β-Adrenergic receptor polymorphisms and response to salmeterol

Michael E. Wechsler, Erik Lehman, Stephen C. Lazarus, Robert F. Lemanske, Homer A. Boushey, Aaron Deykin, John V. Fahy, Christine A. Sorkness, Vernon M. Chinchilli, Timothy J. Craig, Emily DiMango, Monica Kraft, Frank Leone, Richard J. Martin, Stephen P. Peters, Stanley J. Szefler, Wenlei Liu, Elliot Israel

Research output: Contribution to journalArticle

268 Citations (Scopus)

Abstract

Rationale: Several studies suggest that patients with asthmawho are homozygous for arginine at the 16th position of the β2- adrenergic receptor may not benefit from short-acting β-agonists. Objectives: We investigated whether such genotype-specific effects occur when patients are treated with long-acting β-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use. Methods:Wecompared salmeterol response in patients with asthma homozygous for arginine at B16 (B16Arg/Arg) with those homozygous for glycine at B16 (B16Gly/Gly) in two separate cohorts. In the first, subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy. In the second, subjects were randomized to regular therapy with salmeterol while continuing concomitant ICS. Results: In both trials, B16Arg/Arg subjects did not benefit compared with B16Gly/Gly subjects after salmeterol was initiated. In the first cohort, compared with placebo, the addition of salmeterol was associated with a 51.4 L/min lower A.M. peak expiratory flow (PEF; p = 0.005) in B16Arg/Arg subjects(salmeterol, n = 12; placebo, n = 5) as compared with B16Gly/Gly subjects (salmeterol, n = 13; placebo, n = 13). In the second cohort, B16Arg/Arg subjects treated with salmeterol and ICS concurrently (n = 8) had a lower A.M. PEF (36.8 L/min difference, p = 0.048) than B16Gly/Gly subjects (n = 22) treated with the same regimen. In addition, B16 Arg/Arg subjects in the second cohort had lower FEV1 (0.42 L, p = 0.003), increased symptom scores (0.2 units, p = 0.034), and increased albuterol rescue use (0.95 puffs/d, p = 0.004) compared with B16Gly/Gly subjects. Conclusions: Relative to B16Gly/Gly patients with asthma, B16Arg/Arg patients with asthma may have an impaired therapeutic response to salmeterol in either the absence or presence of concurrent ICS use. Investigation of alternate treatment strategies may benefit this group.

Original languageEnglish (US)
Pages (from-to)519-526
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume173
Issue number5
DOIs
StatePublished - Mar 1 2006

Fingerprint

Adrenergic Receptors
Adrenal Cortex Hormones
Asthma
Placebos
Arginine
Therapeutics
Salmeterol Xinafoate
Albuterol
Glycine
Genotype

