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Abstract Allergic rhinitis (AR) is the most frequent IgE-mediated disease, mainly in children and adolescents. Management of AR in the pediatric age may be heterogeneous, and the available guidelines do not adequately consider this issue. As a result, the Italian Society of Pediatric Allergy and Immunology (SIAIP) promoted a Delphi Consensus to define and evaluate the most relevant aspects of AR management in the pediatric setting in Italy. A qualified board of experts prepared a list of statements that a panel of Italian experts voted on using a web platform. Forty-two pediatricians participated. The results showed that all statements had consensus (> 80% of scores 4 + 5). In particular, there was awareness that AR is a type 2 inflammatory disease requiring adequate treatment. Topical drugs should be preferred, as they are better with cycles. Combined antihistamine/corticosteroid is also considered effective and safe in adolescents. In conclusion, AR deserves adequate attention and care. Current medications are safe and effective; treatment should be addressed to dampen type 2 inflammation and relieve complaints.

Abstract Pediatric asthma management is a compelling challenge for every pediatrician. Different aspects require attention and definition. The present Intersocietal Survey aimed to collect real-world experiences from a sample of Italian pediatricians. A web platform was used to collect anonymous answers to the survey questions. Four hundred four pediatricians participated in this initiative promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP), the Society of Preventive and Social Pediatrics (SIPPS), and the Federation of Italian Pediatricians (FIMP). The results showed an extensive participation of primary care pediatricians (72%). There was a large consensus about diagnostic criteria and medication choice. However, treatment duration and device choice were various. Adherence to guidelines on general aspects of practical clinical management was high. In conclusion, the present Intersocietal Survey confirmed that pediatric asthma management is rather satisfactory, even if further improvement should concern a more widespread use of ICS for acute asthma/wheezing attacks, a better definition of the duration of ICS and bronchodilator use, and hospital-primary care integration.

Gut microbiota plays an important role in maintaining respiratory health while providing protection against respiratory illnesses. However, the clinical role of probiotic strains in prevention and treatment of early-onset asthma is still debated. The present study aims to systematically review the available literature on the efficacy of probiotic supplementation, either alone or in combination with other treatments, in managing children with asthma. An electronic search was conducted across multiple databases including PubMed, Web of Science, and EMBASE. The articles reported in English, regardless of year of publication, were reviewed by independent authors for inclusion assessment. Randomized controlled studies evaluating the efficacy of probiotics in children with asthma were included in the study. Of the 203 articles reviewed, 16 were selected and summarized to provide a consistent review, and of these, eight studies reported the anti-asthmatic effects of the treatment with single and multi-strain probiotics alone, seven reported the use of probiotic strains in combination with other treatments, and one was a follow-up study. While some of the studies reported are well conducted and with promising results, no cumulative significant impact was seen for probiotic supplementation on disease parameters of asthma in children. However, the available literature is not sufficient to draw any solid conclusion about the possible use of probiotics in children with asthma, and it is necessary to expand this literature by conducting more well-designed randomized clinical trials to assess the effects of probiotic strains in children with asthma or carrying a high-risk of asthma.

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Respiratory infections are a relevant issue during infancy and childhood, constituting a major source of morbidity and imposing a substantial burden on healthcare systems. Conditions such as bronchiolitis, pneumonia, and influenza exemplify the gravity of these infections among pediatric populations. In the context of this health challenge, resveratrol, a naturally occurring polyphenolic antioxidant has emerged as a focal point of extensive research, known for its antioxidant, anti-inflammatory, and antimicrobial properties. This comprehensive review delves into the compound's extensive antimicrobial activities against a diverse range of bacteria and viruses, both as a standalone agent and in combination with conventional antibiotics. This compound exhibits notable antiviral activity against viruses implicated in severe respiratory infections, offering a potential therapeutic avenue. By exploring the antiviral mechanisms and highlighting the anti-inflammatory potential of resveratrol, this comprehensive overview contributes to a deeper understanding of its applicability in mitigating the complexities associated with pediatric respiratory infections.

