Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

Exposure to indoor allergens and development of allergy

House dust contains several indoor allergens which can elicit hypersensitivity and various atopic symptoms, especially in childhood. This review article focusses on house dust mite hypersensitivity to one of the most important species, Dermatophagoides , as a model. A clear dose-response relationship has been demonstrated between house dust mite allergen exposure in mattress dust samples and sensitization, i.e. serum IgE to Dermatophagoides and positive histamine release from basophil leukocytes to one of the major allergens from Dermatophagoides pteronyssinus, Der p I. 2 μg major allergen of Dermatophagoides /g of dust and 8 μg major allergen of cat/g of dust have been suggested to be threshold concentrations above which the risk of sensitization in genetically predisposed atopic children is significantly increased. Epidemiological studies showed house dust mite allergens to be one of the most important risk factors in the development of atopic airway disease. A relation between age at onset of the first wheezing episode and house dust mite allergen exposure at the age of 1 year has been observed. There are various factors influencing house dust mite growth, and many studies have been performed to reduce house dust mite allergen exposure. Until now, none of the approaches appeared to have achieved sufficient mite and mite allergen reduction.     

Exposure to a high concentration of mite allergen in early infancy is a risk factor for developing atopic dermatitis: A 3-year follow-up study

The cause of allergy is multi-factorial, and the development of an allergic disease seems to be the result of an interaction between genetic and environmental factors. The goal for preventing the development of allergic diseases is to avoid sensitization to allergens. The aim of this work was to study whether or not exposure to environmental allergens early in infancy would influence the occurence of various allergic diseases in later life. On an annual basis, a total of 931 healthy newborns were followed-up until they reached 3 years of age. The occurence of allergic diseases was recorded by trained medical students during visits. Measurement of Dermatophagoides pteronyssinus (Der p 1) concentration in house dust was performed when each baby was 18 and 36 months old. Total and specific immunoglobulin E (IgE) antibodies against Der p 1, cow's milk, and egg white were evaluated at birth and at 18 months of age. The following results were obtained: at 3 years of age, 10.4% had bronchial asthma (BA), 21.4% atopic dermatitis (AD), 7.0% urticaria, and 46.8% had experienced wheezing; higher family allergy scores led to a higher incidence of AD (p=0.0012); exposure to a mite allergen concentration of 1 µg/g of dust may be associated with a higher incidence of AD (p=0.0156); the presence of Der p 1 IgE antibody at 18 months of age was associated with a higher incidence of BA (p=0.0001); and children sensitized to egg whites at 18 months of age had an increased risk of developing AD at 3 years of age (p=0.0187). Hence, early exposure to mite allergen is a risk factor for the development of atopic dermatitis, but seems not to be related to the development of bronchial asthma. Early sensitization to egg whites increases the risk of developing AD. The early detection of serum Der p 1 IgE antibody is associated with a higher incidence of bronchial asthma.     

Teenage asthma after severe infantile bronchiolitis or pneumonia

OBJECTIVE: The purpose of the study was to evaluate asthma at >13 y of age in children with infantile bronchiolitis or pneumonia. METHODS: In 1981-1982, 127 children at <2 y of age were hospitalized for bronchiolitis (n = 81) or pneumonia (n = 46). Respiratory syncytial virus (RSV) infection, eosinophilia and markers of atopy were assessed and recorded on admission. At a median age of 14.9 y, atopic and asthmatic symptoms were screened by a written questionnaire in 98/127 (77%) study subjects. RESULTS: Asthma was present, according to two definitions, in 14% to 23% in the original bronchiolitis and in 12% to 15% in the original pneumonia group. The figures were 8% to 17% in the RSV infection and 16% to 23% in the non-RSV infection group. Early asthma-predictive factors were repeated wheezing, atopic dermatitis and elevated blood eosinophils. All but one of the teenage asthmatics had allergic rhinitis. CONCLUSION: An increased risk for asthma persists until the teenage period after bronchiolitis and pneumonia in infancy. Both early and later atopy were significant risk factors. The present study was unable to demonstrate the association between early RSV infection and teenage asthma.     

