Research questions: Primary questions:* Are the new point-of-care instruments for the measurement of VOCs in exhaled breath feasible for use in children and adolescents aged 6 to 20 years?* Are these techniques able to differentiate between healthy…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Exhaled nitric oxide test and exhaled breath condensate (EBC):
Fraction of exhaled nitric oxide (FeNO) will be obtained with the online NIOX
analyser (Aerocrine, Solna, Sweden) according to ATS/ERS standards [12]. FeNO
is currently considered as gold standard test for non-invasive measurement of
lung inflammation.EBC will be collected by means of an optimised glass tube,
cooled by counter-current circulating ice water, as described previously [2].
Children breathe tidally for ten minutes, while wearing a nose-clip, through a
mouthpiece connected to a two-way non-rebreathing valve (Hans Rudolph Inc,
series 1420, Kansas City, USA). The two-way valve and tubing to the condenser,
serves as a saliva trap. After collection, EBC was rapidly frozen at -80°C
using dry ice and was stored at -80ºC until analysis. Inflammatory markers and
microbiome will be determined in EBC and compared to VOCs profiles as gold
standard for airway inflammation.
VOCs in exhaled breath:
For analysis of VOCs the following exhaled breath techniques will be used:
* eNose Aeonose® from The eNose Company [6]
* Ion mobility Spectrometer (IMS) from Ganshorn [8]
* Gas chromatography mass spectrometry (GC-MS) from Ganshorn (gold standard
VOCs analysis)
All techniques will be randomly studied in all participants.
Procedure of exhaled VOCs techniques:
The child/adolescent will be asked to breath tidally through a mouth piece into
the eNose/IMS. The duration of the procedure depends on the technique but will
not exceed 5 to 10 minutes.
After a pause of 10 minutes the next technique will be performed, and so on.
The total duration of testing will be approximately 60 minutes.
Eating and exercise are prohibited within 60 minutes prior to testing. Drinking
of water is allowed prior to and in between tests. Use of inhalation medication
will be stopped 3 hours before measurements.
All techniques are completely non-invasive. In case of resistance of the child,
the measurements will be terminated.
Outcome:
VOC profiles will be measured with all 4 techniques.
* Each technique will be evaluated in its use (child-friendliness, feasibility)
and adaptations in protocol or technique will be investigated to improve
measurement and feasibility in children.
* Per technique, the discriminative power of the VOC profiles between healthy
children/adolescents and children/adolescents with asthma and/or CF will be
studied.
Secondary outcome
References:
1. Dallinga JW, Robroeks CM, van Berkel JJ, Moonen EJ, Godschalk RW, Jöbsis Q,
Dompeling E, Wouters EF, van Schooten FJ. Volatile organic compounds in exhaled
breath as a diagnostic tool for asthma in children. Clin Exp Allergy
2010;40(1):68-76.
2. Klaassen EM, van de Kant KD, Jöbsis Q, van Schayck OC, Smolinska A, Dallinga
JW, van Schooten FJ, den Hartog GJ, de Jongste JC, Rijkers GT, Dompeling E.
Exhaled biomarkers and gene expression at preschool age improve asthma
prediction at 6 years of age. Am J Respir Crit Care Med 2015;191(2):201-7.
3. Robroeks CM, van Berkel JJ, Dallinga JW, Jöbsis Q, Zimmermann LJ, Hendriks
HJ, Wouters MF, van der Grinten CP, van de Kant KD, van Schooten FJ, Dompeling
E. Metabolomics of volatile organic compounds in cystic fibrosis patients and
controls. Pediatr Res 2010;68(1):75-80.
4. Fens N, van der Schee MP, Brinkman P, Sterk PJ. Exhaled breath analysis by
electronic nose in airways disease. Established issues and key questions. Clin
Exp Allergy 2013;43:705-715.
5. Van der Schee MP, Paff T, Brinkman P, van Aalderen WMC, Haarman EG, Sterk
PJ. Breathomics in lung disease. Chest 2015;147(1):224-231.
6. Product information Aeonose, The eNose company:
http://www.enose.nl/products/aeonose/.
7. Product information eNose, Common Invent: http://www.comon-invent.com/enose/
8. Product information Ion Mobility Spectrometer, Ganshorn:
http://www.ganshorn.nl/index.php?option=com_content&view=article&id=22&Itemid=23
8.
9. Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK,
Williams H: Worldwide time trends in the prevalence of symptoms of asthma,
allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and
Three repeat multicountry cross-sectional surveys. Lancet
2006;368(9537):733-743.
