Health TrialsbyHealthPanel

Longitudinal Preschool Wheeze Biomarker Study

ConditionWheezing
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age1-5
SponsorImperial College London

About this trial

Preschool children (aged 1-5 years) account for 75% of all UK childhood wheezing hospitalisations. This has not changed over 20 years, meaning current treatments are not working and a new approach is needed. Currently, all preschool wheezers are treated with inhaled steroids. However, only about 25% of patients, with allergies, respond well to inhaled steroids; for the other 75%, they are ineffective. This research group has found that some preschool wheezers may have other causes but there are no specific, non-invasive tests to match the right treatment to each child.

The goal of this observational study is to test various bedside tests for this purpose in preschool children with wheeze, to see if they are feasible, accurate and acceptable in this age group.

The research team would like to investigate the following aims:

Aim 1 - To test the proposed panel of simple bedside tests below, to see how accurately they corelate with lower airway infection or inflammation.

Aim 2 - To test the acceptability of these bedside tests are to parents and children, and if they reflect the child's symptoms, symptoms control and medication use.

Aim 3- A small proof-of -concept study, to test if these simple bedside tests, can be used to determine treatment for each individual child.

The panel of simple non-invasive tests that the research team are proposing are:

1. Skin prick tests to common allergies (house dust mite, cat, dog, grass, tree pollen, mixed moulds) 2. Finger prick blood test 3. Phlegm test for bacteria 4. Nose and throat swab for bacteria 5. Lung function test called forced oscillation technique (FOT)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Children aged 1-5 years

More than 2 hospitalisations for acute wheeze in the last year or

At least 1 admission requiring high dependency unit or intravenous bronchodilator therapy in the last year.

Disqualifiers

Alternative respiratory diagnosis such as cystic fibrosis or bronchiectasis.

Trial population

Recruitment will be from the Royal Brompton Hospital, which is a tertiary referral centre for respiratory paediatrics, but also receives direct referrals from GPs in North West London. This target population includes children from all sociodemographic and ethnic backgrounds as referrals are received from across London and the Southeast region.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Bronchoscopy, with bronchoalveolar lavage and endobronchial biopsy

    Procedure/Surgery

    These children who will be having a bronchoscopy (a long thin tube, with a camera at the end, which is put inside the lung to look at and collect samples) as part of their standard clinical management, determined by their own consultants or treating physicians. They will be having lung samples (washings from the lung and a tiny piece of tissue taken from the breathing tubes) taken as part of their usual medical management. The research team will ask for consent to use the leftover samples for the bronchoscopy, for the study

  • Skin prick test

    Diagnostic test

    To identify children with allergies. This test will not be done if the child has had allergy testing in the last 6 months

  • Finger prick blood test

    Diagnostic test

    Finger prick testing will be used for blood samples, and it is the same technique used by children with diabetes, to test their blood sugar levels, and therefore is regularly used in this age group successfully. The research team will be obtain the results within minutes, using a point-of-care device. A few more drops of blood, from the same finger prick sample, will be taken to look at how one of the blood cells work, in more detail, in the laboratory. There is no additional finger prick required for this lab test, and the drops of blood will be collected at the same time, from the same prick, as the point of care test.

  • Forced oscillation technique (FOT)

    Diagnostic test

    Breathing test will be performed using forced oscillation technique (FOT), to see how the child's lungs work and to detect airway inflammation. The test will be explained to the child and completed using our established protocols. This test will only require the child to breathe in and out normally, and therefore can be done in preschool aged children. The current test that is used to check lung function called spirometry cannot be used in preschool children, as it involves following complicated instructions. The aim is to assess how well this newer lung function test is tolerated, in children aged 1-5 years.

