Search

BackgroundPAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma.ObjectiveWe sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level.MethodsWe studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function.ResultsThere was an interaction between asthma status and the PAI-1 polymorphism on FEV1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV1 /FVC (P

BackgroundYounger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations.ObjectivesWe sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children.MethodsWe included 3473 Latino children aged 8-21 years (1696 subjects with physician-diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship.ResultsMaternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors (OR = 0.73, 95% CI: 0.57-0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans (OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma (OR = 0.65, 95% CI: 0.44-0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings (OR = 0.44, 95% CI: 0.23-0.81).Conclusion and clinical relevanceIn contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability.

Rationale: Under-perception of asthma symptoms is associated with poor asthma outcomes., Objective: We assessed the effects of a behavioral intervention for improving perception of airflow limitation and asthma outcomes., Methods: A two-arm randomized controlled trial compared peak expiratory flow (PEF) feedback versus supportive counseling. Latino and Black adolescents with asthma ages 10-17 years old and caregivers were recruited from hospitals in the Bronx, NY. PEF feedback sessions reviewed accuracy of PEF guesses and medication adherence data, and targeted behavior change using motivational interviewing and problem-solving skills training. Supportive counseling received emotional support related to asthma. Both groups received 3 sessions across 6 weeks. All participants were blinded to PEF while guessing PEF during pre-intervention, 1, 6, and 12-month follow-up. Children in PEF feedback saw actual PEF after guesses were locked in during the 6-week intervention. Participants and assessors were blinded to group assignment., Measurements: The primary outcome was under-perception of airflow limitation (divergence between actual PEF and guesses) on home spirometers. Secondary outcomes included daily PEF and forced expiratory volume in 1 second (FEV 1 ), inhaled corticosteroid adherence measured by electronic monitors, Asthma Control Test, and emergency healthcare use for asthma., Results: The sample comprised 354 children ( M = 13.2±2.2 years; 62% Latino, 38% Black) and caregivers. PEF feedback (N = 153 analyzed) demonstrated greater improvements at 1-month follow-up on under-perception of airflow limitation (difference-in-differences, -12.64; 95% CI, -17.54 to -7.74), % personal best PEF (9.89; 95% CI, 7.13 to 12.65), % predicted FEV 1 (4.93; 95% CI, 0.95 to 8.90) and ICS adherence (16.02; 95% CI, 7.15 to 24.89) compared with supportive counseling (N = 152 analyzed). At 12-month follow-up PEF feedback maintained improvements on under-perception of airflow limitation (-13.87; 95% CI, -19.03 to -8.71), higher PEF (14.23; 95% CI, 11.37 to 17.08) and %FEV 1 (5.62; 95% CI, 1.56 to 9.67), and had smaller declines in ICS adherence (17.51; 95% CI, 7.12 to 27.89) versus pre-intervention than supportive counseling. No between-group differences existed for asthma control or healthcare use., Conclusion: The efficacy and sustainability of PEF feedback was established in improving children's perception of airflow limitation, pulmonary function, and medication adherence. Clinical trial registration available at www., Clinicaltrials: gov, ID: NCT02702687.

Background: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers., Objective: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans., Methods: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts., Results: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil transendothelial migration. In contrast, eosinophil transendothelial migration was not inhibited by siRNA knockdown of HTR1A or HTR1B in eosinophils. Surprisingly, these HTRs were intracellular in endothelial cells and an extracellular supplementation with serotonin did not inhibit eosinophil transendothelial migration. This is consistent with the inability of serotonin to cross membranes, the lack of selective serotonin reuptake receptors on endothelial cells, and the studies showing minimal impact of selective serotonin reuptake inhibitors on asthma. To extend our HTR studies to humans with asthma, we examined the CHIRAH and GALA cohorts for HTR SNPs that affect HTR function or are associated with behavior disorders. A polygenic index of SNPs in HTRs was associated with lower lung function in asthmatics., Conclusions: Serotonin receptors mediate 5HTP inhibition of transendothelial migration and HTR SNPs associate with lower lung function. These results may serve to aid in design of novel interventions for allergic inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Walker, Bloodworth, Kountz, McCarty, Green, Ferrie, Campbell, Averill, Beckman, Grammer, Eng, Avila, Farber, Rodriguez-Cintron, Rodriguez-Santana, Serebrisky, Thyne, Seibold, Burchard, Kumar and Cook-Mills.)

