title: Influence of genetic variation of the β2-adrenergic receptor on lung diffusion in patients with cystic fibrosis.
abstract: BACKGROUND
  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(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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy Practice and Science, University of Arizona, 1703 E. Mabel, Tucson, AZ 85721, United States.
authors.forename: Brittany R
authors.initials: BR
authors.lastname: Traylor
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Wheatley
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Skrentny
authors.forename: William T
authors.initials: WT
authors.lastname: Foxx-Lupo
authors.forename: Hanna
authors.initials: H
authors.lastname: Phan
authors.forename: Asad E
authors.initials: AE
authors.lastname: Patanwala
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Morgan
authors.forename: Cori L
authors.initials: CL
authors.lastname: Daines
authors.forename: Ryan
authors.initials: R
authors.lastname: Sprissler
authors.forename: Eric M
authors.initials: EM
authors.lastname: Snyder
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D002248:Carbon Monoxide / Q000378:metabolism; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D004058:Diffusion; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics*; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D002248:Carbon Monoxide; D000420:Albuterol; D010100:Oxygen