title: The Allergic Rhinitis - Clinical Investigator Collaborative (AR-CIC): nasal allergen challenge protocol optimization for studying AR pathophysiology and evaluating novel therapies.
abstract: BACKGROUND
  The Nasal Allergen Challenge (NAC) model allows the study of Allergic Rhinitis (AR) pathophysiology and the proof of concept of novel therapies. The Allergic Rhinitis - Clinical Investigator Collaborative (AR-CIC) aims to optimize the protocol, ensuring reliability and repeatability of symptoms to better evaluate the therapies under investigation.
  
  
  METHODS
  20 AR participants were challenged, with 4-fold increments of their respective allergens every 15 minutes, to determine the qualifying allergen concentration (QAC) at which the Total Nasal Symptom Score (TNSS) of ≥10/12 OR a Peak Nasal Inspiratory Flow (PNIF) reduction of ≥50% from baseline was achieved. At the NAC visit, the QAC was used in a single challenge and TNSS and PNIF were recorded at baseline, 15 minutes, 30 minutes, 1 hour, and hourly up to 12 hours. 10 additional ragweed allergic participants were qualified at TNSS of ≥8/12 AND ≥50% PNIF reduction; the Cumulative Allergen Challenge (CAC) of all incremental doses was used during the NAC visit. 4 non-allergic participants were challenged with the highest allergen concentration.
  
  
  RESULTS
  In the QAC study, a group qualified by only meeting PNIF criteria achieved lower TNSS than those achieving either TNSS criteria or PNIIF+TNSS (p<0.01). During the NAC visit, participants in both studies reached their peak symptoms at 15minutes followed by a gradual decline, significantly different from non-allergic participants. The "PNIF only" group experienced significantly lower TNSS than the other groups during NAC visit. QAC and CAC participants did not reach the same peak TNSS during NAC that was achieved at screening. QAC participants qualifying based on TNSS or TNSS+PNIF managed to maintain PNIF scores.
  
  
  CONCLUSIONS
  Participants experienced reliable symptoms of AR in both studies, using both TNSS and PNIF reduction as part of the qualifying criteria proved better for qualifying participants at screening. Phenotyping based on pattern of symptoms experienced is possible and allows the study of AR pathophysiology and can be applied in evaluation of efficacy of a novel medication. The AR-CIC aims to continue to improve the model and employ it in phase 2 and 3 clinical trials.
authors.affiliation: Departments of Medicine and Biomedical & Molecular Science, Queen's University, Kingston, ON Canada ; Allergy Research Unit, Kingston General Hospital, Kingston, ON Canada.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Ellis
authors.affiliation: Departments of Medicine and Biomedical & Molecular Science, Queen's University, Kingston, ON Canada.
authors.forename: Mena
authors.initials: M
authors.lastname: Soliman
authors.affiliation: Allergy Research Unit, Kingston General Hospital, Kingston, ON Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Steacy
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec, QC Canada.
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Boulay
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec, QC Canada.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON Canada.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Keith
authors.affiliation: Pulmonary Research Group, University of Alberta, Edmonton, AB Canada.
authors.forename: Harissios
authors.initials: H
authors.lastname: Vliagoftis
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Waserman
authors.affiliation: Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Neighbour
keywords: Allergic rhinitis; Clinical investigator collaborative; Nasal allergen challenge