中国人哮喘易感性与染色体5q31～33区连锁关系的初步研究

目的获得中国人相关位点的资料，确定中国人哮喘易感性与染色体５ｑ３１～３３区域的连锁关系。方法采集３２个哮喘家系共１９２份样品，并取３９个正常无关个体为对照；用同位素掺入的聚合酶链反应（ＰＣＲ）法扩增多态性遗传标记Ｄ５Ｓ４３６和Ｄ５Ｓ３９３，通过受累同胞配对法进行Ｄ５Ｓ４３６和Ｄ５Ｓ３９３与哮喘和高血清总ＩｇＥ的连锁分析。结果正常对照分析：Ｄ５Ｓ４３６共获得９个等位片段，多态性信息含量（ＰＩＣ）为０．８０３，杂合度（ＨＥＴ）为０．８２３，Ｄ５Ｓ３９３共有１１个等位片段，ＰＩＣ为０．８９２，ＨＥＴ为０．８９８，表明两个位点均属于高度多态性的遗传标记。连锁分析：Ｄ５Ｓ４３６与哮喘呈连锁状态（Ｐ＜０．０５），Ｄ５Ｓ３９３与哮喘没有连锁关系；Ｄ５Ｓ４３６和Ｄ５Ｓ３９３与高血清总ＩｇＥ都没有显示连锁关系。结论染色体５ｑ３１～３３区可能存在与中国人哮喘易感基因相关的１个或多个位点，是进行中国人哮喘易感基因研究的重要候选区域之一。     

温州地区儿童血清特异性过敏原检测的临床意义

目的了解温州地区不同年龄组儿童哮喘及过敏性疾病的过敏原状况,以指导临床防治。方法采用体外过敏原检测系统(法玛西亚CAP系统)对我院呼吸科门诊及住院患儿468例进行过敏原特异性IgE(sIgE)抗体检测,将所有受检儿童分为婴幼儿、学龄前、学龄期3组,对过敏原状况进行分析比较。结果哮喘发病主要集中于学龄前和婴幼儿期,过敏性鼻炎主要发生于学龄儿童;各种过敏性疾病中过敏性鼻炎sIgE阳性检出率最高,其次是哮喘和过敏性咳嗽;婴幼儿以食物过敏为主,较大年龄儿童以吸入性过敏为主,学龄前儿童两者均可发生;温州地区吸入性过敏原以尘螨为主,食入性以虾为主;在螨sIgE阳性者中哮喘比率最高,其次是过敏性鼻炎和过敏性咳嗽。结论螨及虾是温州地区儿童最常见过敏原。哮喘应在婴幼儿及学龄前期及早进行针对性防治,体外血清过敏原特异性抗体检测CAP系统是婴幼儿及学龄前儿童过敏原检测的方法之一。     

哮喘的基因研究

哮喘是一种多基因遗传性疾病,目前,通过连锁分析,关联研究等方法,发现１１ｑ与特应性有关;控制总ＩｇＥ和气道高反应性的基因位点在染色体５ｑ３１成簇的细胞因子基因簇中,β２受体的突变和哮喘严重性有关;位于１４ｑ的Ｔ细胞抗原受体（ＴＣＲ）和特异性的ＩｇＥ反应连锁,但由于环境因素对哮喘发病的影响及哮喘表型的多样性,使当前基因的研究未取得一致性结论,研究的结果也未能用于哮喘的诊断,治疗衣对可能发生哮喘者的筛     

哮喘的基因研究

哮喘是一种多基因遗传性疾病。目前，通过连锁分析、关联研究等方法，发现１１ｑ与特应性有关；控制总ＩｇＥ和气道高反应性的基因位点在染色体５ｑ３１成簇的细胞因子基因簇中；β２受体的突变和哮喘严重性有关；位于１４ｑ的Ｔ细胞抗原受体（ＴＣＲ）和特异性的ＩｇＥ反应连锁。但由于环境因素对哮喘发病的影响及哮喘表型的多样性，使当前基因的研究未取得一致性结论，研究的结果也未能用于哮喘的诊断、治疗及对可能发生哮喘者的筛选。     

口服螨免疫疗法辅助治疗儿童哮喘疗效观察

目的　观察口服螨免疫疗法对哮喘儿童的辅助治疗作用。方法　应用螨口服脱敏液安慰剂双盲试验对２３ 例哮喘患儿进行１２ 个月的临床观察,并测定血清螨特异性ＩｇＥ（ＳＩｇＥ） 、螨皮肤变应原试验和肺功能检查。结果　服用螨脱敏液的患儿,血清螨ＳＩｇＥ在用药后６ 个月时下降并持续到１２ 个月,治疗１２ 个月时肺功能明显改善,咳嗽发作次数减少,无用药不良反应。结论　口服螨免疫疗法作为吸入激素的辅助疗法治疗螨过敏的哮喘患儿有一定效果。     

