血小板活化因子乙酰水解酶基因多态性与儿童哮喘易感性关系的研究

目的　探讨血小板活化因子乙酰水解酶 (PAF AH)基因多态性与儿童哮喘严重程度的关系。方法　采用等位基因特异性聚合酶链式反应 (AS PCR)技术 ,检测 131例不同严重程度的哮喘患儿及 10 4例健康儿童PAF AH基因第 9外显子Val 2 79Phe基因多态性。结果　轻、中度哮喘组与对照组 3种基因型 (Val 2 79Val、Val 2 79Phe、Phe 2 79Phe)在分布频率上差异无显著性 (P >0 0 5 ) ,但重度哮喘患儿与轻、中度哮喘组及对照组相比 ,差异显著 (P 均 <0 0 5 ) ;Phe等位基因频率重度哮喘组与轻、中度哮喘组及对照组相比差异显著 (P 均 <0 0 5 )。结论　PAF AH基因 (Val 2 79Phe)突变可能为重度哮喘儿童的易感基因之一。     

血小板活化因子乙酰水解酶基因多态性与过敏性紫癜消化道出血的相关性研究

目的从基因水平探讨血小板活化因子乙酰水解酶(PAF-AH)基因第9号外显子Val297Phe单核苷酸多态性与过敏性紫癜(HSP)消化道出血的关系。方法选取516例HSP患者,其中合并消化道出血的182例、非消化道出血的334例,应用聚合酶链式反应(PCR)检测Val279Phe多态性位点的基因型及等位基因分布情况,并测定血浆PAF-AH活性、血小板活化因子(PAF)、α颗粒膜糖蛋白140(GMP-140)、β-血小板球蛋白(β-TG)和血小板第4因子(PF4)的水平。结果 Val279Phe基因型及等位基因频率分布符合HardyWeinberg平衡,纯合突变基因型TT占0.97%、杂合子占6.05%。等位基因频率在消化道出血组为5.22%,明显高于对照组(3.33%),差异有统计学意义(P0.01)。合并消化道出血的GG基因型HSP患者的血浆PAF和GMP-140水平高于非出血组(P0.05),PAF-AH活性以非出血组较高(P0.01),而β-TG和PF4在两组间的差异没有统计学意义(P0.05)。结论 PAF-AH Val279Phe基因多态性与血浆PAF-AH活性、PAF及GMP-140水平有关,PAF-AH Val279Phe基因多态性可能是HSP合并消化道出血的一个风险因素。     

新生儿缺氧缺血性脑病血浆及脑脊液血小板活化因子的变化

目的　观察新生儿缺氧缺血性脑病 (HIE)血浆及脑脊液 (CSF)血小板活化因子 (PAF)的变化 ,探讨PAF在HIE发病中的作用。方法　于急性期和恢复期分别采集患儿血浆和CSF ,采用生物活性法检测血浆及CSF中PAF水平 ,并分析其与脑损伤和 1minApgar评分的关系。 结果　 1.HIE患儿急性期CSF中PAF水平明显高于对照组患儿 (P <0 .0 1) ,且与病情轻重呈明显正相关 (r =0 .6 5　P <0 .0 1) ;急性期中度与重度HIE患儿血浆PAF水平显著高于对照组 (P <0 .0 1) ,且与病情轻重呈明显正相关 (r =0 .5 9　P <0 .0 1) ,而轻度患儿与对照组无明显差异 (P >0 .0 5 ) ;恢复期与对照组比较无显著差异。 2 .血浆PAF水平与CSF中PAF水平呈正相关 ,血浆及CSF中PAF水平与脑损伤程度及 1minApgar评分呈明显正相关。 结论　PAF可能参与新生儿HIE的发病机制 ,CSF中PAF水平可作为判断HIE病情轻重和预后的重要指标     

支气管哮喘患儿尿5项微量蛋白测定及其临床意义

目的　探讨支气管哮喘患儿肾脏受损情况。方法　采用速率免疫散射比浊法和化学显色终点法分别测定 6 6例轻、中、重度支气管哮喘急性发作期患儿的尿视黄醇结合蛋白 (RBP)、白蛋白 (Alb)、转铁蛋白 (TRF)、免疫球蛋白G(IgG)和N 乙酰 β D 氨基葡萄糖苷酶 (NAG)含量 ,并与 32例正常儿童对照组对照。 结果　轻、中、重度哮喘患儿尿RBP、Alb、TRF、NAG含量均高于对照组 (均P <0 0 1) ,尿IgG含量与对照组差别无显著性意义(P >0 0 5 )。尿RBP、NAG含量重度哮喘患儿高于轻、中度哮喘患儿 (均P <0 0 5 ) ,轻度与中度哮喘患儿差别无显著性意义 (均 P >0 0 5 )。尿TRF、Alb含量在轻、中、重度哮喘患儿差别均无显著性意义 (均 P >0 0 5 )。结论　支气管哮喘患儿急性发作期存在肾小球和肾小管轻度或早期损害。     

