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Completed

NCT Number: NCT02743663

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

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.

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Key information

Conditions

Asthma Apnea Bronchial Diseases Dyssomnias Food Allergy Food Hypersensitivity Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Infections Lung Diseases Lung Diseases, Obstructive Nervous System Diseases Obstructive Sleep Apnea Pathological Conditions, Signs and Symptoms Respiration Disorders Respiratory Hypersensitivity Respiratory Sounds Respiratory Tract Diseases Signs and Symptoms Signs and Symptoms, Respiratory Sleep Apnea Syndromes Sleep Apnea, Obstructive Sleep Disorders, Intrinsic Sleep Wake Disorders Virus Virus Diseases Wheeze

Age range

3 year–5 year

Sex eligibility

All sexes

Study type

Observational

Primary location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Bronchodilator response

Procedure

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

Allergy Skin Test

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

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.

Other names: MBW

Forced Oscillation Technique

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.

Other names: FOT

Spirometry

Procedure

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

Salbutamol

Drug

Given during bronchodilator response.

Other names: ventolin

Nasal Brush

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

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

Procedure

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

Other names: BAT

Nasal Swab

Procedure

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

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

The Hospital for Sick Children

Other

Collaborators

  • Dalhousie University

Registry information

Acronym: WheezyER

Important dates

Study start
2014
Primary completion
2020
Study completion
2020
First posted
Apr 19, 2016
Registry last updated
Feb 8, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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