Background: Sleep is associated with important adverse effects in patients with chronic obstructive pulmonary disease (COPD), such as disturbed sleep quality and gas exchange, including hypoxemia and hypercapnia. The effects of inhaled long-acting β2-agonist therapy (LABA) on these disturbances are unclear. Objectives: The aim of the study was to assess the effect of inhaled salmeterol on nocturnal sleeping arterial oxygen saturation (SaO2) and sleep quality. Methods: In a randomized, double-blind, placebo-controlled, crossover study of moderate/severe stable COPD patients, we compared the effects of 4 weeks of treatment with salmeterol 50 µg b.d. and matching placebo on sleeping SaO2 and sleep quality. Overnight polysomnography (PSG) was performed at baseline, and after 4 and 8 weeks in addition to detailed pulmonary function testing. Of 15 patients included, 12 completed the trial (median age 69 years, forced expiratory volume in 1 s, FEV1: 39%). Results: Both mean SaO2 [salmeterol vs. placebo: 92.9% (91.2, 94.7) vs. 91.0% (88.9, 94.8); p = 0.016] and the percentage of sleep spent below 90% of SaO2 [1.8% (0.0, 10.8) vs. 25.6% (0.5, 53.5); p = 0.005] improved significantly with salmeterol. Sleep quality was similar with both salmeterol and placebo on PSG. Static lung volumes, particularly trapped gas volume, tended to improve with salmeterol. Conclusion: We conclude that inhaled LABA therapy improves sleeping SaO2 without significant change in sleep quality.

1.
Celli BR, MacNee W: Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23:932–946.
2.
McNicholas WT: Impact of sleep in COPD. Chest 2000;117(2 suppl):48S–53S.
3.
Catterall JR, Calverley PM, MacNee W, Warren PM, Shapiro CM, Douglas NJ, Flenley DC: Mechanism of transient nocturnal hypoxemia in hypoxic chronic bronchitis and emphysema. J Appl Physiol 1985;59:1698–1703.
4.
Johnson MW, Remmers JE: Accessory muscle activity during sleep in chronic obstructive pulmonary disease. J Appl Physiol 1984;57:1011–1017.
5.
Tirlapur VG, Mir MA: Nocturnal hypoxemia and associated electrocardiographic changes in patients with chronic obstructive airways disease. N Engl J Med 1982;306:125–130.
6.
McNicholas WT, Fitzgerald MX: Nocturnal deaths among patients with chronic bronchitis and emphysema. Br Med J (Clin Res Ed) 1984;289:878.
7.
Fletcher EC, Luckett RA, Miller T, Costarangos C, Kutka N, Fletcher JG: Pulmonary vascular hemodynamics in chronic lung disease patients with and without oxyhemoglobin desaturation during sleep. Chest 1989;95:757–764.
8.
Fleetham J, West P, Mezon B, Conway W, Roth T, Kryger M: Sleep, arousals, and oxygen desaturation in chronic obstructive pulmonary disease. The effect of oxygen therapy. Am Rev Respir Dis 1982;126:429–433.
9.
Calverley PM, Brezinova V, Douglas NJ, Catterall JR, Flenley DC: The effect of oxygenation on sleep quality in chronic bronchitis and emphysema. Am Rev Respir Dis 1982;126:206–210.
10.
Goldstein RS, Ramcharan V, Bowes G, McNicholas WT, Bradley D, Phillipson EA: Effect of supplemental nocturnal oxygen on gas exchange in patients with severe obstructive lung disease. N Engl J Med 1984;310:425–429.
11.
Mulloy E, McNicholas WT: Theophylline improves gas exchange during rest, exercise, and sleep in severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1993;148(4 Pt 1):1030–1036.
12.
McNicholas WT, Calverley PM, Lee A, Edwards JC: Long-acting inhaled anticholinergic therapy improves sleeping oxygen saturation in COPD. Eur Respir J 2004;23:825–831.
13.
Stockley RA, Chopra N, Rice L: Addition of salmeterol to existing treatment in patients with COPD: a 12 month study. Thorax 2006;61:122–128.
14.
Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J: Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775–789.
15.
O’Donnell DE, Voduc N, Fitzpatrick M, Webb KA: Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease. Eur Respir J 2004;24:86–94.
16.
Man WD, Mustfa N, Nikoletou D, Kaul S, Hart N, Rafferty GF, Donaldson N, Polkey MI, Moxham J: Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD. Thorax 2004;59:471–476.
17.
Brouillard C, Pepin V, Milot J, Lacasse Y, Maltais F: Endurance shuttle walking test: responsiveness to salmeterol in COPD. Eur Respir J 2008;31:579–584.
18.
Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A, Anderson J, Maden C: Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003;361:449–456.
19.
Ware JE, Snow K, Kosinski M, Gandek B: SF-36® Health Survey. Manual and Interpretation Guide. Boston, New England Medical Center, Health Institute, 1993.
20.
Johns MW: A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:540–545.
21.
Ryan S, Taylor CT, McNicholas WT: Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 2005;112:2660–2667.
22.
Rechtschaffen A, Kales A: A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Washington, US Government Printing Office, Public Health Service, 1968.
23.
Postma DS, Koeter GH, vd Mark TW, Reig RP, Sluiter HJ: The effects of oral slow-release terbutaline on the circadian variation in spirometry and arterial blood gas levels in patients with chronic airflow obstruction. Chest 1985;87:653–657.
24.
Connaughton JJ, Catterall JR, Elton RA, Stradling JR, Douglas NJ: Do sleep studies contribute to the management of patients with severe chronic obstructive pulmonary disease? Am Rev Respir Dis 1988;138:341–344.
25.
Fletcher EC, Miller J, Divine GW, Fletcher JG, Miller T: Nocturnal oxyhemoglobin desaturation in COPD patients with arterial oxygen tensions above 60 mm Hg. Chest 1987;92:604–608.
26.
O’Donnell DE, Sciurba F, Celli B, Mahler DA, Webb KA, Kalberg CJ, Knobil K: Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD. Chest 2006;130:647–656.
27.
Cormick W, Olson LG, Hensley MJ, Saunders NA: Nocturnal hypoxaemia and quality of sleep in patients with chronic obstructive lung disease. Thorax 1986;41:846–854.
28.
Rennard S, Decramer M, Calverley PM, Pride NB, Soriano JB, Vermeire PA, Vestbo J: Impact of COPD in North America and Europe in 2000: subjects’ perspective of Confronting COPD International Survey. Eur Respir J 2002;20:799–805.
29.
Jones PW, Bosh TK: Quality of life changes in COPD patients treated with salmeterol. Am J Respir Crit Care Med 1997;155:1283–1289.
30.
Collard P, Dury M, Delguste P, Aubert G, Rodenstein DO: Movement arousals and sleep-related disordered breathing in adults. Am J Respir Crit Care Med 1996;154(2 Pt 1):454–459.
31.
Chaouat A, Weitzenblum E, Krieger J, Ifoundza T, Oswald M, Kessler R: Association of chronic obstructive pulmonary disease and sleep apnea syndrome. Am J Respir Crit Care Med 1995;151:82–86.
32.
Ryan S, Taylor CT, McNicholas WT: Predictors of elevated nuclear factor-ĸB-dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 2006;174:824–830.
33.
McNicholas WT, Bonsigore MR: Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities. Eur Respir J 2007;29:156–178.
34.
Sin DD, Man SF: Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation 2003;107:1514–1519.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.