Wheezing requiring hospitalization in early childhood: Predictive factors for asthma in a six-year follow-up

Although asthma is common after wheezing in early childhood, the risk factors for and the prevention of later asthma are poorly understood. During the present follow-up study, a range of possible predictive factors for school-age asthma was evaluated. The study group consisted of 82 children hospitalized for wheezing at age < 2 years in 1992–93. The baseline data were collected on entry to the study. In 1999, the children were re-examined at the median age of 7.2 years. A structured questionnaire was applied to chart the symptoms suggestive of asthma, and the children were examined clinically. An exercise challenge test, as well as skin prick tests (SPT) to common inhalant allergens, was performed. Asthma was present in 33 (40%) children, 30 (91%) having continuous medication for asthma. The significant asthma-predictive factors, present on entry to the study, were blood eosinophilia (p = 0.0008), atopic dermatitis (p = 0.0089), elevated total serum immunoglobulin E (IgE) (p = 0.0452), and a history of earlier episodes of wheezing in infancy (p = 0.0468). SPT positivity in early childhood was also associated with school-age asthma (p = 0.002). In contrast, respiratory syncytial virus (RSV) identification during the index episode of wheezing played a minor role as a predictive factor for asthma. In conclusion, if hospitalization for wheezing occurs in infancy, more than every third child will suffer from asthma at early school age; the risk is significantly increased with recurrent wheezing in infancy and the development of allergic manifestations.     

Allergenexposition und Asthmaentstehung

Background. There has been a tremendous increase in atopic diseases during the past 25 years in industrialized countries. Among other factor, high indoor allergen exposure (house dust mite Dermatophagoides, cat) was considered to be one major risk factor for the increase in asthma prevalence in childhood. MAS-90. In the German Multercentre Allergy Study (MAS-90) only an association between specific sensitization and exposure to house dust mite and cat allergens could be found. There was no association between the prevalence of asthma or wheeze at age 7 and indoor allergen exposure in early childhood. Discussion. Other genetic and exogenous factors seem to have a stronger influence on the development of childhood asthma.     

Outcome of wheezing in early childhood

In Acta Paediatrica 50 y ago, Boesen published a follow-up of children with "asthmatic bronchitis". Recent reinvestigations of children hospitalized because of wheezing in early childhood are remarkably consistent with Boesen's observations. Conclusion: Young children admitted to hospital because of wheezing have a clearly increased risk of subsequent asthma. Recent studies confirm Boesen's observations of the prognostic importance of eosinophilia and an inverse relation between age at admission with wheezing and risk of subsequent asthma. Allergy or atopic dermatitis is predictive of subsequent asthma, whereas family history of allergy has low predictive value in infants.     

Lung function and bronchial hyper-responsiveness 11 years after hospitalization for bronchiolitis

AIM: Atopic infants hospitalized for wheezing not caused by respiratory syncytial virus (RSV) carry the highest risk for later asthma. In the present paper, early risk factors for later lung function abnormalities and for bronchial hyper-responsiveness (BHR) were evaluated in 81 children, hospitalized for bronchiolitis in infancy, at the median age of 12.3 years. METHODS: The basic data, including data on atopy in children and viral aetiology of bronchiolitis, had been collected on entry to the study at less than 2 years of age. Lung function was studied by flow-volume spirometry (FVS), and BHR by methacholine and exercise challenge tests 11.4 years after hospitalization during infancy. RESULTS: RSV aetiology of bronchiolitis was associated with reduced forced vital capacity (FVC; 93.65% of predicted +/- 11.05 vs. 99.57%+/- 12.59, p = 0.009). Early sensitization to inhalant allergens (OR 12.59, 95% CI 2.30-68.77) and maternal smoking during pregnancy (OR 4.58, 95% CI 1.28-16.39) were associated with BHR to exercise, and early atopic dermatitis (OR 3.48, 95% CI 1.09-11.10) was associated with BHR to methacholine. CONCLUSIONS: RSV bronchiolitis was associated with a restrictive pattern of lung function. Early atopy and maternal smoking during pregnancy may play a role in the development and persistence of BHR.     