儿童慢性咳嗽与鼻窦炎的相关性探讨

目的探讨儿童慢性咳嗽与慢性鼻窦炎的关系.方法对咳嗽时间1个月以上的106例2～14岁儿童作临床观察,根据鼻窦片、胸片、螨尘皮试、支气管扩张试验及疗效,将其分为鼻窦炎组21例,鼻窦炎合并咳嗽变异性哮喘(CVA)21例,CVA或哮喘44例,支气管炎等20例.同时做诱导痰细胞学检查.结果慢性咳嗽儿童中39.6%(42/106)有慢性鼻窦炎;鼻窦炎合并CVA组与CVA或哮喘组相似,螨皮试阳性率和支气管扩张试验的阳性率均达40%左右,诱导痰嗜酸粒细胞、肥大细胞含量增高,与单纯鼻窦炎组显著不同.结论上下呼吸道是一个整体,对儿童慢性咳嗽应注意鼻窦炎的伴发,而过敏原皮试阳性、支气管扩张试验阳性及诱导痰嗜酸粒细胞和(或)肥大细胞增多是CVA或哮喘的有力证据.     

儿童支气管哮喘血清特异性IgE检测临床意义

我们采用体外法检查了哮喘患儿血清中的特异性ＩｇＥ（ｓＩｇＥ），旨在分析ｓＩｇＥ在儿童支气管哮喘发病机制中的临床意义，为儿童支气管哮喘的防治工作提供科学依据。临床资料：我院变态反应科１９９７年３月～１９９８年２月间就诊患儿４９例，据《全国小儿呼吸道疾病...     

212例儿童哮喘预后的5年随访研究

目的：探讨儿童哮喘转归和影响发病与预后的因素。方法：对随访5年以上的212例哮喘儿童资料进行回顾性分析。 结果：5年随访中,哮喘停止发作121例（57.1%）,哮喘持续91例（42.9%）。哮喘急性发作的主要诱因为呼吸道感染（71.7%）,其次是过敏原吸入（17.0%）。由呼吸道感染诱发的哮喘患儿（61.2%）较由过敏原（41.7%)或运动（26.3%）诱发者缓解率高（P＜0.05）。湿疹合并过敏性鼻炎、父母哮喘、过敏原诱发的喘息是发展成持续性哮喘的3个危险因素。结论：5年以上的随访中大部分哮喘患儿停止发作。呼吸道感染是儿童哮喘急性发作的主要诱因。由呼吸道感染诱发的哮喘转归较好。特应质及有特应质遗传背景的患儿更有可能发展成持续性哮喘。     

血清特异性IgE和IgG检测在儿童特应性皮炎过敏原诊断中的应用

目的探讨血清特异性IgE和IgG检测在儿童特应性皮炎过敏原诊断中的应用和意义。方法对64例患特应性皮炎的儿童,采用酶联免疫方法检测血清中食物过敏原的特异性IgG,同时采用免疫印迹方法检测血清中食物过敏原和吸入性过敏原的特异性IgE。结果食物过敏原特异性IgG和特异性IgE的检测结果不一致(P<0.01),食物过敏原特异性IgG的总阳性率为93.75%,主要食物过敏原是牛奶和鸡蛋。食物过敏原特异性IgE的总阳性率为46.88%,主要食物过敏原是鸡蛋和鱼虾蟹。吸入性过敏原特异性IgE的总阳性率为34.38%,主要过敏原是尘螨和霉菌。在0～1岁的特应性皮炎患儿中,以食物过敏原特异性IgE阳性多见;1岁以上的患儿吸入性过敏原特异IgE阳性多见,同时合并呼吸道过敏症状增多(P均<0.05)。结论食物过敏原和吸入性过敏原均是引起儿童特应性皮炎的重要原因。联合测定食物过敏原的特异性IgE和特异性IgG是变态反应性皮肤病患儿诊断食物过敏原的有效方法。尽早采取有效的环境控制,对治疗儿童特应性皮炎和预防呼吸道过敏性疾病的发生非常重要。     