Abstract Food supplements are defined as foodstuffs the purpose of which is to supplement the normal diet and which are concentrated sources of nutrients or other substances with a nutritional or physiological effect, often referred to as nutraceuticals, may exert benefit to the human body. Their use is increasing worldwide, including Europe and in Italy. However, some doctors are skeptical about their effectiveness and safety. This reluctance may depend on poor knowledge of the mechanisms of action and clinical evidence in literature. The Italian Society of Pediatric Allergy and Immunology (SIAIP) promoted the institution of an ad hoc Committee. The first initiative performed by this Committee was the administration of a questionnaire to the members of SIAIP. The results of this survey provided interesting results. Most pediatricians know the food supplement concept but frequently need help understanding the mechanisms of action. Most prescribe food supplements, mainly for preventing infections or enhancing immune defense. In addition, they prefer to use food supplements as cycles or add-on therapy. Finally, most participants like to attend events on this issue and contribute to new evidence through trials. In conclusion, this survey underscores the relevance of food supplement issues and attests to interest in this topic. However, there is a need to provide information and promote studies on this matter.

Abstract Resveratrol is a nonflavonoid polyphenolic compound with a chemical structure consisting of two aromatic rings linked by a methylene bridge. It exists in two primary isomers and has a broad range of desirable biological activities, including antioxidant, anti‐inflammatory, antidiabetic, cardioprotective, and antitumor activities. Some antioxidant properties of resveratrol are known with certainty, such as its potential to positively impact cardiovascular health, inflammation, and the metabolism. On the other hand, many uncertainties and controversies plague its efficacy, including issues related to its bioavailability, dosing, human clinical trial results, interactions with other food components and drugs, and individual variability. In brief, although promising results have been observed in in vitro and in vivo studies, the translation of these findings to human health remains uncertain. Many human clinical trials on resveratrol are ongoing or have proven inconclusive, making it challenging to definitively determine its efficacy for specific health conditions and its dose and duration of treatment. Resveratrol may interact with medications and have varying effects on individuals. In conclusion, it is essential to approach resveratrol with a balanced perspective, consulting with healthcare professionals, and considering the evolving scientific evidence when making decisions regarding its clinical use.

AIM: To evaluate the efficacy and tolerability of administering a combined therapy in patients with dry eye syndrome (DES) and associated laryngopharyngeal reflux (LPR). METHODS: The study was retrospective, open, observational, and conducted in a real-life setting. Patients had pathological symptom assessment in dry eye (SANDE) and reflux symptom index (RSI) at baseline. Patients were re-assessed after 1mo and at the end of treatment. The treatment consisted of a three-month course based on the combined therapy: Gastroftal eye drops, one drop three times a day, and Gastroftal tablets, two tablets after lunch and two tablets after dinner. Tear break-up-time (TBUT) test, Schirmer test, RSI, and SANDE questionnaire were evaluated. RESULTS: The study included 253 patients. The mean age was 58±11.19y. TBUT test score and Schirmer's test significantly increased (both P

Severe asthma (SA) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common phenotype in children and adolescents with SA. As a result, anti-inflammatory drugs, mainly corticosteroids (CSs), represent the first choice to reduce type 2 inflammation. However, SA patients may require high inhaled and oral CS doses to achieve and maintain asthma control. Some SA patients, despite the highest CS dosages, can even display uncontrolled asthma. Therefore, the biological era constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing against both IL-4 and IL-13, and has been approved for pediatric severe type 2 asthma. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with SA. There is convincing evidence that dupilumab is a safe and effective option in managing SA as it can reduce asthma exacerbations, reduce CS use, and improve lung function, asthma control, and quality of life, also for caregivers. However, a thorough diagnostic pathway is mandatory, mainly concerning phenotyping. In fact, the ideal eligible candidate is a child or adolescent with a type 2 allergic phenotype.

