Indacaterol improves lung hyperinflation and physical activity in patients with moderate chronic obstructive pulmonary disease - a randomized, multicenter, double-blind, placebo-controlled study

BMC Pulmonary Medicine

Claus Vogelmeier³  Helgo Magnussen¹  Anne Kirsten¹  Felix Krippner²  Henrik Watz¹ 

[1] Pulmonary Research Institute at LungClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Woehrendamm 80, D-22927 Grosshansdorf, Germany;Novartis Pharma GmbH, Nuremberg, Germany;Department of Respiratory Medicine, University of Marburg, University Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Marburg, Germany

关键词: Physical activity;    Bronchodilator treatment;    Lung hyperinflation;    Chronic obstructive pulmonary disease;   

Others  :  1091920
DOI  :  10.1186/1471-2466-14-158

 received in 2014-07-13, accepted in 2014-09-25,  发布年份 2014

【 摘 要 】

Background

Indacaterol is a long-acting beta-2 agonist for once-daily treatment of COPD. We evaluated the effects of indacaterol 150 μg on lung hyperinflation compared with placebo and open-label tiotropium 18 μg. We measured physical activity during treatment with indacaterol 150 μg and matched placebo.

Methods

We performed a randomized, three-period, cross-over study (21 days of treatment separated by two wash-out periods of 13 days) with indacaterol 150 μg or matching placebo and tiotropium 18 μg. Lung function was assessed by body plethysmography and spirometry. Physical activity was measured for one week by a multisensory armband at the end of both treatment periods with indacaterol/matched placebo. The primary endpoint was peak inspiratory capacity at the end of each treatment period.

Results

129 patients (mean age, 61 years; mean post-bronchodilator FEV₁, 64%), were randomized and 110 patients completed the study. Peak inspiratory capacity was 0.22 L greater with Indacaterol at day 21 compared to placebo (p < 0.001). Similar results were observed for tiotropium. Both bronchodilators also significantly improved other parameters of lung hyperinflation compared with placebo. All parameters of physical activity were significantly increased during treatment with indacaterol versus placebo.

Conclusions

Indacaterol 150 μg improved lung hyperinflation in patients with moderate COPD, which was associated with an increase of physical activity.

Trial registration

ClinicalTrials.gov registration number: NCT01012765.

