albuterol and Dyspnea studies

Albuterol: A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.
albuterol : A member of the class of phenylethanolamines that is 4-(2-amino-1-hydroxyethyl)-2-(hydroxymethyl)phenol having a tert-butyl group attached to the nirogen atom. It acts as a beta-adrenergic agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD).

Research Excerpts

Excerpt	Relevance	Reference
"To determine and define the beneficial effects of heliox-driven albuterol therapy on severe asthma exacerbation and clinical factors that affect greater response."	9.11	Beneficial effects of albuterol therapy driven by heliox versus by oxygen in severe asthma exacerbation. ( Chang, HW; Hsu, CW; Huang, YC; Lee, DL; Lee, H, 2005)
"The efficacy of an antitussive-beta 2-sympathomimetic combination (dextromethorphan-salbutamol) was compared with that of a plain antitussive (dextromethorphan) and a placebo in a double-blind trial in 108 out-patients with cough associated with acute respiratory infection."	9.06	The treatment of acute transient cough: a placebo-controlled comparison of dextromethorphan and dextromethorphan-beta 2-sympathomimetic combination. ( Flygare, U; Karttunen, P; Korhonen, R; Korhonen, T; Majander, R; Seuri, M; Silvasti, M; Tukiainen, H, 1986)
" Study participants were randomly allocated to receive 1 of 3 treatments: once-daily tiotropium bromide 5 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0."	5.51	Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial. ( Aito, H; Jauhola, O; Klemola, T; Koponen, P; Kotaniemi-Syrjänen, A; Mäkelä, MJ; Malmberg, LP; Malmström, K; Pelkonen, AS; Rahiala, E; Sarna, S, 2022)
"Magnesium sulfate has been shown to be an effective treatment in older children with asthma exacerbations, but it has not been investigated in acute severe virus-induced wheezing in young children."	5.27	Intravenous magnesium sulfate for acute wheezing in young children: a randomised double-blind trial. ( Dunder, T; Kallio, M; Pokka, T; Pruikkonen, H; Renko, M; Tapiainen, T; Uhari, M, 2018)
"Subjects with acute exacerbation of asthma (FEV1 <50% predicted following 30 min of standardized treatment: 5 mg nebulized albuterol; 0."	5.19	Repeated dyspnea score and percent FEV1 are modest predictors of hospitalization/relapse in patients with acute asthma exacerbation. ( Ferguson, I; House, SL; Johnson, K; Lewis, LM; Liu, J; Matsuda, K; Schneider, JE, 2014)
" Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes."	5.14	Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD. ( Andrews, WT; Donohue, JF; Goodwin, E; Hanrahan, JP; Huang, H; Mahler, DA; Schaefer, K; Tashkin, DP, 2009)
"The effects of salmeterol and fluticasone propionate, alone or in combination, on PEF and breathlessness are seen within days and most of the obtainable effect on these parameters is reached within 2 weeks."	5.11	Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease. ( Anderson, JA; Calverley, P; Jones, P; Pauwels, R; Vestbo, J, 2005)
"Our results indicate that adding theophylline to standard treatment with inhaled bronchodilators provides additional benefits in stable COPD patients by reducing dynamic pulmonary hyperinflation, improving exercise tolerance, dyspnea and QoL."	5.11	[Clinical and functional benefits of adding theophylline to a standard treatment with short acting bronchodilators in patients with COPD]. ( Borzone, G; Díaz, O; Dreyse, J; Lisboa, C; Silva, F, 2005)
"To determine and define the beneficial effects of heliox-driven albuterol therapy on severe asthma exacerbation and clinical factors that affect greater response."	5.11	Beneficial effects of albuterol therapy driven by heliox versus by oxygen in severe asthma exacerbation. ( Chang, HW; Hsu, CW; Huang, YC; Lee, DL; Lee, H, 2005)
"This study was performed to determine if levalbuterol improves dyspnea as assessed by prehospital clinical parameters."	5.10	Effect of levalbuterol on prehospital patient parameters. ( Rodenberg, H, 2002)
" In a crossover study against placebo, albuterol caused a significant increase in expiratory flow and reduced lung hyperinflation and dyspnea at rest, but this was not associated with differences in symptoms with exercise or any relevant parameter of physical performance."	5.10	Effects of exercise and beta 2-agonists on lung function in chronic obstructive pulmonary disease. ( Barisione, G; Beccaria, M; Brusasco, V; Cerveri, I; Corsico, A; Fulgoni, P; Pellegrino, R; Zoia, MC, 2002)
"We tested the hypothesis that the decrease in dyspnea in patients with COPD with inhaled albuterol is in part due to increased diaphragmatic contractility."	5.09	Does inhaled albuterol improve diaphragmatic contractility in patients with chronic obstructive pulmonary disease? ( Hatipoğlu, U; Laghi, F; Tobin, MJ, 1999)
"To evaluate the impact of a week-long course of inhaled albuterol compared with ipratropium on expiratory peak flow, exercise performance, and dyspnea in patients with stable COPD."	5.08	Is an anticholinergic agent superior to a beta 2-agonist in improving dyspnea and exercise limitation in COPD? ( Blosser, SA; Localio, AR; Maxwell, SL; Reeves-Hoche, MK; Zwillich, CW, 1995)
" The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined."	5.07	Mechanism of bronchodilator effect in chronic airflow limitation. ( Guyatt, GH; Jaeschke, R; Keller, J; Newhouse, MT; Singer, J, 1991)
" Therefore, we examined the performance of the 6-min walk test, a rating of dyspnea following the walk test, and three different questionnaires measuring dyspnea in daily activities, in a controlled trial of inhaled salbutamol and oral theophylline in 24 patients with primary fixed chronic airflow limitation."	5.07	Measuring functional status in chronic lung disease: conclusions from a randomized control trial. ( Guyatt, GH; Keller, J; Nogradi, S; Singer, J; Townsend, M, 1991)
"The efficacy of an antitussive-beta 2-sympathomimetic combination (dextromethorphan-salbutamol) was compared with that of a plain antitussive (dextromethorphan) and a placebo in a double-blind trial in 108 out-patients with cough associated with acute respiratory infection."	5.06	The treatment of acute transient cough: a placebo-controlled comparison of dextromethorphan and dextromethorphan-beta 2-sympathomimetic combination. ( Flygare, U; Karttunen, P; Korhonen, R; Korhonen, T; Majander, R; Seuri, M; Silvasti, M; Tukiainen, H, 1986)
"In a single-blind placebo-controlled trial in 12 patients with advanced chronic obstructive pulmonary disease (COPD) we compared the effects of nebulized salbutamol (1 mg), clenbuterol (30 micrograms) and placebo (4 ml of normal saline) on spirometric indices (FVC, FEV1), maximal expiratory flows (Vmax50 and Vmax25), the distance walked in 6 min (6MD), assessment of breathlessness by visual analogue scale (VAS), and estimates by the patients of perceived exertion (RPE)."	5.06	Effects of beta-agonists on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease. ( Galavotti, V; Papiris, S; Sturani, C, 1986)
" There was high agreement in albuterol use for bronchospasm and epinephrine use in anaphylaxis."	4.12	Variation in Prehospital Protocols for Pediatric Respiratory Distress Management in the United States. ( Martin-Gill, C; McCans, K; Owusu-Ansah, S; Ramgopal, S; Varma, S, 2022)
" Efficacy was measured using serial spirometry, transition dyspnea index (TDI), rescue albuterol use, and St."	3.75	Nebulized formoterol provides added benefits to tiotropium treatment in chronic obstructive pulmonary disease. ( Chaudry, I; Denis-Mize, K; Hanania, NA; McGinty, J; Tashkin, DP, 2009)
" We measured breathlessness at rest, using a Borg scale dyspnea index (BSDI) before and after bronchodilator albuterol [salbutamol] 200 micrograms) in 93 patients with OLD drawn from a larger population undergoing routine spirometry."	3.67	The relationship between pulmonary function and dyspnea in obstructive lung disease. ( Colacone, A; Dajczman, E; Kreisman, H; Wolkove, N, 1989)
"Twenty-eight stable COPD patients had their ILPs and FEV1 measured both before and 2 h after the use of a single dose of 18 mcg bronchodilator tiotropium and 50 mcg salmeterol."	2.79	Effects of long-acting bronchodilators and prednisolone on inspiratory lung function parameters in stable COPD. ( Dekhuijzen, PN; Heijdra, YF; Hop, WC; Ramlal, SK; Visser, FJ, 2014)
"We studied 24 patients with moderate COPD (FEV1 59 ± 9% predicted) after inhalation of ipratropium/salbutamol combination or placebo in a double-blind, crossover design."	2.79	Comparing dynamic hyperinflation and associated dyspnea induced by metronome-paced tachypnea versus incremental exercise. ( Bateman, ED; Bateman, ME; Calligaro, GL; Cooper, CB; Raine, RI, 2014)
"In mild-to-moderate COPD, FSC was associated with significant improvements in airway function at rest and during exercise."	2.78	Effect of fluticasone/salmeterol combination on dyspnea and respiratory mechanics in mild-to-moderate COPD. ( Guenette, JA; O'Donnell, DE; Webb, KA, 2013)
"Exacerbations of COPD (ECOPD) are characterized by increased dyspnea due to dynamic pulmonary hyperinflation."	2.77	Randomized controlled trial of a breath-activated nebulizer in patients with exacerbation of COPD. ( Haynes, JM, 2012)
"Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD)."	2.76	Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison. ( Centanni, S; Dahl, R; Dogra, A; Kornmann, O; Kramer, B; Lassen, C; Owen, R, 2011)
"Indacaterol is a novel, inhaled, ultra-long-acting β(2)-agonist bronchodilator for maintenance use in patients with COPD."	2.76	Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. ( Gale, R; Jones, PW; Kramer, B; Mahler, DA; Owen, R, 2011)
"Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation."	2.76	Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients. ( Aiello, M; Chetta, A; Clini, EM; Crisafulli, E; Nicolini, G; Olivieri, D; Tzani, P, 2011)
