Role of biologics in severe food allergy.

PURPOSE OF REVIEW: This review examine the dynamic landscape of food allergy treatment within the context of emerging biologics. Our purpose is to comprehensively evaluate the potential benefits, challenges, and transformative impact associated with the utilization of biologics in comparison to conventional therapeutic modalities. RECENT FINDINGS: This document synthesizes recent scientific investigations to various biologics, such as omalizumab, ligelizumab, dupilumab, and tezepelumab, providing a nuanced understanding of their roles in oral immunotherapy, rapid desensitization, and overall food allergy management. Recent studies and clinical trials highlight the impact of anti-IgE treatment on food allergies, revealing critical findings such as dose-related efficacy, facilitation of rapid desensitization in peanut allergies, and the sustained positive outcomes observed in individuals with multifood allergies. SUMMARY: The use of biologics presents a groundbreaking approach in the treatment of food allergies. The multifaceted action of these agents, along with their potential to overcome the challenges associated with traditional therapies, marks a significant advancement. Despite the persisting challenges of economic constraints and the need for further safety studies, biologics offer a promising avenue for improving the quality of life for individuals with food allergies. Ongoing research and collaborative efforts are imperative to fully realize the transformative potential inherent in these emerging therapeutic frontiers.

Botanical Impurities in the Supply Chain: A New Allergenic Risk Exacerbated by Geopolitical Challenges.

BACKGROUND: The supply chains of food raw materials have recently been heavily influenced by geopolitical events. Products that came from, or transited through, areas currently in conflict are now preferentially supplied from alternative areas. These changes may entail risks for food safety. METHODS: We review the potential allergenicity of botanical impurities, specifically vegetable contaminants, with particular attention to the contamination of vegetable oils. We delve into the diverse types of botanical impurities, their sources, and the associated allergenic potential. Our analysis encompasses an evaluation of the regulatory framework governing botanical impurities in food labeling. RESULTS: Unintended plant-derived contaminants may manifest in raw materials during various stages of food production, processing, or storage, posing a risk of allergic reactions for individuals with established food allergies. Issues may arise from natural occurrence, cross-contamination in the supply chain, and contamination at during production. The food and food service industries are responsible for providing and preparing foods that are safe for people with food allergies: we address the challenges inherent in risk assessment of botanical impurities. CONCLUSIONS: The presence of botanical impurities emerges as a significant risk factor for food allergies in the 2020s. We advocate for regulatory authorities to fortify labeling requirements and develop robust risk assessment tools. These measures are necessary to enhance consumer awareness regarding the potential risks posed by these contaminants.

COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children.

In children, the factors that influence COVID-19 disease and its medium- and long-term effects are little known. Our investigation sought to evaluate the presence of comorbidity factors associated with respiratory long COVID manifestations in children and to study ultrasound abnormalities following SARS-CoV-2 infection. Children, who arrived at the 'Respiratory Diseases of Pediatric Interest Unit' at the Department of Woman, Child, and General and Specialized Surgery of the University of Campania 'Luigi Vanvitelli', were selected during the timeframe from September 2021 to October 2022. The children were diagnosed with a SARS-CoV-2 infection that occurred at least one month before the visit. All patients followed a COVID-19 follow-up protocol, developed by the Italian Society of Pediatric Respiratory Diseases (SIMRI), which included: collection of data regarding SARS-CoV-2 illness and history of known respiratory and allergic diseases; physical examination; BMI assessment; baseline spirometry and after bronchodilation test; six-minute walking test; and lung ultrasound (LUS). In a cohort of 104 participants with respiratory long COVID symptoms (64.7% male, average age 8.92 years), 46.1% had fever with other symptoms, and 1% required hospitalization. BMI analysis showed 58.4% of the cohort was overweight. The LUS was positive in 27.0% of cases. A significant BMI association was observed with COVID-19 symptoms and LUS score (p-value < 0.05). No associations were found with asthma or atopy.

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.

Record of strep throat infections in Italy: what is needed to know about penicillin allergy? The point of view from the Italian Society of Pediatric Allergy and Immunology (SIAIP).

Notifications of invasive group A streptococcal (iGAS) infections have significantly increased in many European Countries compared to the previous season. In Italy, there has been an increase in streptococcal pharyngitis and scarlet fever cases since January 2023, which sparked concerns about a GAS epidemic in the pediatric population. This rise may be ascribed to the GAS infection season that began earlier than usual (off-season outbreak) and the increase in the spread of respiratory viruses and viral coinfections that raised the risk of iGAS disease. Moreover, this phenomenon was also facilitated by increased travel after reduced GAS circulation during the COVID-19 pandemic.The increase in cases of GAS disease has raised some critical issues regarding the potential reactions to administering amoxicillin, the first-line antibiotic therapy, many of which have been erroneously labeled as "allergy."For these reasons, the Italian Society of Pediatric Allergy and Immunology (SIAIP) intends to provide simple clinical indications to help pediatricians manage GAS pharyngitis, discerning the allergic from non-allergic drug hypersensitivity.

