xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05992519</url>
    </required_header>
    <id_info>
      <org_study_id>2023-4791</org_study_id>
      <nct_id>NCT05992519</nct_id>
    </id_info>
    <brief_title>Diagnostic and Translational Values of Point-of-care Blood Eosinophils and Exhaled Nitric Oxide (FeNO) in People Referred by Primary Care for Suspected Asthma</brief_title>
    <acronym>DIVE</acronym>
    <official_title>Diagnostic and Translational Values of Point-of-care Blood Eosinophils and Exhaled Nitric Oxide (FeNO) in People Referred by Primary Care for Suspected Asthma (DIVE)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Université de Sherbrooke</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Association pulmonaire du Québec</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Réseau de Recherche en Santé Respiratoire du Québec</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>AstraZeneca</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Fonds de recherche du Québec</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Université de Sherbrooke</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Asthma is characterised by episodic symptoms (attacks) caused by airway inflammation and&#xD;
        decreased airflow to the lungs. It affects 10% of the Canadian population and is the most&#xD;
        common chronic disease in childhood. Despite its burden and its potential to be&#xD;
        life-threatening, establishing the diagnosis takes time due to difficulty in accessing&#xD;
        specialised breathing tests. Indeed, the current diagnostic strategy relies on a breathing&#xD;
        test (spirometry) and, if non-diagnostic, a subsequent more complicated breathing test&#xD;
        conducted in hospitals (a bronchial provocation test). Our dependence on the latter test must&#xD;
        be confronted to the bottleneck created by our reliance on it and the difficulty to do these&#xD;
        tests in children. Furthermore, within the current framework, people receiving a diagnosis do&#xD;
        not know if they have active airway inflammation - a key feature with predicts increased&#xD;
        susceptibility to asthma attacks and treatment responsiveness.&#xD;
  &#xD;
        Our study's goal is to validate clinically accessible and useful diagnostic tests for&#xD;
        peoplesuspected to have asthma. Specifically, we are interested in alternative tests that are&#xD;
        a) achievable outside the hospital; b) useful markers of airway inflammation/risk c) can&#xD;
        identify people at with a higher likelihood of responding to anti-inflammatory therapy. The&#xD;
        two tests we are mainly interested in are:&#xD;
  &#xD;
          -  Exhaled nitric oxide (measured with a portable handheld machine)&#xD;
  &#xD;
          -  The blood eosinophil count (obtained on a general blood test) +/- Other tests which we&#xD;
             might be able to develop within this cohort (e.g. urine tests)&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        BACKGROUND Asthma affects 10% of the general population but remains a diagnostic challenge.&#xD;
        Considering the difficult access, weak specificity, and low clinical utility of bronchial&#xD;
        provocation tests, more effective diagnostic methods are needed. Blood eosinophils and&#xD;
        exhaled nitric oxide (FeNO) are biomarkers of type-2 inflammation that have established&#xD;
        mechanistic, prognostic and theragnostic values in chronic asthma. Specifically, these&#xD;
        biomarkers identify attack-prone patients with ongoing alarmin, type-2 cytokine, and&#xD;
        chemokine signalling at the epithelial level driving airway hyperresponsiveness and&#xD;
        accelerated lung function decline. Most importantly, these biomarkers also identify those who&#xD;
        benefit the most from anti-inflammatory therapy. Considering the above clinical utilities,&#xD;
        using biomarkers in primary care to diagnose airways disease in people with suspected asthma&#xD;
        would represent a very effective diagnostic strategy.&#xD;
  &#xD;
        HYPOTHESIS: In people with non-diagnostic spirometry and asthma suspected by primary care,&#xD;
        measuring blood eosinophils and FeNO is a feasible diagnostic strategy with good accuracy and&#xD;
        the added value of early mechanistic insight in epithelial signalling pathways.&#xD;
  &#xD;
        OBJECTIVE: To estimate the diagnostic performance parameters of type-2 biomarkers in people&#xD;
        with suspected asthma and a non-diagnostic spirometry. An exploratory analysis of&#xD;
        inflammatory proteins (alarmin, type-2 cytokines, chemokines) in the nasal epithelial lining&#xD;
        fluid (NELF) and serum according to biomarkers will be conducted. This and other secondary&#xD;
        exploratory objectives will lead to better mechanistic and operational insight on the value&#xD;
        of type-2 biomarkers in early disease.&#xD;
  &#xD;
        METHODS: The investigators propose a prospective observational study on the logistical&#xD;
        feasibility, receiver operating characteristics (ROC), and mechanistic value of point-of-care&#xD;
        type-2 inflammatory biomarkers to diagnose asthma (Figure). The study will include 123 people&#xD;
        ≥12 years old with non-diagnostic pre-postbronchodilator spirometry referred by primary care&#xD;
        for a methacholine challenge via the Suspected Asthma pathway of the Centre Hospitalier&#xD;
