Lifestyle factors and sensitization in children - the ALADDIN birth cohort.

BACKGROUND: Several cross-sectional studies indicate that an anthroposophic lifestyle reduces the risk of allergy in children. We initiated the Assessment of Lifestyle and Allergic Disease During Infancy (ALADDIN) birth cohort to elucidate the role of specific factors supposed to mediate this effect. The aims of this study are to describe the ALADDIN cohort and to report patterns of exposure and allergic sensitization during the first years of life. METHODS: The ALADDIN study is a prospective birth cohort study of 330 children from families with an anthroposophic, partly anthroposophic, or nonanthroposophic lifestyle. The children and their parents were following an extensive data collection scheme, including repeated questionnaires and biological samples. Blood samples were collected from the parents and from the child at birth as well as at 6, 12, and 24 months of age. RESULTS: Several lifestyle factors differed between the groups, such as diet, medication, and place of delivery. Children of families with an anthroposophic lifestyle had a markedly decreased risk of sensitization during the first 2 years of life compared with children of nonanthroposophic families with adjusted OR 0.25 (95% CI 0.10-0.64) and P-value 0.004. A similar situation held true for children from families with a partly anthroposophic lifestyle, adjusted OR 0.31 (95% CI 0.15-0.54), and P-value 0.002. CONCLUSIONS: The anthroposophic lifestyle comprises several factors of interest for allergy development and is here shown to be associated with reduced risk of IgE sensitization already in infancy. Identifying the factors responsible for this association would be of significant clinical importance.

IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds.

BACKGROUND: Allergen-specific IgE testing is often performed with crude peanut extract, but the results may be difficult to interpret because of cross-reactions between peanut and other plant allergens. The aim was to investigate IgE reactivity to peanut allergen components in children from a birch-rich region in relation to pollen sensitization and peanut symptoms. METHODS: From a birth cohort, clinical parameters were obtained through questionnaires and IgE antibody levels to peanut and birch pollen were measured. Different peanut/birch sensitization phenotypes were defined among 200 selected children. IgE reactivity to peanut and pollen allergen components was analysed using microarray technique. RESULTS: Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 (n = 46) vs 17% of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 (n = 23), P < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3 reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more often reported peanut symptoms than children with IgE only to Ara h 2 (97%vs 70%, P = 0.016), particularly respiratory symptoms (50%vs 9%, P = 0.002). CONCLUSIONS: IgE analysis to peanut allergen components may be used to distinguish between peanut-sensitized individuals at risk of severe symptoms and those likely to have milder or no symptoms to peanut if sensitized to pollen allergens and their peanut homologue allergens.

Sensitization to inhalant allergens between 4 and 8 years of age is a dynamic process: results from the BAMSE birth cohort.

BACKGROUND: There is limited knowledge of the development of IgE-antibody levels over time in childhood, with respect to persistency and co-sensitization to specific inhalant allergens. METHODS: Data from 2033 children participating in the BAMSE birth cohort was used. Background factors and clinical parameters were obtained and IgE antibody (ab) levels to eight common airborne allergens were measured (>or=0.35 kU(A)/L) when the children were 4 and 8 years of age. RESULTS: Between 4 and 8 years the proportion of children sensitized to any of the inhalant allergens tested increased from 15% to 25%. At 4 years IgE-ab to birch and cat dominated, whereas at the age of 8, there was a considerable increase in the proportion of sensitization to timothy and dog. Except for mites and moulds, IgE-ab levels to all aeroallergens increased significantly between 4 and 8 years among those already sensitized at 4. Transient sensitization to inhalant allergen was uncommon. Furthermore, sensitization to birch pollen at 4 years increased the risk for becoming sensitized to timothy, cat and dog later in life. Such an association was not observed among those sensitized primarily to animal dander. CONCLUSIONS: There is a prominent process of sensitization at pre-school age to inhalant allergens, and in Northern Europe sensitization to birch pollen early in life seems to be important for this process. Such a process has a probable impact on the development of allergic disease in the growing child.

Immunoglobulin G4-antibodies to rBet v 1 and risk of sensitization and atopic disease in the child.

BACKGROUND: In 1993 extremely high levels of birch-pollen were recorded in Stockholm, Sweden. This provided an opportunity to evaluate the effects of aeroallergen exposure (exp.) on the early immune response. OBJECTIVE: To assess the influence of exp. to birch-pollen during pregnancy and infancy on the allergen-specific IgE- and IgG4-antibody (ab) response and the development of atopic disease in children. METHODS: A total of 970 children with atopic heredity and born in Stockholm 1992, 1993 or 1994 were investigated at age 4.5-5 years. They were divided into five groups; high-dose exp. at 1 year of age, high-dose exp. at 0-3 months, low-dose exp. at 0-3 months, high-dose exp. during pregnancy and low-dose exp. during pregnancy. The children were examined and skin prick tested with inhalant and food allergens. IgE abs (against birch-pollen and recombinant Bet v 1(rBet v1)) and IgG4 abs (against rBet v 1) were analysed in serum. All children were assembled in one group to assess the effects of different ab responses (IgE/IgG4) on the development of atopic disease. RESULTS: Children exposed to high doses of birch-pollen during the first 3 months of life more often had detectable levels of IgG4 abs to rBet v 1 than the children in the other groups (P < 0.001), independent of sensitization to birch. Overall, the risk of allergic rhinoconjunctivitis was increased among children sensitized to birch-pollen and appeared more pronounced in children without detectable levels of IgG4 ab to rBet v 1 (Odds ratio 9.4; 95% Confidence interval: 5.5-16.1). IgE sensitization to birch-pollen seemed to have a stronger influence on the development of atopic disease than the IgG4-ab response. CONCLUSION: Exposure to high doses of inhalant allergens during the early postnatal period is associated with detectable levels of allergen-specific IgG4 ab even at 5 years of age. An immune modulating effect by IgG4 on symptoms of allergic rhinoconjunctivitis is suggested in children sensitized to birch.

