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. 2004 Jun;59(6):471–476. doi: 10.1136/thx.2003.019620

Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD

W Man 1, N Mustfa 1, D Nikoletou 1, S Kaul 1, N Hart 1, G Rafferty 1, N Donaldson 1, M Polkey 1, J Moxham 1
PMCID: PMC1747047  PMID: 15170026

Abstract

Background: Some patients with irreversible chronic obstructive pulmonary disease (COPD) experience subjective benefit from long acting bronchodilators without change in forced expiratory volume in 1 second (FEV1). Dynamic hyperinflation is an important determinant of exercise induced dyspnoea in COPD. We hypothesised that long acting bronchodilators improve symptoms by reducing dynamic hyperinflation and work of breathing, as measured by respiratory muscle pressure-time products.

Methods: Sixteen patients with "irreversible" COPD (<10% improvement in FEV1 following a bronchodilator challenge; mean FEV1 31.1% predicted) were recruited into a randomised, double blind, placebo controlled, crossover study of salmeterol (50 µg twice a day). Treatment periods were of 2 weeks duration with a 2 week washout period. Primary outcome measures were end exercise isotime transdiaphragmatic pressure-time product and dynamic hyperinflation as measured by inspiratory capacity.

Results: Salmeterol significantly reduced the transdiaphragmatic pressure-time product (294.5 v 348.6 cm H2O/s/min; p = 0.03), dynamic hyperinflation (0.22 v 0.33 litres; p = 0.002), and Borg scores during endurance treadmill walk (3.78 v 4.62; p = 0.02). There was no significant change in exercise endurance time. Improvements in isotime Borg score were significantly correlated to changes in tidal volume/oesophageal pressure swings, end expiratory lung volume, and inspiratory capacity, but not pressure-time products.

Conclusions: Despite apparent "non-reversibility" in spirometric parameters, long acting bronchodilators can cause both symptomatic and physiological improvement during exercise in severe COPD.

