Fluticasone/Salmeterol Combination Confers Benefits in People With Asthma Who Smoke

Karine L. Clearie; Lorna McKinlay; Peter A. Williamson; Brian J. Lipworth

doi:10.1378/chest.11-0392

Fluticasone/Salmeterol Combination Confers Benefits in People With Asthma Who Smoke

Karine L. Clearie, Lorna McKinlay, Peter A. Williamson, Brian J. Lipworth

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

Abstract

Background: Smoking induces airway inflammation and relative resistance to inhaled steroids. The objective of this study was to evaluate the effects on airway hyperresponsiveness of adding salmeterol to fluticasone vs doubling the dose of fluticasone in patients with asthma who smoked and patients with asthma who did not smoke.

Methods: Sixteen patients with mild to moderate persistent asthma who did not smoke and 15 such patients who smoked completed a double-blind, randomized, placebo-controlled crossover study. They received either a fluticasone/salmeterol combination (FP/SM) (125/25 mu g) two puffs bid (plus fluticasone placebo), or active fluticasone (250 mu g) two puffs bid (plus FP/SM placebo), for 2 weeks each, with baselines after 1-week to 2-week run-in and washout periods. The primary outcome was the change from baseline in the provocative concentration of methacholine required to produce a 20% fall in FEV, (PC20).

Results: In the patients who did not smoke, there were similar improvements in the methacholine PC20 with the use of fluticasone and FP/SM. The patients who smoked gained a benefit from FP/SM but not fluticasone, amounting to a PC difference of 1.6 doubling dilutions (95% CI, 1.0-2.2), P<.01. The provocative dose of mannitol required to produce a 15% fall in FEV, (PD) showed greater improvements with FP/SM than fluticasone in both patients who smoked and did not smoke. Similar differences in airway caliber between those who smoked and did not smoke were observed in FEY, and airway resistance.

Conclusions: FP/SM confers greater improvements in airway hyperresponsiveness and airway caliber in patients with asthma who smoke compared with double the dose of fluticasone. We hypothesize that in the presence of relative steroid resistance, the smooth muscle stabilization conferred by salmeterol is of greater clinical importance in patients who smoke than in those who do not smoke. Trial registry: ClinicalTrials.gov: No.: NCT00830505; URL: www.clinicaltrials.gov CHEST 2012; 141(2):330-338

Original language	English
Pages (from-to)	330-338
Number of pages	9
Journal	Chest
Volume	141
Issue number	2
DOIs	https://doi.org/10.1378/chest.11-0392
Publication status	Published - Feb 2012

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@article{7e1cb0ff168f4b96b6491ab7854b640f,

title = "Fluticasone/Salmeterol Combination Confers Benefits in People With Asthma Who Smoke",

abstract = "Background: Smoking induces airway inflammation and relative resistance to inhaled steroids. The objective of this study was to evaluate the effects on airway hyperresponsiveness of adding salmeterol to fluticasone vs doubling the dose of fluticasone in patients with asthma who smoked and patients with asthma who did not smoke.Methods: Sixteen patients with mild to moderate persistent asthma who did not smoke and 15 such patients who smoked completed a double-blind, randomized, placebo-controlled crossover study. They received either a fluticasone/salmeterol combination (FP/SM) (125/25 mu g) two puffs bid (plus fluticasone placebo), or active fluticasone (250 mu g) two puffs bid (plus FP/SM placebo), for 2 weeks each, with baselines after 1-week to 2-week run-in and washout periods. The primary outcome was the change from baseline in the provocative concentration of methacholine required to produce a 20% fall in FEV, (PC20).Results: In the patients who did not smoke, there were similar improvements in the methacholine PC20 with the use of fluticasone and FP/SM. The patients who smoked gained a benefit from FP/SM but not fluticasone, amounting to a PC difference of 1.6 doubling dilutions (95% CI, 1.0-2.2), P<.01. The provocative dose of mannitol required to produce a 15% fall in FEV, (PD) showed greater improvements with FP/SM than fluticasone in both patients who smoked and did not smoke. Similar differences in airway caliber between those who smoked and did not smoke were observed in FEY, and airway resistance.Conclusions: FP/SM confers greater improvements in airway hyperresponsiveness and airway caliber in patients with asthma who smoke compared with double the dose of fluticasone. We hypothesize that in the presence of relative steroid resistance, the smooth muscle stabilization conferred by salmeterol is of greater clinical importance in patients who smoke than in those who do not smoke. Trial registry: ClinicalTrials.gov: No.: NCT00830505; URL: www.clinicaltrials.gov CHEST 2012; 141(2):330-338",

author = "Clearie, {Karine L.} and Lorna McKinlay and Williamson, {Peter A.} and Lipworth, {Brian J.}",

year = "2012",

month = feb,

doi = "10.1378/chest.11-0392",

language = "English",

volume = "141",

pages = "330--338",

journal = "Chest",

issn = "0012-3692",

publisher = "Elsevier",

number = "2",

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T1 - Fluticasone/Salmeterol Combination Confers Benefits in People With Asthma Who Smoke

AU - Clearie, Karine L.

