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Therapeutic interventions in asthma and airways disease
P181 Better asthma control with montelukast than salmeterol in Arg-16 homozygous children with asthma
  1. K Basu1,
  2. H P Donald2,
  3. B J Lipworth3,
  4. R Tavendale4,
  5. D F Macgregor2,
  6. S A Ogston5,
  7. C N A Palmer4,
  8. S Mukhopadhyay1
  1. 1Royal Alexandra Children's Hospital, Brighton and Sussex Medical School, Brighton, UK
  2. 2Paediatric Asthma and Allergy Research Group, NHS Tayside, Perth, UK
  3. 3Asthma and Allergy Research Group, Division of Medicine and Therapeutics, Ninewells Hospital, Dundee, UK
  4. 4Population Pharmacogenetics Group, Biomedical Research Institute, University of Dundee, Dundee, UK
  5. 5Division of Clinical and Population Sciences and Education, University of Dundee, Dundee, UK

Abstract

Introduction and Objectives Diminished efficacy of salmeterol for improving asthma control is increased in children with asthma homozygous for arginine-16 (Arg16) allele of the ADRB2. Concerns have been raised regarding the efficacy and safety of long-term salmeterol use in patients with asthma. We investigated whether there is a genotype-specific difference in long-term asthma control with montelukast compared to salmeterol in individuals homozygous for Arg16 of ADRB2.

Methods In this pragmatic randomised controlled trial, 62 children (5–18 years) with asthma, carrying Arg/Arg16 genotype and exacerbation of asthma at least once within the previous year, were randomly assigned to receive Flixotide® (fluticasone propionate) via accuhaler (Diskus) dry powder inhaler device plus oral montelukast (Group I); or Seretide® (salmeterol plus equivalent dose of fluticasone) via accuhaler dry powder inhaler device plus placebo for montelukast (Group II). No effort was made to blind the prescribed inhaler. The primary end point was school absence, prospectively measured as individual events over the period of 1 year.

Results No significant difference was observed in school absences (p=0.097) between the treatment groups. The use of reliever medication was significantly decreased in Group I compared to Group II (p=0.004). Total exacerbations were reduced in Group 1 compared to Group 2 (p=0.049). Self-reported symptoms were significantly improved in Group I compared to Group II (morning cough p=0.018; morning wheeze p=0.001; morning dyspnoea p=0.008; night wheeze: p=0.004; night dyspnoea: p=0.001). A significant improvement in quality of life as per the Juniper paediatric asthma quality of life questionnaire was observed in Group I compared to Group II (activity limitation score (p=0.004), symptom score (p=0.009), emotional function score (p=0.002)).

Conclusion In individuals homozygous for Arg16 of the ADRB2 locus, montelukast is an effective step up medication compared with salmeterol. Montelukast, as an asthma controller added on to inhaled steroid, improved asthma symptoms and quality of life, while reducing the use of reliever medication, in comparison to salmeterol. A larger randomised controlled trial is required, comparing asthma control with salmeterol versus montelukast in the genotypic sub-groups in ADRB2, and to explore the cost-effectiveness of genotype-specific controller therapies in children with asthma.

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