Biological Drugs for the Treatment of Uncontrolled Severe Asthma in Children.

The introduction of biological drugs for the treatment of severe allergic asthma in children, almost twenty years ago, had a substantial impact on both the pathology's clinical course and the quality of life of the patients who receive treatment. Over the years, several molecules have been developed that inhibit molecular targets involved in the pathogenesis of the asthmatic disease. Biological drugs demonstrate a significant improvement in several key clinical parameters in patients with severe asthma. In this review, we provide a concise summary of the evidence on biological therapy for children and adolescents with severe asthma.

Anaphylaxis after Shrimp Intake in a European Pediatric Population: Role of Molecular Diagnostics and Implications for Novel Foods.

(1) Background: Tropomyosin is a major cause of shellfish allergy and anaphylaxis triggered by food. It acts as a pan-allergen, inducing cross-reactivity in insects, dust mites, crustaceans, and mollusks. Our study investigates anaphylaxis in children with asthma or atopic diseases after consuming tropomyosin-containing food. (2) Methods: We analyzed the molecular sensitization profiles of pediatric patients at the University of Campania 'Luigi Vanvitelli' from 2017 to 2021, with conditions such as allergic rhinitis, asthma, atopic dermatitis, urticaria, and food allergies. (3) Results: Out of a total of 253 patients aged 1 to 18 years (167 males, 86 females), 21 patients (8.3%) experienced anaphylaxis after shrimp ingestion. All 21 (100%) were sensitized to various tropomyosins: Pen m 1 (100%), Der p 10 (90.5%), Ani s 3 (81%), and Bla g 7 (76.2%). Clinical symptoms included allergic asthma (76.2%), atopic dermatitis (61.9%), urticaria (38.1%), and allergic rhinitis (38.1%). (4) Conclusions: Crustaceans and mollusks are major allergens in Italy and Europe, requiring mandatory declaration on food labels. Italian pediatric patients demonstrated significant anaphylaxis after consuming shrimp, often accompanied by multiple atopic disorders such as asthma, rhinitis, and atopic dermatitis. Considering the cross-reactivity of tropomyosin among various invertebrates and the emergence of 'novel foods' containing insect flours in Europe, there is ongoing debate about introducing precautionary labeling for these products.

Acute pharyngitis in children and adults: descriptive comparison of current recommendations from national and international guidelines and future perspectives.

This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A ß-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates.    Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.

Time effect of dupilumab to treat severe uncontrolled asthma in adolescents: A pilot study.

BACKGROUND: Dupilumab is a new biological drug approved for the treatment of type 2 inflammatory diseases, such as asthma. Dupilumab is a fully humanized monoclonal antibody that acts against both interleukin-4 and interleukin-13 receptors. This study evaluated the time--dependent effect of dupilumab on asthma exacerbations and quality of life in adolescents with uncontrolled severe asthma. MATERIALS AND METHODS: Five adolescents suffering from uncontrolled severe asthma and treated with dupilumab were recruited. All subjects were evaluated for 4, 12, and 24 weeks after the first dose of dupilumab. Outcome measures included lung function, fractional exhaled nitric oxide, asthma control and quality of life assessed by validated questionnaires (Asthma Control Test and Asthma Control Questionnaire). RESULTS: The quality of life improved quickly after 4 weeks of treatment and 80% of adolescents halved the dose of inhaled corticosteroids necessary to control asthma symptoms. These results were still maintained for 24 weeks after start of the therapy. None of the patients had any asthma exacerbation during the study period. CONCLUSION: Results of this study demonstrated that dupilumab was quickly effective to reduce asthma exacerbation and ameliorate quality of life in severe asthmatic adolescents.

IgE-Mediated and Non-IgE-Mediated Fish Allergy in Pediatric Age: A Holistic Approach-A Consensus by Diagnostic Commission of the Italian Society of Pediatric Allergy and Immunology.

