Little is known about trends in morbidity and/or mortality due to asthma in Latin America.
To examine trends in hospitalizations and mortality due to asthma from 1997-2000 to 2011 in Costa Rica.
The ...rates of hospitalization due to asthma were calculated for each sex in 3 age groups from 1997 to 2011. The number of deaths due to asthma was first calculated for all groups and then for each sex in 3 age groups from 2000 to 2011. All analyses were conducted over the entire period and separately for the periods before and after a National Asthma Program (NAP) in 2003. Data also were available for prescriptions for beclomethasone since 2004. All analyses were conducted by using Epi Info.
Substantial reductions were found in hospitalizations and deaths due to asthma in Costa Ricans (eg, from 25 deaths in 2000 to 5 deaths in 2011). Although, the percentage decrement in the rates of hospitalization for asthma in subjects <20 years old was similar before and after the NAP, the reduction in both deaths due to asthma and rates of asthma hospitalizations in older subjects were more pronounced after the NAP, when prescriptions for beclomethasone were also increased by approximately 129%.
In Costa Rica, there was a marked decrement in hospitalizations and mortality due to asthma from 1997-2000 to 2011. In younger subjects, this is likely due to guidelines that, since 1988, recommend inhaled corticosteroids for persistent asthma. In older adults, the NAP probably enhanced reductions in hospitalizations and deaths due to asthma through inhaled corticosteroid use.
Background The relevance of allergic sensitization, as judged by titers of serum IgE antibodies, to the risk of an asthma exacerbation caused by rhinovirus is unclear. Objective We sought to examine ...the prevalence of rhinovirus infections in relation to the atopic status of children treated for wheezing in Costa Rica, a country with an increased asthma burden. Methods The children enrolled (n = 287) were 7 through 12 years old. They included 96 with acute wheezing, 65 with stable asthma, and 126 nonasthmatic control subjects. PCR methods, including gene sequencing to identify rhinovirus strains, were used to identify viral pathogens in nasal washes. Results were examined in relation to wheezing, IgE, allergen-specific IgE antibody, and fraction of exhaled nitric oxide levels. Results Sixty-four percent of wheezing children compared with 13% of children with stable asthma and 13% of nonasthmatic control subjects had positive test results for rhinovirus ( P < .001 for both comparisons). Among wheezing subjects, 75% of the rhinoviruses detected were group C strains. High titers of IgE antibodies to dust mite allergen (especially Dermatophagoides species) were common and correlated significantly with total IgE and fraction of exhaled nitric oxide levels. The greatest risk for wheezing was observed among children with titers of IgE antibodies to dust mite of 17.5 IU/mL or greater who tested positive for rhinovirus (odds ratio for wheezing, 31.5; 95% CI, 8.3-108; P < .001). Conclusions High titers of IgE antibody to dust mite allergen were common and significantly increased the risk for acute wheezing provoked by rhinovirus among asthmatic children.
Background Gene-environment interaction studies using genome-wide association study data are often underpowered after adjustment for multiple comparisons. Differential gene expression in response to ...the exposure of interest can capture the most biologically relevant genes at the genome-wide level. Objective We used differential genome-wide expression profiles from the Epidemiology of Home Allergens and Asthma birth cohort in response to Der f 1 allergen (sensitized vs nonsensitized) to inform a gene-environment study of dust mite exposure and asthma severity. Methods Polymorphisms in differentially expressed genes were identified in genome-wide association study data from the Childhood Asthma Management Program, a clinical trial in childhood asthmatic patients. Home dust mite allergen levels (<10 or ≥10 μg/g dust) were assessed at baseline, and (≥1) severe asthma exacerbation (emergency department visit or hospitalization for asthma in the first trial year) served as the disease severity outcome. The Genetics of Asthma in Costa Rica Study and a Puerto Rico/Connecticut asthma cohort were used for replication. Results IL9 , IL5 , and proteoglycan 2 expression (PRG2) was upregulated in Der f 1–stimulated PBMCs from dust mite–sensitized patients (adjusted P < .04). IL9 polymorphisms (rs11741137, rs2069885, and rs1859430) showed evidence for interaction with dust mite in the Childhood Asthma Management Program ( P = .02 to .03), with replication in the Genetics of Asthma in Costa Rica Study ( P = .04). Subjects with the dominant genotype for these IL9 polymorphisms were more likely to report a severe asthma exacerbation if exposed to increased dust mite levels. Conclusions Genome-wide differential gene expression in response to dust mite allergen identified IL9 , a biologically plausible gene target that might interact with environmental dust mite to increase severe asthma exacerbations in children.
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 FEV1 and FEV1 /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.
Background Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies ...of dust mite allergen on asthma-related phenotypes. Objective We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure. Methods A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle PRGOAL). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study. Results Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV1 with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10−8 ), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10−9 for all cohorts). Rs117902240 was positively associated with FEV1 in children exposed to low dust mite allergen levels, but negatively associated with FEV1 in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV1 /forced vital capacity replicated in the independent cohorts. Conclusions Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV1 in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions.
