Longitudinal Preschool Wheeze Biomarker Study

Imperial College London

Status: Enrolling

Conditions: Wheezing

Treatments: Diagnostic Test: Oropharyngeal swab; Diagnostic Test: Skin prick test; Procedure: Sputum induction; Diagnostic Test: Finger prick blood test; Procedure: Bronchoscopy, with bronchoalveolar lavage and endobronchial biopsy; Diagnostic Test: Forced oscillation technique (FOT)

Study type: Observational

Funder types: Other

Identifiers

NCT06237660

23IC8468

GN3005 (Other Grant/Funding Number)

Details and patient eligibility

About

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)

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 1 to 5 years old

Volunteers: No Healthy Volunteers

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.

Trial design

150 participants in 3 patient groups

Aim 1

Description:

To test the proposed panel of simple bedside tests below, to see how accurately they corelate with lower airway infection or inflammation. The aim is correlate the results from the bronchoscopy with the panel of test proposed, and evaluate if these simple bedside tests can pick up the same level of infection or inflammation and obtain the same results, as the bronchoscopy, which is a much more invasive test, but the only method available at present to get this information.

Treatment:

Procedure: Bronchoscopy, with bronchoalveolar lavage and endobronchial biopsy

Procedure: Sputum induction

Diagnostic Test: Forced oscillation technique (FOT)

Diagnostic Test: Finger prick blood test

Diagnostic Test: Skin prick test

Diagnostic Test: Oropharyngeal swab

Aim 2

Description:

The aim is to test how acceptable these bedside tests are to parents and children, and if they reflect the child's symptoms, symptoms control and medication use.

Treatment:

Procedure: Sputum induction

Diagnostic Test: Forced oscillation technique (FOT)

Diagnostic Test: Finger prick blood test

Diagnostic Test: Skin prick test

Diagnostic Test: Oropharyngeal swab

Aim 3

Description:

Small proof-of-concept study. This is for a feasibility trial of using the proposed tests and deciding the treatment of their wheeze, based on the results of the tests. Children with evidence of allergen sensitisation +/- blood eosinophilia (\>0.3x109/L) will be prescribed regular inhaled corticosteroids. Children who are non-atopic (non-atopic is defined as blood eosinophil of \<0.3x109/L + no evidence of allergen sensitisation) with positive bacterial detection in sputum, will be prescribed four weeks of targeted antibiotics. Children who are non-atopic with no bacteria detected in sputum, will be prescribed only be prescribed short acting bronchodilators as required. All medications will be prescribed, as per the British National Formulary for Children, based on age and weight. The aims of this preliminary study are to understand whether parents will agree to be part of such an interventional trial. This will help the research team when designing a future larger clinical trial.

Treatment:

Procedure: Sputum induction

Diagnostic Test: Forced oscillation technique (FOT)

Diagnostic Test: Finger prick blood test

Diagnostic Test: Skin prick test

Diagnostic Test: Oropharyngeal swab