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Background Wheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood. Objectives We sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma. Methods We conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma. Results Eighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (β = 0.87; 95% CI, 0.74-1.02) and 22% (β = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (β = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress–related metabolites. There were no significant associations between metabolites and allergic sensitization. Conclusions We identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.

Rationale: Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated...

Background: Emotional disorders, including depression and anxiety, are more prevalent in individuals with asthma than in the general population and are associated with poor asthma outcomes. Identification of patients with increased levels of stress and anxiety may be helpful when treating asthma and during asthma counseling. Objective: To further characterize the relationship between asthma symptoms and perceived stress and trait anxiety in an adolescent population. Methods: Adolescents (N = 335) ages 14‐17 years were recruited to examine the effect of stress on health measures. They were included in the present analysis if they reported current asthma, defined as self-reported clinician-diagnosed asthma plus one or more episodes of asthma in the past year. Asthma symptoms were assessed on a 7-point scale by using a standardized questionnaire that targets nocturnal awakening due to asthma, symptoms on awakening, activity limitation, shortness of breath, time spent wheezing, and short-acting bronchodilator use. Stress was measured by using the Perceived Stress Scale (PSS), and trait anxiety was measured by using the State-Trait Anxiety Inventory. Linear regression was used to associate asthma symptoms with PSS and trait anxiety. Results: Thirty-eight adolescents (11.3%), with mean ± standard deviation age 16.7 ± 0.9 years, reported current asthma. Four of the six asthma symptom assessments had significant associations with PSS: symptoms on awakening (β = 4.82, p < 0.001), nocturnal awakening due to asthma (β = 4.47, p Conclusion: Asthma symptom severity is associated with increased perceived stress and trait anxiety. Adolescents with asthma may represent a population that is particularly vulnerable to perceived stress and anxiety, which highlights the importance of considering these factors in asthma counseling.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Background Previous analyses in the WHEALS birth cohort demonstrated that black children are more likely to experience allergic outcomes than white children by age 2 years. The results could not be explained by a host of variables. Objective Assess whether racial disparities persisted to age 10 years and determine whether any differences could be explained by a panel of variables related to early life exposures in WHEALS. Methods At age 10 years, WHEALS children (n = 481) completed skin prick testing, spirometry and methacholine challenge, and a physician examination for eczema and asthma. Allergen-specific immunoglobulin Es (sIgE) and total IgE were measured. Inverse probability weighting with logistic and linear regression models was used to assess associations between race (black or white) and the outcomes. Results Black children fared worse than white children with respect to each outcome. Black children were more likely to have eczema, asthma, sensitization (≥1 sIgE ≥ 0.35 IU/L) and at least 1 positive skin pick test; however, some variability was present in the magnitudes of association within subgroups defined by delivery mode, sex of the child, prenatal indoor dog exposure, and firstborn status. In some subgroups, black children were also more likely to have higher total IgE and worse pulmonary function test measures (PC 20 ≤ 25 mg/mL, % predicted forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1]/FVC, forced expiratory flow from 25% to 75% of vital capacity [FEF25-75]). Confounding did not explain these differences. Conclusion Racial differences persisted in this cohort through age 10 years. Future studies should include potentially important, but rarely studied factors such as segregation and structural racism, because these factors could explain the observed racial differences.

Importance Asthma is the leading chronic illness in US children, but most descriptive epidemiological data are focused on prevalence. Objective To evaluate childhood asthma incidence rates across the nation by core demographic strata and parental history of asthma. Design, Setting, and Participants For this cohort study, a distributed meta-analysis was conducted within the Environmental Influences on Child Health Outcomes (ECHO) consortium for data collected from May 1, 1980, through March 31, 2018. Birth cohort data of children from 34 gestational weeks of age or older to 18 years of age from 31 cohorts in the ECHO consortium were included. Data were analyzed from June 14, 2018, to February 18, 2020. Exposures Caregiver report of physician-diagnosed asthma with age of diagnosis. Main Outcome and Measures Asthma incidence survival tables generated by each cohort were combined for each year of age using the Kaplan-Meier method. Age-specific incidence rates for each stratum and asthma incidence rate ratios by parental family history (FH), sex, and race/ethnicity were calculated. Results Of the 11 404 children (mean [SD] age, 10.0 [0.7] years; 5836 boys [51%]; 5909 White children [53%]) included in the primary analysis, 7326 children (64%) had no FH of asthma, 4078 (36%) had an FH of asthma, and 2494 (23%) were non-Hispanic Black children. Children with an FH had a nearly 2-fold higher incidence rate through the fourth year of life (incidence rate ratio [IRR], 1.94; 95% CI, 1.76-2.16) after which the rates converged with the non-FH group. Regardless of FH, asthma incidence rates among non-Hispanic Black children were markedly higher than those of non-Hispanic White children during the preschool years (IRR, 1.58; 95% CI, 1.31-1.86) with no FH at age 4 years and became lower than that of White children after age 9 to 10 years (IRR, 0.67; 95% CI, 0.50-0.89) with no FH. The rates for boys declined with age, whereas rates among girls were relatively steady across all ages, particularly among those without an FH of asthma. Conclusions and Relevance Analysis of these diverse birth cohorts suggests that asthma FH, as well as race/ethnicity and sex, were all associated with childhood asthma incidence rates. Black children had much higher incidences rates but only during the preschool years, irrespective of FH. To prevent asthma among children with an FH of asthma or among Black infants, results suggest that interventions should be developed to target early life.

Background Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective. Objective Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history. Methods Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated. Results The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females. Conclusions US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.

Childhood sensitization patterns have been previously found to be related to variable risk of early life allergic disease in several birth cohorts.To determine whether these risks persist into later childhood.In the birth cohort of the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, previous latent class analysis based on sensitization to 10 allergens found the following 4 early life sensitization patterns at age 2 years: "highly sensitized," "milk/egg dominated," "peanut and inhalant(s)," and "low to no sensitization." At an age 10 study-specific visit, children were evaluated by an allergist for current asthma and atopic dermatitis through a physical examination and interviews with the child and parent or guardian. Total and specific immunoglobulin E (IgE), spirometry, and methacholine challenge were also completed.Compared with children sensitized to none or 1 allergen, children sensitized to 4 or more food and inhalant allergens at age 2 had the highest risk of current asthma (relative risk [RR], 4.42; 95% confidence interval [CI], 2.58-7.59; P.001) and bronchial hyperresponsiveness (RR, 1.77; 95% CI, 1.29-2.42; P.001). In addition, they had the highest levels of total IgE (geometric mean, 800 IU/mL; 95% CI, 416-1536) among the 4 groups. Risk of current atopic dermatitis did not depend on pattern of sensitization but remained increased for children with any sensitization (RR, 2.23; 95% CI, 1.40-3.55; P.001). No differences in spirometry (forced expiratory volume in 1 second, forced expiratory flow between 25% and 75%, and forced expiratory volume in 1 second/forced vital capacity) were identified.The previously reported importance of a specific pattern of sensitization in early life (sensitization to ≥4 inhalant and food allergens) continues to be associated with an increased risk of asthma, bronchial hyperresponsiveness, and high total IgE at age 10 years.

