Clinical-haematological changes and predictors of severity in acute food protein-induced enterocolitis syndrome reactions at oral food challenge: a multicentre observational study.

BACKGROUND: Oral food challenge (OFC) is the gold standard for diagnosis of acute Food Protein-Induced Enterocolitis Syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-haematological changes and predictors of severity of FPIES reactions at OFC. METHODS: Observational multicentre prospective study. Children aged 0-18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centres in Spain and Italy. OFC Outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed based on published '2017 FPIES Consensus' criteria. Clinical characteristics were recorded, and full blood count was done at baseline, reaction onset and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: 81 children had positive OFC (mild in 11% (9/81), moderate in 61% (49/81), severe in 28% (23/81)). Increase in neutrophils and reduction in eosinophils, basophils and lymphocytes was observed (P-value<0.05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not gender, age, culprit food, cumulative dose and previous reaction severity) was associated with reduced odds of severe reaction compared to giving multiple doses in a single day. CONCLUSION: Distinct haematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may associate a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

Association between the age of solid food introduction and eczema: A systematic review and a meta-analysis.

INTRODUCTION: Eczema is a common childhood ailment responsible for a considerable disease burden. Both timing of introduction to solid food and allergenic food are believed to be related to childhood eczema. Despite the growing body of evidence, the relationship between timing of any solid food introduction (allergenic and/or non-allergenic) and development of eczema has not previously been systematically reviewed. METHODS: PubMed and EMBASE databases were searched using food and eczema terms. Two authors selected papers according to the inclusion criteria and extracted information on study characteristics and measures of association. Meta-analyses were performed after grouping studies according to the age and type of exposure. RESULTS: A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, 2 case-controls, 1 cross-sectional study and 2 randomized controlled trials. Limited meta-analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema. CONCLUSIONS: The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema.

Validation of the Children's Sleep Habits Questionnaire in a sample of Greek children with allergic rhinitis.

BACKGROUND: Obstructive respiratory disorders, such as allergic rhinitis and asthma may impair sleep quality. The aim of this study is to validate the Children's Sleep Habits Questionnaire (CSHQ) for Greek children from 6 to 14 years of age. No validated tool has been developed so far to assess sleep disturbances in Greek school-aged children. METHODS: We examined the reliability and validity of the CSHQ in a sample of children with allergic rhinitis (AR) and a non-clinical population of parents of these children as a proxy measure of children's AR quality of life (QoL) as evaluated by the Pediatric Allergic Rhinitis Quality of Life (PedARQoL) questionnaire. RESULTS: The CSHQ questionnaire Child's Form (CF) had a moderate internal consistency with a Cronbach's alpha 0.671 and Guttman split-half coefficient of 0.563 when correlated with the PedARQoL (CF). There was also a moderate intraclass correlation of ICC=0.505 between the responses to both questionnaires in the two visits. The CSHQ Parent's Form (PF) had a very good internal consistency with a Cronbach's alpha of 0.928 and Guttman split-half coefficient of 0.798. There was a high intraclass correlation of 0.643 between the responses in the two visits. CONCLUSIONS: The Greek version of the CSHQ CF, but particularly the PF has proved to be a very reliable clinical instrument, which can be used in clinical trials for assessing sleep quality in school-aged children with sleep disturbances because of obstructive airway disorders, such as AR.

BSACI guideline for the diagnosis and management of peanut and tree nut allergy.

Peanut nut and tree nut allergy are characterised by IgE mediated reactions to nut proteins. Nut allergy is a global disease. Limited epidemiological data suggest varying prevalence in different geographical areas. Primary nut allergy affects over 2% of children and 0.5% of adults in the UK. Infants with severe eczema and/or egg allergy have a higher risk of peanut allergy. Primary nut allergy presents most commonly in the first five years of life, often after the first known ingestion with typical rapid onset IgE-mediated symptoms. The clinical diagnosis of primary nut allergy can be made by the combination of a typical clinical presentation and evidence of nut specifc IgE shown by a positive skin prick test (SPT) or specific IgE (sIgE) test. Pollen food syndrome is a distinct disorder, usually mild, with oral/pharyngeal symptoms, in the context of hay fever or pollen sensitisation, which can be triggered by nuts. It can usually be distinguish clinically from primary nut allergy. The magnitude of a SPT or sIgE relates to the probability of clinical allergy, but does not relate to clinical severity. SPT of ≥ 8 mm or sIgE ≥ 15 KU/L to peanut is highly predictive of clinical allergy. Cut off values are not available for tree nuts. Test results must be interpreted in the context of the clinical history. Diagnostic food challenges are usually not necessary but may be used to confirm or refute a conflicting history and test result. As nut allergy is likely to be a long-lived disease, nut avoidance advice is the cornerstone of management. Patients should be provided with a comprehensive management plan including avoidance advice, patient specific emergency medication and an emergency treatment plan and training in administration of emergency medication. Regular re-training is required.

