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.
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
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.
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.
Cohort
Prospective
FeNO
Diagnostic testFeNO will be measured before the bronchial provocation test using a FeNO VIOX device
Blood eosinophil count
Diagnostic testa blood test will be performed om the day of bronchial provocation test
Fractional exhaled nitric oxide value: AUC of the ROC analysis to diagnose asthma
Diagnosis of asthma defined as a methacholine PD20 \< 200 mcg
Blood eosinophil count value : ROC analysis AUC to diagnose asthma
Diagnosis of asthma defined as a methacholine PD20 \< 200 mcg
Combination of FeNO + Blood eosinophil count: ROC analysis AUC to diagnose asthma
Diagnosis of asthma defined as a methacholine PD20 \< 200 mcg
Univariate association between biomarkers (blood eosinophils and FeNO) and inflammatory proteins/metabolites (interleukines, chimiokines, alarmins)
concentration of inflammatory proteins/metabolites (interleukine (IL)-4, IL-5, IL-13, thymic stromal lymphopoietin, leukotriene 4, prostaglandine 2) measured in the NELF, serum analyzed according to FeNO and BEC, and the diagnostic. Further exploratory multivariate modelling adjusting for atopy (defined as a history of eczema, rhinoconjunctivitis, or food allergy and/or at least one sensitisation to an airbourne sensitiser) and biological sex.
Biomarker level in asthmatic patients at time of diagnosis
Expressed as n (%) of diagnosed patients per square in a 3×3 grid stratified by combination of biomarkers (eosinophils \<0.15, 0.015-\<0.30, ≥0.30×109/L; FeNO \<25, 25-\<50, ≥50 ppb)
Change in diagnostic delay in asthma patients
the difference (in days) between the date of the non-diagnostic spirometry and the date of the metacholine challenge test
Cost difference between diagnostic strategies
Difference in cost (in Canadian dollars) between the use of biomarkers (FeNO and eosinophil count - analysed separately for traditional vs. point-of-care testing) and the standard methacholine challenge as a second diagnostic step.
Click on the lead sponsor to view all of their trials.
Université de Sherbrooke
Lead sponsor
Association Pulmonaire du Quebec
Collaborator
Fonds de la Recherche en Santé du Québec
Collaborator
Fondation JA DeSève
Collaborator
Opération Enfant Soleil
Collaborator
