Dog introduction alters the home dust microbiota.

Research has largely reported that dog exposure is associated with reduced allergic disease risk. Responsible mechanism(s) are not understood. The goal was to investigate whether introducing a dog into the home changes the home dust microbiota. Families without dogs or cats planning to adopt a dog and those who were not were recruited. Dust samples were collected from the homes at recruitment and 12 months later. Microbiota composition and taxa (V4 region of the 16S rRNA gene) were compared between homes that did and did not adopt a dog. A total of 91 dust samples from 54 families (27 each, dog and no dog; 17 dog and 20 no dog homes with paired samples) were analyzed. A significant dog effect was seen across time in both unweighted UniFrac and Canberra metrics (both P = .008), indicating dog introduction may result in rapid establishment of rarer and phylogenetically related taxa. A significant dog-time interaction was seen in both weighted UniFrac (P < .001) and Bray-Curtis (P = .002) metrics, suggesting that while there may not initially be large relative abundance shifts following dog introduction, differences can be seen within a year. Therefore, dog introduction into the home has both immediate effects and effects that emerge over time.

Prenatal antimicrobial use and early-childhood body mass index.

BACKGROUND/OBJECTIVES: Growing evidence suggests that antibiotic use is associated with childhood body mass index (BMI), potentially via mechanisms mediated by gut microbiome alterations. Less is known on the potential role of prenatal antimicrobial use in offspring obesity risk. We examined whether prenatal antibiotic or antifungal use was associated with BMI at the age of 2 years in 527 birth cohort participants. METHODS/SUBJECTS: Antimicrobial use was obtained from the prenatal medical record. Height and weight were measured at the age of 2 years. Overweight/obesity was defined as a BMI ⩾85th percentile. RESULTS: A total of 303 (57.5%) women used antibiotics and 101 (19.2%) used antifungals during pregnancy. Prenatal antifungal use was not associated with child BMI at the age of 2 years. In the fully adjusted model, prenatal antibiotic use was associated with a 0.20±0.10 (P=0.046) higher mean BMI Z-score at the age of 2 years. Associations between prenatal antibiotic use and childhood BMI varied by trimester of exposure, with first or second-trimester exposure more strongly associated with larger BMI at the age of 2 years for both BMI Z-score (interaction P=0.032) and overweight/obesity (interaction P=0.098) after covariate adjustment. CONCLUSIONS: Prenatal antibiotic, but not antifungal, use is associated with larger BMI at the age of 2 years; associations were stronger for antibiotic exposures in earlier trimesters. Future studies examining whether these associations are due to alterations in the maternal and/or infant microbiome are necessary. Children who are overweight at the age of 2 years are at higher risk for being overweight as they age; prenatal antibiotic use is a potentially modifiable exposure that could reduce childhood obesity.

Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.

Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.

Maternal group B Streptococcus and the infant gut microbiota.

Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant's diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R 2=0.008, P=0.008; Unweighted UniFrac R 2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study.

Combined effects of prenatal medication use and delivery type are associated with eczema at age 2 years.

BACKGROUND: Separately, prenatal antibiotics and Caesarian delivery have been found to be associated with increased risk of allergic diseases. It is not clear whether these factors may modify the effect of each other. OBJECTIVE: To assess whether the associations between delivery types and eczema, sensitization and total IgE at age 2 years were modified by maternal use of prenatal medications. METHODS: Prenatal charts of women enrolled in the WHEALS birth cohort were reviewed for delivery mode and medications prescribed and administered throughout their entire pregnancy, including systemic antibiotics and vaginally applied antifungal medications. The associations between the delivery mode and select medications and, eczema, sensitization (≥ 1 of 10 allergen-specific IgE ≥ 0.35 IU/mL) and total IgE at age 2 years were assessed. RESULTS: There was a lower risk of eczema among vaginally vs. c-section born children (relative risk adjusted for race = aRR = 0.77, 95% CI 0.56, 1.05). Although not statistically significantly different, this association was stronger among the subset of children born vaginally to a mother who did not use systemic antibiotics or vaginal antifungal medications (aRR = 0.69, 95% CI 0.44, 1.08) compared to those born vaginally to mothers who used systemic antibiotics or vaginal antifungals (aRR = 0.81, 95% CI 0.57, 1.14). A protective association between vaginal birth and sensitization (aRR = 0.86, 95% CI 0.72, 1.03) was similar for those children born vaginally to a mother who did not (aRR = 0.87, 95% CI 0.69, 1.10) and who did (RR = 0.85, 95% CI 0.70, 1.04) use systemic antibiotics or vaginal antifungal medications. There were no associations with total IgE. CONCLUSIONS: Children born vaginally had lower risk of eczema and sensitization compared with those born via c-section; however, the protective association with eczema may be slightly weakened when mothers took systemic antibiotics or vaginally applied medications during pregnancy.

