Characteristics and progression of childhood-onset and adult-onset eosinophilic esophagitis.

BACKGROUND AND AIM: The prevalence and incidence of eosinophilic esophagitis (EoE) has been increasing over recent years. However, the natural history remains incompletely understood particularly the differences in disease characteristics and progression of childhood-onset and adult-onset EoE. The aim of this study was to evaluate the disease characteristics and progression of childhood-onset and adult-onset EoE. METHODS: A cross-sectional, questionnaire-based study, on 87 adults and 67 children from 2 major tertiary hospitals in South Australia was conducted. Data of those who were diagnosed with EoE between 1999 and 2018 were collected and correlated with medical records. RESULTS: Of the 87 adults with EoE, 34 (39%) were diagnosed at the age of < 18 years (childhood-onset EoE). Reflux symptoms were more common in childhood-onset EoE, whereas asthma was more common in adult-onset EoE. The median duration of symptoms prior to diagnosis of EoE was > 1-4 years in childhood-onset disease (44%) and ≥ 10 years in adult-onset disease (34%). Food impaction was significantly more common on initial presentation in those with adult-onset EoE, whereas weight loss was more common in childhood-onset EoE. At the time of questionnaire, regurgitation, abdominal pain, and bloating were more common in childhood-onset EoE. Those with childhood-onset EoE were more likely to have multiple symptoms at questionnaire when compared with their adult-onset counterparts. In both groups, 15% (5/34 childhood-onset EoE and 8/53 adult-onset EoE) were asymptomatic at the time of questionnaire. CONCLUSION: Childhood-onset EoE appears to be a progressive disease from childhood to adulthood, however with more inflammatory-type symptoms post transition compared to those with adult-onset EoE.

Zinc-fortified oral rehydration solution improved intestinal permeability and small intestinal mucosal recovery.

A randomized double-blind placebo-controlled study was conducted in children admitted to hospital with gastroenteritis (≥3 loose stools per day). All were treated for 5 days following admission with either zinc (Zn, 3 mg) or without Zn-fortified rice-based oral rehydration solution (ORS). (13)C-sucrose breath test (SBT) and intestinal permeability (lactulose/rhamnose or L/R ratio) were performed concurrently prior to commencement of ORS with or without Zn and at day 5 post-admission. There was a significant improvement in the SBT results in both the Zn-fortified group, median (5th-95th percentile) 2.1% (0.4% to 8.3%) versus 4.4% (0.4% to 10.4%), P < .05, and control group, 1.4% (0.1% to 5.4%) versus 4.3% (0.4% to 11.4%), P < .05, between the day of admission and day 5 post-admission. In the Zn-fortified group, there was also a significant improvement in L/R ratio between the day of admission and day 5 post-admission, 53.0 (19.5-90.6) versus 17.7 (13.4-83.2), P < .05. Low levels of Zn improved intestinal permeability but did not enhance short-term recovery following diarrheal illness.

Awareness of antibiotic prescribing and resistance in primary dental care.

Dentists in primary care account for approximately one in ten of all therapeutic antibiotic prescriptions, but many of these prescriptions may be unnecessary and will contribute to the critically important problem of bacterial resistance. Emerging guidance on antimicrobial stewardship is discussed and the annual European Antibiotic Awareness Day (EAAD), which takes place on 18 November, is highlighted.

13C-sucrose breath test: novel use of a noninvasive biomarker of environmental gut health.

OBJECTIVE: Environmental enteropathy syndrome may compromise growth and predispose to infectious diseases in children in the developing world, including Australian Aboriginal children from remote communities of the Northern Territory. In this study, we described the use of a biomarker (13)C-sucrose breath test (SBT) to measure enterocyte sucrase activity as a marker of small intestinal villus integrity and function. METHODS: This was a hospital-based prospective case-control study of Aboriginal and non-Aboriginal children with and without acute diarrheal disease. Using the SBT, we compared 36 Aboriginal case subjects admitted to a hospital (18 diarrheal and 18 nondiarrheal disease), with 7 healthy non-Aboriginal control subjects. Intestinal permeability using the lactulose/rhamnose (L/R) ratio on a timed 90-minute blood test was performed simultaneously with the SBT. The SBT results are expressed as a cumulative percentage of the dose recovered at 90 minutes. RESULTS: Aboriginal children with acute diarrheal disease have a significantly decreased absorptive capacity, as determined by the SBT, with a mean of 1.9% compared with either Aboriginal children without diarrhea (4.1%) or non-Aboriginal (6.1%) control subjects. The mean L/R ratio in the diarrhea group was 31.8 compared with 11.4 in Aboriginal children without diarrhea. There was a significant inverse correlation between the SBT and the L/R ratio. CONCLUSIONS: The SBT was able to discriminate among Aboriginal children with diarrhea, asymptomatic Aboriginal children with an underlying environmental enteropathy, and healthy non-Aboriginal controls. This test provides a noninvasive, easy-to-use, integrated marker of the absorptive capacity and integrity of the small intestine and could be a valuable tool in evaluating the efficacy of interventions aimed at improving gut health.