Childhood asthma constitutes a significant healthcare burden due to its chronic nature and prevalence, affecting approximately 5–10 % of the pediatric population. Asthma is often heterogeneous and characterized by chronic airway inflammation. It is classified into two main phenotypes based on airway inflammation: T2-high (eosinophilic) and T2-low (neutrophilic/pauci-granulocytic) phenotype. Allergic sensitization is commonly associated with T2-high asthma, involving T helper 2 and innate immunity cells and type 2-associated cytokines, including interleuikin-4 (IL-4), IL-5, and IL-13. Type 2 inflammation is characterized by eosinophilic infiltrate. Asthma and allergic rhinitis share common mechanisms, and their association, known as united airways disease, highlights the close interconnection between upper and lower airways. Effective allergic rhinitis control positively impacts asthma, emphasizing the importance of early identification and personalized therapeutic strategies. One is allergen immunotherapy, a disease-modifying approach demonstrating preventive and therapeutic efficacy in children. However, more research is needed to optimize pediatric allergic rhinitis management.

Allergic disorders are common diseases characterized by type 2 inflammation and typical symptoms. Although pharmacologic treatment can be effective, prolonged administration of drugs can be associated with adverse reactions and seldom reduction of effectiveness. Therefore, complementary medicine is widespread in clinical practice, mainly in pediatric settings, and pleasing to parents.Nutraceuticals, such as ''a food (or part of a food) that provides medical or health benefits, including the prevention and/or treatment of a disease,'' are commonly prescribed by pediatrics as well as self-prescription by parents. There is evidence that some components exert beneficial effects in allergic diseases. In this regard, the supplementation with some food supplements may significantly reduce symptom severity and functional parameters.Some compounds, including micronutrients, vitamins, probiotics, herbal medicines, could positively and safely be used in children with allergic diseases as add-on or preventive remedies. Nutraceuticals should not substitute drugs.

The prevalence of allergic rhinitis is rising, and it is impacting children’s growth and quality of life. To uncover unconventional treatment modalities, research was carried out to clarify the significance of novel components in the pathophysiology of allergic rhinitis. One of these elements was gut microbiota, which plays a crucial role in the development and evolution of allergic disorders. Specifically, dysbiosis, defined as impaired microbiota composition, characterizes allergic disorders. In light of this concept, probiotics (beneficial bacteria) may restore gut dysbiosis, rebalance the immune response, and indirectly influence the clinical course of allergic diseases. In this article, we discussed the role of the gut–lung axis in children and reported on new findings. We also reviewed the most relevant studies about probiotics in patients with allergic rhinitis.

Recurrent respiratory infections (RRIs) account for relevant economic and social implications and significantly affect family life. Local Bacteriotherapy (LB) represents an innovative option in preventing RRIs. Local bacteriotherapy consists of administering “good” and safe bacteria (probiotics) by nasal or oral route. In particular, two strains (Streptococcus salivarius 24SMB and Streptococcus oralis 89a) are commonly used. The present article presents and discusses the literature concerning LB. Infections of airways include the upper and lower respiratory tract. A series of clinical trials investigated the preventive role of LB in preventing upper and lower RIs. These studies demonstrated that LB safely reduced the prevalence and severity of RIs, the use of antibiotics, and absences from school. Therefore, Local Bacteriotherapy may be considered an interesting therapeutic option in RRI prevention.

Iron is a primary component of the human body and exerts many functions, mainly concerning red cells and the immune system. In addition, there is evidence that iron-deficiency anemia is associated with allergic diseases. Type 2 inflammation characterizes allergic diseases. Peripheral eosinophils are a reliable biomarker for type 2 inflammation. Therefore, the present study investigated the possible relationship between iron metabolism and peripheral eosinophils in a large population. Eosinophils also play important roles in immune and tissue homeostasis. A growing body of data suggests tissue eosinophils represent a plastic and heterogeneous population of functional sub-phenotypes, shaped by environmental (systemic and local) factors. The retrospective study included 2,795 subjects who were afferent to the Clinical Chemistry Analysis Laboratory during the year 2022. Men had higher peripheral eosinophil count than women (p

Allergic rhinitis (AR) is a widespread medical condition affecting up to 40% of the general population. Type 2 inflammation determines typical nasal symptoms. In addition, gut and respiratory dysbiosis are present in AR patients. Probiotics have several beneficial effects on immunity, inflammatory pathways, and anti-infective properties. Namely, probiotic supplementation could restore immune response, promote eubiosis, and switch off inflammation. Thus, probiotics have also been investigated in AR. In addition, there is accumulating evidence that some specific strains of probiotics may improve AR. Five meta-analyses on probiotics in AR management were consistently published in the first half of 2022. The conclusions, although not definitive, argue for the possible use of probiotics as part of an add-on strategy in managing patients with allergic rhinitis.

