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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Cystic Fibrosis
• Intervention / Treatment: Diagnostic test: inflammation markers in exhaled breath

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Maastricht University Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 16 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Asthma; 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; non-invasive, cross-sectional, assessment of inflammation markers in exhaled breath with various techniques (observational)
Cystic fibrosis; 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; non-invasive, cross-sectional, assessment of inflammation markers in exhaled breath with various techniques (observational)
Healthy; 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; non-invasive, cross-sectional, assessment of inflammation markers in exhaled breath with various techniques (observational)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Edward Dompeling, MD, PhD, Maastricht University Medical Centre

Publications and helpful links

General Publications

• Bannier MAGE, van de Kant KDG, Jobsis Q, Dompeling E. Feasibility and diagnostic accuracy of an electronic nose in children with asthma and cystic fibrosis. J Breath Res. 2019 May 8;13(3):036009. doi: 10.1088/1752-7163/aae158.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: January 29, 2016
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 18, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: volatile organic compounds; respiratory diseases; paediatrics; breath analysis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Infant, Newborn, Diseases; Bronchial Diseases; Genetic Diseases, Inborn; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Pancreatic Diseases; Fibrosis; Asthma; Cystic Fibrosis
• Other Study ID Numbers: NL 53995.068.15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No