Search

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.

Prescription of daily inhaled corticosteroids for children with persistent asthma is infrequent compared with national practice guidelines. The authors conducted a national, cross-sectional survey of pediatricians and family physicians to identify specialty differences and factors associated with physician nonadherence to National Heart, Lung, and Blood Institute guidelines for prescribing inhaled corticosteroids. Adherence was defined as following the recommendation for >90% of cases. Response rate was 49% (343/694). Pediatrician and family physicians reported similar rates of adherence (54% vs 51%). Pediatricians and family physicians reported different barriers. Although both groups indicated that parent hesitancy and nonadherence were common barriers, the most common barrier for family physicians was a perceived cost of the asthma medications for families. Pediatricians were more likely to indicate that lack of time (21% vs 10%) was a barrier to prescribing inhaled corticosteroids. In multivariate logistic analysis, the lack of a family/practice barrier (odds ratio, 0.27; 95% confidence interval, 0.13, 0.55) and physician agreement with the National Heart, Lung, and Blood Institute recommendation (odds ratio, 4.21; 95% confidence interval, 1.43, 12.3) was associated with self-reported adherence. Interventions to improve prescribing of inhaled corticosteroids should include strategies to address issues specific to pediatricians and family physicians. [ABSTRACT FROM AUTHOR]

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.)

Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes of death in the United States. Despite this fact, our mechanistic understanding of how ACEs impact health is limited. Moreover, interventions for reducing stress presently use a one-size-fits-all approach that involves no treatment tailoring or precision. To address these issues, we developed a combined cross-sectional study and randomized controlled trial, called the California Stress, Trauma, and Resilience Study (CalSTARS), to (a) characterize how ACEs influence multisystem biological functioning in adults with all levels of ACE burden and current perceived stress, using multiomics and other complementary approaches, and (b) test the efficacy of our new California Prec ision I ntervention for S tress and R e silience (PRECISE) in adults with elevated perceived stress levels who have experienced the full range of ACEs. The primary trial outcome is perceived stress, and the secondary outcomes span a variety of psychological, emotional, biological, and behavioral variables, as assessed using self-report measures, wearable technologies, and extensive biospecimens (i.e. DNA, saliva, blood, urine, & stool) that will be subjected to genomic, transcriptomic, proteomic, metabolomic, lipidomic, immunomic, and metagenomic/microbiome analysis. In this protocol paper, we describe the scientific gaps motivating this study as well as the sample, study design, procedures, measures, and planned analyses. Ultimately, our goal is to leverage the power of cutting-edge tools from psychology, multiomics, precision medicine, and translational bioinformatics to identify social, molecular, and immunological processes that can be targeted to reduce stress-related disease risk and enhance biopsychosocial resilience in individuals and communities worldwide.

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: 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.

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.

Background: Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications., Methods: The Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response., Results: Seventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a daily ICS and was predicted by aeroallergen sensitization but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophil counts of 300/μL or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments., Conclusions: In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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: Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking., Methods: In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial., Results: Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events., Conclusions: Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).

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.

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: 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.)

Asthma is a common chronic pediatric respiratory disease associated with significant morbidity. Current guidelines recommend monitoring forced expiratory volume in 1 s (FEV 1 ) as part of the assessment of asthma severity and control; however, many children with asthma have a normal FEV 1 despite significant symptoms. Reduced forced expiratory flow between 25%-75% of forced vital capacity (FEF 25-75 ) may be an important measure of asthma severity and control in children with normal FEV 1 . This study examines the association between FEF 25-75 and asthma-related hospitalizations. Pulmonary function tests and records of 925 children ≤19 years of age seen for an initial evaluation of physician-diagnosed asthma at a community-based asthma clinic between 1999 and 2011 were reviewed. FEV 1 ≥80% predicted and FEF 25-75 ≥60% were considered normal. The associations between FEV 1 and FEF 25-75 and asthma-related hospitalizations were examined using logistic regression models. Thirteen percent ( n =118) of the children were hospitalized for asthma at least once in the previous year. Fifty four percent ( n =501) of the children met criteria for uncontrolled asthma symptoms. Asthma-related hospitalization was associated with reducing categories of FEF 25-75 , but not FEV 1 . Among the 693 children with normal FEV 1 (≥80%), those with FEF 25-75 <60% were more likely to have been hospitalized in the previous year (odds ratio 2.50, confidence interval 1.17-5.35) as compared to those with FEF 25-75 ≥60% of predicted. In a diverse urban cohort of children with asthma, asthma-related hospitalization in the previous year was associated with reduced FEF 25-75 even among those with normal FEV 1 . Our results suggest that FEF 25-75 may provide important information in the assessment and management of asthma in children.

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.

