Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents.

BACKGROUND: Gut microbiota maturation coincides with nervous system development. Cross-sectional data suggest gut microbiota of individuals with and without attention deficit hyperactivity disorder (ADHD) differs. We hypothesized that infant gut microbiota composition is associated with later ADHD development in our on-going birth cohort study, WHEALS. METHODS: Gut microbiota was profiled using 16S ribosomal RNA and the internal transcribed spacer region 2 (ITS2) sequencing in stool samples from 1 month and 6 months of age. ADHD was defined by parent-reported or medical record doctor diagnosis at age 10. RESULTS: A total of 314 children had gut microbiota and ADHD data; 59 (18.8%) had ADHD. After covariate adjustment, bacterial phylogenetic diversity (p = 0.017) and bacterial composition (unweighted UniFrac p = 0.006, R2 = 0.9%) at age 6 months were associated with development of ADHD. At 1 month of age, 18 bacterial and 3 fungal OTUs were associated with ADHD development. At 6 months of age, 51 bacterial OTUs were associated with ADHD; 14 of the order Lactobacillales. Three fungal OTUs at 6 months of age were associated with ADHD development. CONCLUSIONS: Infant gut microbiota is associated with ADHD development in pre-adolescents. Further studies replicating these findings and evaluating potential mechanisms of the association are needed. IMPACT: Cross-sectional studies suggest that the gut microbiota of individuals with and without ADHD differs. We found evidence that the bacterial gut microbiota of infants at 1 month and 6 months of age is associated with ADHD at age 10 years. We also found novel evidence that the fungal gut microbiota in infancy (ages 1 month and 6 months) is associated with ADHD at age 10 years. This study addresses a gap in the literature in providing longitudinal evidence for an association of the infant gut microbiota with later ADHD development.

Increased risk of asthma at age 10 years for children sensitized to multiple allergens.

BACKGROUND: Childhood sensitization patterns have been previously found to be related to variable risk of early life allergic disease in several birth cohorts. OBJECTIVE: To determine whether these risks persist into later childhood. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Participant-level characteristics differ by recruitment setting when evaluating a behavioral intervention targeting adolescents with asthma.

OBJECTIVE: 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. METHODS: 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). RESULTS: Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (p < 0.001) and more caregiver depression (p < 0.001). Clinic-based participants were more likely to have computer/ internet access than participants from the school-based trial (p < 0.001). Both ED and clinic participants were more likely to report controller medication (p's < 0.001) and higher teen emotional support (p's < 0.01) when compared to the schools, but were less likely to report Medicaid (p's < 0.014) and exposure to environmental tobacco smoke (p < 0.001). CONCLUSION: 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.

Social distancing during the COVID-19 pandemic: quantifying the practice in Michigan - a "hotspot state" early in the pandemic - using a volunteer-based online survey.

BACKGROUND: Public Health policies related to social distancing efforts during the COVID-19 pandemic helped slow the infection rate. However, individual-level factors associated with social distancing are largely unknown. We sought to examine social distancing during the COVID-19 pandemic in Michigan, an infection "hotspot" state in the United States early in the pandemic. METHODS: Two surveys were distributed to Michigan residents via email lists and social media following COVID-19 related state mandates in March; 45,691 adults responded to the first survey and 8512 to the second. Staying home ≥ 3 out of 5 previous days defined having more social distancing. Logistic regression models were used to examine potential factors associated with more social distancing. RESULTS: Most respondents were women (86% in Survey 1, 87% in Survey 2). In Survey 1, 63% reported more social distancing, increasing to 78% in Survey 2. Female sex and having someone (or self) sick in the home were consistently associated with higher social distancing, while increasing age was positively associated in Survey 1 but negatively associated in Survey 2. Most respondents felt social distancing policies were important (88% in Survey 1; 91% in Survey 2). CONCLUSIONS: Michiganders responding to the surveys were both practicing and supportive of social distancing. State-level executive orders positively impacted behaviors early in the COVID-19 pandemic in Michigan. Additional supports are needed to help vulnerable populations practice social distancing, including older individuals.

Racial disparities in allergic outcomes persist to age 10 years in black and white children.

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.

Birth Mode, Breastfeeding, Pet Exposure, and Antibiotic Use: Associations With the Gut Microbiome and Sensitization in Children.