Objective: This study examined the associations between attention-deficit/hyperactivity disorder (ADHD) symptoms, underperception of respiratory compromise, and illness representations in Black and Latino children with asthma. We hypothesized that increased child-reported ADHD symptoms, as well as parent reports for their child, would be associated with underperception of respiratory compromise, and maladaptive asthma beliefs., Methods: Two hundred ninety-six parent-child dyads were recruited from pediatric asthma and primary care clinics in the Bronx. Participants completed demographic questionnaires, the Conners-3 ADHD Index to measure ADHD symptoms, and the Asthma Illness Representation Scale to assess asthma beliefs. Perception of respiratory compromise was assessed by programmable electronic peak flow monitors that measured the child's subjective estimates of peak expiratory flow (PEF) and actual PEF, with underperception as the primary measure., Results: Child-reported ADHD symptoms were associated with greater underperception (β = .117, p = .049) of respiratory compromise. Parent-reported ADHD symptoms were associated with greater underperception (β = .129, p = .028) of respiratory compromise. Child-reported ADHD symptoms (β = -.188, p < .001) were associated with more maladaptive asthma beliefs, F(1, 341) = 13.135. Parent-reported ADHD symptoms (β = -.203, p ≤ .001) were associated with more maladaptive asthma beliefs, F(1, 341) = 15.644., Conclusions: ADHD symptoms were associated with a greater underperception of respiratory compromise and more maladaptive asthma beliefs. Deficits of attentional processes and/or hyperactivity levels might be contributing factors. We emphasize the need for psychoeducation and interventions that improve perception and health beliefs in children with comorbid ADHD and asthma., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Children with comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) and asthma are at an increased risk for adverse health outcomes and reduced quality of life. The objective of these analyses was to examine if self-reported ADHD symptoms in children with asthma are associated with asthma control, asthma controller medication adherence, quick relief medication use, pulmonary function, and acute healthcare utilization., Methods: We analyzed data from a larger study testing a behavioral intervention for Black and Latinx children with asthma aged 10-17 years and their caregivers. Participants completed the Conners-3AI self-report assessment for ADHD symptoms. Asthma medication usage data were collected for 3 weeks following baseline via electronic devices fitted to participants' asthma medications. Other outcome measures included the Asthma Control Test, self-reported healthcare utilization, and pulmonary function measured by spirometry testing., Results: The study sample consisted of 302 pediatric participants with an average age of 12.8 years. Increased ADHD symptoms were directly associated with reduced adherence to controller medications, but no evidence of mediation was observed. Direct effects of ADHD symptoms on quick-relief medication use, health care utilization, asthma control, or pulmonary function were not observed. However, the effect of ADHD symptoms on emergency room visits was mediated by controller medication adherence., Discussion: ADHD symptoms were associated with significantly reduced asthma controller medication adherence and indirectly with emergency room visits. There are significant potential clinical implications to these findings, including the need for the development of interventions for pediatric asthma patients with ADHD., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Asthma control improved during the COVID-19 pandemic. This study examined objectively measured medication adherence, asthma morbidity and quality of life (QoL) outcomes in Black and Latinx children by month for January-June 2019 (pre-COVID) compared to January-June 2020 (including first peak of COVID)., Methods: Secondary analyses of 94 children with asthma (ages 10-17 years, 64% Latinx, 36% Black) and their caregivers assigned to the comparison group of a longitudinal RCT intervention trial. Outcomes included mean aggregate electronic adherence for controller medications, oral steroid bursts, acute healthcare utilization, caregiver asthma QoL, and the Asthma Control Test. Repeated measures analyses were conducted due to multiple observations., Results: Adherence to controller medications declined 48% from 2019 to 2020 (LS Mean = 33.9% vs. 17.6%, p =.0004, f =.92) with levels reaching a low in May 2020. A reduction in steroid bursts was observed over the same timeframe, 1.29 vs. 0.61, p  = 0.006, f =.63. Caregiver QoL increased from 2019 to 2020 on total score (5.18 vs. 5.85, p  = 0.002, f =.72), activity limitations (5.04 vs. 5.95), and emotional functioning (5.26 vs. 5.80). Although not statistically significant, a clinically meaningful 62% reduction in acute healthcare visits ( p  = 0.15) was reported in 2020. Children reported better asthma control (OR = 1.47, 95% CI 1.24, 1.73, p  < 0.0001) in 2020 versus 2019 driven by improvements from May to June 2020., Conclusions: Decreased asthma morbidity in minority children during COVID was coupled with decreased adherence to controller medications. This observed decrease in morbidity is not explained by improvements in adherence.

Objective: Examine whether caregiver depressive symptoms at baseline predict longitudinal child asthma outcomes in the two populations with the largest asthma disparities: Mexicans and Puerto Ricans., Methods: Two hundred and sixty-seven Hispanic caregiver-child dyads (Mexican = 188, Puerto Rican = 79; children 5-12 years) were recruited from clinics and hospitals in Phoenix, AZ and the Bronx, NY. The Center for Epidemiological Studies Depression Scale assessed caregiver depressive symptoms; higher scores indicate greater depressive symptomology. Medical records verified child asthma diagnosis. Assessments for outcome variables occurred at baseline, 3, 6, 9, and 12-month follow-ups. Pulmonary function was measured by spirometry, asthma control was measured by the Asthma Control Test, steroid bursts and acute healthcare utilization were assessed by caregiver report and medical records, and adherence was measured by doser devices on controller medications. Structural equation modeling analyzed baseline caregiver depressive symptoms as a predictor of longitudinal child asthma outcomes, and differences between subgroups., Results: Higher caregiver depressive symptoms predicted better pulmonary function ( β = .02, p = .001) in Mexican children, and fewer steroid bursts ( β = -.41, p = .01) and better medication adherence ( β = .02, p = .07) in Puerto Rican children. Caregiver depressive symptoms did not predict pediatric asthma control or acute healthcare utilization in either subgroup., Conclusions: Caregiver depressive symptomology had unexpected effects on child asthma outcomes. Results may be explained by the Hispanic paradox, caregiver resilience, acculturation, and the study's longitudinal nature. Further research is needed on social determinants of health that may influence differences in child asthma outcomes in heterogeneous Hispanic communities.

