检索PubMed、EMBASE、The Cochrane Central Register of Controlled Trials (Clinical Trials),中国生物医学数据库、中国知识网、学位论文和儿童哮喘会议论文等。以文献纳入和排除标准,通过查阅文献制定效应指标的评价标准。进行文献筛选,并进行质量评价,用Revman4.2.10版进行统计分析。无法进行总合的资料进行描述性分析。
结果:共纳入了11篇文献,根据随机方法、分配隐藏、盲法和随访情况描述评分,2篇为A级,8篇为B级,1篇为C级。分析结果显示:1螨变应原SLIT治疗组与对照组比较:症状评分SMD为-1.74(95%CI-2.83~ -0.64),提示治疗组的哮喘评分较对照组明显降低。2两组用药评分的比较:SMD为-1.56(95%CI-2.95~ -0.17),提示哮喘用药评分在治疗组较对照组有显著降低。3肺功能:采用FEV1作为衡量肺功能指标,两组数据的结果分别为FEV1 SMD为0.07(95%CI-0.72~0.86)、FEV1% SMD为-0.02(95%CI-0.85~0.81),提示治疗组与对照组间的肺功能变化没有显著差别。4血清抗体的变化比较:特异性IgE总合的SMD为0.72(95%CI-0.82~2.25),提示SLIT治疗后两组的特异性IgE无显著性差别。而特异性IgG4的SMD为5.05(95%CI2.56~7.54),表明治疗结束后治疗组比对照组的特异性IgG4升高。
结论:螨变应原SLIT有助于控制螨致敏哮喘患儿症状,减少用药,通过提高特异性IgG4恢复机体正常的免疫过程,同时是一种安全的治疗方法。与对照组比较,尚没有足够的证据表明螨变应原SLIT治疗组能显著影响螨致敏哮喘患儿特异性IgE及肺功能变化。
第二部分特异性免疫治疗儿童哮喘疗效影响因素分析
目的:通过标准化尘螨特异性免疫治疗儿童哮喘的临床效果,回顾性分析影响特异性免疫治疗哮喘的预后因素。
方法:收集2007年9月至2010年2月在重庆医科大学附属儿童医院哮喘中心,进行标准化尘螨特异性免疫治疗的99名哮喘患儿,随访至特异性免疫治疗第二年结束。根据患儿临床症状缓解程度进行回顾分析,收集治疗前的肺功能、总IgE、诊断年龄等11项相关因素。用SPSS17.0统计软件进行统计检验、多因素Logistic回归分析,寻找影响特异性免疫治疗效果因素。
结果:99例患儿平均年龄为8.66±0.30岁,男女比例为74/25,其中72例临床症状缓解,而27例未明显缓解。回顾分析两组治疗前的临床资料和病史,共归纳了11项影响因素,进行统计分析。肺功能激发试验、哮喘发病年龄、合并鼻炎,与治疗效果相关,P值分别是0.008、0.001、0.043,而年龄、总IgE、病情分度、家族史、被动吸烟、过敏原、病情分度、性别、合并其他变应性疾病与治疗效果无关。多因素Logistic回归分析,哮喘发病年龄和气道高反应性P分别为0.001和0.012,是影响特异性免疫治疗疗效的独立因素。
结论:对于哮喘发病年龄小于5岁特别是小于3岁,并有明显的气道高反应性的儿童不建议进行特异性免疫治疗。
PARTⅠSystematic Review on Efficacy of Sublingual Immunotherapy for Childhood Asthma with Mite Allergen
Objective: To assess the efficacy of sublingual immunotherapy for asthma in children who are sensitive to mite and provide evidence for clinical therapy and future trial.
Method: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (Clinical Trials), CBM, CNKI were searched till November 30 2008, using the terms (asthma AND specific immunotherapy AND mite AND control trial).According to inclusion and exclusion criteria, articles were evaluated by three reviewers. Randomised controlled trials (RCTs) were assessed according to the Juni assessment .Software RevMan 4.2.10 was used to carry out statistical analysis. Analysis was performed by the method of Standardised Mean Differences (SMD) using a random-effects model. P values < 0.05 were considered statistically significant . Subgroup analyses were performed according to the type of allergen administered and the duration of treatment. The materials which can not be pooled were carried out the descriptive analysis.
