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The Development of Novel Clinical Tests to Diagnose and Monitor Asthma in Preschool Children

Completed
Conditions
Wheeze
Food Allergy
Asthma
Obstructive Sleep Apnea
Virus
Interventions
Procedure: Bronchodilator response
Procedure: Multiple-Breath Washout
Procedure: Allergy Skin Test
Procedure: Forced Oscillation Technique
Procedure: Spirometry
Procedure: Nasal Brush
Procedure: Blood sample
Procedure: Basophil activation test
Procedure: Nasal swab
Registration Number
NCT02743663
Lead Sponsor
The Hospital for Sick Children
Brief Summary

The study will ascertain the ability of preschool lung function tests to distinguish healthy children from those with wheeze, and to differentiate phenotypes of wheezy children (high and low risk for asthma as defined by API) in order to predict response to therapy, and to explore the correlation between preschool lung function test results and symptoms, in order to develop objective methods for monitoring asthma.

Detailed Description

In Canada, the most common chronic disease of childhood is asthma. Childhood asthma places a significant burden on the health care system (refn). No objective preschool asthma diagnostic tools exist, and the current gold-standard, the Asthma Predictive Index, does not provide information about lung function and symptom management. In this study, it is hypothesized that the lung clearance index (LCI), a value derived from the multiple breath washout test, will be the most sensitive, responsive discriminative test for preschool asthma. If it proves useful in the monitoring and diagnosis of preschool asthma, LCI has the potential to improve the clinical management and thus potentially significantly reduce hospitalization rates for preschool children suffering with asthma. In this unique data set, the investigators will also compare the relative utility of the forced oscillation technique (FOT) and preschool spirometry with the LCI in order to detect abnormalities amongst those children at high risk for preschool asthma. In addition, the impact of sleep apnea as a risk factor for and modifier of asthma will be investigated in this study. Furthermore, changes to the composition of the nasal microbiome during and after a wheezing episodes and the role of viral infections in wheezing exacerbations will be explored. Finally, the utility of new methods of diagnosing food allergy, such as the basophil activation test, will be examined in this Canadian cohort.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
121
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Wheezing subjectsBronchodilator responseTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Wheezing subjectsBlood sampleTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Wheezing subjectsNasal swabTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Healthy cohortMultiple-Breath WashoutOne study visit will be completed with healthy participants. At this visit, three breathing tests will be performed: multiple-breath washout, forced oscillation technique, and spirometry. As well, an allergy skin test will be performed at the visit.
Healthy cohortForced Oscillation TechniqueOne study visit will be completed with healthy participants. At this visit, three breathing tests will be performed: multiple-breath washout, forced oscillation technique, and spirometry. As well, an allergy skin test will be performed at the visit.
Healthy cohortSpirometryOne study visit will be completed with healthy participants. At this visit, three breathing tests will be performed: multiple-breath washout, forced oscillation technique, and spirometry. As well, an allergy skin test will be performed at the visit.
Wheezing subjectsForced Oscillation TechniqueTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Wheezing subjectsSpirometryTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Wheezing subjectsBasophil activation testTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Wheezing subjectsAllergy Skin TestTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Wheezing subjectsMultiple-Breath WashoutTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Wheezing subjectsNasal BrushTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Healthy cohortAllergy Skin TestOne study visit will be completed with healthy participants. At this visit, three breathing tests will be performed: multiple-breath washout, forced oscillation technique, and spirometry. As well, an allergy skin test will be performed at the visit.
Wheezing subjectssalbutamolTwo study visits will be completed with wheezing subjects. The baseline visit will be completed within a 5 day window from the child's discharge from the emergency department. The follow-up visit will be completed 3 months after the baseline visit. At both visits, participants will provide a nasal swab and urine sample, complete three breathing tests: multiple-breath washout, forced oscillation technique, and Spirometry. In addition, at the follow-up visit, children will have an allergy skin test done, a nasal brush to collect epithelial cells and provide a blood sample. Whole blood will be used for basophil activation test (BAT). Children age 4+ will also complete post-bronchodilator testing using Salbutamol to capture information about bronchodilator response.
Primary Outcome Measures
NameTimeMethod
Change in Lung Clearance Index (LCI) in wheezing subjects.baseline and 3 months

Determine whether a change in LCI value captured over a 3 month period distinguishes two groups of wheezing children (high vs. low risk for asthma) as determined by the asthma predictive index (API).

Secondary Outcome Measures
NameTimeMethod
Lung epithelial cell immune response in wheezing subjects.Day 1 and 3 months

Epithelial lung cells collected from the inferior turbinate in wheezing subjects will be stimulated with viruses to categorize and differentiate immune cell response in wheezing subjects.

Comparison of spirometric values between wheezy subjects and healthy controls.Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.

Determine if spirometric indices (i.e. FEV1, FEV0.75, FVC, FEV1/FVC,PEF) in preschool children differ between children with no history of wheeze and those with recurrent wheeze.

Viral infections causing wheezingDay 1

A nasal swab collected at Day 1 will be used to determine which viruses are causing wheezing in wheezing subjects.

Obstructive Sleep Apnea (OSA)Day 1, and again 3 months later.

Obstructive sleep apnea symptoms in wheezing preschool aged children, captured using the Pediatric Sleep Questionnaire.

Change in spirometry values in wheezing subjects.baseline and 3 months

Determine whether a change in spirometric indices (i.e. FEV1, FEV0.75, FVC, FEV1/FVC,PEF) over a 3 month period distinguishes two groups of wheezing children (high vs. low risk for asthma) as determined by API.

Comparison of forced oscillation technique (FOT; lung impedence) values between wheezy subjects and healthy controls.Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.

Determine if FOT values in preschool children differ between children with no history of wheeze and those with recurrent wheeze.

Change in nasal microbiome in wheezing subjectsDay 1 and 3 months

A nasal swab collected at Day 1 and again 3 months later will allow us to categorize the change in bacterial and viral communities of the nasal microbiome in wheezing subjects during and post wheezing exacerbations.

Basophil activation test (BAT)Day 1 and 3 months

Determine the ability of the BAT to confirm food allergies in a wheezing cohort.

Change in asthma symptomsbaseline and 3 months

Changes in parental report of symptoms (using the TRACK questionnaire) and clinically assessed symptoms (PRAM scale, ISAAC modified questions) over 3 month time frame.

Change in Forced Oscillation Technique (FOT) values in wheezing subjects.baseline and 3 months

Determine whether a change in FOT values (lung impedence) over 3 month period distinguishes two groups of wheezing children (high vs. low risk for asthma) as determined by API.

Comparison of LCI values between wheezy subjects and healthy controls.Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.

Determine if LCI values in preschool children differ between children with no history of wheeze and those with recurrent wheeze.

Trial Locations

Locations (1)

The Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
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