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    ABSTRACT: The environmental factors driving the recent increase in the prevalence of food allergy (FA) are unclear. Since associations have been demonstrated between microbial exposure and the likelihood of eczema and respiratory allergies, we reviewed the evidence for FA. Medline was systematically searched from inception to the end of July 2012 for studies investigating links between FA and environmental exposures, likely to influence microbial exposure, such as Caesarean delivery, family size, day-care attendance, childhood infections, immunizations and antibiotic use. We selected studies reporting food challenge data, reported doctor-diagnosed (RDD) FA and food sensitization. Methodological differences and study heterogeneity precluded meta-analysis. A total of 46 studies were identified, of which 28 (60.9%) were prospective and 13 (28.3%) used food challenges to diagnose FA. Caesarean delivery was investigated in 13 studies, of which three infant cohorts demonstrated an increase in challenge-proven FA (one cohort) and food sensitization (two cohorts), and one cross-sectional study reported increased RDDFA. Four studies investigated the effect of having siblings, with one infant cohort demonstrating less challenge-proven FA and a cross-sectional study showing a decrease in RDDFA. Attending childcare before 6 months was associated with less challenge-proven FA in one cohort. A cross-sectional survey identified an inverse relationship between hepatitis A serology and peanut sensitization. One of eleven trials investigating probiotics demonstrated a quicker acquisition of milk tolerance amongst allergic infants. Factors influencing microbial exposure may be partly responsible for rising FA burden, but further prospective studies using double-blind placebo controlled food challenges as an outcome are required.
    Pediatric Allergy and Immunology 04/2013;
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    ABSTRACT: This review highlights the progress made in food allergy (FA) and anaphylaxis research in pediatrics published in the journal Pediatric Allergy and Immunology since 2010. Putative risk factors for FA are as follows: a family history of allergic disease, particularly in the mother, low birth order, season of birth, and severe atopic eczema. Obstetric practices, antibiotic use, and home environment are factors deserving further research. Diagnostic decision levels and component-specific IgE are useful in the diagnosis of FA; however, oral food challenges remain the gold standard and may also be a means to reduce parental anxiety and to improve education. Oral immunotherapy studies show promise in increasing the threshold of reactivity of allergic patients and therefore improving their quality of life. In single-nut-allergic patients, introduction of other nuts allows broadening the diet and thus reducing the psychological impact of allergen avoidance. Nutritional deficiencies are not uncommon in food-allergic children and should be specifically assessed. The prescription of injectable adrenaline is still insufficient and not consistent among practitioners, requiring improved training and implementation of guidelines. Current research into the epidemiology and immunological mechanisms of FA and tolerance will enable us to devise strategies to both prevent and treat food allergies.
    Pediatric Allergy and Immunology 12/2012; 23(8):698-706.
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    ABSTRACT: Food allergic adolescents are at higher risk of fatal anaphylaxis than other children. Both allergen avoidance and maintaining access to adrenaline auto-injectors (AAI) are key goals in effective food allergy management, for which written guidance is often supplied. However, adolescents are rarely sufficiently prepared to use adrenaline during anaphylaxis. It is likely that further didactic education would bring limited improvement in management in this population. Focused discussion of each adolescent's perspectives and current management practice may allow more effective behavioural strategies to be adopted. Key areas for appraisal include subjects' experiences after previous allergen exposure with reference to worst response, recognising specific symptoms requiring AAI administration, and appropriate priority being given to timeliness of administering adrenaline. Behavioural strategies should be discussed to increase AAI accessibility. Rigor of allergen avoidance should not be compromised by false reassurance of proximity to emergency medication or medical services. Food allergic adolescents are motivated by the psychological impact of their condition, which often makes them feel different to their peers and may result in bullying. Methods of appropriately empowering adolescents may be considered, such as involvement of close friends and lay organisations to support appropriate management. Open discussion is crucial in engaging with adolescents' reasoning for adopting their chosen management strategies. Further research is warranted to identify cognitive patterns associated with high-risk behaviour, and to design appropriate interventions for the augmentation of adolescent self-management skills.