PURPOSE OF REVIEW: The infant gut microbiota has become a focus of multiple epidemiologic and cohort studies. This microbiome is derived from the mother (via the vaginal canal, maternal skin contact, breastfeeding, and possibly in utero microbial transfer) and is likely influenced by multiple external factors. It is now believed by some experts that colonization and formation of the newborn and alterations of gut microbiota in children are dependent on earlier alterations of the microbiota of mothers during or perhaps even before pregnancy. This review will focus on specific factors (pet keeping, breastfeeding, antibiotic use, and mode of delivery) that influence the infant gut microbiome and atopy. RECENT FINDINGS: This is a review of recent literature describing how pet keeping, breastfeeding, antibiotic use, and mode of delivery influences and changes the infant gut microbiome and atopy. General trends in gut microbiota differences have emerged in different birth cohorts when each external factor is analyzed, but consistency between studies is difficult to replicate. The aforementioned factors do not seem to confer an overwhelming risk for development of atopy alone. This review provides a comprehensive review of early life environmental factors and their influence on the infant gut microbiome and atopy.

In utero metal exposures measured in deciduous teeth and birth outcomes in a racially-diverse urban cohort.

A growing number of studies have examined associations of metal exposures with birth outcomes, however, results from these studies have been inconsistent, and hampered by methodological limitations. We measured direct fetal exposure to three metals (lead, manganese and zinc) during the second and third trimester and examined its association with birth weight and gestational age at delivery. Participants in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), a population-based birth cohort established between September 2003 and December 2007, were invited to donate teeth to the study. Lead, manganese and zinc during the second and third trimesters were measured via high-resolution microspatial mapping of dentin growth rings, a validated biomarker for prenatal metal exposure. Gestational age at delivery and infant birth weight were obtained from the delivery medical record. A total of 145 children had tooth metal measurements and birth outcome data. Mean birth weight was 3431 ±â€¯472 g and mean gestational age at delivery was 39.0 ±â€¯1.3 weeks. Overall, there was a positive association between second (ß = 0.21, 95% CI: 0.05, 0.37, P = 0.01) and third trimester (ß = 0.21, 95% CI: 0.05, 0.37, P = 0.01) tooth manganese and birth weight Z-score; this remained statistically significant after covariate adjustment. There was also a negative association between second trimester tooth lead level and birth weight Z-score (ß = -0.20, 95% CI: -0.38, -0.02, P = 0.02), however, this was attenuated after adjusting for covariates. Mixture analysis revealed similar findings. There was evidence for a sex-specific effect of manganese with birth weight Z-score, with the association stronger in female compared to male infants. Overall, we found evidence suggesting that higher in utero manganese is associated with larger birth weight Z-scores and that these associations may vary by infant sex.

Prenatal pet keeping and caregiver-reported attention deficit hyperactivity disorder through preadolescence in a United States birth cohort.

BACKGROUND: While the keeping of pets has been shown to protect against childhood allergic disease and obesity, less is known regarding potential associations of prenatal pet keeping and attention deficit hyperactivity disorder (ADHD). We sought to examine the associations between prenatal dog or cat keeping with caregiver-reported ADHD in preadolescents in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort (N = 1258). METHODS: At an interview with the caregiver at child age 10-12 years, caregivers reported if the WHEALS child had ever been diagnosed with ADHD. Similarly, during an interview with the mother prenatally, pet keeping (defined as dog or cat kept inside ≥1 h/day) was ascertained. Logistic regression models were fit to examine the association of prenatal pet keeping (dog keeping and cat keeping, separately) with ADHD. RESULTS: A subset of 627 children were included in the analyses: 93 who had ADHD and 534 with neurotypical development. After accounting for confounders and loss to follow-up, maternal prenatal dog exposure was associated with 2.23 times (95% CI: 1.15, 4.31; p = 0.017) greater odds of ADHD among boys. Prenatal dog keeping was not statistically significantly associated with ADHD in girls (odds ratio = 0.27, 95% CI: 0.06, 1.12; p = 0.070). Prenatal cat keeping was not associated with ADHD. CONCLUSIONS: In boys, but not girls, maternal prenatal dog keeping was positively associated with ADHD. Further study to confirm these findings and to identify potential mechanisms of this association (e.g., modification of the gut microbiome, exposure to environmental toxicants or pet-related medications) is needed.

Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis.

