Clinical trial NCT06237660: Longitudinal Preschool Wheeze Biomarker Study
Official title: Development of Non-invasive Biomarkers to Direct Individualised Management of Preschool Wheeze
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Wheezing
Keywords: Preschool wheeze
Preschool asthma
Allergy
Infection
Steroids
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Action Medical Research
name: Masonic Charitable Foundation
name: Royal Brompton & Harefield NHS Foundation Trust
First posted: 2024-02-01
Enrollment: 150
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study 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.

Brief summary: 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)

Detailed description: Research Question:

Can the research team identify simple bedside tests that can give quick, accurate results while being acceptable to parents and children, and can these tests be successfully used in clinical practice, to decide treatment for preschool wheeze?

Participants will be asked to do these simple tests- skin prick test, finger prick blood test, breathing test, throat swab, and a test to catch their phlegm. The researchers will use two tests to identify children who are likely to respond to inhaled steroids: skin tests for allergies and a finger prick blood test. To identify children with bacterial infections in their lungs, where antibiotics will be useful, the team will obtain a sample of sputum (phlegm) after a salty mist inhalation (saline nebuliser), and will test the accuracy of a throat swab that detects bacteria. The research team will also test how cells called neutrophils work in children without allergies or infection with the same finger prick blood test above. A breathing test called forced oscillation will be used to identify children who may respond to their reliever "blue" inhaler during wheezing attacks.

The research team will also recruit a small number of children, for a trial in which their treatment will be guided by their test result, to see if parents are willing to take part in such a study, before designing a larger trial. This study will be the first to show that new tests can identify different types of preschool wheezing and can be used to plan treatment based on individual children's needs. Researchers will compare to see if children who have their treatment based on the simple bedside tests do better than the children who are just given inhaled steroids.

Eligibility criteria: Inclusion Criteria:

Aim 1, 2 and 3:

* 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.

Aim 1 only:

- children undergoing clinically indicated bronchoscopy, as determined by their existing medical team, as part of their standard management

Exclusion Criteria:

* Alternative respiratory diagnosis such as cystic fibrosis or bronchiectasis.

Primary outcomes:
measure: Longitudinal study of skin prick tests as biomarkers of preschool wheeze
timeFrame: 3 years
measure: Longitudinal study of finger-prick point of care test for eosinophil count as a biomarker of preschool wheeze
timeFrame: 3 years
measure: Longitudinal study of blood neutrophil phenotype as a biomarker of airway infection
timeFrame: 3 years
measure: Longitudinal study of blood neutrophil chemotaxis as a biomarker of wheezing phenotype
timeFrame: 3 years
measure: Longitudinal study of oropharyngeal swab and induced sputum PCR as a biomarker of airway infection
timeFrame: 3 years
measure: Longitudinal study of lung function test (FOT) as a biomarker of airway reversibility
timeFrame: 3 years
Secondary outcomes:
measure: Association between eosinophil counts and patient symptom control
timeFrame: 3 years
measure: Patient acceptability of finger prick blood eosinophil count as a non-invasive biomarker in preschool wheeze
timeFrame: 3 years
measure: Patient acceptability of skin prick test as a non-invasive biomarker in preschool wheeze
timeFrame: 3 years
measure: Patient acceptability of forced oscillation technique as a non-invasive biomarker to determine lung function and airway reversibility in preschool wheeze
timeFrame: 3 years
measure: Patient acceptability of oropharyngeal swab and induced sputum PCR as a biomarker of airway infection in preschool wheeze
timeFrame: 3 years
measure: Correlation between eosinophil counts and symptom burden of preschool wheeze to caregivers
timeFrame: 3 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Imperial College London
name: Sejal Saglani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Robinson PFM, Fontanella S, Ananth S, Martin Alonso A, Cook J, Kaya-de Vries D, Polo Silveira L, Gregory L, Lloyd C, Fleming L, Bush A, Custovic A, Saglani S. Recurrent Severe Preschool Wheeze: From Prespecified Diagnostic Labels to Underlying Endotypes. Am J Respir Crit Care Med. 2021 Sep 1;204(5):523-535. doi: 10.1164/rccm.202009-3696OC.