Food allergies (FAs) in children have become increasingly prevalent. While early life factors such as gut microbiome disruptions have been implicated, the association between neonatal antibiotic exposure and subsequent FAs remains a topic of ongoing debate. This nationwide cohort study aimed to investigate the impact of neonatal antibiotic exposure on the development of childhood FA. This population-based retrospective cohort study analyzed data from Clalit-Healthcare-Services, Israel’s largest state-mandated healthcare provider. The cohort included neonates (aged 0–60 days) admitted with fever between 2011 and 2018. Patients with confirmed infectious etiologies were excluded. The cohort was divided into two groups: those who received systemic antibiotics (Antibiotic ( +)) and those who did not (Antibiotic ( −)). FA cases were identified using ICD-9 codes up to age 6. Multivariate logistic regression and survival analysis models were utilized and adjusted for inflammatory markers, maternal atopy, and socioeconomic status. Among 2780 neonates, 1220 received antibiotics, while 1560 did not. The incidence of FAs was significantly higher in the Antibiotic ( +) group compared to the Antibiotic ( −) group (2.5% vs. 1.3%, P = 0.02). Adjusted analysis revealed that systemic antibiotic exposure during the neonatal period was associated with a threefold increased risk of FA up to age 6 (OR = 2.89, 95% CI = 1.34–6.92, P = 0.01). Conclusions : This study provides strong evidence linking neonatal antibiotic exposure to an increased risk of childhood FAs, particularly in the first 2 years of life. The findings highlight the importance of judicious antibiotic use in young infants. What is Known: • Early-life gut microbiome disruption is linked to an increased risk of food allergies (FA). • Antibiotic use in infancy may contribute to FA, but the impact of neonatal antibiotics remains unclear. What is New: • In this large nationwide cohort, neonatal antibiotic exposure was associated with a nearly threefold increased risk of FA by age six, highlighting the need for careful antibiotic use in young infants.

INTRODUCTION:Antibiotics are frequently prescribed in preschool wheezing episodes and acute asthma exacerbations (AAEs), even though antibiotics are not recommended as standard AAE treatment. OBJECTIVE:To systematically present relevant literature about the clinical effects of antibiotics for AAE and conclude with recommendations. METHODS:Systematic search was conducted in Medline ALL, Embase, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. Primary outcomes included AAE duration and length of hospital stay, while secondary outcomes incorporated AAE severity, treatment failure, AAE recurrence risk, spirometry, health costs, and adverse events. SELECTION CRITERIA:Randomised controlled trials and cohort studies were included if they investigated the clinical effect of antibiotics in AAE compared to placebo/standard care. RESULTS:Fifteen studies were included. Evidence for clinical effects of antibiotics in AAE treatment is scarce. Macrolides seem to shorten AAE duration in children; for adults, there is a lack of data. Antibiotics were associated with a longer hospital admission in retrospective observational studies, without evidence in randomised trials. Procalcitonin-guided treatment led to a reduction of antibiotic prescriptions without adverse outcomes. CONCLUSION:Limited evidence is available that macrolides shorten AAE duration in preschool wheezers. For other age groups, there is no clear evidence of beneficial effects of antibiotics.

BACKGROUND:Previous studies identified early-life antibiotic exposure as a risk factor for childhood asthma. However, this association may be confounded by an indication, as antibiotics are often prescribed for respiratory infections, which themselves promote asthma. To mitigate this bias, we aim to assess the unique contribution of postnatal antibiotic therapy, given to non-infected infants for maternal indication, on childhood asthma risk. METHODS:We screened electronic medical records to identify healthy full-term infants born during 2006-2018 to mothers with a positive group B streptococcus (GBS) vaginal culture. Infants with postnatal respiratory symptoms/pneumonia or positive blood/cerebrospinal fluid cultures were excluded. The primary outcome was an asthma diagnosis by age 6 years. We fitted a multivariable quasi-Poisson regression model to assess the unique contribution of antibiotic treatment to asthma diagnosis. As a validation step, we utilized a propensity model in which infants treated with antibiotics were matched 1:3 with infants not treated. RESULTS:The cohort included 14,807 infants, of whom 311 received antibiotics. After controlling for potential confounders, postnatal antibiotic exposure was associated with higher asthma risk (adjusted risk ratio [aRR] = 1.3, 95%; confidence interval [CI] 1.04-1.61, p = .017). Higher asthma risk was validated in the propensity model (aRR = 1.49, 95% CI 1.12-1.96 p = .005). Postnatal antibiotic therapy was also associated with secondary outcomes such as the short-acting beta-ag use (aRR = 1.13, 95% CI 0.99-1.28, p = .072) and allergic rhinitis diagnosis (aRR = 3.00, 95% CI 1.43-6.30, p = .003). CONCLUSIONS:Postnatal antibiotic therapy administrated for maternal GBS, not confounded by infants' infections, was associated with higher childhood asthma risk.

Milk allergy is among the most common food allergies in children. Most children with milk allergy can tolerate baked milk (BM) because the extensive heating abolishes the tertiary structure of the protein and the conformational IgE-binding epitopes. Children with milk allergy who have IgE antibodies, which are predominantly directed against conformational epitopes, and of lower affinity, are more likely to tolerate BM and achieve tolerance to fresh milk by school age. The immune system of these children is characterized by progressive immunomodulation, resulting in a reduction in casein and milk-specific IgE levels and an increase in casein-specific IgG4 levels.