"Current guidelines for the treatment of chronic obstructive pulmonary disease (COPD) recommend the use of long-acting bronchodilators in the maintenance management of COPD."	2.74	Efficacy and safety of nebulized formoterol as add-on therapy in COPD patients receiving maintenance tiotropium bromide: Results from a 6-week, randomized, placebo-controlled, clinical trial. ( Boota, A; Denis-Mize, K; Hanania, NA; Kerwin, E; Tomlinson, L, 2009)
"The regression slope of breathlessness as a function of oxygen consumption (primary outcome), mean ratings of breathlessness throughout exercise and peak ratings of breathlessness were significantly higher with naloxone than normal saline."	2.74	Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD. ( Baird, JC; Kraemer, WJ; Mahler, DA; Murray, JA; Ward, J; Waterman, LA; Zhang, X, 2009)
"In severe or very severe COPD patients with relatively fixed airway obstruction bronchodilators enhance exercise performance obtained with oxygen."	2.73	The effect of bronchodilators and oxygen alone and in combination on self-paced exercise performance in stable COPD. ( Calverley, PM; Cortopassi, F; Cukier, A; Ferreira, CA; Ribeiro, M; Stelmach, R, 2007)
"After a 1-week washout, 8 steroid-naïve COPD patients with AATD (ZZ genotype), within a double-blind randomized cross-over study, were assigned to one of the following 16-week treatments: (1) HFA-BDP 400 microg b."	2.73	Inhaled corticosteroids as additional treatment in alpha-1-antitrypsin-deficiency-related COPD. ( Bertella, E; Boni, E; Corda, L; La Piana, GE; Redolfi, S; Tantucci, C, 2008)
"The effect of treatment on FEV1 and breathlessness (using the Borg scale) was measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes after test treatment."	2.72	Onset of relief of dyspnoea with budesonide/formoterol or salbutamol following methacholine-induced severe bronchoconstriction in adults with asthma: a double-blind, placebo-controlled study. ( Aalbers, R; Bantje, TA; Jonkers, RE, 2006)
"Exacerbations of COPD and health resource usage were positively affected by daily treatment with tiotropium."	2.71	Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. ( Brusasco, V; Hodder, R; Kesten, S; Korducki, L; Miravitlles, M; Towse, L, 2003)
"It has been shown that patients with chronic obstructive pulmonary disease (COPD) develop dynamic hyperinflation (DH), which contributes to dyspnoea and exercise intolerance."	2.71	Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD. ( Boveri, B; Carlucci, P; Casanova, F; Cazzola, M; Centanni, S; Di Marco, F; Milic-Emili, J; Santus, P, 2003)
"A total of 67 stable patients with COPD were recruited at the Kyoto University Hospital."	2.71	A comparison of the effects of salbutamol and ipratropium bromide on exercise endurance in patients with COPD. ( Hajiro, T; Mishima, M; Nishimura, K; Oga, T; Sato, S; Tsukino, M, 2003)
"Subjects quantified their sensation of breathlessness during the challenge tests on a modified Borg scale at the start of the study and every 4 weeks thereafter."	2.70	Potential masking effect on dyspnoea perception by short- and long-acting beta2-agonists in asthma. ( Bijl-Hofland, ID; Cloosterman, SG; Folgering, HT; van der Elshout, FJ; van Schayck, CP; Van Weel, C, 2002)
"Dyspnea is a common complaint during daily activities in patients with advanced COPD."	2.69	The cumulative effect of long-acting bronchodilators, exercise, and inspiratory muscle training on the perception of dyspnea in patients with advanced COPD. ( Berar-Yanay, N; Davidovich, A; Magadle, R; Weiner, M; Weiner, P, 2000)
"Comparisons of breathlessness, exercise volumes, and pressures were made at the highest equivalent work load."	2.68	Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. ( Belman, MJ; Botnick, WC; Shin, JW, 1996)
"Dyspnea was measured by the -5 to +5 category scale at rest and by the 0 to 10 category-ratio scale while breathing through inspiratory resistances of 5, 15, and 30 cm H20/L/s."	2.68	Salmeterol reduces dyspnea and improves lung function in patients with COPD. ( Lentine, T; Mahler, DA; Ramirez-Venegas, A; Ward, J, 1997)
"Indacaterol is a once-daily, long-acting β(2)-agonist bronchodilator that improves dyspnoea and health status in patients with moderate-to-severe COPD."	2.49	Effects of long-acting bronchodilators in COPD patients according to COPD severity and ICS use. ( Dahl, R; Decramer, M; Korn, S; Kornmann, O; Lawrence, D; McBryan, D, 2013)
"Indacaterol studies have shown significant improvements in lung function of COPD patients, and these improvements have also translated into clinically meaningful improvements in patient symptoms and HR-QOL."	2.49	Improving the quality of life in patients with chronic obstructive pulmonary disease: focus on indacaterol. ( Feldman, GJ, 2013)
"Treatment with tiotropium bromide has generally improved patients' health-related quality of life, reduced the number of patients suffering from acute exacerbations, decreased the number of hospitalizations, improved dyspnea, and reduced adverse events compared to placebo."	2.49	Ten years of tiotropium: clinical impact and patient perspectives. ( Connolly, MJ; Hanania, NA; Yohannes, AM, 2013)
"In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data."	2.48	Efficacy of indacaterol 75 μg versus fixed-dose combinations of formoterol-budesonide or salmeterol-fluticasone for COPD: a network meta-analysis. ( Capkun-Niggli, G; Cope, S; Jansen, JP; Kraemer, M; Zhang, J, 2012)
"Chronic obstructive pulmonary disease (COPD) is considered one of the most common chronic diseases in the world."	2.43	[The beta2-adrenergic receptor agonists in the treatment of chronic obstructive pulmonary disease]. ( Chorostowska-Wynimko, J, 2005)
"Chronic obstructive pulmonary disease (COPD) is a common disease with a global impact in terms of morbidity and mortality."	2.43	Improving dyspnea in chronic obstructive pulmonary disease: optimal treatment strategies. ( Rabe, KF, 2006)
"Subjects hospitalized with a COPD exacerbation participated in a comparative clinical effectiveness study of 2 methods of nebulization."	1.91	Response to Bronchodilators Administered via Different Nebulizers in Patients With COPD Exacerbation. ( Alsaid, A; Costello, RW; Cushen, B; Greene, G, 2023)
"Dyspnea has been reported to be a main contributor to exercise avoidance in asthma."	1.48	Exertional dyspnea and operating lung volumes in asthma. ( Bhutani, M; Brotto, AR; Moore, LE; Phillips, DB; Stickland, MK, 2018)
"Life-threatening anaphylactic shock is a rare (1 in 1 million) but documented occurrence in response to subcutaneous immunotherapy."	1.48	Neurologic manifestations in anaphylaxis due to subcutaneous allergy immunotherapy: A case report. ( Mangold, M; Qureshi, M, 2018)
"Physically inactive patients with chronic obstructive pulmonary disease (COPD) exhibit higher rates of exacerbations and symptoms of dyspnoea than active patients."	1.42	Physical activity in COPD patients decreases short-acting bronchodilator use and the number of exacerbations. ( Katajisto, M; Kilpeläinen, M; Koskela, J; Laitinen, T; Lindqvist, A, 2015)
"COPD is commonly diagnosed and treated in patients without airflow obstruction."	1.37	Disease severity and symptoms among patients receiving monotherapy for COPD. ( Bailey, W; Crater, G; Dransfield, MT; Emmett, A; O'Dell, DM; Yawn, B, 2011)
"Patients with COPD are frequently prescribed inhaled corticosteroids (ICS); however, it is unclear whether the treatment with ICS might modify responses to inhaled bronchodilators."	1.34	Outcomes in COPD patients receiving tiotropium or salmeterol plus treatment with inhaled corticosteroids. ( Hodder, R; Kesten, S; Menjoge, S; Viel, K, 2007)
" According to the dose-response curve to methacholine, they were categorized as having either unlimited airway narrowing (UAN group) (n = 20) or response plateau (RP group) (n = 18)."	1.33	Dyspnea perception and reversibility of methacholine-induced unlimited airway narrowing in asthmatics. ( Malakauskas, K; Sakalauskas, R; Sitkauskiene, B; Stravinskaite, K, 2006)
"The EFL in bronchial asthma patients is reversible after bronchodilator administration."	1.33	[Expiratory flow limitation detected by negative expiratory pressure in patients with bronchial asthma]. ( Chen, AH; Chen, RC; Li, JM; Liu, Q; Zhang, NF; Zhong, NS, 2006)
"Chronic obstructive pulmonary disease (COPD) is characterized by the lack or only slight reversibility of obstruction which can be assessed by spirometry after inhalation of short-acting beta 2-mimetic (e."	1.32	[Influence of orthopnoea position on spirometric and plethysmographic parameters in patients with chronic obstructive pulmonary disease ]. ( Krzyzowski, G; Pierzchała, W; Szulakowski, P; Trzaska, M, 2003)
"Patients with COPD with EFL may experience less breathlessness after a bronchodilator, at least during light exercise, than those without EFL."	1.31	Volume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest. ( Boni, E; Chiroli, P; Corda, L; Damiani, GP; Franchini, D; Grassi, V; Pini, L; Tantucci, C, 2002)
" These aerosolized medications are not without the potential for adverse effects."	1.29	Unexpected adverse effects of Freon 11 and Freon 12 as medication propellants. ( Oenbrink, RJ, 1993)
" Bronchial lability was characterized by (1) variability in mean daily peak expiratory flow rate and (2) bronchial responsiveness to either carbachol (as assessed by the threshold dose and the slope of the dose-response curve) or salbutamol (as assessed by the threshold dose and maximal response)."	1.28	Relationship between spontaneous dyspnoea and lability of airway obstruction in asthma. ( Lockhart, A; Marsac, J; Peiffer, C; Razzouk, H; Toumi, M, 1992)