Fish is one of the "big nine" foods triggering allergic reactions. For this reason, fish allergens must be accurately specified on food labels. Fish allergy affects less than 1% of the world population, but a higher prevalence is observed in pediatric cohorts, up to 7%. Parvalbumin is the main fish allergen found in the muscles. In childhood, sensitization to fish allergens occurs most frequently through the ingestion of fish, rarely transcutaneously or by inhalation. Fish allergy symptoms usually appear within two hours of the allergen contact. The diagnosis begins with the collection of the history. If it is suggestive of fish allergy, prick tests or the measurement of serum-specific IgE should be performed to confirm the suspicion. The oral food challenge is the gold standard for the diagnosis. It is not recommended in case of a severe allergic reaction. It is important to make a differential diagnosis with anisakiasis or scombroid poisoning, which have overlapping clinical features but differ in pathogenesis. Traditionally, managing fish allergy involves avoiding the triggering species (sometimes all bony fish species) and requires an action plan for accidental exposures. The present review will analyze IgE- and non-IgE-mediated fish allergy in children from epidemiology, pathogenesis to clinical features. Moreover, clinical management will be addressed with a particular focus on potential nutritional deficiencies.

Time effect of dupilumab to treat severe uncontrolled asthma in adolescents: A pilot study

Background: Dupilumab is a new biological drug approved for the treatment of type 2 inflammatory diseases, such as asthma. Dupilumab is a fully humanized monoclonal antibody that acts against both interleukin-4 and interleukin-13 receptors. This study evaluated the time--dependent effect of dupilumab on asthma exacerbations and quality of life in adolescents with uncontrolled severe asthma. Materials and Methods: Five adolescents suffering from uncontrolled severe asthma and treated with dupilumab were recruited. All subjects were evaluated for 4, 12, and 24 weeks after the first dose of dupilumab. Outcome measures included lung function, fractional exhaled nitric oxide, asthma control and quality of life assessed by validated questionnaires (Asthma Control Test and Asthma Control Questionnaire). Results: The quality of life improved quickly after 4 weeks of treatment and 80% of adolescents halved the dose of inhaled corticosteroids necessary to control asthma symptoms. These results were still maintained for 24 weeks after start of the therapy. None of the patients had any asthma exacerbation during the study period. Conclusion: Results of this study demonstrated that dupilumab was quickly effective to reduce asthma exacerbation and ameliorate quality of life in severe asthmatic adolescents (AU)

Behavioral and Sleep Disorders in Children and Adolescents following COVID-19 Disease: A Case-Control Study.

INTRODUCTION: Recent studies show that neuropsychiatric disorders are the most frequent sequelae of COVID-19 in children. PURPOSE: Our work aimed to evaluate the impact of SARS-CoV-2 infection on behavior and sleep in children and adolescents. MATERIALS AND METHODS: We enrolled 107 patients aged 1.5-18 years who contracted COVID-19 between one year and one month prior to data collection, referred to the University of Campania Luigi Vanvitelli in Italy. We asked their parents to complete two standardized questionnaires for the assessment of behavior (Child Behavior CheckList (CBCL)) and sleep (Sleep Disturbance Scale for Children (SLDS)). We analysed and compared the results with a control group (pre-COVID-19 pandemic). RESULTS: In the COVID-19 group, the major results were found for sleep breathing disorders, sleep-wake transition disorders and disorders of initiating and maintaining sleep for the SDSC questionnaire, and internalizing scale, total scale and anxiety/depression for the CBCL questionnaire. The comparison of the CBCL results of the cases with the controls revealed statistically significant differences for the following items: internalizing scale, externalizing scale, somatic complaints, total score, thought problems [(p < 0.01)], anxious/depressed problems and withdrawn [(p < 0.001)]. CONCLUSIONS: COVID-19 has impacted children's and adolescents' mental health. Adolescents were the most affected patient group for internalizing problems, including anxiety and depression.

Evaluation of Der p 10 in a Cohort of European Children: Role of Molecular Diagnostics and Clinical Features.

Background: Allergy toward the dust mite is steadily increasing on the European continent. This sensitization may be a risk factor for developing sensitization to other mite molecules such as tropomyosin Der p 10. This molecule often correlates with food allergy and the risk of anaphylaxis after ingesting mollusks and shrimps. Materials and Methods: We analyzed the sensitization profiles by ImmunoCAP ISAC of pediatric patients from 2017 to 2021. The patients under investigation were being followed for atopic disorders such as allergic asthma and food allergies. The study aimed to analyze the prevalence of sensitization toward Der p 10 in our pediatric population and assess the related clinical symptoms and reactions after ingestion of foods containing tropomyosins. Results: This study included 253 patients; 53% were sensitized toward Der p 1 and Der p 2; 10.4% were also sensitized to Der p 10. Assessing patients sensitized to Der p 1 or Der p 2, and Der p 10, we observed that 78.6% were affected by asthma (p < 0.005) and had a history of prior anaphylaxis after ingestion of shrimp or shellfish (p < 0.0001). Conclusion: The component-resolved diagnosis gave us a deeper understanding of patients' molecular sensitization profiles. Our study showed that a fair proportion of children sensitive to Der p 1 or Der p 2 are also sensitive to Der p 10. However, many patients sensitized to all three molecules had a high risk of asthma and anaphylaxis. Therefore, the assessment of Der p 10 sensitization should be considered in atopic patients with sensitization to Der p 1 and Der p 2 to avoid encountering possible adverse reactions after ingesting foods containing tropomyosins.

