Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica.

RATIONALE: Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood. OBJECTIVES: To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. METHODS: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses. MEASUREMENTS AND MAIN RESULTS: Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log(10) unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05-0.67; P = 0.01), and increased airway responsiveness (a < or =8.58-mumol provocative dose of methacholine producing a 20% fall in baseline FEV(1) [OR, 0.15; 95% CI, 0.024-0.97; P = 0.05]). CONCLUSIONS: Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.

Dust mite exposure modifies the effect of functional IL10 polymorphisms on allergy and asthma exacerbations.

BACKGROUND: The allergenicity of dust mite exposure might be dependent on variants in the gene for IL-10 (IL10). OBJECTIVES: To evaluate whether dust mite exposure modifies the effect of single nucleotide polymorphisms (SNPs) in IL10 on allergy and asthma exacerbations. METHODS: We genotyped 6 SNPs in IL10 in 417 Costa Rican children and 503 white children in the Childhood Asthma Management Program (CAMP) with asthma and their parents. We used family-based and population-based approaches to test for interactions between IL10 SNPs and dust mite allergen on serum IgE to dust mite in Costa Rica and on asthma exacerbations in Costa Rica and CAMP. RESULTS: Dust mite exposure significantly modified the relation between 3 SNPs in IL10 (rs1800896, rs3024492, and rs3024496) and IgE to dust mite in Costa Rica (P for interaction, .0004 for SNP rs1800896). For each of these SNPs, homozygosity for the minor allele was associated with increased levels of IgE to dust mite with increased dust mite exposure. Homozygosity for the minor allele of each of the 3 SNPs was associated with increased risk of occurrence (approximately 3-fold to 39-fold increase) and frequency of asthma exacerbations among children exposed to > or = 10 microg/g dust mite allergen in Costa Rica. Similar results were obtained for 2 of these SNPs (rs1800896 and rs3024496) among white children in CAMP. CONCLUSION: Our findings suggest that dust mite allergen levels modify the effect of IL10 SNPs on allergy and asthma exacerbations and may partly explain conflicting findings in this field.

Sex-stratified linkage analysis identifies a female-specific locus for IgE to cockroach in Costa Ricans.

RATIONALE: The basis for gender influences on allergen-specific IgEs is unclear. OBJECTIVES: To perform regular and sex-stratified genomewide linkage analyses of IgE to each of three allergens (Ascaris lumbricoides, Blatella germanica [German cockroach]), and Dermatophagoides pteronyssinus [dust mite]) and to conduct an association study of a candidate gene in a linked genomic region. METHODS: Genomewide linkage analyses of allergen-specific IgEs were conducted in 653 members of eight large families of Costa Rican children with asthma. An analysis of the association between single-nucleotide polymorphisms in thymic stromal lymphopoietin (TSLP) and IgE measurements was conducted in 417 parent-child trios in Costa Rica. Significant results were replicated in 470 families of white children in the Childhood Asthma Management Program (CAMP). MEASUREMENTS AND MAIN RESULTS: Among all subjects, there was suggestive evidence of linkage (LOD >/= 2.72) to IgE to Ascaris (on chromosome 7q) and IgE to dust mite (on chromosomes 7p and 12q). In a sex-stratified analysis, there was significant evidence of linkage to IgE to cockroach on chromosome 5q23 (peak LOD, 4.14 at 127 cM) in female subjects. TSLP is located within the 1.5 LOD-unit support interval for this linkage peak and has female-specific effects on lung disease in mice. In a sex-stratified analysis, the T allele of single-nucleotide polymorphism rs2289276 in TSLP was associated with reductions in IgE to cockroach (in Costa Rican girls) and total IgE (in girls in Costa Rica and in CAMP; P value for sex-by-genotype interaction, <0.01 in both studies). CONCLUSIONS: Consistent with findings in murine models, a variant in TSLP may have female-specific effects on allergic phenotypes.

Paternal asthma, mold exposure, and increased airway responsiveness among children with asthma in Costa Rica.

BACKGROUND: Little is known about the determinants of airway hyperresponsiveness (AHR) among children with asthma in Hispanic America. METHODS: We examined the relations among selected familial and environmental factors, markers of allergy, spirometric measures of lung function, and AHR in a cross-sectional study of 403 Costa Rican children with asthma between the ages of 6 and 14 years. Study participants completed a protocol that included questionnaires, spirometry, measurements of serum total and allergen-specific IgE, peripheral blood eosinophil count, and body mass index, and the assessment of airway responsiveness to methacholine (ie, a methacholine challenge test [MCT]). AHR to MCT was defined as the provocative dose of methacholine causing a 20% fall in FEV(1). Linear regression was used for the univariate and multivariate analyses. RESULTS: Of the 403 asthmatic children who underwent an MCT, 350 (86.8%) had AHR to methacholine. In a multivariate analysis, paternal asthma (p = 0.004), parental report of mold/mildew in the child's home (p = 0.04), FEV(1)/FVC ratio (p < 0.0001), and a positive IgE response to Der p 1 (p = 0.008) were significantly associated with AHR among Costa Rican children with asthma. CONCLUSION: Our results suggest that paternal asthma and environmental exposure to mold/mildew are strong determinants of AHR in Costa Rican children with asthma. FEV(1)/FVC ratio may be a useful measure of AHR (a marker of asthma severity) among Costa Ricans and other Hispanic Americans for whom reference values for FEV(1) are not currently available.

Polymorphisms in IL13, total IgE, eosinophilia, and asthma exacerbations in childhood.

BACKGROUND: It is unclear whether single nucleotide polymorphisms (SNPs) in the gene for IL-13 (IL13) influence asthma severity and/or asthma morbidity. OBJECTIVES: To examine the relation between IL13 SNPs and asthma-related phenotypes in 2 independent populations. METHODS: We used family-based methods to test for association between SNPs in IL13 and asthma-related phenotypes in Costa Rican children with asthma. We attempted to reproduce significant findings in white (non-Hispanic) children with asthma in the Childhood Asthma Management Program (CAMP). RESULTS: In Costa Rica and in CAMP, the A allele (Gln) of IL13 coding SNP (rs20541) was significantly associated with increased eosinophil count (P < .011 in both studies) and increased serum total IgE (P < .054 in both studies). The T allele of IL13 promoter SNP (rs1800925) was inversely associated with asthma exacerbations in Costa Rica (P = .069). Although this SNP (rs1800925) was not associated with asthma exacerbations among all white children in CAMP, it was associated with increased risk of asthma exacerbations among children on inhaled corticosteroids (P = .02). CONCLUSION: Polymorphisms in IL13 were significantly associated with serum total IgE and eosinophil count in 2 populations. IL13 polymorphisms may also be associated with asthma exacerbations, and this effect may be dependent on medication use. Our study is the first to report a potential negative interaction between a genetic polymorphism and response to inhaled corticosteroids. CLINICAL IMPLICATIONS: Polymorphisms in IL13 are associated with serum total IgE and eosinophil count and may be associated with asthma exacerbations.

Sensitization to Ascaris lumbricoides and severity of childhood asthma in Costa Rica.

BACKGROUND: Little is known about sensitization (defined as a positive IgE) to helminths and disease severity in patients with asthma. OBJECTIVES: To examine the relationship between sensitization (defined as a positive IgE) to Ascaris lumbricoides and measures of asthma morbidity and severity in a Costa Rican population with low prevalence of parasitic infection but high prevalence of parasitic exposure. METHODS: Cross-sectional study of 439 children (ages 6 to 14 years) with asthma. Linear regression and logistic regression were used for the multivariate statistical analysis. RESULTS: After adjustment for parental education and other covariates, sensitization to Ascaris lumbricoides was associated with having at least 1 positive skin test to allergens (odds ratio, 5.15; 95% CI, 2.36-11.21; P < .001), increased total serum IgE and eosinophils in peripheral blood, reductions in FEV(1) and FEV(1)/forced vital capacity, increased airway responsiveness and bronchodilator responsiveness, and hospitalizations for asthma in the previous year (odds ratio, 3.08; 95% CI, 1.23-7.68; P = .02). CONCLUSION: Sensitization to Ascaris lumbricoides is associated with increased severity and morbidity of asthma among children in Costa Rica. This association is likely mediated by an increased degree of atopy among children with asthma who are sensitized to Ascaris. CLINICAL IMPLICATIONS: In areas with a low prevalence of helminthiasis such as Costa Rica, Ascaris sensitization may be an important marker of severe atopy and disease morbidity in children with asthma.