An updated reappraisal of dupilumab in children and adolescents with moderate-severe atopic dermatitis.

Atopic dermatitis (AD) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common inflammatory pathway in children and adolescents with AD. Anti-inflammatory drugs, mainly corticosteroids (CS) and immunomodulant agents are the primary therapeutic approach to dampening type 2 inflammation. However, AD patients may require long-term high CS doses or drug combinations with possibly significant adverse effects to achieve and maintain disease control. In this regard, the advent of biologics constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing both IL-4 and IL-13 and is approved for pediatric severe AD. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with AD. There is convincing evidence that dupilumab is safe and effective in managing AD. It can reduce skin lesions and associated itching, reduce the need for additional medications, and improve disease control and quality of life. However, a thorough diagnostic pathway is mandatory, especially considering the different AD phenotypes. The ideal eligible candidate is a child or adolescent with AD requiring systemic treatment because of severe clinical manifestations and impaired quality of life.

Tablet allergen immunotherapy: the anaphylaxis issue.

For the first time 15 years ago, tablet allergen immunotherapy (T-AIT) formulations were approved by regulatory agencies for treating allergic rhinitis caused by grass pollen in adults and children aged >5 years. Extensive evidences existed about effectiveness and safety of AIT. However, the safety profile is particularly compelling in children. Generally, T-AIT causes local reactions, mostly in the oral cavity, that are usually mild-to-moderate and often self-resolving. However, systemic allergic reactions are also observed with T-AIT, anaphylaxis representing the most fearsome adverse event, considering that it occurs in subjects treated for allergic rhinitis. Therefore, we conducted a literature search of patients reporting anaphylaxis because of T-AIT. Nine cases of anaphylactic reactions were reported in literature. Notably, no death was reported using T-AIT. This outcome was very important as it underscored the substantial safety of T-AIT. However, T-AIT deserves careful attention, mainly in the pediatric population. In this regard, after the first report of anaphylactic reaction at the first administration of T-AIT, manufacturers recommended that the first dose should be administered in a medical facility in the presence of staff with experience in managing anaphylaxis and the patient should be observed for at least 30 min. Interestingly, reported anaphylactic reactions were due to grass pollen extracts, with no report concerning other allergen extracts. However, it is relevant to note that anaphylactic reactions because of T-AIT are not reported in recent years.

Managing children with frequent respiratory infections and associated wheezing: a preliminary randomized study with a new multicomponent nasal spray.

BACKGROUND: Preschoolers frequently have respiratory infections (RIs), which may cause wheezing in some subjects. Type 2 polarization may favor increased susceptibility to RIs and associated wheezing. Non-pharmacological remedies are garnering increasing interest as possible add-on therapies. The present preliminary study investigated the efficacy and safety of a new multi-component nasal spray in preschoolers with frequent RIs and associated wheezing. METHODS: Some preschoolers with these characteristics randomly took this product, containing lactoferrin, dipotassium glycyrrhizinate, carboxymethyl-beta-glucan, and vitamins C and D3 (Saflovir), two sprays per nostril twice daily for 3 months. Other children were randomly treated only with standard therapy. Outcomes included the number of RIs and wheezing episodes, use of medications, and severity of clinical manifestations. RESULTS: Preschoolers treated add-on with this multicomponent product experienced fewer RIs and used fewer beta-2 agonists than untreated children (P = 0.01 and 0.029, respectively). CONCLUSIONS: This preliminary study demonstrated that a multicomponent product, administered add-on as a nasal spray, could reduce the incidence of RIs and use of symptomatic drugs for relieving wheezing in children.

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.

Controversies in the treatment of mild asthma. What novelties and practical implications?

Mild asthma is prevalent in childhood and causes as many as 30%-40% asthma exacerbations requiring emergency visits. The management of "intermittent" and "mild persistent" asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Recent updates of the guidelines on the strategies to manage these patients are coming, since the role of inflammation in these asthma phenotypes is crucial, as well as the potential side effect and risks of short-acting beta 2 agonists overuse, prescribed as the only "as-needed" treatments. In this paper, we overview the new (r)evolution regarding intermittent and mild persistent asthma management.

The role of bronchodilation testing in children and adolescents with asthma in clinical practice.

The change in forced expiratory volume in 1 s (FEV1) in response to a bronchodilator (ΔFEV1) is a diagnostic tool. Moreover, bronchodilation testing may give clinically relevant outcomes beyond diagnostic purposes. The present study aimed, therefore, to investigate the nationwide role of bronchodilation testing in daily practice. The study included 280 subjects, 202 (72.1%) males and 78 (27.9%) females; the mean age was 11.6 years. Notably, 67 (24%) children had bronchial reversibility (BDR). Age, initial FEV1, FEV1/FVC, and FVC were significantly associated with BDR (OR 1.16, 1.66, 0.71, and 0.67, respectively). Interestingly, 39 (58.2%) children with BDR had no bronchial obstruction. In conclusion, the BDR is usually associated with low values of the lung function parameters, even if within the normal ranges.

The comparison between children and adolescents with asthma provided by the real-world "ControL'Asma" study.