PURPOSE: Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype. METHODS: Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident lymphoma cases within this population were ascertained and matched with up to five controls. Total serum cholesterol, high-density lipoprotein, and low-density lipoprotein were collected from plan databases. Multilevel, multivariable longitudinal models were fit after choosing the best polynomial order by deviance statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined (n = 12,635) as well as six subtypes of the latter. RESULTS: For all categories, lymphoma cases had statistically significantly lower estimated total serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels than controls in the years prior to diagnosis/index date. Between-group differences were most pronounced 3-4 years prior to diagnosis, when cases' cholesterol levels declined steeply. CONCLUSIONS: This analysis is the first to examine changes in serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol levels was evident several years before diagnosis. Our results suggest that cholesterol-related pathways have an important relationship with lymphomagenesis and low cholesterol could be a preclinical lymphoma marker.

Exploring racial differences in IgE-mediated food allergy in the WHEALS birth cohort.

BACKGROUND: Suspected food allergies are the cause of more than 200,000 visits to the emergency department annually. Racial differences in the prevalence of food allergy have also been reported, but the evidence is less conclusive. Researchers continue to struggle with the identification of food allergy for epidemiologic studies. OBJECTIVE: To explore racial differences in IgE-mediated food allergy (IgE-FA) in a birth cohort. METHODS: We used a panel of board-certified allergists to systematically identify IgE-FA to egg, milk, or peanut in a multiethnic birth cohort in which patient medical history, patient symptoms, and clinical data were available through 36 months of age. RESULTS: Of the 590 infants analyzed, 52.9% were male and 65.8% African American. Sensitization (serum specific IgE >0.35 IU/mL) to the food allergens was significantly higher for African American children compared with non-African American children as has been previously reported. No statistically significant racial/ethnic differences in IgE-FA were observed; however, a higher proportion of African American children were designated as having peanut allergy, and the percentage of African American children with an IgE level greater than 95% predictive decision points for peanut was 1.7% vs 0.5% for non-African American children. With the use of logistic regression, race/ethnicity was not significantly associated with IgE-FA (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.17; P = .75) but was associated with sensitization to more than 1 of the food allergens (adjusted odds ratio, 1.80; 95% confidence interval, 1.22-2.65; P = .003). CONCLUSION: We did not observe an elevated risk of IgE-FA for African American children, although established differences in sensitization were observed. Racial/ethnic differences in sensitization must be taken into consideration when investigating disparities in asthma and allergy.

Race-specific Association of Caesarean-Section Delivery with Body Size at Age 2 Years.

OBJECTIVE: African American children are at higher risk of obesity than White children and African American women are more likely to undergo caesarean-section (CS) delivery than White women. CS is associated with childhood obesity; however, little is known whether this relationship varies by race. We examined if the association of CS with obesity at age 2 years varied by race. DESIGN: Longitudinal birth cohort. SETTING: Birth cohort conducted in a health care system in metropolitan Detroit, Michigan with follow-up at age 2 years. PARTICIPANTS: 639 birth cohort participants; 367 children (57.4%) were born to African American mothers and 230 (36.0%) children were born via CS. MAIN OUTCOME MEASURES: Obesity defined as body mass index ≥95th percentile at age 2 years. RESULTS: Slightly more children of African American (n=37; 10.1%) than non-African American mothers (n=18; 6.6%) were obese (P=.12). There was evidence of effect modification between race and delivery mode with obesity at age 2 years (interaction P=.020). In children of African American mothers, CS compared to vaginal birth was associated with a significantly higher odds of obesity (aOR=2.35 (95% CI: 1.16, 4.77), P=.017). In contrast, delivery mode was not associated with obesity at age 2 years in children of non-African American mothers (aOR=.47 (95% CI: .13, 1.71), P=.25). CONCLUSIONS: There is evidence for a race-specific effect of CS on obesity at age 2 years; potential underlying mechanisms may be racial differences in the developing gut microbiome or in epigenetic programming. Future research is needed to determine if this racial difference persists into later childhood.

Association between vitamin D levels and allergy-related outcomes vary by race and other factors.

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.

Birth weight and asthma incidence by asthma phenotype pattern in a racially diverse cohort followed through adolescence.