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.

Background Allergic asthma is an inflammatory disease characterized by a type 2 immune response. Pollens are a common cause of seasonal asthma. Allergic rhinitis (AR) frequently associates with asthma. The treatment usually aims at controlling inflammation and relieving symptoms. Inhaled corticosteroids are the most effective controller and short-acting b2-agonists (SABA) as a reliever for asthma. Oral antihistamines and nasal corticosteroids (NC) are the mainstays for AR. A multicomponent nutraceutical containing perilla, quercetin, and vitamin D3 significantly prevented AR exacerbations in children. Thus, the current study explored the add-on use in adult patients with mild persistent asthma and AR due to grass pollen allergy. Methods The treatment lasted three months. Asthma and AR symptoms, asthma control test, spirometry, nasal eosinophils, and use of rescue medications (SABA and NC) were evaluated in the previous grass season and throughout the treatment. All patients were treated with ciclesonide (320 mcg/day) and cetirizine (10 mg/day). Patients were randomly stratified into Group A, taking the nutraceutical, and Group B using the predetermined therapy. Results 90 patients (13-59 years old) were enrolled, and 84 completed the trial. Group A significantly improved all outcomes (p

Irritable Bowel Syndrome (IBS) is a common disease characterized by alternate symptoms (diarrhea and constipation) and intestinal gas overproduction. A new medical device (Fibergone®), containing Partially Hydrolyzed Guar Gum (PHGG) and Simethicone (SM) has been proposed for managing patients with bowel disorders. PHGG acts also as a prebiotic so increasing the Short-Chain Fatty Acid (SCFA) production, useful for intestinal physiology. This in vitro study investigated the effects exerted by PHGG+SM on SCFA production and their intestinal absorption following in vitro digestive process and fermentation model. An in vitro model evaluated the digestive process and fermentation using simulated digestive fluids and a human intestinal epithelium in vitro model derived from based on intestinal adenocarcinoma Caco-2 cells (ATCC, HTB-37TM) and organized as a functional monolayer on Transwell® inserts. PHGG+SM was added in experiments and compared with a control (non-treated). SCFA production and absorption were assessed. Viability and barrier integrity of the of the intestinal epithelium model were also evaluated. PHGG+SM significantly (p

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, β-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), β-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 β-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.

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

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.

Abstract Introduction Significant variations in the management of bronchiolitis are often recorded, and, in parallel, to recommend a univocal clinical approach is challenging and still questioned. This study is aimed to evaluate the diagnostic and therapeutic management of bronchiolitis in children adopted by Italian pediatricians following the national guidelines. Material and Methods A survey study was designed and carried out by sending an email an open‐ended questionnaire developed by an expert panel of the Scientific Board of the Italian Society of Pediatric Allergology and Immunology (SIAIP). Questions were designed according to the national intersociety consensus document on treatment and prevention of bronchiolitis in newborns and infants. Results Overall, 234 pediatricians were taking part in the study. When diagnosing bronchiolitis, only 44.01% (103/234) of participants correctly followed the national guidelines. All participants (100%) would perform laboratory tests and/or radiological exams. 44.01% administered oxygen (O2) when O2 saturation was minor than 92%. About the therapeutic regimen, marked discrepancies between national guidelines and recorded answers were reported. Indications for hospital admission and discharge criteria were in line with the national guidelines. Conclusions There is a significant practice variation in the management of acute bronchiolitis among Italian physicians. Some wrong attitudes need to be further discouraged, such use of diagnostic procedures and therapeutic approaches. Further research is urgently required to define the best management of patients with bronchiolitis and implement strategies to standardize care and improve the quality of care.