In a cohort of pregnant women patterns of allergic sensitization in adulthood were not found to differ between women with current asthma starting before or after 15 years of age.

The recruitment setting plays a key role in the evaluation of behavioral interventions. We evaluated a behavioral intervention for urban adolescents with asthma in three randomized trials conducted separately in three different settings over the course of 8 years. We hypothesized that characteristics of trial participants recruited from the ED and clinic settings would be significantly different from that of youth participating in the school-based trials. The intervention evaluated was Puff City, a web-based program that uses tailoring to improve asthma management behaviors.The present analysis includes youth aged 13-19 years who reported a physician diagnosis of asthma and symptoms at trial baseline. In the three trials, all participants were randomized post-baseline to a web-based, tailored intervention (treatment) or generic web-based asthma education (control).Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (Compared to participants in the school-based trials, participants recruited from ED and clinic settings differed significantly in terms of healthcare use, as well as psychosocial and sociodemographic factors. These factors can inform intervention content, and may impact external validity of behavioral interventions for asthma.

Background: Recent public health lead crises in urban areas emphasize the need to better understand exposure to environmental toxicants, particularly in higher risk groups. Although African-American children have the highest prevalence of elevated blood lead levels in the United States, little is known about when this trajectory of disproportionate burden of lead exposure first emerges. Objectives: Using tooth-matrix biomarkers that directly measure fetal and early childhood metal levels, the primary goal of this study was to determine if there were racial disparities in lead levels during fetal development and early childhood. Manganese, an essential nutrient that modifies the neurotoxic effects of lead, was also measured. Methods: Pregnant women served by the Henry Ford Health System and living in a predefined geographic area in and around Detroit, Michigan, were recruited during the second trimester or later into the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), a population-based birth cohort. Offspring born between September 2003 and December 2007 were studied in childhood. Child race was parent-reported. Lead and manganese during the second and third trimesters, early postnatal life (birth through age 1year) and early childhood (age 1 through time of tooth shedding, which ranges from 6 to 12years) were measured via high-resolution microspatial mapping of dentin growth rings, a validated biomarker for prenatal and childhood metal exposure. Results: African-American children (N=71) had 2.2 times higher lead levels in the second and third trimesters (both p

Background Infant feeding practices are thought to shape food acceptance and preferences. However, few studies have evaluated whether these affect child diet later in life. Objective The study objective was to examine the association between infant feeding practices and dietary patterns (DPs) in school-aged children. Design A secondary analysis of data from a diverse prospective birth cohort with 10 years of follow-up (WHEALS [Wayne County Health Environment Allergy and Asthma Longitudinal Study]) was conducted. Participants/setting Children from the WHEALS (Detroit, MI, born 2003 through 2007) who completed a food screener at age 10 years were included (471 of 1,258 original participants). Main outcome measures The main outcome was DPs at age 10 years, identified using the Block Kids Food Screener. Statistical analysis performed Latent class analysis was applied for DP identification. Breastfeeding and age at solid food introduction were associated with DPs using a 3-step approach for latent class modeling based on multinomial logistic regression models. Results The following childhood DPs were identified: processed/energy-dense food (35%), variety plus high intake (41%), and healthy (24%). After weighting for loss to follow-up and covariate adjustment, compared with formula-fed children at 1 month, breastfed children had 0.41 times lower odds of the processed/energy-dense food DP vs the healthy DP (95% CI 0.14 to 1.25) and 0.53 times lower odds of the variety plus high intake DP (95% CI 0.17 to 1.61), neither of which were statistically significant. Results were similar, but more imprecise, for breastfeeding at 6 months. In addition, the association between age at solid food introduction and DP was nonsignificant, with each 1-month increase in age at solid food introduction associated with 0.81 times lower odds of the processed/energy-dense food DP relative to the healthy DP (95% CI 0.64 to 1.02). Conclusions A significant association between early life feeding practices and dietary patterns at school age was not detected. Large studies with follow-up beyond early childhood that can also adjust for the multitude of potential confounders associated with breastfeeding are needed.

The effect of dog exposure on the risk of children developing allergic disease remains controversial. Many analyses have not considered that associations may vary within population subgroups.To examine whether associations between living with a dog in the first year of life and allergic outcomes vary within subgroups selected a priori (race, gender and delivery mode).Black (n = 496) and White (n = 196) children enrolled in the WHEALS birth cohort study had a clinical examination at age 2 years to assess eczema and allergen-specific IgE (sIgE) and perform skin prick testing (SPT). Whether the child lived with an indoor dog in the first year of life was assessed through interview, as was doctor diagnosis of asthma at ages 3-6 years.Living with a dog was associated with decreased odds of having ≥ 1 positive SPT (OR = 0.56, 95% CI: 0.34, 0.91) and having eczema (OR = 0.34, 95% CI: 0.20, 0.60). The association with SPT was stronger in those children born via caesarean section (c-section) vs. vaginally (OR = 0.29, 95% CI: 0.12, 0.74 vs. OR = 0.76, 95% CI: 0.43, 1.37, respectively, interaction P = 0.087) and in those who were firstborn vs. not (OR = 0.27, 95% CI: 0.11, 0.67 vs. OR = 0.82, 95% CI: 0.45, 1.47, respectively, interaction P = 0.044). The association with eczema was stronger in children born vaginally compared with those born via caesarean section (OR = 0.17, 95% CI: 0.06, 0.43 vs. OR = 0.65, 95% CI: 0.31, 1.35, respectively, interaction P = 0.025) and was stronger in Black vs. White children (OR = 0.30, 95% CI: 0.15, 0.61 vs. OR = 0.78, 95% CI: 0.29, 2.11, respectively, interaction P = 0.12). Dog keeping was not significantly inversely associated with having ≥ 1 elevated sIgE and only approached statistical significance with asthma.Results likely vary between studies due to variability of specific exposure-outcome associations in subgroups defined by other factors as well as the relative distributions of those subgroups. Important allergic disorder associations will be missed without subgroup analyses.

Purpose Measurement of socioeconomic status (SES) is traditionally based on education, income, and occupation. This information may not be readily available from adolescents participating in research. Methods Using data from school-based randomized trial of an asthma intervention targeting urban adolescents, we compared percent poverty in zip code of residence (% poverty), median housing value, and parental income and education, to teen responses on the Home Affluence Scale for Children (HASC), which included home, car, and computer ownership for the family and eligibility for free school lunch. The association of HASC with measures of asthma control was also assessed. Results Of 422 adolescents, 390 (92%) responded to HASC items (mean HASC = 2.5). HASC was associated with mother's education and household income (both P

Asthma definitions vary widely across research studies and feature a trade-off between inclusivity and precision. Harmonizing definitions across multiple asthma birth cohort studies highlights these challenges.

