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Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD
  1. W D C Man1,
  2. N Mustfa1,
  3. D Nikoletou1,
  4. S Kaul1,
  5. N Hart2,
  6. G F Rafferty1,
  7. N Donaldson3,
  8. M I Polkey2,
  9. J Moxham1
  1. 1Respiratory Muscle Laboratory, Guy’s, King’s and St Thomas’ School of Medicine, King’s College Hospital, London, UK
  2. 2Royal Brompton Hospital, London, UK
  3. 3Department of Statistics (Research & Development), King’s College Hospital, London, UK
  1. Correspondence to:
    Dr W D C Man
    Respiratory Muscle Laboratory, Guy’s, King’s and St Thomas’ School of Medicine, King’s College Hospital, Bessemer Road, London SE5 9PJ, UK; william.mankcl.ac.uk

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.

  • chronic obstructive pulmonary disease
  • salmeterol
  • pressure-time product
  • dynamic hyperinflation
  • respiratory muscles
  • DH, dynamic hyperinflation
  • EELV, end expiratory lung volume
  • EILV, end inspiratory lung volume FEV1, forced expiratory volume in 1 second
  • IC, inspiratory capacity
  • IRV, inspiratory reserve volume
  • ISW, incremental shuttle walk
  • Pao2, Paco2, arterial oxygen and carbon dioxide tensions
  • PEEPi, intrinsic positive end expiratory pressure
  • Pimax, maximum inspiratory pressure
  • Pdi, diaphragmatic pressure
  • Pga, gastric pressure
  • Poes, oesophageal pressure
  • PTP, pressure-time product
  • RV, residual volume
  • Tlco, carbon monoxide transfer factor
  • TLC, total lung capacity
  • VC, vital capacity
  • Vo2peak, peak oxygen consumption
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Footnotes

  • WDCM is a Clinical Research Training Fellow of the Medical Research Council (UK).

  • This study was funded in part by a project grant from GlaxoSmithKline UK (protocol no SMS40312) who provided study drugs and placebo. They were involved in the initial design of the study but had no input in the writing of the final protocol, patient recruitment, data acquisition or analysis, or in the preparation of the manuscript.

  • WDCM has received assistance for travel to international conferences from Schering-Plough, GlaxoSmithKline, Allen & Hanburys. Boehringer-Ingelheim, and Bayer pharmaceutical companies. SK has received lecture fees from GlaxoSmithKline, Astra Zenca and Boehringer-Ingelheim. NH has received assistance for travel to international conferences from Bayer BREAS, 3M, Glaxo Wellcome, Cephalon and MedicAid. MIP has received lecture fees from Astra Zeneca, GlaxoSmithKline, Nutricia and Cephalon, and assistance for travel to international conferences from Glaxo Wellcome, Astra Zeneca, Cephalon, 3M and Ciba. JM has received assistance for travel to international conferences from Schering-Plough and Pfizer. NM, DN, GFR and ND have no conflicts of interest.

  • WDCM was involved in the design of the protocol, recruitment of patients, collection and analysis of data, and wrote the first draft of the manuscript. NM, DN, and SK were involved in recruitment of patients, collection of data, and preparation of the final manuscript. NH and GFR were involved in the design of the study, analysis of the data, and preparation of the final manuscript. ND gave statistical support and was involved in the analysis of data and the preparation of the final manuscript. MIP and JM were the senior investigators with the original idea for the study. They designed the study protocol, helped to write the first draft of the manuscript, supervised the conduct of the study and preparation of the final manuscript.

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