Allergic diseases, such as food allergy (FA), atopic dermatitis (AD), and asthma, are heterogeneous inflammatory immune-mediated disorders that currently constitute a public health issue in many developed countries worldwide. The significant increase in the prevalence of allergic diseases reported over the last few years has closely paralleled substantial environmental changes both on a macro and micro scale, which have led to reduced microbial exposure in early life and perturbation of the human microbiome composition. Increasing evidence shows that early life interactions between the human microbiome and the immune cells play a pivotal role in the development of the immune system. Therefore, the process of early colonization by a "healthy" microbiome is emerging as a key determinant of life-long health. In stark contrast, the perturbation of such a process, which results in changes in the host-microbiome biodiversity and metabolic activities, has been associated with greater susceptibility to immune-mediated disorders later in life, including allergic diseases. Here, we outline recent findings on the potential contribution of the microbiome in the gastrointestinal tract, skin, and airways to the development of FA, AD, and asthma. Furthermore, we address how the modulation of the microbiome composition in these different body districts could be a potential strategy for the prevention and treatment of allergic diseases.

Vitamin D (VD) is an essential hormone for humans. Despite the classical functions of VD in the regulation of calcium-phosphorus homeostasis and bone metabolism, in the last few years, evidence has been accumulated on the pleiotropic effect of VD, as many cells throughout the body express the VD receptor and the enzyme 1α-hydroxylase. 1 This article discusses the actions of VD and the relationship between VD status and the risk to develop various diseases. | VITAMIN D ME TABOLIS MVitamin D is the general term encompassing both vitamin D 2 (ergocalciferol) and vitamin D 3 (cholecalciferol). In humans, VD is mainly synthesized in the skin, whereas only a minor part is derived from dietary sources. Few natural, non-fortified products such as fatty fish or some types of mushrooms contain relevant amounts of VD. The endogenous synthesis pathway starts in the skin, when cutaneous-derived 7-dehydroxycholesterol undergoes photolytic conversion by UVB sunlight to form pre-vitamin D3, rapidly converted to biologically inactive vitamin D3. It then undergoes hydroxylation in the liver by 25-hydroxylase to become 25-(OH) D, the major circulating form of VD in humans. In the kidney, 25(OH) D is further converted to the fully active metabolite 1,25-(OH)2 D by the enzyme 1-α-hydroxylase. This process is finely regulated by parathormone, fibroblast growth factor 23, calcium, and phosphorus and depends on some factors such as ethnicity, latitude, culture, and sunscreen. 2 VD plays a fundamental role in the processes of acquisition and achievement of peak bone mass. 3,4 | E X TR A S K ELE TAL AC TI ON S OF VDIn recent decades, several studies have suggested that VD contributes to diverse processes extending far beyond mineral homeostasis, defined as extraskeletal actions. These observations suggest a critical role for VD in the modulation of immune function, above all during pediatric age, exerted by modulating both innate immunity AbstractSeveral scientific societies established that vitamin D (VD), in its metabolized form 25(OH)D, levels higher than 20 ng/mL are sufficient to ensure optimal bone health, while 25(OH)D levels higher than 30 ng/mL are needed to favor VD extraskeletal actions. However, it has been estimated that approximately 30% of children and 60% of adults worldwide are VD deficient and insufficient, respectively. This is the reason why it is important to provide a practical approach to VD supplementation for infants, children, and adolescents. It is the pediatrician's role to evaluate the modifiable lifestyle risk factors for deficiency, particularly a reduced sun exposure, following an evidence-based approach, and to suggest VD supplementation only when there is a rational reason to support its use. K E Y W O R D S childhood disorders, health, vitamin D3 How to cite this article: Peroni DG, Trambusti I, Di Cicco ME, Nuzzi G. Vitamin D in pediatric health and disease. Pediatr Allergy Immunol. 2020;31(Suppl 24):54-57. https ://doi.

Asthma is the most frequent chronic disease in children, and its pathogenesis involves genetic, epigenetic, and environmental factors. The rapid rise in the prevalence of asthma registered over the last few decades has stressed the need to identify the environmental and modifiable factors associated with the development of the disease. In particular, there is increasing interest in the role of modifiable nutritional factors specific to both the prenatal and post-natal early life as, during this time, the immune system is particularly vulnerable to exogenous interferences. Several dietary factors, including maternal diet during pregnancy, the duration of breastfeeding, the use of special milk formulas, the timing of the introduction of complementary foods, and prenatal and early life supplementation with vitamins and probiotics/prebiotics, have been addressed as potential targets for the prevention of asthma. In this review, we outline recent findings on the potential role of prenatal and perinatal dietary and nutritional interventions for the primary prevention of pediatric asthma. Moreover, we addressed unmet needs and areas for future research in the prevention of childhood-onset asthma.

Asthma and other allergic disorders, such as atopic dermatitis and food allergies, are common chronic health problems in childhood. The rapid rise in the prevalence of these conditions registered over the last few decades has stressed the need to identify the modifiable risk factors associated with the development of these diseases. Breast milk, recognized as the gold standard for healthy growth and development of the newborn, is one of the major factors associated with a lower incidence of allergic and infectious diseases in childhood and young adulthood. Although the underlying mechanisms for these effects are not well understood, breastfeeding leads to immune system maturation. In this narrative review, we summarize existing evidence on breastfeeding and human milk composition in relation to allergic disease prevention or development.

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.

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Children are not small adults and this fact is particularly true when we consider the respiratory tract. The anatomic peculiarities of the upper airway make infants preferential nasal breathers between 2 and 6 months of life. The pediatric larynx has a more complex shape than previously believed, with the narrowest point located anatomically at the subglottic level and functionally at the cricoid cartilage. Alveolarization of the distal airways starts conventionally at 36-37 weeks of gestation, but occurs mainly after birth, continuing until adolescence. The pediatric chest wall has unique features that are particularly pronounced in infants. Neonates, infants, and toddlers have a higher metabolic rate, and consequently, their oxygen consumption at rest is more than double that of adults. The main anatomical and functional differences between pediatric and adult airways contribute to the understanding of various respiratory symptoms and disease conditions in childhood. Knowing the peculiarities of pediatric airways is helpful in the prevention, management, and treatment of acute and chronic diseases of the respiratory tract. Developmental modifications in the structure of the respiratory tract, in addition to immunological and neurological maturation, should be taken into consideration during childhood.

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