Allergic sensitization at school age is a systemic low-grade inflammatory disorder.

BACKGROUND: Systemic low-grade inflammation has been demonstrated in a range of the frequent noncommunicable diseases (NCDs) proposing a shared mechanism, but is largely unexplored in relation to allergic sensitization. We therefore aimed to investigate the possible association with childhood allergic sensitization. METHODS: High-sensitivity C-reactive protein (hs-CRP), interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and chemokine (C-X-C motif) ligand 8 (CXCL8) were measured in plasma at age 6 months (N = 214) and 7 years (N = 277) in children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000 ) birth cohort. Allergic sensitization against common inhalant and food allergens was determined longitudinally at ages ½, 1½, 4 and 6 years by specific IgE assessments and skin prick tests. Associations between inflammatory biomarkers and sensitization phenotypes were tested with logistic regression and principal component analyses (PCAs). RESULTS: Adjusted for gender, recent infections, and a CRP genetic risk score, hs-CRP at 7 years was associated with concurrent elevated specific IgE against any allergen [adjusted OR (aOR) = 1.40; 95% CI, 1.14-1.72; P = 0.001], aeroallergens (aOR, 1.43; 1.15-1.77; P = 0.001), food allergens (aOR, 1.31; 95% CI, 1.02-1.67; P = 0.04), sensitization without any clinical allergy symptoms (aOR = 1.40; 1.06-1.85; P = 0.02), and with similar findings for skin prick tests. The other inflammatory markers were not univariately associated with sensitization, but multiparametric PCA suggested a specific inflammatory response among sensitized children. Inflammatory markers at age 6 months were not associated with subsequent development of sensitization phenotypes. CONCLUSIONS: Elevated hs-CRP is associated with allergic sensitization in school-aged children suggesting systemic low-grade inflammation as a phenotypic characteristic of this early-onset NCD.

High breast milk IL-1ß level is associated with reduced risk of childhood eczema.

BACKGROUND: We recently demonstrated a dual effect of breastfeeding with increased risk of eczema and decreased risk of wheezing in early childhood by increasing breastfeeding length. We hypothesize that immune mediators in breast milk could explain such association either through a direct effect or as a surrogate marker of maternal immune constitution. OBJECTIVE: To investigate the possible association between cytokine and chemokine levels in breast milk and development of eczema and recurrent wheeze during early childhood. METHODS: Levels of 19 pro-inflammatory and immunoregulatory cytokines and chemokines were measured in 223 breast milk samples from mothers in the Copenhagen Prospective Study on Asthma in Childhood2000 (COPSAC) high-risk birth cohort. Eczema and recurrent wheeze at the age of 0-3 years were prospectively diagnosed by COPSAC physicians adherent to predefined validated algorithms. Association analyses were performed by Cox regression adjusting for potential confounding factors and by multivariable principal component analysis. RESULTS: Increased IL-1ß in breast milk (≥ 0.7 pg/mL) was associated with more than a halved risk of eczema before age three (aHR = 0.41; 95% CI = 0.24-0.68; P < 0.001), which remained significant after false discovery rate adjustment (P = 0.008). The principal component analysis confirmed that a mediator pattern dominated by high levels of IL-1ß, IL-17A, and CCL17 and low levels of CXCL1 and TSLP in breast milk protected against eczema (aHR = 0.82; 95% CI = 0.68-0.98; P = 0.03). No associations were observed for recurrent wheeze. CONCLUSIONS AND CLINICAL RELEVANCE: Elevated breast milk IL-1ß level was associated with decreased risk of early childhood eczema suggesting either a direct protective effect of IL-1ß or IL-1b acting as a proxy for a healthy maternal immune system protecting high-risk offspring from eczema.

Early indoor aeroallergen exposure is not associated with development of sensitization or allergic rhinitis in high-risk children.

RATIONALE: Allergen exposure is associated with the development of allergic sensitization in childhood as reflected by global variations in sensitization patterns. However, there is little evidence to support a direct association. OBJECTIVES: To investigate the association between perinatal aeroallergen exposure and sensitization and rhinitis to such allergens later in childhood. METHODS: Allergic sensitization to cat, dog, and house dust mites was diagnosed longitudinally using skin prick tests and specific IgE measurements at ½, 1½, 4, 6, and 13 years in 399 children from the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort. Rhinitis was diagnosed at 7 and 13 years. Allergen exposure was defined as dog or cat in the home during the 3rd trimester of pregnancy or the first year of life and as allergen levels of dog, cat, and house dust mite in bed dust samples at 1 year. Associations between exposure and outcomes were analyzed by logistic regression and stratified for eczema status and test method (skin prick test and specific IgE). RESULTS: We found no association between dog or cat exposure in perinatal life and sensitization or rhinitis during childhood. Similarly, there was no association between levels of allergens in bed dust samples and sensitization or rhinitis during childhood. CONCLUSION: Perinatal indoor aeroallergen exposure does not seem to affect development of allergic sensitization or rhinitis during childhood questioning the relevance of allergen avoidance as a preventive measure. Other factors such as timing of allergen exposure or other environmental adjuvants may contribute in a more complex pathway to sensitization.

Disagreement between skin prick test and specific IgE in young children.

BACKGROUND: Skin prick test (SPT) and measurement of serum-specific IgE (sIgE) level are important tools for the clinician to diagnose allergic sensitization. However, little is known about the agreement between the two methods in young children. METHODS: SPT and sIgE levels were assessed simultaneously for 16 common inhalant and food allergens at age ½, 1½, 4, and 6 years in 389 children from the Copenhagen Prospective Study on Asthma in Childhood2000 (COPSAC2000 ) at-risk birth cohort. Agreement between the two methods for diagnosing inhalant and food allergic sensitization at the four age points was analyzed using kappa statistics. RESULTS: The prevalence of inhalant allergen sensitization increased during childhood diagnosed by both sIgE levels (0.6% to 4.2% to 18.1% to 24.8%, P < 0.0001) and SPT results (1.5% to 3.8% to 8.4% to 15.4%, P < 0.0001). In contrast, the prevalence of food sensitization increased during childhood when diagnosed from sIgE (7.8% to 12.1% to 15.0% to 18.9%, P < 0.0001), but decreased when diagnosed from SPT (5.3% to 5.1% to 3.7% to 3.0%, P = 0.05). Overall, the agreement between SPT and sIgE levels was poor to moderate (all κ-coefficients ≤ 0.60) and decreased from moderate to slight for food allergens by increasing age (κ-coefficients: 0.46 to 0.31 to 0.16 to 0.14). CONCLUSION: There is a substantial disagreement between SPT and sIgE for diagnosing allergic sensitization in young children, which increases with age for food sensitization. Choice of assessment method therefore has major impact on results with wide implications for both clinical practice and research.