A.B. Becker

Infant antibiotic exposure and the development of childhood overweight and central adiposity

Background:Obesity has been associated with disruption of the gut microbiota, which is established during infancy and vulnerable to disruption by antibiotics.Objectives:To investigate the association between early-life antibiotic exposure and subsequent development of overweight and central adiposity.Methods:Provincial health-care records were linked to clinical and survey data from a Canadian longitudinal birth cohort study. Antibiotic exposure during the first year of life was documented from prescription records. Overweight and central adiposity were determined from anthropometric measurements at ages 9 (n=616) and 12 (n=431). Associations were determined by multiple logistic regression.Results:Infants receiving antibiotics in the first year of life were more likely to be overweight later in childhood compared with those who were unexposed (32.4 versus 18.2% at age 12, P=0.002). Following adjustment for birth weight, breastfeeding, maternal overweight and other potential confounders, this association persisted in boys (aOR 5.35, 95% confidence interval (CI) 1.94–14.72) but not in girls (aOR 1.13, CI 0.46–2.81). Similar gender-specific associations were found for overweight at age 9 (aOR 2.19, CI 1.06–4.54 for boys; aOR 1.20, CI 0.53–2.70 for girls) and for high central adiposity at age 12 (aOR 2.85, CI 1.24–6.51 for boys; aOR 1.59, CI 0.68–3.68 for girls).Conclusions:Among boys, antibiotic exposure during the first year of life was associated with an increased risk of overweight and central adiposity in preadolescence, indicating that antibiotic stewardship is particularly important during infancy. Given the current epidemic of childhood obesity and the high prevalence of infant antibiotic exposure, further studies are necessary to determine the mechanisms underlying this association, to identify the long-term health consequences, and to develop strategies for mitigating these effects when antibiotic exposure cannot be avoided.

Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months

BACKGROUND The value of cord blood IgE in predicting the development of asthma and other IgE-mediated allergic diseases is unclear. OBJECTIVE The purpose of this study is twofold: (1) to determine factors affecting cord blood IgE level and (2) to determine whether cord blood IgE predicts the development of asthma and other IgE-mediated allergic diseases in high risk (defined as those with at least one first degree relative with asthma or 2 first degree relatives with other IgE-mediated allergic diseases) infants at 12 months. METHODS The study utilized cord blood obtained from a group of high risk infants who took part in a randomized controlled trial to assess the effectiveness of an intervention program in the primary prevention of asthma and other IgE-mediated allergic diseases. Total IgE and cotinine in the cord blood were measured. Assessment of the infants was done at 12 months for these diseases. RESULTS Sixty-four (17.8%) infants had detectable total IgE in cord blood >0.5 kU/L. The proportion of infants with elevated cord blood IgE was significantly higher among nonwhites, birth during winter months, and those with a maternal history of asthma. There was no correlation between cord blood IgE and cord blood cotinine level. Cord blood IgE was found to be a significant predictor for the development of urticaria due to food allergy but not for other outcomes. CONCLUSION Both genetic and environmental risk factors play a role in determining the level of IgE in cord blood. Cord blood IgE was a significant risk factor for the development of urticaria due to food allergy at 12 months of life. As urticaria due to food allergy is a prodrome for anaphylaxis, measurement of IgE in cord blood may be indicated in infants at high risk for developing allergic diseases so that preventive measures can be applied.

House dust mite allergen levels in two cities in Canada: effects of season, humidity, city and home characteristics

The homes of 120 patients with asthma, 57 in Vancouver and 63 in Winnipeg, were studied. The characteristics of the homes were assessed by a questionnaire. Dust samples were collected and the indoor relative humidity was measured four times during the year covering all four seasons in both cities. Mite allergen levels were determined using monoclonal antibodies against Der p I and Der f I by the ELISA method. The mean levels of both mite allergens in mattress and floor samples in the homes in Vancouver and in Winnipeg were relatively low for all seasons. Mite allergen levels were found to be associated with city, season and individual home differences. They were significantly higher in Vancouver than in Winnipeg. Der p I and Der f I in mattress samples in both cities and Der f I in floor samples in Vancouver, varied by season. The indoor relative humidity level in the homes in Vancouver were also significantly higher than those in Winnipeg. There was, however, no significant association between the levels of indoor relative humidity and the levels of mite allergens after adjusting for variations in city, season and individual home. Although individual home differences were highly associated with mite allergen levels, only a few home characteristics were found to be related to mite allergen levels such as the type and the age of the home, the type of heating, the use of feather pillows and the number of occupants in the homes. Whether low levels of mite allergens are partially responsible for the relatively low prevalence of childhood asthma in Canada remains to be investigated.

Constant infusion of epinephrine, but not bolus treatment, improves haemodynamic recovery in anaphylactic shock in dogs

Objective Epinephrine (Epi) is the treatment of choice for reversing cardiovascular collapse in anaphylactic shock (AS). In this condition, most treatment guidelines have been anecdotally derived and no randomized clinical trials have been conducted. In the present study, we examined the time course of haemodynamic recovery in a canine model of AS when Epi was administered at the initiation of allergen challenge before fully developed shock had occurred.

Novel cytokine peptide‐based vaccines: an interleukin‐4 vaccine suppresses airway allergic responses in mice

Background:  Monoclonal antibodies or soluble receptors have been used to block over‐produced endogenous cytokines. However, they have disadvantages of short half‐lives, high costs, and possible adverse effects. Using interleukin (IL)‐4 as a model target, we sought to develop a novel therapeutic strategy by constructing an IL‐4 peptide‐based vaccine for blocking IL‐4 on a persistent basis, and to evaluate its efficacy in a mouse model of asthma.