        Universitaire de Sherbrooke. After the methacholine challenge, patients will complete&#xD;
        questionnaires, have blood eosinophils measured (by venous blood sample and point-of-care&#xD;
        (POC) capillary blood), FeNO measured (by electroluminescence and POC strip-tests),&#xD;
        nasosorption performed, and serum harvested for allergy testing and inflammatory protein&#xD;
        measurement.&#xD;
  &#xD;
        OUTCOMES: The main analysis will be ROC plots of (1) FeNO alone; (2) blood eosinophils alone;&#xD;
        and (3) the combination of blood eosinophils and FeNO;. The ROC plot will be based on a&#xD;
        methacholine provocative dose ≤190 mcg (~ provocative concentration ≤8 mg/mL). The target&#xD;
        sample size of 123 will have 90% power to compute 3 ROC curves' area under the curve (AUC) ≥&#xD;
        0.7 significantly different from the null hypothesis (AUC=0.5) with a conservatively&#xD;
        corrected two-sided α error &lt; 0.016, assuming a positive/negative case ratio of 2. Secondary&#xD;
        outcomes are the diagnostic and cost-effectiveness of blood eosinophil and FeNO measurement&#xD;
        compared to methacholine challenges; and univariate plus multivariate modelling between blood&#xD;
        eosinophils, FeNO, and inflammatory proteins (alarmins TSLP and IL-33; type-2 cytokines IL-4,&#xD;
        -5, -13; chemokines eotaxin-3 and TARC) measured in the NELF and serum, or metabolites&#xD;
        measured in the urine.&#xD;
  &#xD;
        EXPECTED RESULTS: It is expected that type-2 inflammometry to be a useful alternative&#xD;
        diagnostic pathway with benefits extending beyond diagnostic accuracy thanks to early insight&#xD;
        into the inflammatory phenotype.&#xD;
  &#xD;
        IMPACT: This observational study will support further validation studies and/or trials&#xD;
        assessing POC biomarker-assisted diagnosis and management of asthma in the community setting.&#xD;
        Measuring biomarkers at the time of diagnosis could facilitate a 'predict and prevent'&#xD;
        approach to diagnostic algorithms in airway disease&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">November 7, 2022</start_date>
    <completion_date type="Anticipated">November 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>AUC of the ROC analysis to diagnose asthma</measure>
      <time_frame>FeNO measured on the day of the methacholine challenge (i.e. Baseline visit)</time_frame>
      <description>Diagnosis of asthma defined as a methacholine PD20 &lt; 190 mcg</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Blood eosinophil count: ROC analysis AUC to diagnose asthma</measure>
      <time_frame>Blood eosinophils measured on the day of the methacholine challenge (i.e. Baseline visit)</time_frame>
      <description>Diagnosis of asthma defined as a methacholine PD20 &lt; 190 mcg</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Combination of FeNO + Blood eosinophil count: ROC analysis AUC to diagnose asthma</measure>
      <time_frame>FeNO and blood eosinophils measured on the day of the methacholine challenge (i.e. Baseline visit)</time_frame>
      <description>Diagnosis of asthma defined as a methacholine PD20 &lt; 190 mcg</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Univariate association between biomarkers (blood eosinophils and FeNO) and inflammatory proteins/metabolites</measure>
      <time_frame>Baseline</time_frame>
      <description>Inflammatory proteins/metabolites measured in the NELF, serum, and urine. 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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Operational efficacy of the use of biomarkers as a diagnostic tool:</measure>
      <time_frame>Baseline</time_frame>
      <description>Potential reduction in diagnostic delay in asthma patients: the difference (in days) between the date of the challenge test and the date of the request&#xD;
  Time difference (in minutes/days) for diagnosing asthma using biomarkers (FeNO + eosinophilia) versus a methacholine challenge.&#xD;
  Cost difference between the use of biomarkers (traditional or point-of-care analysed separately) as 2nd diagnosis step versus a standard methacholine challenge test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concordance between traditional biomarker measurements (FeNO using Niox Vero and eosinophils in venous blood) and the new POC method (capillary eosinophils using Sight OLO).</measure>
      <time_frame>Baseline</time_frame>
      <description>Intraclass correlation coefficient (both sides, mixed model for absolute concordance, single measurements)&#xD;
  Estimated fixed Bland-Altman bias for the gold standard versus point-of-care</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biomarker level in asthmatic patients at time of diagnosis</measure>
      <time_frame>Baseline</time_frame>
      <description>Expressed as n (%) of diagnosed patients per square in a 3×3 grid stratified by combination of biomarkers (eosinophils &lt;0.15, 0.015-&lt;0.30, ≥0.30×109/L; FeNO &lt;25, 25-&lt;50, ≥50 ppb)</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">123</enrollment>
    <condition>Asthma</condition>
    <condition>Asthma in Children</condition>
    <condition>Diagnosis</condition>
    <condition>Inflammation</condition>
    <arm_group>
      <arm_group_label>People suspected with asthma</arm_group_label>
