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2.  Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol 
The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients’ threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals.
This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children’s Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre.
A total of 375 participants, aged 1–18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed.
The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population.
PMCID: PMC3850217  PMID: 24028324
Eliciting dose (ED); Food Allergy related Quality of Life Questionnaires-(FAQLQ); Single dose; Peanut thresholds; Oral Food Challenges (OFC); Voluntary Incidental Trace Allergen Labelling (VITAL); Peanut Allergen Threshold Study (PATS)
3.  A 24-h helpline for access to expert management advice for food allergy-related anaphylaxis in children: protocol for a pragmatic randomised controlled trial 
BMJ Open  2012;2(4):e001282.
Anaphylaxis is an important, potentially life-threatening paediatric emergency. It is responsible for considerable morbidity and, in some cases, death. Poor outcomes may be associated with an inability to differentiate between milder and potentially more severe reactions and an associated reluctance to administer self-injectable adrenaline. This study aims to assess the effectiveness of a 24-h telephone access to specialist paediatric allergy expert advice in improving the quality of life of children and their families with potentially life-threatening food allergy (ie, anaphylaxis) compared with usual clinical care.
Methods and analysis
Children aged less than 16 years with food allergy and who carry an adrenaline autoinjector will be recruited from the Paediatric Allergy Clinic at Cork University Hospital, Ireland and baseline disease-specific quality of life will be ascertained using the validated Food Allergy Quality of Life Questionnaire (FAQLQ). Participants will be randomised for a period of 6 months to the 24-h telephone specialist support line or usual care. The primary outcome measure of interest is a change in FAQLQ scores, which will be assessed at 0, 1 and 6 months postrandomisation. Analysis will be on an intention-to-treat basis using a 2×3 repeated measures within-between analysis of variance. Although lacking power, we will in addition assess the impact of the intervention on a range of relevant process and clinical endpoints.
Ethics and dissemination
This trial protocol has been approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The findings will be presented at international scientific conferences and will be reported on in the peer-reviewed literature in early 2013.
PMCID: PMC3425896  PMID: 22893666
Accident & Emergency medicine; Immunology; Paediatrics; Paediatric A&E and ambulatory care
4.  Abformation 
BMJ : British Medical Journal  2008;337(7662):169.
PMCID: PMC2483895
5.  Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy 
IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy.
To investigate the association between filaggrin loss-of-function mutations and peanut allergy.
Case-control study of 71 English, Dutch, and Irish oral food challenge–positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥8 mm and/or peanut-specific IgE ≥15 kUL−1) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis.
Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge–positive patients (P = 3.0 × 10−6; odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10−5; odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis.
Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.
PMCID: PMC3081065  PMID: 21377035
Atopic dermatitis; filaggrin; IgE; peanut allergy; risk factor; AD, Atopic dermatitis; ALSPAC, Avon Longitudinal Study of Parents and Children; FLG, Filaggrin; OR, Odds ratio; SPT, Skin prick test; UK, United Kingdom
6.  Are the dangers of childhood food allergy exaggerated? 
BMJ : British Medical Journal  2006;333(7566):496-498.
PMCID: PMC1557979  PMID: 16946342
7.  Resolution of peanut allergy: case-control study 
BMJ : British Medical Journal  1998;316(7140):1271-1275.
Objectives: To determine whether there are any differences between children who remain mildly or moderately allergic to peanut and children with similar histories but a negative reaction on challenge with peanut.
Design: Case-controls matched for age and sex.
Setting: Children’s day wards in two teaching hospitals.
Intervention: Open food challenge with peanut.
Subjects: 15 children with resolved peanut allergy (resolvers) and 15 with persistent allergy (persisters).
Main outcome measure: Reaction on challenge with peanut, serum total and peanut specific IgE concentrations.
Results: The groups had a similar median age at first reaction to peanut (11 months, range 5-38) and similar symptoms. Allergy to other foods was less common in resolvers (2/15) than persisters (9/15) (P=0.02). On skin prick testing with peanut all 13 resolvers tested but only 3/14 persisters had a weal of <6 mm (P<0.0001). Total and peanut specific IgE concentrations did not differ much between the groups.
Conclusion: Appropriately trained clinicians must be prepared to challenge preschool children with peanut as some will be tolerant despite a history of reactions to peanut and a positive skin prick test with peanut. Preschool children whose apparent peanut allergy is refuted by food challenge show allergy to other foods less often than those in whom peanut allergy persists. The size of weal on skin prick testing to peanut predicts reactivity but not severity on peanut challenge.
Key messages Peanut allergy rarely resolves in older children and adults Skin prick testing with peanut has a high negative predictive value, but some people with positive skin tests do not react to peanut challenge Some preschool children with a convincing history of reaction to peanut may become tolerant of peanut. Such children have fewer other manifestations of atopy than children whose peanut allergy persists Paediatricians must be prepared to undertake peanut challenges or refer children to units that will undertake such challenges
PMCID: PMC28527  PMID: 9554896

Results 1-7 (7)