Maarten O. Hoekstra

Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T helper type 2 cytokines.

Background Decreased exposure to microbial stimuli has been proposed to be involved in the increased prevalence of atopic disease. Such a relationship was indicated by enhanced presence of typical probiotic bacteria in the intestinal flora correlating with reduced prevalence of atopic disease. Recent clinical trials suggested that probiotic bacteria may decrease and prevent allergic symptoms, but which (different) species or strains may contribute is poorly understood.

The effects of selected probiotic strains on the development of eczema (the PandA study)

Background:  Modification of the intestinal microbiota by administration of probiotic bacteria may be a potential approach to prevent allergic disease. We aimed to study primary prevention of allergic disease in high‐risk children by pre‐ and postnatal supplementation of selected probiotic bacteria.

Asthma at 8 years of age in children born by caesarean section

Background: Caesarean section might be a risk factor for asthma because of delayed microbial colonisation, but the association remains controversial. A study was undertaken to investigate prospectively whether children born by caesarean section are more at risk of having asthma in childhood and sensitisation at the age of 8 years, taking into account the allergic status of the parents. Methods: 2917 children who participated in a birth cohort study were followed for 8 years. The definition of asthma included wheeze, dyspnoea and prescription of inhaled steroids. In a subgroup (n = 1454), serum IgE antibodies for inhalant and food allergens were measured at 8 years. Results: In the total study population, 12.4% (n = 362) of the children had asthma at the age of 8 years. Caesarean section, with a total prevalence of 8.5%, was associated with an increased risk of asthma (OR 1.79; 95% CI 1.27 to 2.51). This association was stronger among predisposed children (with two allergic parents: OR 2.91; 95% CI 1.20 to 7.05; with only one: OR 1.86; 95% CI 1.12 to 3.09) than in children with non-allergic parents (OR 1.36; 95% CI 0.77 to 2.42). The association between caesarean section and sensitisation at the age of 8 years was significant only in children of non-allergic parents (OR 2.14; 95% CI 1.16 to 3.98). Conclusions: Children born by caesarean section have a higher risk of asthma than those born by vaginal delivery, particularly children of allergic parents. Caesarean section increases the risk for sensitisation to common allergens in children with non-allergic parents only.

Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time

Background In peanut‐allergic adults, IgE is mainly directed to Ara h1 and Ara h2. More recently, a role for Ara h6 has been suggested. In contrast to adults, IgE in children can fluctuate over time. Therefore, children may have a more dynamic reactivity to peanut.

Maternal Food Consumption during Pregnancy and the Longitudinal Development of Childhood Asthma

RATIONALE Maternal diet during pregnancy has the potential to affect airway development and to promote T-helper-2-cell responses during fetal life. This might increase the risk of developing childhood asthma or allergy. OBJECTIVES We investigated the influence of maternal food consumption during pregnancy on childhood asthma outcomes from 1 to 8 years of age. METHODS A birth cohort study consisting of a baseline of 4,146 pregnant women (1,327 atopic and 2,819 nonatopic). These women were asked about their frequency of consumption of fruit, vegetables, fish, egg, milk, milk products, nuts, and nut products during the last month. Their children were followed until 8 years of age. Longitudinal analyses were conducted to assess associations between maternal diet during pregnancy and childhood asthma outcomes over 8 years. MEASUREMENTS AND MAIN RESULTS Complete data were obtained for 2,832 children. There were no associations between maternal vegetable, fish, egg, milk or milk products, and nut consumption and longitudinal childhood outcomes. Daily consumption of nut products increased the risk of childhood wheeze (odds ratio [OR] daily versus rare consumption, 1.42; 95% confidence interval [95% CI], 1.06-1.89), dyspnea (OR, 1.58; 95% CI, 1.16-2.15), steroid use (OR, 1.62; 95% CI, 1.06-2.46), and asthma symptoms (OR, 1.47; 95% CI, 1.08-1.99). CONCLUSIONS Results of this study indicate an increased risk of daily versus rare consumption of nut products during pregnancy on childhood asthma outcomes. These findings need to be replicated by other studies before dietary advice can be given to pregnant women.

