Background: An association has been reported between early life Staphylococcus aureus nasal carriage and higher risk of childhood eczema, but it is unclear whether this relationship is causal and... Show moreBackground: An association has been reported between early life Staphylococcus aureus nasal carriage and higher risk of childhood eczema, but it is unclear whether this relationship is causal and associations with other bacterial species are unclear.Objective: To examine the associations of early life nasal and nasopharyngeal bacterial carriage with eczema phenotypes, and the direction of any associations identified.Methods: Among 996 subjects of a population-based prospective cohort study, nasal swabs for Staphylococcus aureus, and nasopharyngeal swabs for Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected and cultured from age 6 weeks to 6 years. Never, early, mid-, late transient and persistent eczema phenotypes were identified from parental-reported physician-diagnosed eczema from age 6 months until 10 years. Multinomial regression models and cross-lagged models were applied.Results: Staphylococcus aureus nasal carriage at 6 months was associated with an increased risk of early transient and persistent eczema (OR (95% CI): 2.69 (1.34, 5.39) and 4.17 (1.12, 15.51)). The associations between Staphylococcus aureus nasal carriage and eczema were mostly cross-sectional, and not longitudinal. No associations of Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal bacterial carriage with eczema and eczema phenotypes were observed (OR range (95% CI): 0.71 (0.35, 1.44) to 1.77 (0.84, 3.73)).Conclusions: Early life Staphylococcus aureus nasal carriage, but not Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal carriage, was associated with early transient and persistent eczema. Staphylococcus aureus nasal carriage and eczema were mostly cross-sectionally associated, and not longitudinally, making a causal relationship in either direction unlikely. Show less
Background Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition... Show moreBackground Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school-aged children with and without FLG mutations have differences in T- and B-cell subsets.Methods This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X, and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg), and CD27(+) and CD27(-) memory B cells. Subset analysis was performed in 358 non-AD and 102 AD cases, assessed by parental questionnaires.Results FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children in the general and non-AD population. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg, or memory B-cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cell subsets.Conclusions School-aged children of a general population with FLG mutations have higher Th22 cell numbers, which reflects the immunological response to the skin barrier dysfunction. FLG mutations did not otherwise affect the composition of the adaptive immunity in this general pediatric population. Show less
Boeschoten, S.A.; Boehmer, A.L.; Merkus, P.J.; Rosmalen, J. van; Jongste, J.C. de; Fraaij, P.L.A.; ... ; Hoog, M. de 2020
Rationale: Severe acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU)... Show moreRationale: Severe acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU) admissions between 2003 and 2013 in the Netherlands, with a significant increase during those years of numbers of children without treatment of inhaled corticosteroids (ICS).Objectives: To determine whether steroid-naive children are at higher risk of PICU admission among those hospitalised for SAA. Furthermore, we included the secondary risk factors tobacco smoke exposure, allergic sensitisation, previous admissions and viral infections.Methods: A prospective, nationwide multicentre study of children with SAA (2-18 years) admitted to all Dutch PICUs and four general wards between 2016 and 2018. Potential risk factors for PICU admission were assessed using logistic regression analyses.Measurements and main results: 110 PICU and 111 general ward patients were included. The proportion of steroid-naive children did not differ significantly between PICU and ward patients. PICU children were significantly older and more exposed to tobacco smoke, with symptoms >1 week prior to admission. Viral susceptibility was not a significant risk factor for PICU admission.Conclusions: Children with SAA admitted to a PICU were comparable to those admitted to a general ward with respect to ICS treatment prior to admission. Preventable risk factors for PICU admission were >7 days of symptoms without adjustment of therapy and exposure to tobacco smoke. Physicians who treat children with asthma must be aware of these risk factors. Show less
