Project description:Puerto Ricans have the highest prevalence of and morbidity from asthma of all ethnic groups in the United States. One potential contributor to the high burden of asthma in Puerto Rican children is exposure to stress and violence.To examine whether exposure to stress and violence is associated with an increased risk of asthma among Puerto Rican children.This study was a population-based probability sample of children in the San Juan and Caguas metropolitan areas in Puerto Rico. Information was collected in a household survey of 1,213 children and their primary caretakers.The prevalence of lifetime physician-diagnosed asthma was 39.6%. In the year before the survey, 14% of children had witnessed an act of violence, 7% had been victims of violence, and 6% had been victims of physical or sexual abuse. Although stressful life events and exposure to neighborhood violence were not associated with asthma, a history of physical or sexual abuse was associated with approximately twice the odds of current asthma (odd ratio [OR], 2.52; 95% confidence interval [CI], 1.27-5.00), health care use for asthma (OR, 1.95; 95% CI, 0.96-3.96), and medication use for asthma (OR, 2.35; 95% CI, 1.05-5.26).Physical or sexual abuse is associated with high asthma morbidity among Puerto Rican children. To our knowledge, this is the first report of an association between childhood abuse and asthma. Our findings highlight the importance of screening for asthma among victims of childhood abuse, and to be aware of the possibility of physical or sexual abuse among children with asthma.
Project description:BackgroundLittle is known about the determinants of asthma among youth with high T helper 2 (Th2) immunity. We hypothesized that exposure to violence (ETV) and violence-related distress are associated with asthma in children and adolescents with high Th2 immunity.MethodsWe analyzed data from Puerto Ricans with high Th2 immunity aged 9-20 years in the Puerto Rico Genetics of Asthma and Lifestyle (PR-GOAL) and the Epigenetic Variation of Childhood Asthma in Puerto Ricans (EVA-PR) studies, and in a prospective study (PROPRA). High Th2-immunity was defined as ≥1 positive allergen-specific IgE and/or a total IgE ≥ 100 IU/mL and/or an eosinophil count ≥ 150 cells/μL. Asthma was defined as physician-diagnosed asthma and current wheeze. ETV and violence-related distress were assessed with the validated ETV Scale and Checklist of Children's Distress Symptoms (CCDS) questionnaires, respectively.ResultsIn multivariable analyses, each 1-point increment in ETV score was significantly associated with 1.13-1.17 times increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.01), and each 1-point increment in CCDS score was significantly associated with 1.53-1.54 increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.03). Further, a persistently high ETV score was significantly associated with asthma in PROPRA (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.10-7.29). Similar results were obtained in a sensitivity analysis using an eosinophil count ≥ 300 cells/μL instead of ≥150 cells/μL to define high Th2 immunity.ConclusionsETV during childhood is associated with increased risk of persistent or new-onset asthma in youth with high Th2 immunity.
Project description:BackgroundExposure to gun violence and African ancestry have been separately associated with increased risk of asthma in Puerto Rican children.ObjectiveThe objective of this study was to examine whether African ancestry and gun violence interact on asthma and total IgE in school-aged Puerto Rican children.MethodsThis is a case-control study of 747 Puerto Rican children aged 9 to 14 years living in San Juan, Puerto Rico (n = 472), and Hartford, Connecticut (n = 275). Exposure to gun violence was defined as the child's report of hearing gunshots more than once, and the percentage of African ancestry was estimated using genome-wide genotypic data. Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. Serum total IgE (IU/mL) was measured in study participants. Multivariate logistic and linear regressions were used for the analysis of asthma and total IgE, respectively.ResultsIn multivariate analyses, there was a significant interaction between exposure to gun violence and African ancestry on asthma (P = .001) and serum total IgE (P = .04). Among children exposed to gun violence, each quartile increase in the percentage of African ancestry was associated with approximately 45% higher odds of asthma (95% CI, 1.15-1.84; P = .002) and an approximately 19% increment in total IgE (95% , 0.60-40.65, P = .04). In contrast, there was no significant association between African ancestry and asthma or total IgE in children not exposed to gun violence.ConclusionsOur results suggest that exposure to gun violence modifies the estimated effect of African ancestry on asthma and atopy in Puerto Rican children.