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Selected References

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  1. Aalbers R., Backer V., Kava T. T. K., Omenaas E. R., Sandström T., Jorup C., Welte T. Adjustable maintenance dosing with budesonide/formoterol compared with fixed-dose salmeterol/fluticasone in moderate to severe asthma. Curr Med Res Opin. 2004;20(2):225–240. doi: 10.1185/030079903125002928. [DOI] [PubMed] [Google Scholar]
  2. Appendini L., Patessio A., Zanaboni S., Carone M., Gukov B., Donner C. F., Rossi A. Physiologic effects of positive end-expiratory pressure and mask pressure support during exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1994 May;149(5):1069–1076. doi: 10.1164/ajrccm.149.5.8173743. [DOI] [PubMed] [Google Scholar]
  3. Aubier M., Viires N., Murciano D., Medrano G., Lecocguic Y., Pariente R. Effects and mechanism of action of terbutaline on diaphragmatic contractility and fatigue. J Appl Physiol Respir Environ Exerc Physiol. 1984 Apr;56(4):922–929. doi: 10.1152/jappl.1984.56.4.922. [DOI] [PubMed] [Google Scholar]
  4. Belman M. J., Botnick W. C., Shin J. W. Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996 Mar;153(3):967–975. doi: 10.1164/ajrccm.153.3.8630581. [DOI] [PubMed] [Google Scholar]
  5. Boni E., Corda L., Franchini D., Chiroli P., Damiani G. P., Pini L., Grassi V., Tantucci C. Volume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest. Thorax. 2002 Jun;57(6):528–532. doi: 10.1136/thorax.57.6.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borg G. A. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377–381. [PubMed] [Google Scholar]
  7. Calverley P. M. A., Burge P. S., Spencer S., Anderson J. A., Jones P. W. Bronchodilator reversibility testing in chronic obstructive pulmonary disease. Thorax. 2003 Aug;58(8):659–664. doi: 10.1136/thorax.58.8.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Calverley Peter, Pauwels Romain, Vestbo Jørgen, Jones Paul, Pride Neil, Gulsvik Amund, Anderson Julie, Maden Claire, TRial of Inhaled STeroids ANd long-acting beta2 agonists study group Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003 Feb 8;361(9356):449–456. doi: 10.1016/S0140-6736(03)12459-2. [DOI] [PubMed] [Google Scholar]
  9. Decramer M. Hyperinflation and respiratory muscle interaction. Eur Respir J. 1997 Apr;10(4):934–941. [PubMed] [Google Scholar]
  10. Duranti R., Misuri G., Gorini M., Goti P., Gigliotti F., Scano G. Mechanical loading and control of breathing in patients with severe chronic obstructive pulmonary disease. Thorax. 1995 Feb;50(2):127–133. doi: 10.1136/thx.50.2.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Field S., Sanci S., Grassino A. Respiratory muscle oxygen consumption estimated by the diaphragm pressure-time index. J Appl Physiol Respir Environ Exerc Physiol. 1984 Jul;57(1):44–51. doi: 10.1152/jappl.1984.57.1.44. [DOI] [PubMed] [Google Scholar]
  12. Hadcroft J., Calverley P. M. Alternative methods for assessing bronchodilator reversibility in chronic obstructive pulmonary disease. Thorax. 2001 Sep;56(9):713–720. doi: 10.1136/thorax.56.9.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jones P. W., Bosh T. K. Quality of life changes in COPD patients treated with salmeterol. Am J Respir Crit Care Med. 1997 Apr;155(4):1283–1289. doi: 10.1164/ajrccm.155.4.9105068. [DOI] [PubMed] [Google Scholar]
  14. Jubran A., Tobin M. J. Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. Am J Respir Crit Care Med. 1997 Mar;155(3):906–915. doi: 10.1164/ajrccm.155.3.9117025. [DOI] [PubMed] [Google Scholar]
  15. Kyroussis D., Mills G. H., Polkey M. I., Hamnegard C. H., Koulouris N., Green M., Moxham J. Abdominal muscle fatigue after maximal ventilation in humans. J Appl Physiol (1985) 1996 Oct;81(4):1477–1483. doi: 10.1152/jappl.1996.81.4.1477. [DOI] [PubMed] [Google Scholar]
  16. Kyroussis D., Polkey M. I., Hamnegård C. H., Mills G. H., Green M., Moxham J. Respiratory muscle activity in patients with COPD walking to exhaustion with and without pressure support. Eur Respir J. 2000 Apr;15(4):649–655. doi: 10.1034/j.1399-3003.2000.15d05.x. [DOI] [PubMed] [Google Scholar]
  17. Maesen B. L., Westermann C. J., Duurkens V. A., van den Bosch J. M. Effects of formoterol in apparently poorly reversible chronic obstructive pulmonary disease. Eur Respir J. 1999 May;13(5):1103–1108. doi: 10.1034/j.1399-3003.1999.13e27.x. [DOI] [PubMed] [Google Scholar]
  18. Man W. D-C, Soliman M. G. G., Nikoletou D., Harris M. L., Rafferty G. F., Mustfa N., Polkey M. I., Moxham J. Non-volitional assessment of skeletal muscle strength in patients with chronic obstructive pulmonary disease. Thorax. 2003 Aug;58(8):665–669. doi: 10.1136/thorax.58.8.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Man William D-C, Soliman Mohamed G. G., Gearing Johanne, Radford Sheena G., Rafferty Gerrard F., Gray Barry J., Polkey Michael I., Moxham John. Symptoms and quadriceps fatigability after walking and cycling in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003 Jun 26;168(5):562–567. doi: 10.1164/rccm.200302-162OC. [DOI] [PubMed] [Google Scholar]
  20. Manning H. L., Schwartzstein R. M. Pathophysiology of dyspnea. N Engl J Med. 1995 Dec 7;333(23):1547–1553. doi: 10.1056/NEJM199512073332307. [DOI] [PubMed] [Google Scholar]
  21. Marin J. M., Carrizo S. J., Gascon M., Sanchez A., Gallego B., Celli B. R. Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 May;163(6):1395–1399. doi: 10.1164/ajrccm.163.6.2003172. [DOI] [PubMed] [Google Scholar]
  22. Miller J. M., Moxham J., Green M. The maximal sniff in the assessment of diaphragm function in man. Clin Sci (Lond) 1985 Jul;69(1):91–96. doi: 10.1042/cs0690091. [DOI] [PubMed] [Google Scholar]
  23. Ninane V., Rypens F., Yernault J. C., De Troyer A. Abdominal muscle use during breathing in patients with chronic airflow obstruction. Am Rev Respir Dis. 1992 Jul;146(1):16–21. doi: 10.1164/ajrccm/146.1.16. [DOI] [PubMed] [Google Scholar]
  24. Ninane V., Yernault J. C., de Troyer A. Intrinsic PEEP in patients with chronic obstructive pulmonary disease. Role of expiratory muscles. Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):1037–1042. doi: 10.1164/ajrccm/148.4_Pt_1.1037. [DOI] [PubMed] [Google Scholar]
  25. O'Donnell D. E., Lam M., Webb K. A. Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1557–1565. doi: 10.1164/ajrccm.158.5.9804004. [DOI] [PubMed] [Google Scholar]
  26. Pauwels R. A., Buist A. S., Calverley P. M., Jenkins C. R., Hurd S. S., GOLD Scientific Committee Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001 Apr;163(5):1256–1276. doi: 10.1164/ajrccm.163.5.2101039. [DOI] [PubMed] [Google Scholar]
  27. Rennard S. I., Anderson W., ZuWallack R., Broughton J., Bailey W., Friedman M., Wisniewski M., Rickard K. Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 Apr;163(5):1087–1092. doi: 10.1164/ajrccm.163.5.9903053. [DOI] [PubMed] [Google Scholar]
  28. Saey Didier, Debigare Richard, LeBlanc Pierre, Mador M. Jeffery, Cote Claude H., Jobin Jean, Maltais Francois. Contractile leg fatigue after cycle exercise: a factor limiting exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003 Apr 24;168(4):425–430. doi: 10.1164/rccm.200208-856OC. [DOI] [PubMed] [Google Scholar]
  29. Sinderby C., Spahija J., Beck J., Kaminski D., Yan S., Comtois N., Sliwinski P. Diaphragm activation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 Jun;163(7):1637–1641. doi: 10.1164/ajrccm.163.7.2007033. [DOI] [PubMed] [Google Scholar]
  30. Singh S. J., Morgan M. D., Scott S., Walters D., Hardman A. E. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax. 1992 Dec;47(12):1019–1024. doi: 10.1136/thx.47.12.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stubbing D. G., Pengelly L. D., Morse J. L., Jones N. L. Pulmonary mechanics during exercise in subjects with chronic airflow obstruction. J Appl Physiol Respir Environ Exerc Physiol. 1980 Sep;49(3):511–515. doi: 10.1152/jappl.1980.49.3.511. [DOI] [PubMed] [Google Scholar]
  32. Yan S., Kaminski D., Sliwinski P. Reliability of inspiratory capacity for estimating end-expiratory lung volume changes during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1997 Jul;156(1):55–59. doi: 10.1164/ajrccm.156.1.9608113. [DOI] [PubMed] [Google Scholar]

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