Breath Analysis in Children by New Point-of-care Instruments

Study Overview
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Brief Summary
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In this study new hand-held devices for measuring exhaled breath will be tested in children with asthma, CF, and healthy controls. Main objectives will be feasibility and discriminative value of these techniques.

Detailed Description
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Rationale: Assessment of volatile organic compounds (VOCs) is a new recently developed non-invasive technique to assess airway inflammation. The non-invasive character makes it highly suitable for use in (preschool) children. However, the analysis of VOCs by gas chromatography mass spectrometry technique (GC-MS), the gold standard, is expensive and time consuming. Therefore, new hand-held devices (such as electronic Noses (eNoses) and Ion Mobility Spectrometer techniques) have been developed. However, these new point-of-care instruments have not been studied in children. Objectives: 1) To test whether new point-of-care instruments for the measurement of VOCs in exhaled breath are feasible for use in children aged 6 to 16 years; 2) To explore whether these techniques can differentiate between healthy children, asthmatic children and children with Cystic Fibrosis (CF). Study design: Cross-sectional study design. Several VOCs tests will be performed in all participants.Besides, fraction of exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC) will be measured. Study population: Three groups of children aged 6 to 16 years: 20 healthy children, 20 children with doctor's diagnosed asthma, 20 children with CF. Main study parameters/endpoints: Each technique will be evaluated for its use and feasibility in children. For each technique, VOC profiles between study groups will be evaluated for its discriminative power.

Official Title
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The Feasibility and Diagnostic Value of New Point-of-care Instruments for Breath Analysis in Children With Asthma, Cystic Fibrosis (CF), and Healthy Controls

Conditions
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Asthma, Cystic Fibrosis

Intervention / Treatment
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* Diagnostic Test: inflammation markers in exhaled breath


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 6 to 16 years Healthy group: See exclusion criteria Asthma group: Doctor's diagnosed asthma Cystic Fibrosis group: A diagnosis of cystic fibrosis, confirmed by a sweat test or genetic analysis Exclusion criteria Recent course of prednisone or antibiotics (< 1 month before test) Passive smoking Other chronic inflammatory disease (e.g. inflammatory bowel disease, rheumatic disease, auto-immune disease) Healthy children: No current or history of respiratory symptoms No current or history of allergic rhinitis

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Asthma<br>Inflammation markers in exhaled breath will be used in 20 children aged 6 to 16 years with doctor's diagnosed asthma | Diagnostic Test: inflammation markers in exhaled breath<br>* non-invasive, cross-sectional, assessment of inflammation markers in exhaled breath with various techniques (observational)<br>|
| Cystic fibrosis<br>Inflammation markers in exhaled breath will be used in 20 children aged 6 to 16 years with CF | Diagnostic Test: inflammation markers in exhaled breath<br>* non-invasive, cross-sectional, assessment of inflammation markers in exhaled breath with various techniques (observational)<br>|
| Healthy<br>Inflammation markers in exhaled breath will be used in 20 children aged 6 to 16 years old without respiratory diseases | Diagnostic Test: inflammation markers in exhaled breath<br>* non-invasive, cross-sectional, assessment of inflammation markers in exhaled breath with various techniques (observational)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events directly related to the various point-of-care tests used | Any adverse event of any kind will be noted. Furthermore, each participant will be asked whether the test was easy to perform. This question can be answered on a 5-point scale (0=totally agree that test was easy to perform, 4= totally disagree that test was easy to perform) | Questionnaire will be done directly after specific test (1 day). No long term (S)AE is expected and measurement of each test is only performed once. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and Specificity of new point-of-care Aeonose eNose in diagnosing asthma. | Aeonose eNose measurements will be analysed by in house software program (Aethena) developed by eNose company (Zutphen, Netherlands). To test sensitivity and specificity, first an area under the receiver operating curve must be calculated with the aforementioned software program. Hereafter sensitivity and specificity of the eNose can be calculated. | Measurements will be analysed within 6 to 12 months | 
| Sensitivity and Specificity of new point-of-care Aeonose eNose in diagnosing cystic fibrosis. | Aeonose eNose measurements will be analysed by in house software program (Aethena) developed by eNose company (Zutphen, Netherlands). To test sensitivity and specificity, first an area under the receiver operating curve must be calculated with the aforementioned software program. Hereafter sensitivity and specificity of the eNose can be calculated. | Measurements will be analysed within 6 to 12 months | 
| Sensitivity and Specificity of Ion Mobility Spectrometry in diagnosing asthma. | IMS measurements will be analysed by software program developed for using IMS data (Visual Now, Ganshorn, Dortmund, Germany). By IMS different VOCs peaks are generated. By using the aforementioned software, these peaks can be analysed and sensitivity and specificity between asthma and healthy children can be calculated. | Measurements will be analysed within 6 to 12 months | 
| Sensitivity and Specificity of Ion Mobility Spectrometry in diagnosing cystic fibrosis. | IMS measurements will be analysed by software program developed for using IMS data (Visual Now, Ganshorn, Dortmund, Germany). By IMS different VOCs peaks are generated. By using the aforementioned software, these peaks can be analysed and sensitivity and specificity between CF and healthy children can be calculated. | Measurements will be analysed within 6 to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paediatrics, breath analysis, volatile organic compounds, respiratory diseases