10. ISAAC questionnaire:
http://isaac.auckland.ac.nz/resources/tools.php?menu=tools1
11. Juniper EF, Gruffydd-Jones K, Ward S, Svensson K. Asthma Control
Questionnaire in children: validation, measurement properties, interpretation.
Eur Respir J 2010;36:1410*1416.
12. ATS/ERS recommendations for standardized procedures for the online and
offline measurement of exhaled lower respiratory nitric oxide and nasal nitric
oxide. Am J Respir Crit Care Med 2005;171:912*930.
13. Scott SM, James D, Ali Z. Data analysis for electronic nose systems.
Microchim Acta 2006;156:183-207.
14. Smolinska A, Hauschild AC, Fijten RR, Dallinga JW, Baumbach J, van Schooten
FJ. Current breathomics * a review on data pre-processing techniques and
machine learning in metabolomics breath analysis. J Breath Res 2014;8(2): doi:
10.1088/1752-7155/8/2/027105.
Background summary
Assessing airway inflammation in young children is a challenging task.
Bronchoscopy and the evaluation of bronchoalveolar lavage fluid and/or
endobronchial biopsy samples is considered as the gold standard. However, these
techniques are invasive (general anaesthesia is always required for
bronchoscopy in children!) and therefore not suitable for routine use in
children. Recently, new non-invasive techniques have been developed to assess
airway inflammation for diagnostic or monitoring purposes in (preschool)
children. One of these non-invasive techniques is the measurement of volatile
organic compounds (VOCs) in exhaled breath. VOCs profiles have proven to
accurately differentiate children with asthma from healthy children [1]. We
recently demonstrated that the measurement of VOCs can accurately predict an
asthma diagnosis in wheezing preschool children [2]. Furthermore, VOCs
profiles can differentiate healthy children from children with Cystic Fibrosis
(CF) [3], and between CF patients with and without Pseudomonas aeruginosa
colonization [3]. Therefore, the measurement of VOCs in exhaled breath is a
promising new non-invasive technique for assessing airway inflammation in
children and adults with lung diseases.
VOCs in exhaled breath are usually measured by gas chromatography mass
spectrometry technique (GC-MS), an expensive and time consuming technique. To
make the analysis of VOCs more feasible in common practice, hand-held devices
have been developed that are increasingly used in adult patients [4, 5].
Examples are electronic Noses (eNose) from The eNose Company (Aeonose [6]) and
from Common Invent [7], and an Ion Mobility Spectrometer (IMS) from Ganshorn
[8].
However, these techniques have not been studied in children, and data on
feasibility in children are mostly lacking.
In this study we would like to investigate the feasibility and reliability of
new point-of-care instruments for measurements of VOCs in exhaled breath in
young children aged 6 to 16 years.
Study objective
Research questions:
Primary questions:
* Are the new point-of-care instruments for the measurement of VOCs in exhaled
breath feasible for use in children and adolescents aged 6 to 20 years?
* Are these techniques able to differentiate between healthy children and
adolescents, asthmatic children and adolescents, and children and adolescents
with cystic fibrosis (CF)? e.g. will it result in different VOC profiles?
Secondary question: what is the relationship between the new point-of-care
instruments and the standard breath tests (FeNO and EBC)?
Study design
Study Design: Cross-sectional study during 60 minutes.
Study burden and risks
The burden is very limited because the study takes not more than 60 minutes and
is completely non-invasive (collection of exhaled breath and a short
questionnaire). The collection of exhaled breath is safe and bears no extra
risks.
Children and adolescents with asthma or CF in the study may benefit as the NO
test and the questionnaire may point to respiratory complaints or a respiratory
infection with appropriate clinical evaluation as a consequence.
At the end, after the development of the breath test, many children with and
without serious respiratory diagnoses will benefit as it will improve diagnosis
and treatment.
P. Debyelaan 25
Maastricht 6202 AZ
NL
P. Debyelaan 25
Maastricht 6202 AZ
NL
Listed location countries
Age
Inclusion criteria
Study Population:
3 groups of children and adolescents aged 6-20 years will be randomly selected:
* 20 healthy children and adolescents
* 20 children and adolescents with asthma
* 20 children and adolescents with CF;Inclusion criteria:
* Children and adolescents aged 6 to 20 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
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 and adolescents:
* No current or history of respiratory symptoms (by using ISAAC questionnaire)
* No current or history of allergic rhinitis (by using ISAAC questionnaire)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL53995.068.15 |