Research

Studies (131)

Authors

Clinical Trials (23)

Trial Overview

Trial Outcomes

Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough)

Timeframe	Studies, this research(%)	All Research%
pre-1990	10 (7.63)	18.7374
1990's	18 (13.74)	18.2507
2000's	62 (47.33)	29.6817
2010's	36 (27.48)	24.3611
2020's	5 (3.82)	2.80

Authors	Studies
McCans, K	1
Varma, S	1
Ramgopal, S	1
Martin-Gill, C	1
Owusu-Ansah, S	1
Kotaniemi-Syrjänen, A	1
Klemola, T	1
Koponen, P	1
Jauhola, O	1
Aito, H	1
Malmström, K	1
Malmberg, LP	1
Rahiala, E	1
Sarna, S	1
Pelkonen, AS	1
Mäkelä, MJ	1
Cushen, B	1
Alsaid, A	1
Greene, G	1
Costello, RW	1
Codispoti, CD	1
Bandi, S	1
Patel, P	1
Mahdavinia, M	1
Hodroge, SS	1
Glenn, M	1
Breyre, A	1
Lee, B	1
Aldridge, NR	1
Sporer, KA	1
Koenig, KL	1
Gausche-Hill, M	1
Salvucci, AA	1
Rudnick, EM	1
Brown, JF	1
Gilbert, GH	1
Sauer, R	1
Griff, S	1
Blau, A	1
Franke, A	1
Mairinger, T	1
Grah, C	1
Banzett, RB	1
Schwartzstein, RM	2
Lansing, RW	1
O'Donnell, CR	1
O'Donnell, DE	3
Elbehairy, AF	1
Faisal, A	1
Neder, JA	1
Webb, KA	3
Pruikkonen, H	1
Tapiainen, T	1
Kallio, M	1
Dunder, T	1
Pokka, T	1
Uhari, M	1
Renko, M	1
Mangold, M	1
Qureshi, M	1
Moore, LE	1
Brotto, AR	1
Phillips, DB	1
Bhutani, M	1
Stickland, MK	1
Guenette, JA	1
Feldman, GJ	1
Yohannes, AM	1
Connolly, MJ	1
Hanania, NA	4
Nuijsink, M	1
Hop, WC	2
Jongste, JC	1
Sterk, PJ	1
Duiverman, AE	1
Bel, EH	1
Baldi, BG	1
de Albuquerque, AL	1
Pimenta, SP	1
Salge, JM	1
Kairalla, RA	1
Carvalho, CR	1
Ramlal, SK	1
Visser, FJ	1
Dekhuijzen, PN	1
Heijdra, YF	1
Calligaro, GL	1
Raine, RI	1
Bateman, ME	1
Bateman, ED	1
Cooper, CB	1
Kaplan, A	1
Gruffydd-Jones, K	1
van Gemert, F	1
Kirenga, BJ	1
Medford, AR	1
Schrimpf, M	1
Steudter, E	1
Schneider, JE	1
Lewis, LM	1
Ferguson, I	1
House, SL	1
Liu, J	1
Matsuda, K	1
Johnson, K	1
Bhatt, SP	1
Wells, JM	1
Kim, V	1
Criner, GJ	1
Hersh, CP	1
Hardin, M	1
Bailey, WC	1
Nath, H	1
Kim, YI	1
Foreman, MG	1
Stinson, DS	1
Wilson, CG	1
Rennard, SI	1
Silverman, EK	1
Make, BJ	1
Dransfield, MT	2
Katajisto, M	1
Koskela, J	1
Lindqvist, A	1
Kilpeläinen, M	1
Laitinen, T	1
Füeßl, HS	1
Perez, T	2
Chanez, P	1
Dusser, D	1
Devillier, P	1
Burgel, PR	1
Le Gros, V	1
Decuypère, L	1
Bourdeix, I	1
Deslée, G	1
Richie, RC	1
Singh, AK	1
Gaur, S	1
Kumar, R	1
Ramnarayan, P	1
Chhabra, R	1
Maheshwari, P	1
Tashkin, DP	3
Donohue, JF	3
Mahler, DA	8
Huang, H	1
Goodwin, E	1
Schaefer, K	1
Hanrahan, JP	2
Andrews, WT	1
Murray, JA	1
Waterman, LA	1
Ward, J	4
Kraemer, WJ	1
Zhang, X	1
Baird, JC	2
Boota, A	1
Kerwin, E	1
Tomlinson, L	1
Denis-Mize, K	2
Mukhopadhyay, A	1
Dela Pena, E	1
Wadden, B	1
Procyshyn, M	1
Keang Lim, T	1
Hayes, D	1
Kriss, VM	1
Iocono, JA	1
Dixon, BJ	1
Collins, PB	1
Ballard, HO	1
Pasqua, F	1
Biscione, G	1
Crigna, G	1
Auciello, L	1
Cazzola, M	4
McGinty, J	1
Chaudry, I	1
Cevik, Y	1
Onay, M	1
Akmaz, I	1
Sezigen, S	1
van Noord, JA	1
Aumann, JL	1
Janssens, E	1
Smeets, JJ	1
Zaagsma, J	1
Mueller, A	1
Cornelissen, PJ	1
Kornmann, O	2
Dahl, R	2
Centanni, S	2
Dogra, A	1
Owen, R	2
Lassen, C	1
Kramer, B	2
Bailey, W	1
Crater, G	1
Emmett, A	2
O'Dell, DM	1
Yawn, B	1
Ozier, A	1
Girodet, PO	1
Bara, I	1
Tunon de Lara, JM	1
Marthan, R	1
Berger, P	1
Jones, PW	2
Gale, R	1
Diba, C	1
King, GG	1
Berend, N	1
Salome, CM	1
Tzani, P	1
Crisafulli, E	1
Nicolini, G	1
Aiello, M	1
Chetta, A	1
Clini, EM	1
Olivieri, D	1
Haynes, JM	1
Marrero, E	1
Cope, S	1
Kraemer, M	1
Zhang, J	1
Capkun-Niggli, G	1
Jansen, JP	1
Haran, M	1
Schattner, A	1
Mate, A	1
Starobin, D	1
Haran, G	1
Shtalrid, M	1
Decramer, M	2
Korn, S	1
Lawrence, D	1
McBryan, D	1
Rodenberg, H	1
Sanjuás, C	1
Corsico, A	1
Fulgoni, P	1
Beccaria, M	1
Zoia, MC	1
Barisione, G	1
Pellegrino, R	1
Brusasco, V	2
Cerveri, I	1
Fraser, J	1
Kamps, AW	1
Brand, PL	1
Di Marco, F	1
Milic-Emili, J	1
Boveri, B	1
Carlucci, P	1
Santus, P	1
Casanova, F	1
Witek, TJ	2
Pershad, J	1
Chin, T	1
Hodder, R	2
Miravitlles, M	1
Korducki, L	1
Towse, L	1
Kesten, S	2
Oga, T	1
Nishimura, K	1
Tsukino, M	1
Sato, S	1
Hajiro, T	1
Mishima, M	1
Weiner, P	2
Magadle, R	2
Beckerman, M	1
Berar-Yanay, N	2
Aguilaniu, B	1
Krzyzowski, G	1
Szulakowski, P	1
Trzaska, M	1
Pierzchała, W	1
Witte, KK	1
Morice, A	1
Cleland, JG	1
Clark, AL	1
Calverley, PM	2
Kalberg, C	1
Merchant, K	1
Knobil, K	2
van der Woude, HJ	2
Postma, DS	1
Politiek, MJ	1
Winter, TH	1
Aalbers, R	3
Vestbo, J	1
Pauwels, R	1
Anderson, JA	1
Jones, P	1
Calverley, P	1
Fierro-Carrion, G	1
Mejia-Alfaro, R	1
Lee, DL	1
Hsu, CW	1
Lee, H	1
Chang, HW	1
Huang, YC	1
Dreyse, J	1
Silva, F	1
Díaz, O	1
Borzone, G	1
Lisboa, C	1
Stockley, RA	1
Chopra, N	1
Rice, L	1
Chorostowska-Wynimko, J	1
Lampert, S	1
Schmid, A	1
Wiest, G	1
Hahn, EG	1
Ficker, JH	1
Rabe, KF	1
Brown, RA	1
Allegra, L	1
Matera, MG	1
Page, CP	2
Malakauskas, K	1
Sitkauskiene, B	1
Stravinskaite, K	1
Sakalauskas, R	1
Sciurba, F	1
Celli, B	1
Kalberg, CJ	1
Cukier, A	1
Ferreira, CA	1
Stelmach, R	1
Ribeiro, M	1
Cortopassi, F	1
Ohm, R	1
Aaronson, LS	1
Gabriella Matera, M	1
Jonkers, RE	1
Bantje, TA	1
Lehmann, S	1
Bakke, PS	1
Eide, GE	1
Gulsvik, A	1
Zhang, NF	1
Chen, AH	1
Chen, RC	1
Li, JM	1
Liu, Q	1
Zhong, NS	1
Baumgartner, RA	1
Calhoun, WJ	1
Sahn, SA	1
Sciarappa, K	1
Menjoge, S	1
Viel, K	1
Brouillard, C	1
Pepin, V	1
Milot, J	1
Lacasse, Y	1
Maltais, F	1
Corda, L	2
Bertella, E	1
La Piana, GE	1
Boni, E	2
Redolfi, S	1
Tantucci, C	2
Stark, RD	1
Gambles, SA	1
Manzini, S	1
Perretti, F	1
Abelli, L	1
Evangelista, S	1
Seeds, EA	1
Subratty, AH	1
Zehner, WJ	1
Scott, JM	1
Iannolo, PM	1
Ungaro, A	1
Terndrup, TE	1
Blosser, SA	1
Maxwell, SL	1
Reeves-Hoche, MK	1
Localio, AR	1
Zwillich, CW	1
Laliberté, M	1
Sanfaçon, G	1
Blais, R	1
Oenbrink, RJ	1
Belman, MJ	1
Botnick, WC	1
Shin, JW	1
Teramoto, S	1
Fukuchi, Y	1
Ouchi, Y	1
Maury, E	1
Ioos, V	1
Lepecq, B	1
Guidet, B	1
Offenstadt, G	1
Ramirez-Venegas, A	1
Lentine, T	2
Słomka, A	1
Moy, ML	1
Lantin, ML	1
Harver, A	1
Hatipoğlu, U	1
Laghi, F	1
Tobin, MJ	1
Samet, A	1
Bayoumeu, F	1
Longrois, D	1
Laxenaire, MC	1
Jang, AS	1
Choi, IS	1
Park, CS	1
Karras, DJ	1
Sammon, ME	1
Terregino, CA	1
Lopez, BL	1
Griswold, SK	1
Arnold, GK	1
Heyse-Moore, L	1
Beynon, T	1
Ross, V	1
Taube, C	2
Lehnigk, B	1
Paasch, K	1
Kirsten, DK	1
Jörres, RA	2
Magnussen, H	2
Davidovich, A	1
Weiner, M	1
Casaburi, R	1
Briggs, DD	1
Serby, CW	1
Menjoge, SS	1
Ayers, ML	1
Mejia, R	1
Holz, O	1
Mücke, M	1
van Schayck, CP	1
Bijl-Hofland, ID	1
Cloosterman, SG	1
Folgering, HT	1
van der Elshout, FJ	1
Van Weel, C	1
Willaert, W	1
Daenen, M	1
Bomans, P	1
Verleden, G	1
Franchini, D	1
Chiroli, P	1
