Longitudinal Preschool Wheeze Biomarker Study

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)

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.