Selection of probiotic bacteria for prevention of allergic diseases : immunomodulation of neonatal dendritic cells

Modification of intestinal microbiota early in life by administration of probiotic bacteria may be a potential approach to prevent allergic disease. To select probiotic bacteria for in vivo purposes, we investigated the capacity of probiotic bacteria to interact with neonatal dendritic cells (DC) and studied the ensuing T cell polarizing effect. Immature DC were generated from cord blood‐derived monocytes and maturation was induced by maturation factors (MF), lipopolysaccharide (LPS) plus MF and Bifidobacterium bifidum, B. infantis, Lactobacillus salivarius, Lactococcus lactis alone or combined with MF. After 12 days of co‐culture with DC and Staphylococcus aureus enterotoxin B (SEB) as antigenic stimulus, cytokine production by autologous T cells was determined by intracellular cytokine staining. Additionally, cells were stimulated with CD3 and CD28 monoclonal antibodies and cytokines were measured in supernatants by multiplex assay. The probiotic strains induced partial maturation of DC. Full maturation of DC was induced for all strains tested when MF was added. The percentage of interleukin (IL)‐4 producing T cells was lower in T cell cultures stimulated with B. bifidum matured DC compared to MF and LPS matured DC, which coincided with a higher percentage of interferon (IFN)‐γ‐producing T cells. Furthermore, T cells stimulated by B. bifidum matured DC produced significantly more IL‐10 compared to MF matured DC. Selected species of the Bifidobacterium genus prime in vitro cultured neonatal DC to polarize T cell responses and may therefore be candidates to use in primary prevention of allergic diseases.

Breast feeding, parental allergy and asthma in children followed for 8 years. The PIAMA birth cohort study.

Background: It is unclear how the association between breast feeding and asthma develops with age of the child and how this association over time is influenced by maternal or paternal allergy. These factors—the age of the child and maternal or paternal allergy—might partly explain the conflicting results observed in cross-sectional studies. Methods: The study population consisted of 3115 Dutch children born in 1996/1997 who participated in the PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort study. Data on breast feeding and asthma (based on wheeze, dyspnoea and prescription of inhaled steroids) were collected by yearly questionnaires. At 8 years, specific immunoglobulin E (IgE) to airborne allergens and bronchial responsiveness were measured. Data were analysed by logistic regression and generalised estimating equations (GEEs), and stratified by maternal and paternal allergic status. Results: 35% (n = 1081) of the children were breast fed for >16 weeks. At 8 years of age, 12.6% (n = 392) had asthma. Breast feeding (>16 weeks vs no breast feeding) was significantly associated with a lower asthma prevalence from 3 to 8 years of age, in children of both non-allergic and allergic mothers. The inverse association between breast feeding and sensitisation to airborne allergens at 8 years was non-significant. Breast feeding was not associated with bronchial hyper-responsiveness. No interaction between breast feeding and gender, maternal allergy or paternal allergy was observed in any of the associations. Conclusions: Breast feeding is associated with a lower asthma risk in children until 8 years of age without evidence of attenuation and regardless of the family history of allergy.

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children

Background Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T‐helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre‐dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1‐stimulating infection.

Prediction of asthma in symptomatic preschool children using exhaled nitric oxide, Rint and specific IgE.

Rationale For clinicians it remains very difficult to predict whether preschool children with symptoms suggestive of asthma will develop asthma in later childhood. Objective To investigate whether measurement of fraction of exhaled nitric oxide (FENO), interrupter resistance (Rint) or specific immunoglobulin E (IgE) in 4-year-old children with suggestive symptoms can predict asthma symptoms up to age 8 years. Methods Children were recruited from the PIAMA birth cohort. All children with symptoms suggestive of asthma at age 3 or 4 years, who were invited for medical examination at age 4 (n=848), were eligible. Associations of FENO (n=308), Rint (n=482) and specific IgE (n=380) at 4 years with wheezing and asthma at the ages of 5–8 years were assessed using repeated measurement analyses. The added predictive value of these objective tests was then investigated by including parameters for clinical history in the model. Results FENO and specific IgE measured at 4 years were associated with wheezing and asthma at 8 years. Both tests also remained significant predictors after mutual adjustment and adjustment for clinical history: OR on wheezing at 8 years for FENO (10log-scale, per IQR) 1.6 (95% CI 1.1 to 2.2) and for specific IgE 2.8 (95% CI 1.9 to 4.1). Rint was significantly associated with wheezing at age 6, but not at 7 and 8 years. Conclusions In preschool children with symptoms suggestive of asthma, both FENO and specific IgE measured at age 4, but not Rint, improved the prediction of asthma symptoms until the age of 8 years, independent of clinical history.

Prevalence of immunoglobulin E for fungi in atopic children

Background The prevalence of sensitization to fungi in young atopic patients in relation to age and clinical importance is largely unknown.