Food Allergy Risk: A Comprehensive Review of Maternal Interventions for Food Allergy Prevention.

Food allergy represents a global health problem impacting patients' and caregivers' quality of life and contributing to increased healthcare costs. Efforts to identify preventive measures starting from pregnancy have recently intensified. This review aims to provide an overview of the role of maternal factors in food allergy prevention. Several studies indicate that avoiding food allergens during pregnancy does not reduce the risk of developing food allergies. International guidelines unanimously discourage avoidance diets due to potential adverse effects on essential nutrient intake and overall health for both women and children. Research on probiotics and prebiotics during pregnancy as preventive measures is promising, though evidence remains limited. Consequently, guidelines lack specific recommendations for their use in preventing food allergies. Similarly, given the absence of conclusive evidence, it is not possible to formulate definitive conclusions on the supplementation of vitamins, omega-3 fatty acids (n-3 PUFAs), and other antioxidant substances. A combination of maternal interventions, breastfeeding, and early introduction of foods to infants can reduce the risk of food allergies in the child. Further studies are needed to clarify the interaction between genetics, immunological pathways, and environmental factors.

Mini-Review on Vitamin D in Pediatric Population and its Role in Respiratory and Atopic Disorders.

In recent years, our comprehension of the function of vitamin D has significantly evolved. The ubiquitous presence of the vitamin D receptor (Vitamin D Receptor- VDR) in the body has led to its redefinition from a steroidal hormone primarily involved in skeletal functions to a hormone with pleiotropic effects, exerting its influence on the circulatory, nervous, and immune systems. This has prompted investigations into its potential use in preventing and treating chronic metabolic disorders, cardiovascular diseases, infections, and allergic and autoimmune diseases. This comprehensive review explores the various aspects of vitamin D, including its sources, synthesis, functions, and its impact on different physiological systems. It delves into the epidemiology of vitamin D deficiency, highlighting its occurrence among various age demographics and geographic regions. The impact of vitamin D on the immune system is also explored, elucidating its immunomodulatory and anti-inflammatory properties, particularly in the context of respiratory infections. The review discusses emerging evidence concerning the potential advantages of vitamin D in respiratory diseases, pediatric asthma and atopic dermatitis. It also addresses vitamin D supplementation recommendations for various pediatric populations, including term and preterm infants. The growing concern regarding the global health impacts of insufficient vitamin D levels necessitates further research to bridge gaps in knowledge, particularly in enhancing screening, prevention, and approaches to address vitamin D deficiency from birth onwards. In summary, this comprehensive overview underscores the vital role of vitamin D, highlighting the significance of understanding its multifaceted functions and the need for tailored supplementation strategies, especially in vulnerable populations.

Biological Therapies for Pediatric Atopic Dermatitis - A Review.

Atopic dermatitis (AD) is the most frequent chronic-recurrent inflammatory skin disease in the pediatric age. It has a complex and multifactorial pathogenesis: the two key actors are impaired skin barrier function and immune system dysregulation, which represent the main targets of AD therapy. Monoclonal antibodies have revolutionized the management of moderate-to-severe AD, by selective inhibition of key cytokines in the pathogenetic process. For this reason, there is great interest in exploring AD pathogenetic mechanisms to develop new therapeutic strategies. This review aims to summarize the most recent scientific evidence on available and future biological therapies for the treatment of pediatric AD, emphasizing the molecular mechanisms underlying their action.

Safety of biological therapy in children and adolescents with severe asthma during the COVID-19 pandemic: a case series.

