Publications
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Warner JO, 2017, The foetal origins of allergy, Current Allergy and Clinical Immunology, Vol: 30, Pages: 62-68, ISSN: 1609-3607
The dramatic increases in allergy and allergic diseases which have occurred over the past half-century have been strongly associated with changes in early life events. Changes in lifestyle, which have affected nutrition, allergen and microbial exposures, have been strongly implicated as explanations for changing allergy susceptibility. To what extent these influences affect the foetus during pregnancy rather than the infant post-natally is uncertain. In all probability there is a sequence of events through pregnancy and early post-natal life which in combination change the outcomes. Successful pregnancy is associated with a Th-2, allergy-biased immunological environment which results in virtually all neonates having an apparent allergic pattern of immune responsiveness. Under normal circumstances this is rapidly down-regulated after birth, most likely affected by the evolving human microbiome. Interactions between genetic and environmental variation, both during pregnancy and in the first months of the infant’s life, perturb this normal sequence and lead to a sustained Th-2-biased allergic response. The future for prevention rests in identifying the key influences that should highlight strategies to turn the clock back to an era of low prevalence of allergic diseases.
Munblit D, Treneva M, Peroni DG, et al., 2017, Immune components in human milk are associated with early infant immunological health outcomes: a prospective 3 country analysis, Nutrients, Vol: 9, ISSN: 2072-6643
The role of breastfeeding in improving allergy outcomes in early childhood is still unclear. Evidence suggests that immune mediators in human milk (HM) play a critical role in infant immune maturation as well as protection against atopy/allergy development. We investigated relationships between levels of immune mediators in colostrum and mature milk and infant outcomes in the first year of life. In a large prospective study of 398 pregnant/lactating women in the United Kingdom, Russia and Italy, colostrum and mature human milk (HM) samples were analysed for immune active molecules. Statistical analyses used models adjusting for the site of collection, colostrum collection time, parity and maternal atopic status. Preliminary univariate analysis showed detectable interleukin (IL) 2 and IL13 in HM to be associated with less eczema. This finding was further confirmed in multivariate analysis, with detectable HM IL13 showing protective effect OR 0.18 (95% CI 0.04–0.92). In contrast, a higher risk of eczema was associated with higher HM concentrations of transforming growth factor β (TGFβ) 2 OR 1.04 (95% CI 1.01–1.06) per ng/mL. Parental-reported food allergy was reported less often when IL13 was detectable in colostrum OR 0.10 (95% CI 0.01–0.83). HM hepatocyte growth factor (HGF) was protective for common cold incidence at 12 months OR 0.19 (95% CI 0.04–0.92) per ng/mL. Data from this study suggests that differences in the individual immune composition of HM may have an influence on early life infant health outcomes. Increased TGFβ2 levels in HM are associated with a higher incidence of reported eczema, with detectable IL13 in colostrum showing protective effects for food allergy and sensitization. HGF shows some protective effect on common cold incidence at one year of age. Future studies should be focused on maternal genotype, human milk microbiome and diet influence on human milk immune composition and both short- and long-term h
Warner JO, 2017, Use of temperature-controlled laminar airflow in the management of atopic asthma: clinical evidence and experience, Therapeutic Advances in Respiratory Disease, Vol: 11, Pages: 181-188, ISSN: 1753-4666
Avoidance of allergens in the treatment of asthma has hitherto not achieved significant benefit despite the strong evidence that allergy both increases severity and contributes to exacerbations of asthma. House dust mite, cat and dog allergens are the most common perennial allergic triggers and most avoidance strategies have focused on reducing exposures in bedrooms. Cochrane reviews have suggested that they neither significantly reduce allergen levels nor improve asthma. While the lack of efficacy may be assumed to be a consequence of exposures occurring outside the bedroom, prolonged sleep is associated with increased susceptibility to bronchospasm and airway inflammation. Thus, if efficient reductions in allergen exposure could be achieved during sleep, it might be expected that this would result in significant improvements in control of asthma. The temperature-controlled laminar airflow (TLA) is a system which can be employed over beds in a domestic environment and results in massive reductions in particulate exposure of recumbent subjects, including highly respirable allergens such as Fel. D1 from cats. Trials of TLA have demonstrated highly significant improvements in asthma quality of life and reductions on airway inflammation as monitored by exhaled nitric oxide levels. Furthermore, in patients with the worst disease, severe exacerbation frequency was significantly reduced. Based on UK health-service costs, the use of TLA falls well below the National Institute for Health and Care Excellence (NICE) threshold for the incremental cost effectiveness ratio (ICER) per quality adjusted life year (QALY). Indeed, for those with frequent exacerbations, it is cost saving and should be prescribed for such allergic asthmatic patients.
