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.

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.

Treatment of Allergic Rhinitis in Clinical Practice.

Allergic rhinitis is a prevalent condition among children, with its occurrence reaching up to 40% of the general population in some geographical areas. A type 2 immunity sustains allergic rhinitis. Consequently, type 2 inflammation leads to eosinophilic infiltrate of the nasal mucosa. Allergic inflammation causes the symptom occurrence. Typical nasal symptoms include nasal itching, sneezing, watery rhinorrhea, and nasal congestion. Nasal congestion depends on vasodilation and increased mucus production. These conditions result in nasal obstruction. Nasal obstruction is closely associated with type 2 inflammation. Allergic rhinitis usually occurs in association with other allergic conditions, in particular allergic conjunctivitis and asthma. The effective management of allergic rhinitis involves avoiding triggering allergens and employing pharmacological treatments as per ARIA guidelines. These treatments may include intranasal/oral antihistamines or/and nasal corticosteroids. In particular, antihistamines are particularly indicated for symptoms consequent to mediators' release, mainly concerning histamine. These histamine-dependent symptoms include itching, sneezing, and rhinorrhea. Nasal obstruction, being associated with inflammation, is responsive to corticosteroids, administered mostly intranasally. The fixed combination of a topical antihistamine plus a topical corticosteroid is very effective, but is indicated for adolescents only. However, nasal lavage is safe, cheap, and adequate, thus its use is prevalent. Namely, nasal lavage allows to remove secretions, allergens, mediators. In addition, hypertonic solutions exert a decongestant activity. On the other hand, the allergen-specific immunotherapy is still the only causal treatment. Nutraceuticals have also been used to relieve symptoms. The objective of this review is to explore and compare the traditional and new therapeutic approaches for pollen-induced allergic rhinitis in children.

A Practical Update on Pediatric Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an emerging atopic disease of unknown etiology limited to the esophagus. The pathogenesis is still understood and is likely characterized by type 2 inflammation. Food allergens are the primary triggers of EoE that stimulate inflammatory cells through an impaired esophageal barrier. In children and adolescents, clinical presentation varies with age and mainly includes food refusal, recurrent vomiting, failure to thrive, abdominal/epigastric pain, dysphagia, and food impaction. Upper-gastrointestinal endoscopy is the gold standard for diagnosing and monitoring EoE. EoE therapy aims to achieve clinical, endoscopic, and histological ("deep") remission; prevent esophageal fibrosis; and improve quality of life. In pediatrics, the cornerstones of therapy are proton pump inhibitors, topical steroids (swallowed fluticasone and viscous budesonide), and food elimination diets. In recent years, much progress has been made in understanding EoE pathogenesis, characterizing the clinical and molecular heterogeneity, and identifying new therapeutic approaches. Notably, clinical, molecular, endoscopic, and histological features reflect and influence the evolution of inflammation over time and the response to currently available treatments. Therefore, different EoE phenotypes and endotypes have recently been recognized. Dupilumab recently was approved by FDA and EMA as the first biological therapy for adolescents (≥12 years) and adults with active EoE, but other biologics are still under consideration. Due to its chronic course, EoE management requires long-term therapy, a multidisciplinary approach, and regular follow-ups.

Updates in the diagnosis and practical management of allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) is a widespread disease that can be associated with other conditions, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on the history and documentation of sensitization, such as the production of allergen-specific IgE, preferably using molecular diagnostics. Treatments are based on patient education, non-pharmacological and pharmacological remedies, allergen-specific immunotherapy (AIT), and surgery. Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. AREAS COVERED: This review discusses current and emerging management strategies for AR, covering pharmacological and non-pharmacological remedies, AIT, and biologics in selected cases with associated severe asthma. However, AIT presently remains the unique causal treatment for AR. EXPERT OPINION: The management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered in the fixed association between intranasal antihistamines and corticosteroids, probiotics and other natural substances, and new formulations (tablets) of AIT.

The Practical Role of FEF25-75 in Young Patients with Allergic Rhinitis.