Background It has recently been shown that vitamin D deficiency can increase asthma development and severity and that variations in vitamin D receptor genes are associated with asthma susceptibility. ...Objective We sought to find genetic factors that might interact with vitamin D levels to affect the risk of asthma exacerbation. Methods We conducted a genome-wide study of gene–vitamin D interaction on asthma exacerbations using population-based and family-based approaches on 403 subjects and trios from the Childhood Asthma Management Program. Twenty-three polymorphisms with significant interactions were studied in a replication analysis in 584 children from a Costa Rican cohort. Results We identified 3 common variants in the class I MHC–restricted T cell–associated molecule gene (CRTAM) that were associated with an increased rate of asthma exacerbations based on the presence of a low circulating vitamin D level. These results were replicated in a second independent population (unadjusted combined interaction, P = .00028-.00097; combined odds ratio, 3.28-5.38). One variant, rs2272094, is a nonsynonymous coding polymorphism of CRTAM. Functional studies on cell lines confirmed the interaction of vitamin D and rs2272094 on CRTAM expression. CRTAM is highly expressed in activated human CD8+ and natural killer T cells, both of which have been implicated in asthmatic patients. Conclusion The findings highlight an important gene-environment interaction that elucidates the role of vitamin D and CD8+ and natural killer T cells in asthma exacerbation in a genome-wide gene-environment interaction study that has been replicated in an independent population. The results suggest the potential importance of maintaining adequate vitamin D levels in subsets of high-risk asthmatic patients.
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.
Background Whether Native American ancestry (NAA) is associated with COPD or lung function in a racially admixed Hispanic population is unknown. Methods We recruited 578 Costa Ricans with and without ...COPD into a hybrid case-control/family-based cohort, including 316 members of families of index case subjects. All participants completed questionnaires and spirometry and gave a blood sample for DNA extraction. Genome-wide genotyping was conducted with the Illumina Human610-Quad and HumanOmniExpress BeadChip kits (Illumina Inc), and individual ancestral proportions were estimated from these genotypic data and reference panels. For unrelated individuals, linear or logistic regression was used for the analysis of NAA and COPD (GOLD Global Initiative for Chronic Obstructive Lung Disease stage II or greater) or lung function. For extended families, linear mixed models and generalized estimating equations were used for the analysis. All models were adjusted for age, sex, educational level, and smoking behavior; models for FEV1 were also adjusted for height. Results The average proportion of European, Native American, and African ancestry among participants was 62%, 35%, and 3%, respectively. After adjustment for current smoking and other covariates, NAA was inversely associated with COPD (OR per 10% increment, 0.55; 95% CI, 0.41-0.75) but positively associated with FEV1 , FVC, and FEV1 /FVC. After additional adjustment for pack-years of smoking, the association between NAA and COPD or lung function measures was slightly attenuated. We found that about 31% of the estimated effect of NAA on COPD is mediated by pack-years of smoking. Conclusions NAA is inversely associated with COPD but positively associated with FEV1 or FVC in Costa Ricans. Ancestral effects on smoking behavior partly explain the findings for COPD but not for FEV1 or FVC.
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 (∼3-fold to 39-fold increase) and frequency of asthma exacerbations among children exposed to ≥10 μg/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.
Association of SERPINE2 With Asthma Himes, Blanca E., PhD; Klanderman, Barbara, PhD; Ziniti, John, BA ...
Chest,
09/2011, Letnik:
140, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background The “Dutch hypothesis” suggests that asthma and COPD have common genetic determinants. The serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 ( ...SERPINE2 ) gene previously has been associated with COPD. We sought to determine whether SERPINE2 is associated with asthma and asthma-related phenotypes. Methods We measured the association of 39 SERPINE2 single-nucleotide polymorphisms (SNPs) with asthma-related phenotypes in 655 parent-child trios from the Childhood Asthma Management Program (CAMP), and we measured the association of 19 SERPINE2 SNPs with asthma in a case-control design of 359 CAMP probands and 846 population control subjects. We attempted to replicate primary asthma-related phenotype findings in one independent population and primary asthma affection status findings in two independent populations. We compared association results with CAMP proband expression quantitative trait loci. Results Nine of 39 SNPs had P < .05 for at least one phenotype in CAMP, and two of these replicated in an independent population of 426 people with childhood asthma. Six of 19 SNPs had P < .05 for association with asthma in CAMP/Illumina. None of these replicated in two independent populations. The expression quantitative trait loci revealed that five SNPs associated with asthma in CAMP/Illumina and one SNP associated with FEV1 in CAMP are strongly correlated with SERPINE2 expression levels. Comparison of results to previous COPD studies identified five SNPs associated with both asthma- and COPD-related phenotypes. Conclusions Our results weakly support SERPINE2 as a Dutch hypothesis candidate gene through nominally significant associations with asthma and related traits. Further study of SERPINE2 is necessary to verify its involvement in asthma and COPD.
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