AsthmaWheezyERNCT02743663
The Development of Novel Clinical Tests to Diagnose and Monitor Asthma in Preschool Children
An observational study of Asthma and Wheeze, run by The Hospital for Sick Children at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 to 5 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma, Wheeze, Obstructive Sleep Apnea
- What is being tested?
- Bronchodilator response, Allergy Skin Test and Multiple-Breath Washout
- Type of treatment
- Surgery or procedure
- How many people
- 121 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2014to Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 5 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Wheezing preschool-aged subjects will be recruited within 5 days of their discharge from the Emergency Department at the Hospital for Sick Children. Healthy preschool-aged controls will be recruited from the community (concurrent observational studies being conducted by the PI at the Hospital for Sick Children, children of co-workers)
Who may be able to join
- 3 to 5 years of age (36 to 71 months)
- Diagnosis of Asthma made by a physician in the emergency department
- History of at least two other wheezing episode within the previous 12 months
- Received salbutamol within 4hrs before emergency department visit, during current emergency department visit, or was prescribed salbutamol at discharge from emergency department.
- 3 to 5 years of age (36 to 71 months)
- Free of a respiratory infection for a minimum of 4 weeks prior to the testing visit
Who cannot join
- History or coexistence of renal, chronic pulmonary, cardiac, neurological or systemic disease
- Born pre-term (< 35 weeks GA)
- Insufficient command of the English language
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Asthma, Wheeze, Obstructive Sleep Apnea, Food Allergy, Virus
- Being tested
- Bronchodilator response, Allergy Skin Test, Multiple-Breath Washout, Forced Oscillation Technique, Spirometry
- Keywords
- pediatric, lung ventilation inhomogeneity, preschool, asthma, wheeze
- Medical subject headings
- Asthma, Respiratory Sounds, Sleep Apnea, Obstructive, Food Hypersensitivity, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bronchodilator responseProcedure or surgery
Bronchodilator (Salbutamol - dose dependent on participant prescription) to wheezing subjects. 15 minutes after bronchodilator, spirometry and FOT repeated.
Allergy Skin TestProcedure or surgery
Child will be tested for allergies to 17 different allergens, and positive (histamine) and negative (glycerin) controls, for a total of 19 allergens.
Multiple-Breath WashoutProcedure or surgery
Also called MBW
Facemask in children 3-5 yrs, Wash-in phase: medical air inhaled during tidal breathing until steady state. Bias flow switched to 100% oxygen. Wash-out phase: patient breathes in 100% oxygen until nitrogen levels reach ~2%. Each test in duplicate and average is calculated.
Forced Oscillation TechniqueProcedure or surgery
Also called FOT
Sterile mouthpiece attached to FOT device. Patient is tested seated with noseclips and mouthpiece. FOT device produces oscillations at different frequencies (from that flow into lungs. Device measures resistance and reactance in lungs.
SpirometryProcedure or surgery
Forced exhale manoeuvre completed by participant into flow meter, measuring forced exhale volumes and speed.
salbutamolDrug
Also called ventolin
Given during bronchodilator response.
Nasal BrushProcedure or surgery
Nasal brush of 1 inferior turbinate to collect epithelial cells. Collected on either nare, choice dependent on how clear the nare is (i.e. no mucous, no nasal mucosal edema, no major structural impediments).
Blood sampleProcedure or surgery
8mLs of venous blood collected using a butterfly needle of appropriate gauge. Blood sample used to collect CBC values, total IgE, serum, DNA, plasma, and whole blood.
Basophil activation testProcedure or surgery
Also called BAT
Collect basophils from whole blood sample, and expose cells to food allergens in flow cytometry machine to measure allergic response, if any.