【 授权许可】

   
2014 Watz et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013, 187:347-365.
• [2]Ferguson GT: Why does the lung hyperinflate? Proc Am Thorac Soc 2006, 3:176-179.
• [3]O’Donnell DE, Laveneziana P: Dyspnea and activity limitation in COPD: mechanical factors. COPD 2007, 4:225-236.
• [4]Garcia-Rio F, Lores V, Mediano O, Rojo B, Hernanz A, Lopez-Collazo E, Alvarez-Sala R: Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation. Am J Respir Crit Care Med 2009, 180:506-512.
• [5]Watz H, Waschki B, Meyer T, Magnussen H: Physical activity in patients with COPD. Eur Respir J 2009, 33:262-272.
• [6]Troosters T, Sciurba F, Battaglia S, Langer D, Valluri SR, Martino L, Benzo R, Andre D, Weisman I, Decramer M: Physical inactivity in patients with COPD, a controlled multi-center pilot-study. Respir Med 2010, 104:1005-1011.
• [7]Garcia-Aymerich J, Farrero E, Felez MA, Izquierdo J, Marrades RM, Anto JM: Risk factors of readmission to hospital for a COPD exacerbation: a prospective study. Thorax 2003, 58:100-105.
• [8]Garcia-Aymerich J, Lange P, Benet M, Schnohr P, Anto JM: Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. Thorax 2006, 61:772-778.
• [9]Pitta F, Troosters T, Probst VS, Spruit MA, Decramer M, Gosselink R: Physical activity and hospitalization for exacerbation of COPD. Chest 2006, 129:536-544.
• [10]Waschki B, Spruit MA, Watz H, Albert PS, Shrikrishna D, Groenen M, Smith C, Man WD, Tal-Singer R, Edwards LD, Calverley PM, Magnussen H, Polkey MI, Wouters EF: Physical activity monitoring in COPD: compliance and associations with clinical characteristics in a multicenter study. Respir Med 2012, 106:522-530.
• [11]Shrikrishna D, Patel M, Tanner RJ, Seymour JM, Connolly BA, Puthucheary ZA, Walsh SL, Bloch SA, Sidhu PS, Hart N, Kemp PR, Moxham J, Polkey MI, Hopkinson NS: Quadriceps wasting and physical inactivity in patients with COPD. Eur Respir J 2012, 40:1115-1122.
• [12]Waschki B, Kirsten A, Holz O, Muller KC, Meyer T, Watz H, Magnussen H: Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest 2011, 140:331-342.
• [13]Garcia-Rio F, Rojo B, Casitas R, Lores V, Madero R, Romero D, Galera R, Villasante C: Prognostic value of the objective measurement of daily physical activity in patients with COPD. Chest 2012, 142:338-346.
• [14]Beier J, Beeh KM: Long-acting beta-adrenoceptor agonists in the management of COPD: focus on indacaterol. Int J Chron Obstruct Pulmon Dis 2011, 6:237-243.
• [15]Han J, Dai L, Zhong N: Indacaterol on dyspnea in chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized placebo-controlled trials. BMC Pulm Med 2013, 13:26. BioMed Central Full Text
• [16]Beeh KM, Wagner F, Khindri S, Drollmann AF: Effect of indacaterol on dynamic lung hyperinflation and breathlessness in hyperinflated patients with COPD. COPD 2011, 8:340-345.
• [17]O’Donnell DE, Casaburi R, Vincken W, Puente-Maestu L, Swales J, Lawrence D, Kramer B: Effect of indacaterol on exercise endurance and lung hyperinflation in COPD. Respir Med 2011, 105:1030-1036.
• [18]Rossi A, Centanni S, Cerveri I, Gulotta C, Foresi A, Cazzola M, Brusasco V: Acute effects of indacaterol on lung hyperinflation in moderate COPD: a comparison with tiotropium. Respir Med 2012, 106:84-90.
• [19]Hataji O, Naito M, Ito K, Watanabe F, Gabazza EC, Taguchi O: Indacaterol improves daily physical activity in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2013, 8:1-5.
• [20]Watz H, Krippner F, Kirsten A, Magnussen H, Vogelmeier C: Effects if indacaterol on lung volumes and physical activity in moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012, 185:A2257.
• [21]Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, Van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G: Standardisation of the measurement of lung volumes. Eur Respir J 2005, 26:511-522.
• [22]Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, Van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, Macintyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J: Standardisation of spirometry. Eur Respir J 2005, 26:319-338.
• [23]Criee CP, Sorichter S, Smith HJ, Kardos P, Merget R, Heise D, Berdel D, Kohler D, Magnussen H, Marek W, Mitfessel H, Rasche K, Rolke M, Worth H, Jorres RA: Body plethysmography–its principles and clinical use. Respir Med 2011, 105:959-971.
• [24]Hill K, Dolmage TE, Woon L, Goldstein R, Brooks D: Measurement properties of the SenseWear armband in adults with chronic obstructive pulmonary disease. Thorax 2010, 65:486-491.
• [25]Van Remoortel H, Raste Y, Louvaris Z, Giavedoni S, Burtin C, Langer D, Wilson F, Rabinovich R, Vogiatzis I, Hopkinson NS, Troosters T: Validity of six activity monitors in chronic obstructive pulmonary disease: a comparison with indirect calorimetry. PLoS One 2012, 7:e39198.
• [26]O’Donnell DE: Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006, 3:180-184.
• [27]Donohue JF: Minimal clinically important differences in COPD lung function. COPD 2005, 2:111-124.
• [28]O’Donnell DE, Fluge T, Gerken F, Hamilton A, Webb K, Aguilaniu B, Make B, Magnussen H: Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J 2004, 23:832-840.
• [29]Celli B, ZuWallack R, Wang S, Kesten S: Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes. Chest 2003, 124:1743-1748.
• [30]Caspersen CJ, Powell KE, Christenson GM: Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 1985, 100:126-131.
• [31]Hartman JE, Boezen HM, De Greef MH, Bossenbroek L, Ten Hacken NH: Consequences of physical inactivity in chronic obstructive pulmonary disease. Expert Rev Respir Med 2010, 4:735-745.
• [32]Wen CP, Wai JP, Tsai MK, Yang YC, Cheng TY, Lee MC, Chan HT, Tsao CK, Tsai SP, Wu X: Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011, 378:1244-1253.
• [33]Troosters T, Van der Molen T, Polkey M, Rabinovich RA, Vogiatzis I, Weisman I, Kulich K: Improving physical activity in COPD: towards a new paradigm. Respir Res 2013, 14:115. BioMed Central Full Text
• [34]Beeh KM, Beier J, Donohue JF: Clinical trial design in chronic obstructive pulmonary disease: current perspectives and considerations with regard to blinding of tiotropium. Respir Res 2012, 13:52. BioMed Central Full Text
• [35]Troosters T, Weisman I, Dobbels F, Giardino N, Valluri SR: Assessing the impact of tiotropium on lung function and physical activity in GOLD stage II COPD patients who are naive to maintenance respiratory therapy: a study protocol. Open Respir Med J 2011, 5:1-9.