EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. METHODS: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. RESULTS: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. CONCLUSIONS: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.

An analysis of the psychometric properties of the translated versions of the European Organisation for the Research and Treatment of Cancer QLQ CX24 questionnaire in the two South African indigenous languages of Xhosa and Afrikaans.

This study evaluates the psychometric properties of the Xhosa and Afrikaans version, the European Organization for Research and Treatment of Cancer (EORTC) of the Quality of Life Questionnaire Cervical Cancer Module (QLQ-CX24). Translated Xhosa and Afrikaans versions, EORTC QLQ-CX24 and the core questionnaire (the EORTC QLQ-C30) were completed by 66 Xhosa and 142 Afrikaans speaking women newly diagnosed with cervical cancer. Construct reliability and validity of the EORTC QLQ-CX24 questionnaire were assessed via factor analysis, multi-trait scaling analyses and known group comparisons. The mean age was similar in the groups with a mean age of the Xhosa group (52 year) and Afrikaans group (49.2 year) (P = 0.25). The study groups had a high unemployment rate of, respectively, 52% (Xhosa) and 51% (Afrikaans) (P = 0.35). The Xhosa group had a statistically significant higher incidence of advanced stage (III and IV) disease (P = 0.006). Scale reliability was confirmed by Cronbach's α coefficients for internal consistency, which ranged from 0.73 to 0.81 (Xhosa) and 0.73 to 0.76 (Afrikaans). Clinical validity of both language versions was demonstrated by the ability to discriminate among different stages of cervical cancer. The translated Xhosa and Afrikaans versions of the EORTC QLQ-CX24 were found to be reliable and valid measure of quality of life of women with cervical cancer.

Pathophysiological mechanisms of exercise-induced anaphylaxis: an EAACI position statement.

This document is the result of a consensus on the mechanisms of exercise-induced anaphylaxis (EIAn), an unpredictable and potentially fatal syndrome. A multidisciplinary panel of experts including exercise physiologists, allergists, lung physicians, paediatricians and a biostatistician reached the given consensus. Exercise-induced anaphylaxis (EIAn) describes a rare and potentially fatal syndrome in which anaphylaxis occurs in conjunction with exercise. The pathophysiological mechanisms underlying EIAn have not yet been elucidated although a number of hypotheses have been proposed. This review evaluates the validity of each of the popular theories in relation to exercise physiology and immunology. On the basis of this evidence, it is concluded that proposed mechanisms lack validity, and it is recommended that a global research network is developed with a common approach to the diagnosis and treatment of EIAn in order to gain sufficient power for scientific evaluation.

EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy.

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.

Paediatric oral peanut challenges: a comparison of practice in London and western Switzerland.

BACKGROUND: There are guidelines on how to develop a food challenge protocol, but at present there is no gold standard guidance on method, and separate units produce differing protocols. METHODS: We performed a retrospective analysis of 200 patients' data from the paediatric allergy units in Lausanne and Geneva, Western Switzerland, and St Thomas' Hospital (STH), UK. RESULTS: St Thomas' Hospital has a younger cohort with a lower overall mean spIgE (2.36 kU/l vs. 8.00 kU/l, P = 0.004). The target peanut protein volumes differed: Switzerland 4.4 g vs. STH 8.4 g. Despite this, the dose actually achieved in positive challenges was not significantly different (2.33 g vs. 1.49 g, P = 0.16). 26% of challenges reacted at 4 g or more of peanut protein. CONCLUSIONS: The differences in results highlight how the variation in reasoning behind food challenge alters the outcome. Standardization of food challenges would allow easy comparison between hospitals and geographical areas for research purposes.

The use of adrenaline autoinjectors by children and teenagers.