Background: Allergic sensitization to environmental allergens in the first years of life is a strong predictor of asthma morbidity in children. Allergy immunotherapy can improve asthma and allergy outcomes, but its efficacy in inner-city, atopic children of less than 4 years of age with recurrent wheezing has not yet been established., Objective: To determine whether subcutaneous allergy immunotherapy improves asthma in a population of US inner-city children when started at less than 4 years of age., Methods: In a randomized controlled, open-label phase I-II single-center trial in the Bronx, New York, 58 children with recurrent wheezing or physician-diagnosed asthma were randomized to receive asthma standard of care treatment with or without a 3-year course of multiple allergen subcutaneous immunotherapy., Results: A total of 23 children in the control group and 27 children in the immunotherapy group began the study. A total of 20 of 27 children commencing immunotherapy completed at least 2 years of immunotherapy. There was no difference in asthma medication and symptom scores between the treatment or control groups over time. Similarly, naso-ocular symptoms and allergy medication use were similar in both groups over time. Nevertheless, asthma-related quality of life improved in the immunotherapy group compared with the control group (P = .03)., Conclusion: With the exception of asthma-related quality of life, allergy immunotherapy was ineffective in improving asthma outcomes in this population of inner-city children of less than 4 years of age. These findings suggest that the effects of allergy immunotherapy depend on population-specific factors and highlight the importance of precise predictors of immunotherapy efficacy., Trial Registration: ClinicalTrials.gov Identifier: NCT01028560., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: Severe early-life respiratory illnesses, particularly those caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV), are strongly associated with the development of asthma in children. Puerto Rican children in particular have a strikingly high asthma burden. However, prior studies of the potential associations between early-life respiratory illnesses and asthma in Puerto Rican and other minority populations have been limited., Objectives: We sought to determine whether early-life respiratory illness was associated with asthma in Puerto Rican, Mexican American, and African American children., Methods: Using a logistic regression analysis, we examined the association between early-life respiratory illnesses (report of upper respiratory infection (URI), pneumonia, bronchitis, and bronchiolitis/RSV) within the first two years of life and physician-diagnosed asthma after the age of two in a large cohort of Puerto Rican, Mexican American, and African American children., Measurements and Main Results: While early-life respiratory illnesses were associated with greater asthma odds in Puerto Ricans, Mexican Americans, and African Americans, these associations were stronger among Puerto Rican children. Specifically, in Puerto Ricans, the odds was 6.15 (95% CI: 4.21-9.05) if the child reported at least one of the following respiratory illness: URI, pneumonia, bronchitis or bronchiolitis. The odds were also higher in Puerto Ricans when considering these conditions separately., Conclusions: We observed population-specific associations between early-life respiratory illnesses and asthma, which were especially significant and stronger in Puerto Ricans. Taken together with the known high burden of RSV in Puerto Rico, our results may help explain the high burden of asthma in Puerto Ricans., Competing Interests: The authors have declared that no competing interests exist.

Background: Little research has been conducted that integrates, in one explanatory model, the multitude of factors potentially leading to disparities among Latino children., Purpose: A longitudinal, observational study tested an explanatory model for disparities in asthma control between Mexican and Puerto Rican children with persistent asthma requiring daily controller medication use., Methods: Mexican and Puerto Rican children aged 5-12 years (n = 267) and their caregivers (n = 267) were enrolled and completed interviews and child spirometry at baseline and 3, 6, 9, and 12 months postenrollment. A 12 month retrospective children's medical record review was completed. Participants were recruited from two school-based health clinics and the Breathmobile in Phoenix, AZ, and two inner-city hospital asthma clinics in the Bronx, NY., Results: Statistically significant differences in the social/contextual predictors of asthma illness representations (IRs) were noted between Mexican and Puerto Rican caregivers. The structural equation model results revealed differences in asthma control over time by ethnicity. This model accounted for 40%-48% of the variance in asthma control test scores over 12 months. Caregivers' IRs aligned with the professional model of asthma management were associated with better children's asthma control across 1 year. These results also supported the theoretical notion that IRs change over time impacting caregivers' treatment decisions and children's asthma control., Conclusions: These findings extend a previous cross-sectional model test using a more comprehensive model and longitudinal data and highlight the importance of considering within-group differences for diagnosis and treatment of children coming from the vastly heterogeneous Latino umbrella group., Trial Registration: Trial number NCT01099800., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

Objective: To examine baseline measures of illness-specific panic-fear (ie, the level of anxiety experienced specifically during asthma exacerbations) as a protective factor in pediatric asthma outcomes over a 1-year period., Study Design: The sample comprised 267 children (Mexican, n = 188; Puerto Rican, n = 79; age 5-12 years) from a longitudinal observational study conducted in Phoenix, AZ and Bronx, NY. Assessments were done at baseline and 3, 6, 9, and 12 months. The Childhood Asthma Symptom Checklist was administered at baseline to children and caregivers to assess children's illness-specific panic-fear. Asthma outcome variables quantified longitudinally included pulmonary function, the Asthma Control Test, acute healthcare utilization, and medication adherence, measured by devices attached to inhaled corticosteroids., Results: Child report of illness-specific panic-fear at baseline predicted higher forced expiratory volume in 1 second (FEV 1 ) % across 1-year follow-up in Mexican children (β = 0.17, P = .02), better asthma control in Puerto Rican children (β = 0.45, P = .007), and less acute healthcare utilization for asthma in both groups (Mexicans: β = -0.39, P = .03; Puerto Ricans: β = -0.47, P = .02). Caregiver report of child panic-fear predicted higher FEV 1 % in Mexican (β = 0.30; P = .02) and Puerto Rican (β = 0.19; P = .05) children. Panic-fear was not related to medication adherence., Conclusions: Illness-specific panic-fear had beneficial effects on asthma outcomes in both groups of Latino children. The heightened vigilance associated with illness-specific panic-fear may lead children to be more aware of their asthma symptoms and lead to better strategies for asthma management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association was assessed using multivariable quantile regression. After adjusting for baseline forced expiratory volume in one second and use of controller medications, ICS use was significantly associated with increased BDR only among Mexican Americans (1.56%, P = 0.028) but not African Americans (0.49%, P = 0.426) or Puerto Ricans (0.16%, P = 0.813). Our results demonstrate that ICS augmentation is disproportionate across racial/ethnic groups, where improved BDR is observed in Mexican Americans only. This study highlights the complexities of treating asthma in children, and reinforces the importance of investigating the influence of race/ethnicity on pharmacological response., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Short-acting β 2 -adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10 -9 ). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10 -8 ). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.