Abstract Colonoscopy, since it was first employed over 60 years ago, is now the gold standard method for visualizing the mucosa of the colon, but should be of good quality. Many factors affect quality, including the type of health service organization, type of facility, staff, equipment, patient characteristics, and bowel preparation (BP). The adequacy of bowel cleansing is critical, but, unfortunately, may be inadequate in up to one‐third of procedures. The current article will present and discuss the main BPs and their drawbacks, which include patient‐dependent and procedure‐dependent factors. Cleansing quality depends on the ease/complexity of solution preparation, volume, taste, and timing of consumption. Consequently, important positive factors include simple instructions, easy preparation of the solution, low volume, pleasant taste, short drinking time (e.g.

Introduction Acute upper respiratory infection (AURI) is the most common cause of postinfectious olfactory dysfunction (PIOD). Objective We investigated the prevalence of PIOD in a large group of patients reporting persistent smell impairment perception after the AURI resolution. Methods Olfactometry was performed within 1 month after the common cold resolution and after 1 year in 467 (299 males, mean age 41.7 years) outpatients. The Sniffin' Sticks olfactory test (Burghart instruments, Wedel, Germany) was used. Results Anosmia was documented in 28 (6%) patients, hyposmia in 33 (7%), and cacosmia in 55 (11.7%). After 1 year, PIOD improved in 82 (79.6%) patients re-tested. Conclusion The current study demonstrated that persistent olfactory dysfunction is a relevant symptom in patients with AURI, even though many patients had normal olfactometry. Thus, smell impairment deserves careful attention and requires objective documentation.

Respiratory tract infections (RTIs) are usually characterized by mucus hypersecretion. This condition may worsen and prolong symptoms and signs. For this reason, reducing mucus production and improving mucus removal represent relevant aspects of managing patients with RTIs. In this regard, mucoactive drugs may be effective. Mucoactive agents constitute a large class of compounds characterized by different mechanisms of action. Sobrerol is a monoterpene able to fluidify mucus, increase mucociliary clearance, and exert antioxidant activity. Sobrerol is available in various formulations (granules, syrup, nebulized, and suppository). Sobrerol has been on the market for over 50 years. Therefore, the present article revised the evidence concerning this compound and proposed new possible strategies. The literature analysis showed that several studies investigated the efficacy and safety of sobrerol in acute and chronic RTIs characterized by mucus hyperproduction. Seven pediatric studies have been conducted with favorable outcomes. However, the regulatory agencies recently reduced the treatment duration to three days. Therefore, a future study will test the hypothesis that a combination of oral and topical sobrerol could benefit children and adults with frequent respiratory tract infections. The rationale of this new approach is based on the concept that mucus accumulation could be a risk factor for increased susceptibility to infections.

Abstract The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic. Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

Abstract Background COVID-19 is an emerging issue that has significant consequences on psycho-social well-being. Methods In this regard, a survey was conducted on a large group of adolescents in Italy. The survey investigated four items: concerns and fears, information on the pandemic, provisions of public authorities (e.g., lockdown), and impact on everyday life. Results Adolescents actively participated in the survey. COVID-19 affected emotions and lifestyle. COVID-19 influenced relationships with peers and parents. There were regional differences. Conclusions The current research highlighted the remarkable, healthy, and certainly unexpected, emotional balance of the new generations in the face of a sudden, unpredictable phenomenon capable of jeopardizing life itself. While understanding the gravity of the phenomenon and willingly adapting to all the necessary precautions, the adolescents still seemed to express an excellent ability to manage situations of insecurity and to deal with unfavorable and adverse conditions by adapting to the new routine and finding alternative and innovative means of meeting their social and psychological needs.