血小板活化因子水解酶基因突变与原发性肾病综合征的相关性

目的研究血小板活化因子水解酶（PAF—AH）基因突变与不同类型原发性肾病综合征（PNS）的相关性。方法94例PNS患儿，依据对激素治疗的效应分为激素敏感型NS（SSNS）组37例,激素耐药型NS（SRNS）组26例，激素依赖型NS（SPNS）组31例，239例健康对照组儿童作为对照，应用聚合酶链反应（PER）及聚丙烯酰胺凝胶电泳分析的方法检测其PAF—AH基因第9外显子-994位点基因型及等位基因频率，同时对各种PAF—AH基因型的PNS患儿的病情反复情况进行对比分析。结果NTNS患儿血浆型-PAF—AH基因-994位点基因突变频率显著高于STNS及健康对照组；所有PNS及SSNS、SRNS与健康对照组儿童比较，PAF—AH基因．第9外显子-994位点基因突变频率差异无统计学意义，SDNS组突变频率显著高于健康对照及SSNS组；PAF—AH基因第9外显子-994位点基因GT型或TT型第1年内反复次数显著高于GG型者。结论血浆型PAF—AH基因第9外显子-994位点基因突变的PNS患儿在临床类型上多为NTNS，且易于在以后的治疗中出现依赖倾向。     

转化生长因子β1基因多态性与儿童哮喘易感性研究

目的探讨转化生长因子β1(TGFβ1)基因多态性与儿童哮喘的关系。方法应用聚合酶链反应 -限制性片段长度多态性 (PCR_RFLP)技术对98例哮喘患儿与52例正常儿童进行TGFβ1 基因5′-侧翼区 -509C/T多态性分析 ,并采用双抗体夹心ELISA法检测血清总IgE水平。结果哮喘组基因型分布和等位基因频率与对照组相比 ,差异均无显著性 (P>0.05) ;重度哮喘组基因型分布和等位基因频率与轻度组或对照组相比 ,差异有显著性(P<0.05) ;基因型为TT型的哮喘患儿血清总IgE水平明显高于CC型或CT型 ,差异具有显著性 (P<0.05)。结论TGFβ1 基因 -509C/T突变不是儿童哮喘的高发因素 ,但它可能是重度哮喘的候选基因 ,且突变纯合型与血清总IgE水平升高有关。     

哮喘与血管紧张素转换酶基因插入及缺失多态性关联的研究

对探讨血管紧张素转换酶（ACE）基因插入（I）及缺失（D）多态性与儿童哮喘易感性及病情程度的关联,应用聚合酶链反应（PCR）确定108例哮喘患儿及56例健康儿童的ACE基因型并结合临床病情程度及总IgE水平进行了分析,结果显示,哮喘组和正常对照组儿童ACE基因纯合子缺失型（DD）,插入型（II）,杂合子插入缺失型（ID）的构成比有显著差异,其中DD型在哮喘组的频率为38％,在对照组为16％,两组比较（DD型与II和ID型）有显著差异（P均＜0．05）,优势比（OR）分别为2．44和5,D等位基因频率亦明显高于对照组（P＜0．05）,携带DD基因型的哮喘患儿病情呈中,重度发作的比例和II,ID型比较明显高于轻型组（P＜0．05）,提示：ACE基因DD型与中国北方儿童哮喘的遗传易感性有关,并且与病情的严重程度有关。     

哮喘患儿血浆血栓素B2、6—酮—前列腺素Flα和血小板活化因子水平变化及意义

目的　探讨哮喘患儿血浆血栓素B2 (TXB2 )、6 酮 前列腺素F1α( 6 K PGF1α)及血小板活化因子(PAF)水平的变化及意义。方法　检测 30例哮喘患儿在哮喘发作期及其中 2 4例处于喘息缓解期的血浆TXB2 、6 K PGF1α和PAF水平 ,并以 2 0例健康儿童作为对照。结果　哮喘患儿喘息发作期血浆TXB2 、TXB2 / 6 K PGF1α(T/P)和PAF较对照组及喘息缓解期明显升高 (P分别 <0 .0 1,0 .0 5 ) ;喘息缓解期血浆TXB2 、T/P和PAF与对照组比较无显著差异 (P均 >0 .0 5 ) ;而各组间 6 K PGF1α无显著差异 (P均 >0 .0 5 )。结论　TXA2 、PAF是导致哮喘发作的重要炎性介质 ,在哮喘的免疫发病机制中占有重要地位     