Damiani, GP	1
Pini, L	1
Grassi, V	1
Vialatte, J	1
Mannino, F	1
Mancini, G	1
König, P	1
Cesco, G	1
Peiffer, C	1
Toumi, M	1
Razzouk, H	1
Marsac, J	1
Lockhart, A	1
Guyatt, GH	3
Townsend, M	2
Keller, J	2
Singer, J	2
Nogradi, S	2
Jaeschke, R	1
Newhouse, MT	2
Taurand, P	1
Wolkove, N	1
Dajczman, E	1
Colacone, A	1
Kreisman, H	1
Pugsley, SO	1
Keller, JL	1
Papiris, S	1
Galavotti, V	1
Sturani, C	1
Tukiainen, H	1
Karttunen, P	1
Silvasti, M	1
Flygare, U	1
Korhonen, R	1
Korhonen, T	1
Majander, R	1
Seuri, M	1
Kerr, JW	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Efficacy of Intermittent Tiotropium in Early Childhood Wheezing[NCT03199976]	Phase 4	80 participants (Actual)	Interventional	2016-04-20	Completed
The Efficacy of Intravenous Magnesium in Acute Wheezy Bronchitis in Small Children - a Randomized, Controlled Study[NCT01383655]		61 participants (Actual)	Interventional	2011-03-31	Completed
MN-221-CL-007: A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of MN-221 When Administered Intravenously as an Adjunct to Standard Therapy to Adults With an Acute Exacerbation of Asthma[NCT00838591]	Phase 2	176 participants (Actual)	Interventional	2009-03-31	Completed
Evaluation of the Prevalence and the Reversibility of the Lung Hyperinflation in Uncontrolled Persistent Asthmatic Patients With Dyspnea[NCT01573364]		450 participants (Actual)	Observational	2011-02-28	Completed
Study of the Predictive Value of Airway Obstruction Reversibility on the Effectiveness of Indacaterol (Onbrez® Breezhaler ®) 150 mcg Once Daily in Patients With Moderate to Severe COPD[NCT01272362]	Phase 4	625 participants (Actual)	Interventional	2010-04-30	Completed
A Two-Week, Randomized, Modified-Blind, Double-Dummy, Parallel-Group Efficacy and Safety Study of Arformoterol Tartrate Inhalation Solution Twice-Daily, Tiotropium Once-Daily, and Arformoterol Tartrate Inhalation Solution Twice-Daily and Tiotropium Once D[NCT00424528]	Phase 4	235 participants (Actual)	Interventional	2006-12-31	Completed
Role of Endorphins in the Perception of Dyspnea in Patients With Chronic Obstructive Pulmonary Disease[NCT00458419]		17 participants (Actual)	Interventional	2005-09-30	Completed
A 6-Week Trial to Compare the Efficacy and Safety of Concomitant Treatment With Formoterol Fumarate Inhalation Solution 20 Mcg Twice Daily and Tiotropium 18 Mcg Once Daily to Tiotropium 18 Mcg Once Daily Alone in the Treatment of Patients With Chronic Obs[NCT00507234]	Phase 3	128 participants (Actual)	Interventional	2007-03-31	Completed
A Remotely Supervised Exercise Program for Lung Cancer Patients Undergoing Chemoradiation[NCT03500393]		4 participants (Actual)	Interventional	2018-06-22	Terminated (stopped due to feasibility of study recruitment)
An Evaluation of Lung Function and Symptoms in Patients With Chronic Obstructive Pulmonary Disease (COPD) on Long-Acting Bronchodilator Monotherapy[NCT00791518]		1,084 participants (Actual)	Observational	2008-12-31	Completed
A 26-week Treatment, Multicenter, Randomized, Double Blind, Double Dummy, Placebo-controlled, Adaptive, Seamless, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of Two Doses of Indacaterol (Selected From 75, 150, 300 & 600 µg o.d.) i[NCT00463567]	Phase 2/Phase 3	2,059 participants (Actual)	Interventional	2007-04-30	Completed
A 26-week Treatment, Multi-center, Randomized, Double-blind, Double- Dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, and Safety of Indacaterol (150 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease, Using Salmeterol ([NCT00567996]	Phase 3	1,002 participants (Actual)	Interventional	2007-11-30	Completed
A 52-week Treatment, Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol (300 and 600 µg Once Daily) in Patients With Chronic Obstructive Pulmonary D[NCT00393458]	Phase 3	1,732 participants (Actual)	Interventional	2006-10-31	Completed
A Phase 4, Randomized, Double-blind, Multicenter, Placebo-Controlled Two Way Cross-Over Study to Evaluate Changes in Oxygen Consumption and Cardiac Function in COPD Patients With Resting Hyperinflation After Administration of Symbicort pMDI 160/4.5 μg.[NCT02533505]	Phase 4	51 participants (Actual)	Interventional	2015-08-25	Completed
A 6-week, Multicenter, Randomized, Double-blind, Placebo and Active-controlled, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF 5259 pMDI (HFA Glycopyrronium Bromide Via Pressurized Metered Dose Inhaler) in Subject[NCT03084796]	Phase 2	733 participants (Actual)	Interventional	2017-07-28	Completed
The Effect of Neck Stabilization Exercise Plus Cardiopulmonary Rehabilitation on Pulmonary Function of SCI[NCT04500223]		13 participants (Actual)	Interventional	2020-04-01	Completed
A Prospective, Randomized, Controlled, Single Center Trial of the Use of Heliox in Children Admitted to the Hospital With Status Asthmaticus[NCT00410150]	Phase 2	42 participants (Actual)	Interventional	2006-04-30	Terminated (stopped due to Study was stopped after interim analysis and slow enrollment.)
The Cardiopulmonary Effect of Inhaled Beta-2-agonists on Adult Ventrucular Septal Defect Patients With Persistant or Surgically Corrected Conditions - The VENTI Trial[NCT02914652]	Phase 4	96 participants (Actual)	Interventional	2016-10-15	Completed
Adiposity and Airway Inflammation in HIV-Associated Airway Disease[NCT02975258]		102 participants (Actual)	Observational	2015-09-30	Completed
Effects of Expiratory Positive Airway Pressure on Dyspnea and Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease[NCT02566915]		19 participants (Anticipated)	Interventional	2015-08-31	Enrolling by invitation
The Various Effects of Gaseous Albuterol on Serum Lactate[NCT02073747]		28 participants (Actual)	Interventional	2015-04-30	Completed
Change of Inspiratory Peak Flow After Bronchial Dilatation on Patients With Moderate to Severe COPD[NCT00561886]	Phase 4	40 participants (Actual)	Interventional	2007-04-30	Completed
The RETORNUS Study: Dual Training to Restore the Function of Respiratory Muscles in Stroke Patients[NCT02125760]		129 participants (Actual)	Interventional	2011-03-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trough FEV1 is defined as the measurement collected approximately 24 hours after the first in-clinic double-blind dose at Week 0. Change is calculated as Week 2 24 hour post first dose FEV1 - Week 0 pre-first dose FEV1. (NCT00424528)
Timeframe: Following 2 weeks of dosing

Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing

Intervention	Liters (Mean)
Arformoterol 15 Mcg Twice Daily	0.086
Tiotropium 18 Mcg Once Daily	0.080
Arformoterol /Tiotropium	0.154

Trough Inspiratory Capacity is defined as the measurement collected approximately 24 hours after the first in clinic double-blind treatment dose at week 0. Change is calculated as Week 2 24 hr post dose IC - Week 0 pre first dose IC. (NCT00424528)
Timeframe: 2 weeks

Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score

Intervention	Liters (Mean)
Arformoterol 15 Mcg Twice Daily	0.074
Tiotropium 18 Mcg Once Daily	0.023
Arformoterol /Tiotropium	0.150

A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important. (NCT00424528)
Timeframe: 2 weeks

Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score

Intervention	Participants (Number)
Arformoterol 15 Mcg Twice Daily	50
Tiotropium 18 Mcg Once Daily	44
Arformoterol /Tiotropium	60

A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important. (NCT00424528)
Timeframe: 2 weeks

Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B)

Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks

Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks

Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B)

Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B)

Transition Dyspnea Index (TDI) Focal Score

Intervention	Percentage of participants (Number)
Arformoterol 15 Mcg Twice Daily	66.67
Tiotropium 18 Mcg Once Daily	57.14
Arformoterol /Tiotropium	77.92

Intervention	Liters (Mean)
Arformoterol 15 Mcg Twice Daily	0.094
Tiotropium 18 Mcg Once Daily	0.054
Arformoterol /Tiotropium	0.217

Intervention	Hours (Median)
Arformoterol 15 Mcg Twice Daily	0.39
Tiotropium 18 Mcg Once Daily	0.72
Arformoterol /Tiotropium	0.17

Intervention	Hours (Median)
Arformoterol 15 Mcg Twice Daily	0.76
Tiotropium 18 Mcg Once Daily	1.29
Arformoterol /Tiotropium	0.39

Intervention	Liters (Mean)
Arformoterol 15 Mcg Twice Daily	0.118
Tiotropium 18 Mcg Once Daily	0.130
Arformoterol /Tiotropium	0.242

Intervention	Liters (Mean)
Arformoterol 15 Mcg Twice Daily	0.104
Tiotropium 18 Mcg Once Daily	0.080
Arformoterol /Tiotropium	0.221

TDI Focal score (range -9 to 9) is defined as the sum of function impairment, magnitude of task, and magnitude of effort (each on a -3 to 3 scale). A score of -9 is maximum worsening and 9 is maximum improvement. (NCT00424528)
Timeframe: 2 weeks

Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication

Intervention	Units on a scale (Mean)
Arformoterol 15 Mcg Twice Daily	2.28
Tiotropium 18 Mcg Once Daily	1.79
Arformoterol /Tiotropium	3.13

Baseline is FEV1 measurement collected prior to the first double-blind dose at week 0. Change defined as Week 0 FEV1 - Week 2 pre first dose FEV1. (NCT00424528)
Timeframe: 2 weeks

Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication

Intervention	Liters (Mean)
	Week 0: immediately post first dose; N=76, 78, 78	Week 0: 30 minutes post first dose; N=75, 78, 76	Week 0: 1 hour post first dose; N=75, 78, 77	Week 0: 2 hours post first dose; N=76, 78, 77	Week 0: 4 hours post first dose; N=75, 77, 77	Week 0: 6 hours post first dose; N=72, 74, 77	Week 0: 8 hours post first dose; N=70, 73, 77	Week 0: 10 hours post first dose; N=69, 71, 76	Week 0: 12 hours post first dose; N=69, 71, 75	Week 2: immediately post first dose; N=71, 75, 74	Week 2: 30 minutes post first dose; N=70, 74, 74	Week 2: 1 hour post first dose; N=71, 75, 73	Week 2: 2 hours post first dose; N=71, 73, 74	Week 2: 4 hours post first dose; N=69, 72, 74	Week 2: 6 hours post first dose; N=69, 72, 73	Week 2: 8 hours post first dose; N=69, 70, 74	Week 2: 10 hours post first dose; N=69, 71, 71	Week 2: 12 hours post first dose; N=63, 67, 71	Week 2: immediately post second dose; N=65, 67, 72	Week 2: 12.5 hours post first dose; N=65, 66, 72	Week 2: 13 hours post first dose; N=63, 68, 72	Week 2: 14 hours post first dose; N=65, 71, 72	Week 2: 16 hours post first dose; N=63, 70, 71	Week 2: 23 hours post first dose; N=70, 74, 74	Week 2: 24 hours post first dose; N=69, 73, 74
Arformoterol /Tiotropium	0.139	0.183	0.189	0.239	0.223	0.214	0.194	0.190	0.199	0.240	0.280	0.308	0.330	0.279	0.266	0.220	0.205	0.189	0.235	0.270	0.272	0.292	0.240	0.145	0.154
Arformoterol 15 Mcg Twice Daily	0.132	0.163	0.182	0.193	0.155	0.128	0.102	0.101	0.044	0.154	0.188	0.185	0.213	0.154	0.123	0.067	0.054	0.035	0.115	0.143	0.159	0.182	0.114	0.040	0.086
Tiotropium 18 Mcg Once Daily	-0.20	0.056	0.106	0.140	0.120	0.125	0.109	0.111	0.094	0.066	0.126	0.163	0.195	0.164	0.143	0.138	0.109	0.101	0.040	0.063	0.061	0.068	0.048	-0.006	0.080