IgE的低亲和力受体与过敏性哮喘

ＩｇＥ的低亲和力受体（ＣＤ２３）存在于Ｂ细胞、单核／巨噬细胞等多种细胞上，自向可裂解为多种可溶性ＣＤ２３，受白细胞介素４和γ干扰素等多种细胞因子的调节。它具有促进Ｂ细胞分化、调节ＩｇＥ合成和分泌的功能，与过敏性哮喘关系密切。过敏性哮喘患者Ｂ细胞和肺泡巨噬细胞中ＣＤ２３阳性率显著高于非过敏性哮喘患者及健康人，且与患者血清ＩｇＥ含量和病情严重程度呈正相关。提示ＣＤ２３在过敏性哮喘的发病机制和治疗上有重要价值。     

Associations between atopic markers in asthma and intestinal helminth infections in Cuban schoolchildren

Total serum IgE (tIgE), allergen-specific IgE (sIgE), and skin prick test (SPT) are commonly used markers for atopy and atopic disease. The association between these measures and their relationship to clinical symptoms differs in affluent and non-affluent countries. We investigated the role of intestinal helminth infections in observed variations in atopic markers and asthma, and possible diagnostic and epidemiological consequences. A cross-sectional study was conducted in Cuban schoolchildren (n = 1285; 4-14 yrs). Atopy was determined by SPT, sIgE, and tIgE; asthma by International Study of Asthma and Allergies in Childhood questionnaire; and intestinal helminth infections by stool examination. Percentages of tIgE, sIgE, and SPT positives were 88.9%, 25.5%, and 16.5%, respectively. Asthma was found in 20.8%, and helminth infections in 20.9% of the children. All three atopic markers were significantly associated with each other and with asthma. Median tIgE levels were higher in helminth-infected than in uninfected children, irrespective of their status of atopy/asthma. Discordant results between SPT and sIgE were observed in 22.6% of the children. Among SPT positives, 41% were sIgE negative. The proportion of SPT negatives among sIgE positives was 74% in helminth-infected and 58.4% in uninfected children (p < 0.05). Helminth infections affected tIgE levels, reconfirming the limited value of tIgE for diagnosis of atopy and asthma in tropical areas. Higher frequencies of sIgE than positive SPTs were observed, especially in helminth-infected children. This corresponds with current hypothesis on the role of helminths in atopy. However, the observed proportion of sIgE negatives among children with positive SPT suggests that other mechanisms may also be involved.     

Atopy patch testing in children with asthma and rhinitis symptoms allergic to house dust mite

The atopy patch test (APT) is generally used to assess immunoglobulin E (IgE) mediated sensitization to allergens in patients with atopic dermatitis, but its diagnostic role in children with respiratory allergy is still controversial. The aim of the study was to evaluate APT with house dust mite (HDM) in children with asthma and rhinitis symptoms allergic to HDM and its relevance to skin prick test (SPT) diameters and specific IgE levels. The study population consisted of 33 children, aged 8-16 yr (median: 12 yr) with asthma and 30 children with allergic rhinitis in the same age range (median: 11 yr). All patients had positive SPT results and high serum specific IgE levels for Dermatophagoides pteronyssinus APT was performed on back skin of all patients with 200 index of reactivity (IR)/ml of D. pteronyssinus allergen extracts in petrolatum (Stallerpatch) and evaluated at 72 h. Of 63 patients, 16 (25%) showed a positive patch test result. APT with HDM showed 30% (10/33) positivity among the patients with asthma and 20% (6/30) positivity among the patients with allergic rhinitis. APT presented no significant correlation with age, SPT diameter, serum total and specific IgE levels for D. pteronyssinus, nasal provocation test or pulmonary function test results. Patch testing with HDM may partly identify mite sensitive children with respiratory allergy. Positive APT results may imply that delayed hypersensitivity reactions play a role in children with asthma and rhinitis allergic to HDM.     

Status of children with cow's milk allergy in infancy by 10 years of age

To assess the development of milk protein tolerance and atopic diseases in children diagnosed for cow's milk allergy (CMA) in infancy, we conducted re-examinations of 56 CMA subjects at the age of 10 y using 204 age-matched controls. The children underwent clinical examinations and skin prick tests (SPT), and their IgE-specific antibodies to milk and five other food allergens were determined. By the age of 10 y, all but four subjects had become tolerant to at least small amounts of milk protein. However, gastrointestinal symptoms relating to more abundant milk consumption were reported by 45% of the study subjects and 15% of the controls (p < 0.001). The incidence figures for asthma, allergic rhinitis and dermatitis, as well as the occurrence of recurrent otitis, were three to four times higher than in the controls. Positive SPTs were seen in two-thirds of the subjects, the figure being highest (83%) in those with dermatitis onset CMA. Seven subjects showed positive titres of IgE-class milk-specific antibodies, and five showed a clinical response. CONCLUSION: This re-examination study showed that CMA in infancy, even when properly treated, has significant clinical consequences by posing special risks for respiratory atopy and persistence of atopic dermatitis as well as positive SPT and recurrent ear infections. However, each of these clinical manifestations seems to have an independent curriculum unrelated to the persistence of CMA itself.     