House dust mite sensitivity in childhood asthma.

The clinical features of perennial asthmatic children with a skin or bronchial reaction to the house dust mite (Dermatophagoides pteronyssinus) were compared with those of asthmatic children without mite sensitivity. Mite sensitive asthma was characterised by an early age of onset of symptoms, these being predominantly nocturnal. A history of wheezing precipitated by dust exposure, during vacuuming, bedmaking, or dusting was present in 52% of cases. Asthmatic children with mite sensitivity were more likely to have been born at the time of the year when mite counts were highest. This was consistent with the idea that allergy may be associated with a period of susceptibility to sensitisation in early infancy.     

影响儿童哮喘尘螨特异性免疫疗效的因素分析

目的：探讨影响尘螨过敏性哮喘患儿特异性免疫治疗（SIT）疗效的因素。方法：监测99例哮喘患儿接受标准化屋尘螨SIT半年（S1期）、1年（S2期）、1年半（S3期）、2年（S4期）以后的哮喘控制水平,分析患儿初诊年龄、哮喘病程、哮喘程度分级、初始血清特异性（sIgE）浓度、是否合并过敏性鼻炎或异位性皮炎、是否合并吸入糖皮质激素治疗及疗程中出现局部和全身副作用情况对哮喘控制水平的影响。 结果：随着SIT疗程的进行,临床控制病例显著增加,未控制病例则明显减少（P<0.01）;患儿初诊年龄在S1和S3期,以及合并过敏性鼻炎或异位皮炎在S1期均显著影响了哮喘的控制水平（均P<0.01）;SIT治疗各期临床控制组的初始血清sIgE浓度均显著高于临床未控制组（均P<0.05）;S1和S2期初始哮喘程度分级较高的患儿较初始哮喘程度分级较低的患儿达到临床控制的比例显著增高（均P<0.05）。结论：SIT的长期疗效可能与疗程长短及总剂量呈正相关;治疗前初始血清sIgE浓度高的患儿较浓度低的患儿可能更早达到临床控制。     

The Natural History of IgE Sensitisation and Atopic Disease in Early Childhood

ABSTRACT. We have prospectively followed 57 children of atopic parents up to 5 years of age, documenting clinical atopic disease and allergen skin test reactions. The cumulative prevalences of the clinical features of atopic disease over the 5 years were: atopic dermatitis (58%), wheeze (49%), recurrent wheeze (33%), rhinitis (68%) and immediate food reactions (18%). Atopic dermatitis and immediate food reactions predominated in infancy (birth to 20 months) while wheezing was more prominent in later childhood (20 months to 5 years). Rhinitis was common in both infancy and childhood. IgE sensitisation to ingested allergens was prominent in early infancy and was usually transient. Inhaled allergen sensitisation occurred later in infancy and was generally permanent with wheal sizes tending to increase with age. There was a significant association between IgE sensitisation to ingested but not inhaled allergens and all atopic manifestations in infancy, with the exception of rhinitis. In contrast IgE sensitisation to inhaled allergens was associated with rhinitis and wheeze in later childhood. We found two clinical groups. One group, with only ingested allergen sensitisation had a high incidence of atopic dermatitis but low incidence of respiratory symptoms at 5 years of age. The other group, who developed evidence of IgE sensitisation to inhaled allergens, had a high incidence of rhinitis and wheeze but low incidence of atopic dermatitis at 5 years of age.     