It is unknown whether family members with detectable specific immunoglobulin E (sIgE) and/or allergic symptoms to pets are more or less likely to reside in a household with pets. We cross-sectionally investigated potential relationships between family members’ allergic sensitization and symptoms to dogs and cats and current household pet-keeping practices, using birth cohort data. Blood samples taken from children enrolled in a birth cohort and their biological mothers and fathers, when the children were aged 18 years, were assessed for sIgE to dog and cat allergens. Interviews assessed subjects’ self-reported pet exposure symptoms, current household pet-keeping practices, and socioeconomic characteristics. Overall, household dog or cat keeping was not associated with sIgE to these animals and/or self-reported allergic symptoms in the presence of these animals, even after controlling for factors such as education and household income. In subgroup analyses, current household dog keeping among dog-symptomatic teens (n 40) was significantly lower than among teens who were not dog symptomatic (n 289), at 48.8 and 61.1%, respectively (p 0.036). Current household cat keeping was significantly lower among cat-symptomatic mothers (n 27) compared with mothers who were not cat symptomatic (n 120), at 24.3 and 37.0%, respectively (p 0.015). However, when considering those who were both sensitized and reported symptoms, only the mother and cat-keeping associations persisted (p 0.049). When cat-sensitized mothers report allergic symptoms to cats, these pets may be less likely to be kept in homes. Elevated dog and cat allergen sIgE does not appear to be associated with the keeping of these pets. (Allergy Asthma Proc 34:504 –510, 2013; doi: 10.2500/aap.2013.34.3698)

Introduction Microbial-related exposures in early life stimulate immune development and may protect against allergic disease manifestations later in life. Parental pacifier sucking in early life may offer protection through the transfer of beneficial oral microbes from parent to offspring. Methods Using maternal-child pairs from the Microbes, Allergy, Asthma and Pets cohort(N=141), we investigated whether pacifier cleaning methods reported at 6-months of age were associated with differences in serum total IgE over the first 18 months of life(cord, 6-months, and 18-months). Linear mixed effect models were used to model log-transformed total IgE trajectories. Results Of 128 mothers completing an interview at 6 months, 74(58%) reported current child pacifier use. Of these 74, 30(41%) reported pacifier cleaning by sterilization, 53(72%) reported handwashing the pacifier, and 9(12%) reported parental pacifier sucking. Pacifier sterilization or handwashing were not associated with serum total IgE trajectory. A significant time interaction was detected for pacifier sucking(p=0.079), indicating that the trajectory shape differed between children of pacifier-sucking versus non-pacifier sucking parents. Specifically, parental pacifier sucking appeared to suppress serum IgE levels beginning around 10 months(p=0.048), and continued to diverge through 18 months(p=0.014). Conclusions These results show an association between parental pacifier sucking and lower early-life total IgE production. Further research is needed to assess whether these differences are due to the transfer of parental oral microbes, and if allergic disease risk later in life is sustained. These findings support a previous Swedish study reporting a protective effect of parental pacifier sucking on the risk of allergic diseases in children. Difference in total IgE trajectory by parental sucking of pacifiers - among children who used pacifiers at 6-months of age.

Asthma interventions targeting urban adolescents are rare, despite a great need. Motivating adolescents to achieve better self-management of asthma is challenging, and the literature suggests that certain subgroups are more resistant than others. We conducted a school-based, randomized controlled trial (RCT) to evaluate Puff City, a Web-based, tailored asthma intervention, which included a referral coordinator, and incorporated theory-based strategies to target urban teens with characteristics previously found to be associated with lack of behavior change.To identify eligible teens, we administered questionnaires on asthma diagnoses and symptoms to ninth through 12th graders of participating schools during a scheduled English class. We randomized eligible, consenting students to Puff City (treatment) or generic asthma education (control).We randomized 422 students (98% African-American, mean age = 15.6 years). At 12-month follow-up, adjusted odds ratios (aORs) (95% confidence intervals) indicated intervention benefit for treatment teens for symptom-days and restricted activity days (analyzed as categorical variables) as aOR = .49 (.24-.79), p = .006 and .53 (.32-.86), p = .010, respectively. Among teens meeting baseline criteria for rebelliousness, treatment teens reported fewer symptom-days, symptom-nights, school absences, and restricted activity days: aOR = .30 (.11-.80), .29 (.14-.64), .40 (.20-.78), and .23 (.10-.55); all p.05. Among teens reporting low perceived emotional support, treatment students reported only fewer symptom-days than controls: aOR = .23 (.06-.88), p = .031. We did not observe statistically significant differences in medical care use.Results suggest that a theory-based, tailored approach, with a referral coordinator, can improve asthma management in urban teens. Puff City represents a viable strategy for disseminating an effective intervention to high-risk and hard-to-reach populations.

Background and objective: There is conflicting evidence of the effect of environmental tobacco smoke (ETS) on the development of allergic diseases in children. Studies have shown that this relationship differs depending on maternal history of the disease. We employed the rigour of propensity score methods to assess this relationship using data from a birth cohort. Methods: Using n = 662 children from the Wayne County Health,Environment,Allergy and Asthma Longitudinal Study, we assessed the relationship between early-life ETS and subsequent allergic sensitization via a positive skin prick test (SPT+) or at least one specific immunoglobulin E (IgE) 0.35 (sIgE+) in children aged 2‐3 years. Propensity score estimation followed by full and nearest neighbour matching was compared with standard multivariable regression models. Results: Among children without a maternal history of allergic disease, ETS was positively associated with allergic sensitization in children with an adjusted odds ratio (aOR) for SPT+ of 2.32 (95% confidence interval (CI):1.28‐4.22)andtheaORforsIgE+was2.53(95%CI: 1.43‐4.48). Contrarily, for children with a positive maternal history, the aOR for SPT+ and sIgE+ was 0.56 (95% CI: 0.24‐1.32) and 0.43 (95% CI: 0.20‐0.91), respectively. Conclusions: Using propensity score methods to rigorously control for confounding factors, ETS exposure was found to reduce the risk of allergic sensitization in children with a positive maternal history. There is a strong association between early-life ETS and the development of allergic sensitization for children aged 2‐3 years without maternal history.