BackgroundThe role of timing and diversity of allergenic food introduction in the development of childhood allergic sensitization and atopic diseases is controversial. ObjectiveTo examine whether... Show moreBackgroundThe role of timing and diversity of allergenic food introduction in the development of childhood allergic sensitization and atopic diseases is controversial. ObjectiveTo examine whether timing and diversity of allergenic food introduction are associated with allergic sensitization, allergy and eczema in children until age 10 years. Materials and methodsThis study among 5,202 children was performed in a population-based prospective cohort. Timing (age ≤6 months vs. >6 months) and diversity (0, 1, 2 and ≥3 foods) of allergenic food (cow's milk, hen's egg, peanut, tree nuts, soy and gluten) introduction were assessed by questionnaires at ages 6 and 12 months. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by questionnaire. Data on parental-reported physician-diagnosed eczema were obtained from birth until age 10 years. ResultsChildren introduced to gluten at age ≤6 months had a decreased risk of eczema (aOR (95% CI): 0.84 (0.72, 0.99)), compared with children introduced to gluten at age >6 months. However, timing of allergenic food introduction was not associated with allergic sensitization or physician-diagnosed allergy. Children introduced to ≥3 allergenic foods at age ≤6 months had a decreased risk of physician-diagnosed inhalant allergy (0.64 (0.42, 0.98)), compared with children not introduced to any allergenic food at age ≤6 months. However, diversity of allergenic food introduction was not associated with allergic sensitization, physician-diagnosed food allergy or eczema. ConclusionNeither timing nor diversity of allergenic food introduction was consistently associated with childhood allergic sensitization, allergy or eczema. Show less
Early-life nutrition is an important modifiable determinant in the development of a child’s immune system, and may thereby influence the risk of allergic sensitization and atopic diseases. However,... Show moreEarly-life nutrition is an important modifiable determinant in the development of a child’s immune system, and may thereby influence the risk of allergic sensitization and atopic diseases. However, associations between overall dietary patterns and atopic diseases in childhood remain unclear. We examined associations of diet quality in early life with allergic sensitization, self-reported physician-diagnosed inhalant and food allergies, eczema, and asthma among 5225 children participating in a population-based cohort in the Netherlands. Diet was assessed during pregnancy, infancy, and childhood using validated food-frequency questionnaires. We calculated food-based diet quality scores (0–10 or 0–15), reflecting adherence to dietary guidelines. At age 10 years, allergic sensitization was assessed with skin prick tests. Information on physician-diagnosed inhalant and food allergies, eczema, and asthma was obtained with questionnaires. We observed no associations between diet quality during pregnancy and allergic sensitization (odds ratio (OR) = 1.05 per point in the diet score, 95% confidence interval (CI): 0.99, 1.13), allergies (0.96, 95% CI: 0.88, 1.04), eczema (0.99, 95% CI: 0.93, 1.06), or asthma (0.93, 95% CI: 0.85, 1.03) in childhood. Also, diet quality in infancy or childhood were not associated with atopic outcomes in childhood. Our findings do not support our hypothesis that a healthy dietary pattern in early life is associated with a lower risk of allergic sensitization or atopic diseases in childhood Show less
BackgroundThe protection of breastfeeding against respiratory tract infections in the first year of life has often been suggested. Few studies examined the effect of breastfeeding on respiratory... Show moreBackgroundThe protection of breastfeeding against respiratory tract infections in the first year of life has often been suggested. Few studies examined the effect of breastfeeding on respiratory tract infections after infancy. ObjectiveTo examine the association between breastfeeding with lower respiratory tract infections (LRTI) and upper respiratory tract infections (URTI) after infancy up to 4 years of age (n = 5322). MethodsThis study was embedded in The Generation R study, a Dutch population-based prospective cohort study from fetal life until young adulthood. Information on breastfeeding duration (never; <3 months; 3–6 months; ≥6 months) and dose (never; partially until 4 months; predominantly until 4 months) were collected by questionnaire at 2, 6, and 12 months of age. Information on doctor attendance for LRTI and URTI were obtained by questionnaire at 2, 3, and 4 years of age. ResultsBreastfeeding for 6 months or longer was significantly associated with a reduced risk of LRTI up to 4 years of age (aOR: 0.71; 95% CI: 0.51–0.98). Similar ORs for LRTI were found with breastfeeding for less than 3 months and 3–6 months. Although in the same direction, weaker ORs were found for URTI and breastfeeding duration. The same trend was found for partial and predominant breastfeeding until 4 months and LRTI and URTI. ConclusionBreastfeeding duration for 6 months or longer is associated with a reduced risk of LRTI in pre-school children. These findings are compatible with the hypothesis that the protective effect of breastfeeding for respiratory tract infections persist after infancy therefore supporting current recommendations for breastfeeding for at least 6 months. Show less
