Improvements in Symptom-Limited Exercise Performance Over 8 h With Once-Daily Tiotropium in Patients With COPD

Maltais, François; Hamilton, Alan; Marciniuk, Darcy; Hernández, Paul; Sciurba, Frank C.; Richter, Kai; Kesten, Steven; O’Donnell, Denis E.

doi:10.1378/chest.128.3.1168

Cited by 279 publications

(254 citation statements)

References 22 publications

(19 reference statements)

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“…25 Our findings on day 14 post-dose demonstrate a greater increase in IC with triple therapy compared with the other treatments. SFC therapy alone 26 and TIO alone 27 are known to increase IC, and hence reduce hyperinflation, leading to improvements in exercise capacity. We have shown that greater increases in IC can be achieved when both of these inhalers are used together, compared with the individual treatments, and accordingly would expect this to translate into further improvements in exercise capacity.…”

Section: Discussionmentioning

confidence: 99%

Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD

Singh

Brooks

Hagan

et al. 2008

Thorax

166

108

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Background: The combination of salmeterol and fluticasone propionate (SFC) and tiotropium bromide (TIO) are commonly used treatments in chronic obstructive pulmonary disease (COPD) but there are few data on their effectiveness when used together. We compared the effects of SFC 50/500 mg twice daily in addition to TIO 18 mg once daily with the individual treatments alone. Methods: 41 patients with COPD participated in a randomised, double blind, double dummy, three way crossover study with 2 week washout periods between treatments. Lung function assessment included plethysmography and spirometry. The primary end point was post-dose specific airways conductance (sGaw) area under the curve (AUC 0-4 h ) on day 14. Results: AUC 0-4 h sGaw was significantly higher on day 14 after SFC+TIO compared with TIO (22%) or SFC alone (27%) (both p,0.001). SFC+TIO significantly improved trough forced expiratory volume in 1 s compared with TIO alone (212 ml, p,0.001) and SFC alone (110 ml, p = 0.017) on day 14. Inspiratory capacity measurements also showed significant benefits for triple therapy over individual components on day 14. Subjects receiving SFC+TIO had clinically relevant improvements in Transition Dyspnoea Index (TDI) total score of 2.2 compared with TIO alone (p,0.001) (but not SFC alone, 0.7; NS) and used significantly less rescue medication (1.0 occasion less daily than TIO (p,0.001) and 0.6 less than SFC (p = 0.01)). Conclusion: SFC+TIO triple therapy led to greater improvements in bronchodilation compared with TIO and SFC alone. The advantages of triple therapy are observed across a range of physiologically important parameters, including airway conductance and lung volumes. Triple therapy also led to patient related benefits by improving TDI and use of rescue medication. Trial registration number: NCT00325169.Chronic obstructive pulmonary disease (COPD) is a multi-component disease with inflammation playing a key role, even in the early stages. 1 It is characterised by airflow obstruction that is both progressive and poorly reversible. 2 Drug treatments for COPD aim to control symptoms, maximise pulmonary function and reduce exacerbation rates. 2 The inhaled anticholinergic tiotropium (TIO) provides effective bronchodilation over 24 h and reduces symptoms. 3 4 These effects are associated with a reduction in exacerbation rates. 5 The long acting beta agonist (LABA) salmeterol is an alternative inhaled bronchodilator therapy and is often prescribed in a combination inhaler with the anti-inflammatory corticosteroid fluticasone propionate (FP). [6][7][8][9] This combination of salmeterol and FP (SFC) has demonstrated a broad range of anti-inflammatory effects 10 that are greater than those seen with inhaled corticosteroid (ICS) monotherapy 11 and the likely explanation for this is a molecular interaction (synergy) between the LABA and ICS. 12 The anti-inflammatory and bronchodilator effects of SFC provides greater symptom control, pulmonary function improvement and exacerbation reduction compared with eith...

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Section: Discussionmentioning

confidence: 99%

Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD

Singh

Brooks

Hagan

et al. 2008

Thorax

166

108

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“…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).…”

Section: Symptom-limited Incremental Testmentioning

confidence: 99%

Recommendations on the use of exercise testing in clinical practice

Palange¹,

Ward²,

Carlsen³

et al. 2006

European Respiratory Journal

549

390

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Evidence-based recommendations on the clinical use of cardiopulmonary exercise testing (CPET) in lung and heart disease are presented, with reference to the assessment of exercise intolerance, prognostic assessment and the evaluation of therapeutic interventions (e.g. drugs, supplemental oxygen, exercise training). A commonly used grading system for recommendations in evidence-based guidelines was applied, with the grade of recommendation ranging from A, the highest, to D, the lowest.For symptom-limited incremental exercise, CPET indices, such as peak O 2 uptake (V9O 2 ), V9O 2 at lactate threshold, the slope of the ventilation-CO 2 output relationship and the presence of arterial O 2 desaturation, have all been shown to have power in prognostic evaluation. In addition, for assessment of interventions, the tolerable duration of symptom-limited high-intensity constant-load exercise often provides greater sensitivity to discriminate change than the classical incremental test. Field-testing paradigms (e.g. timed and shuttle walking tests) also prove valuable.In turn, these considerations allow the resolution of practical questions that often confront the clinician, such as: 1) ''When should an evaluation of exercise intolerance be sought?''; 2) ''Which particular form of test should be asked for?''; and 3) ''What cluster of variables should be selected when evaluating prognosis for a particular disease or the effect of a particular intervention?''

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“…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.…”

Section: Introductionmentioning

confidence: 99%