Objective: Clinical practice guidelines recommend that physicians provide asthma education to patients and their families. To characterize parents' and children's perception of physician practice, we examined: (i) proportion of parents and children reporting physician discussion of asthma education topics; (ii) age-group differences in children's report; (iii) site differences in children's and parents' report; (iv) sociodemographic and disease characteristics associated with children's report; and (v) the relation between children's report and adherence to daily controller medications., Methods: We conducted a cross-sectional study of 125 children with asthma (mean age = 11.3 years; 62% were male) and their parents. Parents provided demographic and disease data. Children reported whether physicians had ever discussed each of 16 asthma education topics with them. We used logistic regression to examine age-group and site differences in children's report of physician discussion of each topic. Multivariate linear regression was used to determine associations between demographic (e.g., child age, race) and disease (e.g., symptom severity) variables and topics discussed., Results: On average, 34.7% of children reported physician discussion of a topic; 8-10-year-olds reported significantly fewer topics discussed than children aged 11 and older (p < .05). Whereas parents' report differed by practice setting, children's report did not. In multivariate analyses, child age (β = 0.46 (SE: 0.17); p < .01), persistent symptoms (β = 1.59 (SE: 0.80); p < .05), and number of outpatient asthma visits (β = 0.19 (SE: 0.08); p < .05) remained significantly associated with number of topics discussed., Conclusion: These results suggest that the majority of children either may not receive, or may not recall receiving, information from their physicians about the fundamentals of asthma management. Physicians have an invaluable teaching opportunity in the medical office visit and should consider capitalizing on this opportunity to build children's sense of self-efficacy and competence in their self-care.

Background: Asthma disproportionately affects low-income and medically underserved children; additional tools are needed in the effort to improve asthma care., Objectives: We reviewed the implementation of a telephone case management program provided by community health workers (CHWs) as an alternative to home visits, to examine its efficiency, acceptability, and capacity to identify and address challenges with asthma management., Methods: This retrospective cohort study included children (and their caregivers) presenting for scheduled visits to a comprehensive asthma clinic at an urban, public hospital during 2007., Results: Overall, 83.2% of caregivers were contacted for follow-up. Of those not reachable, one-third had been discharged from the clinic, and most of the remainder later returned for a subsequent visit. Latino patients were more likely not to be reached by telephone (p < .001). Following the implementation of telephone case management, the number of patient visits to the asthma clinic increased by almost one-third., Conclusions: Telephone case management identified problems which were successfully addressed through improved patient care practices and system changes within the clinic. Telephone case management by CHWs can be an efficient, acceptable mechanism to supplement comprehensive asthma care in a diverse, urban pediatric population.

Physician-leaders are needed to address the widening gap in health disparities in an increasingly complex health care system. To be effective leaders, physicians need specific training; yet despite its importance, leadership training is rarely addressed during graduate medical education. As a result, most physician leadership training occurs after residency training. To address this gap in medical education, in 2004 the authors developed the Pediatric Leadership for the Underserved (PLUS) program at the University of California, San Francisco. The PLUS program incorporates leadership development into the framework of standard clinical training by providing specific sessions in personal leadership development and in related skills such as team building, negotiation, and conflict management. Leadership training is explicitly tied to clinical experiences to maximize relevance and opportunities for "real-time" application of new skills and knowledge. In addition, the curriculum includes sessions to develop and implement a three-year longitudinal child health project. Trainees are organized into advising groups to provide structured faculty and peer-peer advising. Key lessons learned in the implementation include the importance of having a skill-based, rather than a topic-based curriculum, and of exposing trainees to concrete examples of the many career paths of physician-leaders. Early outcomes from 2004 to 2009 include program evaluation data, trainee accomplishments, and postgraduate careers. This paper aims to inform other training programs about the development and feasibility of a residency program that incorporates leadership and underserved medicine curricula into the framework of standard clinical training.

Background: Ethnic-specific interactions between different asthma medications are not well described., Objective: To determine whether the use of leukotriene modifiers is associated with the magnitude of bronchodilator responsiveness among Mexican American and Puerto Rican children with persistent asthma., Methods: A cross-sectional study of 84 Mexican American and 192 Puerto Rican children, with persistent asthma who were aged 8 to 16 years. Within each group, bronchodilator responsiveness to albuterol, objectively assessed via spirometry, was compared between participants using leukotriene modifiers and those not using leukotriene modifiers., Results: Leukotriene modifier use was associated with a clinically significant increase in percentage change in forced expiratory volume in 1 second of 11.8 (P < .001) in Puerto Rican children, but there was no significant change in percentage change in forced expiratory volume in 1 second (-3.2, P=.57) in Mexican American children. This finding persisted after controlling for the use of inhaled corticosteroids. In addition, among the Puerto Rican children, the association between leukotriene modifier use and augmented bronchodilator responsiveness was greatest in those younger than 12 years., Conclusions: Among children with persistent asthma, use of leukotriene modifiers is associated with augmented bronchodilator responsiveness to albuterol in Puerto Ricans, but not Mexican Americans. This ethnic-specific, drug-drug interaction highlights the need for the further understanding of asthma pharmacogenetics among children from different ethnic groups to improve asthma outcomes.