Epidemiology of atopy in 220 children. Diagnostic reliability of skin prick tests and total and specific IgE levels

BACKGROUND: We have prospectively studied 220 children attending our Division because they suffered from atopic dermatitis (AD), asthma, and allergic rhinitis (AR), to assess the epidemiology of atopic diseases, and effectiveness of the diagnostic tests commonly used in allergic children. METHODS: Among the 220 children there were 142 males (64.5%) and 78 females (35.5%) aged as follows: 57 (25.9%) 0-2 year-old, 48 (21.8%) 2-4 year-old, 49 (22.3%) 4-6 year-old, 66 (30%) >6 year-old. The diagnosis included family and personal history, physical examination, skin prick tests (SPT) and total and specific IgE (sIgE) levels. We tested inhalant and food allergens. RESULTS: There were 101 asthmatic, 88 with AD, and 31 children with AR. The analysis of variance confirmed the age influence of PRIST with a high significance (p=0.0001). SPTs were prevalent in all groups for Der p, but casein only in 1 group, and Lolium perenne only in 2 groups. RAST showed a higher uniformity, that is CM (cow's milk) and egg for one group, Der p and Lolium perenne for the remaining groups Several correlations among diagnostic tests and the age of children were evaluated with the analysis of variance. CONCLUSIONS: We emphasize that atopic diseases are genetically transmitted, that AD develops at a younger age than asthma (p=0.0052), and that SPTs have a greater effectiveness for inhalant allergens, positive at all age levels; in food allergy (FA) SPTs are less adequate and feasible.     

Urine leukotriene E4 and eosinophil cationic protein in nasopharyngeal aspiration from young wheezy children

Respiratory syncytial virus (RSV) infection is a risk factor for the development of asthma. It is very hard to distinguish bronchiolitis with respiratory virus infection from allergic asthma at first wheezing attack in early childhood. To distinguish wheezing children with RSV bronchiolitis from asthmatic children, we measured leukotriene E(4)(LTE(4)) in urine and ECP in nasopharyngeal aspiration (NPA) at first day of admission with wheezing attack. Thirty-two non-atopic children younger than the age of 3 yr with RSV induced bronchiolitis, 35 atopic asthmatic children with/without respiratory viral infection, and 23 children who exhibited no evidence of atopy, asthma, or virus infections as controls were selected in this study. We measured urinary LTE(4) and ECP level in NPA from subjects. Urinary LTE(4) concentrations in children with asthma were significantly higher than urinary LTE(4) in bronchiolitis and in controls (240.8 +/- 129.8 vs. 162.8 +/- 73.9 vs. 85.1 +/- 31.6 pg/ml). Children with RSV infection demonstrated higher urinary LTE(4) levels compared to children without RSV infection among asthmatic children. ECP in NPA was significantly correlated with urinary LTE(4) (r = 0.57, p < 0.01) in children entered this study who had detectable levels for both LTE(4) and ECP. In summary, Urinary LTE(4) concentrations may be suggested to useful mediators for differential diagnosis of wheezy diseases in early childhood. RSV infection also is associated with synergizing LT biosynthesis and this study demonstrated ECP in NPA was significantly correlated with urinary LTE(4) and may suggest that cysteinyl leukotriene initiate the production of ECP in early childhood, which could contribute to the development of wheeze.     

Value of skin prick test and atopy patch test in mite-induced respiratory allergy and/or atopic eczema/dermatitis syndrome

AIM: The atopy patch test (APT) was introduced to assess sensitization to inhalant allergens in patients with atopic/eczema dermatitis syndrome (AEDS), but its diagnostic role in subjects with respiratory allergy is scantly investigated. We sought to evaluate the response to APT and to skin prick tests (SPT) with mite extracts in subjects with persistent respiratory symptoms (rhinoconjunctivitis, rhinosinusitis, asthma), with AEDS, and with both the diseases. METHODS: Eighty-nine patients were included in the study, 75 (84.3%) children and 14 (15.7%) adults, 54 (60.7%) males and 35 (39.3%) females (median age 5.4 years). They were divided in 3 groups, respectively formed by 47 (mean age 12.3+/-11.6 years), 15 (mean age 2.2+/-2.5 years), and 27 (mean age 6.2+/-6.3 years) subjects, according to the presence of only respiratory symptoms, only AEDS, or both, and underwent to usual SPT with mite extracts and to APTs done by mite extract in Finn chambers and removed after 48 hours, with readings after 20 minutes and 24 hours. RESULTS: Of the 89 patients, 24 showed a positive SPT and 69 a positive APT; in 17 both SPT and APT were positive, while 13 were negative to the 2 tests. The APT was more frequently positive than SPT not only in the 2 groups with AEDS -- 32/42 (86.5%) vs 8/42 (21.6%) -- but also in the group with only respiratory symptoms -- 37/47 (78.7%) vs 16/47 (34%). CONCLUSION: These results confirm the high value of APT in patients with mite-induced AEDS and suggest that its routine use might improve also the diagnosis of respiratory allergy to house dust mites.     