The risk of developing eczema is thought to be influenced by both genetic and environmental factors. Prenatal factors including the intrauterine environment may influence risk. We examined the relationship of maternal total IgE obtained during pregnancy to the incidence of atopic dermatitis in their 2 year-old offspring. Subjects were participants in an unselected Detroit area birth cohort. Serum IgE was measured from 458 mothers in the third trimester of pregnancy along with prenatal family and environmental histories. Children were evaluated at approximately two years of age for current or past eczema by maternal questionnaire and physician examination. Among the 458 children, 20.3% (n=93) had a doctor confirmed diagnosis of eczema. Prenatal IgE was higher among women whose children developed AD versus women whose children did not. [Geometric means and 95% confidence intervals 52.7 IU/ml (40.9–68.0) versus 32.9 IU/ml (28.0–38.7), p= 0.010] The association was only seen in a subgroup of 181 women without allergic sensitization (specific IgE > 0.35 IU/ml) to a panel of 8 common allergens. Of the women without allergic sensitization, the mean serum IgE was 24.1 IU/ml (15.5–37.6) among those whose children had a diagnosis of eczema. The mean serum IgE was 11.2 IU/ml (9.2–13.6) among those whose children did not have a diagnosis of eczema (p-value 0.002). Maternal prenatal IgE level among women who are not sensitized to common allergens is associated with increased risk of eczema in offspring.

Background Elevated cord blood IgE may be associated with a higher risk of allergic disease. Objective To determine whether cord blood IgE is associated with allergic biomarkers or allergic disorders in young adults. Methods Data was collected from 670 subjects 18–21 years of age that were among 835 original participants in the Detroit Childhood Allergy Study, a general risk, population-based birth cohort. Cord blood IgE was assessed in relation to biomarkers associated with allergy and asthma including total IgE, allergen-specific IgE, blood eosinophilia, and spirometry. Cord blood IgE was also analyzed for associations to subsequent allergic disease including atopic dermatitis, allergic rhinitis, and asthma. Results Cord blood IgE, analyzed as a continuous measure, was modestly correlated with total IgE (r = 0.18, P P = .031). The relationship between cord IgE and sensitization was stronger among teens with no pet exposure in the first year of life (OR = 1.43, 95% CI, 1.16–1.77; P = .001). No relationship was found between cord IgE and blood eosinophil counts or lung function. In addition, no consistent association of cord blood IgE to asthma, allergic rhinitis, or atopic dermatitis was apparent. Conclusions An elevated cord blood IgE level modestly correlates with elevated total IgE and is associated with a slightly higher likelihood of allergic sensitization among young adults. However, cord IgE is not a strong predictor of clinical allergic disorders in this age group.

Regulatory T cells (Treg cells) are an important area of investigation in human health and disease. In this study, the trajectory of percentage of Treg cells (defined as CD4+CD25+Foxp3+CD127− lymphocytes) was measured in the blood of 208 women during pregnancy and up to three additional times in the postpartum period (1, 6 and 12 months postpartum). Whether the trajectory was affected by gravidity, parity, neonatal sex, pet exposure, maternal atopic and asthma status, smoking, maternal race or other pregnancy factors was examined. Multilevel models were fit using full maximum likelihood methods and included both random and fixed effects. Overall, percentages of Treg cells increased from the prenatal to the postpartum period. Among women who were not atopic, nulliparous women had lower percentages of Treg cells over time compared with parous women. Atopic women with pets in the home during pregnancy had lower percentages of Treg cells than atopic women who did not have pets. The trajectory was not affected by the other factors investigated. We conclude that within-woman change in percentages of Treg cells may vary by time in relation to delivery, as well as by maternal atopic status and exposure to pets and number of prior births. The data did not indicate an overall decline in Treg cells in the postpartum period. Future work to better identify the role of Treg cells in successful pregnancy would ideally include a set of well characterized women sampled serially starting prior to pregnancy and throughout the postpartum period.

The ability to identify potentially resistant participants early in the course of an intervention could inform development of strategies for behavior change and improve program effectiveness.The objective of this analysis was to identify factors related to nonresponse (i.e., lack of behavior change) to an asthma management intervention for urban teenagers. The intervention targeted several behaviors, including medication adherence, having a rescue inhaler nearby, and smoking.A discriminate analysis was conducted using data from a randomized trial of the intervention. Included in this analysis are participants who reported a physician diagnosis of asthma, completed a baseline questionnaire, were randomized to the treatment group, completedor=2 of 4 educational sessions, and completedor=2 of 3 follow-up questionnaires. Ninety students met criteria for inclusion in this subgroup analysis.In logistic regression models for medication adherence, nonresponse was related to low baseline asthma self-regulation, odds ratio = 3.6 (95% confidence interval = 1.3-9.5). In models for having an inhaler nearby, nonresponse was related to low baseline self-regulation and to rebelliousness, OR = 4.7 (1.6-13.2) and 5.6 (1.7-18.0), respectively. Nonresponse to smoking messages was related to rebelliousness, low emotional support, and low religiosity, ORs = 7.6 (1.8-32.3), 9.5 (1.4-63.5), and 6.6 (1.5-29.8) respectively.Certain variables had the ability to discriminate the likelihood of response from that of nonresponse to an asthma program for urban, African American adolescents with asthma. These variables can be used to identify resistant subgroups early in the intervention, allowing the application of specialized strategies through tailoring. These types of analyses can inform behavioral interventions.

Epidemiologic research shows that pets influence human health, demonstrating both protective and deleterious health risks; therefore, valid definitions of pet exposure would enhance research. The authors determined how well young adults aged 18 years report their early childhood pets. Subjects in an established birth cohort from Detroit, Michigan, born in 1987–1989 (n = 820) were asked a series of questions about pets in the home during their first 6 years of life. Pet recall was compared with annual prospectively collected parental report from 12–18 years prior. Exposure to cats was correctly reported on average 86.3% of the time (95% confidence interval: 85.0, 87.5) and dogs 79.2% (95% confidence interval: 77.7, 80.6) of the time (P

Asthma and obesity disproportionately affect US African-American youth. Among youth with asthma, obesity has been associated with poor control. The impact of gender on this association is unclear. We examined these relationships in a sample of urban, African-American adolescents with asthma. Questionnaires were used to identify high school students with asthma, and to examine the association of body mass index (BMI) to asthma morbidity, by gender. Of 5967 students completing questionnaires, 599 (10%) met criteria for asthma and 507 had data sufficient for inclusion in further analyses (46% male, mean age = 15.1 yr). Univariately, BMI > 85th percentile was significantly related only to reported emergency department visits (ED) and school days missed for any reason, Odds Ratio (95% Confidence Interval) = 1.7(1.1–2.7), p = 0.01 and 1.8(1.1–3.0), p = 0.01, respectively. A significant gender-BMI interaction (p < 0.05) was observed in multivariate models for ED visits, hospitalizations and school days missed for asthma. In gender-specific models, adjusted Risk Ratios for BMI > 85th and ED visits, hospitalizations, and school days missed because of asthma were 1.7(0.9–3.2), 6.6(3.1–14.6) and 3.6(1.8–7.2) in males. These associations were not observed in females. Gender modifies the association between BMI and asthma-related morbidity among adolescents with asthma. Results have implications for clinical management as well as future research.

