The Prognostic Value of Eight Immunohistochemical Markers Expressed in the Tumor Microenvironment and on Hodgkin Reed-Sternberg Cells in Pediatric Patients With Classical Hodgkin Lymphoma.

Immunohistochemical markers are associated with treatment outcome in adults with classical Hodgkin Lymphoma (cHL). Studies in children are scarce and inconsistent. We investigated in 67 children with cHL, whether the expression of CD15, CD30, PAX5, PD-1, PD-L1, CD68, CD163 and TARC at diagnosis is associated with disease free survival (DFS) and with interim remission status. Low CD15 and low TARC expression were associated with relapsed disease. Low expression of PD-L1 was associated with complete remission at interim PET-scan. Our data suggest a difference between pediatric and adult cHL. This underlines the importance of future research into specific prognostic factors in pediatric cHL, indispensable for improvement of treatment in this population.

25-Hydroxyvitamin D concentrations, asthma and eczema in childhood: The generation R study.

BACKGROUND & AIMS: A role of vitamin D in the development of respiratory and allergic disease in children remains unclear. It may be likely that vitamin D has an effect on airway inflammation, but only few studies examined the effect in children. We aimed to examine whether serum 25-hydroxyvitamin D (25(OH) vitamin D) concentrations are associated with the fraction of exhaled nitric oxide (FeNO), airway interrupter resistance (Rint), physician diagnosed asthma ever, wheezing and eczema in a population-based cohort study in 6 year old children. METHODS: Serum 25(OH) vitamin D concentration was assessed in 3815 children. 25(OH) vitamin D concentrations ≥75 nmol/L were considered as sufficient, between 50 and 75 nmol/L as insufficient, and <50 nmol/L as deficient. FeNO and Rint were measured at the research center. Data on physician diagnosed asthma, wheezing, and eczema were obtained by parent-reported questionnaires. RESULTS: In comparison with sufficient 25(OH) vitamin D concentration, deficient concentrations were associated with elevated FeNO of ≥25 ppb (OR: 2.54; 95% CI: 1.34-4.80). In addition, deficient and insufficient 25(OH) vitamin D concentrations were associated with a lower Rint (Z-score: -1.26; 95% CI: -1.66 to -0.85) (ß: -0.75; 95% CI: -1.08 to -0.42), and increased risks of eczema (OR: 1.65; 95% CI: 1.13-2.41) (OR: 1.44; 95% CI: 1.06-1.95). Insufficient 25(OH) vitamin D concentration were associated with a decreased risk of physician diagnosed asthma ever (OR: 0.59; 95% CI: 0.38-0.94). CONCLUSIONS: Our results indicate that lower 25(OH) vitamin D levels are associated with elevated FeNO levels, but lower Rint values. Lower 25(OH) vitamin D levels are also associated with a decreased risk for asthma diagnoses but an increased risk for eczema.

Breastfeeding and the risk of respiratory tract infections after infancy: The Generation R Study.

BACKGROUND: The 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. OBJECTIVE: To 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). METHODS: This 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. RESULTS: Breastfeeding 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. CONCLUSION: Breastfeeding 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.

Infant feeding and anti-tissue transglutaminase antibody concentrations in the Generation R Study.

