Background Recommendations have been issued on healthy complementary feeding (CF) strategies for infants, to reduce food allergy. This is a study of routine guidance provided by Greek pediatricians on the timing of CF for healthy infants and those at high risk for allergy. Methods Pediatricians in Greece completed an anonymous online questionnaire covering demographic information and recommended CF, specifically the foods, preparation methods, supplements, time interval between introduction of new foods for infants at low and high risk for allergy, and foods delayed in the case of high allergy risk. Results The respondents (n=233) recommended introducing: at 6 months, fruits, starchy non-gluten-grains, vegetables, olive oil and meat; at 7 months, gluten-rich grains; at 8 months, yogurt, hard-boiled egg and legumes; at 8.5 months, fish; at 9 months, nuts. A longer interval between new foods (≥ 4 days) was recommended, for low-risk infants, by male pediatricians (p=0.04), and for infants at high risk of allergy, by pediatricians with no subspecialty (p<0.001) and those practicing in a rural/semi-urban area (p=0.002). Pediatric practice of < 15 years was a predictor for earlier introduction of egg, seafood, gluten-rich grains, legumes and nuts for infants at high risk of allergy, and parenthood and male sex for egg and grains. Conclusions Greek pediatricians use a food introduction schedule for CF of infants, and, although not explicitly recommended in current guidelines, they delay introduction of common food allergens and suggest longer time intervals between introduction of new foods, especially for infants at high risk of allergy.

Background: From early life, respiratory viruses are implicated in the development, exacerbation and persistence of respiratory conditions such as asthma. Complex dynamics between microbial communities and host immune responses, shape immune maturation and homeostasis, influencing health outcomes. We evaluated the hypothesis that the respiratory virome is linked to systemic immune responses, using peripheral blood and nasopharyngeal swab samples from preschool-age children in the PreDicta cohort. Methods: Peripheral blood mononuclear cells from 51 children (32 asthmatics, 19 healthy controls), participating in the 2-year multinational PreDicta cohort were cultured with bacterial (Bacterial-DNA, LPS) or viral (R848, Poly:IC, RV) stimuli. Supernatants were analyzed by Luminex for the presence of 22 relevant cytokines. Virome composition was obtained using untargeted high troughput sequencing of nasopharyngeal samples. The metagenomic data were used for the characterization of virome profiles and the presence of key viral families (Picornaviridae, Anelloviridae, Siphoviridae). These were correlated to cytokine secretion patterns, identified through hierarchical clustering and principal component analysis. Results: High spontaneous cytokine release was associated with increased presence of Prokaryotic virome profiles and reduced presence of Eukaryotic and Anellovirus profiles. Antibacterial responses did not correlate with specific viral families or virome profile, however, low antiviral responders had more Prokaryotic and less Eukaryotic virome profiles. Anelloviruses and Anellovirus-dominated profiles were equally distributed amongst immune response clusters. The presence of Picornaviridae and Siphoviridae was associated with low interferon-λ responses. Asthma or allergy did not modify these correlations. Conclusions: Antiviral cytokines responses at a systemic level reflect the upper airway virome composition. Individuals with low innate interferon responses have higher abundance of Picornaviruses (mostly Rhinoviruses) and bacteriophages. Bacteriophages, particularly Siphoviridae appear to be sensitive sensors of host antimicrobial capacity, while Anelloviruses are not affected by TLR-induced immune responses.

This systematic review evaluates the potential therapeutic options for desensitization of patients with IgE-mediated tree nut allergy, focusing, but not limited to, on immunotherapy. We searched three bibliographic databases for studies published until July 2022 for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, and almond) with allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT) or subcutaneous (SCIT) delivery, or with other disease-modifying treatments. We included 26 studies, but the heterogeneity of the studies prevented pooling and meta-analysis. Immunotherapy with hazel pollen extracts might benefit patients with a secondary nut allergy due to cross-reactivity with PR-10 or profilin panallergens but is unlikely to be beneficial in patients with a severe nut allergy caused by seed storage proteins. Sublingual immunotherapy has a moderate efficacy but a favorable safety profile. Oral immunotherapy (OIT), single, or multi-nut, with or without omalizumab, is the most studied approach. In general, tree nut OIT is effective in conferring protection from accidental exposures, with safety similar to that demonstrated by peanut OIT. The observed cross-desensitization between tree nuts straightly affects the management options for multi-nut allergic patients.

Background The maturation of innate immune responses in health and atopy is still incompletely understood. Methods We aimed to evaluate age-related trajectories of the TLR3 and TLR7/8 pathways across the lifespan and whether these differ between healthy and atopic individuals. Peripheral blood mononuclear cells (PBMCs) were isolated from 39 otherwise healthy atopic and 39 non-atopic subjects, aged 0-45 years. Selected cytokines involved in antiviral responses were measured by Luminex in culture supernatants of poly(I:C)- and R848-stimulated PBMCs. The non-parametric correlation between age and cytokine expression and differences in developmental trajectories between healthy and atopic were estimated. Patterns of cytokine development were identified with principal component analysis. Results Normal innate immune maturation entails significant and progressive age-related changes in the production of IL-1β, TNF-α, MIP-1β, MCP-3, IP-10, IL-10, IL-12p70 and IFN-γ upon TLR3 and/or TLR7/8 stimulation. Individual cytokines made small contributions to the observed variability; chemokines MCP-3 and IP-10 were key contributors. The development of these pathways deviated in atopic subjects with significant differences observed in the trajectories of IL-1β, MIP-1β and IL-10 synthesis. Conclusion TLR3 and TLR7/8 pathways mature during childhood, while atopy is associated with an abnormal maturation pattern. Suboptimal responses in Th1, inflammatory cytokine and chemokine production may be implicated in poor antiviral immunity in atopics, while deficient maturation of IL-10 producing capacity in the breaking of tolerance.