Munblit D, Treneva M, Peroni DG, et al., 2016, Colostrum and mature human milk of women from London, Moscow and Verona: determinants of immune composition, Nutrients, Vol: 8, ISSN: 2072-6643
Cytokines and growth factors in colostrum and mature milk may play an important role in infant immune maturation, and may vary significantly between populations. We aimed to examine associations between environmental and maternal factors, and human milk (HM) cytokine and growth factor levels. We recruited 398 pregnant/lactating women in United Kingdom, Russia and Italy. Participants underwent skin prick testing, questionnaire interview, colostrum and mature milk sampling. HM cytokine and growth factor levels were quantified by electro-chemiluminescence. We found significant geographical variation in growth factor levels, but no evidence of variation between sites in cytokine detectability. There was an inverse correlation between time of milk sampling and growth factor levels in colostrum for HGF and TGFβ1; and 3 but not TGFβ2, and levels were significantly higher in colostrum than mature milk for all growth factors. The kinetics of decline were different for each growth factor. Cytokines were present at much lower levels than growth factors, and the decline over time was less consistent. HM growth factors and cytokine levels vary between populations for unknown reasons. Levels of HM mediators decline at different rates postpartum, and these findings suggest specific biological roles for HM growth factors and cytokines in early postnatal development.
Minshall E, Patel H, Francis N, et al., 2016, Local chemokine profiling in eosinophilic esophagitis: the Synthetic Absorptive Matrix test, Pediatric Allergy and Immunology, Vol: 28, Pages: 100-102, ISSN: 1399-3038
We describe a novel method of sampling the esophageal lining fluid in children and show that levels of eotaxin-1 and MCP-4 differentiate those children with a histological diagnosis of EoE from those without. This article is protected by copyright. All rights reserved.
Wopereis H, Sim K, Shaw A, et al., 2016, Decreased microbial conversion of lactic acid into butyrate in infants developing eczema, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: Wiley, Pages: 168-169, ISSN: 0105-4538
Gore C, Griffin R, Rothenberg T, et al., 2016, New patient-reported experience measure for children with allergic disease: development, validation and results from integrated care., Archives of Disease in Childhood, Vol: 101, Pages: 935-943, ISSN: 0003-9888
OBJECTIVES: To develop and validate a new allergy-specific patient-reported experience measure (PREM) for children and their parents, and to collect feedback in an integrated care setting. DESIGN: Two allergy-specific PREMs were produced using focus groups, cognitive testing, two prospective validation studies (collaboration: Royal College of Paediatrics and Child Health, Picker Institute Europe, Imperial College/London): 'Your Allergy Care', for children aged 8-16 years; 'Your Child's Allergy Care', for parents of children aged 0-7 years. SETTING: Community event, primary/secondary/tertiary allergy care settings. MAIN OUTCOME MEASURES: Performance of PREMs in validation study; reported experience of allergy care. PARTICIPANTS: 687 children with allergic conditions and their parents/carers. RESULTS: In total, 687 questionnaires were completed; 503/687 (253 child; 250 parent) for the final survey. In both surveys, demographic variations were not associated with differences in results. Although 71% of patients reported one or more allergic conditions (food allergy/eczema/hay fever/asthma), 62% required multiple visits before receiving final diagnosis. Overall, patient experience was good for communication with patient/parent, competence and confidence in ability, and 73% felt looked after 'very well' and 23% 'quite well'. Areas for improvement included communication with nurseries/schools, more information on side effects, allergic conditions and allergen/irritant avoidance. Allergy care in primary/emergency care settings was associated with higher problem-scores (worse experience) than in specialist clinics. CONCLUSIONS: These new PREMs will allow allergy-specific patient experience reporting for children and parents and help identification of priority areas for improvement and commissioning of care. Efforts towards better allergy care provision must be targeted at primary and emergency care settings and underpinned by improving communication between healthcare provi
Mavroudi A, Chrysochoou EA, Boyle RJ, et al., 2016, Validation study of the pediatric allergic rhinitis quality of life questionnaire, Asian Pacific Journal of Allergy and Immunology, Vol: 34, Pages: 159-165, ISSN: 0125-877X