Background: Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response., Objective: We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings., Methods: A meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10 -6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations., Results: A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10 -6 ). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10 -3 ) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10 -3 ). Additionally, the reported association of the L3MBTL4-ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified., Conclusions and Clinical Relevance: This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment., (© 2019 John Wiley & Sons Ltd.)

Background: Acculturation is an important predictor of asthma in Latino youth, specifically Mexican Americans. Less is known about acculturation and pulmonary function measures., Objective: We sought to estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups., Methods: We included 1849 Latinos (302 Caribbean Spanish, 193 Central or South Americans, 1136 Mexican Americans, and 218 other Latino children) aged 8 to 21 years from 4 urban regions in the United States. Acculturation measures include nativity status, age of immigration, language of preference, and generation in the United States. We used multivariable logistic and linear regression models to quantify the association of acculturation factors with the presence of asthma (case-control study) and pulmonary function (case-only study), adjusting for demographic, socioenvironmental, and clinical variables., Results: For all acculturation measures (nativity status, age of immigration, language of preference, and generation in the United States), greater levels of acculturation were associated with greater odds of asthma. Among cases, high (English preference) and medium (equal preference for Spanish and English) levels of language acculturation were associated with decreased bronchodilator response compared with low (Spanish preference) levels (P = .009 and .02, respectively). Similarly, high language acculturation was associated with increased FEV 1 compared with low language acculturation (P = .02). There was insufficient evidence of heterogeneity for associations across Latino subgroups., Conclusions: Acculturation was associated with diagnosed asthma and pulmonary function in Latino children and is an important factor to consider in the management of Latino youth with asthma., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies., Objective: We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility., Methods: We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups., Results: We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10 -6 ), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10 -3 , combined P = 2.6 × 10 -7 ). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P < .001). In addition, lower expression of SMAD2 was associated with more frequent exacerbations among Puerto Ricans with asthma., Conclusion: Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations., (Copyright © 2018. Published by Elsevier Inc.)

The global prevalence, morbidity and mortality related to childhood asthma among children has increased significantly over the last 40 years. Although asthma is recognized as the most common chronic disease in children, issues of underdiagnosis and undertreatment persist. There are substantial global variations in the prevalence of asthma symptoms in children, with up to 13-fold differences between countries. The rising number of hospital admissions for asthma may reflect an increase in asthma severity, poor disease management and/or the effect of poverty. The financial burden of asthma is relatively high within developed countries (those for which data is available) spending 1 to 2% of their healthcare budget on this condition. Established in 1989, the Global Initiative for Asthma (GINA) attempts to raise awareness about the increasing prevalence of asthma, improve management and reduce the burden of asthma worldwide. Despite global efforts, GINA has not achieved its goal, even among developed nations. There are multiple barriers to reducing the global burden of asthma, including limited access to care and/or medications, and lack of prioritization as a public healthcare priority. In addition, the diversity of healthcare systems worldwide and large differences in access to care require that asthma management guidelines be tailored to local needs., Competing Interests: The authors have no competing interests to declare., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.)

Background: Secondhand smoke (SHS) exposures have been linked to asthma-related outcomes but quantitative dose-responses using biomarkers of exposure have not been widely reported., Objectives: Assess dose-response relationships between plasma cotinine-determined SHS exposure and asthma outcomes in minority children, a vulnerable population exposed to higher levels of SHS and under-represented in the literature., Methods: We performed analyses in 1172 Latino and African-American children with asthma from the mainland USA and Puerto Rico. We used logistic regression to assess relationships of cotinine levels ≥0.05 ng/mL with asthma exacerbations (defined as asthma-related hospitalisations, emergency room visits or oral steroid prescription) in the previous year and asthma control. The shape of dose-response relationships was assessed using a continuous exposure variable in generalised additive logistic models with penalised splines., Results: The OR for experiencing asthma exacerbations in the previous year for cotinine levels ≥0.05 ng/mL, compared with <0.05 ng/mL, was 1.40 (95% CI 1.03 to 1.89), while the OR for poor asthma control was 1.53 (95% CI 1.12 to 2.13). Analyses for dose-response relationships indicated increasing odds of asthma outcomes related with increasing exposure, even at cotinine levels associated with light SHS exposures., Conclusions: Exposure to SHS was associated with higher odds of asthma exacerbations and having poorly controlled asthma with an increasing dose-response even at low levels of exposure. Our results support the conclusion that there are no safe levels of SHS exposures., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Rationale: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response., Objectives: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children., Methods: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR., Measurements and Main Results: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P < 3.53 × 10 -7 ) and suggestive (P < 7.06 × 10 -6 ) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings., Conclusions: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.

Objective: In the United States, Puerto Ricans and African Americans have lower prevalence of breastfeeding and worse clinical outcomes for asthma compared with other racial/ethnic groups. We hypothesize that the history of breastfeeding is associated with increased forced expiratory volume in 1 second (FEV 1 ) % predicted and reduced asthma exacerbations in Latino and African American youths with asthma., Methods: As part of the Genes-environments & Admixture in Latino Americans (GALA II) Study and the Study of African Americans, asthma, Genes & Environments (SAGE II), we conducted case-only analyses in children and adolescents aged 8-21 years with asthma from four different racial/ethnic groups: African Americans (n = 426), Mexican Americans (n = 424), mixed/other Latinos (n = 255), and Puerto Ricans (n = 629). We investigated the association between any breastfeeding in infancy and FEV 1 % predicted using multivariable linear regression; Poisson regression was used to determine the association between breastfeeding and asthma exacerbations., Results: Prevalence of breastfeeding was lower in African Americans (59.4%) and Puerto Ricans (54.9%) compared to Mexican Americans (76.2%) and mixed/other Latinos (66.9%; p < 0.001). After adjusting for covariates, breastfeeding was associated with a 3.58% point increase in FEV 1 % predicted (p = 0.01) and a 21% reduction in asthma exacerbations (p = 0.03) in African Americans only., Conclusion: Breastfeeding was associated with higher FEV 1 % predicted in asthma and reduced number of asthma exacerbations in African American youths, calling attention to continued support for breastfeeding.