BACKGROUND:Early life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits. OBJECTIVE:To investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW). METHODS:A total of 200 otherwise healthy 1- to 18-month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10 mg/kg daily for 7 days followed by 5 mg/kg daily for 7 days) or placebo. Infants were followed for 2 to 4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of the study treatment), and after 6 months. RESULTS:Upper airway MMP-9 levels were highly correlated with IL-8 levels at all 3 time points: randomization, day 14, and 6 months (r = 0.80; P < .0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (P = .0085), but no longer different after 6 months. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (P = .49, .39, respectively). CONCLUSION:Azithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV. TRIAL REGISTRATION:This study is a secondary analysis of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial registered at Clinicaltrials.gov (NCT02911935).

• This analysis identified associations between the fecal microbiome of mothers during pregnancy and offspring at ages 3– 6 months, 1 and 3 years with childhood asthma phenotypes

BACKGROUND: Accumulating evidence suggests that the upper airway bacterial microbiota is implicated in asthma inception, severity, and exacerbation. Unlike bacterial microbiota, the role of the upper airway fungal microbiome (mycobiome) in asthma control is poorly understood.RESEARCH QUESTION: What are the upper airway fungal colonization patterns among children with asthma and their relationship with subsequent loss of asthma control and exacerbation of asthma? STUDY DESIGN AND METHODS: The study was coupled with the Step Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (ClinicalTrials.gov Identifier: NCT02066129) clinical trial. The upper airway mycobiome was investigated using Internal transcribed spacer 1 (ITS1) sequencing of nasal blow samples collected from children with asthma when asthma was well controlled (baseline, n = 194) and during early signs of loss of asthma control (yellow zone [YZ], n = 107).RESULTS: At baseline, 499 fungal genera were detected in the upper airway samples, with two commensal fungal species, Malassezia globosa and Malassezia restricta, being most dominant. The relative abundance of Malassezia species varies by age, BMI, and race. Higher relative abundance of M globosa at baseline was associated with lower risk of future YZ episodes (P = .038) and longer time to development of first YZ episode (P = .022). Higher relative abundance of M globosa at YZ episode was associated with lower risk of progression from YZ episode to severe asthma exacerbation (P = .04). The upper airway mycobiome underwent significant changes from baseline to YZ episode, and increased fungal diversity was correlated highly with increased bacterial diversity (r = 0.41).INTERPRETATION: The upper airway commensal mycobiome is associated with future asthma control. This work highlights the importance of the mycobiota in asthma control and may contribute to the development of fungi-based markers to predict asthma exacerbation.

Asthma is associated with significant morbidity. The gut microbiome has been shown to effect asthma development and exacerbation. In this study, we tested an oral supplement containing Boswellia serrata (Indian frankincense) tree resin on allergic pulmonary inflammation and gut microbiome. An OVA based allergic airway model was used and mice were orally gavaged 100 mg/kg of Boswellia serrata as a supplementation throughout asthma sensitization and challenge. Treated mice showed significant weight loss, lower total lung leukocytes, eosinophil and Th2 cytokines, improved histology scoring and reduced reactivity to methacholine challenge. Asthmatic mice without Boswellia serrata supplementation showed a decrease in overall bacterial diversity, while treated mice were protected against loss. Boswellia serrata treated mice had a significant increase in Bifidobacterium, which was identified as Bifidobacterium pseudolongum. Oral administration of B. pseudolongum also reduced airway inflammation, suggesting Boswellia serrata may work as an anti-asthma agent via increases in B. pseudolongum from prebiotic influences.

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 weeks, and an observational phase of 18–48 months. Two hundred participants were enrolled during three consecutive RSV seasons beginning in the fall of 2016 and were randomized to receive oral azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for an additional 7 days, or matched placebo. The study hypothesis is that in infants hospitalized with RSV bronchiolitis, the addition of azithromycin therapy to routine bronchiolitis care would reduce the likelihood of developing post-RSV recurrent wheeze (≥3 episodes). The primary clinical outcome is the occurrence of a third episode of wheezing, which is evaluated every other month by phone questionnaires and during yearly in-person visits. A secondary objective of the APW-RSV II clinical trial is to examine how azithromycin therapy changes the upper airway microbiome composition, and to determine if these changes are related to the occurrence of post-RSV RW. Microbiome composition is characterized in nasal wash samples obtained before and after the study treatments. This clinical trial may identify the first effective intervention applied during severe RSV bronchiolitis to reduce the risk of post-RSV RW and ultimately asthma.

Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated food allergy characterized by delayed gastrointestinal symptoms such as vomiting and diarrhea. Severe acute FPIES reaction may result in dehydration, hypotension, and metabolic acidosis.1 The most common food that causes FPIES is cow's milk, although other foods have been described as causing FPIES. Current guidelines recommend avoiding the culprit food and conducting a reevaluation by an oral food challenge (OFC) at least 12 months after the initial reaction.