Background. Type-2 inflammation commonly marks asthma in childhood. Also, gut and lung dysbiosis is detectable in patients with asthma. Strain-related probiotic supplementation may restore a physiological immune response, dampen airway inflammation, and repair dysbiosis. Therefore, the probiotics in pediatric asthma management (PROPAM) study is aimed at demonstrating that Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) mixture could reduce asthma exacerbations in children, followed in a primary care setting. Methods. The study was randomized, placebo-controlled, and double-blind. It involved 11 Italian primary care pediatricians. The probiotic mixture (containing Ligilactobacillus salivarius LS01 1×109 live cells and Bifidobacterium breve B632 1×109 live cells) or placebo was taken twice daily (1 sachet in the morning and 1 in the evening) for eight weeks and subsequently once daily for a further eight weeks. Outcomes included number, severity, and duration of asthma exacerbations, intensity of maintenance and as need treatments, and safety. Results. The per-protocol population included 422 children (mean age seven years, 240 males and 182 females). The probiotic mixture significantly reduced the number of asthmatic exacerbations (OR=3.17). In addition, the number of children with two exacerbations was less than a third in the active group (OR=3.65). Conclusions. This PROPAM study demonstrated that probiotic strains Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) were safe and significantly reduced by more than a third the frequency of asthma exacerbations. At present, the first-line treatment of asthma is still drug-based, but specific strains of probiotics may be auxiliary remedies.

Cataract surgery is widespread. The surgical procedure is associated with damage to the epithelial barrier and interruption of the corneal innervation. In addition, pathological events sustain signs and symptoms that may persist for a long time. Recently, a fixed combination of alpha-glycerylphosphorylcholine and D-Panthenol (Oftassiale) has been available as eye drops. The present study investigated the effects of an Oftassiale therapy in 20 patients undergoing cataract surgery. A comparison group included 20 patients treated with topical hyaluronic acid. Standard prophylactic and anti-inflammatory treatment was prescribed to all patients. Clinical signs and symptoms were assessed over time. In vivo confocal microscopy (IVCM) was performed accordingly. Oftassiale treatment significantly reduced clinical features and improved IVCM outcomes. In addition, therapy was well-tolerated, and no clinically significant adverse events occurred. In conclusion, this study confirmed that IVCM helps assess the tunnel after cataract surgery due to its ability to provide microscopic details in vivo. Topical therapy with alpha-glycerylphosphorylcholine and D-Panthenol eye drops promoted and stabilized the reepithelialization process. This fixed combination also accelerated and modulated the repair of the corneal innervation. Moreover, this treatment was well-tolerated and safe.

Vaccination against viral and bacterial pathogens represents a challenging issue in allergic subjects, mainly concerning patients undergoing allergen immunotherapy (AIT). For this reason, an international survey has been performed involving a panel of experts who responded to a series of questions, also concerning the COVID-19 impact on allergen immunotherapy and vaccinations.The results showed that co-administration of vaccines and AIT requires caution, mainly during the pandemic era. Moreover, the choice of AIT product should be oriented considering also the safety profile.

Abstract Cetirizine is a second-generation antihistamine, derived from the metabolism of hydroxyzine, highly specific for the H1 receptors, and with marked antiallergic properties. Although its history began more than 30 years ago, it remains one of the most used drugs in children with a leading role in the medical care of children with allergic diseases. Cetirizine use is licensed for paediatric patients for the treatment of allergic rhinitis, and chronic spontaneous urticaria, in Europe in children older than 2 years old and in the USA in children older than 6 months old. This review provides a practical update on the use of cetirizine in children and adolescents.

Abstract The upper airways (UA) should be considered as a functional unit. Current functional anatomy divides URT in three, mutually dependent, “junction boxes”: i) the ostio-meatal complex (OMC), ii) the spheno-ethmoidal recess (SER), and iii) the rhinopharynx (RP). Correct ventilation and effective mucociliary clearance of these sites significantly affect the healthy physiology of the entire respiratory system. The OMC, SER, and RP obstruction is the first pathogenic step in the inflammatory/infectious cascade of UA disorders. The inflammation of the respiratory mucosa is the main pathogenic factor for airway obstruction. Moreover, bacterial biofilm (a strategy modality of bacterial survival) is an important local cause of systemic antibiotic ineffectiveness, recurrent infections, and antibiotic resistance. Health microbiota guarantees UA wellness; on the contrary, dysbiosis promotes and worsens UA infections. Allergy, namely type 2 inflammation, is a common cause of UA obstruction such as promoting in turn infections. Fiberoptic endoscopy is a mandatory diagnostic tool in clinical practice. Nasal cytology, mainly concerning flow cytometry, allows defining rhinitis phenotypes so allowing a precision medicine approach. Several conventional therapeutic approaches are available, but efficacy and safety should be ever properly considered before the prescription. Also, complementary medicine plays a fruitful role in the management of UA diseases. National and real-world studies are reported and discussed as they may be useful in daily clinical practice.

