PEAnut Anaphylaxis Predictors (PEAAP)

Hunter Medical Research Institute, Australia, University of Newcastle, Australia, Thrasher Research Fund, Hunter Childrens Research Foundation, Australia, Aerocrine AB

Peanut allergy can be life-threatening. Current diagnostic techniques for peanut allergy have high sensitivity, but not high specificity. This clinical trial will test the validity of a novel blood biomarker (compared with current testing) as a diagnostic predictor of anaphylaxis to peanut.

Children aged 2-17 years with suspected peanut allergy will be invited to participate in the study. They will have a questionnaire, a skin prick test to peanut, 2 breathing tests (spirometry and fraction of exhaled nitric oxide (FeNO)), and a blood test (specific peanut antibodies, allergic immune responses - including the novel blood biomarker - and genetic testing to identify novel potential molecular and genetic markers of food allergy in the future. The genetic testing component will be optional). The breathing test is not required for those under 6 years. The final step is an open label peanut food challenge with incremental doses of peanut, (routine practise) as per the Australasian Society of Clinical Immunology and Allergy (ASCIA) food challenge protocol.The endpoints in the food challenge will be signs of allergy or anaphylaxis as per PRACTicing ALLergology (PRACTALL) consensus report for oral food challenges OR completion of the ASCIA food challenge protocol. Outcome: The primary outcome of the project is to confirm that a novel blood biomarker has a higher diagnostic accuracy as compared to current best testing in predicting anaphylaxis at open label peanut challenge. Secondary outcome: Will be to determine the value of the biomarker, FeNO and Ara h2 specific Immunoglobulin E (sIgE) (individually and in combination) at predicting anaphylaxis or clinical allergy at open label peanut challenge.

Children aged 2-17 years with suspected peanut allergy who require peanut food challenge to confirm clinical allergy, will be recruited for the study. They will undergo a preceding questionnaire, peanut skin prick testing, spirometry, fraction of exhaled nitric oxide (FeNO) measurement, serum peanut and Ara h2 specific immunoglobulin E (sIgE) antibodies, and collection of blood biomarker prior to food challenge. The primary endpoint will be anaphylaxis at open label peanut challenge, with the primary exposure of interest will be the serum biomarker.

Measurement of exhaled nitric oxide, according to American Thoracic Society/ European Thoracic Society (ATS/ERS) standardised procedures (Not required for those age less than 6 years).

Measurement of lung flows/volumes, according to ATS/ERS standardised procedures (Not required for those age less than 6 years).

Correlation of blood biomarker levels in patients with successful or unsuccessful peanut food challenge

Open label peanut challenge conducted according to ASCIA's peanut challenge protocol and PRACTALL consensus report

The primary outcome of the project is to confirm that a novel blood biomarker has a higher diagnostic accuracy as compared to current best testing in predicting anaphylaxis at open label peanut challenge.

Blood biomarker in combination with FeNO, and/or Ara h2 sIgE predicting anaphylaxis at peanut food challenge

The secondary outcome will be to determine the value of the biomarker, FeNO and Ara h2 sIgE (individually and in combination) at predicting anaphylaxis or clinical allergy at open label peanut challenge.

Inclusion Criteria: Children aged 2 - 17 years with an allergy to peanut and require peanut challenge to confirm peanut allergy. Exclusion Criteria: Children with Peanut Skin Prick Test (SPT) wheal size greater than 10mm as these children are likely to have clinical peanut allergy (no clinical indication for food challenge).

Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, Dubois AE, Beyer K, Eigenmann PA, Spergel JM, Werfel T, Chinchilli VM. Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol. 2012 Dec;130(6):1260-74. doi: 10.1016/j.jaci.2012.10.017. No abstract available.

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.

American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005 Apr 15;171(8):912-30. doi: 10.1164/rccm.200406-710ST. No abstract available.

Percival E, Bhatia R, Preece K, McEvoy M, Collison A, Mattes J. Change in exhaled nitric oxide during peanut challenge is related to severity of reaction. Allergy Asthma Clin Immunol. 2020 Jul 21;16:64. doi: 10.1186/s13223-020-00464-8. eCollection 2020.