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 ¼ 3,343) and African American (n ¼ 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 (NO 2 ), sulfur dioxide, particulate matter not greater than 10 mm in diameter, and particulate matter not greater than 2.5 mm in diameter. Within each region, we performed logistic regression to determine the relationship between early-life exposure to air pollutants and subsequent asthma diagnosis. 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 NO 2 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 NO 2 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.

Background Bronchial airway expression profiling has identified inflammatory subphenotypes of asthma, but invasiveness of this technique has limited its application to childhood asthma. Objectives To determine if the nasal transcriptome can proxy expression changes in the lung airway transcriptome in asthma. To determine if the nasal transcriptome can distinguish subphenotypes of asthma. Methods Whole transcriptome RNA-sequencing (RNA-seq) was performed on nasal airway brushings from 10 controls and 10 subjects with asthma, which was compared to established bronchial and small airway transcriptomes. Targeted RNA-seq nasal expression analysis was used to profile 105 genes in 50 subjects with asthma and 50 controls for differential expression and clustering analyses. Results We found 90.2% overlap in expressed genes and strong correlation in gene expression (ρ=0.87) between the nasal and bronchial transcriptomes. Previously observed asthmatic bronchial differential expression was strongly correlated with asthmatic nasal differential expression (ρ=0.77, p=5.6×10−9). Clustering analysis identified Th2-high and Th2-low subjects differentiated by expression of 70 genes including IL-13, IL-5, POSTN, CLCA1, and SERPINB2. Th2-high subjects were more likely to have atopy (O.R.=10.3, p=3.5×10−6), atopic asthma (OR=32.6, p=6.9×10−7), high blood eosinophils (OR=9.1, 2.6×10−6), and rhinitis (OR=8.3, p=4.1×10−6) compared to Th2-low subjects. Nasal IL-13 expression levels were 3.9-fold higher in asthmatic participants who experienced asthma exacerbation in the past year (p=0.01). Several differentially expressed nasal genes were specific to asthma and independent of atopic status. Conclusion Nasal airway gene expression profiles largely recapitulate expression profiles in the lung airways. Nasal expression profiling can be used to identify individuals with IL13-driven asthma and a Th2-skewed systemic immune response. Clinical Implications Nasal airway gene expression profiling can be used to easily identify the Th2-high subphenotype of asthma in children and also other genes dyregulated in the asthmatic airway but independent of atopic status.

BackgroundEpidemiologic studies have demonstrated an association between acute exposure to ambient fine particles and both mortality and morbidity. Less is known about the relative impacts of the specific chemical constituents of particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) on hospital admissions.ObjectiveThis study was designed to estimate the risks of exposure to PM2.5 and several species on hospital admissions for respiratory diseases among children.Data and MethodsWe obtained data on daily counts of hospitalizations for children < 19 and < 5 years of age for total respiratory diseases and several subcategories including pneumonia, acute bronchitis, and asthma for six California counties from 2000 through 2003, as well as ambient concentrations of PM2.5 and its constituents, including elemental carbon (EC), organic carbon (OC), and nitrates (NO3). We used Poisson regression to estimate risks while controlling for important covariates.ResultsWe observed associations between several components of PM2.5 and hospitalization for all of the respiratory outcomes examined. For example, for total respiratory admissions for children < 19 years of age, the interquartile range for a 3-day lag of PM2.5, EC, OC, NO3, and sulfates was associated with an excess risk of 4.1% [95% confidence interval (CI), 1.8–6.4], 5.4% (95% CI, 0.8–10.3), 3.4% (95% CI, 1.1–5.7), 3.3% (95% CI, 1.1–5.5), and 3.0% (95% CI, 0.4–5.7), respectively. We also observed associations for several metals. Additional associations with several of the species, including potassium, were observed in the cool season.ConclusionComponents of PM2.5 were associated with hospitalization for several childhood respiratory diseases including pneumonia, bronchitis, and asthma. Because exposure to components (e.g., EC, OC, NO3, and K) and their related sources, including diesel and gasoline exhaust, wood smoke, and other combustion sources, are ubiquitous in the urban environment, it likely represents an identifiable and preventable risk factor for hospitalization for children.

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 5,493 Latinos with and without asthma from three 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% confidence interval [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=0.001). 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 forced expiratory volume in the first second (−77±19 ml, p=5.8×10−5 and −83±19 ml, p=1.1×10−5, respectively) and forced vital capacity (−100±21 ml, p=2.7×10−6 and −107±22 ml, p=1.0×10−6, respectively). Conclusion Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos.

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 ¼ 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 ¼ 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. Keywords: obesity; asthma control; race and ethnicity; age; sex Obesity and asthma are among the most challenging health conditions affecting children and adolescents in the United States. Among this segment of the population, obesity (1) and asthma (2) prevalence vary by sex. For example, obesity is more common among boys (18.6%) than among girls (15%) aged 2-19 years old (1). This is also true for asthma with boys (10.5%) being more likely to have asthma than girls (8.2%) (2). Given these sex differences, obesity and asthma should be examined among boys and girls separately.Further variations on obesity and asthma are observed across age and race/ethnicity (1, 2). It is estimated that 32.6% of US children ages 6-11 years and 33.6% of adolescents ages 12-19 are overweight or obese (1). The prevalence of obesity is significantly higher among Mexican (23.9%) and African American (23.7%) children compared with non-Hispanic whites (16.1%) (1). Moreover, there are sex-specific differences in Obesity and asthma are common health conditions among US children. Obesity is associated with asthma control, although the mechanism is not well-understood. What This Study Adds to the FieldWorse asthma control is uniformly associated with increased body mass index in boys. Boys who were obese had increased odds of having worse asthma control than their normal-weight counterparts after adjusting for selected characteristics. For girls, this associat...