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Wechsler, M. E., Lehman, E., Lazarus, S. C., Lemanske, R. F., Boushey, H. A., Deykin, A., ... Israel, E. (2006). β-Adrenergic receptor polymorphisms and response to salmeterol. American journal of respiratory and critical care medicine, 173(5), 519-526. https://doi.org/10.1164/rccm.200509-1519OC
Wechsler, Michael E. ; Lehman, Erik ; Lazarus, Stephen C. ; Lemanske, Robert F. ; Boushey, Homer A. ; Deykin, Aaron ; Fahy, John V. ; Sorkness, Christine A. ; Chinchilli, Vernon M. ; Craig, Timothy J. ; DiMango, Emily ; Kraft, Monica ; Leone, Frank ; Martin, Richard J. ; Peters, Stephen P. ; Szefler, Stanley J. ; Liu, Wenlei ; Israel, Elliot. / β-Adrenergic receptor polymorphisms and response to salmeterol. In: American journal of respiratory and critical care medicine. 2006 ; Vol. 173, No. 5. pp. 519-526.
@article{c3ac20dd958d484988682fa13e4d9d87,
title = "β-Adrenergic receptor polymorphisms and response to salmeterol",
abstract = "Rationale: Several studies suggest that patients with asthmawho are homozygous for arginine at the 16th position of the β2- adrenergic receptor may not benefit from short-acting β-agonists. Objectives: We investigated whether such genotype-specific effects occur when patients are treated with long-acting β-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use. Methods:Wecompared salmeterol response in patients with asthma homozygous for arginine at B16 (B16Arg/Arg) with those homozygous for glycine at B16 (B16Gly/Gly) in two separate cohorts. In the first, subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy. In the second, subjects were randomized to regular therapy with salmeterol while continuing concomitant ICS. Results: In both trials, B16Arg/Arg subjects did not benefit compared with B16Gly/Gly subjects after salmeterol was initiated. In the first cohort, compared with placebo, the addition of salmeterol was associated with a 51.4 L/min lower A.M. peak expiratory flow (PEF; p = 0.005) in B16Arg/Arg subjects(salmeterol, n = 12; placebo, n = 5) as compared with B16Gly/Gly subjects (salmeterol, n = 13; placebo, n = 13). In the second cohort, B16Arg/Arg subjects treated with salmeterol and ICS concurrently (n = 8) had a lower A.M. PEF (36.8 L/min difference, p = 0.048) than B16Gly/Gly subjects (n = 22) treated with the same regimen. In addition, B16 Arg/Arg subjects in the second cohort had lower FEV1 (0.42 L, p = 0.003), increased symptom scores (0.2 units, p = 0.034), and increased albuterol rescue use (0.95 puffs/d, p = 0.004) compared with B16Gly/Gly subjects. Conclusions: Relative to B16Gly/Gly patients with asthma, B16Arg/Arg patients with asthma may have an impaired therapeutic response to salmeterol in either the absence or presence of concurrent ICS use. Investigation of alternate treatment strategies may benefit this group.",
author = "Wechsler, {Michael E.} and Erik Lehman and Lazarus, {Stephen C.} and Lemanske, {Robert F.} and Boushey, {Homer A.} and Aaron Deykin and Fahy, {John V.} and Sorkness, {Christine A.} and Chinchilli, {Vernon M.} and Craig, {Timothy J.} and Emily DiMango and Monica Kraft and Frank Leone and Martin, {Richard J.} and Peters, {Stephen P.} and Szefler, {Stanley J.} and Wenlei Liu and Elliot Israel",
year = "2006",
month = "3",
day = "1",
doi = "10.1164/rccm.200509-1519OC",
language = "English (US)",
volume = "173",
pages = "519--526",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "5",

}

Wechsler, ME, Lehman, E, Lazarus, SC, Lemanske, RF, Boushey, HA, Deykin, A, Fahy, JV, Sorkness, CA, Chinchilli, VM, Craig, TJ, DiMango, E, Kraft, M, Leone, F, Martin, RJ, Peters, SP, Szefler, SJ, Liu, W & Israel, E 2006, 'β-Adrenergic receptor polymorphisms and response to salmeterol', American journal of respiratory and critical care medicine, vol. 173, no. 5, pp. 519-526. https://doi.org/10.1164/rccm.200509-1519OC

β-Adrenergic receptor polymorphisms and response to salmeterol. / Wechsler, Michael E.; Lehman, Erik; Lazarus, Stephen C.; Lemanske, Robert F.; Boushey, Homer A.; Deykin, Aaron; Fahy, John V.; Sorkness, Christine A.; Chinchilli, Vernon M.; Craig, Timothy J.; DiMango, Emily; Kraft, Monica; Leone, Frank; Martin, Richard J.; Peters, Stephen P.; Szefler, Stanley J.; Liu, Wenlei; Israel, Elliot.

In: American journal of respiratory and critical care medicine, Vol. 173, No. 5, 01.03.2006, p. 519-526.

Research output: Contribution to journalArticle

TY - JOUR

T1 - β-Adrenergic receptor polymorphisms and response to salmeterol

AU - Wechsler, Michael E.

AU - Lehman, Erik

AU - Lazarus, Stephen C.

AU - Lemanske, Robert F.

AU - Boushey, Homer A.

AU - Deykin, Aaron

AU - Fahy, John V.

AU - Sorkness, Christine A.

AU - Chinchilli, Vernon M.

AU - Craig, Timothy J.

AU - DiMango, Emily

AU - Kraft, Monica

AU - Leone, Frank

AU - Martin, Richard J.

