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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	3 Years - 5 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02743663
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	The Hospital for Sick Children
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Padmaja Subbarao, MD
Principal Investigator Affiliation	The Hospital for Sick Children
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Canada
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Asthma, Wheeze, Obstructive Sleep Apnea, Food Allergy, Virus

Additional Details

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.

Arms & Interventions

Arms

: 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.

: 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.

Interventions

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.

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.

Procedure: - Spirometry

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

Drug: - salbutamol

Given during bronchodilator response.

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.

Procedure: - Nasal swab

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

Contact a Trial Team

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International Sites

The Hospital for Sick Children, Toronto, Ontario, Canada

Status

Recruiting

Address

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8

Site Contact

padmaja.subbarao@sickkids.ca

416-813-7654

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