Nasal swabProcedure or surgery
Gentle swabbing of both nasal openings to collect mucous sample for analysis of microbial contents (i.e. bacteria, virus, fungi).
| Study group | Role | What they receive |
|---|---|---|
| Wheezing subjects | Two 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. Receives: Procedure: Bronchodilator response; Procedure: Allergy Skin Test; Procedure: Multiple-Breath Washout; Procedure: Forced Oscillation Technique; Procedure: Spirometry; Drug: salbutamol; Procedure: Nasal Brush; Procedure: Blood sample; Procedure: Basophil activation test; Procedure: Nasal swab | |
| Healthy cohort | One 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. Receives: Procedure: Allergy Skin Test; Procedure: Multiple-Breath Washout; Procedure: Forced Oscillation Technique; Procedure: Spirometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Lung Clearance Index (LCI) in wheezing subjects.
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).
Measured: baseline and 3 months
Secondary outcomes (11)
Obstructive Sleep Apnea (OSA)
Obstructive sleep apnea symptoms in wheezing preschool aged children, captured using the Pediatric Sleep Questionnaire.
Measured: Day 1, and again 3 months later.
Change in asthma symptoms
Changes in parental report of symptoms (using the TRACK questionnaire) and clinically assessed symptoms (PRAM scale, ISAAC modified questions) over 3 month time frame.
Measured: baseline and 3 months
Change in Forced Oscillation Technique (FOT) values in wheezing subjects.
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.
Measured: baseline and 3 months
Change in spirometry values in wheezing subjects.
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.
Measured: baseline and 3 months
Comparison of LCI values between wheezy subjects and healthy controls.
Determine if LCI values in preschool children differ between children with no history of wheeze and those with recurrent wheeze.
Measured: Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.
Comparison of forced oscillation technique (FOT; lung impedence) values between wheezy subjects and healthy controls.
Determine if FOT values in preschool children differ between children with no history of wheeze and those with recurrent wheeze.
Measured: Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.
Comparison of spirometric values between wheezy subjects and healthy controls.
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.
Measured: Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.
Change in nasal microbiome in wheezing subjects
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.
Measured: Day 1 and 3 months
Viral infections causing wheezing
A nasal swab collected at Day 1 will be used to determine which viruses are causing wheezing in wheezing subjects.
Measured: Day 1
Basophil activation test (BAT)
Determine the ability of the BAT to confirm food allergies in a wheezing cohort.
Measured: Day 1 and 3 months
Lung epithelial cell immune response in wheezing subjects.
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.
Measured: Day 1 and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2016 (estimated)
- Study startJun 2014
- Primary completionDec 2020
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Dalhousie University
- Responsible party
- Principal investigator, Padmaja Subbarao, The Hospital for Sick Children
- Investigators
- Padmaja Subbarao, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02743663
- Sponsor's protocol ID
- 1000041089
- Acronym
- WheezyER
- Status last verified
- Feb 2021
- First submitted
- 13 Jan 2016
- Last updated
- 8 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Development of Novel Clinical Tests to Diagnose and Monitor Asthma in Preschool Children
- ClinicalTrials.gov ID
- NCT02743663
- Acronym / sponsor ID
- WheezyER / 1000041089
- Conditions
- Asthma, Wheeze, Obstructive Sleep Apnea, Food Allergy, Virus
- Keywords
- pediatric, lung ventilation inhomogeneity, preschool, asthma, wheeze
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Dalhousie University
- Study start
- Jun 2014
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 19 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Wheezing subjects | – | Procedure: Bronchodilator response, Procedure: Allergy Skin Test, Procedure: Multiple-Breath Washout, Procedure: Forced Oscillation Technique, Procedure: Spirometry, Drug: salbutamol, Procedure: Nasal Brush, Procedure: Blood sample, Procedure: Basophil activation test, Procedure: Nasal 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 cohort | – | Procedure: Allergy Skin Test, Procedure: Multiple-Breath Washout, Procedure: Forced Oscillation Technique, Procedure: SpirometryOne 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. |
Who may qualify
- Ages
- 3 to 5 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Wheezing preschool-aged subjects will be recruited within 5 days of their discharge from the Emergency Department at the Hospital for Sick Children. Healthy preschool-aged controls will be recruited from the community (concurrent observational studies being conducted by the PI at the Hospital for Sick Children, children of co-workers)
Key inclusion criteria (6 listed)
- 3 to 5 years of age (36 to 71 months)
- Diagnosis of Asthma made by a physician in the emergency department
- History of at least two other wheezing episode within the previous 12 months
- Received salbutamol within 4hrs before emergency department visit, during current emergency department visit, or was prescribed salbutamol at discharge from emergency department.
