Influence of Genetic variation of the β2-Adrenergic receptor on lung diffusion in patients with cystic fibrosis - 04/09/11
Corresponding author. Department of Pharmacy Practice and Science, University of Arizona, 1703 E. Mabel, Tucson, AZ 85721, United States. Tel.: +1 520 626 4124; fax: +1 520 626 7355.Abstract |
Rationale |
Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the β2-adrenergic receptors mediates mucociliary clearance and bronchodilation. We sought to determine the influence of an inhaled β-agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DM), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO2) in subjects with CF, when compared to matched healthy subjects, according to genetic variation of the β2-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/m2; 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, DM, VC and SaO2 before and 30, 60, and 90 min following the administration of inhaled albuterol. Subjects were stratified according to genetic variation of ADRB2, Gln27Gln vs. Glu27Glu/Gln27Glu.
Results |
Within the healthy group, there were no differences in DLCO, DM, VC, DM/VC at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu27Glu/Gln27Glu group had higher DM/VC and SaO2 when compared to the Gln27Gln group at baseline (p < 0.05). Both genotype groups demonstrated a significant decline in VC and an improvement in DM/VC and SaO2 in response to albuterol. Subjects with the Glu27 genotype experienced a greater improvement in DM/VC 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 SaO2 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.
Le texte complet de cet article est disponible en PDF.Résumé |
Highlights |
► Albuterol improved alveolar conductance in CF patients with the Glu27 allele of ADRB2. ► This increase in alveolar conductance with albuterol did not occur in healthy control subjects. ► The increase in alveolar conductance following albuterol administration resulted in an improvement in SaO2.
Le texte complet de cet article est disponible en PDF.Keywords : β-adrenergic, Lung diffusion, Oxygen saturation, Cystic fibrosis, Genetics
Abbreviations : DLCO, DLNO, DM, VC, DM/VC, SaO2, ADRB2, CFTR, VO2, FEV1, FVC, MEFV, FEF25-75, Glu, Gln
Plan
Vol 24 - N° 5
P. 610-616 - octobre 2011 Retour au numéro
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