Objective: To investigate the relationship between food allergy and symptoms of anxiety and depression among ethnic minority, low socioeconomic status (SES) children and their caregivers., Study Design: Pediatric patients ages 4-12 years with and without food allergy and their caregivers were recruited from urban pediatric outpatient clinics. Statistical analyses were used to examine the prevalence of symptoms of anxiety and depression among patients and their caregivers with and without food allergy, adjusting for asthma., Results: Eighty patients ranging from ages 4 to 12 years, with a mean age of 8.1 years, and their caregivers participated in the study. Food allergy was associated with significantly higher t scores on the Multidimensional Anxiety Scale for Children (MASC) Total (P = .007), MASC Humiliation Rejection, (P = .02) and MASC Social Anxiety (P = .02) among pediatric patients, adjusting for asthma. Food allergy was not associated with child depression symptoms, nor was there a significant difference in anxiety or depression symptoms among caregivers of patients with and without food allergy., Conclusions: Food allergy appears to be associated with increased symptoms of social anxiety and higher levels of anxiety overall, but not depression, in ethnic minority children of lower socioeconomic status. This finding was not due to confounding by asthma. Food allergy was not associated with higher levels of depression or anxiety symptoms among caregivers of pediatric patients with food allergy. Future studies should investigate potential pathways between food allergy and anxiety that may be unique to children in underserved populations, and develop interventions to reduce anxiety in children with food allergy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ethnic minority children bear a disproportionate amount of the US asthma burden. We compared asthma morbidity and pulmonary function (%FEV 1 ) in two Caribbean groups living in the Bronx, NY: Puerto Rican and Afro-Caribbean children. Caregiver-child dyads (Puerto Rican: n = 113, M age = 9.89 ± 2.05; Afro-Caribbean: n = 47, Mage = 10.35 ± 2.08) responded to sociodemographic and asthma-related questions, and children's %FEV 1 was measured. Puerto Rican children had significantly greater (past year) asthma morbidity, yet there were no significant differences in %FEV 1 . This discrepancy between objective pulmonary function and asthma morbidity suggests the importance of considering sociocultural factors in pediatric asthma care.

Background: Asthma disproportionately affects minority populations and is associated with psychosocial stress such as racial/ethnic discrimination. We aimed to examine the association of perceived discrimination with asthma and poor asthma control in African American and Latino youth., Methods: We included African American (n = 954), Mexican American (n = 1,086), other Latino (n = 522), and Puerto Rican Islander (n = 1,025) youth aged 8 to 21 years from the Genes-Environments and Admixture in Latino Americans study and the Study of African Americans, Asthma, Genes, and Environments. Asthma was defined by physician diagnosis, and asthma control was defined based on the National Heart, Lung, and Blood Institute guidelines. Perceived racial/ethnic discrimination was assessed by the Experiences of Discrimination questionnaire, with a focus on school, medical, and public settings. We examined the associations of perceived discrimination with each outcome and whether socioeconomic status (SES) and global African ancestry modified these associations., Results: African American children reporting any discrimination had a 78% greater odds of experiencing asthma (OR, 1.78; 95% CI, 1.33-2.39) than did those not reporting discrimination. Similarly, African American children faced increased odds of poor asthma control with any experience of discrimination (OR, 1.97; 95% CI, 1.42-2.76) over their counterparts not reporting discrimination. These associations were not observed among Latino children. We observed heterogeneity of the association between reports of discrimination and asthma according to SES, with reports of discrimination increasing the odds of having asthma among low-SES Mexican American youth (interaction P = .01) and among high-SES other Latino youth (interaction P = .04)., Conclusions: Perceived discrimination is associated with increased odds of asthma and poorer control among African American youth. SES exacerbates the effect of perceived discrimination on having asthma among Mexican American and other Latino youth., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Skin pigmentation is a complex trait that varies largely among populations. Most genome-wide association studies of this trait have been performed in Europeans and Asians. We aimed to uncover genes influencing skin colour in African-admixed individuals. We performed a genome-wide association study of melanin levels in 285 Hispanic/Latino individuals from Puerto Rico, analyzing 14 million genetic variants. A total of 82 variants with p-value ≤1 × 10 -5 were followed up in 373 African Americans. Fourteen single nucleotide polymorphisms were replicated, of which nine were associated with skin colour at genome-wide significance in a meta-analysis across the two studies. These results validated the association of two previously known skin pigmentation genes, SLC24A5 (minimum p = 2.62 × 10 -14 , rs1426654) and SLC45A2 (minimum p = 9.71 × 10 -10 , rs16891982), and revealed the intergenic region of BEND7 and PRPF18 as a novel locus associated with this trait (minimum p = 4.58 × 10 -9 , rs6602666). The most significant variant within this region is common among African-descent populations but not among Europeans or Native Americans. Our findings support the advantages of analyzing African-admixed populations to discover new genes influencing skin pigmentation.

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10 -64 ) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation., Competing Interests: The authors declare that no competing interests exist.