Differential activation of signal transducer and activator of transcription 6 in B cells from allergic children and their non-allergic siblings.

BACKGROUND: The germline (GL) epsilon promoter is regulated by IL-4 and is essential for class switching to IgE. IL-4-induced gene expression is largely mediated through activation of latent transcription factor STAT6 (signal transducer and activator of transcription 6). OBJECTIVE: We investigated whether increased levels of IgE in allergic individuals may be associated with alteration in the level or activation of STAT6 and subsequent increase in GL epsilon promoter activity. METHODS: Electrophoretic mobility shift assay and Western blotting assays were used to investigate the level of expression and activation of STAT6 in Epstein-Barr virus (EBV)-transformed B cell lines from children with birch pollen allergy and their non-allergic siblings. The activity of the GL epsilon promoter was tested in a transient transfection assay. RESULTS: STAT6 was expressed at the same level in all B cell lines tested. In two out of five sibling pairs STAT6 was activated by IL-4 more efficiently in the allergic individuals but in the three other pairs the opposite was found. In transient transfections, no difference in IL-4-induced GL epsilon promoter function was detected, although basal promoter activity varied between allergic and healthy siblings in two out of five pairs. CONCLUSIONS: We demonstrate for the first time that upon IL-4 signalling STAT6 transcription factor activation differs in B cells from different individuals. Although we did not find any association between STAT6 activation and allergy, we do not exclude a possibility that stronger activation of this transcription factor is associated with an expression of allergic phenotype.

Exposure to high doses of birch pollen during pregnancy, and risk of sensitization and atopic disease in the child.

BACKGROUND: The role of maternal allergen exposure during pregnancy in sensitization and development of atopic disease in the child remains controversial. In the spring of 1993, extremely high levels of birch pollen were recorded in Stockholm, Sweden. In 1994, the corresponding pollen levels were low. The aim of this study was to assess the influence of exposure during pregnancy to high/low doses of birch pollen on the risk of sensitization and development of atopic disease in children. In addition, a comparison was made with children exposed to birch pollen in early infancy. METHODS: Three hundred and eighty-seven children with atopic heredity, born in Stockholm in July-October 1993 or 1994 (mothers exposed during pregnancy), were investigated at age 4.5 years. The children were clinically examined and were skin prick tested (SPT) with inhalant and food allergens. IgE antibodies (RAST) against birch pollen and recombinant birch pollen allergen (rBet v 1) were analysed in serum. A comparison was made with a similar group of children exposed during the same incident, but in the first 3 months of life, in 1993. RESULTS: The children of mothers high-dose exposed during pregnancy in 1993 tended to be more sensitized (SPT > or = 3 mm) to birch pollen than the children with low-dose exposure during the corresponding period in 1994 (7.6 and 4.6%, respectively, OR: 1.7; 95% CI: 0.7-4.1). A similar but weak tendency was seen for positive RAST analyses (> or =0.35 kU/l) against birch pollen and rBet v 1. Children of mothers high-dose exposed during pregnancy were significantly less sensitized to birch pollen than the children high-dose exposed in early infancy (17.9%, OR: 0.4; 95% CI: 0.2-0.7). There was an overall trend towards a slightly increased prevalence of bronchial asthma, allergic rhinoconjunctivitis and atopic dermatitis in the group with mothers high-dose exposed during pregnancy, compared to those with low exposure. CONCLUSION: Exposure of the mother during pregnancy to high levels of birch pollen resulted in a tendency towards increased risk of sensitization to the same allergen and symptoms of atopic disease in children with atopic heredity. Furthermore, our data indicate that exposure of the mother during pregnancy to inhalant allergens is less likely to result in sensitization in the child than exposure of the child in early infancy.

Peanut oil in vitamin A and D preparations: reactions to skin test and manifestation of symptoms.