    Pediatric Allergy and Immunology 11/2012;
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    ABSTRACT: BACKGROUND: Peanut allergy (PA) is rare in countries in which peanuts are introduced early into infants' diets. Learning Early About Peanut Allergy (LEAP) is an interventional study aiming to assess whether PA can be prevented by oral tolerance induction. OBJECTIVE: We sought to characterize a population screened for the risk of PA. METHODS: Subjects screened for the LEAP interventional trial comprise the LEAP screening study cohort. Infants were aged 4 to 10 months and passed a prescreening questionnaire. RESULTS: This analysis includes 834 infants (mean age, 7.8 months). They were split into the following: group I, patients with mild eczema and no egg allergy (n = 118); group II, patients with severe eczema, egg allergy, or both but 0-mm peanut skin prick test (SPT) wheal responses (n = 542); group III, patients with severe eczema, egg allergy, or both and 1- to 4-mm peanut wheal responses (n = 98); and group IV, patients with greater than 4-mm peanut wheal responses (n = 76). Unexpectedly, many (17%) in group II had peanut-specific IgE sensitization (≥0.35 kU/L); 56% of group III were similarly sensitized. In contrast, none of the patients in group I and 91% of those in group IV had peanut-specific IgE sensitization. Sensitization on skin testing to peanut (SPT response of 1-4 mm vs 0 mm) was associated with egg allergy and severe eczema (odds ratio [OR], 2.31 [95% CI, 1.39-3.86] and 2.47 [95% CI, 1.14-5.34], respectively). Similar associations were observed with specific IgE sensitization. Black race was associated with a significantly higher risk of peanut-specific IgE sensitization (OR, 5.30 [95% CI, 2.85-9.86]). Paradoxically, for a given specific IgE level, black race was protective against cutaneous sensitization (OR, 0.15 [95% CI, 0.04-0.61]). CONCLUSION: Egg allergy, severe eczema, or both appear to be useful criteria for identifying high-risk infants with an intermediate level of peanut sensitization for entry into a PA prevention study. The relationship between specific IgE level and SPT sensitization needs to be considered within the context of race.
    The Journal of allergy and clinical immunology 11/2012;
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    ABSTRACT: It is unclear whether the initial route of allergen exposure in early life could influence the subsequent development of allergy, with cutaneous sensitization leading to peanut allergy (PA), and tolerance induced by oral exposure. The skin- and gastrointestinal (GI)-homing markers, cutaneous lymphocyte antigen (CLA) and α4β7 integrin, are used to determine whether the state of PA correlates with peanut-specific CLA responses, with tolerance associated with predominant α4β7 responses. CLA+ and α4β7+ memory T cells were isolated and cultured with peanut extract to assess their proliferation. Stimulation indices were compared in peanut allergic and non-allergic (NA) groups, and peanut-specific cytokine production was measured. In peanut allergic patients, peanut-specific proliferation predominates in the skin-homing CLA+ subset, whilst peanut-tolerant groups have a mixed CLA/α4β7 response (P = 0.008). Comparison with a control food antigen (ovalbumin) showed that these differences are allergen specific. Cytokine responses showed trends towards Th1 skewing in the GI-homing α4β7+ cells of peanut-tolerant groups and Th2 skewing in the skin-homing CLA+ cells of peanut allergic patients. The predominance of the CLA+ response to peanut in peanut allergic patients is consistent with the hypothesis that allergic sensitization occurs through the skin. The predominant α4β7+ response in peanut-tolerant groups suggests that allergen exposure through the GI tract induces tolerance.
    Allergy 03/2012; 67(3):336-42.
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    ABSTRACT: Some have suggested a protective effect of tuberculosis (TB) infection on allergic disease risk, but few studies have examined the association between the two. We therefore investigated whether TB disease and bacillus Calmette-Guérin (BCG) vaccination in early life protect against allergic disease. Information on allergic disease symptoms, past TB disease, and BCG vaccination as well as potential confounding factors was gathered by parental questionnaire from a randomly selected subset of 23,901 8- to 12-yr-old schoolchildren in 20 centers in both developed and developing countries. Children were also physically examined for flexural eczema and underwent skin prick testing. Pooled odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) across study centers were calculated, using random effects meta-analysis models. There were 245 (1.0%) reported cases of TB disease, and 66.3% (15,857) of all children received the BCG vaccine. Asthma, hay fever, and flexural eczema symptoms in the past year as well as flexural eczema on skin examination were all positively linked to a history of TB (adjusted pooled OR 'wheeze in the past year' = 2.27, 95% CI 1.52-3.41; adjusted pooled OR 'hay fever symptoms in the past year' = 2.23, 1.22-4.09; adjusted pooled OR 'flexural eczema symptoms in the past year' = 3.21, 2.01-5.12; adjusted pooled OR 'flexural eczema on skin examination' = 4.04, 1.71-9.56). Even higher risk estimates were seen for severe asthma and eczema symptoms [adjusted OR = 4.02 (2.17-7.47) and adjusted OR = 6.31 (2.19-18.17), respectively]. There was no significant association between past TB and skin prick test positivity (adjusted pooled OR = 1.32, 0.87-2.02). BCG vaccination during the first year of life was also not associated with any of the allergy outcomes. We found a uniform positive association between TB and all allergic disease outcomes, including eczema on skin examination. As this was a cross-sectional study, it is unclear whether this positive association is attributable to a causal relationship, and further longitudinal studies are required.
    Pediatric Allergy and Immunology 12/2011; 23(4):324-31.
