A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce.

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta-analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed using random-effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower-middle, 12 in upper-middle, and only two in high-income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta-analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta-analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high-income countries.

Current options in the management of tree nut allergy: A systematic review and narrative synthesis.

Tree nut allergy is a lifelong and potentially life-threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions symptomatically. To evaluate potential therapeutic options for desensitizing patients with IgE-mediated tree nut allergy, we systematically searched three bibliographic databases for studies published until January 2024. We looked for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, almond, pecan, macadamia nut, and brazil nut). We focused on allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT), or subcutaneous (SCIT) delivery, or other disease-modifying treatments. We found 19 studies that met our criteria: 3 studies investigated sublingual immunotherapy, 5 studied oral immunotherapy to a single tree nut, and 6 used multi-food oral immunotherapy with or without omalizumab. The remaining studies investigated the effectiveness of monoclonal antibodies or IgE-immunoadsorption in multi-food allergic patients, including patients with tree nut allergy. The heterogeneity of the studies prevented pooling and meta-analysis. Oral immunotherapy, single or multi-nut, with or without omalizumab, was the most studied approach and appears effective in conferring protection from accidental exposures. Omalizumab monotherapy is the only approved alternative management for reducing allergic reactions that may occur with accidental exposure.

Levels of IgE sensitization drive symptom thresholds in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common respiratory disease encompassing a variety of phenotypes. Patients can be sensitized to 1 or more allergens. There are indications that polysensitization is associated with more severe disease. However, the extent to which the level of sensitization is associated with clinical disease variability, underlying the distinct nature of AR from AR+ conjunctivitis or AR+ asthma, is not known. OBJECTIVE: To evaluate phenotypical differences between monosensitized and polysensitized patients with AR and to quantify their symptomatic variability. METHODS: A total of 565 patients with a confirmed diagnosis of AR were included in this cross-sectional study. Of those, 155 were monosensitized and 410 were polysensitized. Interactions between sensitization levels and the reporting of different symptoms of AR and co-morbidities, disease duration, and impact were assessed. Furthermore, patients were stratified into monosensitized, oligosensitized, and polysensitized to assess whether the effect of sensitization on the phenotype was ranked. RESULTS: Polysensitized patients reported itchy eyes significantly more often (P = .001) and had a higher number of ocular (P = .005), itch-related (P = .036), and total symptoms (P = .007) than monosensitized patients. In addition, polysensitized adults and children more often reported wheeze (P = .015) and throat-clearing (P = .04), respectively. Polysensitization was associated with more burdensome AR based on a visual analog scale (P = .005). Increased sensitization level was reflected in more itchy eyes, a higher number of ocular, itch-related, and total number of symptoms, and disease burden. CONCLUSION: With an increasing number of sensitizations, patients with AR experience an increased diversity of symptoms. Multimorbidity-related symptoms increase with sensitization rank, suggesting organ-specific thresholds.

Respiratory virome profiles reflect antiviral immune responses.

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 and 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 analysed by Luminex for the presence of 22 relevant cytokines. Virome composition was obtained using untargeted high throughput 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 among immune response clusters. The presence of Picornaviridae and Siphoviridae was associated with low interferon-λ responses. Asthma or allergy did not modify these correlations. CONCLUSION: Antiviral cytokine 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 correlated with TLR-induced immune responses.

The role of respiratory syncytial virus- and rhinovirus-induced bronchiolitis in recurrent wheeze and asthma-A systematic review and meta-analysis.

