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

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ClinicalTrials.gov Identifier: NCT02743663
Recruitment Status : Recruiting
First Posted : April 19, 2016
Last Update Posted : May 4, 2018
Sponsor:
Collaborator:
Dalhousie University
Information provided by (Responsible Party):
Padmaja Subbarao, 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.

Condition or disease Intervention/treatment
Asthma Wheeze Obstructive Sleep Apnea Food Allergy Virus 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

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.

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Study Type : Observational
Estimated Enrollment : 160 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Development of Novel Clinical Tests to Diagnose and Monitor Asthma in Preschool Children
Study Start Date : June 2014
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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.
Procedure: Bronchodilator response
Bronchodilator (Salbutamol - dose dependent on participant prescription) to wheezing subjects. 15 minutes after bronchodilator, spirometry and FOT repeated.

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.

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.
Other Name: MBW

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.
Other Name: FOT

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

Drug: salbutamol
Given during bronchodilator response.
Other Name: ventolin

Procedure: 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).

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.

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.
Other Name: BAT

Procedure: Nasal swab
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.
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.

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.
Other Name: MBW

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.
Other Name: FOT

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




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. Obstructive Sleep Apnea (OSA) [ Time Frame: Day 1, and again 3 months later. ]
    Obstructive sleep apnea symptoms in wheezing preschool aged children, captured using the Pediatric Sleep Questionnaire.

  2. Change in asthma symptoms [ Time Frame: baseline 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.

  3. Change in Forced Oscillation Technique (FOT) values in wheezing subjects. [ Time Frame: 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.

  4. Change in spirometry values in wheezing subjects. [ Time Frame: 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.

  5. 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. ]
    Determine if LCI values in preschool children differ between children with no history of wheeze and those with recurrent wheeze.

  6. 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. ]
    Determine if FOT values in preschool children differ between children with no history of wheeze and those with recurrent wheeze.

  7. 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. ]
    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.

  8. Change in nasal microbiome in wheezing subjects [ Time Frame: Day 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.

  9. Viral infections causing wheezing [ Time Frame: Day 1 ]
    A nasal swab collected at Day 1 will be used to determine which viruses are causing wheezing in wheezing subjects.

  10. Basophil activation test (BAT) [ Time Frame: Day 1 and 3 months ]
    Determine the ability of the BAT to confirm food allergies in a wheezing cohort.

  11. Lung epithelial cell immune response in wheezing subjects. [ Time Frame: 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.


Biospecimen Retention:   Samples With DNA
Venous blood samples collected and divided into DNA pellet, plasma, serum, and whole blood. Small portion of sample sent for Total IgE and CBC. The eosinophil and IgE information will be used to assist with categorizing wheezy subjects into API categories. The DNA sample will be analyzed using genome-wide association studies (GWAS), and looking for single-nucleotide polymorphism (SNPs) that are known to be associated with asthma. The whole blood samples will be used for the basophil activation test; Urine samples; Nasal swab samples; Nasal brush samples;


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Ages Eligible for Study:   3 Years to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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)

Criteria

Inclusion Criteria (Wheezing Subjects):

  • 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.

Inclusion Criteria (Healthy Controls):

  • 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 (both subjects and controls):

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02743663


Contacts
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Contact: Padmaja Subbarao, MD 416-813-7654 ext 302196 padmaja.subbarao@sickkids.ca

Locations
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Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Principal Investigator: Padmaja Subbarao, MD         
Sub-Investigator: Kathy Boutis, MD         
Sub-Investigator: Geoffrey N Maksym, MD         
Sub-Investigator: Reshma Amin, MD         
Sub-Investigator: Indra Narang, MD         
Sub-Investigator: Theo Moraes, MD         
Sub-Investigator: Thomas Eiwegger, MD         
Sub-Investigator: Suzanne Schuh, MD         
Sponsors and Collaborators
The Hospital for Sick Children
Dalhousie University
Investigators
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Principal Investigator: Padmaja Subbarao, MD The Hospital for Sick Children

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Responsible Party: Padmaja Subbarao, Staff Respirologist, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT02743663     History of Changes
Other Study ID Numbers: 1000041089
First Posted: April 19, 2016    Key Record Dates
Last Update Posted: May 4, 2018
Last Verified: May 2018

Keywords provided by Padmaja Subbarao, The Hospital for Sick Children:
pediatric
lung ventilation inhomogeneity
preschool
asthma
wheeze

Additional relevant MeSH terms:
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Asthma
Lung Diseases, Obstructive
Lung Diseases
Anti-Asthmatic Agents
Sleep Apnea, Obstructive
Food Hypersensitivity
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Sleep Apnea Syndromes
Apnea
Respiration Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists