Background
The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, ...IgE‐mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost‐effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost‐effectiveness of AIT for these conditions.
Methods
We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations.
Results
Twenty‐three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost‐effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost‐effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost‐effectiveness threshold of £20 000/quality‐adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost‐effective with an incremental cost‐effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost‐effective for very high‐risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost‐effectiveness of AIT for food allergy.
Conclusions
Overall, the evidence to support the cost‐effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost‐effective for people with allergic rhinitis with or without asthma and in high‐risk subgroups for venom allergy. We were unable to draw any conclusions on the cost‐effectiveness of AIT for food allergy.
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.
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.
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.
Background
Complaints of ‘food allergy’ are increasing. Standardized surveys of IgE sensitization to foods are still uncommon and multicountry surveys are rare. We have assessed IgE sensitization to ...food‐associated allergens in different regions of Europe using a common protocol.
Methods
Participants from general populations aged 20–54 years in eight European centres (Zurich, Madrid, Utrecht, Lodz, Sophia, Athens, Reykjavik and Vilnius) were asked whether they had allergic symptoms associated with specific foods. Weighted samples of those with and without allergic symptoms then completed a longer questionnaire and donated serum for IgE analysis by ImmunoCAP for 24 foods, 6 aeroallergens and, by allergen microarray, for 48 individual food proteins.
Results
The prevalence of IgE sensitization to foods ranged from 23.6% to 6.6%. The least common IgE sensitizations were to fish (0.2%), milk (0.8%) and egg (0.9%), and the most common were to hazelnut (9.3%), peach (7.9%) and apple (6.5%). The order of prevalence of IgE sensitization against different foods was similar in each centre and correlated with the prevalence of the pollen‐associated allergens Bet v 1 and Bet v 2 (r = 0.86). IgE sensitization to plant allergen components unrelated to pollen allergens was more evenly distributed and independent of pollen IgE sensitization (r = −0.10). The most common foods containing allergens not cross‐reacting with pollens were sesame, shrimp and hazelnut.
Discussion
IgE sensitization to foods is common, but varies widely and is predominantly related to IgE sensitization to pollen allergens. IgE sensitization to food allergens not cross‐reacting with pollens is rare and more evenly distributed.
Background
We investigated the accuracy of tests used to diagnose food allergy.
Methods
Skin prick tests (SPT), specific‐IgE (sIgE), component‐resolved diagnosis and the atopy patch test (APT) were ...compared with the reference standard of double‐blind placebo‐controlled food challenge. Seven databases were searched and international experts were contacted. Two reviewers independently identified studies, extracted data, and used QUADAS‐2 to assess risk of bias. Where possible, meta‐analysis was undertaken.
Results
Twenty‐four (2831 participants) studies were included. For cows’ milk allergy, the pooled sensitivities were 53% (95% CI 33–72), 88% (95 % CI 76–94), and 87% (95% CI 75–94), and specificities were 88% (95% CI 76–95), 68% (95% CI 56–77), and 48% (95% CI 36–59) for APT, SPT, and sIgE, respectively. For egg, pooled sensitivities were 92% (95% CI 80–97) and 93% (95% CI 82–98), and specificities were 58% (95% CI 49–67) and 49% (40–58%) for skin prick tests and specific–IgE. For wheat, pooled sensitivities were 73% (95% CI 56–85) and 83% (95% CI 69–92), and specificities were 73% (95% CI 48–89) and 43% (95% CI 20–69%) for SPT and sIgE. For soy, pooled sensitivities were 55% (95% CI 33–75) and 83% (95% CI 64–93), and specificities were 68% (95% CI 52–80) and 38% (95% CI 24–54) for SPT and sIgE. For peanut, pooled sensitivities were 95% (95% CI 88–98) and 96% (95% CI 92–98), and specificities were 61% (95% CI 47–74), and 59% (95% CI 45–72) for SPT and sIgE.
Conclusions
The evidence base is limited and weak and is therefore difficult to interpret. Overall, SPT and sIgE appear sensitive although not specific for diagnosing IgE‐mediated food allergy.
EAACI Molecular Allergology User's Guide Matricardi, P. M.; Kleine-Tebbe, J.; Hoffmann, H. J. ...
Pediatric allergy and immunology,
20/May , Letnik:
27, Številka:
S23
Journal Article
Recenzirano
Odprti dostop
The availability of allergen molecules (‘components’) from several protein families has advanced our understanding of immunoglobulin E (IgE)‐mediated responses and enabled ‘component‐resolved ...diagnosis’ (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low‐abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross‐reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE‐mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross‐reactive panallergens from plant (lipid transfer proteins, polcalcins, PR‐10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE‐mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.
Although the ubiquitous detection of polybrominated diphenyl ether (PBDE) and organophosphate flame retardants (PFRs) in indoor dust has raised health concerns, only very few epidemiological studies ...have assessed their impact on human health. Inhalation of dust is one of the exposure routes of FRs, especially in children and can be hazardous for the respiratory health. Moreover, PFRs are structurally similar to organophosphate pesticides, which have been associated with allergic asthma. Thus, we investigated whether the concentrations of PFRs and PBDEs in indoor dust are associated with the development of childhood asthma. We selected 110 children who developed asthma at 4 or at 8 years old and 110 matched controls from a large prospective birth cohort (BAMSE – Barn, Allergy, Milieu Stockholm Epidemiology). We analyzed the concentrations of 7 PFRs and 21 PBDEs in dust collected around 2 months after birth from the mother's mattress. The abundance rank in dust was as follows: TBOEP⪢TPHP>mmp‐TMPP>EHDPHP~TDCIPP>TCEP~TCIPP~BDE‐209⪢BDE‐99>BDE‐47>BDE‐153>BDE‐183>BDE‐100. There was no positive association between the FRs in mattress dust and the development of childhood asthma. In contrast, dust collected from mattresses of the mothers of children who would develop asthma contained significant lower levels of TPHP and mmp‐TMPP. This study provides data on a wide range of PFRs and PBDEs in dust samples and development of asthma in children.
Background
We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut‐allergic population characterized under a common ...protocol.
Methods
Sixty‐eight peanut‐allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom‐eliciting dose was established by double‐blind placebo‐controlled food challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1–3, 6, 8–9, profilin and CCD was determined using ImmunoCAP.
Results
Seventy‐eight percent of peanut allergics were sensitized to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut‐allergic population. Geographical differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitization to rAra h 1 and 2 was exclusively observed in early‐onset peanut allergy. Peanut‐tolerant subjects were frequently sensitized to rAra h 8 or 9 but not to storage proteins. Sensitization to Ara h 2 ≥ 1.0 kUA/l conferred a 97% probability for a systemic reaction (P = 0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (P = 0.0185 and P = 0.0436, respectively).
Conclusion
Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥ 1.0 kUA/l is significantly associated with the development of systemic reactions to peanut.
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