Diagnosing Asthma With Clinically Accessible, Non-invasive, and Efficient Tests: a Child-inclusive Translational Investigation

NCT07011394 | Recruiting

• 1 other identifier: 2024-5346
• Study Type: observational
• Target: 123
• Locations: 1 country
• Sites: 3

Brief Summary

Asthma is a common inflammatory respiratory disease affecting 11% of Canadians, but its diagnosis remains challenging, leading to delays in treatment or overtreatment. Spirometry with a reversibility test and bronchial provocation testing (BPT), considered the gold standard, are the reference diagnostic methods. However, access to BPT is limited as it is performed in hospital settings. Type 2 inflammation biomarkers, the fractional exhaled nitric oxide (FeNO) and blood eosinophils (EOS), represent a potential alternative. In addition to their prognostic and theragnostic value, these markers predict a good response to inhaled corticosteroids in individuals aged ≥ 6 years with asthma. However, their use remains restricted to pulmonologists in specialized clinics and is not recommended as a diagnostic tool in Quebec. Despite studies demonstrating their diagnostic value in specialized settings, these tests remain underexplored in primary care and insufficiently studied in children under 12 years. The objective of ou study is to evaluate the relevance and performance of FeNO and blood eosinophils in the diagnosis of asthma in children referred in primary care with non-diagnostic spirometry.

Conditions

Diagnosis; Inflammation; Asthma in Children; Asthma

Keywords

observationnal study; asthma diagnosis; FeNO and eosinophil blood count; children

Outcome Measures

Primary Outcomes (3)

• Fractional exhaled nitric oxide value: AUC of the ROC analysis to diagnose asthma

  Diagnosis of asthma defined as a methacholine PD20 \< 200 mcg

  FeNO measured on the day of the methacholine challenge (i.e. Baseline visit)

• Blood eosinophil count value : ROC analysis AUC to diagnose asthma

  Diagnosis of asthma defined as a methacholine PD20 \< 200 mcg

  Blood eosinophils measured on the day of the methacholine challenge (i.e. Baseline visit)

• Combination of FeNO + Blood eosinophil count: ROC analysis AUC to diagnose asthma

  Diagnosis of asthma defined as a methacholine PD20 \< 200 mcg

  Time Frame: FeNO and blood eosinophils measured on the day of the methacholine challenge (i.e. Baseline visit)

Secondary Outcomes (5)

• Univariate association between biomarkers (blood eosinophils and FeNO) and inflammatory proteins/metabolites (interleukines, chimiokines, alarmins)

  Baseline

• Biomarker level in asthmatic patients at time of diagnosis

  Baseline

• Change in diagnostic delay in asthma patients

  Baseline

• Cost difference between diagnostic strategies

  Baseline

• Ecological footprint of asthma diagnostic delay

  Baseline

Study Arms (1)

Patients aged 6-18 with suspected asthma, referred by primary care for methacholine BPT

Patients will be recruited from a larger study, Propulsion Santé, which investigates the usefulness of FeNO and BEC in prioritizing patients whith suspected asthma for bronchial provocation testing in primary care. 1,500 participants will be invited to receive spirometry at 3 centers: CHUS, CHUSJ, and Montreal Children's Hospital. If spirometry is non-diagnostic, patients aged 6 to 18 years who are referred for methacholine challenge testing will be offered the opportunity to participate in the DIVE2 study.In addition to a medical assessment and standardized questionnaires (ACQ5, ACT, and EQ-5D), participants will undergo FeNO and BEC measurements, and additional blood tests (complete blood count with differential, C-reactive protein, total and specific serum immunoglobulin E, and biobank sample collection). a nasosorption and urine analysis will be performed as part of this protocol.

Diagnostic Test: FeNO; Diagnostic Test: Blood eosinophil count

Interventions

FeNO DIAGNOSTIC_TEST

FeNO will be measured before the bronchial provocation test using a FeNO VIOX device

Patients aged 6-18 with suspected asthma, referred by primary care for methacholine BPT

Blood eosinophil count DIAGNOSTIC_TEST

a blood test will be performed om the day of bronchial provocation test

Patients aged 6-18 with suspected asthma, referred by primary care for methacholine BPT

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Patients will be recruited in through two pathways in 3 centers (CHUS, CHUSJ, and Montreal Children's Hospital) 1. In collaboration with the respiratory physiology department of participating centers, patients scheduled for a methacholine challenge test will receive an invitation letter for the study along with their test appointment notice. They will be informed about the study's purpose, procedures, and provided with contact details to reach out to the research team if they wish to decline participation or have any questions. If no refusal is received, the clinical inhalation therapist will contact them to confirm their eligibility. 2. Through the Propulsion Santé study, patients will be scheduled for their respiratory test, which will include eosinophil count and FeNO measurement. If their spirometry results are inconclusive for diagnosis, they will be offered the opportunity to participate in the DIVE2 study.

You may qualify if:

• Individuals aged 6 to \<18 years, presenting symptoms suggestive of asthma
• Patients referred for a methacholine bronchial provocation test by primary care (defined as non-pulmonologist, non-ENT specialist, non-allergist)
• Spirometry inconclusive

You may not qualify if:

• Use of an inhaled or systemic corticosteroid in the previous 48 hours;
• Smoking in the previous 6 hours; history of viral and/or bacterial respiratory infection in the past 4 weeks;
• major cardiopulmonary disease, including: a) chronic obstructive pulmonary disease (COPD), defined by all of the following: i) aged ≥ 40 years , ii) permanent obstruction on spirometry (FEV1/FVC \<0.7) and iii) a smoking history of \>10 pack-years or known alpha-1-antitrypsin deficiency, b) lung conditions deemed significant by the investigator, including cystic fibrosis and bronchiectasis, and c) unstable heart disease.

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Association Pulmonaire du Quebec: collaborator
• Fonds de la Recherche en Santé du Québec: collaborator
• Fondation JA DeSève: collaborator
• Opération Enfant Soleil: collaborator

Study Sites (3)

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

NOT YET RECRUITING

Montreal Children's Hospital

Montreal, Quebec, H4A 3H9, Canada

NOT YET RECRUITING

CIUSSS de l'Estrie - CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

Related Publications (1)

• Gronnier M, Desy L, Pouliot L, Lemieux SE, Vezina FA, Lachapelle P, Counil FP, Duval M, Cliche D, Lemaire-Paquette S, Coulibaly L, Hudon C, Lands LC, Ducharme FM, Tse S, Couillard S. Integrating blood eosinophils and exhaled nitric oxide (FeNO) in asthma diagnostic pathways for adults and children: the PROPULSION SANTE observational study with translational sub-studies (DIVE, DIVE2)-protocols. BMJ Open Respir Res. 2025 Nov 27;12(1):e003750. doi: 10.1136/bmjresp-2025-003750.

  PMID: 41314665 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma, serum, nasal epithelial lining fluid by nasosorption, urine sample

MeSH Terms

Conditions

Disease; Inflammation; Asthma

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Central Study Contacts

Simon Couilard, MD MSc

CONTACT

+1-819-346-1110; s.couillard@usherbrooke.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2025
• First Posted: June 8, 2025
• Study Start: April 9, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Data of this study may be shared if the investigators proposed use of the data has been approved by the study principal investigator and an institutional research ethics committee.

Locations

CA (3)