A brief psychological intervention for mothers of children with food allergy can change risk perception and reduce anxiety: Outcomes of a randomized controlled trial.

BACKGROUND: Mothers of children with food allergy have increased anxiety, which may be influenced by healthcare professionals' communication of risk. OBJECTIVE: To evaluate a brief psychological intervention for reducing anxiety in mothers of children with food allergy. METHODS: Two hundred mothers of children with food allergy were recruited from allergy clinics. A computer-generated randomization list was used to allocate participants to a single-session cognitive behavioural therapy intervention including a risk communication module, or standard care. Anxiety and risk perception were assessed at 6 weeks and 1 year. Primary outcome was state anxiety at 6 weeks. Secondary outcomes included state anxiety at 1 year, risk perception at 6 weeks and 1 year, and salivary cortisol response to a simulated anaphylaxis scenario at 1 year. RESULTS: We found no significant difference in the primary outcome state anxiety at 6 weeks, with mean 31.9 (SD 10.2) intervention, 34.0 (10.2) control; mean difference 2.1 (95% CI -0.9, 5.0; P=.17). There was significantly reduced state anxiety at 6 weeks in the intervention group, in the subgroup of participants with moderate/high anxiety at enrolment (103/200, 52%), with mean 33.0 (SD 9.3) intervention, 37.8 (SD 10.0) control; mean difference 4.8 (95% CI 0.9, 8.7; P=.016; Cohen's d effect size 0.50). The psychological intervention also reduced risk perception and salivary cortisol response (P=.032; effect size 0.36). CONCLUSION: We found evidence that a brief psychological intervention which incorporates accurate risk information may impact on anxiety, risk perception and physiological stress response in mothers of children with food allergy.

Community healthcare professionals overestimate the risk of fatal anaphylaxis for food allergic children.

BACKGROUND: Fatal food anaphylaxis is rare, but a major concern for people with food allergy and their carers. We evaluated whether community healthcare professionals accurately estimate risk of fatal anaphylaxis for food allergic children, and whether accurate risk estimation is related to competence in recognizing and managing anaphylaxis. METHODS: We enrolled 90 community healthcare professionals in a cross-sectional survey - 30 primary care nurses, 30 school first aiders, 30 community pharmacists. Participant risk estimates for fatal and non-fatal anaphylaxis, and all-cause fatalities, were measured using a risk ladder. Participant anaphylaxis knowledge was assessed by questionnaire, and practical skills using a simulated anaphylaxis scenario. RESULTS: In all three groups, participants significantly overestimated the risk of fatal anaphylaxis for food allergic children, by a mean factor of 13.5-fold (95% CI 5.0, 31.6), but did not overestimate non-fatal anaphylaxis risk or all-cause fatality risk. We found no evidence of a relationship between successful adrenaline administration and risk estimation. CONCLUSIONS AND CLINICAL RELEVANCE: In conclusion, we have found evidence that community pharmacists, school first aiders and primary care nurses in the UK systematically overestimate the risk of fatal anaphylaxis for a food allergic child. This overestimation may result in increased patient and carer anxiety. Community practitioners who manage childhood food allergy and anaphylaxis need to be educated about the level of risk for fatal anaphylaxis in such children.

Can we identify patients at risk of life-threatening allergic reactions to food?

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions.

Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review.

BACKGROUND: Specific allergen immunotherapy (SIT) is an effective allergy treatment, but it is unclear whether SIT is effective for atopic eczema (AE). We undertook a systematic review to assess SIT efficacy and safety for treating AE. METHODS: We searched databases, ongoing clinical trials registers, and conference proceedings up to July 2015. Randomized controlled trials (RCTs) of SIT using standardized allergen extracts, compared with placebo/control, for treating AE in patients with allergic sensitization were eligible. RESULTS: We identified 12 eligible trials with 733 participants. Interventions included subcutaneous (six trials), sublingual (four trials), oral or intradermal SIT in children/adults allergic to house dust mite (10 trials), grass pollen or other inhalants. Risk of bias was moderate, with high loss to follow-up and nonblinding as the main concerns. For our primary outcomes, three studies (208 participants) reported no significant difference - patient-reported global disease severity improvement RR 0.75 (95% CI 0.45, 1.26); and eczema symptoms mean difference -0.74 on a 20-point scale (95% CI -1.98, 0.50). Two studies (85 participants) reported a significant difference - SIT improved global disease severity RR 2.85 (95% CI 1.02, 7.96); and itch mean difference -4.20 on a 10-point scale (95% CI -3.69, -4.71). Meta-analysis was limited due to extreme statistical heterogeneity. For some secondary outcomes, meta-analyses showed benefits for SIT, for example investigator-rated improvement in eczema severity RR 1.48 (95% CI 1.16, 1.88; six trials, 262 participants). We found no evidence of adverse effects. The overall quality of evidence was low. CONCLUSION: We found no consistent evidence that SIT is effective for treating AE, but due to the low quality of evidence further research is needed to establish whether SIT has a role in AE treatment.

