Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease

Abstract

This study examined the effects of bronchodilator-induced reductions in lung hyperinflation on breathing pattern, ventilation and dyspnoea during exercise in chronic obstructive pulmonary disease (COPD). Quantitative tidal flow/volume loop analysis was used to evaluate abnormalities in dynamic ventilatory mechanics and their manipulation by a bronchodilator.In a randomised double-blind crossover study, 23 patients with COPD (mean¡SEM forced expiratory volume in one second 42¡3% of the predicted value) inhaled salmeterol 50 mg or placebo twice daily for 2 weeks each. After each treatment period, 2 h after dose, patients performed pulmonary function tests and symptom-limited cycle exercise at 75% of their maximal work-rate.After salmeterol versus placebo at rest, volume-corrected maximal expiratory flow rates increased by 175¡52%, inspiratory capacity (IC) increased by 11¡2% pred and functional residual capacity decreased by 11¡3% pred. At a standardised time during exercise, salmeterol increased IC, tidal volume (VT), mean inspiratory and expiratory flows, ventilation, oxygen uptake (V9O 2 ) and carbon dioxide output. Salmeterol increased peak exercise endurance, V9O 2 and ventilation by 58¡19, 8¡3 and 12¡3%, respectively. Improvements in peak V9O 2 correlated best with increases in peak VT; increases in peak VT and resting IC were interrelated. The reduction in dyspnoea ratings at a standardised time correlated with the increased VT.Mechanical factors play an important role in shaping the ventilatory response to exercise in chronic obstructive pulmonary disease. Bronchodilator-induced lung deflation reduced mechanical restriction, increased ventilatory capacity and decreased respiratory discomfort, thereby increasing exercise endurance. Several recent studies have shown that improvements in exertional dyspnoea following bronchodilator therapy in chronic obstructive pulmonary disease (COPD) correlate well with reductions in lung hyperinflation, as indicated by increases in inspiratory capacity (IC) [1][2][3][4][5]. However, the relationship between bronchodilator-induced increases in IC and improvements in symptoms and exercise performance is complex and poorly understood. Given the multifactorial nature of dyspnoea and exercise limitation in COPD, it remains unclear why small increases in resting IC (in the order of 0.3 L) appear to be clinically important. The current study extends previous studies conducted in the present authors9 laboratory using ipratropium bromide by, in addition, examining the effect of a bronchodilator (salmeterol) on plethysmographic lung volume components at rest and on breathing pattern and ventilatory capacity during exercise. Moreover, the study was designed to advance understanding of the mechanisms of bronchodilatorinduced dyspnoea relief, especially the role of reduced mechanical restriction.It has previously been shown that acute-on-chronic hyperinflation during exercise severely constrains tidal volume (VT) expansion, and that this dynamic mechanical restriction makes ...

Recommendations on the use of exercise testing in clinical practice

“…75-80% peak work-rate) have been used to demonstrate the positive effects of interventions such as bronchodilator therapy [252,253,262]; oxygen [263] and heliox [254] administration during exercise; bronchoscopic lung volume reduction [264]; and rehabilitation [265,266]. By using this approach, it is possible to demonstrate a significant improvement in endurance time, mostly due to a reduction in lung dynamic hyperinflation and dyspnoea at isotime (table 3).…”

“…The Borg scale has been used extensively to detect changes in dyspnoea after therapeutic interventions, particularly in COPD patients [247][248][249][250][251][252][253][254].…”

Bronchodilator effects of indacaterol and formoterol in patients with COPD

“…These agents include the twice-daily β 2 -agonists, formoterol and salmeterol, and the once-daily anticholinergic, tiotropium. Long-acting bronchodilators may improve exercise tolerance [2][3][4] as a result of bronchodilation and reduction of both static and dynamic hyperinflation.…”

Exercise and dyspnoea in COPD

“…In these circumstances, it is clear that neuromechanical dissociation is an important factor producing breathlessness during exercise that is most marked towards the end of exercise when the endinspiratory lung volume comes to within a few hundred millilitres of the total lung capacity (TLC) [29], a change that is also seen in severely breathless patients admitted to hospital reporting breathlessness at rest [30]. Measurements of EELV are normally made by asking the patient to perform an inspiratory capacity (IC) manoeuvre, and good data have been taken during exercise that show the TLC to be apparently constant.…”