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McGarry M.E.,University of California at San Francisco | Castellanos E.,University of California at San Francisco | Thakur N.,University of California at San Francisco | Oh S.S.,University of California at San Francisco | And 15 more authors.
Chest | Year: 2015

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: Th e 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. © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Source


Nishimura K.K.,University of California at San Francisco | Galanter J.M.,University of California at San Francisco | Roth L.A.,University of California at San Francisco | Oh S.S.,University of California at San Francisco | And 19 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2013

Rationale: Air pollution is a known asthma trigger and has been associatedwith short-termasthmasymptoms,airway inflammation,decreased lung function, and reduced response to asthma rescuemedications. 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 airmonitoring stationswere used to estimate average annual exposure to five air pollutants: ozone, nitrogen dioxide (NO2), sulfur dioxide, particulatematter not greater than 10 mm in diameter, and particulatematter not greater than 2.5 mmindiameter. Within each region, we performed logistic regression to determine the relationship between early-life exposure to air pollutants and subsequent asthmadiagnosis.Arandom-effectsmodelwasusedtocombinetheregionspecific 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 associatedwith anodds ratio of 1.17 for physician-diagnosedasthma (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. © 2013 by the American Thoracic Society. Source


Drake K.A.,University of California at San Francisco | Torgerson D.G.,University of California at San Francisco | Gignoux C.R.,University of California at San Francisco | Galanter J.M.,University of California at San Francisco | And 26 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014

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. © 2013 American Academy of Allergy, Asthma & Immunology. Source


Tcheurekdjian H.,Case Western Reserve University | Via M.,University of California at San Francisco | De Giacomo A.,University of California at San Francisco | Corvol H.,University of California at San Francisco | And 8 more authors.
Journal of Allergy and Clinical Immunology | Year: 2010

Background: Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies. Objective: To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A 4 hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans. Methods: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers. Results: In heterozygotes and homozygotes for the minor allele at LTA4H single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in FEV1 after albuterol administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans but not Mexicans. Conclusion: LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma. © 2010 American Academy of Allergy, Asthma & Immunology. Source


Borrell L.N.,City University of New York | Oh S.S.,Center for Tobacco Control Research and Education | Tcheurekdjian H.,Case Western Reserve University | Tcheurekdjian H.,Allergy Immunology Associates Inc. | And 10 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2013

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 variedwith race andethnicity (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. Copyright © 2013 by the American Thoracic Society. Source

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