Transient wheezing in young children has been reported to be independent of atopy. Although persistence of early wheezing has been associated with factors related to allergy in multiple studies, transient wheezing has not been similarly studied. The Childhood Allergy Study birth cohort was the source of these data. Transient wheezing was defined as history of wheezing in the past 12 months at ages 1, 2, and/or 4 years, but not at 6 years, and evaluated in relationship to aeroallergen-specific circulating IgE and positive skin testing as markers of an atopic profile. Testing for IgE and skin-prick testing to dust mites, dogs, cats, ragweed, and timothy were performed at the age of 6 years. Other variables in logistic regression analyses were sex; breast-feeding; birth order; parental allergy and smoking history; and household pets, daycare, fever, and antibiotic use in the 1st year of life. Of 372 children, 128 (34.4%) experienced transient wheezing and 175 (47.0%) never wheezed. Atopy was not associated with transient wheezing (adjusted odds ratio for a positive allergen-specific IgE test = 1.2, p = 0.66; skin-prick test = 0.8, p = 0.47). Boys were more likely to be transient wheezers (adjusted relative risk [RR] = 1.7; 95% confidence interval [CI], 1.1-2.8; p = 0.018). Transient wheeze was associated with antibiotic treatment in the first 6 months of life (adjusted RR = 1.6; 95% CI, 1.0-2.6; p = 0.048). We confirm previous observations that transient wheezing in young children is not associated with an atopic predisposition.

Strategies for identifying urban youth with asthma have not been described for high school settings. African-American high school students are rarely included in asthma studies, despite a high risk of asthma mortality when compared to other age and race groups. Identification and follow-up of children with uncontrolled respiratory symptoms are necessary to reduce the burden of asthma morbidity and mortality, especially in underserved areas. We describe a process used to identify high school students who could benefit from intervention based on self-report of asthma and/or respiratory symptoms, and the costs associated with symptom-identification. Letters announcing a survey were mailed to parents of 9th-11th graders by an authorized vendor managing student data for the school district. Scan sheets with student identifiers were distributed to English teachers at participating schools who administered the survey during a scheduled class. Forms were completed by 5,967 of the 7,446 students assigned an English class (80% response). Although prevalence of lifetime asthma was 15.8%, about 11% of students met program criteria for enrollment through report of an asthma diagnosis and recent symptoms, medication use, or health care utilization. Another 9.2% met criteria by reported symptoms only. Cost of symptom-identification was $5.23/student or $32.29/program-eligible student. There is a need for school-based asthma programs targeting urban adolescents, and program initiation will likely require identification of students with uncontrolled symptoms. The approach described was successfully implemented with a relatively high response rate. Itemized expenses are presented to facilitate modifications to reduce costs. This information may benefit providers, researchers, or administrators targeting similar populations.

Background The high prevalence of asthma among urban African American (AA) populations has attracted research attention, whereas the prevalence among rural AA populations is poorly documented. Objective We sought to compare the prevalence of asthma among AA youth in rural Georgia and urban Detroit, Michigan. Methods The prevalence of asthma was compared in population-based samples of 7297 youth attending Detroit public high schools and in 2523 youth attending public high schools in rural Georgia. Current asthma was defined as a physician diagnosis and symptoms in the previous 12 months. Undiagnosed asthma was defined as multiple respiratory symptoms in the previous 12 months without a physician diagnosis. Results In Detroit, 6994 (95.8%) youth were AA compared with 1514 (60.0%) in Georgia. Average population density in high school postal codes was 5628 people/mile 2 in Detroit and 45.1 people/mile 2 in Georgia. The percentages of poverty and of students qualifying for free or reduced lunches were similar in both areas. The prevalence of current diagnosed asthma among AA youth in Detroit and Georgia was similar: 15.0% (95% CI, 14.1-15.8) and 13.7% (95% CI, 12.0-17.1) ( P = .22), respectively. The prevalence of undiagnosed asthma in AA youth was 8.0% in Detroit and 7.5% in Georgia ( P = .56). Asthma symptoms were reported more frequently among those with diagnosed asthma in Detroit, whereas those with undiagnosed asthma in Georgia reported more symptoms. Conclusions Among AA youth living in similar socioeconomic circumstances, asthma prevalence is as high in rural Georgia as it is in urban Detroit, suggesting that urban residence is not an asthma risk factor.

It is unknown if teenagers and caregivers give similar responses when interviewed about the teen's asthma. We analyzed data for 63 urban African-American teen-caregiver pairs. Caregivers underestimated teen smoking by 30%, gave lower estimates for teen exposure to passive smoke, and disagreed with teens on controller medication usage. Teen-caregiver responses were not significantly different for estimates of symptom-days, activity limitations, or nights awakened; nor were they significantly different for report of emergency department visits or hospitalizations. Agreement was weak for perceived asthma control and severity. Teen-caregiver agreement on asthma depends on the type of information being sought.

Background: Children with heightened airway responsiveness have a greater tendency to develop asthma symptoms. Many existing studies describing this relationship have relied on self-reported symptoms that may be prone to recall bias. In addition, few studies have examined the relationship of airway hyperresponsiveness (AHR) to indicators of asthma severity such as health-care utilization. Objective: To determine whether a positive response to methacholine challenge in children without current or physician-diagnosed asthma at age 6 to 8 years is predictive of the subsequent onset of asthma requiring medical evaluation or treatment in the ensuing 5 years. Methods: Data were obtained from subjects in a population-based birth cohort (n 835) enrolled from 1987 to 1989, who were members of a large medical group practice component of a health maintenance organization (HMO). We analyzed a subset of subjects (n 245) who had completed a methacholine challenge at age 6 to 8 years, had no current or physician-diagnosed asthma, and were still served by the same medical group. These children were followed up from the time of methacholine challenge until HMO disenrollment or through June 2001 (ages 11 to 13 years), whichever came first. Pharmacy claims data and diagnostic codes from physician-patient encounters were evaluated for incident asthma. Incident cases of clinical asthma were defined as any child with two outpatient visits or one hospitalization, one emergency department encounter associated with an asthma diagnostic code (ie, 493.XX), or any child filling prescriptions for two bronchodilators or one antiinflammatory asthma medicine. Methacholine responsiveness was interpreted using American Thoracic Society criteria. Results: Asthma incidence did not differ based on methacholine challenge results for children with normal, borderline, and mild AHR. No child in the study demonstrated moderate-to-severe AHR. Conclusion: Our data suggest that AHR with a borderline or weakly positive result in a methacholine challenge in children 6 to 8 years old without current or physician-diagnosed asthma is not related to increased health-care utilization for asthma in the ensuing 5 years. (CHEST 2005; 128:2420–2426) Abbreviations: AHR airway hyperresponsiveness; ATS American Thoracic Society; CI confidence interval; HMO health maintenance organization; ICD International Classification of Diseases; PC20 provocative concentration of a substance causing a 20% fall in FEV1 ;P D20 provocative dose of a substance causing a 20% fall in FEV1; RR relative risk