Background: The Paediatric Allergic Rhinitis Quality of Life Questionnaire (Ped-AR-QoL) is the first tool developed for the assessment of health-related quality of life (QoL) in Greek children with allergic rhinitis (AR). Objective: The aim of the current study was to validate the child and parent forms of the Ped-AR-QoL in children aged 6-14 years-old who suffered from AR and were followed in a pediatric allergy clinic. Methods: The Ped-AR-QoL, which was completed by 112 children and their parents, was correlated to the generic QoL questionnaire (Disabkids), which is already valid in Greece for children with chronic disorders, as well as with expert opinions on the severity of disease. Results: The Ped-AR-QoL child and parent forms had very good internal consistency (α values of 0.797 and 0.872, respectively), while there was a moderate positive correlation of the disease-specific questionnaire with most of the subscales of the generic questionnaire. There has been a statistically significant association between the Ped-AR-QoL and the expert perception of disease severity. Conclusions: The Ped-AR-QoL had very good reliability and convergent validity when compared with the generic Disabkids QoL. The significance of the association between the disease-specific questionnaire and the expert opinion is an important finding validating the questionnaire. The Ped-AR-QoL may become a helpful tool which can be used in everyday clinical practice by clinicians and it may also be used for assessing therapeutic interventions in clinical trials.
Turner PJ, Warner JO, 2016, Allergy, The Science of Paediatrics Mrcpch Mastercourse, Publisher: Elsevier, ISBN: 9780702063138
This book is "innovative and original in assisting the reader to apply the principles of science to paediatric practice".
Brazier P, Schauer U, Hamelmann E, et al., 2016, Economic analysis of temperature-controlled laminar airflow (TLA) for the treatment of patients with severe persistent allergic asthma, BMJ Open Respiratory Research, Vol: 3, ISSN: 2052-4439
Boyle RJ, Tang MLK, Chiang WC, et al., 2016, Prebiotic-supplemented partially hydrolysed cow’s milk formula for the prevention of eczema in high risk infants: a randomised controlled trial, Allergy, Vol: 71, Pages: 701-710, ISSN: 1398-9995
BackgroundPrevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes.ObjectiveTo evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high risk infants [ISRCTN65195597].MethodsWe conducted a parallel-group, multi-centre, randomised double-blind controlled trial of pHF-OS versus standard cow's milk formula. Infants with a family history of allergic disease were randomised (stratified by centre/maternal allergy) to active (n=432) or control (n=431) formula until 6 months age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomised at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomised, immune markers at 6 months, and adverse events.ResultsEczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks age, versus 93/324 (28.7%) control (OR 0.98 95%CI 0.68, 1.40; P=0.90), and 107/347 (30.8%) pHF-OS versus 112/370 (30.3%) control in all infants randomised (OR 0.99 95%CI 0.71, 1.37; P=0.94). pHF-OS did not change most immune markers including total/specific IgE, however pHF-OS reduced cow's milk-specific IgG1 (p<0.0001), and increased regulatory T cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events.ConclusionpHF-OS does not prevent eczema in the first year in high risk infants. The immunological changes found require confirmation in a separate cohort.
Spergel JM, Warner JO, 2016, Pharmacotherapies Early in Life to Prevent the Atopic March, Allergy, Immunity and Tolerance in Early Childhood: The First Steps of the Atopic March, Pages: 303-319, ISBN: 9780124202269
The progression of atopic dermatitis to asthma is considered part of the atopic march. Various strategies have been examined to prevent this progression. In related diseases such as inflammatory bowel disease, disease-modifying agents exist and affect the natural history of disease. These agents can be broken down into three broad classes: primary, secondary, and tertiary agents. Primary strategies have preliminary success in preventing atopic dermatitis with barrier creams, but additional longitudinal studies are needed to see whether the benefit is maintained. Secondary strategies using antihistamines, topical medications for atopic dermatitis or asthma, have not been able to prevent the progression of atopic dermatitis to asthma or change the natural history of asthma. However, specific immunotherapy has shown benefit in one well-designed study. Tertiary prevention agents that help with symptom and disease flare-ups are successful with the use of maintenance medications for asthma or atopic dermatitis. Additional studies are needed to find the optimal method to prevent development of the atopic march.