BACKGROUND: Celiac disease (CD) has emerged as a common, but largely undiagnosed health problem. Numerous studies examined the influence of infant nutrition on the development of diagnosed CD. However, results are still inconsistent. In addition, the effect of infant feeding practices on the development of potential forms of CD might be different. OBJECTIVE: The objective was to examine whether the timing of gluten introduction and breastfeeding duration are associated with CD autoimmunity (CDA) in children at the age of 6 y. DESIGN: This study was embedded in the Generation R Study, a population-based prospective cohort study. Participants included 1679 Dutch children who were positive for human leukocyte antigen (HLA) DQ2/DQ8. Data on the timing of gluten introduction (<6 mo compared with ≥6 mo) and duration of breastfeeding (<6 mo compared with ≥6 mo) were obtained by questionnaire. Serum samples were analyzed for anti-tissue transglutaminase (anti-tTG) concentrations at age 6 y. Anti-tTG concentrations were categorized into negative (<7 U/mL) and positive (≥7 U/mL) values. Positive anti-tTG concentrations were further categorized based on ≥10 times the upper limit of normal (ULN) values of the test kit (≥7-70 and ≥70 U/mL). Multivariable logistic regression analyses were performed. RESULTS: Positive anti-tTG concentrations were found in 43 children, 26 of whom had concentrations ≥10 times the ULN (≥70 IU/mL). The introduction of gluten from the age of 6 mo onward and breastfeeding for ≥6 mo were not significantly associated with positive anti-tTG concentrations. In addition, the timing of gluten introduction and duration of breastfeeding were not significantly associated with positive anti-tTG concentrations below or above 10 times the ULN. CONCLUSIONS: Delayed introduction of gluten beyond the age of 6 mo does not increase the risk of CDA. In addition, breastfeeding for ≥6 mo does not decrease the risk of CDA in children at 6 y of age.

Dietary patterns and respiratory symptoms in pre-school children: the Generation R Study.

Overall diet in early childhood may affect the development of respiratory symptoms. This study examined whether childhood dietary patterns are associated with respiratory symptoms in Dutch pre-school children, and whether this association could be explained by energy intake. A prospective cohort study was performed in 2,173 children aged ≤ 4 yrs. Data on asthma-related symptoms were obtained by questions from the age-adapted version of the "International Study of Asthma and Allergies in Childhood" questionnaires. Data on respiratory tract infections, defined as episodes of physician attended fever with respiratory symptoms, was obtained by questionnaire. Principal components analysis was used to develop dietary patterns at 14 months of age. Compared with low adherence, high adherence to the "Western" dietary pattern was significantly associated with frequent wheeze at 3 yrs of age (relative risk (RR) 1.39, 95% CI 1.02-1.89) and frequent shortness of breath (RR 1.44, 95% CI 1.03-2.01) and respiratory tract infections (RR 1.54, 95% CI 1.08-2.19) at 4 yrs of age. However, this association was partially explained by energy intake. A "Western" diet may increase the risk of frequent respiratory symptoms at 3 and 4 yrs of age. In some measure, this association was explained by energy intake.

The introduction of allergenic foods and the development of reported wheezing and eczema in childhood: the Generation R study.

OBJECTIVE: To examine whether the timing of introduction of the allergenic foods cow's milk, hen's egg, peanuts, tree nuts, soy, and gluten is associated with eczema and wheezing in children 4 years of age or younger. DESIGN: Population-based prospective cohort study from fetal life until young adulthood. SETTING: Rotterdam, the Netherlands, from April 2002 through January 2006. PARTICIPANTS: A total of 6905 preschool children participating in the Generation R study. MAIN EXPOSURE: Timing of introduction of cow's milk, hen's egg, peanuts, tree nuts, soy, and gluten collected by questionnaires at 6 and 12 months of age. MAIN OUTCOME MEASURES: Information on the outcomes eczema and wheezing were obtained by questions from the age-adapted version of the "International Study of Asthma and Allergies in Childhood" core questionnaire and questionnaire data on parentally reported physician diagnosis for eczema. RESULTS: Of 6905 children, wheezing was reported in 31% at age 2 years and in 14% at ages 3 and 4 years. Eczema was reported in 38%, 20%, and 18% of children at the ages of 2, 3, and 4 years, respectively. The introduction of cow's milk, hen's egg, peanuts, tree nuts, soy, and gluten before the age of 6 months was not significantly associated with eczema or wheezing at any age after adjustment for potential confounders (P > .10 for all comparisons). The results did not alter after stratification according to the child's history of cow's milk allergy and parental history of atopy. CONCLUSION: This study does not support the recommendation for delayed introduction of allergenic foods after age 6 months for the prevention of eczema and wheezing.