Background: National asthma guidelines recommend that patients with persistent asthma regularly use an inhaled corticosteroid (ICS) in addition to as-needed albuterol, yet recent debates question whether this combination is equally efficacious in all ethnicities., Objective: To examine the effect of ICS use on bronchodilator responsiveness to albuterol in 3 different ethnic populations., Methods: A cross-sectional study of 106 Mexican Americans, 246 Puerto Ricans, and 163 African Americans with physician-diagnosed persistent asthma. Asthma severity, ethnicity, and medication use were evaluated using spirometry and questionnaires. Percentage change in forced expiratory volume in 1 second (FEV) was compared in patients who used ICSs vs those who used a short-acting beta2-agonist as their only asthma medication., Results: Inhaled corticosteroid use was associated with improvements in the percentage change in FEV1 after albuterol administration in Mexican Americans (21.7%, P = .01) and Puerto Ricans (18.5%, P = .02) but not in African Americans (3.0%, P = .73)., Conclusions: Inhaled corticosteroid use is associated with augmented bronchodilator responsiveness to albuterol in Mexican Americans and Puerto Ricans, but not in African Americans, with persistent asthma. This underscores the need for an improved understanding of ethnic-specific drug-drug interactions, particularly in those subgroups experiencing the highest burden of asthma morbidity and mortality in the United States.

In response to the 'asthma epidemic', local organisations in San Francisco formed the Yes We Can Urban Asthma Partnership, which uses a comprehensive medical/social model for paediatric asthma care. The Yes We Can Urban Asthma Partnership reaches out to high-risk children in different clinical settings: urgent visits, the hospital, a comprehensive specialty asthma clinic, and through an expanded community health worker programme. This article highlights the initial development, implementation, and evaluation of the success of this innovative management programme to address the problem of paediatric asthma in underserved urban areas.

Prescription of daily inhaled corticosteroids for children with persistent asthma is infrequent compared with national practice guidelines. The authors conducted a national, cross-sectional survey of pediatricians and family physicians to identify specialty differences and factors associated with physician nonadherence to National Heart, Lung, and Blood Institute guidelines for prescribing inhaled corticosteroids. Adherence was defined as following the recommendation for >90% of cases. Response rate was 49% (343/694). Pediatrician and family physicians reported similar rates of adherence (54% vs 51%). Pediatricians and family physicians reported different barriers. Although both groups indicated that parent hesitancy and nonadherence were common barriers, the most common barrier for family physicians was a perceived cost of the asthma medications for families. Pediatricians were more likely to indicate that lack of time (21% vs 10%) was a barrier to prescribing inhaled corticosteroids. In multivariate logistic analysis, the lack of a family/practice barrier (odds ratio, 0.27; 95% confidence interval, 0.13, 0.55) and physician agreement with the National Heart, Lung, and Blood Institute recommendation (odds ratio, 4.21; 95% confidence interval, 1.43, 12.3) was associated with self-reported adherence. Interventions to improve prescribing of inhaled corticosteroids should include strategies to address issues specific to pediatricians and family physicians.

Specific concerns from 706 parents regarding their children's (M age = 8.0, SD = 3.9) use of daily asthma medications were systematically identified and organized. 270 (38.2%) of 706 parents expressed a total of 470 concerns (M = 1.74, SD = 0.93; Range 1-5), including concerns about side effects (48.9%; e.g., growth retardation); aspects of the regimen (29.3%; e.g., medication amount); and "steroid" use (10.4%). Independent predictors of parental concern included use of inhaled corticosteroids (OR = 1.60, 95% CI 1.07-2.40), nasal corticosteroids (OR = 1.70, 95% CI 1.21-2.38), and alternative therapies (OR = 1.84, 95% CI 1.32-2.56). Providers should be prepared to address a wide range of medication concerns, especially those related to side effects.

Pediatric asthma programs have struggled to integrate children's medical and social needs. We developed and piloted an integrated team model for asthma care for low-income children through the Yes We Can Urban Asthma Partnership. Program evaluation demonstrated increases in prescribing controller medications (p <0.05), use of action plans (p<0.001), and the use of mattress covers (p<0.001); and decrease in asthma symptoms (p<0.01). Additional changes occurred within the local system of asthma care to support ongoing efforts to improve asthma management. We conclude that pediatric asthma programs can effectively target the social and medical needs of children in a sustainable manner.