新生儿缺氧缺血性脑损伤与血小板活化因子的关系

目的　探讨新生儿缺氧缺血性脑损伤 (HIBD)时血浆血小板活化因子 (PAF)水平的变化。方法　建立血浆PAF的生物学测定方法 ,检测 75例缺氧缺血性脑病 (HIE)新生儿发病首日及病后 10d(恢复期 )血浆PAF水平 ,并与 3 0例健康新生儿PAF水平进行对比。结果　不同临床分度HIE患儿血浆PAF水平与对照组PAF均有显著性差异。中、重度HIE患儿发病首日血浆PAF水平明显高于病后 10d及正常对照组 (t =9.51,10 .14　P均 <0 .0 1)。结论　PAF参与新生儿HIBD的全过程     

急性发作期哮喘患儿诱导痰中白细胞介素-5水平变化及其临床意义

目的　观察急性发作期哮喘患儿诱导痰中白细胞介素 5 (IL 5 )水平变化及其与哮喘发作期病情分度的关系 ,探讨其在哮喘发病机制中的作用和在临床诊治中的意义。方法　按随机分层设计 ,6 5例急性发作期哮喘患儿被分为轻、中、重度发作组 ,34例健康儿童作为对照组。采用超声雾化高渗盐水诱导痰液 ,以酶联免疫法(ELISA)测定诱导痰中IL 5水平 ,同时进行诱导痰中嗜酸细胞 (EOS)计数 ,测定用力呼气比值 (FEV1)。结果　哮喘急性发作期患儿诱导痰中EOS计数、IL 5水平均高于健康儿童组 ,FEV1则低于健康儿童组 ,差异均具有显著性(P <0 .0 1)。急性发作期哮喘患儿轻、中、重度各组间诱导痰中EOS逐渐增高 ,但差异无显著性 (P >0 .0 5 ) ;而IL 5水平随发作程度的加重而明显升高 ,轻、中、重度发作各组间两两比较差异均有显著性 (P <0 .0 5 ) ;重度哮喘患儿FEV1低于轻、中度哮喘 (P <0 .0 5 )。痰液中IL 5水平与EOS计数之间呈显著正相关 (r =0 .4 82 ,P <0 .0 5 ) ,与FEV1值之间呈显著负相关 (r =- 0 .6 4 7,P <0 .0 1)。结论　诱导痰中IL 5水平可能较EOS计数更能准确反映哮喘患儿气道炎症和哮喘发作时的病情程度 ,可以作为临床评价哮喘病情和药物疗效的准确灵敏的指标。     

神经激肽A在哮喘患儿血浆含量变化的动态研究

目的　动态研究哮喘患儿血浆神经激肽A(NKA)含量变化规律 ,探讨NKA与小儿哮喘的关系。方法　用酶联免疫方法 ,动态测定 35例不同严重程度哮喘小儿血浆NKA在哮喘发作期及其临床症状缓解期的含量变化。结果　 (1 )小儿哮喘发作期血浆NKA含量 [(2 56± 1 53)ng/L]高于自身症状缓解期 [(70± 66)ng/L]及正常对照组 [(38± 6)ng/L] ,差异有非常显著意义 (q分别为9 497、8 599,P均 <0 0 1 ) ;哮喘症状缓解期血浆NKA含量较正常对照组差异无显著意义 (q =1 2 4 5 ,P >0 0 5)。 (2 )哮喘小儿病情加重 ,血浆NKA含量亦随之增高 ,重度哮喘发作时血浆NKA含量 [(2 96± 1 70 )ng/L]明显高于轻、中度哮喘发作时含量 [(1 90± 99)ng/L] ,差异有显著意义 (q =3 77,P <0 0 5)。结论　小儿哮喘发作期血中NKA含量明显增高 ,病情愈重增高越明显 ,随哮喘症状缓解血中NKA含量下降至正常水平 ;血中NKA含量的变化与小儿哮喘的发作及缓解关系密切     

