TY - JOUR
T1 - Influence of Genetic variation of the β 2-Adrenergic receptor on lung diffusion in patients with cystic fibrosis
AU - Traylor, Brittany R.
AU - Wheatley, Courtney M.
AU - Skrentny, Thomas T.
AU - Foxx-Lupo, William T.
AU - Phan, Hanna
AU - Patanwala, Asad E.
AU - Morgan, Wayne J.
AU - Daines, Cori L.
AU - Sprissler, Ryan
AU - Snyder, Eric M.
PY - 2011/10
Y1 - 2011/10
N2 - Rationale: Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the β 2-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 (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 β 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; FEV 1 = 72 ± 27 vs. 92 ± 12%pred; VO 2peak = 45 ± 25 vs. 99 ± 24%pred, p < 0.05 for FEV 1 and VO 2peak, 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 27Gln vs. Glu 27Glu/Gln 27Glu. 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 27Glu/Gln 27Glu group had higher D M/V C and SaO 2 when compared to the Gln 27Gln 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.
AB - Rationale: Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the β 2-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 (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 β 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; FEV 1 = 72 ± 27 vs. 92 ± 12%pred; VO 2peak = 45 ± 25 vs. 99 ± 24%pred, p < 0.05 for FEV 1 and VO 2peak, 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 27Gln vs. Glu 27Glu/Gln 27Glu. 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 27Glu/Gln 27Glu group had higher D M/V C and SaO 2 when compared to the Gln 27Gln 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.
KW - β-adrenergic
KW - Cystic fibrosis
KW - Genetics
KW - Lung diffusion
KW - Oxygen saturation
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U2 - 10.1016/j.pupt.2011.06.001
DO - 10.1016/j.pupt.2011.06.001
M3 - Article
C2 - 21703359
AN - SCOPUS:80052426143
VL - 24
SP - 610
EP - 616
JO - Pulmonary Pharmacology and Therapeutics
JF - Pulmonary Pharmacology and Therapeutics
SN - 1094-5539
IS - 5
ER -