Boyle RJ, 2015, Effects of pre-natal vitamin D supplementation with partial correction of vitamin D deficiency on early life healthcare utilisation: a randomised controlled trial, PLOS One, ISSN: 1932-6203
Umasunthar T, Leonardi-Bee J, Turner PJ, et al., 2015, Incidence of food anaphylaxis in people with food allergy: a systematic review and meta-analysis., Clinical & Experimental Allergy, Vol: 45, Pages: 1621-1636, ISSN: 1365-2222
BACKGROUND: Food allergy is a common cause of anaphylaxis, but the incidence of anaphylaxis in food allergic people is unknown. METHODS: We undertook a systematic review and meta-analysis, using the inverse variance method. Two authors selected studies by consensus, independently extracted data and assessed study quality using the Newcastle-Ottawa assessment scale. We searched Medline, Embase, PsychInfo, CINAHL, Web of Science, LILACS and AMED between January 1946 and September 2012, and recent conference abstracts. We included registries, databases or cohort studies which described the number of food anaphylaxis cases in a defined population and time period, and applied an assumed population prevalence of food allergy. RESULTS: We included data from 34 studies. There was high heterogeneity between study results, possibly due to variation in study populations, anaphylaxis definition and data collection methods. In food allergic people, medically-coded food anaphylaxis had an incidence rate of 0.14 per 100 person years (95% CI 0.05, 0.35; range 0.01, 1.28). In sensitivity analysis using different estimated food allergy prevalence, the incidence varied from 0.11 to 0.21 per 100 person years. At age 0-19 the incidence rate for anaphylaxis in food allergic people was 0.20 (95%CI 0.09, 0.43; range 0.01, 2.55; sensitivity analysis 0.08, 0.39). At age 0-4 an incidence rate of up to 7.00 per 100 person years has been reported. In food allergic people, hospital admission due to food anaphylaxis had an incidence rate of 0.09 (95% CI 0.01, 0.67; range 0.02, 0.81) per 1000 person years; 0.20 (95% CI 0.10, 0.43; range 0.04, 2.25) at age 0-19 and 0.50 (0.26, 0.93; range 0.08, 2.82) at age 0-4. CONCLUSION: In food allergic people, the incidence of food allergic reactions which are coded as anaphylaxis by healthcare systems is low at all ages, but appears to be highest in young children. This article is protected by copyright. All rights reserved.
Munblit D, Sheth S, Abrol P, et al., 2015, Exposures influencing total IgA level in colostrum, Journal of Developmental Origins of Health and Disease, Vol: 7, Pages: 61-67, ISSN: 2040-1744
Immunoglobulin A (IgA) is a predominant immunoglobulin present in human breast milk and is known to play an important role in infant gutimmunity maturation. Breast milk composition varies between populations, but the environmental and maternal factors responsible for thesevariations are still unclear. We examined the relationship between different exposures and levels of IgA in colostrum. The objective of this studywas to examine whether exposures analysed influence levels of IgA in colostrum. The present study used 294 colostrum samples from the MecMilkInternational cohort, collected from women residing in London, Moscow and Verona. Samples were analysed in automated Abbott ArchitectAnalyser. We found an inverse correlation between time postpartum and colostrum total IgA level (r = −0.49, P< 0.001). Adjusting for maternalparity, smoking, fresh fruit and fish consumption and allergen sensitization, multiple regression model showed that IgA levels were influenced bycolostrum collection time (P<0.0001) and country of collection (P< 0.01). Mode of delivery influence did not appear to be significant inunivariate comparisons, once adjusted for the above maternal characteristics it showed a significant influence on total IgA (P = 0.01).We conclude that the concentration of IgA in colostrum drops rapidly after birth and future studies should always consider this factor in analysis.IgA concentration varied significantly between countries, with the highest level detected in Moscow and lowest in Verona. Mode of delivery effectshould be confirmed on larger cohorts. Further work is needed to determine ways to correct for IgA decline over time in colostrum, and to find thecause of variations in IgA levels between the countries.