OBJECTIVE: Because asthma is a disease that changes over time, the Italian Society of Pediatric Allergy and Immunology launched a nationwide study on asthma control (the ControL'Asma study). The intent was to test the hypothesis that children with asthma could present a different pattern compared to adolescents. In the study, we compared children with adolescents in a real-world setting by analyzing the asthma control grade and other asthma-related parameters. METHODS: This cross-sectional real-world study included 471 asthmatic children (

Obesity and Asthma: An Intriguing Link in Childhood and Adolescence.

BACKGROUND: Asthma is a chronic disease characterized by airway inflammation. Obesity is common and may be associated with asthma. OBJECTIVE: The objective of this study is to investigate the possible relationship between asthma control and obesity in children. METHODS: A nationwide study included 462 children and adolescents, 319 (69%) males, mean age 11.3 years. Asthma control grade, asthma control test, body mass index calculated as percentiles, and lung function were evaluated. RESULTS: Obesity affected 64 (13.9%) children with asthma. This outcome underlined the high prevalence of obesity in children and adolescents with asthma. On the other hand, obesity did not affect the asthma control as well as lung function. CONCLUSION: This study showed that body weight did not affect asthma control and lung function in a large population of children and adolescents with asthma followed in Italian tertiary allergy/asthma centers and adequately managed.

Turbinate Hypertrophy, Allergic Rhinitis, and Otitis Media.

PURPOSE OF REVIEW: Otitis media (OM) is a disease with high prevalence in infancy; it has a substantial burden on healthcare resources, and a relevant impact on the quality of life of families. The link between OM and allergic rhinitis (AR) is still debated. However, there is agreement about the relevance of type 2 inflammation on turbinate hypertrophy (TH) generation. There is also evidence that TH is associated with middle ear dysventilation: a pathogenic factor promoting OM. Therefore, a vicious circle among AR, TH, and OM may occur. RECENT FINDINGS: There are some recent studies exploring this issue through different approaches, such as epidemiological, mechanistic, and therapeutic. Identifying allergy as a pathogenic factor for OM could improve the management of OM patients. Vice versa, suspecting AR in OM patients, could be reasonable in selected patients. The current narrative review provides an overview of the evidence concerning the potential role of AR, and associated TH, in OM patients.

Turbinate Hypertrophy, Allergic Rhinitis, and Otitis Media.

PURPOSE OF REVIEW: Otitis media (OM) is a disease with high prevalence in infancy; it has a substantial burden on healthcare resources and a relevant impact on the quality of life of families. The link between OM and allergic rhinitis (AR) is still debated. However, there is agreement about the relevance of type 2 inflammation on turbinate hypertrophy (TH) generation. There is also evidence that TH is associated with middle ear dysventilation: a pathogenic factor promoting OM. Therefore, a vicious circle among AR, TH, and OM may occur. RECENT FINDINGS: There are some recent studies exploring this issue through different approaches, such as epidemiological, mechanistic, and therapeutic. Identifying allergy as a pathogenic factor for OM could improve the management of OM patients. Vice versa, suspecting AR in OM patients could be reasonable in selected patients. The current narrative review provides an overview of the evidence concerning the potential role of AR, and associated TH, in OM patients.

The real-world "ControL'Asma" study: a nationwide taskforce on asthma control in children and adolescents.

BACKGROUND: Asthma control is the goal of asthma management. A nationwide study on this aspect was launched by the Italian Society of Paediatric Allergy and Immunology (ControL'Asma study). OBJECTIVE: To define variables associated with different asthma control grades in a nationwide population of asthmatic children and adolescents. METHODS: This cross-sectional real-world study included 480 asthmatic children and adolescents (333 males, median age 11.2 years) consecutively enrolled in 10 third level pediatric allergy clinics. According to the Global Initiative for Asthma (GINA) document, history, medication use, perception of asthma symptoms assessed by visual analog scale (VAS), clinical examination, lung function, childhood asthma control test (cACT)/asthma control test (ACT), and asthma control level were evaluated. RESULTS: Considering GINA criteria, asthma was well controlled in 55% of patients, partly controlled in 32.4%, and uncontrolled in 12.6%. Regarding cACT/ACT, asthma was uncontrolled in 23.2%. Patients with uncontrolled asthma had the lowest lung function parameters and VAS scores, more frequent bronchial obstruction and reversibility, and used more oral and inhaled corticosteroids (CS). CONCLUSIONS: The ControL'Asma study, performed in a real-world setting, showed that asthma in Italian children and adolescents was usually more frequent in males. Asthmatic patients had an early onset and allergic phenotype with very frequent rhinitis comorbidity. Uncontrolled and partly controlled asthma affected about half of the subjects, and the assessment of asthma symptom perception by VAS could be a reliable tool in asthma management.

Steroid-sparing effect of mepolizumab in children with severe eosinophilic nonallergic asthma.