Background and aim  It is still unclear whether patients with severe asthma are at greater risk of developing severe COVID-19, particularly pediatric allergic patients under biologic therapy. Studies targeting pediatric patients are currently limited; thus, this study aims to assess the clinical characteristics of young patients with severe asthma under biological therapies during the COVID-19 pandemic. Methods We collected data from February 2020 to April 2021. Patients with severe asthma treated with biological therapies (omalizumab and mepolizumab) have been enrolled. We described demographic data, clinical features, therapies, comorbidities, and laboratory findings for each patient. For patients who got COVID-19, we also described the severity of the disease, the need for hospitalization, and specific therapy. Results A total of 14 patients were included in the study, 11 (78.6%) of them under treatment with omalizumab and 3 (21.6%) with mepolizumab. We identified four patients (28.6%) who tested positive for SARS-CoV-2. Two patients treated with mepolizumab had an asymptomatic disease, and two patients treated with omalizumab had mild disease. Only one patient with mild COVID-19 required hospitalization and specific therapy because of severe obesity. Conclusions No differences regarding the SARS-CoV-2 infection have been found between the two treatments groups. Furthermore, any poor outcome has been observed, confirming the safety of biological therapies. The limited number of patients enrolled and the lack of a control group did not establish a significant risk for infections for these patients.

Addition of a nutraceutical to montelukast or inhaled steroid in the treatment of wheezing during COVID-19 pandemic: a multicenter, open-label, randomized controlled trial.

Background and aim Recurrent wheezing is often triggered by viral respiratory infections. The aims of our study were: i) to evaluate whether the addition of a nutraceutical (Leucodif®), could improve the efficacy of montelukast or inhaled steroids (ICS) compared to the single treatment; ii) to verify whether a treatment is more effective than another. Our study was biased by the COVID-19 pandemic, which resulted in a lockdown of almost two months in Italy. Methods The multicenter, open-label study enrolled 84 children aged 2-6 years diagnosed with recurrent wheezing and randomized them into four treatment arms for three months: ICS treatment; ii) montelukast; iii) montelukast + Leucodif; iv) ICS + Leucodif. Children were assessed at baseline and after one, two, and three months of treatment using the TRACK score for both the caregiver and the physician. Results Out of the 84 patients, 18 patients received ICS therapy, 22 patients ICS + Leucodif, 24 patients montelukast, and 20 patients montelukast + Leucodif. All four treatments resulted in a significant reduction in symptoms with no differences among the various groups. Conclusions Our study demonstrates that montelukast therapy appears to be equally effective as ICS therapy and that the addition of the nutraceutical Leucodif does not appear to improve the treatment outcome. However, in our opinion our study was strongly influenced and biased by the lockdown due to the COVID-19 pandemic, which inherently resulted in reduced exposure to the viruses that commonly cause respiratory infections in children.

Rapid response to dupilumab treatment in children with moderate-to-severe atopic dermatitis: A case series.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by itch and clinical heterogeneity regarding the age of onset, morphology, distribution, and severity of lesions. Severe AD has a significant impact on the quality of life of affected children and their caregivers. Children with moderate-severe AD inadequately controlled with topical therapy have limited treatment options, such as systemic corticosteroids or phototherapy, often prescribed as off-label treatments, often with unfavorable benefit-to-risk ratio adverse events. Dupilumab is a fully human monoclonal antibody with proven effectiveness and a relatively safe adverse effect profile in patients with type 2 inflammatory diseases, including AD. We report three pediatric cases of severe AD successfully treated with dupilumab.

Evaluation of safety and tolerability of a rush up-dosing allergen-specific immunotherapy with grass pollen, birch, hazel, and alder allergoid in children with allergic rhinoconjunctivitis, with or without asthma.

BACKGROUND Usually, the number of injections required to achieve the maintenance dose in subcutaneous immunotherapy (SCIT) is relatively small for some of the currently used allergens, but this may still be uncomfortable for patients, thus compromising adherence and compliance. OBJECTIVE The purpose of this study was to evaluate the safety and tolerability of a dose acceleration of a conventional induction schedule using an allergoid extract of grass pollen, birch, hazel, and alder, needed to achieve the ideal maintenance dose. METHODS In this open-label study, 34 patients with allergic rhinoconjunctivitis, with or without asthma, were treated with SCIT using an allergoid for grass pollen or birch or mix trees with an increase in accelerated induction dose comprising only 3 injections, one per week, compared to a conventional induction pattern in five injections (once a week). Safety determination was assessed by evaluating local and systemic adverse events. Tolerability was evaluated by patients and physicians who performed the treatment. RESULTS No treatment-related adverse events were observed in any of the patients undergoing rush SCIT. No local reactions, no systemic reactions of any degree (WAO Grade) have been observed. Tolerability has always been rated as very good by both patients and physician. CONCLUSIONS The induction phase, needed to achieve the monthly maintenance dose for a pollen extract, can be greatly accelerated, ensuring a tolerability comparable to that of the conventional schedule.

Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology.

The current systematic review presented and discussed the most recent studies on acute cough in pediatric age. After that, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to pediatric patients, such as infants, children, and adolescents, with acute cough. An acute cough is usually consequent to upper respiratory tract infections and is self-resolving within a few weeks. However, an acute cough may be bothersome, and therefore remedies are requested, mainly by the parents. An acute cough may significantly affect the quality of life of patients and their family.Several algorithms for the management of acute cough have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, and, also, in accordance to the Italian National Health System, which regularly follows the child from birth to all lifelong. Based on our findings, infants from 6 months, children, and adolescents with acute cough without cough pointers can be safely managed using well-known medications, preferably non-sedative agents, such as levodropropizine and/or natural compounds, including honey, glycerol, and herb-derived components.

Respiratory infections in allergic children: the preventive role of a multicomponent nutraceutical.

Allergic children with respiratory infections (RI) are a demanding challenge for the paediatrician. Antibiotic prescription represents a critical problem, mainly concerning the growing issue of resistance. To prevent RI would be therefore a goal in clinical practice. In this regard, modulation of immune system may have a critical role. The aim of the present study was to measure the number of respiratory infections and the use of antibiotics in two groups of children suffering from allergic rhinoconjunctivitis. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). The children were visited at baseline and after 1 year. The number of RI and of antibiotic courses was the primary outcomes. Children in AG reported a significant reduced number of RI and of antibiotic course in comparison with CG (p=0.01 and 0.002 respectively). In conclusion, the current study showed that a course with a multicomponent nutraceutical could reduce the number of respiratory infections and consequently the use of antibiotics in children with allergic rhinoconjunctivitis.

An update on biological therapies for pediatric allergic diseases.

Allergic diseases represent a global health burden. Patients with allergic diseases may experience disability, reduced quality of life and productivity, emotional distress, and social restrictions, especially in the most severe cases. Current advances in unveiling the pathogenesis of allergic disorders have paved the way for the development of novel therapeutic strategies. Biological drugs have been widely studied in pediatric allergic asthma, with strong evidence of efficacy and safety. Moreover, promising results derive from studies on other conditions such as atopic dermatitis, chronic spontaneous urticaria, and food allergy. This review analyzes recent evidence on the role of biologic therapies for allergic diseases, focusing on the pediatric age.

Small airways in children with allergic rhinoconjunctivitis: the potential role of a multicomponent nutraceutical.

Allergic rhinitis and asthma are closely linked. A progression from rhinitis to overt asthma is common. FEF25-75 is a spirometry parameter that could reflect small airways patency and could reliably predict early bronchial involvement in allergic rhinitis patients. MEF50 very strongly correlates with FEF25-75. The aim of this study was to evaluate possible spirometry change in two groups of children suffering from AR over time. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). The children were visited at baseline, at the end of the nutraceutical course, and after 1 year. FEV1, FVC, and MEF50 were the primary outcomes. After one year, children in AG had significantly higher MEF50 than CG children (p=0.009). In conclusion, the present study showed that a course with a multicomponent nutraceutical could prevent the MEF50 decline in children with allergic rhinoconjunctivitis.

Complementary treatment of allergic rhinoconjunctivitis: the role of the nutraceutical Lertal(R).