Are cats and dogs the major source of endotoxin in homes?

UNLABELLED: Previous studies have suggested that exposure to cats and dogs during early childhood reduces the risk of allergic disease, possibly by increasing home endotoxin exposure. This study asked the question of whether cats and dogs are the dominant influence on dust endotoxin concentrations in homes after considering other variables reportedly associated with endotoxin. The presence of cats or dogs in homes, household and home characteristics, and dust endotoxin concentrations from 5 locations were assessed in 966 urban and suburban homes. Whether considered together as pets or as cats and dogs separately, the presence of cats and dogs significantly contributed to living room and bedroom floor endotoxin concentrations, but not to bed endotoxin concentrations. However, the two variables consistently related to endotoxin in all home sites were the home occupant density (occupants/room) and cleanliness of the home. Our data suggest that reducing occupant density and improving home cleanliness would reduce home endotoxin concentrations more than removing pet cats or dogs from the home. PRACTICAL IMPLICATIONS: Many studies have shown that early childhood exposure to indoor cats or dogs is associated with a reduced risk of later allergic disease and asthma. An important question is whether alteration in allergic risk associated with cat and dog exposure results from increased endotoxin exposure or from some other associated exposure. Our findings show that cats and dogs are not the dominant source of endotoxin in homes; rather, the density of human occupation and poor cleaning contribute more consistently to higher home endotoxin concentrations especially in the beds.

Lifetime dog and cat exposure and dog- and cat-specific sensitization at age 18 years.

BACKGROUND: Prior research about whether keeping a dog or cat at home causes allergies to that pet has been limited to outcomes in early childhood. OBJECTIVE: Evaluate the association between lifetime dog and cat exposure and allergic sensitization to the specific animal at 18 years of age. METHODS: Participants enrolled in the Detroit Childhood Allergy Study birth cohort during 1987-1989 were contacted at the age 18 years. Sensitization to dog or cat was defined as animal-specific IgE ≥ 0.35 kU/L. Annual interview data from childhood and follow-up interviews at age 18 years were used to determine lifetime indoor dog and cat exposure (indoor was defined when the animal spent >50% of their time inside the house). Exposure was considered in various ways: first year, age groups and cumulative lifetime. Analyses were conducted separately for dogs and cats. RESULTS: Among males, those with an indoor dog during the first year of life had half the risk [relative risk (RR)=0.50, 95% confidence interval (CI) 0.27, 0.92] of being sensitized to dogs at age 18 compared with those who did not have an indoor dog in the first year. This was also true for males and females born via c-section (RR=0.33, 95% CI 0.07, 0.97). Overall, teens with an indoor cat in the first year of life had a decreased risk (RR=0.52, 95% CI 0.31, 0.90) of being sensitized to cats. Neither cumulative exposure nor exposure at any other particular age was associated with either outcome. CONCLUSIONS AND CLINICAL RELEVANCE: The first year of life is the critical period during childhood when indoor exposure to dogs or cats influences sensitization to these animals.

Factors associated with nonresponse to a computer-tailored asthma management program for urban adolescents with asthma.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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, completed >or=2 of 4 educational sessions, and completed >or=2 of 3 follow-up questionnaires. Ninety students met criteria for inclusion in this subgroup analysis. RESULTS: 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. CONCLUSIONS: 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.

Gender differences in the association of overweight and asthma morbidity among urban adolescents with asthma.

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.

Prenatal exposure to household pets influences fetal immunoglobulin E production.