BACKGROUND: Although adrenaline is recommended as first line treatment for anaphylaxis, it is often not utilized. There has been a debate about when adrenaline autoinjectors should be prescribed and how many should be dispensed. OBJECTIVES: To see how many adrenaline autoinjectors were used during anaphylactic reactions and to determine why they were not used in situations where they were clinically indicated. METHODS: Patients were recruited prospectively at 14 paediatric allergy clinics throughout UK. Participants completed a questionnaire covering demographic data, atopic status and details of allergic reactions in the previous year and reasons for using more than one device. RESULTS: A total of 969 patients were recruited of whom 466 (48.1%, 95% CI: 37.9-58.2) had had at least one reaction in the previous year; 245 (25.3%, 95% CI: 16.2-34.4) of these reactions were anaphylaxis. An adrenaline autoinjector was used by 41 (16.7%, 95% CI: 11.7-21.3) participants experiencing anaphylaxis. Thirteen participants received more than one dose of adrenaline, for nine of these a health professional gave at least one. The commonest reasons for using more than one were severe breathing difficulties (40%), lack of improvement with first dose (20%) and miss-firing (13.3%). The commonest reasons for not using adrenaline in anaphylaxis were 'thought adrenaline unnecessary' (54.4%) and 'unsure adrenaline necessary' (19.1%). Many with wheeze did not use their autoinjector. CONCLUSIONS AND CLINICAL RELEVANCE: Adrenaline is used by only a minority of patients experiencing anaphylaxis in the community. Thirteen of the 41 patients with anaphylaxis who used their autoinjector needed another dose of adrenaline. Further research is needed to consider how to best encourage the usage of adrenaline when clinically indicated in anaphylaxis.

The diagnosis of IgE-mediated food allergy in childhood.

IgE-mediated food allergy is a common condition in childhood and a recognized public health concern. An accurate diagnosis of food allergy facilitates the avoidance of the allergen - and cross-reactive allergens - and allows for safe dietary expansion. The diagnosis of food allergy relies on a combination of rigorous history, physical examination, allergy tests [skin prick tests (SPT) and/or serum-specific IgE] and oral food challenges. Diagnostic cut-off values for SPT and specific IgE results have improved the diagnosis of food allergy and thereby reduced the need to perform oral food challenges. This clinical case series seeks to highlight a contemporary approach to the diagnosis of food allergy in children strategies.

Acquisition of tolerance to egg and peanut in African food-allergic children with atopic dermatitis.

BACKGROUND: There are no previous data on tolerance development in children with atopic dermatitis (AD) and concomitant food allergy in low- and middle-income settings. OBJECTIVES: To determine the rate of tolerance acquisition to egg and peanut 5 years after diagnosing food allergies in South African (SA) children with AD, and to explore factors influencing tolerance acquisition. METHODS: Five years after first diagnosing food allergy in 37 SA children with egg and/or peanut allergy, they were reassessed for their allergies by questionnaire, skin-prick tests (SPTs) and ImmunoCAP-specific IgE (sIgE) tests (Thermo Fisher Scientific/Phadia, Sweden) to egg white, ovomucoid, peanut and Arachis hypogaea allergen 2 (Ara h 2), and incremental food challenges. RESULTS: Eighteen of 25 originally egg-allergic patients and 19 of 24 originally peanut-allergic children were followed up at a median age of 8 years and 3 months and 9 years and 6 months, respectively. A high percentage of children (72.2%) outgrew their egg allergy, and 15.8% outgrew their peanut allergy. Allergic comorbidity remained high, with asthma increasing over time, and AD remaining moderate in severity in the cohort overall. At diagnosis, sIgE egg white ≤9.0 kU/L and sIgE ovomucoid ≤2.0 kU/L were associated with tolerance development to egg 5 years later. At follow-up, sIgE egg white ≤0.70 kU/L, sIgE ovomucoid ≤0.16 kU/L, SPT egg-white extract ≤1 mm and SPT fresh egg ≤5 mm were associated with tolerance. At diagnosis, sIgE Ara h 2 ≤1.7 kU/L and SPT peanut ≤10 mm were associated with tolerance development to peanut 5 years later. At follow-up, sIgE peanut ≤0.22 kU/L, sIgE Ara h 2 ≤0.18 kU/L and SPT peanut ≤5.5 mm were associated with tolerance. CONCLUSIONS: Egg allergy was outgrown in 72.2% and peanut allergy in 15.8% of SA children 5 years after diagnosis of AD. This is in keeping with findings derived from studies in higher socioeconomic settings, and can help to guide the counselling of patients with allergies to these foods of high nutritional value.

