Influence of Genetic variation of the β2-Adrenergic receptor on lung diffusion in patients with cystic fibrosis

Rationale: Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the beta(2)-adrenergic receptors mediates mucociliary clearance and bronchodilation. We sought to determine the influence of an inhaled beta-agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-capillary membrane conductance (D-M), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO(2)) in subjects with CF, when compared to matched healthy subjects, according to genetic variation of the beta(2)-adrenergic receptor (ADRB2). Methods: To determine this we recruited 18 subjects with CF and 20 healthy subjects (age = 23 +/- 7 vs. 24 +/- 4years; ht = 168 +/- 8 vs. 174 +/- 12 cm; wt = 64 +/- 16 vs. 70 +/- 13 kg; BMI = 23 +/- 4 vs. 23 +/- 3 kg/m(2); FEV1 = 72 +/- 27 vs. 92 +/- 12%pred; VO2peak = 45 +/- 25 vs. 99 +/- 24%pred, p < 0.05 for FEV1 and VO2peak, mean +/- SD, for CF and healthy, respectively). The study involved measurement of DLCO, D-M, V-C and SaO(2) before and 30, 60, and 90 min following the administration of inhaled albuterol. Subjects were stratified according to genetic variation of ADRB2, Gln(27)Gln vs. Glu(27)Glu/Gln(27)Glu. Results: Within the healthy group, there were no differences in DLCO, D-M, V-C, D-M/V-C at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu(27)Glu/Gln(27)Glu group had higher D-M/V-C and SaO(2) when compared to the Gln(27)Gln group at baseline (p < 0.05). Both genotype groups demonstrated a significant decline in V-C and an improvement in D-M/V-C and SaO(2) in response to albuterol. Subjects with the Glu(27) genotype experienced a greater improvement in D-M/V-C with albuterol when compared to subjects homozygous for Gln at amino acid 27. Conclusion: These results suggest that there are differences in lung diffusion and peripheral SaO(2) according to genetic variation of the ADRB2 at position 27 which could play a potential role in dosing options or adjustments that may be required according to genotype. (C) 2011 Elsevier Ltd. All rights reserved.