Nutraceuticals represent interesting therapeutic options in clinical practice. In this regard, a new compound has been designed: Lertal®. It contains quercetin, perilla extract, and vitamin D3. These agents exert anti-allergic and anti-inflammatory activities. This article reports and discusses the results of four clinical studies conducted in adult and paediatric patients suffering from AR. Outcomes provided evidence that Lertal® may significantly prevent clinical worsening when prescribed as add-on to continuous antihistaminic treatment and also prevent clinical exacerbations, such as the need of rescue medication, when used alone as preventive strategy in AR patients.

Biologics in Children with Allergic Diseases.

The prevalence of allergic diseases has been remarkably increased in the last decades. The global health burden of these conditions is substantial, since patients may experience disability, anxiety and emotional distress, social restrictions, and reduced quality of life and productivity, in particular, in the most severe cases. Recent advances in understanding the pathophysiology of allergic disorders have allowed identifying novel therapeutic strategies for the treatment of severe and uncontrolled allergic diseases. Although most studies have been performed in allergic asthma, biological drugs targeting other allergic diseases such as chronic spontaneous urticaria, atopic dermatitis, and food allergy are showing promising results. In this review, the most recent evidence on biologic therapies for allergic diseases, focusing on the pediatric age has been presented.

Upper Respiratory Tract Infection-Associated Acute Cough and the Urge to Cough: New Insights for Clinical Practice.

Upper respiratory tract infection (URTI)-associated acute cough is the most common symptom both in children and adults worldwide and causes economic and social problems with significant implications for the patient, the patient's family, and the health care system. New pathogenic mechanisms in acute cough, including the urge to cough (UTC) mechanisms, have been recently identified. The brainstem neural network, pharyngeal sensory innervation, airway mechanical stimulation, inflammatory mediators, and postnasal drip actively participate in the onset and maintenance of acute cough and the urge to cough phenomenon. However, there is still no effective pharmacological treatment capable of interfering with the pathophysiologic mechanisms involved in URTI-associated acute cough. Moreover, severe adverse events frequently occur in administering such cough medications, mainly in children. New evidence has been provided concerning polysaccharides, resins, and honey as potential cough relievers with high antitussive efficiency, effect on the UTC, and minimal side effects.

Biologics to Treat Severe Asthma in Children and Adolescents: A Practical Update.

Background: Severe asthma represents a significant challenge for children and adolescents. At the same time, it often places a burden on patients, caregivers, and society, mainly related to morbidity, mortality, and health care resources. In children and adolescents, severe asthma is mostly characterized by type 2 inflammation, which leads to bronchial eosinophilia that may be suppressed by corticosteroids. However, in this age group, a high dosage of inhaled corticosteroids combined with systemic corticosteroids sometimes results in unacceptable side effects, such as reduced growth velocity and reduced bone mineral density. Therefore, there is increasing and enthusiastic interest in today's biologics, including omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. There is growing evidence that they may be effective and safe add-on options for children and adolescents. In 2009, omalizumab was approved by the European Medicines Agency as the first available therapeutic option for allergic asthma in patients as young as 6 years of age, followed by a similar approval by the U.S. Food and Drug Administration in 2016. Previously, omalizumab was marketed for this indication in patients ≥ age 12. Subsequent biologics, namely mepolizumab, reslizumab, and benralizumab, are IL-5 targeted agents that are presently approved in some countries for severe eosinophilic asthma starting at 6 years of age. Dupilumab is targeted against the IL-4 receptor α-chain, and it has been approved in the United States and the European Union as an add-on maintenance therapy in patients ≥12 years of age. Conclusion: This review presents the most recent evidence on approved biologics for the treatment of severe asthma and discusses the unmet needs and future perspective, focusing on the pediatric and adolescent age groups.

A polycentric, randomized, parallel-group, study on Lertal®, a multicomponent nutraceutical, as preventive treatment in children with allergic rhinoconjunctivitis: phase II.