Biological nutrient removal in membrane bioreactors: denitrification and phosphorus removal kinetics.

The impact of including membranes for solid liquid separation on the kinetics of nitrogen and phosphorus removal was investigated. To achieve this, a membrane bioreactor (MBR) biological nutrient removal (BNR) activated sludge system was operated. From batch tests on mixed liquor drawn from the MBR BNR system, denitrification and phosphorus removal rates were delineated. Additionally the influence of the high total suspended solids concentrations present in the MBR BNR system and of the limitation of substrate concentrations on the kinetics was investigated. Moreover the ability of activated sludge in this kind of system to denitrify under anoxic conditions with simultaneous phosphate uptake was verified and quantified. The denitrification rates obtained for different mixed liquor (ML) concentrations indicate no effect of ML concentration on the specific denitrification rate. The denitrification took place at a single specific rate (K(2)) with respect to the ordinary heterotrophic organisms (OHOs, i.e. non-PAOs) active mass. Similarly, results have been obtained for the P removal process kinetics: no differences in specific rates were observed for different ML or substrate concentrations. From the P removal batch tests results it seems that the biological phosphorus removal population (PAO) consists of 2 different sets of organisms denitrifying PAO and aerobic PAO.

Design and performance of BNR activated sludge systems with flat sheet membranes for solid-liquid separation.

The use of immersed membranes for solid-liquid separation in biological nutrient removal activated sludge (BNRAS) systems was investigated at lab scale. Two laboratory-scale BNR activated sludge systems were run in parallel, one a MBR system and the other a conventional system with secondary settling tanks. Both systems were in 3 reactor anaerobic, anoxic, aerobic UCT configurations. The systems were set up to have, as far as possible, identical design parameters such as reactor mass fractions, recycles and sludge age. Differences were the influent flow and total reactor volumes, and the higher reactor concentrations in the MBR system. The performances of the two systems were extensively monitored and compared to identify and quantify the influence of the membranes on system response. The MBR UCT system exhibited COD, FSA, TKN, TP and TSS removals that were consistently equivalent or superior to the conventional system. Better P removal in the MBR was attributed to lower observed P uptake in the anoxic zone. High nitrate loads to the anoxic reactor appeared to be the determining factor in stimulating P uptake. The MBR UCT system had a greater sludge production than the conventional system. This was partly attributable to the retention of all solids in the MBR reactor. For steady state design this increase is accommodated by increasing the influent unbiodegradable particulate COD fraction. Additionally an attempt was made to determine the Alpha values in the oxygen transfer rate. This paper briefly summarises and compares the results from both systems, and the conclusions that can be drawn from these results.

Respiratory comorbidity in South African children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an early and important step in the propagation of the allergic march, enhancing food and respiratory allergies via epicutaneous sensitisation to allergens. OBJECTIVES: To determine the prevalence and patterns of aeroallergen sensitisation, asthma and allergic rhinitis in South African (SA) children with AD. METHODS: This was a prospective, observational study in a paediatric university hospital in Cape Town, SA. Children with moderate to severe AD, aged 6 months - 10 years, were recruited randomly and investigated for food sensitisation and allergy. They were assessed for sensitisation to aeroallergens by the immuno solid-phase allergen chip test. House-dust mite DerP and DerF, dust mite Eur m, Timothy grass, Bermuda grass, tree pollen, mould (Alternaria), cat and dog sensitisation patterns were analysed. Symptoms of asthma and allergic rhinitis were elicited using a questionnaire modified from the International Study of Asthma and Allergies in Childhood study questions. RESULTS: One hundred participants (59 black Africans and 41 of mixed ethnicity) were enrolled (median age 42 months). Of the participants, 39% had symptoms of asthma and 53% symptoms of allergic rhinitis; 89% tested positive to at least one aeroallergen, most commonly house-dust mite DerP or DerF (81%), dust mite Eur m (51%), Timothy grass (36%) and cat (35%). Asthma, allergic rhinitis and aeroallergen sensitisation all increased with increasing age, while food allergy decreased with age. Food allergy was not an independent risk factor for respiratory allergies. Children were sensitised to indoor allergens (house-dust mite, pets) from an early age, while pollen allergies increased with age. CONCLUSIONS: In this cohort of SA children with moderate to severe AD, comorbidity with respiratory allergies was high. The prevalence of respiratory allergies increased with age while food allergy decreased with age, in keeping with the pattern of the allergic march. Seasonal allergies increased with age, while house-dust mite and pet allergy peaked in younger children, in keeping with early exposure via a defective skin barrier. Early and effective restoration of the skin barrier in AD may be a target for reducing aeroallergen-related diseases.

Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies: An AIRWAYS Integrated Care Pathways (ICPs) programme item (Action Plan B3 of the European Innovation Partnership on active and healthy ageing) and the Global Alliance against Chronic Respiratory Diseases (GARD), a World Health Organization GARD research demonstration project.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

Pathologic features of the femoral head in Mseleni disease.

Severe but atypical osteoarthritic deformities were found in each of 12 femoral heads removed during total hip arthroplasty for Mseleni disease. Although degenerative and regenerative changes were present throughout the cartilage, there was a paucity of eburnation. Histomorphometric analysis of bone at the line of excision indicated that mild osteomalacia was present in four of the 12 specimens. The percentage of the endosteum occupied by osteoid was 9.7 +/- 7.96 (SD) in the patients with Mseleni disease, compared with 5.6 +/- 4.33 in seven African black and 4.1 +/- 2.13 in 13 American white control subjects. The mean thickness of the osteoid seams was not increased. The findings suggest that osteomalacia is not a major pathogenetic factor in Mseleni disease.

Limited Pap screening associated with reduced risk of cervical cancer in South Africa.

BACKGROUND: We investigated the effect of Pap smear screening on the incidence of invasive cancer of the cervix in the Western Cape, South Africa where screening is limited. METHODS: Data were derived from a case-control study of the association of hormonal contraceptives and invasive cervical cancer. Incident cases (n = 524) of invasive cervical cancer who presented at two tertiary hospitals and controls (n = 1540) series matched for age, race, and place of residence were interviewed. Information on a wide range of variables was collected including whether the women had previously had a Pap smear taken and the number and timing of smears. Odds ratios (OR) and 95% CI were calculated using multiple logistic regression. RESULTS: The OR of cervical cancer was reduced among women who had ever had a smear (OR = 0.3, 95% CI: 0.3-0.4). The OR declined with increasing number of smears to 0.2 for >/=>3 smears (trend P = 0.0003). Among women who had a smear <5 years previously the OR was 0.3, but even if the smear was taken >/=15 years previously the women remained at reduced risk (OR = 0.5). CONCLUSION: The data suggest that even limited Pap smear screening reduces the risk of cervical cancer. Should a screening programme be successfully implemented, the incidence of cervical cancer might be reduced by as much as 70%.

Observer variation in detecting lymphadenopathy on chest radiography.

OBJECTIVE: To assess inter- and intra-observer agreement in the detection of lymphadenopathy on chest radiography in children at risk for tuberculosis. PATIENTS AND METHODS: Retrospective examination of the antero-posterior and lateral chest radiographs of children aged 1 month to 11 years discharged from the short-stay ward of the Red Cross Children's Hospital, Cape Town, with a diagnosis of tuberculosis or pneumonia. Four paediatric pulmonologists viewed the radiographs independently. The main outcome measures were inter- and intra-observer agreement on the presence or absence of lymphadenopathy, reported as present, absent or equivocal, and expressed as weighted kappa statistics. RESULTS: Weighted kappa for the six pairs of observers ranged from 0.14 (95%CI 0.02-0.30) to 0.52 (95%CI 0.35-0.69). After a 3-month interval, intra-observer agreement ranged from 0.44 (95%CI 0.25-0.62) to 0.71 (95%CI 0.56-0.87). The average weighted kappa for inter-observer agreement was 0.33, and the average intra-observer kappa was 0.55. CONCLUSIONS: There was 'fair' inter- and 'moderate' intra-observer agreement among paediatric pulmonologists in detecting lymphadenopathy on chest radiography in children. Caution is necessary when basing clinical decisions on the presence of lymphadenopathy on chest radiography.