Munblit D, Treneva M, Peroni D, et al., 2015, Colostrum immune composition and immunological outcomes using principal component analysis (PCA), Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 111-111, ISSN: 0105-4538
Umasunthar T, Procktor A, Hodes M, et al., 2015, Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial, ALLERGY, Vol: 70, Pages: 855-863, ISSN: 0105-4538
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Brough HA, Turner PJ, Wright T, et al., 2015, Dietary management of peanut and tree nut allergy: what exactly should patients avoid?, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 45, Pages: 859-871, ISSN: 0954-7894
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Jones KDJ, Ali R, Khasira MA, et al., 2015, Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial, BMC MEDICINE, Vol: 13, ISSN: 1741-7015
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- Citations: 38
Chakravorty S, Tallett A, Hay H, et al., 2015, Assessing the care experiences of people living with sickle cell disease to inform the development of a patient reported experience measure (PREM), 55th Annual Scientific Meeting of the British-Society-for-Haematology, Publisher: WILEY-BLACKWELL, Pages: 25-26, ISSN: 0007-1048
Munblit D, Boyle RJ, Warner JO, 2015, Factors affecting breast milk composition and potential consequences for development of the allergic phenotype, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 45, Pages: 583-601, ISSN: 0954-7894
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- Citations: 44
Gore RB, Boyle RJ, Gore C, et al., 2015, Effect of a novel temperature-controlled laminar airflow device on personal breathing zone aeroallergen exposure, INDOOR AIR, Vol: 25, Pages: 36-44, ISSN: 0905-6947
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Boyle RJ, Procktor A, Hodes M, et al., 2015, Epinephrine Autoinjector Use One Year after Training: A Randomised Controlled Comparison of Two Different Devices, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB209-AB209, ISSN: 0091-6749
Spergel JM, Warner JO, 2015, Pharmacotherapies Early in Life to Prevent the Atopic March, Allergy, Immunity and Tolerance in Early Childhood: The First Steps of the Atopic March, Pages: 303-319, ISBN: 9780127999302
The progression of atopic dermatitis to asthma is considered part of the atopic march. Various strategies have been examined to prevent this progression. In related diseases such as inflammatory bowel disease, disease-modifying agents exist and affect the natural history of disease. These agents can be broken down into three broad classes: primary, secondary, and tertiary agents. Primary strategies have preliminary success in preventing atopic dermatitis with barrier creams, but additional longitudinal studies are needed to see whether the benefit is maintained. Secondary strategies using antihistamines, topical medications for atopic dermatitis or asthma, have not been able to prevent the progression of atopic dermatitis to asthma or change the natural history of asthma. However, specific immunotherapy has shown benefit in one well-designed study. Tertiary prevention agents that help with symptom and disease flare-ups are successful with the use of maintenance medications for asthma or atopic dermatitis. Additional studies are needed to find the optimal method to prevent development of the atopic march.
Jones KDJ, Huenten-Kirsch B, Laving AMR, et al., 2014, Inflammatory bowel disease in Africa: hiding in plain sight?, IMMUNOLOGY, Vol: 143, Pages: 123-123, ISSN: 0019-2805
DeBaun MR, Rodeghier M, Cohen R, et al., 2014, Factors predicting future ACS episodes in children with sickle cell anemia, AMERICAN JOURNAL OF HEMATOLOGY, Vol: 89, Pages: E212-E217, ISSN: 0361-8609
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Boyle R, Warner JO, 2014, No relationship between biochemical measures of liver function and food sensitisation in infancy, European-Academy-of-Allergy-and-Clinical-Immunology Congress, Publisher: WILEY-BLACKWELL, Pages: 381-381, ISSN: 0105-4538
Tang ML, Nauta A, Rijnierse A, et al., 2014, Hypo-antigenic and immune modulatory properties of a partially hydrolyzed cow's milk formula supplemented with prebiotic oligosaccharides, European-Academy-of-Allergy-and-Clinical-Immunology Congress, Publisher: WILEY-BLACKWELL, Pages: 310-310, ISSN: 0105-4538
Wopereis H, Sim K, Shaw A, et al., 2014, The developmental gut microbiota is modulated towards a pattern closer to breastfed infants by a partially hydrolyzed cow's milk formula supplemented with specific prebiotic oligosaccharides, European-Academy-of-Allergy-and-Clinical-Immunology Congress, Publisher: WILEY-BLACKWELL, Pages: 315-315, ISSN: 0105-4538
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Bakshi D, Hanna H, Gore R, et al., 2014, Analysis of changes in airborne pollutant levels in response to nocturnal temperature controlled laminar airflow treatment, European-Academy-of-Allergy-and-Clinical-Immunology Congress, Publisher: WILEY-BLACKWELL, Pages: 454-454, ISSN: 0105-4538
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