Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children

Background: Antigen-specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear. This study aimed to analyse the expression of FcεRI on peripheral blood mononuclear cells (PBMCs) from atopic children with and without asthma, and non-atopic/non-asthmatic age-matched healthy controls. Methods: We performed multiparameter flow cytometry on PBMC from 391 children across three community cohorts and one clinical cohort based in Western Australia. Results: We confirmed expression of FcεRI on basophils, monocytes, plasmacytoid and conventional DCs, with higher proportions of all cell populations expressing FcεRI in atopic compared to non-atopic children. Further, we observed that levels of FcεRI expression were elevated across plasmacytoid and conventional DC as well as basophils in atopic asthmatic compared to atopic non-asthmatic children also after adjusting for serum IgE levels. Conclusion: Our data suggest that the expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children. Given the significant immune modulatory effects observed as a consequence of FcεRI expression, this altered expression pattern is likely to contribute to asthma pathology in children

Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease.

Repeated cycles of infection-associated lower airway inflammation drive the pathogenesis of persistent wheezing disease in children. In this study, the occurrence of acute respiratory tract illnesses (ARIs) and the nasopharyngeal microbiome (NPM) were characterized in 244 infants through their first five years of life. Through this analysis, we demonstrate that >80% of infectious events involve viral pathogens, but are accompanied by a shift in the NPM toward dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change frequently precedes the detection of viral pathogens and acute symptoms. Colonization of illness-associated bacteria coupled with early allergic sensitization is associated with persistent wheeze in school-aged children, which is the hallmark of the asthma phenotype. In contrast, these bacterial genera are associated with "transient wheeze" that resolves after age 3 years in non-sensitized children. Thus, to complement early allergic sensitization, monitoring NPM composition may enable early detection and intervention in high-risk children

Trajectories of childhood immune development and respiratory health relevant to asthma and allergy.

Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk 'atopic' cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma

Acute respiratory tract infections in childhood

• Most acute respiratory infections (ARIs) in developed countries are viral in aetiology, uncomplicated and self-limiting. • Human metapneumovirus is a leading cause of ARIs in early childhood. • Respiratory viral infections are associated with most asthma exacerbations, particularly in children; rhinoviruses are the most commonly implicated virus. • The use of antibiotics in treating ARIs should only be considered in the presence of bacterial sequelae. • Although most children with ARIs can be managed in the community setting, some may be better referred to hospital. • Prevention strategies for ARIs include avoidance of environmental tobacco smoke exposure and immunisation against pneumococcal disease, invasive Haemophilus influenzae type b infection and, in some children, influenza

Do early-life viral infections cause asthma?

Epidemiologic associations between viral lower respiratory infections (LRIs) and asthma in later childhood are well known. However, the question of whether such infections cause asthma or unmask asthma in a susceptible host has still not been settled. Most early evidence centered on the role of the respiratory syncytial virus; however, recent studies highlight a potential role for human rhinovirus as a risk factor for asthma. The links between early-life viral LRI and subsequent asthma are generally via wheeze; however, the presence of wheeze does not give any information about why the child is wheezing. Wheeze in early life is, at best, a fuzzy phenotype and not specific for subsequent asthma. The risk of asthma after viral LRI is increased in the presence of allergic sensitization in early life and if the infection is more severe. Atopy-associated mechanisms also appear to be involved in viral-induced acute exacerbations of asthma, especially in prolonging symptomatology after the virus has been cleared from the lungs. Breaking the nexus between viral respiratory infections and asthma may be possible with interventions designed to inhibit atopy-related effectors mechanisms from participating in the host response to respiratory viral infections. (J Allergy Clin Immunol 2010125:1202-5.

Piloting a web-based continuing professional development program for asthma education

Purpose: Continuing professional development is an integral component of modern medical practice, yet traditional educational methods are impractical for many Primary Care Physicians. Web-based programs may fulfill the requirements of busy practitioners who have difficulty attending formal education sessions. Methods: We piloted the use of a learning management system to deliver asthma education materials to Primary Care Physicians in both Australia and Italy in their native languages. Each group of Physicians accessed an education module which contained content pages, self-tests, a quiz and a survey. Details of how the Physicians used the system, their preferences and performance on the assessment were monitored. Results: The learning management system was well received by both Italian and Australian Physicians. Thirty-eight (18 Australian, 20 Italian) Physicians used the system. Participants visited an average of 8.8 pages, with a mean time per hit of 2.9 min. Formative assessment was undertaken by 63.2% and summative assessment by 68.4% of participants. There were no substantial differences in performance between Physicians from both countries. Italian physicians tended to use the system after hours whereas Australian Physicians appear to do so between patient visits. Conclusions: Simple web-based systems are suitable for delivering educational materials to Primary Care Physicians in a manner likely to be used

Support for 2 variants of eczema

Background Studies investigating the natural history and risk factors for eczema have historically considered eczema as a single entity, without regard for the individual's atopic status. The association between atopy and eczema is complex, and as many as ⅔ of patients with eczema are not atopic. Objective To investigate the risk factors for eczema in relation to the child's atopic status in a cohort of high-risk children. Methods A prospective birth cohort of 263 children was followed for 5 years and closely examined for eczema. Antenatal and postnatal data on environmental exposures were collected by interview. Skin prick test to define atopic status was performed at 6 months and 2 and 5 years of age. Results Of the subjects, 66.1% had eczema in the first 5 years, and the majority (85.5%) reported onset of rash in the first year. A third of those with eczema were not atopic (nonatopic/intrinsic eczema). Children with atopic eczema (extrinsic eczema) were more likely to be male, to have been breast-fed longer, and to have a history of food allergies, allergic rhinitis, and current wheeze. Nonatopic eczema was more common in girls, and an association was found with early daycare attendance. Conclusion This study supports the presence of 2 variants of eczema: atopic eczema occurring early in childhood and nonatopic eczema with early daycare attendance. It is likely that environmental factors have a different effect on these 2 variants of eczema, and future studies should thus consider eczema as 2 variants in determining the effect of attributable risks

Dendritic Cell Immaturity during Infancy Restricts the Capacity To Express Vaccine-Specific T-Cell Memory

The capacity of the immune system in infants to develop stable T-cell memory in response to vaccination is attenuated, and the mechanism(s) underlying this developmental deficiency in humans is poorly understood. The present study focuses on the capacity for expression of in vitro recall responses to tetanus and diphtheria antigens in lymphocytes from 12-month-old infants vaccinated during the first 6 months of life. We demonstrate that supplementation of infant lymphocytes with “matured” dendritic cells (DC) cultured from autologous CD14(+) precursors unmasks previously covert cellular immunity in the form of Th2-skewed cytokine production. Supplementation of adult lymphocytes with comparable prematured autologous DC also boosted vaccine-specific T-cell memory expression, but in contrast to the case for the infants, these cytokine responses were heavily Th1 skewed. Compared to adults, infants had significantly fewer circulating myeloid DC (P < 0.0001) and plasmacytoid DC (P < 0.0001) as a proportion of peripheral blood mononuclear cells. These findings suggest that deficiencies in the numbers of antigen-presenting cells and their functional competence at 12 months of age limit the capacity to express effector memory responses and are potentially a key factor in reduced vaccine responsiveness in infants