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Cited by 116Allergic Rhinitis and SensitizationAsthma and respiratory diseasesFood Allergy and Anaphylaxis Research

The Allergic Rhinitis – Clinical Investigator Collaborative (AR-CIC): nasal allergen challenge protocol optimization for studying AR pathophysiology and evaluating novel therapies

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Ellis, Anne K, Soliman, Mena, Steacy, Lisa, Boulay, Marie-Ève, Boulet, Louis-Philippe, Keith, Paul K, Vliagoftis, Harissios, Waserman, Susan +1 more·2015·Allergy, Asthma & Clinical Immunology
DOI 10.1186/s13223-015-0082-0PMC PMC4419495
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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.

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  • In nasal provocation, a ≥40% reduction in PNIF is considered positive.

    “In nasal provocation, a ≥40% reduction in PNIF is considered positive [44,76,77].”

    From Position Paper on Nasal Obstruction: Evaluation and Treatment (2018) · cites this paper as [76]

    The Methods (Nasal allergen challenge; page unavailable) specify a ≥50% PNIF reduction, or a TNSS score of ≥10/12, as the QAC qualifying criterion—not a ≥40% PNIF reduction. The Discussion (page unavailable) likewise describes a 50% PNIF fall, together with a TNSS score of 8/12, for the CAC study. (LLM, conf=0.88)

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Authors
Ellis, A. K., Soliman, M., Steacy, L., Boulay, M.-È., Boulet, L.-P., Keith, P. K., Vliagoftis, H., Waserman, S., & Neighbour, H.
Affiliations
  • Queen's University (CA)
  • Kingston General Hospital (CA)
  • Institut universitaire de cardiologie et de pneumologie de Québec (CA)
  • McMaster University (CA)
  • University of Alberta (CA)
Corresponding author
Ellis, Anne K
ORCID
Venue
Allergy, Asthma & Clinical Immunology
Publisher
Springer Science and Business Media LLC
Published
2015-04-24
Volume
11
Issue
1
Pages
16-16
ISSN
  • 1710-1484 (ISSN-L)
  • 1710-1492
DOI
10.1186/s13223-015-0082-0
PMC
PMC4419495
OpenAlex
W2041568269
Cited by
116
References
2
Citations by year
2026: 13 · 2025: 18 · 2024: 9 · 2023: 13 · 2022: 13 · 2021: 13 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 1
FWCI
5.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Allergy Asthma and Clinical Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Université Laval
  • Queen's University
  • Mitacs
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
Keywords
allergic rhinitis, nasal allergen challenge, Total Nasal Symptom Score, peak nasal inspiratory flow, ragweed allergy

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