Allergic rhinitis (AR) is a relevant risk factor asthma as it may frequently precede asthma onset. There is evidence that lung function may be early impaired in AR patients. In this regard, the forced expiratory flow at 25%-75% of vital capacity (FEF25-75) could be a reliable marker of bronchial impairment in AR. Therefore, the present study investigated the practical role of FEF25-75 in young people with AR. The parameters included history, body mass index (BMI), lung function, bronchial hyperresponsiveness (BHR), and fractional exhaled nitric oxide (FeNO). This cross-sectional study included 759 patients (74 females and 685 males, mean age of 29.2 years) suffering from AR. The study demonstrated a significant association between low FEF25-75 values and BMI (OR 0.80), FEV1 (OR 1.29), FEV1/FVC (OR 1.71), and BHR (OR 0.11). Stratifying the patients on the basis of the presence (or absence) of BHR, sensitization to house dust mites (OR 1.81), AR duration (OR 1.08), FEF25-75 (OR 0.94), and FeNO (OR 1.08) were associated with BHR. Stratifying patients based on high FeNO values (>50 ppb), BHR was associated with high FeNO (OR 39). In conclusion, the present study showed that FEF25-75 was associated with low FEV1 and FEV1/FVC and BHR in AR patients. Therefore, spirometry should be considered in the long-term workup of patients with allergic rhinitis as impaired FEF25-75 might suggest an initial progression toward asthma.

Molecular Allergy Diagnostics in Children with Cow's Milk Allergy: Prediction of Oral Food Challenge Response in Clinical Practice.

Background: Cow's milk allergy (CMA) is the most common food allergy in early childhood. Children with CMA require a precise and punctual diagnosis. Oral food challenge (OFC) is the gold-standard procedure for diagnosing allergies, but it is laborious and requires a particular setting. The aim of the study was to identify the cutoff value of serum allergen-specific IgE values able to predict a positive response to OFC. Methods: Children with suspected CMA performed OFC with cow's milk (CM) or derivatives. Total IgE and specific IgE to raw CM, α-lactalbumin, ß-lactoglobulin, and casein were measured. Results: Seventy-two children performed OFC, and 30 (41.6%) had a positive response. The significant predictive factors were sensitization to raw CM extract (p = 0.03), α-lactalbumin (p = 0.013), ß-lactoglobulin (p = 0.09), and casein (p = 0.019). The cutoff was, respectively: 5.13 kUA/L for raw CM, 1.47 for α-lactalbumin, 1.35 for ß-lactoglobulin, and 4.87 for casein. Conclusions: This study allowed us to define a set of cutoff values for CM protein-specific IgE. However, these cutoffs should be interpreted not as a diagnostic tool for CMA but only predictive of response to OFC in a specific territory. Thus, the practical message may be that a value above the cutoff allows a good approximation to identify children to be started on OFC.

Hyperthyroidism in a 15-year-old adolescent treated with Dupilumab for severe allergic asthma and atopic dermatitis.

Dupilumab is a biologic, acting on IL-4 and IL-13 pathways. Dupilumab has a pediatric indication for treating severe asthma and atopic dermatitis. We report a pediatric case concerning paucisymptomatic, transient, and self-resolving hyperthyroidism. The updated literature includes the case of an adult patient who reported with hyperthyroidism, which was transient and self-resolving. Despite that these cases were transient and self-resolving, we would suggest that thyroid function assessment could be included in the follow-up of patients treated with Dupilumab. Dupilumab discontinuation is not required pending endocrinological assessment, mainly if there is an optimal clinical response to the biologic.

Hyperthyroidism in a 15-year-old adolescent treated with Dupilumab for severe allergic asthma and atopic dermatitis

Dupilumab is a biologic, acting on IL-4 and IL-13 pathways. Dupilumab has a pediatric indication for treating severe asthma and atopic dermatitis. We report a pediatric case concerning paucisymptomatic, transient, and self-resolving hyperthyroidism. The updated literature includes the case of an adult patient who reported with hyperthyroidism, which was transient and self-resolving. Despite that these cases were transient and self-resolving, we would suggest that thyroid function assessment could be included in the follow-up of patients treated with Dupilumab. Dupilumab discontinuation is not required pending endocrinological assessment, mainly if there is an optimal clinical response to the biologic (AU)

Oral Immunotherapy for Children with Cow's Milk Allergy: A Practical Approach.

