Response of Lung Volumes to Inhaled Salbutamol in a Large Population of Patients With Severe Hyperinflation

Flüge²,

Gerken³

et al. 2004

Eur Respir J

764

581

The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease.A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44 ¡ 13% pred): 96 patients received 18 mg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient9s maximal work capacity were compared.On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105¡40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9¡0.3 Borg scale units.In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.

Section: Effect Of Tiotropium On Resting Lung Volumessupporting

confidence: 89%

Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD

Flüge²,

Gerken³

et al. 2004

Eur Respir J

764

581

“…In keeping with numerous previous bronchodilator studies, the FEV1/FVC ratio was unchanged, indicating that increases in FEV1 were mainly the result of volume recruitment [2,3,[23][24][25].…”

Section: Effect Of Salmeterol On Resting Lung Volumessupporting

confidence: 88%

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

Voduc²,

Fitzpatrick³

et al. 2004

Eur Respir J

331

273

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 ...

“…Improvements in the forced expiratory volume in one second (FEV1) post-BD signify reduced resistance in the larger airways, as well as in alveolar units, with rapid time constants for lung emptying. In more advanced chronic obstructive pulmonary disease (COPD; in contrast to asthma), post-BD increases in FEV1 mainly occur as a result of lung volume recruitment; the ratio of FEV1 to forced vital capacity (FVC) is unaltered or actually decreases in response to BD [2][3][4][5][6]. Measurements of timed vital capacity or forced expiratory volume in six seconds appear to be more sensitive than FVC in detecting enhanced lung emptying after pharmacotherapy [7,8].…”

mentioning

confidence: 99%

“…Recent studies have shown that substantial reductions (i.e. .0.5 L) in lung hyperinflation can occur after acute short-and long-acting BD treatment in the presence of only modest improvements in FEV1 [2][3][4][5][6][9][10][11]. BD therapy is often associated with small but consistent increases in maximal expiratory flow rates in the effort-independent mid-volume range where tidal breathing occurs [3,4].…”

mentioning

confidence: 99%

“…Thus, patients may remain flow-limited but can now accomplish the required alveolar ventilation at a lower operating lung volume and, therefore, at a reduced oxygen cost of breathing. Patients who show expiratory flow limitation during spontaneous resting breathing (as determined by the negative expiratory pressure technique) and those with more severe resting lung hyperinflation have demonstrated the greatest lung volume reduction with BDs [6,10,11].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Lung hyperinflation in COPD: the impact of pharmacotherapy

Laveneziana²

2006

Eur Respir Rev

Improvement in airway function in response to bronchodilator therapy is generally confirmed by simple spirometry. However, improvements in maximal expiratory flow rates have been shown to correlate poorly with important patient-centred outcomes, such as reduced exertional dyspnoea and improved exercise performance. Recent studies have suggested that attendant reductions in end-expiratory lung volume as a result of bronchodilator-induced improvements in lung emptying may be more closely associated with symptom relief and increased exercise capacity than traditional spirometric indices. To the extent that chronic lung hyperinflation and the superimposition of acute dynamic hyperinflation (in response to increased ventilation or expiratory flow limitation) result in excessive loading and weakening of the inspiratory muscles, then pharmacological lung volume reduction should have important mechanical and sensory benefits for the patient.The present article will examine the mechanisms of lung deflation following short-term bronchodilator therapy. The physiological links between reduced hyperinflation, improved dyspnoea and exercise endurance will be examined, and the emerging evidence for the additive effects of combining various modern pharmacological therapies will be reviewed.