The objective of this study was to determine whether racial differences in patterns of asthma care persist in a healthcare environment when financial barriers to health care are minimized. The study cohort consisted of African-American (AA) and Caucasian (C) patients, 18-50 years old, enrolled in a large HMO and hospitalized for asthma in 1993-1995. Baseline and 1-year follow-up data were collected from the HMO computerized database. Of the 193 patients in the cohort, 124 (65.3%) were AA and 67 (34.7%) were C. AAs were younger (mean = 36.2, SD = 9.9) than Cs (mean = 39.4, SD = 9.1), had a lower median household income, and made more asthma-related emergency department (ED) visits (45.2%) than Cs (22.4%) during the 1 year after the initial hospitalization (all p values0.001). During the same time period, Cs made more asthma-related primary care (70.2%) and allergy/pulmonary visits (38.8%) than AAs (47.6% and 27%, respectively). Although there were no significant racial differences in the rehospitalization rate, AA Medicaid contract patients (32%) had more rehospitalizations for asthma than AA regular contract patients (15.8%). These differential patterns in the use of asthma-related healthcare in this study indicate that the provision of health insurance alone is not sufficient to promote optimal levels of asthma management by all beneficiaries. Asthma education programs targeted for low-income AA patients may improve inappropriate healthcare use patterns.

Managed care plan members provide a population for analysis that minimizes the financial barriers to routine medical care that have been linked to high rates of asthma-related hospitalization, emergency care, and mortality among urban African Americans. We examined patterns of asthma care among 464 African American (AA) and 1,609 Caucasian (C) asthma patients, age 15 to 45 yr, in a southeast Michigan managed care system during 1993. Compared with C, AA had fewer visits to asthma specialists (0.32 versus 0.50 visits/yr, p = 0.002), and filled fewer prescriptions for inhaled steroids (1.44 versus 1.74 Rx/yr, p = 0.038), while being more likely to visit the emergency department with asthma (0.71 versus 0.28 visits/yr, p0. 001), to be hospitalized with asthma (0.08 versus 0.03 admissions/yr, p = 0.002), or to have filled prescriptions for oral steroids (0.91 versus 0.59 Rx/yr, p0.001). AA were equally likely to have visited a primary care physician for asthma (0.95 versus 0.93 visits/yr, p = 0.81). Similar physician visit profiles and discrepancies in the use of oral steroids persisted when analyzing exclusively low socioeconomic status subgroups. These results suggest that ethnic differences in patterns of asthma-related health care persist within managed care settings and are only partially due to financial barriers.

African-American children use the emergency department (ED) for asthma care more than their Caucasian counterparts.We sought to compare ED utilization for asthma care by race, adjusting for prescriptions filled for antiinflammatory medications, type of index visit (specialist vs nonspecialist), and demographic variables.An index asthma visit was identified for a cohort of managed care enrollees aged 4 to 11 years. Information on asthma encounters and drug claims data was evaluated during a prospective observation period of 12 months.African-American race was associated with one or more ED visits during the observation period (relative risk [RR] = 1.8, 95% CI = 1.3 to 2.5, p0.01). After adjusting for index visit type, prescriptions filled, and selected demographic variables, African-American race remained associated with post-index ED utilization (adjusted RR = 1.6, 95% CI = 1.0 to 2.4, p = 0.05). Additional findings included an inverse relationship between African-American race and antiinflammatory medications among children with nonspecialist index visits (RR = 0.5, 95% CI = 0.3 to 0.9, p = 0.02) and a positive relationship between African-American race and hospitalization after an ED visit for asthma care (RR = 10.2, 95% CI = 1.4 to 74.8, p0.01).African-American children were more likely to use ED asthma care even after adjusting for the type of index visit, prescriptions filled for antiinflammatory medications, and selected demographic variables. Racial differences in ED utilization for asthma care could be caused by a higher prevalence of uncontrolled or undertreated disease among African-American children not receiving specialty care.

Racial disparities are present in many facets of health and disease. Allergy and asthma are no exceptions. Secondary results from cross-sectional and cohort studies have provided information on the scope of racial disparities in allergic sensitization in the United States. African American/Black individuals tend to be sensitized more frequently than White individuals. Little is known about rates in other race groups. Genetics are unlikely to be the sole or major cause of the observed differences. Home dust allergen and endotoxin levels cannot explain the differences. Studies that have been designed to specifically address the sources of these racial disparities are needed. A “Multilevel Framework” that considers the roles of the individual, family and community presents an excellent approach to guide design of future studies of the causes of these disparities. Understanding the causes of the disparities could lead to interventions that would improve the health of all individuals.

S A T U R D A Y Cathryn J. Luria, MD, Alexandra R. Sitarik, MS, Suzanne Havstad, MA, Ganesa R. Wegienka, PhD, Haejin Kim, MD, Edward M. Zoratti, MD, FAAAAI, Christine L. M. Joseph, PhD, AndreaCassidy-Bushrow, PhD; Division of Allergy and Clinical Immunology, Henry Ford Health System, Detroit, MI, Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, Henry Ford Health System, Division of Allergy and Clinical Immunology, Detroit, MI, Henry Ford Health System, Detroit, MI. RATIONALE: The relationship between asthma symptoms and perceived stress and trait anxiety is not well understood. METHODS: Adolescents ages 14-17 years were recruited to examine the effect of stress on health measures. They were included in the present analysis if they reported current asthma, defined as self-reported cliniciandiagnosed asthma plus one or more episodes of asthma in the past year. Asthma symptomswere assessed on a 7-point Likert scale using six asthma control questionnaire items targeting nocturnal awakening due to asthma, symptoms upon awakening, activity limitation, shortness of breath, time spent wheezing, and short-acting bronchodilator (SABA) use. Stress was measured using the perceived stress scale (PSS), and trait anxiety was measured using the State-Trait Anxiety Inventory. Linear regression was used to associate asthma symptoms with PSS and trait anxiety. RESULTS: Of335adolescents recruited, 38 (11.3%) reportedcurrent asthma. Four of the six asthma symptom assessments had significant associations with PSS: symptoms upon awakening (b54.8, p-value