AU - McKinlay, Lorna

AU - Williamson, Peter A.

AU - Lipworth, Brian J.

PY - 2012/2

Y1 - 2012/2

N2 - Background: Smoking induces airway inflammation and relative resistance to inhaled steroids. The objective of this study was to evaluate the effects on airway hyperresponsiveness of adding salmeterol to fluticasone vs doubling the dose of fluticasone in patients with asthma who smoked and patients with asthma who did not smoke.Methods: Sixteen patients with mild to moderate persistent asthma who did not smoke and 15 such patients who smoked completed a double-blind, randomized, placebo-controlled crossover study. They received either a fluticasone/salmeterol combination (FP/SM) (125/25 mu g) two puffs bid (plus fluticasone placebo), or active fluticasone (250 mu g) two puffs bid (plus FP/SM placebo), for 2 weeks each, with baselines after 1-week to 2-week run-in and washout periods. The primary outcome was the change from baseline in the provocative concentration of methacholine required to produce a 20% fall in FEV, (PC20).Results: In the patients who did not smoke, there were similar improvements in the methacholine PC20 with the use of fluticasone and FP/SM. The patients who smoked gained a benefit from FP/SM but not fluticasone, amounting to a PC difference of 1.6 doubling dilutions (95% CI, 1.0-2.2), P<.01. The provocative dose of mannitol required to produce a 15% fall in FEV, (PD) showed greater improvements with FP/SM than fluticasone in both patients who smoked and did not smoke. Similar differences in airway caliber between those who smoked and did not smoke were observed in FEY, and airway resistance.Conclusions: FP/SM confers greater improvements in airway hyperresponsiveness and airway caliber in patients with asthma who smoke compared with double the dose of fluticasone. We hypothesize that in the presence of relative steroid resistance, the smooth muscle stabilization conferred by salmeterol is of greater clinical importance in patients who smoke than in those who do not smoke. Trial registry: ClinicalTrials.gov: No.: NCT00830505; URL: www.clinicaltrials.gov CHEST 2012; 141(2):330-338

AB - Background: Smoking induces airway inflammation and relative resistance to inhaled steroids. The objective of this study was to evaluate the effects on airway hyperresponsiveness of adding salmeterol to fluticasone vs doubling the dose of fluticasone in patients with asthma who smoked and patients with asthma who did not smoke.Methods: Sixteen patients with mild to moderate persistent asthma who did not smoke and 15 such patients who smoked completed a double-blind, randomized, placebo-controlled crossover study. They received either a fluticasone/salmeterol combination (FP/SM) (125/25 mu g) two puffs bid (plus fluticasone placebo), or active fluticasone (250 mu g) two puffs bid (plus FP/SM placebo), for 2 weeks each, with baselines after 1-week to 2-week run-in and washout periods. The primary outcome was the change from baseline in the provocative concentration of methacholine required to produce a 20% fall in FEV, (PC20).Results: In the patients who did not smoke, there were similar improvements in the methacholine PC20 with the use of fluticasone and FP/SM. The patients who smoked gained a benefit from FP/SM but not fluticasone, amounting to a PC difference of 1.6 doubling dilutions (95% CI, 1.0-2.2), P<.01. The provocative dose of mannitol required to produce a 15% fall in FEV, (PD) showed greater improvements with FP/SM than fluticasone in both patients who smoked and did not smoke. Similar differences in airway caliber between those who smoked and did not smoke were observed in FEY, and airway resistance.Conclusions: FP/SM confers greater improvements in airway hyperresponsiveness and airway caliber in patients with asthma who smoke compared with double the dose of fluticasone. We hypothesize that in the presence of relative steroid resistance, the smooth muscle stabilization conferred by salmeterol is of greater clinical importance in patients who smoke than in those who do not smoke. Trial registry: ClinicalTrials.gov: No.: NCT00830505; URL: www.clinicaltrials.gov CHEST 2012; 141(2):330-338

U2 - 10.1378/chest.11-0392

DO - 10.1378/chest.11-0392

M3 - Article

C2 - 21636667

SN - 0012-3692

VL - 141

SP - 330

EP - 338

JO - Chest

JF - Chest

IS - 2

ER -

Fluticasone/Salmeterol Combination Confers Benefits in People With Asthma Who Smoke

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