Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol

Abstract

BackgroundThe 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.Methods/AimsThis 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.ConclusionThe 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.

How does dose impact on the severity of food‐induced allergic reactions, and can this improve risk assessment for allergenic foods?

“…The available data can be found in epidemiological studies of populations, clinical case reports, and studies using graded food challenges and are summarized in Table . A recently introduced research tool is the single‐dose food challenge, originally designed to validate reference doses derived from dose distribution models.…”

“…Zurzolo et al introduced single‐dose challenges to validate the EDs calculated from population dose‐distribution curves: a single dose (corresponding to a specific ED value, for example ED05 for the food in question, derived from a dose distribution curve) is given to unselected individuals with the relevant allergy and the occurrence and characteristics of any reactions recorded. In the only study published to date, the ED05 for peanut was validated (1.5 mg peanut protein), with 8 of 378 individuals meeting predetermined criteria for a positive, objective reaction.…”

The skin barrier function gene SPINK5 is associated with challenge‐proven IgE‐mediated food allergy in infants

“…Replication was sought in an additional panel of 203 food‐allergic children and 330 nonatopic controls drawn from the Peanut Allergen Threshold Study (PATS) of peanut allergy, the Probiotic and Peanut Oral ImmunoTherapy (PPOIT) study, Barwon Infant Study (BIS) and the Melbourne Atopy Cohort Study (MACS) (see Figure ). Replication sample ethics approvals for each study were as follows: PATS: HRECApp32166A and 2012P002475; PPOIT: approved by RCH Human Research and Ethics Committee HREC 27086Q; MACS: initial approval by the Mercy Maternity Hospital Ethics Committee (R88/06), 18‐year follow‐up, including collection of DNA, was approved by the Royal Children's Hospital (HREC 28035); BIS: Barwon Health Human Research Ethics Committee HREC (10/24).…”

“…Replication was sought in an additional panel of 203 food-allergic children and 330 nonatopic controls drawn from the Peanut Allergen Threshold Study (PATS) of peanut allergy, 23 the Probiotic and Peanut Oral ImmunoTherapy (PPOIT) study, 24 Barwon Infant Study (BIS) 25 and the Melbourne Atopy Cohort Study (MACS) 26 (see Figure S1). Replication sample ethics approvals for each study were as follows: PATS: HRECApp32166A and 2012P002475; For the replication analysis, case phenotypes were defined through a combination of challenge-proven outcomes where available (BIS cohort), or by evidence of sensitization (SPT or sIgE) with clear history of immediate-type clinical reactions within 1-2 hours of exposure (PPOIT and PATS cohorts), or using accepted 95% positive predictive values for SPT wheal sizes (MACS cohort) 27 (Table S1).…”

Measured Indoor Aerosol Concentration Arising from Commonly-Used Food and Medicinal Powders: A Pilot Study

“…A study in adults (Wensing et al, 2002) noted mild reactions at as low as 0.1 mg ingested peanut protein. More recently, Zurzolo et al (2013) report that the eliciting dose for a peanut allergic reaction, in 5% of the peanut allergic population, is 1.5 mg of peanut protein.…”