      <description>Patients will receive an in invitation letter at the time of BPT scheduling. In the week proceeding the test, the clinical inhalation therapist will discuss the project and schedule the study visit on the day of the BPT. The study visit will be done prior to BPT whenever possible.&#xD;
  Baseline visit:&#xD;
  Medical history&#xD;
  5-item Asthma Control Questionnaire (ACQ-5)&#xD;
  FeNO measurement (NIOX VERO device)&#xD;
  Nasosorption for nasal epithelial lining fluid (NELF) biobanking&#xD;
  blood tests (complete blood count with differential, C-reactive protein, total and specific serum immunoglobulin E, biobank), capillary blood eosinophils (Sight OLO),&#xD;
  urine sample (biobank)</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>¸FeNO</intervention_name>
      <description>FeNO measured with a NIOX VERO device after the methacholine challenge</description>
      <arm_group_label>People suspected with asthma</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Serum, plasma, whole blood&#xD;
  &#xD;
        Nasosorption for NELF (nasal epithelial lining fluid)&#xD;
  &#xD;
        Urine sample&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          The study has a collaboration agreement with the respiratory physiology service. In this&#xD;
          context, a research invitation letter will be sent with confirmation of the appointment.&#xD;
          The letter indicates that participation is voluntary and provides the expected length of&#xD;
          the appointment (20-30 minutes), a QR code referring them to an online version of the&#xD;
          Information and Consent Form (ICF), and a cell phone number and email address for the&#xD;
          research team, with a phone number for individuals to state their refusal to be contacted.&#xD;
          In the week preceeding the challenge, the clinical inhalation therapist will call&#xD;
          non-objecting pre-screened patients to discuss the project and plan the study visit.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  aged ≥ 12 years who have symptoms suggestive of asthma,&#xD;
  &#xD;
            -  referred by their primary care provider (defined as a non-respirologist,&#xD;
               non-allergist, non-otolaryngologist) using the CHUS suspected asthma decision-making&#xD;
               algorithm. Under that algorithm, patients have non-diagnostic pre- and&#xD;
               post-bronchodilator spirometry and no contraindications to a methacholine challenge.&#xD;
  &#xD;
            -  Free and informed consent must be given by the patient (and their legal guardian, if&#xD;
               applicable).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Use of an inhaled or systemic corticosteroid in the previous 48 hours;&#xD;
  &#xD;
            -  Smoking in the previous 6 hours; history of viral and/or bacterial respiratory&#xD;
               infection in the past 4 weeks;&#xD;
  &#xD;
            -  major cardiopulmonary disease, including: a) chronic obstructive pulmonary disease&#xD;
               (COPD), defined by all of the following: i) aged ≥ 40 years , ii) permanent&#xD;
               obstruction on spirometry (FEV1/FVC &lt;0.7) and iii) a smoking history of &gt;10 pack-years&#xD;
               or known alpha-1-antitrypsin deficiency, b) lung conditions deemed significant by the&#xD;
               investigator, including cystic fibrosis and bronchiectasis, and c) unstable heart&#xD;
               disease.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>12 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <overall_contact>
      <last_name>Simon Couillard, MD MSc</last_name>
      <phone>+1-819-346-1110</phone>
      <phone_ext>15037</phone_ext>
      <email>s.couillard@usherbrooke.ca</email>
    </overall_contact>
    <location>
      <facility>
        <name>Centre de Recherche du CHUS</name>
        <address>
          <city>Sherbrooke</city>
          <state>Quebec</state>
          <zip>J1H5N4</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Simon Couillard, MD MSc</last_name>
        <phone>+18193461110</phone>
        <phone_ext>15037</phone_ext>
        <email>s.couillard@usherbrooke.ca</email>
      </contact>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Asthma</mesh_term>
      <mesh_term>Inflammation</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05992519
  org study id: 2023-4791
  nct id: NCT05992519
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Asthma is characterised by episodic symptoms (attacks) caused by airway inflammation and
        decreased airflow to the lungs. It affects 10% of the Canadian population and is the most
        common chronic disease in childhood. Despite its burden and its potential to be
        life-threatening, establishing the diagnosis takes time due to difficulty in accessing
        specialised breathing tests. Indeed, the current diagnostic strategy relies on a breathing
        test (spirometry) and, if non-diagnostic, a subsequent more complicated breathing test
        conducted in hospitals (a bronchial provocation test). Our dependence on the latter test must
        be confronted to the bottleneck created by our reliance on it and the difficulty to do these
        tests in children. Furthermore, within the current framework, people receiving a diagnosis do
        not know if they have active airway inflammation - a key feature with predicts increased
        susceptibility to asthma attacks and treatment responsiveness.
  
