Our study demonstrates that sublingual immunotherapy is effective in children and that it maintains the clinical efficacy for 4 to 5 years after discontinuation.

SummaryThe gastrointestinal system plays a central role in immune system homeostasis. It is the main route of contact with the external environment and is overloaded every day with external stimuli, sometimes dangerous as pathogens (bacteria, protozoa, fungi, viruses) or toxic substances, in other cases very useful as food or commensal flora. The crucial position of the gastrointestinal system is testified by the huge amount of immune cells that reside within it. Indeed, gut-associated lymphoid tissue (GALT) is the prominent part of mucosal-associated lymphoid tissue (MALT) and represents almost 70% of the entire immune system; moreover, about 80% of plasma cells [mainly immunoglobulin A (IgA)-bearing cells] reside in GALT. GALT interacts strictly with gastrointestinal functions in a dynamic manner; for instance, by increasing intestinal permeability in replay to particular stimulations, or orientating the immune response towards luminal content, allowing either tolerance or elimination/degradation of luminal antigens, or sometimes provoking damage to the intestinal mucosa, such as in coeliac disease or food allergy. The immune mechanisms implicated in these actions are very complex and belong to both innate and adaptive immunity; innate immunity supplies an immediate non-specific response that is indispensable before specific adaptive immunity, which needs 7-10 days to be efficacious, takes place. The results of their interactions depend upon different contexts in which contact with external agents occurs and may change according to different genetic settings of the hosts.

Asthma is one of the most common chronic respiratory diseases worldwide. It affects all ages but frequently begins in childhood. Initiation and exacerbations may depend on individual susceptibility, viral infections, allergen exposure, tobacco smoke exposure, and outdoor air pollution. The aim of this review was to analyze the role of the gut–lung axis in asthma development, considering all asthma phenotypes, and to evaluate whether microbe-based therapies may be used for asthma prevention. Several studies have confirmed the role of microbiota in the regulation of immune function and the development of atopy and asthma. These clinical conditions have apparent roots in an insufficiency of early life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts. Commensal microbes are necessary for the induction of a balanced, tolerogenic immune system. The identification of commensal bacteria in both the gastroenteric and respiratory tracts could be an innovative and important issue. In conclusion, the function of microbiota in healthy immune response is generally acknowledged, and gut dysbacteriosis might result in chronic inflammatory respiratory disorders, particularly asthma. Further investigations are needed to improve our understanding of the role of the microbiome in inflammation and its influence on important risk factors for asthma, including tobacco smoke and host genetic features.

This study represents the first analysis of the safety of SLIT concerning the allergen dose employed in the treatment. There is evidence that AE occurrence is substantially not dose-dependent. This fact highlights two main clinical aspects: the elevated tolerability of SLIT in general and the safety of HAD regimen.

Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.

Background:The minimum age to start specific immunotherapy with inhalant allergens in children has not been clearly established, and position papers discourage its use in children younger than 5 years.Objective: To assess the safety of high-dose sublingual-swallow immunotherapy (SLIT) in a group of children younger than 5 years.Methods: Sixty-five children (51 boys and 14 girls; age range, 38 -80 months; mean Ϯ SD age, 60 Ϯ 10 years; median age, 60 months) were included in this observational study. They were treated with SLIT with a build-up phase of 11 days, culminating in a top dose of 300 IR (index of reactivity) and a maintenance phase of 300 IR 3 times a week. The allergens used were house dust mites in 42 patients, grass pollen in 11 patients, olive pollen in 5 patients, Parietaria pollen in 4 patients, and cypress pollen in 3 patients. All adverse reactions and changes in the treatment schedule were compared in 2 subgroups: children 38 to 60 months old and children 61 to 80 months old.Results: The average cumulative dose of SLIT was 36,900 IR. Adverse reactions were observed in 11 children, none of them severe enough to require discontinuation of immunotherapy. Six reactions occurred in the 60 months or younger age group and 7 in the older than 60 months age group, with no differences between these 2 groups.Conclusion: High-dose immunotherapy in children younger than 5 years does not cause more adverse reactions than in children aged 5 to 7 years. There is no reason to forbear studies on safety and efficacy of these preparations in young children.Ann Allergy Asthma Immunol. 2005;95:254-258.

Recent studies suggest that swimming in chlorinated pools during infancy may increase the risks of lower respiratory tract infection. The aim of the present study was to assess the influence of swimming in chlorinated pools on the risks of bronchiolitis and its late consequences.A total of 430 children (47% female; mean age 5.7 yrs) in 30 kindergartens were examined. Parents completed a questionnaire regarding the child's health history, swimming practice and potential confounders.Attendance at indoor or outdoor chlorinated pools ever before the age of 2 yrs was associated with an increased risk of bronchiolitis (OR 1.68; 95% CI 1.08-2.68; p50.03), which was exposuredependent for both types of pool (p-value for trend ,0.01). Associations persisted, and were even strengthened, by the exclusion of other risk factors. Among children with no parental antecedents of atopic disease or no day-care attendance, odds ratios for bronchiolitis amounted to 4.45 (1.82-10.9; p50.001) and 4.44 (1.88-10.5; p50.007) after .20 h spent in chlorinated pools during infancy. Infant swimmers who developed bronchiolitis also showed higher risks of asthma and respiratory allergies later in childhood.Swimming pool attendance during infancy is associated with a higher risk of bronchiolitis, with ensuing increased risks of asthma and allergic sensitisation.

Grafts of adipose tissue from adult Rosa26 mice from different sites of the body, irrespective of the sex of the donor, share with the mammary fat the property of giving rise to milk-secreting epithelial cells when exposed to the microenvironment of the mammary gland in pregnant and lactating females. To rule out the possibility that the labeled mammary glandular tissue was derived from stem cells associated with the stroma vascular part of the grafts, we injected into the mammary gland a pure suspension of adipocytes obtained by treating a fragment of adipose tissue with collagenase. X-gal-positive cells were inserted into the alveoli of the native gland, and electron microscopy showed that the labeled cells had transformed into milk-secreting glandular cells. At the site of the adipocyte injection, the labeled alveoli contained a mixture of X-galpositive and X-gal-negative cells, and a single epithelial cell was occasionally stained in an otherwise unlabeled alveolus. This suggests that growing ducts individually recruit adjacent adipocytes that transdifferentiate into secretory epithelial cells as they became part of the glandular alveoli. After dissociation, the isolated adipocytes retained the morphology and protein markers typical of differentiated fat cells but expressed high levels of stem cell genes and the reprogramming transcription factor Klf4. Thus, the well-documented osteogenic, chondrogenic, myogenic, and angiogenic transformation of preadipocytes associated with the stroma vascular component of the adipose tissue may reflect an intrinsic capability of adipocytes to reprogram their gene expression and transform into different cytotypes.