- 3 to 5 years of age (36 to 71 months)
Key exclusion criteria (3 listed)
- History or coexistence of renal, chronic pulmonary, cardiac, neurological or systemic disease
- Born pre-term (< 35 weeks GA)
- Insufficient command of the English language
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bronchodilator responseBronchodilator (Salbutamol - dose dependent on participant prescription) to wheezing subjects. 15 minutes after bronchodilator, spirometry and FOT repeated. | Procedure or surgery | Wheezing subjects |
| Allergy Skin TestChild will be tested for allergies to 17 different allergens, and positive (histamine) and negative (glycerin) controls, for a total of 19 allergens. | Procedure or surgery | Healthy cohort, Wheezing subjects |
| Multiple-Breath WashoutAlso: MBWFacemask in children 3-5 yrs, Wash-in phase: medical air inhaled during tidal breathing until steady state. Bias flow switched to 100% oxygen. Wash-out phase: patient breathes in 100% oxygen until nitrogen levels reach ~2%. Each test in duplicate and average is calculated. | Procedure or surgery | Healthy cohort, Wheezing subjects |
| Forced Oscillation TechniqueAlso: FOTSterile mouthpiece attached to FOT device. Patient is tested seated with noseclips and mouthpiece. FOT device produces oscillations at different frequencies (from that flow into lungs. Device measures resistance and reactance in lungs. | Procedure or surgery | Healthy cohort, Wheezing subjects |
| SpirometryForced exhale manoeuvre completed by participant into flow meter, measuring forced exhale volumes and speed. | Procedure or surgery | Healthy cohort, Wheezing subjects |
| salbutamolAlso: ventolinGiven during bronchodilator response. | Drug | Wheezing subjects |
| Nasal BrushNasal brush of 1 inferior turbinate to collect epithelial cells. Collected on either nare, choice dependent on how clear the nare is (i.e. no mucous, no nasal mucosal edema, no major structural impediments). | Procedure or surgery | Wheezing subjects |
| Blood sample8mLs of venous blood collected using a butterfly needle of appropriate gauge. Blood sample used to collect CBC values, total IgE, serum, DNA, plasma, and whole blood. | Procedure or surgery | Wheezing subjects |
| Basophil activation testAlso: BATCollect basophils from whole blood sample, and expose cells to food allergens in flow cytometry machine to measure allergic response, if any. | Procedure or surgery | Wheezing subjects |
| Nasal swabGentle swabbing of both nasal openings to collect mucous sample for analysis of microbial contents (i.e. bacteria, virus, fungi). | Procedure or surgery | Wheezing subjects |
Primary outcome
Change in Lung Clearance Index (LCI) in wheezing subjects.
Time frame: 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).
11 secondary outcomes
Obstructive Sleep Apnea (OSA)
Time frame: Day 1, and again 3 months later.
Change in asthma symptoms
Time frame: baseline and 3 months
Change in Forced Oscillation Technique (FOT) values in wheezing subjects.
Time frame: baseline and 3 months
Change in spirometry values in wheezing subjects.
Time frame: baseline and 3 months
Comparison of LCI values between wheezy subjects and healthy controls.
Time frame: Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.
Comparison of forced oscillation technique (FOT; lung impedence) values between wheezy subjects and healthy controls.
Time frame: Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.
Comparison of spirometric values between wheezy subjects and healthy controls.
Time frame: Day 1 for wheezing subjects and healthy controls, and again 3 months later for wheezing subjects.
Change in nasal microbiome in wheezing subjects
Time frame: Day 1 and 3 months
Viral infections causing wheezing
Time frame: Day 1
Basophil activation test (BAT)
Time frame: Day 1 and 3 months
Lung epithelial cell immune response in wheezing subjects.
Time frame: Day 1 and 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Padmaja Subbarao, MD principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma and Wheeze, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Lung Clearance Index (LCI) in wheezing subjects. (time frame: baseline and 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2021.