Abstract Antihistamines are currently one of the most commonly administered categories of drugs. They are used to treat symptoms that are secondary to histamine release, which is typical of certain allergic conditions, including rhinitis, conjunctivitis, asthma, urticaria, and anaphylaxis. Cetirizine belongs to the second-generation family, so, it is very selective for peripheral H1 receptors, is potent and quickly relieves symptoms, exerts additional anti-allergic/anti-inflammatory effects, and is usually well-tolerated. It has been marketed 30 years ago. In these years, a remarkable body of evidence has been built. The current review provides a practical update on the use of cetirizine in clinical practice.

Abstract Tryptophan metabolic pathway is involved in pathogenic mechanisms of asthma. This study aimed to evaluate tryptophan metabolites and neopterin in a group of asthmatic children. Tryptophan metabolites and neopterin were measured in asthmatic children (121, 71 males, 50 females, mean age 11.6 + 3.2 years) and well-matched healthy controls (63, 32 males, 31 females, mean age 10.7 + 2.6 years). Tryptophan, kynurenine, and neopterin levels were significantly higher in asthmatic children than in healthy controls (p

Abstract 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

Background: The fern test is a method for assessing the characteristics of the nasal section in the treatment of patients with mucous dysfunction of the airway. Objective: The aim of this study was to investigate the role of the fern test in patients with rhinitis and to assess the classification of each type of rhinitis (types I-IV) in clinical practice. Methods: A cross-sectional study, which included consecutive patients from a third level Rhinology Unit, worked with 182 patients with rhinitis and 30 healthy subjects as control. The patients were subdivided according to their type of rhinitis: allergic rhinitis (59), infectious rhinitis (32), polyps (31), NARES (Non-allergic rhinitis with eosinophilia syndrome) (30) and NARNE (non-allergic rhinitis with neutrophils) (30). Results: The control subjects had only type I or II rhinitis, whereas patients with rhinitis usually showed type III or IV. Allergic rhinitis and nasal polyps had the most serious deterioration according to the fern test (type IV). Conclusions: The fern test is effective for assessing mucus alterations in patients with rhinitis and it could be included as a new parameter in the study of rhinitis as a potential biomarker of the function of damaged epithelial cells.

Background Acute bacterial conjunctivitis (ABC) is a relatively common medical condition caused by different pathogens. Although it rarely threatens vision, it is one of the most common conditions that cause red eyes and may be accompanied by discomfort and discharge. The study aimed to identify and characterize inpatients with ABC treated with topical antibiotics. Methods The EHRead® technology, based on natural language processing (NLP) and machine learning, was used to extract and analyze the clinical information in the electronic health records (EHRs) of antibiotic-treated patients with conjunctivitis and admitted to five hospitals in Spain between January 2014 and December 2018. Categorical variables were described by frequency, whereas numerical variables included the mean, standard deviation, median, and quartiles. Results From a source population of 2,071,812 adult patients who attended the participating hospitals in the study period, 11,110 patients diagnosed with acute conjunctivitis were identified. Six thousand five hundred eighty-three patients were treated with antibiotics, comprising the final study population. Microbiology was tested only on 12.1% of patients. Antibiotics, mainly tobramycin, and corticosteroids, mainly dexamethasone, were usually prescribed. NSAIDs were also used in about 50% of patients, always combined with antibiotics. Conclusions The present study provided a realistic representation of the hospital practice concerning managing patients with acute antibiotic-treated conjunctivitis. The diagnosis is usually based on the clinical ground, microbiology is rarely tested, few bacteria species are involved, and local antibiotics are frequently associated with corticosteroids and/or NSAIDs. Moreover, this study provided clinically relevant outcomes, based on new technology, that could be applied in clinical practice.

