Clinician and Staff Perspectives on Implementing Adverse Childhood Experience (ACE) Screening in Los Angeles County Pediatric Clinics.

PURPOSE: To understand clinician and clinical staff perspectives on the implementation of routine Adverse Childhood Experience (ACE) screening in pediatric primary care. METHODS: We conducted a qualitative evaluation in 5 clinics in Los Angeles County, California, using 2 rounds of focus group discussions: during an early phase of the initiative, and 7 months later. In the first round, we conducted 14 focus group discussions with 67 participants. In the second round, we conducted 12 focus group discussions with 58 participants. Participants comprised clinic staff involved in ACE screening, including frontline staff that administer the screening, medical clinicians that use screening to counsel patients and make referrals, and psychosocial support staff who may receive referrals. RESULTS: Themes were grouped into 3 categories: (1) screening acceptability and perceived utility, (2) implementation and quality improvement, and (3) effects of screening on patients and clinicians. Regarding screening acceptability and perceived utility, clinicians generally considered ACE screening to be acceptable and useful. In terms of implementation and quality improvement, significant barriers included: insufficient time for screening and response, insufficient training, and lack of clarity about referral networks and resources that could be offered to patients. Lastly, regarding effects of screening, clinicians expressed that ACE screening helped elicit important patient information and build trust with patients. Further, no adverse events were reported from screening. CONCLUSIONS: Clinic staff felt ACE screening was feasible, acceptable, and beneficial within pediatric care settings to improve trauma-informed care and that ACE screening could be strengthened by addressing time constraints and limited referral resources.

Acculturation is associated with asthma burden and pulmonary function in Latino youth: The GALA II study.

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 FEV1 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.

An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos.

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.

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

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.).

A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma.

Short-acting ß2-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.

Genome-wide association study of inhaled corticosteroid response in admixed children with asthma.

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.

Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma.

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 ß-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.

Secondhand smoke exposure and asthma outcomes among African-American and Latino children with asthma.

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.

Breastfeeding associated with higher lung function in African American youths with asthma.

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 (FEV1) % 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 FEV1% 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 FEV1% predicted (p = 0.01) and a 21% reduction in asthma exacerbations (p = 0.03) in African Americans only. CONCLUSION: Breastfeeding was associated with higher FEV1% predicted in asthma and reduced number of asthma exacerbations in African American youths, calling attention to continued support for breastfeeding.

Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes-Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies.

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.

Individualized therapy for persistent asthma in young children.

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.

Genetic ancestry influences asthma susceptibility and lung function among 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.

Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos.

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.

A genome-wide association study of bronchodilator response in Latinos implicates rare variants.

BACKGROUND: The primary rescue medication to treat acute asthma exacerbation is the short-acting ß2-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.

Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial.

IMPORTANCE: Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. OBJECTIVE: To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. INTERVENTION: Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child's signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. RESULTS: A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed. CONCLUSIONS AND RELEVANCE: Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01272635.

Socioeconomic status and asthma control in African American youth in SAGE II.

OBJECTIVE: African Americans are disproportionately burdened by asthma. We assessed the individual and joint contribution of socioeconomic status (SES) on asthma morbidity among African American youth. METHODS: We examined 686 African Americans (8-21 years) with asthma. To account for the joint effects of SES, a composite index was derived from maternal educational attainment, household income, and insurance status. Ordinal logistic regression was used to estimate the individual and joint effect of SES on asthma control. Models were adjusted for age, sex, controller medication use, in utero smoke exposure, family history of asthma, family history of rhinitis, breastfeeding, daycare attendance, and mold exposure. RESULTS: Participants were classified as Poorly Controlled Asthma (40.8%), Partially Controlled Asthma (29.7%), or Controlled Asthma (30.2%). Of the individual SES indicators, low income was the strongest predictor of poor asthma control. Children with low income had worse asthma control than those with higher income (OR 1.39; 95% CI 0.92-2.12). The SES index ranged from 4-9. SES was associated with 17% increased odds of poor asthma control with each decrease in the index (95% CI 1.05-1.32). The SES index was associated with asthma-related symptoms, nocturnal awakenings, limited activity, and missed school days. CONCLUSIONS: The negative effects of SES were observed along the entire socioeconomic gradient, and the adverse asthma outcomes observed in African American youth were not limited to the very poor. We also found that the SES index may be a more consistent and useful predictor of poor asthma outcomes than each indicator alone.

Childhood obesity and asthma control in the GALA II and SAGE II studies.

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.

Early-life air pollution and asthma risk in minority children. The GALA II and SAGE II studies.

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.

Socioeconomic status and childhood asthma in urban minority youths. The GALA II and SAGE II studies.

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.