血清Clara 细胞分泌蛋白、总IgE与嗜酸性粒细胞阳离子蛋白在儿童哮喘检测中的临床意义

目的探讨血清Clara细胞分泌蛋白（CC16）、总IgE和嗜酸性粒细胞阳离子蛋白（ECP）检测在哮喘儿童中的意义。方法采用酶联免疫吸附法（ELISA）测定59例哮喘患儿急性发作期血清CC16水平,同时应用UniCAP100变态反应检测仪检测血清总IgE、ECP;另设30例健康儿童作为健康对照组。结果与健康对照组比较,哮喘组血清CC16水平显著降低、血清总IgE、ECP水平显著增高（t=2.93,2.72,4.52Pa〈0.01）;中重度哮喘发作患儿血清CC16水平显著低于轻度发作患儿（t=5.26P〈0.05）,中重度哮喘发作患儿血清总IgE显著高于轻度发作患儿（t=3.89P〈0.05）,血清ECP水平在哮喘轻度发作组与中重度发作组比较无统计学差异（t=1.57P〉0.05）;哮喘组血清CC16与总IgE呈显著负相关（r=-0.602P〈0.05）,血清CC16与ECP（r=0.153P〉0.05）及总IgE与ECP（r=0.290P〉0.05）无相关。结论血清CC16降低与总IgE、ECP水平增高在儿童哮喘发病过程中发挥重要作用;血清总IgE、CC16可反映哮喘发作严重程度;血清ECP水平高低并不能反映呼吸道炎症严重程度。     

急性发作期哮喘患儿诱导痰中白细胞介素-5水平变化及其临床意义

目的：观察急性发作期哮喘患儿诱导痰中白细胞介素-5(IL -5)水平变化及其与哮喘发作期病情分度的关系，探讨其在哮喘发病机制中的作用和在临床诊治中的意义。方法：按随机分层设计，65例急性发作期哮喘患儿被分为 轻、中、重度发作组，34例健康儿童作为对照组。采用超声雾化高渗盐水诱导痰液，以酶联 免疫法(ELISA)测定诱导痰中IL5水平，同时进行诱导痰中嗜酸细胞(EOS)计数，测定用力 呼气比值(FEV-1)。结果：哮喘急性发作期患儿诱导痰中EOS计数、IL-5 水平均高于健康儿童组，FEV-1则低于健康儿童组，差异均具有显著性(P 0.05)；而IL-5水平随发作程度的加重而明显升高，轻、中、重度发作各组间两两比较差异均有显著性(P<0.05)；重度哮喘患儿FEV-1低于轻、中度哮喘(P<0.05) 。痰液中IL-5水平与EOS计数之间呈显著正相关(r=0.482，P<0.05)，与F EV-1值之间呈显著负相关(r=-0.647，P<0.01)。结论：诱导痰中IL-5水平可能较EOS计数更能准确反映哮喘患儿气道炎症和哮喘发作时的病情程度，可以作为临床评价哮喘病情和药物疗效的准确灵敏的指标。     

Study of growth in prepubertal asthmatics

Objective The aim of this pilot study was to assess whether long standing asthma affects growth in prepubertal Egyptian children before initiation of long-term corticosteroid therapy. Methods Children with asthma were divided into two groups according to asthma severity, moderate (n=24) and severe (n=14) and were compared for their physical and skeletal growth with a control group (n=15) using standard deviation score (SDS) and oneway ANOVA (analysis of variance) test. Results No statistically significant differences were found between various growth parameters (weight, height, BMI, upper segment lower segment ratio, and skin fold thickness in asthmatic and normal children, although a positive correlation was found between the age at which the asthma presented and the height in all asthmatic children, r=0.288, p=0.036. The bone age standard deviation scores (SDS) were 0.97 mean, −0.165 and −0.572 for controls, moderate and severe asthmatics respectively (P<0.05), and significant inter group difference between the 2 asthmatic groups (moderate and severe) and the controls was found. Conclusion The authors conclude that there was no significant major effect of asthma per se on growth parameters in children, but that skeletal maturation was influenced by long standing asthma.     