Background: Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk., Methods: We included Latino children, adolescents, and young adults aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function., Results: RSV infection (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 9.1, 95%CI 7.2-11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7, 95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted., Conclusions: A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population., Competing Interests: The authors have declared that no competing interests exist.

Background: Pest allergen sensitization is associated with asthma morbidity in urban youth but minimally explored in Latino populations. Specifically, the effect of mouse sensitization on the risk of asthma exacerbation has been unexplored in Latino subgroups., Objective: To evaluate whether pest allergen sensitization is a predictor of asthma exacerbations and poor asthma control in urban minority children with asthma., Methods: Latino and African American children (8-21 years old) with asthma were recruited from 4 sites across the United States. Logistic regression models evaluated the association of mouse or cockroach sensitization with asthma-related acute care visits or hospitalizations., Results: A total of 1,992 children with asthma in the Genes-environments and Admixture in Latino American (GALA-II) and Study of African-Americans, Asthma, Genes, and Environments (SAGE-II) cohorts were studied. Asthmatic children from New York had the highest rate of pest allergen sensitization (42% mouse, 56% cockroach), with the lowest rate in San Francisco (4% mouse, 8% cockroach). Mouse sensitization, more than cockroach, was associated with increased odds of acute care visits (adjusted odds ratio [aOR], 1.47; 95% CI, 1.07-2.03) or hospitalizations (aOR, 3.07; 95% CI, 1.81-5.18), even after controlling for self-reported race and site of recruitment. In stratified analyses, Mexican youth sensitized to mouse allergen did not have higher odds of asthma exacerbation. Other Latino and Puerto Rican youth sensitized to mouse had higher odds of hospitalization for asthma (aORs, 4.57 [95% CI, 1.86-11.22] and 10.01 [95% CI, 1.77-56.6], respectively) but not emergency department visits., Conclusion: Pest allergen sensitization is associated with a higher odds of asthma exacerbations in urban minority youth. Puerto Rican and Other Latino youth sensitized to mouse were more likely to have asthma-related hospitalizations than Mexican youth., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Environmental exposures to indoor allergens are major contributors to asthma symptoms, particularly in inner cities. The effectiveness of household allergen reduction as an adjunct to National Asthma Education Prevention Program guideline-based pharmacologic therapy in asthma has not been prospectively studied., Objective: To study the effect of individualized allergen reduction on ability to reduce asthma pharmacologic therapy over 40 weeks., Methods: We performed a randomized controlled trial to determine the effect of multifaceted indoor allergen avoidance measures on the ability to reduce asthma controller therapy in adults and children residing in New York City who were both sensitized and exposed to at least 1 indoor allergen. Asthma treatment and control were optimized in all subjects before randomization., Results: A total of 125 subjects were randomized to receive individualized household allergen reduction and 122 received a sham intervention. Subjects in the intervention group significantly reduced all measured allergen levels (cat, dog, dust mite allergens in the bedroom, cockroach and mouse allergens in the kitchen and bedroom); those in the control group reduced only dust mite and mouse allergens in the bedroom and cockroach allergen in the kitchen. Participants in the intervention arm reduced National Asthma Education Prevention Program-based therapy from step 4.4 at randomization to 3.50 postintervention (range, 0-6); participants in the control arm reduced medication from step 4.4 to 3.4 (P = .76). There were no differences in other measured asthma outcomes., Conclusions: Targeted allergen avoidance measures do not allow for reduction in asthma pharmacologic therapy compared with usual care in patients already receiving optimal controller therapy., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking., Objectives: To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry., Methods: The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 μm and ≤2.5 μm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry., Measurements and Main Results: A 5 μg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 μm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function., Conclusions: Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

Given the large availability of nicotinic acetylcholine receptors (nAChRs) throughout the brain, and the wide range of neurotransmitter systems affected (norepinephrine, serotonin and dopamine), nicotine influences a wide variety of cognitive domains such as sensorial, motor, attention, executive function, learning and memory. This article reviews current state of the art research on the effects of nicotine upon cognition. There are different neurobiological mechanisms involved in acute/chronic smoking and nicotine abstinence. Smoking reinforcement could be due to the initial cognitive improvement, that is, individuals can learn that smoking temporarily increases cognitive functioning (improving some components of attention and memory). These acute nicotine effects improve (i) cognitive performance above smokers' normal levels, and (ii) cognitive disruption resulting from nicotine abstinence. Both neurobiological effects act as reinforcers to nicotine use, greatly contributing to the development of nicotine dependence. However, heavy smoking is associated with cognitive impairment and cognitive decline in middle age. Future clinical research should investigate the role of positive and negative cognitive effects of nicotine in smoking cessation treatment. This is clearly an important scientific issue, with insufficient current data from which to draw definitive conclusions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Rationale: Asthma clinical guidelines suggest written asthma action plans are essential for improving self-management and outcomes., Objectives: To assess the efficacy of written instructions in the form of a written asthma action plan provided by subspecialist physicians as part of usual asthma care during office visits., Methods: A total of 407 children and adults with persistent asthma receiving first-time care in pulmonary and allergy practices at 4 urban medical centers were randomized to receive either written instructions (n = 204) or no written instructions other than prescriptions (n = 203) from physicians., Measurements and Main Results: Using written asthma action plan forms as a vehicle for providing self-management instructions did not have a significant effect on any of the primary outcomes: (1) asthma symptom frequency, (2) emergency visits, or (3) asthma quality of life from baseline to 12-month follow-up. Both groups showed similar and significant reductions in asthma symptom frequency (daytime symptoms [P < 0.0001], nocturnal symptoms [P < 0.0001], β-agonist use [P < 0.0001]). There was also a significant reduction in emergency visits for the intervention (P < 0.0001) and control (P < 0.0006) groups. There was significant improvement in asthma quality-of-life scores for adults (P < 0.0001) and pediatric caregivers (P < 0.0001)., Conclusions: Our results suggest that using a written asthma action plan form as a vehicle for providing asthma management instructions to patients with persistent asthma who are receiving subspecialty care for the first time confers no added benefit beyond subspecialty-based medical care and education for asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 00149461).