A novel study design to investigate the early-life origins of asthma in children (SAGE study).

This is a description of the Study of Asthma, Genes and the Environment (SAGE), a novel birth cohort created from provincial healthcare administrative records. It is a general population‐based cohort, composed of children at high and low risk for asthma, living in urban and rural environments in Manitoba, Canada. The SAGE study captures the complete longitudinal healthcare records of children born in 1995 and contains detailed information on early‐life exposures, such as antibiotic utilization and immunization, in relationship to the development of asthma. Nested within the birth cohort is a case‐control study, which was created to collect information on home environmental exposures from detailed surveys and home dust sampling, to confirm asthma status in children and use this data to validate healthcare database measures of asthma, to determine differences in immune system responsiveness to innate and adaptive immune stimuli in asthma, to genotype children for genes likely associated with the development of asthma and to study the epigenetic regulation of pre‐established protective vs allergic immune responses. The SAGE study is a multidisciplinary collaboration of researchers from pediatric allergy, population health, immunology, and genetic and environmental epidemiology. As such, it serves as a fertile, interdisciplinary training ground for graduate students, and postdoctoral and clinician fellows.

The bronchodilator effect and pharmacokinetics of theobromine in young patients with asthma

The bronchodilator effect of a 10 mg/kg dose of theobromine (3,7-dimethylxanthine) was compared with that of 5 mg/kg of theophylline (1,3-dimethylxanthine) in young patients with asthma. Bronchodilation, as assessed by forced vital capacity, forced expiratory volume in the first second, forced expiratory flows at 25%, 50%, and 75% of vital capacity, and percent of forced expiratory volume in the first second/forced vital capacity did not differ significantly between the two drugs. After each drug bronchodilation peaked at 2 hours and lasted for 6 hours, although it was not always statistically significant for theobromine. The mean peak serum concentrations of both drugs, the time at which peak serum concentrations occurred, and elimination half-life values were similar for theobromine and theophylline.

Fast food consumption counters the protective effect of breastfeeding on asthma in children

Background Fast food consumption and childhood asthma have rapidly increased in recent decades. During the same period there has been an increased rate of prolonged breastfeeding.

Modes of Infant Feeding and the Risk of Childhood Asthma: A Prospective Birth Cohort Study

Objective To determine whether different modes of infant feeding are associated with childhood asthma, including differentiating between direct breastfeeding and expressed breast milk. Study design We studied 3296 children in the Canadian Healthy Infant Longitudinal Development birth cohort. The primary exposure was infant feeding mode at 3 months, reported by mothers and categorized as direct breastfeeding only, breastfeeding with some expressed breast milk, breast milk and formula, or formula only. The primary outcome was asthma at 3 years of age, diagnosed by trained healthcare professionals. Results At 3 months of age, the distribution of feeding modes was 27% direct breastfeeding, 32% breastfeeding with some expressed breast milk, 26% breast milk and formula, and 15% formula only. At 3 years of age, 12% of children were diagnosed with possible or probable asthma. Compared with direct breastfeeding, any other mode of infant feeding was associated with an increased risk of asthma. These associations persisted after adjusting for maternal asthma, ethnicity, method of birth, infant sex, gestational age, and daycare attendance (some expressed breast milk: aOR, 1.64, 95% CI, 1.12‐2.39; breast milk and formula, aOR, 1.73, 95% CI, 1.17‐2.57; formula only: aOR, 2.14, 95% CI, 1.37‐3.35). Results were similar after further adjustment for total breastfeeding duration and respiratory infections. Conclusions Modes of infant feeding are associated with asthma development. Direct breastfeeding is most protective compared with formula feeding; indirect breast milk confers intermediate protection. Policies that facilitate and promote direct breastfeeding could have impact on the primary prevention of asthma.

Fecal Short-Chain Fatty Acid Variations by Breastfeeding Status in Infants at 4 Months: Differences in Relative versus Absolute Concentrations

Our gut microbiota provide a number of important functions, one of which is the metabolism of dietary fiber and other macronutrients that are undigested by the host. The main products of this fermentation process are short-chain fatty acids (SCFAs) and other intermediate metabolites including lactate and succinate. Production of these metabolites is dependent on diet and gut microbiota composition. There is increasing evidence for the role of SCFAs in host physiology and metabolic processes as well as chronic inflammatory conditions such as allergic disease and obesity. We aimed to investigate differences in fecal SCFAs and intermediate metabolites in 163 infants at 3–5 months of age according to breastfeeding status. Compared to no exposure to human milk at time of fecal sample collection, exclusive breastfeeding was associated with lower absolute concentrations of total SCFAs, acetate, butyrate, propionate, valerate, isobutyrate, and isovalerate, yet higher concentrations of lactate. Further, the relative proportion of acetate was higher with exclusive breastfeeding. Compared to non-breastfed infants, those exclusively breastfed were four times more likely (aOR 4.50, 95% CI 1.58–12.82) to have a higher proportion of acetate relative to other SCFAs in their gut. This association was independent of birth mode, intrapartum antibiotics, infant sex, age, recruitment site, and maternal BMI or socioeconomic status. Our study confirms that breastfeeding strongly influences the composition of fecal microbial metabolites in infancy.