The aim of this study was to establish whether there is a link between sensitisation to peanut and exposure to peanut oil in vitamin A and D preparations. Forty-one children with a positive in vivo or in vitro test towards peanut were included. Twenty-one children had consumed vitamins A and D in oil solution, 14 in water solution, and 6 both types. Refined and unrefined peanut oils were obtained and skin prick test extracts were prepared. None of the children exhibited a positive SPT in response to the refined peanut extract. In contrast, 15 children exhibited a positive SPT to the unrefined extract. There was no significant difference in the number of children reacting clinically to peanut exposure who had received vitamins A and D in oil-based or water-based formulations. However, children with clinical allergy to peanut and who had exclusively consumed vitamin A and D in peanut oil, exhibited a greater number of different allergic symptoms upon consumption of peanut compared with clinical allergic children who had consumed the vitamins in water solution or both types (p<0.01). This study indicates that sensitisation to peanut during childhood through consumption of vitamins A and D in oil-based solution seems unlikely, but its consumption may contribute to the development of a wider range of clinical symptoms due to peanut exposure.

Atopy in children of families with an anthroposophic lifestyle.

BACKGROUND: Increased prevalence of atopic disorders in children may be associated with changes in types of childhood infections, vaccination programmes, and intestinal microflora. People who follow an anthroposophic way of life use antibiotics restrictively, have few vaccinations, and their diet usually contains live lactobacilli, which may affect the intestinal microflora. We aimed to study the prevalence of atopy in children from anthroposophic families and the influence of an anthroposophic lifestyle on atopy prevalence. METHODS: In a cross-sectional study, 295 children aged 5-13 years at two anthroposophic (Steiner) schools near Stockholm, Sweden, were compared with 380 children of the same age at two neighbouring schools in terms of history of atopic and infectious diseases, use of antibiotics and vaccinations, and social and environmental variables. Skin-prick tests were done for 13 common allergens, and we took blood samples from children and their parents for analysis of allergen-specific serum IgE-antibodies. FINDINGS: At the Steiner schools, 52% of the children had had antibiotics in the past, compared with 90% in the control schools. 18% and 93% of children, respectively, had had combined immunisation against measles, mumps, and rubella, and 61% of the children at the Steiner schools had had measles. Fermented vegetables, containing live lactobacilli, were consumed by 63% of the children at Steiner schools, compared with 4.5% at the control schools. Skin-prick tests and blood tests showed that the children from Steiner schools had lower prevalence of atopy than controls (odds ratio 0.62 [95% CI 0.43-0.91]). There was an inverse relation between the number of characteristic features of an anthroposophic lifestyle and risk of atopy (p for trend=0.01). INTERPRETATION: Prevalence of atopy is lower in children from anthroposophic families than in children from other families. Lifestyle factors associated with anthroposophy may lessen the risk of atopy in childhood.

IgG subclass antibody responses to birch pollen in sibling pairs discordant for atopy.

Birch pollen allergen specific IgG and IgE antibodies were analysed in the sera of fourteen sibling pairs discordant for atopy. In addition, eight unrelated children free of atopic disease were included in the study. The presence of Bet v 1 specific antibodies in the sera were analysed by an immunoblotting assay. All but one (13/14) of the atopic children had detectable anti-Bet v 1 antibodies of the IgG1 and IgG4 subclasses. The child lacking IgG1 and IgG4 antibodies to Bet v 1 was the only allergic child lacking IgE to Bet v 1. In contrast, only one of the non-atopic siblings (1/14) displayed detectable IgG1 antibodies to Bet v 1. Furthermore, among the non-atopic siblings none (0/14), had detectable IgG4 antibodies to Bet v 1. In the unrelated control group no detectable IgG1 or IgG4 anti-Bet v 1 were detected (0/8). Thus of the non-atopic children only one out of 22 children displayed IgG1 anti-Bet v 1 antibodies. Taken together, it appears that the non-atopic children in general have no/low allergen specific IgG to birch pollen.

Effects of maternal diet during late pregnancy and lactation on the development of atopic diseases in infants up to 18 months of age--in-vivo results.

One hundred and sixty-two women with respiratory allergy to animal danders and/or pollens were randomly allocated to a diet consisting of either a very low ingestion of hens' egg and cows' milk or a daily ingestion of one hens' egg and about 11 of cows' milk during the last 3 months of pregnancy. One hundred and sixty-three infants were followed prospectively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly. No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy. The numbers of skin-prick tests positive to ovalbumin, ovomucoid, beta-lactoglobulin and cows' milk were likewise not influenced by differences in the maternal diet during late pregnancy. Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy.

Ketotifen in pollen-induced asthma: a double blind placebo-controlled study.

Twenty-nine children with an average age of 10.5 years were studied with respect to the protective effect of ketotifen on pollen-induced bronchial asthma. All of them were sensitive to deciduous tree pollen, the diagnosis being verified by bronchial challenge. The children were stratified in matched pairs and randomly allocated to two treatment groups, placebo or ketotifen 1 mg twice daily. The study was double-blind and was performed during the whole of the deciduous tree pollen season. Daily pollen counts were made, allergic symptoms were noted, additional medication was given and the expiratory pulmonary flow was recorded. During the birch pollen peak the ketotifen group showed significantly fewer, and less severe asthma and rhinoconjunctivitis than the placebo group. The anti-asthmatic medication was also used significantly less than in the placebo group. Ketotifen appeared to have good protective properties in the treatment of pollen-induced asthma and rhinoconjunctivitis.