Responses to immunisation with Hib conjugate vaccine in Australian breastfed and formula-fed infants.

OBJECTIVE: There are conflicting reports as to whether breastfed infants respond with higher antibody levels to conjugate Haemophilus influenzae type b (Hib) vaccine compared with formula-fed infants. These observations prompted us to investigate the effect of feeding method on the antibody concentration to Hib polyribosylribitol (PRP) both prior to and 3 months after the primary course of immunisation with Hib (PRP-OMP). METHODS: We measured plasma concentrations of IgG antibody to Hib PRP by enzyme-linked immunosorbent assay in blood samples from a total of 272 breastfed and formula-fed infants prior to immunisation (7 weeks of age, n = 82 and n = 148, respectively) and again 3 months after completion of the primary course of immunisation with Hib PRP-OMP (7 months of age, n = 88 and n = 132, respectively). RESULTS: Breastfeeding was associated with lower plasma antibody titres at both times (P < 0.01, T-test) with 49% of breastfed infants having anti-PRP concentrations below 1.0 microg/mL at age 7 months. There was no reported invasive Hib disease in this cohort of infants, and nationally the effectiveness of the Hib vaccination programme remains high. CONCLUSIONS: These data suggest that breastfeeding may be associated with immunomodulation of infant Hib immunisation responses with this immunisation regime. Further research is needed to determine whether differences in antibody concentration described here are primarily determined by factors directly attributed to breastfeeding or whether other environmental factors may play a significant role.

Interleukin-2 in human milk: a potential modulator of lymphocyte development in the breastfed infant.

Development of lymphocyte subpopulations and response to antigen exposure will be influenced by the limited ability of neonates to produce cytokines. In the case of cytokines such as interleukin (IL)-2 which are potent T lymphocyte regulators but poorly produced by newborn infants, the supply of cytokines through human milk could alleviate an immunological deficit and potentially aid the maturation of the immune system. We analysed human milk from 52 mothers (15-357 days postpartum) by ELISA to determine levels of aqueous IL-2, as well as production by human milk cells. IL-2 was detectable (>8 pg/mL) in the aqueous phase of 81% of all day 1 samples with no significant difference found in the mean concentration over 3 consecutive days. IL-2 was produced constitutively at detectable levels by 57% of milk cell samples and production was significantly increased by stimulation with Con A (380%). No correlation was found between aqueous and cellular IL-2, however there was a significant correlation between milk aqueous IL-2 and serum IL-2. This is the first report of IL-2 in the aqueous phase of human milk. A supply of exogenous IL-2 in human milk may provide the suckling infant with important immunological signals during a significant stage of T cell development.

Dietary nucleotides do not alter erythrocyte long-chain polyunsaturated fatty acids in formula-fed term infants.

There have been conflicting reports regarding the effectiveness of dietary nucleotides (NT) to regulate tissue desaturases and hence stimulate accumulation of both n-6 and n-3 long-chain polyunsaturated fatty acids (LCPUFA). The aim of this study was to examine the effect of NT-supplemented cow's milk-based formula on erythrocyte phospholipid FA status in a large randomized controlled trial involving a well-nourished infant population born at term. Formula-fed infants were allocated to control formula with an innate level of NT at 10 mg/L (n = 102), or formula fortified with NT at 34 mg/L (n = 98). A parallel group of breastfed infants was included as a reference. Peripheral blood samples were collected by venipuncture at 7 mon of age and erythrocyte phospholipid FA determined by capillary GC. Erythrocyte LCPUFA levels did not differ between the NT-supplemented and control formula groups and were reduced in both groups compared with breastfed infants. We conclude that there is no induction of LCPUFA accumulation in erythrocyte phospholipids of term, formula-fed infants following 7 mon of NT supplementation.

Cytokine production by human milk cells and peripheral blood mononuclear cells from the same mothers.

Samples of milk (n = 80) and venous blood were collected at 5 weeks postpartum from 82 lactating mothers. Human milk cells and peripheral blood mononuclear cells were isolated and the production of interleukin-1beta, interleukin-6, and tumor necrosis factor-a in the absence and presence of lipopolysaccharide was determined by enzyme-linked immunosorbent assay. Human milk cells spontaneously produced significantly less interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha than peripheral blood mononuclear cells in the absence of stimulation. In vitro stimulation of human milk cells with lipopolysaccharide (500 ng/ml) for 24 hr increased cytokine production by approximately 40-50%, whereas peripheral blood mononuclear cells responded to lipopolysaccharide (200 ng/ml) with increased cytokine production of up to 350%. These observations suggest that cells in milk are capable of active involvement in the production of the interleukin-1beta, interleukin-6, and tumor necrosis factor-a in the mammary gland and have the capacity to respond to further stimulation after leaving the breast.

