Yonsei Med J.  2009 Apr;50(2):182-188.

Effect of beta2-Adrenergic Receptor Polymorphism in Asthma Control of Patients Receiving Combination Treatment

• Kim SH
• Ye YM
• Hur GY
• Lee HY
• Jee YK
• Lee SH
• Holloway J
• Park HS

Abstract

PURPOSE
Combination treatment of inhaled corticosteroid (ICS) plus long-acting beta2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the beta2-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 microgram/day) plus terbutaline (5 microgram prn). as needed. During the 24-week active treatment period, they received budesonide 160 microgram and formoterol 4.5 microgram 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.

Keyword

beta2-adrenergic receptor polymorphism; long-acting beta2-agonist; bronchodilating effect

MeSH Terms

Administration, Inhalation
Adrenal Cortex Hormones/*administration & dosage
Adrenergic beta-Agonists/*administration & dosage
Adult
Asthma/*drug therapy/*genetics
Female
Genotype
Humans
Male
Middle Aged
Receptors, Adrenergic, beta-2/*genetics
Young Adult

Figure

• 

  Fig. 1 Mean (SD) % predicted value of FEV1 (A), FVC (B) and MMEF (C) during the study period (-2-0 weeks: run-in period; 0-24 weeks: active treatment) for both ADRB2 codon 16 genotype groups (Arg/Arg; Arg/Gly or Gly/Gly). *p values for Arg/Arg compared with Arg/Gly or Gly/Gly at each time point. FEV1, forced expiratory volume in 1sec; FVC, forced vital capacity; MMEF, maximal mid-expiratory flow; ADRB2, β2-adrenergic receptor.

• 

  Fig. 2 Mean (SD) symptom scores (A) and quality of life scores (B) during the active treatment period for both ADRB2 codon 16 genotype groups (Arg/Arg; Arg/Gly or Gly/Gly). ADRB2, β2-adrenergic receptor; ACQ, Asthma Control Questionnaire; AQLQ, Asthma Quality of Life Questionnaire. *p values for Arg/Arg compared with Arg/Gly or Gly/Gly at each time point.

• 

  Fig. 3 Changes of morning PEF [(A): Arg/Arg genotype group (●), y = 89.59 + 5.99×<1 - 0.97^TIME>; Arg/Gly or Gly/Gly genotype group (○), y = 74.81 + 3.13×<1 - 0.95^TIME>], and evening PEF [B: Arg/Arg genotype group (●), y = 90.78 + 6.49×<1 - 0.97^TIME>; Arg/Gly to Gly/Gly genotype group (○), y= 75.30 + 3.52×<1 - 0.97^TIME>] during the study period, analyzed by non-linear regression and plotted as individual revisable PEFR. ↑ indicates days to reach the plateau PEFR value in each genotype. PEFR, peak expiratory flow rate.

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