Baseline is FEV1 collected prior to first double-blind dose at week 0. Change is defined as Week 0 FEV1 percent predicted - Week 2 pre first dose FEV1 percent predicted. (NCT00424528)
Timeframe: 2 weeks

Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint

Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week

Intervention	Percent of predicted FEV1 (Mean)
	Week 0: Immediately post first dose; N=76, 78, 78	Week 0: 30 minutes post first dose; N=75, 78, 76	Week 0: 1 hour post first dose; N-75, 78, 77	Week 0: 2 hours post first dose; N=76, 78, 77	Week 0: 4 hours post first dose; N=75, 77, 77	Week 0: 6 hours post first dose; N=72, 74, 77	Week 0: 8 hours post first dose; N=70, 73, 77	Week 0: 10 hours post first dose; N=69, 71, 76	Week 0: 12 hours post first dose; N=69, 71, 75	Week 2: Immediately post first dose; N=71, 75, 74	Week 2: 30 minutes post first dose; N=70, 74, 74	Week 2: 1 hour post first dose; N=71, 75, 73	Week 2: 2 hours post first dose; N=71, 73, 74	Week 2: 4 hours post first dose; N=69, 72, 74	Week 2: 6 hours post first dose; N=69, 72, 73	Week 2: 8 hours post first dose; N=69, 70, 74	Week 2: 10 hours post first dose; N=69, 71, 71	Week 2: 12 hours post first dose; N=63, 67, 71	Week 2: Immediately post second dose; N=65, 67, 72	Week 2: 12.5 hours post first dose; N=65, 66, 72	Week 2: 13 hours post first dose; N=63, 68, 72	Week 2: 14 hours post first dose; N=65, 71, 72	Week 2: 16 hours post first dose; N=63, 70, 71	Week 2: 23 hours post first dose; N=70, 74, 74	Week 2: 24 hours post first dose; N=69, 73, 74
Arformoterol /Tiotropium	4.7	6.1	6.3	8.1	7.5	7.3	6.6	6.5	6.7	8.0	9.3	10.2	11.0	9.2	8.8	7.4	6.8	6.3	7.8	9.0	9.1	9.8	8.0	4.8	5.2
Arformoterol 15 Mcg Twice Daily	4.3	5.5	6.1	6.6	5.3	4.4	3.5	3.3	1.6	5.1	6.2	6.2	7.1	5.1	4.0	2.0	1.8	1.3	3.8	4.9	5.4	6.0	3.9	1.3	2.8
Tiotropium 18 Mcg Once Daily	-0.6	2.0	3.5	4.7	4.0	4.1	3.5	3.7	2.9	1.9	4.0	5.2	6.3	5.1	4.7	4.4	3.5	3.4	1.1	2.0	1.8	2.0	1.4	-0.2	2.6

Intervention	Liters (Mean)
	Week 0: Immediately post first dose; N=76, 78, 78	Week 0: 30 minutes post first dose; N=75, 78, 76	Week 0: 1 hour post first dose; N=75, 78, 77	Week 0: 2 hours post first dose; N=76, 78, 77	Week 0: 4 hours post first dose; N=75, 77, 77	Week 0: 6 hours post first dose; N=72, 74, 77	Week 0: 8 hours post first dose; N=70, 73, 77	Week 0: 10 hours post first dose; N=69, 71, 76	Week 0: 12 hours post first dose; N=69, 71, 75	Week 2: Immediately post first dose; N=71, 75, 74	Week 2: 30 minutes post first dose; N=70, 74, 74	Week 2: 1 hour post first dose; N=71, 75, 73	Week 2: 2 hours post first dose; N=71, 73, 74	Week 2: 4 hours post first dose; N=69, 72, 74	Week 2: 6 hours post first dose; N=69, 72, 73	Week 2: 8 hours post first dose; N=69, 70, 74	Week 2: 10 hours post first dose; N=69, 71, 71	Week 2: 12 hours post first dose; N=63, 67, 71	Week 2: Immediately post second dose; N=65, 67, 72	Week 2: 12.5 hours post first dose; N=65, 66, 72	Week 2: 13 hours post first dose; N=63, 68, 72	Week 2: 14 hours post first dose; N=65, 71, 72	Week 2: 16 hours post first dose; N=63, 70, 71	Week 2: 23 hours post first dose; N=70, 74, 74	Week 2: 24 hours post first dose; N=69, 73, 74
Arformoterol /Tiotropium	0.259	0.323	0.351	0.429	0.392	0.371	0.338	0.346	0.344	0.389	0.461	0.487	0.526	0.461	0.413	0.349	0.323	0.301	0.360	0.399	0.424	0.459	0.374	0.226	0.250
Arformoterol 15 Mcg Twice Daily	0.276	0.312	0.344	0.376	0.291	0.242	0.207	0.209	0.131	0.293	0.343	0.350	0.380	0.265	0.202	0.136	0.098	0.087	0.210	0.262	0.307	0.343	0.215	0.082	0.138
Tiotropium 18 Mcg Once Daily	-0.031	0.122	0.197	0.248	0.206	0.195	0.159	0.175	0.146	0.055	0.203	0.224	0.290	0.221	0.209	0.214	0.158	0.124	0.034	0.087	0.082	0.110	0.098	-0.011	0.115

Overall: Average of the levalbuterol usage in days per week over the 2 week period. Mean number of days/week=number of days levalbuterol used during time period, divided by number of days in the period, multiplied by 7. An actuation is one puff of levalbuterol. (NCT00424528)
Timeframe: 2 weeks

Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day

Intervention	Days per week (Mean)
	Baseline: Number of days used per week	Overall: Number of days used per week
Arformoterol /Tiotropium	4.57	1.38
Arformoterol 15 Mcg Twice Daily	4.44	2.16
Tiotropium 18 Mcg Once Daily	4.27	1.94

Overall: Average of the usage in number of actuations per day over the 2 week period. An actuation is one puff of levalbuterol. Mean number of actuations/day=number actuations used during time period, divided by number of days in time period. (NCT00424528)
Timeframe: 2 weeks

Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline

Intervention	Actuations per day (Mean)
	Baseline: Number of actuations per day	Overall: Number of actuations per day
Arformoterol /Tiotropium	3.08	0.68
Arformoterol 15 Mcg Twice Daily	3.24	1.18
Tiotropium 18 Mcg Once Daily	2.77	1.00

12 hour peak change in FEV1 is defined as maximum of the post dose changes through the nominal 12 hour assessment. (NCT00424528)
Timeframe: 2 weeks

Mean mMRC Dyspnea Scale Scores for Participants With Post-albuterol FEV1 <50% and >=50%

Intervention	Liters (Mean)
	Week 0; N=76, 79, 78	Week 2; N=71, 75, 74
Arformoterol /Tiotropium	0.311	0.379
Arformoterol 15 Mcg Twice Daily	0.264	0.273
Tiotropium 18 Mcg Once Daily	0.218	0.265

The 5-point mMRC Dyspnea Scale measures the level of dyspnea (trouble breathing) experienced by participants. Scores range from 0 (none) to 4 (very severe). (NCT00791518)
Timeframe: Day 1 of a 1-day study

Mean Modified Medical Research Council (mMRC) Dyspnea Scale Scores for Participants With Post-albuterol FEV1 <80% and >=80%

Intervention	points on a scale (Mean)
Participants With Diagnosed COPD and Post-albuterol FEV1 <50%	1.9
Participants With Diagnosed COPD and Post-albuterol FEV1 >=50%	1.6

Mean Number of Puffs From All Short-acting Bronchodilators Used in the Past Two Weeks in Participants With an FEV1 of <50% and >=50%

Intervention	points on a scale (Mean)
Participants With Diagnosed COPD and Post-albuterol FEV1 <80%	1.7
Participants With Diagnosed COPD and Post-albuterol FEV1 >=80%	1.6

The average number of puffs from all short-acting bronchodilators used in the past 2 weeks was calculated. (NCT00791518)
Timeframe: Day 1 of a 1-day study

Mean Puffs From All Short-acting Bronchodilators Used in the Past Two Weeks in Participants With an FEV1 of <80% and >=80%

Intervention	puffs (Mean)
Participants With Diagnosed COPD and Post-albuterol FEV1 <50%	5.2
Participants With Diagnosed COPD and Post-albuterol FEV1 >=50%	2.8

The average number of puffs from all short-acting bronchodilators used in the past 2 weeks was calculated. (NCT00791518)
Timeframe: Day 1 of a 1-day study

Number of Participants Who Had a COPD Exacerbation Requiring Hospitalization With Post-albuterol FEV1 <50% and >=50%

Intervention	puffs (Mean)
Participants With Diagnosed COPD and Post-albuterol FEV1 <80%	3.8
Participants With Diagnosed COPD and Post-albuterol FEV1 >=80%	2.3