Cow milk allergy (CMA) is a prevalent disease in childhood. Natural history is usually favorable as CMA can disappear by school age in many subjects. Diagnosis corresponds to treatment, as an elimination diet is a solution. However, cow's milk (CM) is real food, hardly replaceable. Thus, CM reintroduction represents a demanding challenge in clinical practice. The induction of CM tolerance could be achievable using oral immunotherapy (OIT), such as the administration of increasing milk quantities until reaching tolerance. However, the OIT schedule and procedure need to be better standardized, and performance may vary widely. Therefore, the present study reports the practical experience of a third-level pediatric allergy center in managing children with CMA and submitting them to OIT. OFC and OIT are relatively safe procedures as the reaction rate is low. Almost two-thirds of the OIT subjects tolerated CM. Reactions were associated with high IgE levels. Therefore, the present experience, developed by a qualified center, may suggest and propose a practical approach for managing children with CMA. After the initial workup, including a thorough history, physical examination, and laboratory tests, OFC and, when indicated, OIT could be performed in most children with CMA.

Role of FEF25-75 in managing children with newly-diagnosed asthma in clinical practice.

Background Reversible bronchial obstruction characterizes asthma. Spirometry is the gold standard to assess airflow, and FEV1 is the most reliable parameter in this regard. However, many children with asthma have FEV1 within the normal range despite uncontrolled asthma and worsening. Therefore, FEF25-75 has been proposed as a valuable marker of early airflow impairment. This study aimed at investigating FEF25-75 in a cohort of children with newly diagnosed asthma. Methods 381 children (122 females, mean age 11.6 years) were consecutively visited and had a new asthma diagnosis. In addition, Spirometry, type-2 phenotyping, asthma control assessment, and ACT were performed. Results 72 (18.9%) asthmatic children had impaired FEF25-75, such as <65% of predicted. Low FEF25-75 was associated with lower FVC and FEV1/FVC values (OR 1.11 and 1.32, respectively). Children with normal FEV1 but impaired FEF25-75 had more frequently uncontrolled asthma (15.8% vs. 32.4%) than children with both parameters within the normal range. Conclusions FEF25-75 deserves adequate and careful consideration in children with asthma, and the presence of impaired FEF25-75 values suggests a more compelling approach.

Probiotics in Children with Asthma.

A type-2 immune response usually sustains wheezing and asthma in children. In addition, dysbiosis of digestive and respiratory tracts is detectable in patients with wheezing and asthma. Probiotics may rebalance immune response, repair dysbiosis, and mitigate airway inflammation. As a result, probiotics may prevent asthma and wheezing relapse. There is evidence that some probiotic strains may improve asthma outcomes in children. In this context, the PROPAM study provided evidence that two specific strains significantly prevented asthma exacerbations and wheezing episodes. Therefore, oral probiotics could be used as add-on asthma therapy in managing children with asthma, but the choice should be based on documented evidence.

Comparing available treatments for pollen-induced allergic rhinitis in children.

INTRODUCTION: Pollen-induced allergic rhinitis (PIAR) is a widespread disease in children, and its prevalence is rapidly evolving. In addition, it may be associated with other atopic diseases, in particular asthma. In most cases, PIAR can be treated effectively by avoiding exposure to responsible allergens and using symptomatic treatments, including intranasal/oral antihistamines or/and nasal corticosteroids, according to ARIA guidelines. In recent decades, new medicines have been studied and developed: allergen-specific immunotherapy (AIT), anti-IgE antibodies, and probiotics. In addition, nutraceuticals have also been used as add-on treatments. This review aims to discuss and compare the old and new therapeutic strategies for PIAR in children. AREAS COVERED: Allergic rhinitis is a type 2 inflammatory disease. The management of patients with PIAR entails medications, AIT, and ancillary therapies. In addition, children with PIAR and associated severe asthma may be inclusively treated with biologics. Namely, subjects with allergic comorbidities could benefit from biological agents. However, AIT presently remains the unique causal treatment for PIAR. EXPERT OPINION: New strategies may include combined treatments, mainly concerning fixed associations with antihistamines and corticosteroids, nutraceutical products, and new AIT formulations.