Clinical Science (2013) 124, (521–528) (Printed in Great Britain)
PDFTailored second-line therapy in asthmatic children with the Arg16 genotype
Brian J. Lipworth*, Kaninika Basu†‡, Helen P. Donald‡, Roger Tavendale§, Donald F. Macgregor‡, Simon A. Ogston∥, Colin N. A. Palmer§ and Somnath Mukhopadhyay†‡
*Asthma and Allergy Research Group, Division of Medicine and Therapeutics, University of Dundee, Dundee DD2 4BF, Scotland, U.K., †Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Brighton and Sussex Medical School, Brighton BN2 5BE, U.K., ‡Children's Asthma and Allergy Unit, Perth Royal Infirmary, NHS Tayside, University of Dundee, Perth PH1 1NX, Scotland, U.K., §Population Pharmacogenetics Group, Biomedical Research Institute, University of Dundee, Dundee DD2 4BF, Scotland, U.K., and ∥Division of Clinical and Population Sciences and Education, University of Dundee, Dundee DD2 4BF, Scotland, U.K.
Key words: asthma, β2 receptor, children, genotype, montelukast, salmeterol.
Abbreviations: ANCOVA, analysis of co-variance; CI, confidence interval; FDA, Food and Drug Administration; FEV1, forced expiratory volume in 1 s; LABA, long-acting β2 agonists; PAQLQ, Paediatric Asthma Quality of Life Questionnaire.
Correspondence: Dr Brian J. Lipworth (email b.j.lipworth@dundee.ac.uk).
The Arg16 β2 receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular LABA (long-acting β2 agonists). We therefore evaluated using montelukast as an alternative to salmeterol as tailored second-line asthma controller therapy in children expressing this susceptible genotype. A total of 62 persistent asthmatic children with the homozygous Arg16 genotype were randomized to receive salmeterol (50 μg, b.i.d.) or montelukast (5 or 10 mg, once daily) as an add-on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast compared with salmeterol {difference in score=−0.40 [95% CI (confidence interval), −0.22 to −0.58]; P=0.005}. Salbutamol use was also reduced with montelukast compared with salmeterol [difference in score=−0.47 (95% CI, −0.16 to −0.79); P<0 .0001=".0001" against="against" and="and" both="both" difference="difference" fev="fev" greater="greater" improvements="improvements" in="in" life="life" montelukast="montelukast" no="no" occurred="occurred" of="of" quality="quality" salmeterol="salmeterol" scores="scores" sub="sub" symptom="symptom" there="there" was="was" whereas="whereas" with="with">1
(forced expiratory volume in 1 s). In conclusion, montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arg16 genotype, a move towards a personalized medicine approach to management. CLINICAL PERSPECTIVES
- The FDA has recently highlighted concerns about long-term safety of LABA exposure, especially in children.
- Our study evaluated second-line therapy in 15% of genetically susceptible asthmatic children possessing the Arg16 genotype.
- We show that patients with the Arg16 genotype may fare better by using montelukast than salmeterol as add-on therapy to inhaled corticosteroids. This in turn provides evidence for genotype directed personalized medicine.
Received 1 October 2012/23 October 2012; accepted 5 November 2012
Published as Immediate Publication 5 November 2012, doi:10.1042/CS20120528
© The Authors Journal compilation © 2013 Biochemical Society
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