Project description:RationaleEpigenetic and/or genetic variation in the gene encoding the receptor for adenylate-cyclase activating polypeptide 1 (ADCYAP1R1) has been linked to post-traumatic stress disorder in adults and anxiety in children. Psychosocial stress has been linked to asthma morbidity in Puerto Rican children.ObjectivesTo examine whether epigenetic or genetic variation in ADCYAP1R1 is associated with childhood asthma in Puerto Ricans.MethodsWe conducted a case-control study of 516 children ages 6-14 years living in San Juan, Puerto Rico. We assessed methylation at a CpG site in the promoter of ADCYAP1R1 (cg11218385) using a pyrosequencing assay in DNA from white blood cells. We tested whether cg11218385 methylation (range, 0.4-6.1%) is associated with asthma using logistic regression. We also examined whether exposure to violence (assessed by the Exposure to Violence [ETV] Scale in children 9 yr and older) is associated with cg11218385 methylation (using linear regression) or asthma (using logistic regression). Logistic regression was used to test for association between a single nucleotide polymorphism in ADCYAP1R1 (rs2267735) and asthma under an additive model. All multivariate models were adjusted for age, sex, household income, and principal components.Measurements and main resultsEACH 1% increment in cg11218385 methylation was associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.6; P = 0.03). Among children 9 years and older, exposure to violence was associated with cg11218385 methylation. The C allele of single nucleotide polymorphism rs2267735 was significantly associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.02-1.67; P = 0.03).ConclusionsEpigenetic and genetic variants in ADCYAP1R1 are associated with asthma in Puerto Rican children.
Project description:RationaleStress is associated with asthma morbidity in Puerto Ricans (PRs), who have reduced bronchodilator response (BDR).ObjectivesTo examine whether stress and/or a gene regulating anxiety (ADCYAP1R1) is associated with BDR in PR and non-PR children with asthma.MethodsThis was a cross-sectional study of stress and BDR (percent change in FEV1 after BD) in 234 PRs ages 9-14 years with asthma. We assessed child stress using the Checklist of Children's Distress Symptoms, and maternal stress using the Perceived Stress Scale. Replication analyses were conducted in two cohorts. Polymorphisms in ADCYAP1R1 were genotyped in our study and six replication studies. Multivariable models of stress and BDR were adjusted for age, sex, income, environmental tobacco smoke, and use of inhaled corticosteroids.Measurements and main resultsHigh child stress was associated with reduced BDR in three cohorts. PR children who were highly stressed (upper quartile, Checklist of Children's Distress Symptoms) and whose mothers had high stress (upper quartile, Perceived Stress Scale) had a BDR that was 10.2% (95% confidence interval, 6.1-14.2%) lower than children who had neither high stress nor a highly stressed mother. A polymorphism in ADCYAP1R1 (rs34548976) was associated with reduced BDR. This single-nucleotide polymorphism is associated with reduced expression of the gene for the β2-adrenergic receptor (ADRB2) in CD4(+) lymphocytes of subjects with asthma, and it affects brain connectivity of the amygdala and the insula (a biomarker of anxiety).ConclusionsHigh child stress and an ADCYAP1R1 single-nucleotide polymorphism are associated with reduced BDR in children with asthma. This is likely caused by down-regulation of ADRB2 in highly stressed children.
Project description:Background and objectivesAlthough community violence may influence asthma morbidity by increasing stress, no study has assessed exposure to gun violence and childhood asthma. We examined whether exposure to gun violence is associated with asthma in children, particularly in those reporting fear of leaving their home.MethodsCase-control study of 466 children aged 9-14 years with (n = 234) and without (n = 232) asthma in San Juan, Puerto Rico. Lifetime exposure to gun violence was defined as hearing a gunshot more than once. We also assessed whether the child was afraid to leave his/her home because of violence. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for the statistical analysis. All multivariate models were adjusted for age, gender, household income, parental asthma, environmental tobacco smoke, prematurity and residential distance from a major road.ResultsCases were more likely to have heard a gunshot more than once than control subjects (n = 156 or 67.2% vs. n = 122 or 52.1%, P < 0.01). In a multivariate analysis, hearing a gunshot more than once was associated with asthma (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.1-1.7, P = 0.01). Compared with children who had heard a gunshot not more than once and were not afraid to leave their home because of violence, those who had heard a gunshot more than once and were afraid to leave their home due to violence had 3.2 times greater odds of asthma (95% CI for OR = 2.2-4.4, P < 0.01).ConclusionsExposure to gun violence is associated with asthma in Puerto Rican children, particularly in those afraid to leave their home. Stress from such violence may contribute to the high burden of asthma in Puerto Ricans.