INTRODUCTION: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis. RSV-induced bronchiolitis has been associated with preschool wheeze and asthma in cohort studies where the comparison groups consist of healthy infants. However, recent studies identify rhinovirus (RV)-induced bronchiolitis as a potentially stronger risk factor for recurrent wheeze and asthma. AIM: This systematic review and meta-analysis aimed to compare the associations of RSV- and RV-induced bronchiolitis with the development of preschool wheeze and childhood asthma. METHODS: We performed a systematic search of the published literature in five databases by using a MeSH term-based algorithm. Cohort studies that enrolled infants with bronchiolitis were included. The primary outcomes were recurrent wheeze and asthma diagnosis. Wald risk ratios and odds ratios (ORs) were estimated, along with their 95% confidence intervals (CIs). Individual and summary ORs were visualized with forest plots. RESULTS: There were 38 studies included in the meta-analysis. Meta-analysis of eight studies that had data on the association between infant bronchiolitis and recurrent wheeze showed that the RV-bronchiolitis group were more likely to develop recurrent wheeze than the RSV-bronchiolitis group (OR 4.11; 95% CI 2.24-7.56). Similarly, meta-analysis of the nine studies that had data on asthma development showed that the RV-bronchiolitis group were more likely to develop asthma (OR 2.72; 95% CI 1.48-4.99). CONCLUSION: This is the first meta-analysis that directly compares between-virus differences in the magnitude of virus-recurrent wheeze and virus-childhood asthma outcomes. RV-induced bronchiolitis was more strongly associated with the risk of developing wheeze and childhood asthma.

Differential maturation trajectories of innate antiviral immunity in health and atopy.

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 from birth to adulthood 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 subjects 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-1ß, TNF-α, MIP-1ß, 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-1ß, MIP-1ß, and IL-10 syntheses. 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. Moreover, the deficient maturation of IL-10 synthesis may be implicated in the breaking of tolerance, characterizing the onset of atopic disease.

Detection of local allergic rhinitis in children with chronic, difficult-to-treat, non-allergic rhinitis using multiple nasal provocation tests.

BACKGROUND: There is little evidence on the incidence and characteristics of local allergic rhinitis (LAR) in children. Most studies have included subjects with perennial rhinitis only, and results are based on the investigation of no more than three allergens per study. Our aim was to determine the proportion of children with LAR amongst children with chronic, difficult-to-treat, perennial or seasonal, rhinitis but no evidence of sensitization to aeroallergens, or other alternative diagnosis. METHODS: We performed multiple nasal provocation tests (M-NPTs) with four locally relevant aeroallergens (Phleum pratense, Olea europea, Alternaria alternata, and Dermatophagoides pteronyssinus) in children with absence of aeroallergen sensitization, seen during a calendar year in a specialized rhinitis clinic. We additionally performed single NPT to children with allergic rhinitis (AR; positive control group). The result of the NPT was based on symptoms and acoustic rhinometry. Identification of nasal hyper-reactivity (NHR) triggers was through a questionnaire. RESULTS: Local allergic rhinitis was confirmed in 29.2% (7/24) of the negative SPT/blood testing population. All but one of the children reacted to one allergen and one to two. All AR children had positive single NPT with results similar to the LAR. There were no differences in age at examination and rhinitis onset, gender distribution, family atopy, and past or current environment of residency, while the prevalence of reported NHR triggers was comparable amongst the three groups. CONCLUSION: This is the first pediatric study where the seasonal or perennial rhinitis population was thoroughly tested for LAR against four aeroallergens. LAR is present in a considerable proportion of children with chronic, difficult-to-treat rhinitis and no sensitization to aeroallergens, and therefore, the performance of NPT should be strongly considered in these cases. There were no distinct clinical characteristics between LAR, AR, and non-allergic rhinitis in children.

Long-Term Results of Combination Treatment with Single-Dose Ranibizumab plus Photodynamic Therapy for Retinal Angiomatous Proliferation.