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    ABSTRACT: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies; the urticaria, angio-oedema or mastocytosis pathway is the fifth pathway. The pathways focus on defining the competences required to improve the equity of care received by children with allergic conditions. The urticaria, angio-oedema or mastocytosis pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence. The pathway was reviewed by a broad group of stakeholders including the public and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. Three pathways are described: urticaria with or without angio-oedema, angio-oedema without weals, and mastocytosis. The results are presented in four parts: evidence review, mapping, external review and core knowledge documents. Acute urticaria has many causes and is often not allergic in origin. It is frequently of relatively short duration and easily managed with antihistamines alone. However, at the other extreme, causes of chronic urticaria and angio-oedema are difficult to diagnose and treatment can be complex. Thus defining the competence required for each extreme is critical to ensure optimal care. The evidence review identified that allergy testing and thyroid function testing were helpful in the investigation of chronic urticaria, that increasing the dose of antihistamine was effective in treating urticaria and that ciclosporin A and prednisolone were effective second line treatments. From the common presentation of acute (intermittent) urticaria to the uncommon presentations of chronic urticaria, angio-oedema and cutaneous mastocytosis, this pathway is a tool to assist health professionals to differentiate and manage these conditions.
    Archives of Disease in Childhood 11/2011; 96 Suppl 2:i34-7.
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    ABSTRACT: Exclusive breastfeeding for at least 4 months is recommended by many governments and allergy organizations to prevent allergic disease. To investigate whether exclusive breastfeeding protects against childhood eczema. Study subjects comprised 51,119 randomly selected 8- to 12-year-old schoolchildren in 21 countries. Information on eczema and breastfeeding was gathered by parental questionnaire. Children were also examined for flexural eczema and underwent skin prick testing. Odds ratios (ORs) were calculated for each study centre and then pooled across populations. There was a small increase in the risk of reported 'eczema ever' in association with 'breastfeeding ever' and breastfeeding < 6 months [pooled adjusted OR 1·11, 95% confidence interval (CI) 1·00-1·22 and OR 1·10, 95% CI 1·02-1·20, respectively]. There was no significant association between reported 'eczema ever' and breastfeeding > 6 months (pooled adjusted OR 1·09, 95% CI 0·94-1·26). Risk estimates were very similar for exclusive breastfeeding < 2 months, 2-4 months and > 4 months and for eczema symptoms in the past 12 months and eczema on skin examination. As for more severe eczema, breastfeeding per se conveyed a risk reduction on sleep disturbed eczema (pooled adjusted OR 0·71, 95% CI 0·53-0·96), but this effect was lost where children had been exclusively breastfed for > 4 months (pooled adjusted OR 1·02, 95% CI 0·67-1·54). Allergic sensitization and a history of maternal allergic disease did not modify any of these findings. Although there was a protective effect of ever having been breastfed on more severe disease, we found no evidence that exclusive breastfeeding for 4 months or longer protects against eczema. Our results are consistent with findings from a recent systematic review of prospective studies. The U.K. breastfeeding guidelines with regard to eczema should be reviewed. Intervention studies are now required to explore how and when solids should be introduced alongside breastfeeding to aid protection against eczema and other allergic diseases.
    British Journal of Dermatology 08/2011; 165(6):1280-9.
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    ABSTRACT: Allergic rhinitis is common worldwide, with significant morbidity and impact on quality of life. In patients who don't respond adequately to anti-allergic drugs. Subcutaneous allergen immunotherapy is effective although requires specialist administration. Sublingual immunotherapy may represent an effective and safer alternative. This Cochrane systematic review is an update of one published in 2003. We searched Cochrane ENT Group Trials Register, Central, PubMed, EMBASE, CINAHL, Web of Science, Biosis Previews, Cambridge Scientific Abstarcts, mRCT and additional sources. We included randomised, double-blind, placebo- controlled trials of sublingual immunotherapy in adults and children. Two authors selected studies and assessed them for quality. Data were put into RevMan 5.0 for a statistical analysis. We used standardised mean difference (SMD), with a random effect model to combine data. Sixty studies were included, with 49 suitable for meta-analysis. We found significant reductions in symptoms (SMD -0.49; 95%CI (-0.64 to -0.34, P < 0.00001)) and medication requirements (SMD -0.32; 95%CI (-0.43 to -0.21, P < 0.00001)) compared with placebo. None of the trials reported severe systemic reactions, anaphylaxis or use of Adrenaline. This updated review reinforces the conclusion of the original 2003 Cochrane Review that sublingual immunotherapy is effective for allergic rhinitis and appears a safe route of administration.
    Allergy 03/2011; 66(6):740-52.
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    ABSTRACT: The International Study of Asthma and Allergies in Childhood (ISAAC) is the largest epidemiological study ever performed and the only truly global allergy study. This review summarises the childhood eczema-related findings from ISAAC and discusses how these fit into our current understanding of eczema aetiology, with particular emphasis on worldwide time trends in eczema prevalence, climatic and dietary risk factors, breastfeeding, the role of skin barrier impairment and allergic sensitisation.
    Allergologia et Immunopathologia 01/2011; 39(3):174-82.
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