        Our study's goal is to validate clinically accessible and useful diagnostic tests for
        peoplesuspected to have asthma. Specifically, we are interested in alternative tests that are
        a) achievable outside the hospital; b) useful markers of airway inflammation/risk c) can
        identify people at with a higher likelihood of responding to anti-inflammatory therapy. The
        two tests we are mainly interested in are:
  
          -  Exhaled nitric oxide (measured with a portable handheld machine)
  
          -  The blood eosinophil count (obtained on a general blood test) +/- Other tests which we
             might be able to develop within this cohort (e.g. urine tests)
  BACKGROUND Asthma affects 10% of the general population but remains a diagnostic challenge.
        Considering the difficult access, weak specificity, and low clinical utility of bronchial
        provocation tests, more effective diagnostic methods are needed. Blood eosinophils and
        exhaled nitric oxide (FeNO) are biomarkers of type-2 inflammation that have established
        mechanistic, prognostic and theragnostic values in chronic asthma. Specifically, these
        biomarkers identify attack-prone patients with ongoing alarmin, type-2 cytokine, and
        chemokine signalling at the epithelial level driving airway hyperresponsiveness and
        accelerated lung function decline. Most importantly, these biomarkers also identify those who
        benefit the most from anti-inflammatory therapy. Considering the above clinical utilities,
        using biomarkers in primary care to diagnose airways disease in people with suspected asthma
        would represent a very effective diagnostic strategy.
  
        HYPOTHESIS: In people with non-diagnostic spirometry and asthma suspected by primary care,
        measuring blood eosinophils and FeNO is a feasible diagnostic strategy with good accuracy and
        the added value of early mechanistic insight in epithelial signalling pathways.
  
        OBJECTIVE: To estimate the diagnostic performance parameters of type-2 biomarkers in people
        with suspected asthma and a non-diagnostic spirometry. An exploratory analysis of
        inflammatory proteins (alarmin, type-2 cytokines, chemokines) in the nasal epithelial lining
        fluid (NELF) and serum according to biomarkers will be conducted. This and other secondary
        exploratory objectives will lead to better mechanistic and operational insight on the value
        of type-2 biomarkers in early disease.
  
        METHODS: The investigators propose a prospective observational study on the logistical
        feasibility, receiver operating characteristics (ROC), and mechanistic value of point-of-care
        type-2 inflammatory biomarkers to diagnose asthma (Figure). The study will include 123 people
        ≥12 years old with non-diagnostic pre-postbronchodilator spirometry referred by primary care
        for a methacholine challenge via the Suspected Asthma pathway of the Centre Hospitalier
        Universitaire de Sherbrooke. After the methacholine challenge, patients will complete
        questionnaires, have blood eosinophils measured (by venous blood sample and point-of-care
        (POC) capillary blood), FeNO measured (by electroluminescence and POC strip-tests),
        nasosorption performed, and serum harvested for allergy testing and inflammatory protein
        measurement.
  
