Atopic Diseases In Early Childhood Research Articles

Association between neopterin in cord blood, urinary neopterin in early childhood and the development of atopic dermatitis, asthma and hay fever

It is generally accepted that the increased prevalence of atopic disease is due to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release large amounts of neopterin. Thus, the determination of neopterin concentrations is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1-type immune response. We evaluated whether neopterin concentrations in the neonatal cord blood could be a valuable marker predicting atopic disease in early childhood and whether there is a difference in actually determined urinary neopterin concentrations in children with and without atopic disease. Five hundred and five children born during 1997-1999 were enrolled, with cord blood neopterin data available at birth. The International study of asthma and allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning urinary samples were collected and urinary neopterin concentration was measured by high-pressure liquid chromatography. By the average age of 6 yr, the prevalence of atopic disease in the last 12 months was 31%. There was no significant correlation between cord blood and urinary neopterin concentrations at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary neopterin concentrations were significant lower in children with a family history of atopic disease (p = 0.02). In this study, cord blood neopterin concentration was not a predictor for atopic disease in early childhood. Family history of atopic disease was associated with lower urinary neopterin levels at age 6 yr, which might mirror a Th1/Th2 imbalance.

THE ASSOCIATION BETWEEN HLA-DR, -DQ GENES AND SUSCEPTIBILITY TO ATOPY IN A BIRTH COHORT

ISEE-202 Introduction: Atopic disease in early childhood plays a major role in the development of asthma in childhood or adolescence. Different human leukocyte antigen (HLA) class II alleles have been associated with the development of atopic asthma and responsiveness of allergen exposure. HLA class II molecules were found in neonates’ immune system. However, the relationship between the atopic disease in early childhood and HLA-DR and -DQ genes remains unclear. Aim: Our aim is to determine the association between HLA-DR and -DQ genes and susceptibility to atopy in a birth cohort at one year follow-up. Methods: Four private maternity hospitals were randomly selected to participate and recruit pairs of mothers and neonates. A questionnaire was administered to collect demographic data, home environment, family disease histories, and information about atopic symptoms including early-onset transient wheezing, atopic dermatitis, and eczema, diagnosed by paediatricians. The questionnaire was completed by neonates’ parents when neonates were followed up to the age of 1 year by telephone interview. The levels of cord blood IgE (cIgE) and maternal total IgE (sIgE) and allergen-specific IgE were determined by the Pharmacia UniCAP IgE assay test system. HLA-DR and -DQ alleles were typed using the Dynal AllSet+™ “low resolution” SSP kit. Results: Between July 2001 and May 2003, 187 mother and neonate pairs participated in this study. A total of 184 neonates completed the HLA-DR and -DQ genotyping. The frequencies of HLA-DR and -DQ genes, maternal sensitization, sIgE > 100 IU/ml, and cIgE ≥ 0.35 IU/ml were not different between the four areas. No association was found between cIgE and HLA-DR and -DQ genes or atopic symptoms. Physician diagnosed atopic symptoms were associated with the HLA-DQB1*02 allele (X2= 10.38, p<0.0013). After adjusting for possible potential risk factors, the sIgE > 100 IU/ml (Odds Ratio (OR) =5.01, 95% ci= [1.22, 27.14]), and HLA-DQB1*02 (OR = 8.09, 95% CI= [1.91, 36.74]) were risk factors for atopic symptoms in children at one year follow-up. Conclusion: Although, no allergen-specific IgE data were found in infants, we suggest that HLA-DQB1*02 and maternal atopy are important risk factors for atopic symptoms in early stage of childhood. Elucidating this interaction at the molecular level may allow for more targeted treatment and prevention of atopic diseases.

Atopic eczema in early childhood could be protective against Type 1 diabetes.

According to the Th1/Th2 paradigm Type 1 diabetes and atopic diseases are assumed to be mutually exclusive on the individual level. We analysed the association between Type 1 diabetes and atopic diseases in a case-control design in order to test the hypothesis that atopic diseases in early childhood could protect against Type 1 diabetes. We carried out a nationwide population-based case-control study enrolling 760 cases newly-diagnosed with Type 1 diabetes under five years of age between July 1992 and December 1995 and 1871 controls randomly selected from the general population and individually matched on sex, age and place of residence. Information on atopic diseases was obtained by a mailed parent-administered questionnaire. Data were analysed by multivariate logistic regression adjusting for potential confounders (family history of diabetes, social status, duration of overall breast feeding, number of children in family, maternal age at delivery). Atopic eczema was less frequent in diabetic (13.3%) than in non-diabetic children (18.0%) and was significantly associated with a reduced risk of Type 1 diabetes. The adjusted odds ratio was 0.71 (95% CI 0.53-0.96). Hay fever and asthma were not significantly associated with diabetes risk (OR 0.98 (95% CI 0.47-2.01) and 1.46 (95% CI 0.70-3.06), respectively). In this large population-based case-control study in pre-school children an inverse association was observed between atopic eczema and Type 1 diabetes. Thus, in accordance with the Th1/Th2 paradigm development of atopic eczema in early childhood could be protective against childhood Type 1 diabetes.

Peripheral blood eosinophilia in infants at 3 months of age is associated with subsequent development of atopic disease in early childhood

Background: We tested the hypothesis that eosinophilia in peripheral blood and nasal mucosa of infants is an early sign of allergic disease. Methods: The appearance of eosinophilic leukocytes in peripheral blood and nasal mucosa was studied prospectively in 67 infants up to 18 months of age, with or without a family history of atopy. Results: Eosinophilia was associated with simultaneous presence or subsequent development of atopic disease at 3, 9, and 18 months of age, but not significantly so at 6 months. At 3 months children in whom atopic disease developed later during the observation period had significantly higher numbers of blood eosinophils than children without atopy ( p < 0.01). Thus pronounced eosinophilia (>7 × 10 8 cells/L) at that age was associated with moderate or severe allergic disease during the 18-month observation period. These children continued to have eosinophilia throughout the follow-up period. Blood eosinophilia at 3 months of age also correlated significantly to cord blood IgE levels and to skin prick test reactivity later during the follow-up period. Nasal eosinophilia was a common finding and therefore had little diagnostic or predictive value. Conclusions: Elevated eosinophil counts in peripheral blood of apparently healthy infants at 3 months of age is associated with a subsequent diagnosis of atopic disease. (J A LLERGY C LIN I MMUNOL 1995;95:694-8.)

The natural history of IgE sensitisation and atopic disease in early childhood.

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.

689 BREAST FEEDING AND PREVENTION OF ATOPIC ECZEMA

The offspring of parents suffering from atopic disease are at higher risk of developing eczema, asthma and other manifestations of allergy compared with children of non-atopic parents. In a group of 31 such “high risk” neonates, breast feeding was employed as the exclusive form of infant feeding for the first 8 weeks or longer after birth. Followup for 12 to 36 months (mean 20.6 months) showed the development of clinical eczema in 4, compared with 19 of 31 matched controls fed cow's milk formula. Serum IgE concentration at one year of age was elevated in the artificially fed (121 ± 39 IU/ml) and normal in the breast fed (17 ± 8 IU/ml). The incidence of positive radioallergosorbent test for IgE antibodies to cow's milk, complement activation in vivo after challenge with cow's milk, and of respiratory disease characterized by bronchospasm, was higher in the cow's milk fed group. These data confirm the positive beneficial effect of breast feeding in the prevention of atopic disease in early childhood.