Allergologie pédiatrique. Quoi de neuf ? Une revue de la littérature internationale d''octobre 2002 à septembre 2003

Most epidemiological studies published in 2002-2003 confirm, in a large number of children, the results of previous studies. Most important results show that the risk of severe and persistent atopy and/or asthma is significantly higher in children with numerous risk factors than in children with a limited number of risk factors. Moreover, risks of severity and persistence are increased in children with early onset allergic disease, and with severe symptoms at the time of diagnosis. Effects of early exposure to furred pets are related to the degree of exposure at home, but are also modulated by the degree of exposure in the general population. In contrast with previous results, a large pediatric study shows that, at the age of 5 years, the prevalence of atopic diseases is inversely correlated with the number of vaccine infections. The efficacy of sublingual-swallow hyposensitization is long-lasting (up to 4-5 years after the discontinuation of treatment) in children with asthma due to house dust mite allergy. In contrast, individualized homeopathy, as an adjunct in the treatment of childhood asthma, is not superior to placebo in improving the quality of life of children with mild to moderate asthma. Supplementation of infant formulas with viable but not heat-inactivated probiotic bacteria is beneficial in the management of atopic dermatitis and cow's milk allergy. Finally the prevalence of peanut allergy has significantly increased between 1989 and 1994-1996 in European children, and at present, in France, the management in schools of children with food allergy is clearly inadequate.     

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.     

Influence of month of birth on house dust mite allergy

We determined the birth month of a sample of 208 patients with bronchial asthma or rhinitis and positive skin test to house dust mite. The majority of patients were born in the summer and autumn months. The increased incidence of house dust mite allergy in patients born in the months of July to September, when house dust mites are most abundant, corresponds to a relative risk of 1.43. It is important that exposure to house dust mites in early childhood is kept to a minimum as exposure to allergens may influence the development of allergic disease in later life.     

Weight gain in infancy and post‐bronchiolitis wheezing

Aim: Low birth weight, high birth weight and excessive weight gain after birth may be risk factors for asthma in childhood, but their associations with wheezing in early childhood are poorly studied. The aim of the study was to evaluate birth weight, weight gain in early infancy and overweight in infancy assessed by weight for length (WFL) as risk factors for wheezing after hospitalization for bronchiolitis in early infancy. Methods: In all, 127 full‐term infants hospitalized for bronchiolitis at age <6 months have been followed up until the mean age of 1.5 years. The weights and lengths of the infants were measured on admission to hospital and at the control visit. Birth weights were obtained from the hospital records. Results: Both occurrence and recurrence of post‐bronchiolitis wheezing were associated with birth weight >4000 g and the recurrence of post‐bronchiolitis wheezing with WFL >110% at age 1.5 years. The associations were robust to adjustments with gender and allergy. Higher weight gain from birth to hospitalization at age <6 months was associated with wheezing in the subgroup of children with birth weight >4000 g. Conclusion: High birth weight and the development of overweight may be associated with post‐bronchiolitis wheezing in infancy.     

Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review

One of the major questions regarding long-term side effects of bronchiolitis by respiratory syncytial virus (RSV) is whether or not it induces asthma in later life. In this quantitative review, the data of 10 controlled studies are analysed. METHODS: Follow-up studies of RSV bronchiolitis published between January 1978 and December 1998 were identified through a MEDLINE search. Studies were selected if (i) postnatal age at the time of the initial illness was below 12 mo, (ii) all children were hospitalized for RSV bronchiolitis, (iii) the diagnosis RSV was virologically confirmed in all cases, and (iv) a control group was used. RESULTS: Six studies met all selection criteria. Up to 5 y of follow-up after RSV bronchiolitis in infancy, 40% of children reported wheezing as compared to only 11% in the control group (p <0.001). Between 5 and 10 y of follow-up 22% of the bronchiolitis group reported wheezing against 10% of the control group (p = 0.19). The incidence of recurrent wheezing as defined by three or more wheezing episodes also decreased with increasing years of follow-up: at 5 or more years of follow-up the difference between the RSV group and the control group was no longer significant. Furthermore, the presence of either a personal and/or a family history of either atopy and/or asthma did not differ between the two groups. CONCLUSIONS: Wheezing is common after RSV bronchiolitis in infancy. It may persist for > or = 5 y of follow-up. However, no significant difference between the RSV bronchiolitis and the control group was observed regarding recurrent wheezing by 5 y of follow-up. No significant difference between the RSV bronchiolitis and the control group were found regarding a personal history of atopy, a family history of atopy and/or asthma. Therefore it seems unlikely that RSV bronchiolitis is a cause of atopic asthma in later life.     