Asthma – A Disease of How We Breathe: Role of Breathing Exercises and Pranayam

To describe the role of breathing exercises or yoga and/or pranayama in the management of childhood asthma. We conducted an updated literature search and retrieved relevant literature on the role of breathing exercises or yoga and/or pranayama in the management of childhood asthma. We found that the breathing exercises or yoga and/or pranayama are generally multi-component packaged interventions, and are described as follows: Papworth technique, Buteyko technique, Yoga and/or Pranayam. These techniques primarily modify the pattern of breathing to reduce hyperventilation resulting in normalisation of CO2 level, reduction of bronchospasm and resulting breathlessness. In addition they also change the behaviour, decrease anxiety, improve immunological parameters, and improve endurance of the respiratory muscles that may ultimately help asthmatic children. We found 10 clinical trials conducted in children with asthma of varying severity, and found to benefit children with chronic (mild and moderate) and uncontrolled asthma, but not acute severe asthma. Breathing exercises or yoga and/or pranayama may benefit children with chronic (mild and moderate) and uncontrolled asthma, but not acute severe asthma. Before these techniques can be incorporated into the standard care of asthmatic children, important outcomes like quality of life, medication use, and patient reported outcomes need to be evaluated in future clinical trials.     

Management of severe asthma in children

The majority of children with asthma are classified as mild/moderate and can be successfully managed with regular inhaled corticosteroids and bronchodilators. However, more than 5% of asthmatic children continue to have sub-optimal control despite apparently appropriate therapy. These children suffer significant morbidity including poor school attendance, adverse effects on family life and consume disproportionate health care resources. True therapy resistant asthma is rare in children and paediatricians should focus on ensuring the correct diagnosis, identifying and managing modifiable risk factors for difficult to control asthma before using the label severe asthma. Management of severe asthma requires a multidisciplinary approach. Symptomatic children on Step 4 (less than 5 years) or Step 5 (more than 5 years) of British Thoracic Society/SIGN Asthma Guideline or in children with diagnostic uncertainty should be referred to the local tertiary paediatric respiratory service.     

Vitamin A status in children with asthma

Low vitamin A levels have been found in a number of diseases in children. The aim of this study was to examine the vitamin A status in children with asthma and to correlate the changes with severity of disease. Serum levels of vitamin A, retinol‐binding protein (RBP), and albumin were estimated in 35 asthmatic children (24 males) in the age group of 2–12 years (mean 5.89 years) and 29 controls (19 males). Both study and control groups were similar with respect to age, sex, and overall nutritional status. Twenty‐four children in the study group (68.6%) had moderate to severe persistent asthma and eight children had mild persistent asthma. Only three patients suffered from mild intermittent asthma. Vitamin A levels in children with asthma (mean ± SD 22.14 ± 5.38 µg/dl) were found to be significantly lower than their controls (mean ± SD 27.54 ± 4.83 µg/dl) (p = 0.0001). Age, age of onset of asthma, and gender had no correlation with serum vitamin A levels. Low serum vitamin A levels (< 20 µg/dl) were observed four times more commonly in the study group (28.6%) than controls (6.9%). Severity of asthma had a negative correlation with serum vitamin A levels (r = ? 0.61, p = 0.0001). Children with severe persistent asthma had markedly low serum vitamin A levels (mean ± SD 13.42 ± 5.19 µg/dl) as compared with mild intermittent asthma (mean ± SD 24.61 ± 2.32 µg/dl). Therapeutic trials are needed to prove whether low vitamin A levels contribute to asthma severity and the clinical utility of vitamin A supplementation in asthmatic children.     

Identifying problematic severe asthma in the individual child – does lung function matter?*

Aim: Measures of lung function (usually FEV₁ <80% predicted) are used to classify asthma severity in both adults and children, despite evidence that lung function impairment is less pronounced in the paediatric asthma population. The present study assesses the relevance of lung function measurements as discriminators of severe childhood asthma. Methods: Fifty‐one school‐aged children with problematic severe asthma, 37 mild‐to‐moderate asthmatics and 29 healthy controls underwent a comprehensive clinical work‐up. Problematic severe asthma was defined in patients exhibiting poor asthma control despite high‐dose inhaled corticosteroid treatment and at least one other asthma controller drug. Mild‐to‐moderate asthmatic children used low‐dose inhaled steroids and reported minimal asthma symptoms. Results: Baseline FEV₁ values were significantly reduced in children with problematic severe asthma, yet FEV₁ <80% predicted showed a low sensitivity (41%) for discriminating severe vs. mild‐to‐moderate asthma. Receiver‐operated characteristic analysis estimated the optimal cut‐off of FEV₁ to be 90% predicted in this population (sensitivity 61%, specificity 83%). Baseline FEV₁/FVC and FEF_25–75 values were not superior to FEV₁ in discriminating problematic severe asthma, and neither exhaled nitric oxide levels nor bronchial hyperresponsiveness differentiated between the two asthmatic study populations. Conclusion: Spirometric measurements are insensitive discriminators of problematic severe asthma in childhood.