BACKGROUND: Early life pet exposure may protect against allergic sensitization during childhood. Few studies have evaluated the effect of prenatal pet exposure on potential neonatal markers of allergic risk. OBJECTIVE: The aim of this study was to investigate whether maternal exposure to pets affects cord blood IgE levels in a population-based, general risk, ethnically mixed birth cohort. METHODS: Pet keeping during pregnancy was ascertained from women residing in a defined area of Wayne County Michigan and recruited from five staff model obstetric clinics. Maternal venous blood was analysed for total and allergen-specific IgE along with cord blood total IgE from 1049 infants. RESULTS: Compared with infants from households with no cats or dogs kept indoors during pregnancy, infants whose homes had either cats or dogs had significantly reduced mean cord IgE levels [0.34 IU/mL (95% CI 0.30-0.38) vs. 0.24 IU/mL (0.20-0.27), P=0.025]. Similar effects were apparent in cat-only households [0.21 IU/mL (0.16-0.27), P=0.020] and dog-only households [0.24 IU/mL (0.19-0.29), P=0.045]. There was no effect on results when excluding mothers who reported avoiding pets due to allergy-related concerns. CONCLUSION: Mothers with either cats or dogs in their home during pregnancy deliver children with lower cord blood IgE levels compared with mothers who do not live with these pets, supporting the hypothesis that pet exposure influences immune development in a manner that is protective for atopy and is operant even before birth.

A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects.

Biomarkers associated with asthma aetiology and exacerbation have been sought to shed light on this multifactorial disease. One candidate is the serum concentration of the Clara cell secretory protein (CC16, sometimes referred to as CC10 or uteroglobin). In this review, we examine serum CC16's relation to asthma aetiology and exacerbation. There is evidence that acute exposures to certain pulmonary irritants can cause a transient increase in serum CC16 levels, and limited evidence also suggests that a transient increase in serum CC16 levels can be caused by a localized pulmonary inflammation. Research also indicates that a transient increase in serum CC16 is not associated with measurable pulmonary damage or impairment of pulmonary function. The biological interpretation of chronic changes in serum CC16 is less clear. Changes in serum CC16 concentrations (either transient or chronic) are not specific to any one agent, disease state, or aetiology. This lack of specificity limits the use of serum CC16 as a biomarker of specific exposures. To date, many of the critical issues that must be understood before serum CC16 levels can have an application as a biomarker of effect or exposure have not been adequately addressed.

Passive cigarette smoke exposure of infants: importance of nonparental sources.

OBJECTIVE: To learn whether cigarette smoking by persons other than parents significantly contributes to the passive environmental tobacco smoke (ETS) exposure of infants. STUDY DESIGN: A cohort of infants prospectively followed up from birth to age 2 years with monthly questionnaires concerning smoking by different categories of adults coming into contact with the infants. SETTING: Health maintenance organization members residing in several suburban communities of Detroit, Mich, defined by contiguous ZIP codes. SUBJECTS: Ninety-seven (83%) of 117 healthy, full-term infants, thought to be at high risk of allergic disease based on cord blood IgE, who were born to eligible mothers and who completed 24 months of follow-up. MAIN OUTCOME MEASURES: Average of bimonthly urinary cotinine-creatinine ratios (CCRs) during the 2 years of the study. RESULTS: There were significant correlations (r

Quantitative IgE antibody assays in allergic diseases.

During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously. Elevated egg-specific IgE antibody levels in infancy are associated with significantly increased risk for development of inhalant allergies later in childhood. In cases of inhalant allergy, specific IgE antibody levels correlate closely with results of inhalation challenge studies in cat-sensitive persons. Also, mite-specific IgE antibody levels correlate significantly with the mite allergen contents of reservoir dust in the homes of mite-sensitive persons. Immunoassays for quantitation of specific IgE antibodies may be used to document allergen sensitization over time and to evaluate the risk of reaction on allergen exposure. However, immunoassays and skin tests are not entirely interchangeable, and neither will replace the other in appropriate circumstances.

Predicting asthma severity from allergic sensitivity to cockroaches in pregnant inner city women.

OBJECTIVE: To measure and compare cockroach (CR)-specific immunoglobin E (IgE) in sera from pregnant women with mild, moderate and severe asthma. STUDY DESIGN: CR IgE levels were measured in stored sera collected during the Collaborative Perinatal Project. Three matched groups of 93 women were formed: group I (mild), history of asthma but no acute exacerbation; group II (moderate), acute asthma exacerbation; group III (severe), required hospitalization for a diagnosis of status asthmaticus. ANOVA was used to compare the three means. RESULTS: Mean CR IgE paralleled prenatal asthma severity. Mean values were 6.50, 13.12 and 28.99 kU/L for groups I, II and III, respectively (P = .06). High allergen sensitivity, defined as CR IgE > 60 kU/L, was identified in 8 of the 93 study samples. The prevalence of high allergen sensitivity increased as clinical asthma became more severe. Sixty-two percent (5/8) of the high allergen sensitivity occurred in group III. CONCLUSION: There appears to be a positive correlation between sensitivity to CR allergens and asthma severity during pregnancy, and these findings support further evaluation of CR allergen sensitivity as a predictor of asthma severity in pregnancy.