Overweight does not increase asthma risk but may decrease allergy risk at school age after infantile bronchiolitis

Aim: Increasing evidence suggests that overweight children are at increased risk of asthma. The association between weight gain and allergy is more complex. The aim was to evaluate the association between overweight or obesity and asthma, allergy, bronchial reactivity or atopic sensitization at school age in children with bronchiolitis in infancy. Subjects and methods: Eighty‐one children hospitalized for bronchiolitis at <24 months of age attended control visits at 7.2 and 12.3 years of ages. The visits consisted of medical examinations, weight and height measurements, body mass index (BMI) calculations, skin prick tests and exercise challenge tests. BMI >1.3 SD from age‐ and gender‐specific references meant overweight and BMI >2.0 SD obesity. Results: Current or previous overweight or obesity did not increase the risk of asthma, allergy, bronchial reactivity or atopic sensitization at 7.2 or 12.3 years of age. Previous and current obesity decreased the risk of atopic dermatitis, and current overweight and obesity decreased the risk of sensitization to outdoor allergens at 12.3 years of age. Conclusion: Previous or current overweight does not increase asthma or allergy risk but current obesity may decrease allergy risk at school age after bronchiolitis in infancy.     

The National Asthma Campaign Manchester Asthma and Allergy Study

The ^NACManchester Asthma and Allergy Study is a prospective study of the development of asthma and allergies in childhood. The subjects (995 children at age 3 years) were recruited in utero by screening parents in the antenatal clinic using skin prick testing and a questionnaire regarding allergic diseases. Children were assigned to risk groups according to parental atopic status (high risk, both parents atopic; medium risk, one parent atopic; low risk, neither parent atopic). A subgroup of those at high risk (with no pets in the home) was randomized to stringent environmental control (allergen impermeable covers for the parental and infant bed, hot washing of bedding weekly, HEPA vacuum cleaner, hard floor for the nursery), and the remainder followed a normal regime. The children have been followed prospectively. The environmental influences are very clearly defined. Measurements of environmental exposures include levels of house dust mite; cat and dog allergens during pregnancy and early life; pet ownership and exposure; childcare arrangements; number of siblings; vaccination uptake; thorough dietary questionnaire; and endotoxin exposure. Further unique objective outcome in the cohort is the assessment of lung function in preschool children using specific airways resistance, which at age 3 years clearly reflects both genetic and environmental influences.     

儿童血清过敏原与哮喘发生关系的探讨

目的探讨儿童血清特异性Ig E(s Ig E)过敏原与哮喘发生的关系。方法采用免疫印迹法对2004年12月至2013年4月就诊的2 239例1~14岁单纯哮喘患儿(n=1 415)和非过敏性疾病患儿(n=824)的血清s Ig E过敏原进行检测,分别建立所有样本、不同年龄及不同性别单纯哮喘与非过敏性疾病的病例对照模型,采用多因素logistic回归分析探讨过敏原与哮喘发生的关系。结果 2 239例患儿中,血清s Ig E阳性者1 028例(45.91%),过敏原阳性率居于前三位的为户尘螨(15.68%)、屋尘(14.29%)和霉菌类(13.40%)。病例对照研究结果显示,户尘螨、霉菌类、屋尘、腰果/花生/黄豆是哮喘发病的危险因素(P0.05);不同年龄组与哮喘发生相关的过敏原有所不同,1岁~组儿童仅屋尘与哮喘的发生有关,户尘螨和屋尘是3~14岁儿童哮喘发生的危险因素,而霉菌类是6~14岁儿童哮喘发生的危险因素(P0.05);户尘螨和屋尘是男、女儿童哮喘发生的危险因素(P0.05),而腰果/花生/黄豆和霉菌类仅是男性儿童哮喘发生的危险因素(P0.05)。结论户尘螨、屋尘、霉菌类为哮喘患儿最常见过敏原,且与哮喘发生关系极为密切。