OBJECTIVE: Low birth weight (LBW) has been shown to be an independent risk factor for asthma. We hypothesized that LBW would have its greatest impact on early onset disease. METHODS: A racially diverse cohort of children born from 1983 to 1985 at two hospitals, one urban and one suburban in the same metropolitan area, and oversampled for babies weighing ≤2500 g, was identified retrospectively when the children were 6 years of age and followed periodically. At the age 17 years study visit, cohort members and their parent/guardians were separately interviewed face-to-face regarding the subject's history of asthma using the standardized ISAAC questionnaire. We measured the cumulative incidence of asthma from birth through adolescence defined by age of diagnosis and persistence/remittance. RESULTS: Six-hundred and eighty teens (82.6% of the original cohort) were included in the analyses, 387 with LBW and 293 of normal birth weight. The prevalence of physician-diagnosed "Current Asthma" was associated with LBW (p = 0.003 for trend), with patterns stronger in males and whites. LBW was associated most strongly with Late Onset Persistent asthma (current asthma that was diagnosed after 8 years); p for trend 0.032. This trend was again most evident in males and whites. None of the asthma categories classified as "remittent" were statistically associated with LBW. CONCLUSIONS: LBW was not associated with diagnosed asthma that remitted before age 17 years. LBW was associated with asthma diagnosis in mid-childhood that persisted through adolescence, suggesting that the asthmagenic effects of LBW can become evident post the early years of childhood and persist into adulthood.

Does pet-keeping modify the association of delivery mode with offspring body size?

Caesarean-section (CS) delivery increases risk of childhood obesity, and is associated with a distinct early-life gut microbiome, which may contribute to obesity. Household pets may alter human gut microbiome composition. We examined if pet-keeping modified the association of CS with obesity at age 2 years in 639 Wayne County Health, Environment, Allergy and Asthma Longitudinal Study birth cohort participants. Pet-keeping was defined as having a dog or cat (indoors ≥1 h/day) at child age 2 years. We used logistic regression to test for an interaction between CS and pet-keeping with obesity (BMI ≥ 95th percentile) at age 2 years, adjusted for maternal obesity. A total of 328 (51.3 %) children were male; 367 (57.4 %) were African American; 228 (35.7 %) were born by CS; and 55 (8.6 %) were obese. After adjusting for maternal obesity, CS-born children had a non-significant (P = 0.25) but elevated 1.4 (95 % CI 0.8, 2.5) higher odds of obesity compared to those born vaginally. There was evidence of effect modification between current pet-keeping and delivery mode with obesity at age 2 years (interaction P = 0.054). Compared to children born vaginally without a pet currently in the home, children born via CS without a pet currently in the home had a statistically significant (P = 0.043) higher odds (odds ratio 2.00; 95 % CI 1.02, 3.93) of being obese at age 2 years. Pets modified the CS-BMI relationship; whether the underlying mechanism is through effects on environmental or gut microbiome requires specific investigation.

Atopic phenotypes identified with latent class analyses at age 2 years.

BACKGROUND: Atopic sensitization (ie, atopy) is the most commonly reported risk factor for asthma. Recent studies have begun to suggest that atopy, as conventionally defined, might be an umbrella term that obfuscates more specific allergic disease types. OBJECTIVE: We sought to determine whether distinct and meaningful atopic phenotypes exist within a racially diverse birth cohort using 10 allergen-specific serum IgE (sIgE) measurements from children aged 2 years. METHODS: Using the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort (62% black), we analyzed sIgE data on 10 allergens (Dermatophagoides farinae, dog, cat, timothy grass, ragweed, Alternaria alternata, egg, peanut, milk, and German cockroach) obtained from 594 children at age 2 years. Conventional atopy was defined as at least 1 sIgE level of 0.35 IU/mL or greater. RESULTS: A 4-class solution (latent class model) was the best fit. Class types were labeled "low to no sensitization" (76.9% of sample), "highly sensitized" (2.7%), "milk and egg dominated" (15.3%), and "peanut and inhalant(s)" (5.1%). Almost one third (32.2%) of the low to no sensitization group met the criteria for conventional atopy. The highly sensitized group was significantly associated with a doctor's diagnosis of asthma after age 4 years (odds ratio [OR], 5.3; 95% CI, 1.6-17.4), whereas the milk and egg dominated and peanut and inhalant(s) groups were not (ORs of 1.6 [95% CI, 0.8-3.0] and 1.8 [95% CI, 0.6-4.9], respectively). Children of black race were more likely to be in the 3 multisensitized groups (P = .04). CONCLUSION: Classification by sIgE patterns defined groups whose membership is more strongly associated with atopic dermatitis, wheeze, and asthma compared with conventional atopy.

Transforming growth factor beta (TGFß1) in breast milk and indicators of infant atopy in a birth cohort.

