Denise Serebrisky

CpG Oligodeoxynucleotides Can Reverse Th2-Associated Allergic Airway Responses and Alter the B7.1/B7.2 Expression in a Murine Model of Asthma

CpG oligodeoxynucleotides (CpG-ODN) administered during Ag sensitization or before Ag challenge can inhibit allergic pulmonary inflammation and airway hyperreactivity in murine models of asthma. In this study, we investigated whether CpG-ODN can reverse an ongoing allergic pulmonary reaction in a mouse model of asthma. AKR mice were sensitized with conalbumin followed by two intratracheal challenges at weekly intervals. CpG-ODN was administered 24 h after the first Ag challenge. CpG-ODN administration reduced Ag-specific IgE levels, bronchoalveolar lavage fluid eosinophils, mucus production, and airway hyperreactivity. We found that postchallenge CpG-ODN treatment significantly increased IFN-γ concentrations and decreased IL-13, IL-4, and IL-5 concentrations in bronchoalveolar lavage fluids and spleen cell culture supernatants. Postchallenge CpG-ODN treatment also increased B7.1 mRNA expression and decreased B7.2 mRNA expression in lung tissues. These results suggest that CpG-ODN may have potential for treatment of allergic asthma by suppressing Th2 responses during IgE-dependent allergic airway reactions. The down-regulation of Th2 responses by CPG-ODN may be associated with regulation of the costimulatory factors B7.1 and B7.2.

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.

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.

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.

Effect of secondhand smoke on asthma control among black and Latino children

BACKGROUND Among patients with asthma, the clinical effect and relative contribution of maternal smoking during pregnancy (in utero smoking) and current secondhand smoke (SHS) exposure on asthma control is poorly documented, and there is a paucity of research involving minority populations. OBJECTIVES We sought to examine the association between poor asthma control and in utero smoking and current SHS exposure among Latino and black children with asthma. METHODS We performed a case-only analysis of 2 multicenter case-control studies conducted from 2008-2010 with similar protocols. We recruited 2481 Latino and black subjects with asthma (ages 8-17 years) from the mainland United States and Puerto Rico. Ordinal logistic regression was used to estimate the effect of in utero smoking and current SHS exposures on National Heart, Lung, and Blood Institute-defined asthma control. RESULTS Poor asthma control among children 8 to 17 years of age was independently associated with in utero smoking (odds ratio [OR], 1.5; 95% CI, 1.1-2.0). In utero smoking through the mother was also associated with secondary asthma outcomes, including early-onset asthma (OR, 1.7; 95% CI, 1.1-2.4), daytime symptoms (OR, 1.6; 95% CI, 1.1-2.1), and asthma-related limitation of activities (OR, 1.6; 95% CI, 1.2-2.2). CONCLUSIONS Maternal smoking while in utero is associated with poor asthma control in black and Latino subjects assessed at 8-17 years of age.

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.

Validity of clinical prediction rules for isolating inpatients with suspected tuberculosis. A systematic review.

OBJECTIVE: Declining rates of tuberculosis (TB) in the United States has resulted in a low prevalence of the disease among patients placed on respiratory isolation. The purpose of this study is to systematically review decision rules to predict the patient’s risk for active pulmonary TB at the time of admission to the hospital.DATA SOURCES: We searched MEDLINE (1975 to 2003) supplemented by reference tracking. We included studies that reported the sensitivity and specificity of clinical variables for predicting pulmonary TB, used Mycobacterium TB culture as the reference standard, and included at least 50 patients.REVIEW METHOD: Two reviewers independently assessed study quality and abstracted data regarding the sensitivity and specificity of the prediction rules.RESULTS: Nine studies met inclusion criteria. These studies included 2,194 participants. Most studies found that the presence of TB risk factors, chronic symptoms, positive tuberculin skin test (TST), fever, and upper lobe abnormalities on chest radiograph were associated with TB. Positive TST and a chest radiograph consistent with TB were the predictors showing the strongest association with TB (odds ratio: 5.7 to 13.2 and 2.9 to 31.7, respectively). The sensitivity of the prediction rules for identifying patients with active pulmonary TB varied from 81% to 100%; specificity ranged from 19% to 84%.CONCLUSIONS: Our analysis suggests that clinicians can use prediction rules to identify patients with very low risk of infection among those suspected for TB on admission to the hospital, and thus reduce isolation of patients without TB.

Do Patients of Subspecialist Physicians Benefit from Written Asthma Action Plans

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

Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001

Prediction of peak flow values followed by feedback improves perception of lung function and adherence to inhaled corticosteroids in children with asthma

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