Project description:BackgroundPuerto Ricans share a disproportionate burden of childhood asthma in the United States. Little is known about the impact of low parental numeracy (a health literacy skill) on asthma morbidity in Puerto Rican children. Our objective was to examine whether low parental numeracy is associated with increased asthma morbidity in Puerto Rican children.MethodsThis was a cross-sectional study of 351 children with asthma, aged 6 to 14 years, living in San Juan, Puerto Rico. Parents of study participants completed a modified version of the Asthma Numeracy Questionnaire. Multivariate linear or logistic regression was used to examine the relation between low parental numeracy (defined as no correct answers in the modified Asthma Numeracy Questionnaire) and indicators of asthma morbidity (severe asthma exacerbations, core measures of asthma exacerbations, and lung function measures). All multivariate models were adjusted for age, sex, household income, reported use of inhaled corticosteroids in the previous 6 months, and exposure to secondhand tobacco smoke.ResultsLow parental numeracy was associated with increased odds of visits to the ED or urgent care for asthma (adjusted OR [aOR]=1.7, 95% CI=1.03-2.7, P=.04). The association between low parental numeracy and hospitalizations for asthma was significant only among children not using inhaled corticosteroids (aOR=2.8, 95% CI=1.4-5.6, P=.004). There was no association between low parental numeracy and use of systemic steroids or lung function measures.ConclusionsLow parental numeracy is associated with increased asthma morbidity in Puerto Rican children.
Project description:BackgroundLong-term effects of sulfur dioxide (SO2 ) exposure on children, a vulnerable population, are largely unknown. Further, how long-term SO2 affects Puerto Rican children living in the island of Puerto Rico, a group with high asthma prevalence, is unclear. We evaluated the effects of annual average 1-hour daily maximum SO2 average on asthma, atopy, total immunoglobulin E (IgE), and lung function in Puerto Rican children.MethodsA cohort of 678 children (351 with asthma, 327 without asthma) was recruited in Puerto Rico from 2009 to 2010. Annual average 1-hour daily maximum SO2 exposure was interpolated utilizing publicly available monitoring data. Multivariable logistic and linear regression was used for the analysis of asthma, atopy (defined as an IgE ?0.35 IU/mL to at least one of five common aero-allergens), total IgE, and lung function measures (forced vital capacity [FVC], forced expiratory volume in 1?second [FEV1], and FEV1/FVC ratio).ResultsAnnual SO2 exposure (per 1?ppb) was significantly associated with asthma (odds ratio [OR]?=?1.42; 95% confidence interval [CI]?=?1.05-1.91) and atopy (OR?=?1.35; 95% CI?=?1.02-1.78). Such exposure was also significantly associated with lower FEV1/FVC in all children (??=?-1.42; 95% CI?=?-2.78 to -0.08) and in children with asthma (??=?-2.39; 95% CI=?-4.31 to -0.46). Annual SO2 exposure was not significantly associated with total IgE, FEV1, or FVC.ConclusionsAmong Puerto Rican children in Puerto Rico, long-term SO2 exposure is linked to asthma and atopy. In these children, long-term SO2 exposure is also associated with reduced FEV1/FVC, particularly in those with asthma.
Project description:Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans.To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors.A cross-sectional study was conducted of 560 children ages 6-14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates.Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P = 0.001) and atopy, and a lower FEV(1)/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P = 0.04) cases.Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.
Project description:BackgroundExposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms.MethodsEpigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by p value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).ResultsThree CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10-7 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05.ConclusionsPending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.