Prebiotic-supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial.

BACKGROUND: Prevention 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. OBJECTIVE: To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high-risk infants [ISRCTN65195597]. METHODS: We conducted a parallel-group, multicentre, randomized double-blind controlled trial of pHF-OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events. RESULTS: Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (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. CONCLUSION: pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.

Exposures influencing total IgA level in colostrum.

Immunoglobulin A (IgA) is a predominant immunoglobulin present in human breast milk and is known to play an important role in infant gut immunity maturation. Breast milk composition varies between populations, but the environmental and maternal factors responsible for these variations are still unclear. We examined the relationship between different exposures and levels of IgA in colostrum. The objective of this study was to examine whether exposures analysed influence levels of IgA in colostrum. The present study used 294 colostrum samples from the MecMilk International cohort, collected from women residing in London, Moscow and Verona. Samples were analysed in automated Abbott Architect Analyser. We found an inverse correlation between time postpartum and colostrum total IgA level (r=-0.49, P<0.001). Adjusting for maternal parity, smoking, fresh fruit and fish consumption and allergen sensitization, multiple regression model showed that IgA levels were influenced by colostrum collection time (P<0.0001) and country of collection (P<0.01). Mode of delivery influence did not appear to be significant in univariate 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 effect should be confirmed on larger cohorts. Further work is needed to determine ways to correct for IgA decline over time in colostrum, and to find the cause of variations in IgA levels between the countries.

Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial.

BACKGROUND: Previous work has shown patients commonly misuse adrenaline autoinjectors (AAI). It is unclear whether this is due to inadequate training, or poor device design. We undertook a prospective randomized controlled trial to evaluate ability to administer adrenaline using different AAI devices. METHODS: We allocated mothers of food-allergic children prescribed an AAI for the first time to Anapen or EpiPen using a computer-generated randomization list, with optimal training according to manufacturer's instructions. After one year, participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen, JEXT or Auvi-Q), without device-specific training. We assessed ability to deliver adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one year after initial training, and following device switch. Primary outcome was successful adrenaline administration at six weeks, assessed by an independent expert. Secondary outcomes were success at one year, success after switching device, and adverse events. RESULTS: We randomized 158 participants. At six weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%) participants allocated to EpiPen were successful - RR 1.00 (95% CI 0.68-1.46). Success rates at one year were also similar, but digital injection was more common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007). When switched to a new device without specific training, success rates were higher with Auvi-Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001). CONCLUSIONS: AAI device design is a major determinant of successful adrenaline administration. Success rates were low with several devices, but were high using the audio-prompt device Auvi-Q.

Mechanisms of allergic disease - environmental and genetic determinants for the development of allergy.

Allergic disease can be viewed as an early manifestation of immune dysregulation. Environmental exposures including maternal inflammation, diet, nutrient balance, microbial colonization and toxin exposures can directly and indirectly influence immune programming in both pregnancy and the postnatal period. The intrauterine microclimate is critical for maternal and fetal immunological tolerance to sustain viable pregnancy, but appears susceptible to environmental conditions. Targeting aspects of the modern environment that promote aberrant patterns of immune response is logical for interventions aimed at primary prevention of allergic disease. Defining the mechanisms that underpin both natural and therapeutic acquisition of immunological tolerance in childhood will provide insights into the drivers of persistent immune dysregulation. In this review, we summarize evidence that allergy is a consequence of intrauterine and early life immune dysregulation, with specific focus on contributing environmental risk factors occurring preconception, in utero and in the early postnatal period. We explore the immunological mechanisms which underpin tolerance and persistence of allergic disease during childhood. It is likely that future investigations within these two domains will ultimately provide a road map for the primary prevention of allergic disease.

Factors affecting breast milk composition and potential consequences for development of the allergic phenotype.

There is conflicting evidence on the protective role of breastfeeding in relation to allergic sensitization and disease. The factors in breast milk which influence these processes are still unclear and under investigation. We know that colostrum and breast milk contain a variety of molecules which can influence immune responses in the gut-associated lymphoid tissue of a neonate. This review summarizes the evidence that variations in colostrum and breast milk composition can influence allergic outcomes in the infant, and the evidence that maternal and environmental factors can modify milk composition. Taken together, the data presented support the possibility that maternal dietary interventions may be an effective way to promote infant health through modification of breast milk composition.

