Using Specific Tests in Preschool Children With Wheeze to Help us Determine the Necessity of Inhaled Corticosteroid Therapy (Feasibility Study). (TAILOR)

Biomarkers in Preschool Children With Wheeze to TArget Therapy wIth inhaLed cORticosteroids (TAILOR): a Feasibility Study".

Wheezing is common in preschool children and affects quality of life. Although asthma treatments such as inhaled steroids (ICS), which reduce swelling (inflammation) in the airways are used in this age group, they are often ineffective. That is because only some preschool children have the type of inflammation (known as Type 2 inflammation) that responds to ICS, thus many children are being unnecessarily exposed to side effects. It is difficult diagnosing Type 2 inflammation through history and examination, thus other indicators are needed to ensure ICS are only given to children who will benefit. These indicators are commonly known as biomarkers, and we are trying to find out if they are useful. We want to measure three biomarkers, without changing children's treatment. The first is blood eosinophils. which can be measured using a finger prick sample (like the blood drop used for measuring sugar levels in diabetic children). The second is to determine if allergic sensitization is present to allergens that are breathed in; these will be house dust mite, grass pollen, tree pollen, cat and dog hair. The final biomarker is a molecule that is produced in the airways of preschool children with Type 2 inflammation, called nitric oxide (NO). This is easily obtained, by having children breathe through a mask and collecting their breath in a bag, measuring NO later on. The children will be followed up with monthly electronic questionnaires and 3-monthly visits (virtual or face-to-face) for a year to evaluate whether these markers individually or in combination relate to subsequent wheezing outcomes, and how acceptable the measurements are to families using a questionnaire and focus group approach. The results will form the basis of the design of a national trial of biomarker-driven therapy in such children.

Study Overview

• Status: Active, not recruiting
• Conditions: Wheezing
• Intervention / Treatment: Diagnostic test: Blood eosinophil count; Diagnostic test: Atopic sensitization; Diagnostic test: FeNO (offline method)

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children aged one to five years old presenting either to primary care with wheezing episodes or to emergency departments or urgent care centres with an acute attack of wheeze or children identified from primary care records and have been diagnosed with wheezing by their GP or paediatrician.

Description

Inclusion Criteria:

1. Patients aged one to five years old presenting to primary care or emergency department or urgent care centre or identified from primary care records and have been diagnosed with wheezing by their GP or paediatrician who has decided to prescribe any bronchodilator, ICS or montelukast on clinical grounds
2. Parents/Carers able to understand and familiarize themselves with the study and are willing to provide informed consent

Exclusion Criteria:

1. Inability to understand and cooperate with study procedures
2. Significant co-morbidity (respiratory or otherwise), for example cystic fibrosis (excluding atopic disorders such as eczema, allergic rhinitis and food allergy)
3. Withholding or withdrawal of informed consent
4. Severe procedural anxiety (needle phobia)
5. Child is already enrolled in another study involving investigational medicinal product (CTIMP)
6. History of anaphylaxis or near-fatal asthma that resulted in intubation / assisted ventilation.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Preschool children with a history of wheeze, aged 1 to 5 years old; This is a pragmatic, observational study involving preschool children with wheeze aged one to five years old. All treatment and routine monitoring decisions will be at the discretion of their treating general practitioner (GP) or paediatrician (as per usual clinical practice), blinded to the study measurements. The following three biomarker tests will be performed a) atopic sensitisation, b) blood eosinophil count and c) FeNO (off-line method).

Diagnostic test: Blood eosinophil count; Peripheral blood eosinophil count will be measured from a finger prick blood sample, using the Haemocue machine, allowing a result in approximately 2 minutes. The test will allow to assess the presence or not of eosinophilia and if it can predict future wheezing exacerbations and response to inhaled corticosteroids (ICS).; Diagnostic test: Atopic sensitization; Skin prick tests will be performed to: (a) house dust mite, (b) grass pollen, (c) tree pollen, (d) cat hair, (e) dog hair, as well as normal saline and histamine which will act as negative and positive controls respectively. In addition, skin prick tests will allow the assessment of which aeroallergen is the most useful predictor of outcomes in preschool children.; Diagnostic test: FeNO (offline method); The child will breathe normally into a sample bag that will be collected for later analysis of FeNO levels. The test will be performed twice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute attacks of wheeze defined as requiring an unscheduled health care visit	Exacerbation of the wheezing condition that will require a visit to a hospital that was not scheduled. This will be determined with monthly electronic questionnaires sent by email to the parents of preschool children with wheeze, as well as by follow-up face-to-face visits in primary care every 3 months.	1 year follow-up period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carer days off work	Days the parent/carer has taken off work in order to be with their child that has an acute wheezing. This will be determined with monthly electronic questionnaires sent by email to the parents of preschool children with wheeze, as well as by follow-up face-to-face visits in primary care every 3 months.	1 year follow-up period
Children unable to attend childcare facility	Assessing the number of days a child did not attend a childcare facility due to exacerbation of his/her wheezing condition. This will be determined with monthly electronic questionnaires sent by email to the parents of preschool children with wheeze, as well as by follow-up face-to-face visits in primary care every 3 months.	1 year follow-up period
Use of oral corticosteroids	In case a child has been prescribed oral corticosteroids, this has to be declared so that we can assess treatment effectiveness according to the biomarkers tested. This will be determined with monthly electronic questionnaires sent by email to the parents of preschool children with wheeze, as well as by follow-up face-to-face visits in primary care every 3 months.	1 year follow-up period
Use of inhaled β-2 agonist (rescue therapy)	In case a child has been prescribed β-2 agonists, this has to be declared so that we can assess treatment effectiveness according to the biomarkers tested. This will be determined with monthly electronic questionnaires sent by email to the parents of preschool children with wheeze, as well as by follow-up face-to-face visits in primary care every 3 months.	1 year follow-up period
Assessment id respiratory or wheezing condition is under control	• Assessment if children's respiratory or wheezing condition is under control by using the TRACKTM score questionnaire (Test for Respiratory and Asthma Control in Kids)	1 year follow-up period

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Asthma UK Centre for Applied Research
• Investigators: Principal Investigator: Andrew Bush, MD FHEA FRCP FRCPCH FERS FAPSR, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: June 22, 2021
• First Submitted That Met QC Criteria: June 25, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Biomarkers; Wheezing; ICS; Preschool; Inhaled Corticosteroids; Wheeze
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Respiratory Sounds
• Other Study ID Numbers: 21IC6984; 300524 (Registry Identifier: IRAS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No