RESUMO
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.
Assuntos
Antígenos de Dermatophagoides/imunologia , Predisposição Genética para Doença , Hipersensibilidade/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Pyroglyphidae/imunologia , Animais , Criança , Costa Rica , Feminino , Genótipo , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/sangue , Interleucina-10/imunologia , MasculinoRESUMO
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.
Assuntos
Asma/imunologia , Saúde da Família , Fungos , Exposição por Inalação/efeitos adversos , Hipersensibilidade Respiratória/imunologia , Adolescente , Asma/diagnóstico , Criança , Costa Rica , Estudos Transversais , Feminino , Humanos , Masculino , Cloreto de Metacolina , Análise Multivariada , Hipersensibilidade Respiratória/diagnósticoRESUMO
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.
Assuntos
Asma/genética , Eosinofilia/genética , Imunoglobulina E/sangue , Interleucina-13/genética , Polimorfismo de Nucleotídeo Único , Asma/diagnóstico , Criança , Costa Rica , Feminino , Humanos , Masculino , FenótipoRESUMO
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.