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

NCT ID: NCT02743663

Last Updated: 2021-02-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

121 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-06-30

Study Completion Date

2020-12-31

Brief Summary

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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

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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

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Asthma Wheeze Obstructive Sleep Apnea Food Allergy Virus

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Bronchodilator response

Intervention Type PROCEDURE

Bronchodilator (Salbutamol - dose dependent on participant prescription) to wheezing subjects. 15 minutes after bronchodilator, spirometry and FOT repeated.

Allergy Skin Test

Intervention Type PROCEDURE

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 Washout

Intervention Type PROCEDURE

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 Technique

Intervention Type PROCEDURE

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.

Spirometry

Intervention Type PROCEDURE

Forced exhale manoeuvre completed by participant into flow meter, measuring forced exhale volumes and speed.

salbutamol

Intervention Type DRUG

Given during bronchodilator response.

Nasal Brush

Intervention Type PROCEDURE

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 sample

Intervention Type PROCEDURE

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 test

Intervention Type PROCEDURE

Collect basophils from whole blood sample, and expose cells to food allergens in flow cytometry machine to measure allergic response, if any.

Nasal swab

Intervention Type PROCEDURE

Gentle swabbing of both nasal openings to collect mucous sample for analysis of microbial contents (i.e. bacteria, virus, fungi).

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.

Allergy Skin Test

Intervention Type PROCEDURE

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 Washout

Intervention Type PROCEDURE

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 Technique

Intervention Type PROCEDURE

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.

Spirometry

Intervention Type PROCEDURE

Forced exhale manoeuvre completed by participant into flow meter, measuring forced exhale volumes and speed.

Interventions

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Bronchodilator response

Bronchodilator (Salbutamol - dose dependent on participant prescription) to wheezing subjects. 15 minutes after bronchodilator, spirometry and FOT repeated.

Intervention Type PROCEDURE

Allergy Skin Test

Child will be tested for allergies to 17 different allergens, and positive (histamine) and negative (glycerin) controls, for a total of 19 allergens.

Intervention Type PROCEDURE

Multiple-Breath Washout

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.

Intervention Type PROCEDURE

Forced Oscillation Technique

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.

Intervention Type PROCEDURE

Spirometry

Forced exhale manoeuvre completed by participant into flow meter, measuring forced exhale volumes and speed.

Intervention Type PROCEDURE

salbutamol

Given during bronchodilator response.

Intervention Type DRUG

Nasal Brush

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).

Intervention Type PROCEDURE

Blood sample

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.

Intervention Type PROCEDURE

Basophil activation test

Collect basophils from whole blood sample, and expose cells to food allergens in flow cytometry machine to measure allergic response, if any.

Intervention Type PROCEDURE

Nasal swab

Gentle swabbing of both nasal openings to collect mucous sample for analysis of microbial contents (i.e. bacteria, virus, fungi).

Intervention Type PROCEDURE

Other Intervention Names

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MBW FOT ventolin BAT

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* History or coexistence of renal, chronic pulmonary, cardiac, neurological or systemic disease
* Born pre-term (\< 35 weeks GA)
* Insufficient command of the English language
Minimum Eligible Age

3 Years

Maximum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Dalhousie University

OTHER

Sponsor Role collaborator

The Hospital for Sick Children

OTHER

Sponsor Role lead

Responsible Party

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Padmaja Subbarao

Staff Respirologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Padmaja Subbarao, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

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The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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Canada

Other Identifiers

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1000041089

Identifier Type: -

Identifier Source: org_study_id

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