Lung function response to 12-week treatment with combined inhalation of long-acting beta2 agonist and glucocorticoid according to ADRB2 polymorphism in patients with chronic obstructive pulmonary disease

Abstract

Recent reports suggest that beta(2)-adrenergic receptor (ADRB2) genotypes are associated with therapeutic responses to beta(2) agonists in asthmatics. However, few studies have investigated therapeutic responses to beta(2) agonists in chronic obstructive pulmonary disease (COPD) patients. This study investigated immediate bronchodilator response and lung function responses following a 12-week treatment with a long-acting beta(2) agonist combined with a steroid inhaler in patients with COPD with various ADRB2 genotypes. One hundred four patients with chronic obstruction were genotyped for codon 16 and 27 polymorphisms of the ADRB2 gene. The immediate bronchodilator response to beta(2)-agonist treatment was evaluated after inhalation of 400 microg salbutamol. In addition, long-term response was evaluated using observed change in spirometric values before and after the treatment with salmeterol (50 microg) combined with fluticasone propionate (500 microg) inhalation twice daily for 12 weeks. In terms of codon 16 variants, the immediate bronchodilator response to salbutamol was 6.4 +/- 0.8% (% predicted value) in Arg/Arg patients, 4.9 +/- 0.7% in Arg/Gly patients, and 5.8 +/- 1.2% in Gly/Gly patients (p = 0.418). The FEV(1) changes following the 12-week treatment were 7.0 +/- 1.2% in Arg/Arg patients, 3.0 +/- 1.5% in Arg/Gly patients, and 7.2 +/- 1.2% in Gly/Gly patients (p = 0.229). Similarly, there was no difference between codon 27 variants in terms of immediate bronchodilator response or FEV1 changes after 12 weeks of treatment. We were unable to demonstrate an association between ADRB2 genotype and the effect on lung function of 12-week treatment with combined long-acting beta(2) agonist and glucocorticoid inhalation or on the immediate bronchodilator response to a short-acting beta(2) agonist in patients with COPD.