Results: 11 articles which involved 722 participants identified were eligible randomised controlled trials and included。We observed symptom scores SMD = -1.74(95%CI-2.83~ -0.64)which indicated sublingual immunotherapy for children asthma with mite allergen could reduce asthma symptom scores .In term of treatment duration and the type of allergen administered, we performed subgroup analysis indicated sublingual immunotherapy with mite allergen could reduce asthma symptom scores during 4and6 months whereas increasing duration of treatment beyond 12 months does appear to increase the treatment e?ect and reduce asthma symptom scores in Dermatophagoides pteronyssinus (D.p)group. There was significantly heterogeneity, most likely due to widely differing scoring systems between studies. Medication scores SMD=-1.56(95%CI-2.95~ -0.17)suggest that medication scores was lower in treatment group than in control group. According to treatment duration and the type of allergen administered, we performed subgroup analysis indicated sublingual immunotherapy with mite allergen could reduce medication scores in Dermatophagoides pteronyssinus (D.p.) group but not in mixed allergen of D.p / D.f (Dermatophagoides farinae).We use the FEV1 to weigh the lung function. The results of change were FEV1 SMD=0.07(95%CI-0.72~0.86) and FEV1% SMD=-0.02(95%CI-0.85~0.81). There were not significant change between treatment group and control group. Antibody levels of blood serum, specific IgE in two groups of change tendencies were not significant. But the specific IgG4 change in the treatment group is higher than the control group.
Conclusion: Sublingual immunotherapy with mite allergen is helpful for reducing the child allergy asthma symptom and medication scores, restoring normal immunologic process. Increasing duration of treatment does not clearly increase efficacy. Meanwhile it is safe for children. But there are not enough evidence to indicate that the Sublingual Immunotherapy with mite allergen treatment group and the control group are different in the specificity IgE level and the lung function. Further multi-centre and large scale RCTs are still needed to be performed to evaluate the efficacy of Sublingual immunotherapy for asthma in children who are sensitive to mite. Further research is required concentrating on optimising allergen dosage and patient selection.
PARTⅡPrognosis factors in predicting clinical response to specific immunotherapy of children with asthma
Objective: By analysis of pretreatment parameters used in diagnosing asthma, serum total IgE (t-IgE) levels, onset age and bronchial hyperresponsiveness and so on, we tried to identify whether these factors can be used to predict clinical response of children with allergic asthma post treated by specific immunotherapy(SIT).
Methods: 99 children with asthma during Sep, 2007 to Feb, 2009 who had undergone 2 years of SIT administered by means of the subcutaneous immunotherapy routes were recruited in this study. All cases with or without improvement were analyzed by Logistic regression analysis for 11 related factors of clinical response to SIT. Software SPSS17.0 was used to carry on statistical analysis.
Results: The average onset age of these 99 children with asthma was 8.66±0.30 years. The proportion of boys and girls was 74/25. Good response to SIT was found in 72 cases (72%) of 99 total patients. 11factors were calculated and tested for correlation with clinical response to SIT. A significant correlation was found among asthma onset age, bronchial hyperresponsiveness, asthma with rhinitis and the clinical response to SIT. The results of Logistic regression analysis indicated that the odds ratio of asthma onset age (X1) was 3.422 (95% CI = 1.064～7.404, P = 0.001) , and the odds ratio of bronchial hyperresponsiveness (X2) was 1.341 (95% CI = 1.065～1.685, P = 0.012).
Conclusion: These results suggested that children with asthma whose onset age is younger than 5 years old, especially younger than 3 years old might not be suitable to carry on SIT. If those children are accompanied by the predominant bronchial hyperresponsiveness, they are not more suitable to take SIT.
引文
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