COVID-19 and the differences in physiological background between children and adults and their clinical consequences.

The SARS-CoV-2 pandemic has indeed been one of the most significant problems facing the world in the last decade. It has affected (directly or indirectly) the entire population and all age groups. Children have accounted for 1.7 % to 2 % of the diagnosed cases of COVID-19. COVID-19 in children is usually associated with a mild course of the disease and a better survival rate than in adults. In this review, we investigate the different mechanisms which underlie this observation. Generally, we can say that the innate immune response of children is strong because they have a trained immunity, allowing the early control of infection at the site of entry. Suppressed adaptive immunity and a dysfunctional innate immune response is seen in adult patients with severe infections but not in children. This may relate to immunosenescence in the elderly. Another proposed factor is the different receptors for SARS-CoV-2 and their differences in expression between these age groups. In infants and toddlers, effective immune response to viral particles can be modulated by the pre-existing non-specific effect of live attenuated vaccines on innate immunity and vitamin D prophylaxis. However, all the proposed mechanisms require verification in larger cohorts of patients. Our knowledge about SARS-CoV-2 is still developing.

Cough reflex sensitivity in various phenotypes of childhood asthma.

Cough is a major symptom in some children with asthma, but the relationship between cough and the severity of asthma is defined insufficiently. As cough represents common problem of pediatrics, several objective methods for its assessment were developed. Cough reflex sensitivity (CRS) test with capsaicin is one of the most important tools for studying cough. In the present study, we aimed to study the CRS in various phenotypes of childhood asthma. We found that, in general, CRS was increased in asthmatic children compared with controls. The most evident increase of CRS was observed during acute asthma exacerbation, in children suffering from asthma with concomitant allergic rhinitis, and in atopic asthmatics. Interestingly, we noted a significant decline in lung function after capsaicin CRS. Various laboratory and clinical characteristics of asthmatic children influence cough sensitivity to a different extent. Cough reflex sensitivity measurement can add valuable information beside the commonly used spirometric and inflammometric methods in the management of asthmatic children.

Reproducibility of atopy patch tests with food and inhalant allergens.

Although atopy patch tests (APT) seem a valuable additional tool in the diagnostic work-up for food allergy in children with atopic eczema/dermatitis syndrome, the immunopathology and some technical aspects of testing remain controversial. Few published data are available on the reproducibility of APT with inhalants and only two studies include fresh food allergens. In this study we therefore investigated the reproducibility of duplicate APT (left versus right side of the back) with native and commercially available food (cow s milk, hen s egg, tomato, wheat flour) and with inhalant allergens (Dermatophagoides pteronyssinus and mixed grasses) in a large unselected population of children. We tested a population of 277 Italian school children with three APT allergens: fresh food (cow s milk, hen s egg, tomato and wheat flour), standardised food allergens in petrolatum (the same four foods) and standardised inhalant allergens routinely used for skin prick testing. For the four food allergens (applied in the natural form or as the standardised commercial preparation) from one- to three quarters of the APT gave positive results on one side and negative reactions on the opposite side (Cohen s K coefficient between 0.38, fresh tomato and 0.81, fresh cow s milk). Conversely, APT with inhalant allergens were invariably reproducible (Cohen s K = 1.00). The possible technical and immunologic reasons explaining why reproducibility of APT differed for the two types of allergens await an answer from extensive controlled studies.

Food allergens and respiratory symptoms.

Food allergy may be clinically expressed by a variety of respiratory symptoms, which can be provoked either by IgE- or cellular mediated reactions. Among the diagnostic procedures, newly introduced atopy patch test seems to be important for diagnosis of cellular, delayed immune reactions. We studied the prevalence of positive atopy patch tests with food and inhalant allergens and the correlation between the positivity of atopy patch tests and questionnaire derived atopic and nonatopic espiratory symptoms and diseases in an unselected children population. We found a correlation between the positive patch test result with wheat and cough after physical effort, allergic rhino-conjunctivitis, and bronchitis recidivans. The subjects with positive skin reaction to egg suffered from allergic rhino-conjunctivitis and bronchial asthma. Food and inhalant allergens play an important role in the induction and exacerbation of some respiratory allergic diseases. The positive correlation of positive results of skin tests and history of some respiratory diseases and symptoms also on the population level confirm the importance of these tests in the diagnostic work-up of these allergic diseases.

The prevalence of atopy in asthmatic children correlates strictly with the prevalence of atopy among nonasthmatic children.

BACKGROUND: Because asthma preferentially burdens persons with atopy, atopy is simplistically considered a primary 'cause' of asthma. Yet at the population level, the percentage of asthma cases 'attributable' to atopy ranges from less than 10% to more than 60%. Seeking to understand the rationale for the variability of atopy-attributable cases of asthma, we systematically reviewed the results of our own previous epidemiological studies and several studies conducted by others in children. METHODS: From each of the 37 random pediatric populations selected by a Medline search combining the key words 'IgE or skin tests or hypersensitivity, immediate' with 'epidemiological studies, cross-sectional, case-control, prevalence, longitudinal, epidemiology of asthma' (12 from our previous pediatric surveys and a further 25 reported from 19 studies in children), we extracted the population prevalence of asthma and atopy among asthmatic subjects and among the nonasthmatic part of the population. RESULTS: No correlation was found between the prevalence of asthma (range 1.8-44.1%) and atopy (range 5.8-63.9%) in these 37 populations of children (r = 0.052, p = 0.761). Nevertheless, the prevalence of atopy among asthmatics strictly correlated with the prevalence of atopy in nonasthmatics (r = 0.900, p < 0.001, slope 1.364). CONCLUSION: The prevalence of asthma and atopy varies worldwide and at various time points and independently undergoes the influence of powerful environmental factors. The almost perfect correlation we found between atopy in asthmatics and atopy in the nonasthmatic part of the childhood population shows that the prevalence of atopy in asthma depends on environmental factors that simultaneously induce atopy in asthmatic and nonasthmatic subjects.

Allergen skin weal/radioallergosorbent test relationship in childhood populations that differ in histamine skin reactivity: a multi-national survey.

BACKGROUND: Histamine skin reactivity (HSR, the dimension of the skin weal elicited by histamine 10 mg/mL) is a variable that differs in children from different European countries and increases over time in the same place (Italy). OBJECTIVE: In this epidemiologic study, we investigated to what extent differences in HSR influence the relationship between positive allergen skin prick tests (ASPTs) and serum-specific IgE concentrations. METHODS: Between October 2001 and February 2002, 591 unselected 9-10-year-old schoolchildren drawn from five small towns in central Poland (Starachowice), central Italy (Ronciglione, Guardea) and Libya (Al-Azyzia, near the Mediterranean sea and Samno, 900 km south of the coast) were analysed for histamine, common ASPT and for serum total and specific IgE. RESULTS: HSR differed markedly in children from the three countries (Libya>Italy>Poland) whereas serum total IgE concentrations remained the same. The prevalence of children with measurable serum specific IgE (> or = 0.35 kU) or with a positive ASPT for five common allergens was high in Italy, lower in Poland and far lower in Libya. A 3-mm ASPT weal corresponded to a serum-specific IgE concentration that was two to threefold higher in children with low HSR compared with children with high HSR (P = 0.008). CONCLUSION: These findings suggest that HSR--a variable that differs in schoolchildren populations from the three countries studied--independently influences the results of ASPT and its influence should be considered when ASPT are assessed in international studies. The HSR differences found in the populations reported here probably reflect a complex, dynamic, environmental interaction that should be monitored in the different parts of the world.