Background: IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders., Objective: We sought to identify genetic variants associated with IgE levels in Latinos., Methods: We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies., Results: We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of a polymorphism in the zinc finger protein 365 gene (ZNF365) with total IgE levels (rs200076616, P = 2.3 × 10(-8)). We next identified 4 admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) at which local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower IgE levels (P = 4.95 × 10(-8)). All but 22q13.1 were replicated in an independent sample of Latinos, and 2 of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified 6 genome-wide significant single nucleotide polymorphisms in Latinos, 2 of which replicated in European Americans. Another single nucleotide polymorphism was peak-wide significant within 14q23.2 in African Americans (rs1741099, P = 3.7 × 10(-6)) and replicated in non-African American samples (P = .011)., Conclusion: We confirmed genetic associations at 6 genes and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse multiethnic populations to uncover novel loci associated with total IgE levels., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Obesity is associated with poor asthma control, increased asthma morbidity, and decreased response to inhaled corticosteroids. We hypothesized that obesity would be associated with decreased bronchodilator responsiveness in children and adolescents with asthma. In addition, we hypothesized that subjects who were obese and unresponsive to bronchodilator would have worse asthma control and would require more asthma controller medications., Methods: In the Study of African Americans, Asthma, Genes, and Environments (SAGE II) and the Genes-environments and Admixture in Latino Americans (GALA II) study, two identical, parallel, case-control studies of asthma, we examined the association between obesity and bronchodilator response in 2,963 black and Latino subjects enrolled from 2008 to 2013 using multivariable logistic regression. Using bronchodilator responsiveness, we compared asthma symptoms, controller medication usage, and asthma exacerbations between nonobese (< 95th% BMI) and obese (≥ 95th% BMI) subjects., Results: The odds of being bronchodilator unresponsive were 24% (OR, 1.24; 95% CI, 1.03-1.49) higher among obese children and adolescents compared with their not obese counterparts after adjustment for age, race/ethnicity, sex, recruitment site, baseline lung function (FEV1/FVC), and controller medication. Bronchodilator-unresponsive obese subjects were more likely to report wheezing (OR, 1.38; 95% CI, 1.13-1.70), being awakened at night (OR, 1.34; 95% CI, 1.09-1.65), using leukotriene receptor inhibitors (OR, 1.33; 95% CI, 1.05-1.70), and using inhaled corticosteroid with long-acting β2-agonist (OR, 1.37; 95% CI, 1.05-1.78) than were their nonobese counterpart. These associations were not seen in the bronchodilator-responsive group., Conclusions: Obesity is associated with bronchodilator unresponsiveness among black and Latino children and adolescents with asthma. The findings on obesity and bronchodilator unresponsiveness represent a unique opportunity to identify factors affecting asthma control in blacks and Latinos.

Background: Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest., Objective: To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children., Methods: We analyzed 5493 Latinos with and without asthma from 3 independent studies. For each participant, we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry., Results: Native American ancestry was associated with lower odds of asthma (OR = 0.72, 95% CI: 0.66-0.78, P = 8.0 × 10(-15)), while African ancestry was associated with higher odds of asthma (OR = 1.40, 95% CI: 1.14-1.72, P = .001). These associations were robust to adjustment for covariates related to early life exposures, air pollution, and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of FEV1 (-77 ± 19 mL; P = 5.8 × 10(-5) and -83 ± 19 mL; P = 1.1 x 10(-5), respectively) and forced vital capacity (-100 ± 21 mL; P = 2.7 × 10(-6) and -107 ± 22 mL; P = 1.0 x 10(-6), respectively)., Conclusion: Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent., Objective: We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping., Methods: Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci., Results: We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies., Conclusions: Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21., (Published by Mosby, Inc.)

Background: The primary rescue medication to treat acute asthma exacerbation is the short-acting β₂-adrenergic receptor agonist; however, there is variation in how well a patient responds to treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR)., Objective: To identify genetic variation associated with bronchodilator drug response in Latino children with asthma., Methods: We performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity., Results: We identified 7 genetic variants associated with BDR at a genome-wide significant threshold (P < 5 × 10(-8)), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency, <5%) and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified 5 significant peaks; fine mapping within these peaks identified 2 rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells., Conclusion: Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in SLC genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multiethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Rationale: The burden of asthma is highest among socioeconomically disadvantaged populations; however, its impact is differentially distributed among racial and ethnic groups., Objectives: To assess the collective effect of maternal educational attainment, annual household income, and insurance type on childhood asthma among minority, urban youth., Methods: We included Mexican American (n = 485), other Latino (n = 217), and African American (n = 1,141) children (aged 8-21 yr) with and without asthma from the San Francisco Bay Area. An index was derived from maternal educational attainment, annual household income, and insurance type to assess the collective effect of socioeconomic status on predicting asthma. Logistic regression stratified by racial and ethnic group was used to estimate adjusted odds ratios (aOR) and their 95% confidence intervals (CI). We further examined whether acculturation explained the socioeconomic-asthma association in our Latino population., Measurements and Main Results: In the adjusted analyses, African American children had 23% greater odds of asthma with each decrease in the socioeconomic index (aOR, 1.23; 95% CI, 1.09-1.38). Conversely, Mexican American children have 17% reduced odds of asthma with each decrease in the socioeconomic index (aOR, 0.83; 95% CI, 0.72-0.96) and this relationship was not fully explained by acculturation. This association was not observed in the other Latino group., Conclusions: Socioeconomic status plays an important role in predicting asthma, but has different effects depending on race and ethnicity. Further steps are necessary to better understand the risk factors through which socioeconomic status could operate in these populations to prevent asthma.