BACKGROUND: Lertal®, an oral nutraceutical, contains extract of Perilla, quercetin, and Vitamin D3. The current polycentric, randomized, parallel-group, controlled study aimed in the Phase II to evaluate the efficacy and safety of Lertal® in preventing allergic rhinitis (AR) exacerbations in children after the end of the pharmacological treatment phase. MATERIALS AND METHODS: One hundred twenty-eight children completed Phase II. Sixty-four children continued Lertal® treatment (Lertal® Group: LG) and 64 ones did not assume any medication (Observation Group: OG) for 4-12 weeks. The study endpoints were the number, intensity, and duration of AR exacerbations, and the length of symptom-free time. RESULTS: Children of LG halved the risk (HR = 0.54) of having AR exacerbation. Children of LG had significantly (p = 0.039) less AR exacerbations than OG children. In children with AR exacerbations, the total number of days in which each patient took at least one rescue medication was significantly (p = 0.018) lesser in LG children than OG ones. In the global population, the cumulative days treated with rescue medication was significantly (p < 0.0001) higher in OG than in LG. There was no clinically relevant adverse event. CONCLUSIONS: The present study documented that prolonged Lertal® assumption was safe and able to significantly reduce, such as halving, the risk of AR exacerbation, their duration and the use of rescue medications, after the suspension of the one-month antihistamine treatment. Therefore, Lertal® could be envisaged as an effective preventive treatment in AR children able to guarantee long symptom-free time. TRIAL REGISTRATION: Clinical trial registration: ClinicalTrials gov ID NCT03365648 .

A starch, glycyrretinic, zinc oxide and bisabolol based cream in the treatment of chronic mild-to-moderate atopic dermatitis in children: a three-center, assessor blinded trial.

BACKGROUND: Atopic dermatitis (AD) is a very common chronic inflammatory and eczematous skin condition characterized by flares and remissions. Skin barrier alteration or dysfunction is the most relevant patogenetic factor. Topical corticosteroids are the mainstay treatment of AD, especially during flare periods. The daily use of emollients and moisturizers is also considered a relevant adjunctive strategy to improve skin barrier function and skin appearance in AD patients. Long-term use of topical corticosteroids is associated with important drawbacks and side effects. A corticosteroid-free cream containing starch, glycyrretinic acid, zinc oxide and bisabolol (Dermamid™; Difa Cooper, Caronno Pertusella, Varese, Italy) has been designed for the treatment of acute eczematous conditions like diaper dermatitis. However, this formulation could be particularly suitable also for AD. We evaluated in a three-center, assessor-blinded prospective 6-week treatment trial the efficacy and tolerability of this cream in children with chronic mild-to-moderate atopic dermatitis. METHODS: A total of 30 children (mean age 5 years, 18 males and 12 females) with chronic mild to moderate AD, affecting face, lower and upper limbs or trunk, were enrolled after parents' written informed consent. Exclusion criteria were a condition of immunosuppression, acute flares or a positive history of allergy to one of the components of the cream. The primary outcome was the evolution total eczema severity score (TESS) calculated as the sum of the single eczema severity score for each body area involved. Single area Eczema Severity Score (ESS) was calculated assessing eczema, infiltration, lichenification and scraching lesions using a 4-point scale grade (with 0=no sign, and 4=severe sign). A secondary endpoint was the percentage of subjects reaching at least 50% of TESS reduction at week 6 in comparison with baseline. The TESS was evaluated at baseline and after 3 and 6 weeks of treatment (twice daily application) in an assessor-blind fashion. RESULTS: At baseline the mean (SD) TESS was 11.6 (4.7). TESS was reduced significantly (P=0.0001) to 5.7 (3) after 3 weeks (-51%), and to 3.0 (2.3) at week 6 (-74%). Similar reductions were observed for single area ESS values. The percentage of subjects with at least a >50% reduction of TESS value at the end of the study was 87%. The product was very well tolerated. Only for one patient a mild burning sensation at the application site was reported. All the subjects concluded the trial. CONCLUSIONS: This trial supports the efficacy and the tolerability of a corticosteroid-free cream containing starch, glycyrretinic acid and bisabolol in the treatment of chronic mild to moderate atopic dermatitis in children.