BACKGROUND: The infant gut's ability to suppress immunologic reactions to food proteins could be influenced by levels of TGFß in breast milk. We hypothesized that lower levels of TGFß(1) in the breast milk (BM) of mothers in the WHEALS birth cohort are associated with atopy at infant age 2-3 yrs. METHODS: We used data collected during infancy in addition to the results of skin prick tests (SPT+) and measures of specific IgE >0.35 IU/ml (spIgE) to milk, egg, and peanut at infant age 2-3 years. Infants were classified as food allergic (FA) based on parental report of infant symptoms/diagnoses and information from clinical assessments. RESULTS: Data for 304 cohort members were analyzed. Among non-black infants, BM-TGFß(1) was lower for those classified as FA (vs. no FA) and those SPT+ (vs., SPT-), geometric mean = 1100 pg/ml vs. 1417pg/ml, p = 0.081; and 1100 pg/ml vs. 1415pg/ml, p = 0.064, respectively. Among infants of non-atopic mothers, BM-TGFß(1) was lower for those with elevated (vs. not elevated) sIgE, geometric mean = 1347 pg/ml vs. 1651 pg/ml, p = 0.047. Using logistic regression, adjusted odds ratios describing the association of BM-TGFß1 to the presence of atopic indicators in the infant were in the hypothesized direction only for non-black infants of non-atopic mothers: aORs for FA, sIgE and SPT+ were 0.08, 0.34, and 0.26 respectively; p = 0.091, 0.13, and 0.23. CONCLUSION: Immune benefit of BM-TGFß(1) could inform prevention strategies. Evidence of an association appears greatly influenced by infant race and maternal atopy. More research can determine if these relationships represent a modifiable risk factor for the development of food allergy in certain subgroups.

Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles.

BACKGROUND: Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population. OBJECTIVE: To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults. METHODS: Participants included 18- to 21-year-old members (n = 540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. Phorbol myristate acetate-stimulated whole blood interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, IL-17A, IL-17F, IL-22, and interferon-γ secretory responses were analyzed for associations comparing participants with allergic vs nonallergic asthma phenotypes with those without asthma. RESULTS: T-helper cell type (TH) 2-polarized responses, measured as higher mean IL-5 and IL-13 secretions and lower ratios of interferon-γ and IL-12 to 3 TH2 cytokines (IL-4, IL-5, or IL-13), were observed only in participants with allergic asthma. Nonallergic asthma was associated with TH1-polarized responses, including higher adjusted interferon-γ secretion compared with participants with allergic asthma and, surprisingly, those without asthma (odds ratio 2.5, confidence interval 1.2-5.1, P < .01). CONCLUSION: As expected, young adults with a history of an allergic asthma phenotype exhibited a TH2-polarized cytokine response after polyclonal stimulation. However, TH1 polarization was observed in patients with a history of nonallergic asthma. Allergic and nonallergic asthma are associated with etiologically distinct immune endotypes, underscoring the importance of discriminating these endotypes in research analyses and clinical management.

Prenatal dog-keeping practices vary by race: speculations on implications for disparities in childhood health and disease.

OBJECTIVE: There is consistent evidence demonstrating that pet-keeping, particularly of dogs, is beneficial to human health. We explored relationships between maternal race and prenatal dog-keeping, accounting for measures of socioeconomic status that could affect the choice of owning a pet, in a demographically diverse, unselected birth cohort. DESIGN: Self-reported data on mothers' race, socioeconomic characteristics and dog-keeping practices were obtained during prenatal interviews and analyzed cross-sectionally. Robust methods of covariate balancing via propensity score analysis were utilized to examine if race (Black vs White), independent of other participant traits, influenced prenatal dog-keeping. SETTING: A birth cohort study conducted in a health care system in metropolitan Detroit, Michigan between September 2003 and November 2007. PARTICIPANTS: 1065 pregnant women (n=775 or 72.8% Black), between ages 21 and 45, receiving prenatal care. MAIN OUTCOME MEASURES: Participant's self-report of race/ethnicity and prenatal dog-keeping, which was defined as her owning or caring for > or =1 dog for more than 1 week at her home since learning of her pregnancy, regardless of whether the dog was kept inside or outside of her home. RESULTS: In total, 294 women (27.6%) reported prenatal dog-keeping. Prenatal dog-keeping was significantly lower among Black women as compared to White women (20.9% vs 45.5%, P<.001), and remained significantly different even after propensity score analysis was applied. CONCLUSION: Findings suggest that there are persistent racial differences in dog-keeping not fully explained by measures of socioeconomic status. Racial differences in prenatal dog-keeping may contribute to childhood health disparities.