The number of participants who had a COPD exacerbation (defined as worsening of COPD symptoms) requiring hospitalization was calculated. (NCT00791518)
Timeframe: Day 1 of 1-day study

Number of Participants Who Had a COPD Exacerbation Requiring Hospitalization With Post-albuterol FEV1 <80% and >=80%

Intervention	participants (Number)
Participants With Diagnosed COPD and Post-albuterol FEV1 <50%	16
Participants With Diagnosed COPD and Post-albuterol FEV1 >=50%	32

The number of participants who had a COPD exacerbation (defined as worsening of COPD symptoms) requiring hospitalization was calculated. (NCT00791518)
Timeframe: Day 1 of a 1-day study

Number of Participants Who Had a COPD Exacerbation Requiring Oral Corticosteroids and/or Antibiotics With Post-albuterol FEV1 <50% and >=50%

Intervention	participants (Number)
Participants With Diagnosed COPD and Post-albuterol FEV1 <80%	41
Participants With Diagnosed COPD and Post-albuterol FEV1 >=80%	7

The number of participants with a COPD exacerbation (worsening of COPD symptoms) requiring treatment with oral corticosteroids and/or antibiotics was calculated. (NCT00791518)
Timeframe: Day 1 of 1-day study

Number of Participants Who Had a COPD Exacerbation Requiring Oral Corticosteroids and/or Antibiotics With Post-albuterol FEV1 <80% and >=80%

Intervention	participants (Number)
Participants With Diagnosed COPD and Post-albuterol FEV1 <50%	79
Participants With Diagnosed COPD and Post-albuterol FEV1 >=50%	284

Number of Participants With Reports of Diagnosis and/or Treatment for Specific Cardiovascular (Heart), Psychiatric (Anxiety or Depression), and/or Bone Disorders in the <80%, >=80%, <50%, and >=50% FEV1 Groups

Intervention	participants (Number)
Participants With Diagnosed COPD and Post-albuterol FEV1 <80%	246
Participants With Diagnosed COPD and Post-albuterol FEV1 >=80%	117

The number of participants with the indicated affected medical conditions were counted. (NCT00791518)
Timeframe: Day 1 of a 1-day study

Number of Participants With the Categorized Post-albuterol Forced Expiratory Volume in One Second/Forced Vital Capacity (FEV1/FVC) Ratios

Intervention	participants (Number)
	Hypertension	Coronary artery disease	Edema	Atherosclerosis	Arrhythmia	Heart failure	Stable angina	Peripheral vascular disease	Valvular heart disease	Pulmonary edema	Ischemic heart disease without cardiomyopathy	Cardiomyopathy	Ischemic heart disease with cardiomyopathy	Cardiomegaly	Left ventricular dysfunction	Diastolic dysfunction	Cerebrovascular disease	Left ventricular hypertrophy	Stroke	Cardiac arrest	Myocardial infarction	Transient ischemic attack	Unstable angina	Generalized anxiety disorder	Major depressive disorder, recurrent episode	Social anxiety disorder (social phobia)	Panic disorder	Major depressive disorder, single episode	Post-traumatic stress disorder	Attention deficit/hyperactivity disorder	Osteoporosis	Osteopenia
Participants With Diagnosed COPD and Post-albuterol FEV1 <50%	123	26	23	20	16	10	13	6	6	6	5	4	5	3	1	1	2	2	0	0	1	0	0	37	30	7	7	4	4	4	29	11
Participants With Diagnosed COPD and Post-albuterol FEV1 <80%	389	87	69	50	40	26	25	22	18	11	10	8	11	8	5	5	5	4	1	2	1	0	2	113	107	24	24	17	14	9	92	32
Participants With Diagnosed COPD and Post-albuterol FEV1 >=50%	400	85	55	41	40	23	19	25	19	9	7	7	6	6	7	6	3	3	4	3	1	2	2	114	122	34	29	19	18	9	89	31
Participants With Diagnosed COPD and Post-albuterol FEV1 >=80%	134	24	9	11	16	7	7	9	7	4	2	3	0	1	3	2	0	1	3	1	1	2	0	38	45	17	12	6	8	4	26	10

The ratio is calculated as the amount of air expelled from the lungs in one second after a full inspiration (FEV1) divided by the volume of air that can forcibly be blown out after a full inspiration (FVC). (NCT00791518)
Timeframe: Day 1 of a 1-day study

Percentage of Participants Whose Post-albuterol FEV1 Was <50% Predicted Normal

Intervention	participants (Number)
	<=0.70	>0.70
Participants With Diagnosed COPD	689	383

The percentage of participants on long-acting bronchodilator (LABD) monotherapy who met spirometric criteria for chronic obstructive pulmonary disease (COPD) and who had a post-albuterol FEV1 (the amount of air expelled from the lungs in one second after a full inspiration) <50% predicted normal was calculated. Predicted normal values for FEV1 were calculated using the reference values from the third National Health and Nutrition Examination Survey (NHANES III). Values are based on the participants' age, height, sex, and race; thus, normal values vary based on participants' demographics. (NCT00791518)
Timeframe: Day 1 of a 1-day study; 15-30 min post-albuterol (self-administered)

Percentage of Participants Whose Post-albuterol Forced Expiratory Volume in One Second (FEV1) Was <80% Predicted Normal

Intervention	percentage of participants (Number)
	<50% predicted normal	>=50% predicted normal
Participants With Diagnosed COPD	23	77

The percentage of participants on long-acting bronchodilator (LABD) monotherapy who had a post-albuterol FEV1) <80% predicted normal was calculated. FEV1 is the amount of air that can be expelled from the lungs in one second after a full inspiration. Predicted normal values for FEV1 were calculated using the reference values from the third National Health and Nutrition Examination Survey (NHANES III). Values are based on the participants' age, height, sex, and race; thus, normal values vary based on participants' demographics. (NCT00791518)
Timeframe: Day 1 of a 1-day study; 15-30 min post-albuterol (self-administered)

"The Percentage of Days of Poor Control Reported Over the 26 Week Treatment Period"

Intervention	percentage of participants (Number)
	<80% predicted normal	>=80% predicted normal
Participants With Diagnosed COPD	70	30

"A Chronic Obstructive Pulmonary Disease (COPD) day of poor control was defined as any day in the participant's diary with a score ≥2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). Score for each symptom ranges from 0-3; a higher number indicates a more severe symptom. The model contained baseline percentage of days of poor control as well as FEV1 reversibility components as covariates." (NCT00463567)
Timeframe: up to 26 weeks

Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 1 Hour to 4 Hour Post Morning Dose After 2 Weeks of Treatment

Intervention	Percentage of days (Least Squares Mean)
Indacaterol 150 µg (Continued Into Stage 2)	31.5
Indacaterol 300 µg (Continued Into Stage 2)	30.8
Tiotropium (Continued Into Stage 2)	31.0
Placebo (Continued Into Stage 2)	34.0

"Interim Analysis: Stage 1.~Spirometry was conducted according to internationally accepted standards. Standardized with respect to time (AUC 1h-4h) for FEV1 measurements taken from 1 hour to 4 hour post morning dose on Day 14. Standardized FEV1 AUC was calculated by the trapezoidal rule. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates." (NCT00463567)
Timeframe: Day 14, After 2 Weeks of treatment in Stage 1

Trough Forced Expiratory Volume in 1 Second (FEV1) Assessed by Spirometry 24 Hour Post Dose After 12 Weeks of Treatment

Intervention	Liters (Least Squares Mean)
Indacaterol 150 µg	1.53
Indacaterol 300 µg	1.58
Tiotropium 18 µg	1.49
Placebo	1.30
Indacaterol 75 µg	1.50
Indacaterol 600 µg	1.53
Formoterol 12 µg	1.52

FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates. (NCT00463567)
Timeframe: after 12 weeks of treatment

Trough Forced Expiratory Volume in 1 Second (FEV1) Assessed by Spirometry 24 Hour Post Dose After 2 Weeks of Treatment

Intervention	Liters (Least Squares Mean)
Indacaterol 150 µg (Continued Into Stage 2)	1.46
Indacaterol 300 µg (Continued Into Stage 2)	1.46
Tiotropium 18 µg (Continued Into Stage 2)	1.42
Placebo (Continued Into Stage 2)	1.28

"Interim Analysis: Stage 1.~Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates." (NCT00463567)
Timeframe: Day 15, After 2 Weeks of treatment in Stage 1

"Percentage of COPD Days of Poor Control During 26 Weeks of Treatment"

Intervention	Liters (Least Squares Mean)
Indacaterol 150 µg	1.49
Indacaterol 300 µg	1.52
Tiotropium 18 µg	1.45
Placebo	1.31
Indacaterol 75 µg	1.46
Indacaterol 600 µg	1.51
Formoterol 12 µg	1.42