Food-labeling issues for severe food-allergic consumers.

PURPOSE OF REVIEW: Food label represent the primary and only source of information before consuming a food product. Deputy government agencies on five continents require allergenic ingredients to be declared when used in prepackaged foods to assist patients in identifying allergenic foods and to help them to choose wisely. Unfortunately, the mandatory allergen list and legislation regarding food labels and reference doses is not uniform and varies by country. This may add difficulties to food-allergic patients, especially those with severe food allergy. RECENT FINDINGS: A new definition of food allergy severity (the DEFASE grid, developed by the World Allergy Organization), aims to assist clinicians in the identification of the at-risk patients. The FASTER ACT and Natasha's Laws has made important improvements such as the entry of sesame as a major allergen in the United States, and increased evidence of allergens on the food label within prepackaged for direct sale (PPDS) in the UK. The recent introduction of Vital 3.0 brought important new features such as an updated reference doses for many foods. SUMMARY: Currently, there are still considerable differences regarding food labels in different countries. Growing public and scientific attention to the problem promises to increase the food safety for allergens. Among the next improvements, we expect a reconsideration of the food reference doses, a harmonization of the food oral challenge process, and the promulgation of regulatory rules for the precautionary labeling.

Sensitization to nsLTP: A Retrospective Study in An Italian Pediatric Population over the Last Decade.

Background: Food allergy is common in the Mediterranean, especially concerning lipid transfer proteins (LTPs) allergy. LTPs are widespread plant food allergens in fruits, vegetables, nuts, pollen, and latex. Also, LTPs are prevalent food allergens in the Mediterranean area. They can sensitize via the gastrointestinal tract and cause a wide range of conditions: from mild reactions, such as oral allergy syndrome, to severe reactions, such as anaphylaxis. LTP allergy in the adult population is well described in the literature, concerning both the prevalence and clinical characteristics. However, there is poor knowledge about its prevalence and clinical manifestation in children living in the Mediterranean. Materials and Methods: This study, including 800 children aged from 1 to 18 years, investigated the prevalence of 8 different molecules of nonspecific LTP over time in an Italian pediatric population visited over the last 11 years. Results: About 52% of the test population was sensitized to at least one LTP molecule. For all the LTPs analyzed, sensitization increased over time. In particular, using the years 2010 through 2020 as a comparison, the major increases were observed for the LTPs of the English walnut Jug r 3, the peanut Ara h 9, and the plane tree Pla a 3 (about 50%); the increase of the LTP of the Hazelnut Cor a 8 was about 36%, and that of the LTP of the artemisia Art v 3 was approximately 30%. Conclusions: The latest evidence in the literature indicates an increase in food allergy prevalence in the general population, including children. Therefore, the present survey represents an interesting perspective about the pediatric population of the Mediterranean area, exploring the trend of LTP allergy.

An Overview on the Primary Factors That Contribute to Non-Allergic Asthma in Children.

The prevalence of non-allergic asthma in childhood is low, peaking in late adulthood. It is triggered by factors other than allergens, like cold and dry air, respiratory infections, hormonal changes, smoke and air pollution. In the literature, there are few studies that describe non-allergic asthma in pediatric age. Even though it is a less common disorder in kids, it is crucial to identify the causes in order to keep asthma under control, particularly in patients not responding to conventional treatments. In this review, we discuss non-IgE-mediated forms of asthma, collecting the latest research on etiopathogenesis and treatment.

Vitamin D status can affect COVID-19 outcomes also in pediatric population.

Background: vitamin D influences the immune system and the inflammatory response. It is known that vitamin D supplementation reduces the risk of acute respiratory tract infection. In the last two years, many researchers have investigated vitamin D's role in the pathophysiology of COVID-19 disease. Results: the findings obtained from clinical trials and systematic reviews highlight that most patients with COVID-19 have decreased vitamin D levels and low levels of vitamin D increase the risk of severe disease. This evidence seems to be also confirmed in the pediatric population. Conclusions: further studies (systematic review and meta-analysis) conducted on children are needed to confirm that vitamin D affects COVID-19 outcomes and to determine the effectiveness of supplementation and the appropriate dose, duration and mode of administration.