Variations in transforming growth factor beta in human milk are not related to levels in plasma.

There is considerable variability in the concentrations of transforming growth factor beta (TGFbeta) in human milk from individual women which is not readily explained by maternal factors such as smoking or illness. A potential correlate is the maternal plasma level of TGFbeta since changes in plasma concentration of TGFbeta in response to a number of pathological conditions have been well documented. The purpose of this study was to investigate the relationship between the concentration of TGFbeta1 and TGFbeta2 in a single sample of human milk and plasma obtained on the same day from 80 lactating mothers at 5 weeks postpartum. The concentration of TGFbeta1 and TGFbeta2 in the aqueous fraction of human milk ranged from 228 to 3542 pg/ml (647, 438-799; median, 25th-75th percentiles) and 98 to 13 855 pg/ml (955, 535-1999) respectively and in paired samples of plasma from 440 to 19 460 (4026, 3245-6656) and 92 to 1739 (620, 391-925) respectively. Thus, in milk the median ratio of TGFbeta1 to TGFbeta2 was 1:1.6 whereas the corresponding median ratio in plasma was 7:1. There was no correlation between the concentration of either isoform of TGFbeta in milk and the corresponding TGFbeta in plasma.

Nutritional effect of including egg yolk in the weaning diet of breast-fed and formula-fed infants: a randomized controlled trial.

BACKGROUND: Egg yolks can be a source of docosahexaenoic acid (DHA) and iron but are often associated with adverse consequences on plasma cholesterol. OBJECTIVE: Our goal was to investigate the effect of consumption of 4 egg yolks/wk on infant DHA status and hemoglobin, ferritin, and plasma cholesterol concentrations. Secondary outcomes included plasma iron, transferrin, and transferrin saturation. DESIGN: This was a randomized controlled trial comparing no dietary intervention, consumption of 4 regular egg yolks/wk, and consumption of 4 n-3 fatty acid-enriched egg yolks/wk in breast-fed and formula-fed infants from 6 to 12 mo of age. Erythrocyte DHA concentrations, cholesterol, and iron status were assessed at 6 and 12 mo of age. RESULTS: Of the 82 breast-fed infants recruited, 23 of 28 (no intervention), 23 of 27 (regular eggs), and 24 of 27 (n-3 eggs) completed the trial. Of the 79 formula-fed infants enrolled, 23 of 27 (no intervention), 24 of 26 (regular eggs), and 20 of 26 (n-3 eggs) completed the trial. Erythrocyte DHA concentrations were 30-40% higher after the n-3 egg intervention than after treatment with regular eggs or no eggs in both breast-fed and formula-fed infants. Egg treatment had no significant effect on plasma cholesterol, hemoglobin, ferritin, and transferrin but did result in improvements in plasma iron and transferrin saturation compared with no egg treatment. CONCLUSIONS: n-3 Fatty acid-enriched eggs may provide a means of increasing dietary DHA during the second 6 mo of life. Egg yolks may also be a useful source of iron during the weaning period and can be safely included in the weaning diet with no perturbations in plasma cholesterol.

A randomized trial of supplementation with docosahexaenoic acid-rich tuna oil and its effects on the human milk cytokines interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha.

BACKGROUND: Increased consumption of n-3 long-chain polyunsaturated fatty acids (PUFAs) has been recommended during pregnancy and lactation. The production of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs) can be modified by dietary n-3 PUFAs. OBJECTIVE: We sought to determine whether dietary supplementation of lactating women with docosahexaenoic acid (DHA) can modulate the concentration of cytokines in the aqueous phase of human milk and the production of cytokines by human milk cells (HMCs) and PBMCs. DESIGN: In this double-blind, prospective, randomized trial, mothers of healthy full-term infants were asked to consume daily a nutritional supplement of 2000 mg oil containing either placebo (n = 40), 300 mg DHA + 70 mg eicosapentaenoic acid (EPA; n = 40), or 600 mg DHA + 140 mg EPA (n = 40). The fatty acid composition of plasma, PBMCs, milk, and HMCs from lactating mothers at 4 wk postpartum was measured by gas chromatography. The concentration of interleukin 6 and tumor necrosis factor alpha in milk and the production of interleukin 1beta, tumor necrosis factor alpha, and interleukin 6 by PBMCs and HMCs after stimulation with lipopolysaccharide was measured by enzyme-linked immunosorbent assay. RESULTS: At 4 wk postpartum, 82 mothers were still breast-feeding their infants. DHA increases in maternal plasma, PBMCs, milk, and HMCs were proportional to dietary DHA. There was no relation between tissue DHA status and cytokine concentrations. CONCLUSIONS: Consumption of < or = 600 mg DHA and 140 mg EPA/d for 4 wk increased n-3 PUFA concentrations in relevant tissues but did not cause perturbations in cytokine concentrations in human milk.