Objective: To examine child and caregiver anxiety and depression as predictors of children's perception of pulmonary function, quick-relief medication use, and pulmonary function., Method: 97 children with asthma, ages 7 to 11 years old, reported their anxiety and depressive symptoms and completed spirometry. Caregivers completed a psychiatric interview. Children's predictions of their peak expiratory flow were compared with actual values across 6 weeks. Quick-relief medication use was assessed by Dosers., Results: Children's anxiety symptoms were associated with over-perception of respiratory compromise and greater quick-relief medication use. Children's depressive symptoms were associated with greater quick-relief medication use, but not perception of pulmonary function. Children of caregivers with an anxiety or depressive disorder had lower pulmonary function than children of caregivers without anxiety or depression., Conclusions: Child anxiety was associated with a subjective pattern of over-perception. Caregiver anxiety and depression were risk factors for lower lung function assessed by objective measurement.

Background: Atopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors., Objective: We sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma., Methods: Aeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models., Results: In baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[β] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[β] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin., Conclusions: Puerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Rationale: Air pollution is a known asthma trigger and has been associated with short-term asthma symptoms, airway inflammation, decreased lung function, and reduced response to asthma rescue medications., Objectives: To assess a causal relationship between air pollution and childhood asthma using data that address temporality by estimating air pollution exposures before the development of asthma and to establish the generalizability of the association by studying diverse racial/ethnic populations in different geographic regions., Methods: This study included Latino (n = 3,343) and African American (n = 977) participants with and without asthma from five urban regions in the mainland United States and Puerto Rico. Residential history and data from local ambient air monitoring stations were used to estimate average annual exposure to five air pollutants: ozone, nitrogen dioxide (NO₂), sulfur dioxide, particulate matter not greater than 10 μm in diameter, and particulate matter not greater than 2.5 μm in diameter. Within each region, we performed logistic regression to determine the relationship between early-life exposure to air pollutants and subsequent asthma diagnosis. A random-effects model was used to combine the region-specific effects and generate summary odds ratios for each pollutant., Measurements and Main Results: After adjustment for confounders, a 5-ppb increase in average NO₂ during the first year of life was associated with an odds ratio of 1.17 for physician-diagnosed asthma (95% confidence interval, 1.04-1.31)., Conclusions: Early-life NO₂ exposure is associated with childhood asthma in Latinos and African Americans. These results add to a growing body of evidence that traffic-related pollutants may be causally related to childhood asthma.

Rationale: Obesity is associated with increased asthma morbidity, lower drug responsiveness to inhaled corticosteroids, and worse asthma control. However, most prior investigations on obesity and asthma control have not focused on pediatric populations, considered environmental exposures, or included minority children., Objectives: To examine the association between body mass index categories and asthma control among boys and girls; and whether these associations are modified by age and race/ethnicity., Methods: Children and adolescents ages 8-19 years (n = 2,174) with asthma were recruited from the Genes-environments and Admixture in Latino Americans (GALA II) Study and the Study of African Americans, Asthma, Genes, and Environments (SAGE II). Ordinal logistic regression was used to estimate odds ratios (OR) and their confidence intervals (95% CI) for worse asthma control., Measurements and Main Results: In adjusted analyses, boys who were obese had a 33% greater chance of having worse asthma control than their normal-weight counterparts (OR, 1.33; 95% CI, 1.04-1.71). However, for girls this association varied with race and ethnicity (P interaction = 0.008). When compared with their normal-weight counterparts, obese African American girls (OR, 0.65; 95% CI, 0.41-1.05) were more likely to have better controlled asthma, whereas Mexican American girls had a 1.91 (95% CI, 1.12-3.28) greater odds of worse asthma control., Conclusions: Worse asthma control is uniformly associated with increased body mass index in boys. Among girls, the direction of this association varied with race/ethnicity.

Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk., Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis., Methods: We selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis., Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos., Conclusions: This extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Failure to detect respiratory compromise can lead to emergency healthcare use and fatal asthma attacks. The purpose of this study was to examine the effect of predicting peak expiratory flow (PEF) and receiving feedback on perception of pulmonary function and adherence to inhaled corticosteroids (ICS)., Methods: The sample consisted of 192 ethnic minority, inner-city children (100 Puerto Rican, 54 African-American, 38 Afro-Caribbean) with asthma and their primary caregivers recruited from outpatient clinics in Bronx, New York. Children's PEF predictions were entered into an electronic spirometer and compared with actual PEF across 6 weeks. Children in one study were blinded to PEF (n=88; no feedback) and children in a separate study were able to see PEF (n=104; feedback) after predictions were locked in. Dosers were attached to asthma medications to monitor use., Results: Children in the feedback condition displayed greater accuracy (p<0.001), less under-perception (p<0.001) and greater over-perception (p<0.001) of respiratory compromise than children in the no feedback condition. This between-group difference was evident soon after baseline training and maintained across 6 weeks. The feedback condition displayed greater adherence to ICS (p<0.01) and greater quick-relief medication use (p<0.01) than the no feedback condition., Conclusions: Feedback on PEF predictions for ethnic minority, inner-city children may decrease under-perception of respiratory compromise and increase adherence to controller medications. Children and their families may shift their attention to asthma perception and management as a result of this intervention.