Background The relationship between obesity and asthma is an area of debate. Objective To investigate the association of elevated body mass index (BMI) at a young age and young adult asthma. Methods BMI, questionnaires, and serologic tests results were analyzed in participants of a predominantly white, middle-class, population-based birth cohort from Detroit, Michigan at 6 to 8 and 18 years of age. Asthma diagnosis was based on medical record data. Allergen specific IgE was analyzed using UniCAP, with atopy defined as 1 or more allergen specific IgE levels of 0.35 kU/L or higher. Overweight was defined as a BMI in 85th percentile or higher. Results A total of 10.6% of overweight males at 6 to 8 years of age had current asthma at 18 to 20 years of age compared with 3.2% of males who were normal or underweight (relative risk [RR], 3.3; 95% confidence interval [CI], 1.0-11.0; P =.048). A total of 19.6% of females who were overweight at 6 to 8 years of age had asthma compared with 10.3% of females who were normal or underweight (RR, 1.9; 95% CI, 0.9-3.9; P =.09). After adjustment for atopy at 6 to 8 years of age, overweight males had an adjusted RR of 4.7 (95% CI, 1.4-16.2; P =.01), and overweight females had an adjusted RR of 1.7 (95% CI, 0.8-3.3; P =.15). Change in BMI between 6 to 8 years of age and 18 to 20 years of age was also examined. Patients with persistently elevated BMI exhibited increased risk of asthma as young adults (RR, 2.4; 95% CI, 1.2-4.7) but not with an increasing BMI (RR, 0.8; 95% CI, 0.3-2.2) or a decreasing BMI (RR, 0.8; 95% CI, 0.3-2.2). Conclusion Overweight males 6 to 8 years of age have increased risk of asthma as young adults. Being overweight remains a predictor of asthma after adjustment for early atopy. A similar but not statistically significant trend was also seen among overweight females. Overweight body habitus throughout childhood is a risk factor for young adult asthma.

Prior studies have shown relationships between serum immunoglobulin E (IgE) and asthma.To investigate relationships between total and allergen-specific IgE concentrations and lung function in young adults.Measurements of total IgE, allergen-specific IgE to 6 common allergens, and spirometry (forced expiratory volume in one second [FEV(1)], forced vital capacity [FVC], FEV(1)/FVC, and percent change in FEV(1) after bronchodilation) were used to calculate correlations between the logarithmically transformed IgE values and measures of lung function among participants in a birth cohort not selected for risk of allergic disease stratified by current asthma, prior asthma, or no asthma.The 428 participants were 51.6% female, 93% white, and 18.4 (standard deviation = 0.6) years old. Forty-eight (11.2%) had current asthma, 55 (12.9%) had a history of asthma, and 325 (75.9%) never had asthma. For males with current asthma, correlations between total IgE and FEV(1)% and FVC% were -0.51 (P = .06) and -0.70 (P = .005), respectively. For females with current asthma, the only significant correlation was between total IgE and the FEV(1)/FVC ratio (-0.55, P = .001). After excluding smokers and individuals without detectable allergen-specific IgE, the negative correlations for both males and females remained statistically significant. The correlations among males or females with prior asthma or no history of asthma were minimal and not statistically significant. The sum of the allergen-specific IgEs showed the same pattern of relationships to lung function as did total IgE.Our results show significant negative correlations that vary by gender between both total and allergen-specific IgE and measurements of lung function in young adults with current asthma.

Background Sex hormones may play an important role in observed gender differences in asthma incidence and severity, as well as in the observed changes in asthma symptoms during times of hormonal fluctuation (i.e.; premenstrual, pregnancy, etc.). This pilot study sought to demonstrate the feasibility of data collection methods to investigate the effects of sex hormones on lung function in women. Findings A cohort of 13 women (6 with and 7 without prior asthma diagnoses) who were having menstrual periods and were not taking hormones collected urine samples daily for measurement of estrogen (estrone E1C) and progesterone (Pregnanediol-glucuronide PDG) metabolites over the course of a menstrual segment (bleeding episode plus the following bleeding-free interval). Hormones were used to estimate menstrual segment phase (follicular versus luteal) based on a published algorithm. Daily bleeding and FEV1 measurements were recorded and percent predicted FEV1 was calculated. Percent predicted FEV1 decreased over the course of the follicular but not the luteal phase. More specifically, among women without a prior asthma diagnosis, the E1C/PDG ratio and E1C and PDG were individually associated with FEV1 in the follicular phase. No associations were found between hormones and percent predicted FEV1 in the luteal phase or among asthmatic women. E1C was associated with FEV1 in the five days before bleeding onset only among non-asthmatic women. Discussion A study of contiguous daily hormones and symptoms over menstrual segments from a large group of women with and without asthma is needed to better determine within-woman cyclicity of the observed patterns.

The literature suggests that depression is an important comorbidity in asthma that can significantly influence disease management and quality of life (QOL).To study the effect of coexisting depressive symptoms on the effectiveness of self-management interventions in urban teens with asthma.We analyzed data from a randomized controlled trial of Puff City, a web-based, tailored asthma management intervention for urban teens, to determine whether depression modulated intervention effectiveness for asthma control and QOL outcomes. Teens and caregivers were classified as depressed based on responses collected from baseline questionnaires.Using logistic regression analysis, we found that a lower percentage of treatment students had indicators of uncontrolled asthma compared with controls (adjusted odds ratios1). However, for teens depressed at baseline, QOL scores at follow-up were significantly higher in the treatment group compared with the control group for the emotions domain (adjusted relative risk, 2.08; 95% confidence interval, 1.2-3.63; P = .01; interpreted as emotional QOL for treatment students increased by a factor of 2.08 above controls). Estimates for overall QOL and symptoms QOL were borderline significant (adjusted relative risk, 1.57; 95% confidence interval, 0.93-2.63; P = .09; and adjusted relative risk, 1.72; 95% confidence interval, 0.94-3.15; P = .08; respectively). Among teens not depressed at baseline, no significant differences were observed between treatment and control groups in QOL domains at follow-up.Our results suggest that depression modified the relationship between the effectiveness of an asthma intervention and emotional QOL in urban teens. Further assessment of self-management behavioral interventions for asthma should explore the mechanism by which depression may alter the intervention effect.

Asthma is more common in black children than in white children. Allergic sensitization has been shown to be associated with increased likelihood of asthma. This study was designed to determine whether there are racial differences in the allergens to which children are sensitized in the Detroit metropolitan area and determine whether sensitization was associated with wheeze outcomes. Pregnant women were recruited for the Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study birth cohort to follow the health of their children in the Detroit metropolitan area. Specific IgE (sIgE) was measured for Alternaria, cat, cockroach, dog, Dermatophagoides farinae, short ragweed, timothy grass, egg, milk, and peanut in blood samples from the children at age 2 years. A positive allergen sIgE was defined as ≥0.35 IU/mL. Mothers reported their child's race and completed interviews at age 2 years about characteristics of wheezing episodes in their child (frequency, medication, acute care, or emergency department visit). Black children (n = 384) were more likely than white children (n = 180) to have been positive for each of the allergens tested and also tended to have positive responses to a greater number of allergens (four or more allergens: 9.2% versus 3.5%). Children who had two or more positive sIgEs (adjusted odds ratio [aOR] = 2.68; 95% 95% confidence interval [CI], 1.33, 5.46) or three or more positive sIgEs (aOR = 2.67, 95% CI, 1.19, 6.01) were more likely to have wheezed four or more times in the last 12 months. Racial differences in sensitization at this young age may contribute to the racial difference in asthma prevalence at later ages.