AU - Peters, Stephen P.

AU - Szefler, Stanley J.

AU - Liu, Wenlei

AU - Israel, Elliot

PY - 2006/3/1

Y1 - 2006/3/1

N2 - Rationale: Several studies suggest that patients with asthmawho are homozygous for arginine at the 16th position of the β2- adrenergic receptor may not benefit from short-acting β-agonists. Objectives: We investigated whether such genotype-specific effects occur when patients are treated with long-acting β-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use. Methods:Wecompared salmeterol response in patients with asthma homozygous for arginine at B16 (B16Arg/Arg) with those homozygous for glycine at B16 (B16Gly/Gly) in two separate cohorts. In the first, subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy. In the second, subjects were randomized to regular therapy with salmeterol while continuing concomitant ICS. Results: In both trials, B16Arg/Arg subjects did not benefit compared with B16Gly/Gly subjects after salmeterol was initiated. In the first cohort, compared with placebo, the addition of salmeterol was associated with a 51.4 L/min lower A.M. peak expiratory flow (PEF; p = 0.005) in B16Arg/Arg subjects(salmeterol, n = 12; placebo, n = 5) as compared with B16Gly/Gly subjects (salmeterol, n = 13; placebo, n = 13). In the second cohort, B16Arg/Arg subjects treated with salmeterol and ICS concurrently (n = 8) had a lower A.M. PEF (36.8 L/min difference, p = 0.048) than B16Gly/Gly subjects (n = 22) treated with the same regimen. In addition, B16 Arg/Arg subjects in the second cohort had lower FEV1 (0.42 L, p = 0.003), increased symptom scores (0.2 units, p = 0.034), and increased albuterol rescue use (0.95 puffs/d, p = 0.004) compared with B16Gly/Gly subjects. Conclusions: Relative to B16Gly/Gly patients with asthma, B16Arg/Arg patients with asthma may have an impaired therapeutic response to salmeterol in either the absence or presence of concurrent ICS use. Investigation of alternate treatment strategies may benefit this group.

AB - Rationale: Several studies suggest that patients with asthmawho are homozygous for arginine at the 16th position of the β2- adrenergic receptor may not benefit from short-acting β-agonists. Objectives: We investigated whether such genotype-specific effects occur when patients are treated with long-acting β-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use. Methods:Wecompared salmeterol response in patients with asthma homozygous for arginine at B16 (B16Arg/Arg) with those homozygous for glycine at B16 (B16Gly/Gly) in two separate cohorts. In the first, subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy. In the second, subjects were randomized to regular therapy with salmeterol while continuing concomitant ICS. Results: In both trials, B16Arg/Arg subjects did not benefit compared with B16Gly/Gly subjects after salmeterol was initiated. In the first cohort, compared with placebo, the addition of salmeterol was associated with a 51.4 L/min lower A.M. peak expiratory flow (PEF; p = 0.005) in B16Arg/Arg subjects(salmeterol, n = 12; placebo, n = 5) as compared with B16Gly/Gly subjects (salmeterol, n = 13; placebo, n = 13). In the second cohort, B16Arg/Arg subjects treated with salmeterol and ICS concurrently (n = 8) had a lower A.M. PEF (36.8 L/min difference, p = 0.048) than B16Gly/Gly subjects (n = 22) treated with the same regimen. In addition, B16 Arg/Arg subjects in the second cohort had lower FEV1 (0.42 L, p = 0.003), increased symptom scores (0.2 units, p = 0.034), and increased albuterol rescue use (0.95 puffs/d, p = 0.004) compared with B16Gly/Gly subjects. Conclusions: Relative to B16Gly/Gly patients with asthma, B16Arg/Arg patients with asthma may have an impaired therapeutic response to salmeterol in either the absence or presence of concurrent ICS use. Investigation of alternate treatment strategies may benefit this group.

UR - http://www.scopus.com/inward/record.url?scp=33645110637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645110637&partnerID=8YFLogxK

U2 - 10.1164/rccm.200509-1519OC

DO - 10.1164/rccm.200509-1519OC

M3 - Article

C2 - 16322642

AN - SCOPUS:33645110637

VL - 173

SP - 519

EP - 526

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5

ER -