Incidence of food anaphylaxis in people with food allergy: a systematic review and meta-analysis.

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.

Effect of a novel temperature-controlled laminar airflow device on personal breathing zone aeroallergen exposure.

Temperature-controlled laminar airflow improves symptoms in atopic asthmatics, but its effects on personal allergen exposure are unknown. We aimed to evaluate its effects on personal cat allergen and particulate exposures in a simulated bedroom environment. Five healthy volunteers lay under an active and an inactive temperature-controlled laminar airflow device for 175 min, in a simulated bedroom containing bedding from a cat owner. Total airborne particles (≥0.5 - ≥10 µm diameter) were quantified with a laser particle counter. Airborne allergen was sampled with Institute of Occupational Medicine filters. Inhaled exposure was sampled with nasal air samplers. Allergen-containing particles were quantified by immunoassay. Treatment reduced total airborne particles (>0.5 µm diameter) by >99% (P < 0.001) and reduced airborne allergen concentration within the breathing zone (ratio of median counts = 30, P = 0.043). Treatment reduced inhaled allergen (ratio of median counts = 7, P = 0.043). Treatment was not associated with a change in airborne allergen concentration outside of the breathing zone (P = 0.160). Temperature-controlled laminar airflow treatment of individuals in an allergen-rich experimental environment results in significant reductions in breathing zone allergenic and non-allergenic particle exposure, and in inhaled cat allergen exposure. These findings may explain the clinical benefits of temperature-controlled laminar airflow.

Developments in the field of allergy in 2013 through the eyes of Clinical and Experimental Allergy.

2013 was another exciting year for allergy in general and Clinical and Experimental Allergy in particular. In the field of asthma and rhinitis, there continued to be a focus on heterogeneity and phenotypes with increasing use of biostatistical techniques to determine clusters of similar populations. Obesity- and aspirin-associated disease are intriguing associations with asthma which were explored in a number of papers. We published a number of excellent papers on mechanisms of airway inflammation and how this relates to physiology, pathology, genetics and biomarkers in both human and experimental model systems. In terms of mechanisms, there is less on individual cell types in allergic disease at the moment, but the immunology of allergic disease continued to fascinate our authors. Another area that was popular both in the mechanisms and in the epidemiology sections was early life events and how these lead to allergic disease, with an increasing focus on the role of the microbiome and how this influences immune tolerance. In the clinical allergy section, oral immunotherapy for food allergy is clearly a major topic of interest at the moment as was in vitro testing to distinguish between sensitization and allergic disease. There was less on inhalant allergy this year, but a good representation from the drug allergy community including some interesting work on non-IgE-mediated mechanisms. In the allergen section, important new allergens continue to be discovered, but the major focus as in the last couple of years was on working out how component-resolved approaches can improve diagnosis and management of food and venom allergy.

Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis.

BACKGROUND: Food allergy is a common cause of anaphylaxis, but the incidence of fatal food anaphylaxis is not known. The aim of this study was to estimate the incidence of fatal food anaphylaxis for people with food allergy and relate this to other mortality risks in the general population. METHODS: We undertook a systematic review and meta-analysis, using the generic inverse variance method. Two authors selected studies by consensus, independently extracted data and assessed the quality of included studies using the Newcastle-Ottawa assessment scale. We searched Medline, Embase, PsychInfo, CINAHL, Web of Science, LILACS or AMED, between January 1946 and September 2012, and recent conference abstracts. We included registries, databases or cohort studies which described the number of fatal food anaphylaxis cases in a defined population and time period and applied an assumed population prevalence rate of food allergy. RESULTS: We included data from 13 studies describing 240 fatal food anaphylaxis episodes over an estimated 165 million food-allergic person-years. Study quality was mixed, and there was high heterogeneity between study results, possibly due to variation in food allergy prevalence and data collection methods. In food-allergic people, fatal food anaphylaxis has an incidence rate of 1.81 per million person-years (95%CI 0.94, 3.45; range 0.63, 6.68). In sensitivity analysis with different estimated food allergy prevalence, the incidence varied from 1.35 to 2.71 per million person-years. At age 0-19, the incidence rate is 3.25 (1.73, 6.10; range 0.94, 15.75; sensitivity analysis 1.18-6.13). The incidence of fatal food anaphylaxis in food-allergic people is lower than accidental death in the general European population. CONCLUSION: Fatal food anaphylaxis for a food-allergic person is rarer than accidental death in the general population.