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Effect of β2-Adrenergic Receptor Polymorphism in Asthma Control of Patients Receiving Combination Treatment

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초록

Purpose: Combination treatment of inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the β2-adrenergic receptor (ADRB2) polymorphism on lung function and asthma control with regular use of combination treatment of an inhaled ICS plus LABA. Materials and Methods: 43 Korean asthmatics who were symptomatic despite regular ICS use for at least 3 months were enrolled. For a 2-week run-in period, they received ICS (budesonide 800 μg/day) plus terbutaline (5 μg prn). as needed. During the 24-week active treatment period, they received budesonide 160 μg and formoterol 4.5 μg b.i.d. as maintenance and rescue medication. Pulmonary function and quality of life scores were monitored every 8 weeks; morning/evening peak expiratory flow meter (PEFR) was recorded daily. Patients were genotyped for ADRB2 Arg16Gly using single base extension methodology. Results: During the run-in period, there were no significant between-group differences in lung function; after 8 weeks of active treatment, Arg/Arg patients had significantly higher forced expiratory volume in 1 secord (FEV1) and maximal mid-expiratory flow (MMEF) (p = 0.023 and p = 0.021, respectively), and better asthma control and quality of life after 24 weeks (p = 0.016 and p = 0.028, respectively). During treatment, there was a greater improvement in morning/evening PEFR in Arg/Arg patients. Conclusion: Asthmatic patients with the Arg/Arg genotype at codon 16 of ADRB2 achieve better asthma control with long-term regular use of combined budesonide and formoterol treatment, suggesting that the ADRB2 genotype may dictate choice of treatment strategy.

Abstract

Purpose: Combination treatment of inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the β2-adrenergic receptor (ADRB2) polymorphism on lung function and asthma control with regular use of combination treatment of an inhaled ICS plus LABA. Materials and Methods: 43 Korean asthmatics who were symptomatic despite regular ICS use for at least 3 months were enrolled. For a 2-week run-in period, they received ICS (budesonide 800 μg/day) plus terbutaline (5 μg prn). as needed. During the 24-week active treatment period, they received budesonide 160 μg and formoterol 4.5 μg b.i.d. as maintenance and rescue medication. Pulmonary function and quality of life scores were monitored every 8 weeks; morning/evening peak expiratory flow meter (PEFR) was recorded daily. Patients were genotyped for ADRB2 Arg16Gly using single base extension methodology. Results: During the run-in period, there were no significant between-group differences in lung function; after 8 weeks of active treatment, Arg/Arg patients had significantly higher forced expiratory volume in 1 secord (FEV1) and maximal mid-expiratory flow (MMEF) (p = 0.023 and p = 0.021, respectively), and better asthma control and quality of life after 24 weeks (p = 0.016 and p = 0.028, respectively). During treatment, there was a greater improvement in morning/evening PEFR in Arg/Arg patients. Conclusion: Asthmatic patients with the Arg/Arg genotype at codon 16 of ADRB2 achieve better asthma control with long-term regular use of combined budesonide and formoterol treatment, suggesting that the ADRB2 genotype may dictate choice of treatment strategy.

참고문헌 (27)

  1. O’Byrne PM, "Budesonide", formoterol combination therapy as both maintenance and reliever medication in asthma, 2005, pp.171, 129~136
  2. Pauwels RA, "Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group", N Engl J Med, 337, pp.1405~1411 (1997)
  3. "Global initiative for asthma (gina) global strategy for asthma managemetn and prevention: National Instritutes of Health, National Heart" (2006), Lung and Blood Institute
  4. Israel E, "The effect of polymorphisms of the beta(2)- adrenergic receptor on the response to regular use of albuterol in asthma", Am J Respir Crit Care Med, 162, pp.75~80 (2000)
  5. Israel E, "Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial", Lancet, 364, pp.1505~1512 (2004)
  6. Wechsler ME, "beta-Adrenergic receptor polymorphisms and response to salmeterol", Am J Respir Crit Care Med, 173, pp.519~526 (2006)
  7. Palmer CN, "Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol", Thorax, 61, pp.940~944 (2006)
  8. Lee DK, "The arginine-16 beta2-adrenoceptor polymorphism predisposes to bronchoprotective subsensitivity in patients treated with formoterol and salmeterol", Br J Clin Pharmacol, 57, pp.68~75 (2004)
  9. Cho SH, "Association between bronchodilating response to short-acting betaagonist and non-synonymous single-nucleotide polymorphisms of beta-adrenoceptor gene", Clin Exp Allergy, 35, pp.1162~1167
  10. Taylor DR, "Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma", Am J Respir Crit Care Med, 172, pp.700~703 (2005)
  11. Hancox RJ, "Polymorphism of the beta2- adrenoceptor and the response to long-term beta2-agonist therapy in asthma", Eur Respir J, 11, pp.589~593 (1998)
  12. Taylor DR, "Asthma exacerbations during long term beta agonist use: influence of beta(2) adrenoceptor polymorphism", Thorax, 55, pp.762~767 (2000)
  13. Bleecker ER, "Salmeterol response is not affected by beta2- adrenergic receptor genotype in subjects with persistent asthma", J Allergy Clin Immunol, 118, pp.809~816 (2006)
  14. Bleecker ER, "Effect of ADRB2 polymorphisms on response to longacting beta2-agonist therapy: a pharmacogenetic analysis of two randomised studies", Lancet, 370, pp.2118~2125 (2007)
  15. Choudhry S, "Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma", Am J Respir Crit Care Med, 171, pp.563~570 (2005)
  16. Rho HJ, "Factors influencing quality of life of asthmatic patients in Korea", J Asthma Allergy Clin Immunol, 20, pp.209~221 (2000)
  17. Liggett SB, "Polymorphisms of the beta2-adrenergic receptor and asthma", Am J Respir Crit Care Med, 156, pp.S156~S162 (1997)
  18. Holloway JW, "Association of beta2-adrenergic receptor polymorphisms with severe asthma", Clin Exp Allergy, 30, pp.1097~1103 (2000)
  19. Contopoulos-Ioannidis DG, "Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes", J Allergy Clin Immunol, 115, pp.963~972 (2005)
  20. Reihsaus E, "Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects", Am J Respir Cell Mol Biol, 8, pp.334~339 (1993)
  21. Martinez FD, "Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing", J Clin Invest, 100, pp.3184~3188 (1997)
  22. Drysdale CM, "Complex promoter and coding region beta 2- adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness", Proc Natl Acad Sci U S A, 통권 : 97, pp.10483~10488 (2000)
  23. Munakata M, "Molecular-based haplotype analysis of the beta 2-adrenergic receptor gene (ADRB2) in Japanese asthmatic and non-asthmatic subjects", Allergol Int, 55, pp.191~198 (2006)
  24. Green SA, "Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonistpromoted regulatory properties", Biochemistry, 33, pp.9414~9419 (1994)
  25. Green SA, "Influence of beta 2-adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells", Am J Respir Cell Mol Biol, 13, pp.25~33 (1995)
  26. Green SA, "The Ile164 beta(2)- adrenoceptor polymorphism alters salmeterol exosite binding and conventional agonist coupling to G(s)", Eur J Pharmacol, 421, pp.141~147 (2001)
  27. Green SA, "A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor", J Biol Chem, 268, pp.23116~23121 (1993)

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