  • Sputum induction

    Procedure/Surgery

    Sputum induction is a test of obtaining phlegm after inhalation of salt water mist (saline nebuliser) and this will allow the research team to look for any relationships between infection in the lungs and the accuracy of the less invasive, nose and throat swabs. The research team will obtain phlegm samples, with a quick suction after patients have inhaled the salty mist (saline nebuliser) which will help loosen up their phlegm. If the child can cough it up, they will be encouraged to do it.

  • Oropharyngeal swab

    Diagnostic test

    Swabs from children's nose and throats (similar to swab tests that are done for Covid tests), that will be used to test for bacterial infection

Treatment groups

150 Participants
are divided into 3 treatment groups
Group A: Aim 16 interventions
Group B: Aim 25 interventions
Group C: Aim 35 interventions

Trial outcomes

Primary outcomes

1

Longitudinal study of skin prick tests as biomarkers of preschool wheeze

Specificity, sensitivity and longitudinal stability of skin prick tests to six common allergens (measured by size of wheal in response to skin prick, measured in mm) as a biomarker of allergen sensitisation.

Time frame
3 years
2

Longitudinal study of finger-prick point of care test for eosinophil count as a biomarker of preschool wheeze

Specificity, sensitivity and longitudinal stability of a finger-prick point of care test for eosinophil count (measured as cells per cubic mm) as a biomarker of eosinophilic inflammation.

Time frame
3 years
3

Longitudinal study of blood neutrophil phenotype as a biomarker of airway infection

Specificity, sensitivity and longitudinal stability of blood neutrophil phenotype (measured as mean fluorescence intensity for indicative phenotype markers) as a biomarker of airway infection.

Time frame
3 years
4

Longitudinal study of blood neutrophil chemotaxis as a biomarker of wheezing phenotype

Specificity, sensitivity and longitudinal stability of blood neutrophil chemotaxis (measured in micrometers per minute) as a biomarker of wheezing phenotype.

Time frame
3 years

Secondary outcomes

1

Association between eosinophil counts and patient symptom control

Measurement of eosinophil counts (measured as cells per cubic mm) in relation to patient symptom control, using the Test for Respiratory and Asthma Control in Kids (TRACK), a caregiver-completed validated questionnaire for preschool-aged children (measured as mean symptom score). TRACK is a 5-item standardized questionnaire, with each item being scored from 0 to 20 points on a 5-point Likert-type scale. Total score ranging from 0 to 100. Higher scores indicate better respiratory and asthma control; a score of less than 80 points suggests that a child's breathing problems might not be controlled.

Time frame
3 years
2

Patient acceptability of finger prick blood eosinophil count as a non-invasive biomarker in preschool wheeze

Determining the patient acceptability of finger prick blood eosinophil count as a non invasive biomarker test, using the Visual Analogue Scale (VAS) of pain intensity. The scale ranges from 0 to 10, with 0 being no pain or discomfort and 10 for worst pain possible. Higher scores indicate worse tolerability.

Time frame
3 years
3

Patient acceptability of skin prick test as a non-invasive biomarker in preschool wheeze

Determining the patient acceptability of skin prick test as a non invasive biomarker test, using the Visual Analogue Scale (VAS) of pain intensity. The scale ranges from 0 to 10, with 0 being no pain or discomfort and 10 for worst pain possible. Higher scores indicate worse tolerability.

Time frame
3 years
4

Patient acceptability of forced oscillation technique as a non-invasive biomarker to determine lung function and airway reversibility in preschool wheeze

Determining the patient acceptability of forced oscillation technique as a non invasive biomarker test, to determine lung function and airway reversibility in preschool children, using the Visual Analogue Scale (VAS) of pain intensity. The scale ranges from 0 to 10, with 0 being no pain or discomfort and 10 for worst pain possible. Higher scores indicate worse tolerability.

Time frame
3 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Imperial College London

Lead sponsor

Action Medical Research

Collaborator

Masonic Charitable Foundation

Collaborator

Royal Brompton & Harefield NHS Foundation Trust

Collaborator

Source ClinicalTrials.gov
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