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。     

Wheezy babies--wheezy adults? Review on long-term outcome until adulthood after early childhood wheezing.

Population-based birth cohort studies have documented that about 30% of children suffer from wheezing during respiratory infection before their third birthday. Recurrent wheezing is common in early childhood, but most patients outgrow their symptoms by school age. However, recent long-term postbronchiolitis follow-up studies from Sweden and Finland have revealed that asthma is present in about 40% of young adults and over half of the cases are relapses after many symptom-free years. In population studies, the principal predictors for later asthma have been parental asthma, recurrent wheezing, atopy and eosinophilia. In the Swedish postbronchiolitis study, atopic diathesis through the development of clinical atopy, and early passive smoking through bronchial hyper-reactivity or later active smoking led to adult asthma. The Finnish postbronchiolitis follow-up stressed early recurrence of wheezing, wheezing induced by less invasive viruses than respiratory syncytial virus (RSV), early-life atopy and eosinophilia and parental asthma as predictors for adult asthma. CONCLUSION: The majority of wheezing infants and children outgrow their symptoms by school age, but based on recent long-term follow-up studies, asthma relapses are common in young adults. These studies have highlighted parental asthma, maternal smoking and wheezing induced by other viruses than RSV as predictive factors for later asthma.     

Wheezy babies—wheezy adults? Review on long-term outcome until adulthood after early childhood wheezing

Population-based birth cohort studies have documented that about 30% of children suffer from wheezing during respiratory infection before their third birthday. Recurrent wheezing is common in early childhood, but most patients outgrow their symptoms by school age. However, recent long-term postbronchiolitis follow-up studies from Sweden and Finland have revealed that asthma is present in about 40% of young adults and over half of the cases are relapses after many symptom-free years.
In population studies, the principal predictors for later asthma have been parental asthma, recurrent wheezing, atopy and eosinophilia. In the Swedish postbronchiolitis study, atopic diathesis through the development of clinical atopy, and early passive smoking through bronchial hyper-reactivity or later active smoking led to adult asthma. The Finnish postbronchiolitis follow-up stressed early recurrence of wheezing, wheezing induced by less invasive viruses than respiratory syncytial virus (RSV), early-life atopy and eosinophilia and parental asthma as predictors for adult asthma.
Conclusion: The majority of wheezing infants and children outgrow their symptoms by school age, but based on recent long-term follow-up studies, asthma relapses are common in young adults. These studies have highlighted parental asthma, maternal smoking and wheezing induced by other viruses than RSV as predictive factors for later asthma.     

Inflammation markers and symptom activity in children with bronchial asthma. Influence of atopy and eczema

Background. Eosinophil cationic protein (ECP) has been reported to reflect the eosinophil inflammatory activity in asthma. However, the relative impact of asthma symptoms and atopic eczema upon serum (s)-ECP in asthmatic children has not been established.
Objectives. To examine s-ECP levels and s-myeloperoxidase (MPO) in relation to asthma symptoms and atopic eczema in asthmatic children.
Methods. S-ECP and s-MPO were assessed in relation to symptom activity, lung function, exercise induced bronchoconstriction and bronchial responsiveness in 101 children; median age 9 years, range 1-16 years; with moderate to severe asthma, admitted to Voksentoppen Center.
Result. S-ECP was significantly higher in children with persistent compared to episodic or no asthma symptoms in the past four weeks, S-ECP was also higher in children with atopic compared to non-atopic asthma, as well as in those with active compared to past history of no history of atopic eczema. SMPO was higher in children with persistent asthma symptoms, but did not differ in relation to atopy of eczema state. Persistent asthma symptoms had the greatest impact upon s-ECP levels, followed by atopy and active eczema.
Conclusion. S-ECP may be used in assessing symptom activity in asthmatic children, but with the realisation that active eczema and the presence of atopy may also influence levels.