Title: How can we optimise inhaled beta2 agonist dose as 'reliever' medicine for wheezy pre-school children?
Funder: Department of Health (England)

Abstract: Recurrent attacks of wheeze are common in pre-school children. A diagnosis of asthma is usually made as the symptoms become more frequent. Over a million children in the UK have asthma. These children are mostly treated with an inhaled bronchodilator, salbutamol, as 'reliever' medication for their acute spells of wheeze. However, neither the efficacy of salbutamol nor the minimum effective dose have been established for children under the age of 7 years. As a result, a wide dose range (200 - 1000 micrograms of salbutamol) is commonly prescribed in both general practice and hospital, and some young children who may respond poorly to salbutamol may continue to experience recurrent attacks of wheeze despite this treatment. In this age group, we are thus commonly administering a medicine with inadequate knowledge of clinical response. The aim of the work is to use an evidence-based approach to determine the minimum dose of salbutamol required for effective bronchodilatation in these children, by calibrating the range of doses used in current clinical practice against serial, objective measurements of improvement in airway calibre (response). We will also seek to define the extent of variation in the dose of inhaled salbutamol required to produce a clinically significant response in these children, and test if a simple saliva-based test can identify the 'poor responders'. We will attempt to define the dose of inhaled salbutamol that is appropriate for 3-7 year olds with wheeze, and to separate the 'good responders' from the 'poor responders', by using a non-invasive, validated lung function test (Rint). We will recruit 3-7 year olds with recurrent wheeze, administer a range of doses of inhaled salbutamol and measure the response using Rint. We will relate this response to the dose of inhaled salbutamol administered to the child, and will also measure salbutamol concentration in a urine sample approximately 30 minutes after inhalation, as the 'gold standard' for lung bioavailability. We will also collect a saliva sample to determine whether a DNA test that can be performed in the outpatient setting is able to separate the 'poor responders' to salbutamol from the 'normal responders'. This work is likely to lead to a number of benefits for 3-7 year olds with recurrent wheeze. It will provide an evidence base for general practitioners and hospital doctors for determining the dose of inhaled salbutamol to be prescribed for a child with recurrent wheeze. Currently, there is no clear data indicating whether or not inhaled salbutamol is an effective bronchodilator in this age group of patients. The finding of a good bronchodilator response with salbutamol in adults and older children with asthma has largely been extrapolated to this younger age group. Yet, recurrent wheeze, whether or not it leads to a diagnosis of asthma, is a very common problem in this age group, and it has become common practice to prescribe salbutamol, on the basis of this extrapolation. This work will provide substantive evidence to indicate whether or not this extrapolation is correct, while also defining the dose range for prescribing purpose. From our clinical experience, including reports from parents, we expect that a sub-population of children with recurrent wheeze will show a poor response to salbutamol. We will seek to identify whether a simple clinic-based saliva test is able to differentiate the 'poor responders' to salbutamol from the 'normal responders'. Such a test could be of potential benefit to the 'poor responders' who can be treated with alternative 'relievers' in place of salbutamol.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: RESPIRATORY