PURPOSE: To present functional and anatomic outcomes of combination therapy with ranibizumab and photodynamic therapy (PDT) in a series of retinal angiomatous proliferation (RAP) cases. METHODS: A total of 17 eyes of 17 patients with RAP were included. Thirteen eyes were treatment naïve and 4 were already on ranibizumab monotherapy. Combined treatment with single-dose ranibizumab and PDT was performed on all treatment-naïve cases. Follow-up was performed every month for 6-38 months, using optical coherence tomography and indocyanine green angiography when necessary. RESULTS: Overall, 6 out of 7 treatment-naïve cases with stage I or II disease manifested complete angiographic resolution of the hot spot with a single injection of ranibizumab plus PDT. In stage III disease, 7 out of 10 eyes showed persistent leakage immediately after the combined treatment. The rate of hot spot occlusion was found to correlate with the stage of disease (p = 0.05). There was a significant improvement in posttreatment BCVA for all patients regardless of disease stage (p = 0.02), which was more evident in the earlier stages. Improvement was also greater for treatment-naïve patients (p = 0.03). The posttreatment improvement in BCVA was strongly correlated with hot spot occlusion (p < 0.001). CONCLUSIONS: Single-dose modified anti-VEGF treatment in combination with PDT may provide long-term regression at the initial stages of RAP.

Energy Efficient Monitoring of Metered Dose Inhaler Usage.

Life-long chronic inflammatory diseases of the airways, such as asthma and Chronic Obstructive Pulmonary Disease, are very common worldwide, affecting people of all ages, race and gender. One of the most important aspects for the effective management of asthma is medication adherence which is defined as the extent to which patients follow their prescribed action plan and use their inhaler correctly. Wireless telemonitoring of the medication adherence can facilitate early diagnosis and management of these diseases through the use of an accurate and energy efficient mHealth system. Therefore, low complexity audio compression schemes need to be integrated with high accuracy classification approaches for the assessment of adherence of patients that use of pressurized Metered Dose Inhalers (pMDIs). To this end, we propose a novel solution that enables the energy efficient monitoring of metered dose inhaler usage, by exploiting the specific characteristics of the reconstructed audio features at the receiver. Simulation studies, carried out with a large dataset of indoor & outdoor measurements have led to high levels of accuracy (98 %) utilizing only 2 % of the recorded audio samples at the receiver, demonstrating the potential of this method for the development of novel energy efficient inhalers and medical devices in the area of respiratory medicine.

Epigenetic modifications in cutaneous malignant melanoma: EZH2, H3K4me2, and H3K27me3 immunohistochemical expression is enhanced at the invasion front of the tumor.

Cancer stem cells and the misregulation of epigenetic modifications have been identified to possess a determinative role in carcinogenesis. The purpose of this study was to investigate the expression profile of EZH2 and H3K4me2 and H3K27me3, which constitute stem cell-like "bivalent" domains, in cutaneous malignant melanoma. A comparative analysis of their immunohistochemical expression between the invasion front (IF) and the inner tumor mass was also evaluated. Immunohistochemical methodology was performed on sections of 89 melanoma lesions from 79 patients. The 3 markers studied were identified in the cell nuclei of melanoma cells, nevus cells, and normal epidermal keratinocytes. A specific distribution pattern of H3K4me2 and H3K27me3 was found, as stronger levels were localized at the IF of the tumor (P = 0.034 and P < 0.01, respectively). In general, H3K4me2 and H3K27me3 levels were lower in metastatic with respect to primary melanoma cases (P = 0.0065 and P = 0.027, respectively). Advanced melanoma demonstrated significantly lower H3K4 immunohistochemical expression than did cases of lowest Clark level (I) (P = 0.038) or low Breslow depth (≤1 mm; P < 0.001). Furthermore, EZH2 expression in melanoma cells was higher compared with that in nevus cells (P = 0.02). A positive correlation between EZH2-H3K27me3 (P = 0.03) and H3K4me2-H3K27me3 (P < 0.01) in melanoma cells was also found. Our results suggest the possibility that combined immunohistochemical expression of EZH2, H3K4me2, and H3K27me3 might identify cancer cells with potential stem cell properties, particularly at the IF of this malignancy. This hypothesis should be further investigated, as many of the epigenetic changes are reversible via pharmacologic manipulations and new therapies, overpassing the resistance of advanced melanoma, may be developed.