BACKGROUND: Asthma is characterized by a chronic airway inflammation, usually sustained by type 2 immunity. Bronchial and peripheral eosinophilia are biomarkers for type 2 asthma. Biologicals are the most effective treatment for severe asthma at present. Mepolizumab is an antagonist of interleukin-5 (IL-5), the most relevant cytokine involved in eosinophilia. OBJECTIVE: This case report evaluated the effectiveness of mepolizumab in two girls with severe eosinophilic non-allergic asthma. MATERIALS AND METHODS: Two female children with severe eosinophilic nonallergic asthma were treated with mepolizumab for two years. Clinical findings, lung function, peripheral eosinophils, asthma control, and bronchial endoscopy were performed. RESULTS: Biologicals reduced the eosinophilia, asthma exacerbations, and improved lung function in both patients. The treatment was also safe and well-tolerated. CONCLUSION: Mepolizumab represents an effective therapeutic option in the management of severe pediatric asthma.

Natural remedies for acute post-viral cough in children.

The post-viral acute cough is the most common symptom in childhood. Consequently, the use of cough relievers is frequent. Many products for treating cough contain natural components. An ancient tradition has always established herbal medicine and honey as effective and safe means to relieve cough. Nevertheless, very few studies adequately investigated the real effectiveness and safety of natural products in treating acute cough. There is some evidence, provided by pediatric randomized controlled trials, about honey, one multicomponent product (containing Plantagolanceolata, Grindelia robusta, Helichrysum italicum, and honey), and Pelargonium sidoides. Other group of substances, including glycerol and isolated natural compounds, can help manage cough but robust evidence still lacks in children. There is an urgent need to perform rigorous studies that confirm the natural products' efficacy and safety for relieving post-viral acute cough.Key points: Acute post-viral cough is prevalent in childhood and adolescence. There is a growing interest concerning the use of natural remedies for post-viral cough. Many herbal medicines could be used satisfactorily for this issue.

Chronic cough in childhood: A systematic review for practical guidance by the Italian Society of Pediatric Allergy and Immunology.

The current systematic review presented and discussed the most recent studies on pediatric chronic cough. In addition, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to a pediatric patient with chronic cough.Several algorithms on chronic cough management have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, from birth until adulthood. Based on our findings, children and adolescents with chronic cough without cough pointers can be safely managed, initially using the watchful waiting approach and, successively, starting empirical treatment based on cough characteristics. Unlike other algorithms that suggest laboratory and instrumental investigations as a first step, this review highlighted the importance of a "wait and see" approach, consisting of parental reassurance and close clinical observation, also due to inter-professional collaboration and communication between general practitioners and specialists that guarantee better patient management, appropriate prescription behavior, and improved patient outcome. Moreover, the neonatal screening program provided by the Italian National Health System, which intercepts several diseases precociously, allowing to treat them in a very early stage, helps and supports a "wait and see" approach.Conversely, in the presence of cough pointers or persistence of cough, the patient should be tested and treated by the specialist. Further investigations and treatments will be based on cough etiology, aiming to intercept the underlying disease, prevent potentially irreversible tissue damage, and improve the general health of patients affected by chronic cough, as well as the quality of life of patients and their family.

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

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

Non-pharmacological remedies for post-viral acute cough.

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.

ControL'Asma Project: new insights.

The Italian Society of Paediatric Allergy and Immunology has developed the project "ControL'Asma," a nationwide study involved ten third-level pediatric allergy clinics across Italy. The first findings of the "ControL'Asma" project showed that asthma was more frequent in males, had an early onset and allergic phenotype with very frequent rhinitis comorbidity, uncontrolled, and partly controlled asthma affected about the half of subjects, and the assessment of asthma symptom perception by VAS could be a reliable tool in the asthma management.

Allergen immunotherapy and asthma.

Allergen immunotherapy (AIT) represents at present the unique disease-modifying treatment strategy for IgE-mediated allergic diseases. AIT can induce clinical improvement of allergic asthma, including reduced symptoms, medication use, and improvement of quality of life, with a long-lasting effect after cessation of treatment. Notably, the current asthma guidelines are now recommending sublingual immunotherapy as an add-on therapy for asthma in adults and adolescents with house dust mite allergy. Clinical indications of AIT, with particular reference to pediatric asthma, mechanisms of clinical and immunological tolerance to allergens, and the potential biomarkers predicting clinical response are discussed.

Allergy and Otitis Media in Clinical Practice.

PURPOSE OF REVIEW: Otitis media (OM) is a disease with very high prevalence in infancy, substantial burden on healthcare resources, and relevant impact on the quality of life of families. The link between OM and allergy is controversial and still debated. However, a fundamental premise has to be placed before introducing this topic: there is the need to use clear and unambiguous terms. Literature abounds with misleading terms that significantly affect the methodology and consequently the outcomes. Moreover, it is essential to differentiate patients according to the OM type (i.e., acute OM, OM with effusion, and chronic suppurative OM), the allergic disease, and mainly the age. RECENT FINDINGS: There are some recent studies exploring this issue through different approaches, such as epidemiological, mechanistic, and therapeutic. To identify allergy as a pathogenic factor for OM could improve the management of OM patients. Vice versa, to suspect allergy in OM patients could be reasonable in selected patients. The current narrative review provides an overview of the evidence concerning the potential role of allergy in OM. As there are conflicting findings, a possible interpretation of pathophysiological events and a pragmatic approach are proposed.