Background Allergy-related studies that include biological measurements of vitamin D preceding well-measured outcomes are needed. Objective We sought to examine the associations between early-life vitamin D levels and the development of allergy-related outcomes in the racially diverse Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study birth cohort. Methods 25-Hydroxyvitamin D (25[OH]D) levels were measured in stored blood samples from pregnancy, cord blood, and age 2 years. Logistic regression models were used to calculate odds ratios (ORs) with 95% CIs for a 5 ng/mL increase in 25(OH)D levels for the following outcomes at age 2 years: eczema, skin prick tests (SPTs), increased allergen-specific IgE level (≥0.35 IU/mL), and doctor's diagnosis of asthma (3-6 years). Results Prenatal 25(OH)D levels were inversely associated with eczema (OR, 0.85; 95% CI, 0.75-0.96). The association was stronger in white children (white children: OR, 0.79; 95% CI, 0.57-1.09; black children: OR, 0.96; 95% CI, 0.82-1.12), although this was not statistically significant. Cord blood 25(OH)D levels were inversely associated with having 1 or more positive SPT responses and aeroallergen sensitization. Both associations were statistically significant in white children (positive SPT response: OR, 0.50; 95% CI, 0.32-0.80; ≥1 aeroallergen sensitization: OR, 0.50; 95% CI, 0.28-0.92) in contrast with black children (positive SPT response: OR, 0.88; 95% CI, 0.68-1.14; ≥1 aeroallergen sensitization: OR, 0.85; 95% CI, 0.65-1.11). 25(OH)D levels measured concurrently with outcome assessment were inversely associated with aeroallergen sensitization (OR, 0.79; 95% CI, 0.66-0.96) only among black children (white children: OR, 1.21; 95% CI, 0.87-1.69). Conclusions Prenatal and cord blood 25(OH)D levels were associated with some allergy-related outcomes, with a general pattern indicating that children with higher 25(OH)D levels tend to have fewer allergy-related outcomes.

The risk of developing eczema is thought to be influenced by both genetic and environmental factors. Prenatal factors including the intrauterine environment may influence risk. We examined the relationship of maternal total IgE obtained during pregnancy to the incidence of atopic dermatitis in their 2 year-old offspring. Subjects were participants in an unselected Detroit area birth cohort. Serum IgE was measured from 458 mothers in the third trimester of pregnancy along with prenatal family and environmental histories. Children were evaluated at approximately two years of age for current or past eczema by maternal questionnaire and physician examination. Among the 458 children, 20.3% (n=93) had a doctor confirmed diagnosis of eczema. Prenatal IgE was higher among women whose children developed AD versus women whose children did not. [Geometric means and 95% confidence intervals 52.7 IU/ml (40.9–68.0) versus 32.9 IU/ml (28.0–38.7), p= 0.010] The association was only seen in a subgroup of 181 women without allergic sensitization (specific IgE > 0.35 IU/ml) to a panel of 8 common allergens. Of the women without allergic sensitization, the mean serum IgE was 24.1 IU/ml (15.5–37.6) among those whose children had a diagnosis of eczema. The mean serum IgE was 11.2 IU/ml (9.2–13.6) among those whose children did not have a diagnosis of eczema (p-value 0.002). Maternal prenatal IgE level among women who are not sensitized to common allergens is associated with increased risk of eczema in offspring.

Background To assess bias and generalizability of results in randomized controlled trials (RCT), investigators compare participants to non-participants or early- to late-participants. Comparisons can also inform the recruitment approach, especially when working with challenging populations, such as urban adolescents. In this paper, we describe characteristics by participant status of urban teens eligible to participate in a RCT of a school-based, web-based asthma management program. Methods The denominator for this analysis was all students found to be eligible to participate in the RCT. Data were analyzed for participants and non-participants of the RCT, as well as for students that enrolled during the initially scheduled recruitment period (early-participants) and persons that delayed enrollment until the following fall when recruitment was re-opened to increase sample size (late-participants). Full Time Equivalents (FTEs) of staff associated with recruitment were estimated. Results Of 1668 teens eligible for the RCT, 386 enrolled early, and 36 enrolled late, leaving 1246 non-participants. Participants were younger (p < 0.01), more likely to be diagnosed, use asthma medication, and have moderate-to-severe disease than non-participants, odds ratios (95% Confidence Intervals) = 2.1(1.7-2.8), 1.7(1.3-2.1), 1.4(1.0-1.8), respectively. ORs were elevated for the association of late-participation with Medicaid enrollment, 1.9(0.7-5.1) and extrinsic motivation to enroll, 1.7(0.6-5.0). Late-participation was inversely related to study compliance for teens and caregivers, ORs ranging from 0.1 to 0.3 (all p-values < 0.01). Early- and late-participants required 0.45 FTEs/100 and 3.3 FTEs/100, respectively. Conclusions Recruitment messages attracted youth with moderate-to-severe asthma, but extending enrollment was costly, resulting in potentially less motivated, and certainly less compliant, participants. Investigators must balance internal versus external validity in the decision to extend recruitment. Gains in sample size and external validity may be offset by the cost of additional staff time and the threat to internal validity caused by lower participant follow-up. Trial Registration ClinicalTrials.gov: NCT00201058

Sex hormones may play an important role in observed gender differences in asthma incidence and severity. Regulatory T cells (Treg cells) are presumed to be involved in asthma and may vary with hormone levels. To investigate the effects of sex hormones on levels of Treg cells (percentage of CD4+CD25+Foxp3+ lymphocytes that are CD127−), a cohort of 13 women (6 with and 7 without an asthma diagnosis) had blood drawn multiple times over the course of a bleeding segment (bleeding interval plus the following bleeding-free interval) and collected urine samples daily for measurement of estrogen (estrone E1C) and progesterone (pregnanediol-glucuronide PDG) metabolites. The samples from non-asthmatic women indicated no association between bleeding segment day and Treg cells. Asthmatic women showed a 3% increase in Treg cell percentage with each successive day over the bleeding segment. Among non-asthmatic women, Treg cell percentages were not associated with PDG levels on the same day, or 1, 2 or 3 days before Treg cell measurement. E1C was positively correlated with the Treg cell percentage measured only on the same day – a 5% increase in E1C was associated with a 1.4% increase in Treg cell percentage. Among asthmatic women, only E1C was associated with Treg cell percentages after adjusting for PDG on the same day and 1 and 2 days before Treg cell measurement. A 5% increase in E1C was associated with a 2.3% increase in Treg cell percentage. A larger study of contiguous cycles to better determine within-woman cyclicity of the observed patterns is needed.