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Purpose of Review: The introduction of high-quality and standardized extracts for immunotherapy has renewed the interest in the treatment of pediatric allergic asthma that represents a high-prevalence disease., Recent Findings: In addition to clinical trials, several systematic reviews and metaanalyses were published, confirming overall the clinical efficacy of allergen immunotherapy in pediatric asthma. In addition, new data on the preventive effect of the treatment on asthma onset were published. Despite this, many intriguing questions emerged, in parallel to the development of knowledge., Summary: Allergen immunotherapy is overall effective for the treatment of asthma in children, but a class-effect should not be claimed, rather the efficacy of each single product. According to the recent findings, the challenge for the future research will be to clarify: when to start immunotherapy in children, which are (if they exist) the predictive biomarkers for efficacy in the single individual, the magnitude of the preventive effect and the optimal duration of the treatment.

Purpose of Review: Asthma is the most common chronic disease in pediatric age. Childhood-onset asthma, as opposed to adult-onset asthma, is typically characterized by a personal and often a family history of atopy and related markers of type 2-mediated inflammation. However, the interplay between atopy and asthma development is more complex than a linear dose-response relationship., Recent Findings: Family and personal history of atopic diseases have been confirmed as major risk factors for asthma occurrence and persistence in children. Early life and multiple sensitizations to aeroallergens significantly increase the risk of asthma development in school age. Early life lower respiratory tract viral infections, especially caused by rhinovirus, also increase the susceptibility to atopic asthma in childhood. Human rhinovirus type C receptor CDHR3 polymorphisms have been shown to affect receptor epithelial expression, activation, and asthma development and exacerbation severity in children. Atopic sensitization and respiratory viral infections can synergistically enhance the susceptibility to asthma through multiple mechanisms, including the IgE-mediated inhibition of innate antiviral responses to rhinovirus. Emerging evidence shows that several nonatopic factors are also involved in the asthma pathogenesis in genetically predisposed individuals, including early life exposure to environmental factors, and lung and gut microbiome composition., Summary: The current review outlines recent data on the complex role of atopy in asthma pathogenesis and persistence, and addresses new research topics such as the role of epigenetics and the lung microbiome.

Background: Atopic dermatitis (AD) often predates the development of allergic sensitization in the so-called atopic march. Several studies have pointed out epidermal barrier impairment as a major cause of this evolution., Objective: The present study aimed to assess atopic skin integrity by means of transepidermal water loss (TEWL) and Corneometer, and to investigate possible correlations between barrier integrity measurements and the degree of sensitization to aeroallergens (allergy score)., Methods: Sixty-one children (6 months to 17 years old) with AD were clinically evaluated by the Scoring Atopic Dermatitis index. TEWL and Corneometer evaluations were performed on lesion sites as well as on healthy skin. The subjects underwent skin-prick testing, and the severity of allergic sensitization was assessed for each patient by summing all wheal diameters (the allergy score). The same tests were performed in 20 children without AD., Results: In patients with AD, TEWL and Corneometer results were found to be higher and lower, respectively, on eczematous areas in comparison with healthy skin, and differences were significantly correlated to the Scoring Atopic Dermatitis index (p < 0.0001 and p = 0.007, respectively). The TEWL result was significantly higher in nonlesional skin of the patients with AD compared with that of individuals without AD (p = 0.017). Of the patients with AD, 59% were sensitized to inhalant allergens; allergy scores were positively correlated with both AD duration (r = 0.63; p < 0.0001) and nonlesional skin TEWL values (r = 0.46; p = 0.002). No significant correlation was found between allergy scores and skin parameters in subjects without AD., Conclusion: Patients with AD are affected by barrier function impairment, even on noneczematous skin. This defect is associated with greater aeroallergen sensitization and may contribute to allergic respiratory symptom development.

The contribution of beta 2-agonist treatment per se and the effect of beta 2-agonists plus allergen exposure was evaluated in two groups of thirteen asthmatic children being treated respectively at sea level during the period of maximal allergen exposure and at high altitude in an environment free of the offending allergens. Bronchial hyperreactivity was evaluated by standardised exercise tests before and after treatment with salbutamol controlled release tablets (4 mg). Challenges were performed at the beginning and after 2 and 4 weeks of treatment. A fourth test was performed 2 days after stopping the treatment. Children treated with salbutamol at sea level (exposure to allergen) showed baseline delta PEF of 16.9 +/- 3.4 and 13.7 +/- 4.2, 20.7 +/- 4.3, 26.0 +/- 5.1 respectively for the second, third and fourth test. Children treated at high altitude showed respectively delta PEF of 34.9 +/- 5.1, 31.1 +/- 4.9, 26.5 +/- 5.4, 27.9 +/- 5.0. These data suggest that oral salbutamol per se is not responsible for an increase in bronchial responsiveness, but eventually suggest that treatment with beta 2-agonists at the same time as continued allergen exposure may be responsible for an increase in bronchial hyperresponsiveness.

We studied the effects of reduced allergen exposure on bronchial hypereactivity (BHR) in two groups of asthmatic children allergic to house dust mites (HDM) living at high altitude for 9 continuous mo. In the first group the serum levels of total and HDM-specific IgE showed significant decreases after 3 mo (p < 0.001 and p < 0.02, respectively) and after 9 mo (p < 0.001). Three months after returning home the total IgE levels had increased significantly (p < 0.001). The mean percentage fall in peak expiratory flow after exercise testing improved after 3 and 9 mo (p < 0.05), but it had deteriorated after 3 mo at home (p < 0.01). The methacholine PD20-FEV1 increased after 3 mo (p = 0.001) and further after 9 mo (p < 0.001), with a decrease after the 3-mo period at sea level (p = 0.01). In the second cohort there was a significant increase in HDM PD20-FEV1 after 6 and 9 mo (p < 0.001), with a slight decrease of magnitude of the allergen-induced late reaction. Histamine PD20-FEV1 significantly increased after 6 and 9 mo at high altitude, particularly in the challenges performed after the HDM bronchial provocation (p < 0.01). Our data demonstrate that allergen avoidance in asthmatic children not only decreases nonspecific BHR but also decreases allergen sensitivity, late allergen-induced bronchial reactions, and enhancement of BHR by allergen challenge.

A cohort of 12 asthmatic children was followed over several months, during which they moved back and forth from an allergen-free to an allergen-rich environment at high and low altitude, respectively. The children were treated with non-steroidal anti-asthmatic drugs as clinically needed. Histamine PC20-FEV1 was unaltered during the study period, whereas serum levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) showed significant changes when the children were exposed to the offending allergens. The total IgE significantly increased during exposure. The serum levels of myeloperoxidase (MPO) as well as of chemotactic factors for both neutrophils and eosinophils were unaltered during allergen exposure. We conclude that the serum markers of eosinophil activity ECP and EPX are sensitive indices of allergen exposure in asthmatic atopic children.