Factors related to methacholine airway responsiveness in children.

Studies of airway responsiveness (AR) have typically used similar dose schedules of methacholine for adults and children despite large ranges in subject size. Reported declines in AR with increasing age in children could be due to maturational changes or to proportionately smaller doses of methacholine in taller (older) children. Other investigators have related both height and various measures of lung function to AR. We examined data related to AR in 471 children, aged 6 to 8 yr, from a birth cohort. Each child underwent spirometry followed by sequential challenge with five doses of methacholine, ranging from 0.025 to 25 mg/ml, given with a dosimeter. Continuous slope and end FEV(1)-change indexes of responsiveness were computed. Using stepwise regression modeling, we found no significant association between AR and either height or age after entering a variable reflecting asthma or wheezing. In contrast, we found that baseline measures of FVC, FEV(1)/FVC, and FEF(25-75%) were significantly related to AR after controlling for other variables (p = 0.001). However, when all three of the latter measures were added to models, FEF(25-75%) was most closely related to AR. We conclude that after control for other variables, FEF(25-75%) and FVC, but not height, are significantly related to methacholine responsiveness in children.

Racial differences in physiologic parameters related to asthma among middle-class children.

BACKGROUND: Asthma morbidity and mortality are higher in the United States for African-American (AA) children when compared to European-American (EA) children. STUDY OBJECTIVES: To explore racial differences in physiologic factors associated with pediatric asthma severity. DESIGN: Cross-sectional. METHODS: We analyzed data from two groups of children in suburban Detroit, one of which contains non-urban, middle-class AA children, a group not usually included in childhood asthma studies. All children were 6 to 8 years of age. Clinical evaluations included medical history, physical examination, skin testing, spirometry, and methacholine challenge. RESULTS: The study population (n = 569) was 14% African American, 51% of the participants were male, and the mean age was 6.8 +/- 0.4 years. Socioeconomic status (parental education) was similar overall by race, although some strata-specific differences were observed. The prevalence of physician-diagnosed asthma was 10% for both AA and EA groups. AA children were more reactive to methacholine than EA children (42% vs 22%, respectively; p = 0.001), and had significantly higher total IgE than EA children (geometric mean, 60. 6 vs 27.5 IU/mL; p = 0.001). Serum IgE was related to methacholine reactivity in EA children (p = 0.001), but not AA children (p = 0. 73). These differences remained after adjustment for gender, age, parental education, parental smoking, and maternal smoking during pregnancy. CONCLUSIONS: Our data support previous reports of racial differences in lung volume, airway responsiveness, and serum IgE concentrations. We found a racial difference in the relationship between total serum IgE and airway responsiveness that is unreported elsewhere. Overall, our results suggest that AA children may be predisposed to asthma.

Identification of bovine IgG as a major cross-reactive vertebrate meat allergen.

BACKGROUND: Although beef is a main source of protein in Western diets, very little has been published on allergic reactions to beef or the main allergens implicated in these reactions. The aim was to evaluate the IgE antibody response to beef in suspected meat-allergic subjects and assess cross-reactivity of beef with other vertebrate meats. METHODS: Fifty-seven sera from suspected meat-allergic subjects were tested by grid blot for specific IgE antibodies to vertebrate meats (beef, lamb, pork, venison, and chicken), and the patterns of recognition of meat proteins were assessed by immunoblot studies. RESULTS: A 160-kDa band, identified as bovine IgG, was detected in raw beef in 83% (10/12) of beef-allergic subjects but in only 24% of the beef-tolerant subjects. IgE reactivity to a band of similar mol. mass was detected also in lamb and venison, but rarely in pork or chicken. Complete inhibition of the IgE reactivity to the bovine IgG was obtained with lamb, venison, and milk. IgE reactivity to this band also completely disappeared when beef or lamb extracts were separated under reducing conditions, indicating conformational epitopes. CONCLUSIONS: Bovine IgG appears to be a major cross-reacting meat allergen that could predict beef allergy. Further studies with oral IgG challenges should be performed to document the conclusion that in vitro reactivity correlates with clinical hypersensitivity. The role of bovine IgG in other bovine products such as milk, dander, or hair must also be studied, and the hypothesis that it is a cross-reacting allergen with other mammalian products validated.