        OUTCOMES: The main analysis will be ROC plots of (1) FeNO alone; (2) blood eosinophils alone;
        and (3) the combination of blood eosinophils and FeNO;. The ROC plot will be based on a
        methacholine provocative dose ≤190 mcg (~ provocative concentration ≤8 mg/mL). The target
        sample size of 123 will have 90% power to compute 3 ROC curves' area under the curve (AUC) ≥
        0.7 significantly different from the null hypothesis (AUC=0.5) with a conservatively
        corrected two-sided α error < 0.016, assuming a positive/negative case ratio of 2. Secondary
        outcomes are the diagnostic and cost-effectiveness of blood eosinophil and FeNO measurement
        compared to methacholine challenges; and univariate plus multivariate modelling between blood
        eosinophils, FeNO, and inflammatory proteins (alarmins TSLP and IL-33; type-2 cytokines IL-4,
        -5, -13; chemokines eotaxin-3 and TARC) measured in the NELF and serum, or metabolites
        measured in the urine.
  
        EXPECTED RESULTS: It is expected that type-2 inflammometry to be a useful alternative
        diagnostic pathway with benefits extending beyond diagnostic accuracy thanks to early insight
        into the inflammatory phenotype.
  
        IMPACT: This observational study will support further validation studies and/or trials
        assessing POC biomarker-assisted diagnosis and management of asthma in the community setting.
        Measuring biomarkers at the time of diagnosis could facilitate a 'predict and prevent'
        approach to diagnostic algorithms in airway disease
  observational model: Cohort
  time perspective: Prospective
  measure: AUC of the ROC analysis to diagnose asthma
  time frame: FeNO measured on the day of the methacholine challenge (i.e. Baseline visit)
  description: Diagnosis of asthma defined as a methacholine PD20 < 190 mcg
  measure: Blood eosinophil count: ROC analysis AUC to diagnose asthma
  time frame: Blood eosinophils measured on the day of the methacholine challenge (i.e. Baseline visit)
  description: Diagnosis of asthma defined as a methacholine PD20 < 190 mcg
  measure: Combination of FeNO + Blood eosinophil count: ROC analysis AUC to diagnose asthma
  time frame: FeNO and blood eosinophils measured on the day of the methacholine challenge (i.e. Baseline visit)
  description: Diagnosis of asthma defined as a methacholine PD20 < 190 mcg
  measure: Univariate association between biomarkers (blood eosinophils and FeNO) and inflammatory proteins/metabolites
  time frame: Baseline
  description: Inflammatory proteins/metabolites measured in the NELF, serum, and urine. 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.
  measure: Operational efficacy of the use of biomarkers as a diagnostic tool:
  time frame: Baseline
  description: Potential reduction in diagnostic delay in asthma patients: the difference (in days) between the date of the challenge test and the date of the request
  Time difference (in minutes/days) for diagnosing asthma using biomarkers (FeNO + eosinophilia) versus a methacholine challenge.
  Cost difference between the use of biomarkers (traditional or point-of-care analysed separately) as 2nd diagnosis step versus a standard methacholine challenge test.
  measure: Concordance between traditional biomarker measurements (FeNO using Niox Vero and eosinophils in venous blood) and the new POC method (capillary eosinophils using Sight OLO).
  time frame: Baseline
  description: Intraclass correlation coefficient (both sides, mixed model for absolute concordance, single measurements)
  Estimated fixed Bland-Altman bias for the gold standard versus point-of-care
  measure: Biomarker level in asthmatic patients at time of diagnosis
  time frame: Baseline
  description: 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)
  arm group label: People suspected with asthma
  description: Patients will receive an in invitation letter at the time of BPT scheduling. In the week proceeding the test, the clinical inhalation therapist will discuss the project and schedule the study visit on the day of the BPT. The study visit will be done prior to BPT whenever possible.
  Baseline visit:
  Medical history
  5-item Asthma Control Questionnaire (ACQ-5)
  FeNO measurement (NIOX VERO device)
  Nasosorption for nasal epithelial lining fluid (NELF) biobanking
  blood tests (complete blood count with differential, C-reactive protein, total and specific serum immunoglobulin E, biobank), capillary blood eosinophils (Sight OLO),
  urine sample (biobank)
  intervention type: Diagnostic Test
  intervention name: ¸FeNO
  description: FeNO measured with a NIOX VERO device after the methacholine challenge
  arm group label: People suspected with asthma
  Serum, plasma, whole blood
  
        Nasosorption for NELF (nasal epithelial lining fluid)
  
        Urine sample
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 12 Years
  maximum age: N/A
  last name: Simon Couillard, MD MSc
  phone: +1-819-346-1110
  phone ext: 15037
  email: s.couillard@usherbrooke.ca
  facility: 
  status: Recruiting
  contact: 
  country: Canada
  responsible party type: Sponsor
  mesh term: Asthma
  mesh term: Inflammation
  sharing ipd: Undecided