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.

The post-viral acute cough (PAC) is a widespread symptom, mainly in childhood and adolescence, and is usually associated with an acute upper respiratory infection, namely the common cold. The use of cough relievers is, therefore, impressive, as documented by the market data. There are many medical devices and dietary supplements for treating PAC, which contain non-pharmacological components. Ancient people used traditional herbs to treat PAC. Thus, a well-established tradition considers natural remedies as an effective and safe way to relieve PAC. The herbal agents include polyphenols, flavonoids, saponins, glucosides, and alkaloids. Also, the European Medicine Agency has recognized the value of plant extracts and other natural substances to treat PAC. Nevertheless, a few studies investigated the role of non-pharmacologic remedies for PAC. There is some evidence for honey, glycerol, Althea officinalis, Drosera rotundifolia, Grindelia, Hedera helix, Pelargonium sidoides, Sambucus nigra, Thymus vulgaris, hyaluronic acid, and saline solutions. However, further rigorous studies should confirm natural products' efficacy and safety to relieve PAC.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a common disorder. From a clinical and immunopathological point of view, different phenotypes and endotypes have been identified. As asthma is frequent comorbidity, biological agents for treating CRSwNP associated with asthma may be an attractive strategy. Biological agents have several mechanisms, such as antagonizing IgE, interleukin (IL) 4, IL-5, and IL-13. However, a workup is mandatory, mainly concerning pheno-endotyping. In this regard, clinical cytological grading (CCG) has been proposed as a useful tool to manage patients with CRSwNP as it allows us to define clinical and immunopathological phenotypes able to identify the ideal candidate for biologics. In particular, the mixed cellular pattern, such as eosinophils and mast cells, could be sensitive to anti-IL-4 agents. There is still a need for well-established indications, criteria of responsiveness, duration, and safety. Moreover, personalized medicine could be opportunely integrated and/or alternated with intranasal corticosteroids to prevent relevant adverse events.

To the Editor An elegant study reported dysmorphic cells and syncytia in the deceased's lungs for COVID-19. The authors reasonably considered that most of these syncytia-forming cells were pneumocytes, as identified by specific biomarkers. However, cellular dysmorphism and syncytia are pathological features common in other respiratory infections caused by different viruses, including the human respiratory syncytial virus (HRSV) and Epstein-Barr virus (EBV), as correctly documented...

Chronic rhinosinusitis (CRS) includes two main phenotypes: without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP). CRSwNP may be associated with comorbidity, mainly concerning asthma, aspirin intolerance, and allergy. CRSwNP patients may also be evaluated by clinical-cytological grading (CCG). The current study investigated the prevalence and characteristics of the different CCG and phenotypes in CRSwNP outpatients examined in clinical practice. This retrospective cross-sectional study enrolled 791 consecutive CRSwNP outpatients (424 males, mean age 48.8 years). In the total population, asthma was a common comorbidity (30.8%) as well as aspirin intolerance (24.8%), and allergy (50.8%). As concerns CCG-grading, 210 (26.5%) outpatients had low-grade, 366 (46.3%) medium, and 215 (27.2%) high. As regards cytological phenotypes, 87 (11%) had neutrophilic type, 371 (46.3%) eosinophilic, 112 (14.2%) mast cell, and 221 (27.9%) mixed. High-grade CCG was significantly associated with more frequent asthma, aspirin intolerance, allergy, recurrent surgery, and mixed cytological phenotype. Low-grade CCG was characterized by fewer comorbidities and operations, and neutrophilic phenotype. Therefore, the present study confirmed that CCG is a useful tool in the management of outpatients with CRSwNP. CRSwNP is frequently associated with asthma, aspirin intolerance, and allergy comorbidity. High-grade CCG is frequently characterized by a mixed cytological phenotype, thus, by more severe progress. These real-world outcomes underline that CRSwNP deserves adequate attention for careful management and optimal identification of the best-tailored therapy; CCG and cytological phenotyping could be fruitful tools in clinical practice. Asthma and aspirin intolerance should be adequately investigated in all CRS patients.