A Proof-of-Concept Study to evaluate the benefit from add-on therapy with montelukast versus salmeterol in children with asthma carrying the Arg/Arg-16 β2-receptor genotype

This thesis details my journey as a research nurse describing the design, pre-study application process and performance of one of the first genotype-stratified randomised controlled studies in children with asthma. Backgroundβ2-agonist response may be affected by β2 adrenoreceptor genotype (ADRB2). The arginine-16 (Arg 16) variant of this gene predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. There follows the presentation of a proof-of-principle randomised controlled trial of add-on therapy to inhaled steroids, with either oral montelukast or inhaled salmeterol, on children carrying the susceptible Arg-16 genotype over a 1-year period.MethodsI have explored methodological issues of importance in the design of this complex study in children. I have also analysed some of the practical aspects of the ethics-related issues associated with the study, the response of parents and children, and how these issues were managed within the context of this study.ResultsAsthmatic children with the Arg-16 genotype appear to have better asthma control when prescribed montelukast compared to salmeterol, when added to inhaled corticosteroid, over a 12 month period. Sixty two asthmatic children with the Arg-16 genotype were randomised to receive montelukast 5/10mg once daily or salmeterol twice daily as add on therapy to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast compared to salmeterol: p = 0.005. Salbutamol use was also reduced with montelukast compared with salmeterol: p < 0.0001, and improvements were also found in symptom and quality of life scores with montelukast in comparison to salmeterol. ConclusionsMontelukast may be suitable as tailored second line controller therapy instead of salmeterol inasthmatic children expressing the susceptible Arg-16 genotype - moving towards apersonalised medicine approach to management. The study has suggested the need for larger studies which explore the role of genotyping in improving the care of children with asthma.It has also provided the opportunity to explore the issues around consenting and recruiting children within the context of prospective genotyping progressing to randomisation, and the subsequent allocation of children to specific pharmacological interventions on the basis of genotype.

Name dc:type.qualificationname

Master of Science

Level dc:type.qualificationlevel

Master's Thesis

Grantor dc:publisher.institution

University of Dundee

Year dc:date.issued

2015

Author dc:creator

• Donald, Helen

Advisor dc:contributor.advisor

• Palmer, Colin

Language dc:language

eng

Identifier

oai:discovery.dundee.ac.uk:studenttheses/261dd011-919d-473a-afbe-9c5585dfc879

OAI identifier oai:identifier

oai:discovery.dundee.ac.uk:studenttheses/261dd011-919d-473a-afbe-9c5585dfc879