How can we optimise inhaled beta2 agonist dose as 'reliever' medicine for wheezy pre-school children? Study protocol for a randomised controlled trial.
Asthma is a common problem in children and, if inadequately controlled, may seriously diminish their quality of life. Inhaled short-acting beta2 agonists such as salbutamol are usually prescribed as 'reliever' medication to help control day-to-day symptoms such as wheeze. As with many medications currently prescribed for younger children (defined as those aged 2 years 6 months to 6 years 11 months), there has been no pre-licensing age-specific pharmacological testing; consequently, the doses currently prescribed (200-1000 μg) may be ineffective or likely to induce unnecessary side effects. We plan to use the interrupter technique to measure airway resistance in this age group, allowing us for the first time to correlate inhaled salbutamol dose with changes in clinical response. We will measure urinary salbutamol levels 30 min after dosing as an estimate of salbutamol doses in the lungs, and also look for genetic polymorphisms linked to poor responses to inhaled salbutamol.



This is a phase IV, randomised, controlled, observer-blinded, single-centre trial with four parallel groups (based on a sparse sampling approach) and a primary endpoint of the immediate bronchodilator response to salbutamol so that we can determine the most appropriate dose for an individual younger child. Simple randomisation will be used with a 1:1:1:1 allocation.



The proposed research will exploit simple, non-invasive and inexpensive tests that can mostly be performed in an outpatient setting in order to help develop the evidence for the correct dose of salbutamol in younger children with recurrent wheeze who have been prescribed salbutamol by their doctor.



EudraCT2014-001978-33, ISRCTN15513131. Registered on 8 April 2015.
Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Eastern Road, Brighton, East Sussex, BN2 3BE, UK. s.mukhopadhyay@bsms.ac.uk.
Somnath
S
Mukhopadhyay
Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Eastern Road, Brighton, East Sussex, BN2 3BE, UK.
Paul
P
Seddon
Brighton and Sussex Clinical Trials Unit, 16 Bloomsbury House, Bloomsbury Street, Brighton, East Sussex, BN2 1HQ, UK.
Gemma
G
Earl
Haydn's Wish Charity for Asthma and Allergy Research, 27 Valley Dene, Newhaven, East Sussex, BN9 9NF, UK.
Emma
E
Wileman
Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Eastern Road, Brighton, East Sussex, BN2 3BE, UK.
Liz
L
Symes
Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Eastern Road, Brighton, East Sussex, BN2 3BE, UK.
Cathy
C
Olden
AP-HP, Hôpital d'Enfants Robert Debré, Unité d'Epidémiologie Clinique and Inserm, CIE5, Paris, France.
Corinne
C
Alberti
Brighton and Sussex Clinical Trials Unit, 16 Bloomsbury House, Bloomsbury Street, Brighton, East Sussex, BN2 1HQ, UK.
Stephen
S
Bremner
Department of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton, East Sussex, BN2 4GJ, UK.
Alison
A
Lansley
Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
Colin N A
CN
Palmer
Unité Fonctionnelle de Physiologie-Explorations Fonctionnelles Respiratoires (EFR), Hôpital Armand-Trousseau, 26 Avenue du Docteur Arnold Netter, 75571, Paris Cedex 12, France.
Nicole
N
Beydon
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000420:Albuterol / Q000008:administration & dosage* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D006801:Humans; D012135:Respiratory Sounds / Q000187:drug effects*; D018401:Sample Size
D058666:Adrenergic beta-2 Receptor Agonists; D000420:Albuterol
Asthma; Children; Dose finding; Paediatric; Salbutamol; Wheeze