Non-invasive Differential Diagnosis of Noisy Breathing Infants and Toddlers

Study Overview
=================
Brief Summary
-----------------
Almost 50% of all children have at least 1 episode of noisy breathing before the age of 2 years and almost 25% of these children have more episodes of noisy breathing. The lack of an objective technique for diagnosing noisy breathing children often leads to overrated diagnosis of wheezing, whereas there may be other noisy breathing phenotypes, like rattling, that don't favor from the same therapeutic treatment. Presumably, different underlying pathophysiological mechanisms are involved with different biomarker profiles characteristic for different phenotypes. The goal of this study is to optimize the diagnosis of noisy breathing infants and toddlers. Children will be followed for a treatment period of 6 weeks and will visit the paediatrician 3 times (week 0, 3 and 6). During the consultations breath sound analysis will be performed and a breath sample and a nasal mucus will be collected to analyse biomarker profiles. Both methods for diagnosing noisy breathing infants are non-invasive and will be compared to the standard procedure of the paediatrician which consists of auscultation and palpation of the chest. An objective and non-invasive method for diagnosing noisy breathing infants and toddler will pave the way for more cost-effective and personalized prescription of therapies which will increase the quality of life of children with noisy breathing.

Official Title
-----------------
Non-invasive Differential Diagnosis of Noisy Breathing Infants and Toddlers Based on Biomarker Profiles in Exhaled Breath and Nasal Mucus and Based on Breath Sound Analysis

Conditions
-----------------
Wheezing, Noisy Breathing Infants, Noist Breathing Toddlers, Rattling

Intervention / Treatment
-----------------
* Device: diagnosing noisy breathing in infants and toddlers


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: clinical diagnosis of noisy breathing (wheezing or rattling) Exclusion Criteria: born before pregnancy week 37 congenital or genetic conditions (Down syndrome, Klinefelter's syndrome, …) acquired chronic respiratory diseases (bronchopulmonary dysplasy, lung fibrosis, …)

Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 18 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Wheezing<br> | Device: diagnosing noisy breathing in infants and toddlers<br>* breath sampling and nasal mucus sampling to analyze biomarkers and breath sound analysis to diagnose noisy breathing.<br>|
| Other: Rattling<br> | Device: diagnosing noisy breathing in infants and toddlers<br>* breath sampling and nasal mucus sampling to analyze biomarkers and breath sound analysis to diagnose noisy breathing.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Noisy breathing diagnosis made by pediatrician based on anamnesis and auscultation | Noisy breathing diagnosis is made by the same pediatrician and is based on intensity and duration of both wheeze and rattle are scored on a scale of 0 to 10, whit 0 indicating not present and 10 indicating very high intensity or of continuous duration. | week 0 | 
| Noisy breathing diagnosis made by pediatrician based on anamnesis and auscultation | Noisy breathing diagnosis is made by the same pediatrician and is based on intensity and duration of both wheeze and rattle are scored on a scale of 0 to 10, whit 0 indicating not present and 10 indicating very high intensity or of continuous duration.which differentiate wheezing and rattling infants and toddlers. Comparing diagnosis based on these biomarker profiles to the diagnosis made by the pediatrician based on auscultation and palpation. | week 3 | 
| Noisy breathing diagnosis made by pediatrician based on anamnesis and auscultation | Noisy breathing diagnosis is made by the same pediatrician and is based on intensity and duration of both wheeze and rattle are scored on a scale of 0 to 10, whit 0 indicating not present and 10 indicating very high intensity or of continuous duration.which differentiate wheezing and rattling infants and toddlers. Comparing diagnosis based on these biomarker profiles to the diagnosis made by the pediatrician based on auscultation and palpation. | Week 6 | 
| exhaled breath volatiles | exhaled breath volatiles analyzed with Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) and Gas Chromatography Mass Spectrometry (GC-MS) | week 0 | 
| exhaled breath volatiles | exhaled breath volatiles analyzed with Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) and Gas Chromatography Mass Spectrometry (GC-MS) | week 3 | 
| exhaled breath volatiles | exhaled breath volatiles analyzed with Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) and Gas Chromatography Mass Spectrometry (GC-MS) | week 6 | 
| respiratory pathogens | respiratory pathogens present in a nasopharyngeal swab detected using PCR | week 0 | 
| respiratory pathogens | respiratory pathogens present in a nasopharyngeal swab detected using PCR | week 3 | 
| respiratory pathogens | respiratory pathogens present in a nasopharyngeal swab detected using PCR | week 6 | 
| level of inflammation markers | level of inflammation markers in the nasopharyngeal swab using multiplex immune-assay | week 0 | 
| level of inflammation markers | level of inflammation markers in the nasopharyngeal swab using multiplex immune-assay | week 3 | 
| level of inflammation markers | level of inflammation markers in the nasopharyngeal swab using multiplex immune-assay | week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breath sound recordings evaluated by expert panel of pediatricians | Intensity and duration of both wheeze and rattle are scored on a scale of 0 to 10, whit 0 indicating not present and 10 indicating very high intensity or continuous over the recording. | week 0 | 
| Breath sound recordings evaluated by expert panel of pediatricians | Intensity and duration of both wheeze and rattle are scored on a scale of 0 to 10, whit 0 indicating not present and 10 indicating very high intensity or continuous over the recording. | week 3 | 
| Breath sound recordings evaluated by expert panel of pediatricians | Intensity and duration of both wheeze and rattle are scored on a scale of 0 to 10, whit 0 indicating not present and 10 indicating very high intensity or continuous over the recording. | week 6 | 
| Treatment response assessed by online journal for parents | Parents are asked what type of noisy breathing symptoms their child had during the day. Options are: (1) Wheezing; (2) Rattling; (3) Both, but mostly wheezing; (4) Both, but mostly rattling; (5) Both in equal amounts, (6) No noisy breathing today. In the online questionnaire sound fragments of wheezing and rattling are available incase parents are in doubt. | week 6 | 
| Recurrence of symptoms assessed by follow up questionnaire | Online questionnaire asks about noisy breathing symptoms in the past 3 months, their frequency and seriousness. In the online | 3 months after week 6 | 
| Recurrence of symptoms assessed by follow up questionnaire | Online questionnaire asks about noisy breathing symptoms in the past 3 months, their frequency and seriousness. In the online | 6 months after week 6 | 
| Recurrence of symptoms assessed by follow up questionnaire | Online questionnaire asks about noisy breathing symptoms in the past 3 months, their frequency and seriousness. In the online | 9 months after week 6 | 
| Recurrence of symptoms assessed by follow up questionnaire | Online questionnaire asks about noisy breathing symptoms in the past 3 months, their frequency and seriousness. In the online | 12 months after week 6 |