"Participants rated their symptoms on a scale of 0=none to 3=severe. A Chronic Obstructive Pulmonary Disease (COPD) day of poor control was defined as any day in the participants diary with a score >=2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). The mixed model used baseline percentage of days of poor control, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates." (NCT00567996)
Timeframe: Up to 26 weeks

St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 Weeks of Treatment

Intervention	Percentage of days (Least Squares Mean)
Indacaterol 150 μg	34.1
Salmeterol 50 μg	34.1
Placebo	38.1

SGRQ is a health related quality of life questionnaire consisting of 76 items in three sections: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health status. The mixed model used baseline SGRQ total score, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates. (NCT00567996)
Timeframe: Week 12

Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment

Intervention	Score on a scale (Least Squares Mean)
Indacaterol 150 μg	36.4
Salmeterol 50 μg	38.5
Placebo	42.6

Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates. (NCT00567996)
Timeframe: Week 12

Percentage of Days of Poor Control During 52 Weeks of Treatment

Intervention	Liters (Least Squares Mean)
Indacaterol 150 μg	1.45
Salmeterol 50 μg	1.39
Placebo	1.28

Percentage of days of poor control was defined as the number of days in the patient diary with a score ≥ 2 (scale of 0-3, a higher number means more severe symptoms) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness) over 52 weeks divided by the number of evaluable days (days with ≥ 2 symptoms with scores). The analysis included baseline percentage of days of poor control, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates. (NCT00393458)
Timeframe: Baseline to end of study (Week 52)

Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85

Intervention	Percentage of days (Least Squares Mean)
Indacaterol 300 μg Plus Placebo to Formoterol	33.6
Indacaterol 600 μg Plus Placebo to Formoterol	30.0
Formoterol 12 μg Plus Placebo to Indacaterol	33.5
Placebo to Indacaterol Plus Placebo to Formoterol	38.3

FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates. (NCT00393458)
Timeframe: Week 12 + 1 day, Day 85

Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter HR

Intervention	Liters (Least Squares Mean)
Indacaterol 300 μg Plus Placebo to Formoterol	1.48
Indacaterol 600 μg Plus Placebo to Formoterol	1.48
Formoterol 12 μg Plus Placebo to Indacaterol	1.38
Placebo to Indacaterol Plus Placebo to Formoterol	1.31

Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter SaO2

Intervention	ΔHR: beats/min (Least Squares Mean)
Symbicort pMDI	-2.481
Placebo	-2.831

Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter VCO2

Intervention	SaO2: % (Least Squares Mean)
Symbicort pMDI	0.422
Placebo	0.181

Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Consumption (VO2; Obtained Via a Metabolic Cart)

Intervention	ΔVCO2: mL/min (Least Squares Mean)
Symbicort pMDI	5.994
Placebo	-4.251

Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Pulse (Defined as VO2/Heart Rate [HR]; VO2 is Obtained Via a Metabolic Cart; Used as a Surrogate for Stroke Volume)

Intervention	mL/min (Least Squares Mean)
Symbicort pMDI	11.366
Placebo	1.252

Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Spirometry.

Intervention	mL/min/beats/min (Least Squares Mean)
Symbicort pMDI	0.256
Placebo	0.168

FEV1/FVC. For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in the Modified Borg Scale for Dyspnea

Intervention	ratio (Least Squares Mean)
Symbicort pMDI	0.017
Placebo	-0.002

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). Modified Borg scale for dyspnea was self-administered at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21). The Borg scale is a 1-item instrument through which a subject reports dyspnea symptoms on a scale of 0-10 to quantify the intensity of dyspnea (where 10 is most intense). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Change in RR

Intervention	units on a scale (Least Squares Mean)
Symbicort pMDI	-0.452
Placebo	-0.248

Change in Ti/Ttot

Intervention	breaths/min (Least Squares Mean)
Symbicort pMDI	-0.193
Placebo	-0.430

Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in fractional inspiratory time (Ti/total cycle time [Ttot]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Change in Ve

Intervention	ratio (Least Squares Mean)
Symbicort pMDI	0.012
Placebo	-0.004

Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in minute ventilation (Ve). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Change in Vt

Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in tidal volume (Vt). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Change in Vt/Ti

Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in mean inspiratory flow (tidal volume [Vt]/inspiratory time [Ti]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Change From Pre-dose (Visit 2)to Post-dose (Visit 5) Assessment in Spirometry.

Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and IC (using an slow vital capacity [SVC] maneuver; IC/total lung capacity [TLC] will be used as a measure of resting hyperinflation). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Change From Baseline in FEV1 AUC(0-12h) Normalized by Time at Week 6

"Change from baseline in FEV1 AUC(0-12h), normalized by time, at the end of treatment (Week 6).~Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours).~Definitions:~AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;" (NCT03084796)
Timeframe: Baseline, Week 6

Change From Baseline in FEV1 AUC(0-12h) Normalized by Time on Day 1

"Change from baseline in FEV1 AUC(0-12h), normalized by time, on Day 1.~Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours).~Definitions:~AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;" (NCT03084796)
Timeframe: Baseline, Day 1

Number of Patients Achieving Onset of Action - Change From Baseline in Post-dose FEV1 ≥100 mL on Day 1

Number of patients achieving onset of action was defined as a change from baseline in post-dose FEV1 ≥100 mL on Day 1. These are the patients who contributed to the results, reported as median and 95% CI for 'time to onset of action' presented in Outcome Measure 8, above. (NCT03084796)
Timeframe: Day 1

Time to Onset of Action (Change From Baseline in Post-dose FEV1 ≥ 100 mL) on Day 1

Time to onset of action is defined as the time (in minutes) from receiving the study drug on Day 1, until the FEV1 change from baseline is ≥100 mL. (NCT03084796)
Timeframe: Day 1

Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF)

"Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Fridericia-corrected QT interval (QTcF).~Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR)

"Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Heart rate (HR)~Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5m, +55m, and at +2.5 h." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval

"Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - PR Interval~Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval

"Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - QRS Interval~Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in Average EXACT-Respiratory Symptom (E-RS) Total Score During Inter-Visit Periods and the Entire Treatment Period

"Change from baseline in average EXACT-Respiratory Symptom (E-RS) total score during inter-visit periods and the entire treatment period~E-RS in COPD uses 11 respiratory symptom items from the 14-item EXAcerbations of COPD tool (EXACT). E-RS total score quantifies respiratory symptom severity on a scale ranging from 0 to 40. Higher E-RS total scores indicate more severe symptoms and a declining total score indicates health improvement. E-RS questionnaire was completed by the patient each evening (e-diary).~Definitions:~For details on baseline, inter-visit periods, and the entire treatment period, please refer to outcome measure #15." (NCT03084796)
Timeframe: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period

Change From Baseline in Average Use of Rescue Medication During Inter-Visit Periods and the Entire Treatment Period

"Evaluate the change from baseline in average use of rescue medication (number of puffs/day) during the inter-visit periods and the entire treatment period.~Results are shown as number of puffs/day; a decrease (implies improvement) from baseline in average use of rescue medication.~Definitions:~Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3 (Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0);" (NCT03084796)
Timeframe: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period

Change From Baseline in FEV1 AUC(0-4h) Normalized by Time on Day 1 and at Week 6

"Change from baseline in FEV1 AUC(0-4h), normalized by time on Day 1 of treatment (Week 0).~Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 and at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (4 hours).~Definitions:~AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-4h)=Mean FEV1 after inhalation, measured at prespecified times for up to 4-h observation period (0-4h), normalized by time;" (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in FEV1 Peak(0-4h) at Day 1 and Week 6

"Change from baseline in FEV1 peak(0-4h) (L) on Day 1 and at Week 6.~Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication.~Definitions:~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; Peak(0-4h)=Maximum FEV1 between 0 and 4 h." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in FVC AUC(0-12h), Normalized by Time on Day 1 and at Week 6

"Change from baseline in FVC AUC(0-12h), normalized by time, on Day 1 and at the end of treatment (Week 6).~Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours).~Definitions:~AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-12h)=Mean FVC after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;" (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in FVC AUC(0-4h) Normalized by Time on Day 1 and at Week 6

"Change from baseline in FVC AUC(0-4h), normalized by time, on Day 1 and at the end of treatment (Week 6).~Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours).~Definitions:~AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-4)=Mean FVC after inhalation, measured at prespecified times for up to 4-h observation period (0-4 h), normalized by time;" (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in FVC Peak(0-4h) on Day 1 and at Week 6

"Change from baseline in FVC peak(0-4h) (L) on Day 1 and at the end of treatment at Week 6. Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication.~Definitions:~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; Peak(0-4h)=Maximum FEV1 between 0 and 4 h." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Change From Baseline in Percentage of Rescue Medication-Free Days During Inter-Visit Periods and the Entire Treatment Period

"Evaluate the number of rescue medication-free days compared with baseline. Results are shown as percentage (%) of rescue medication-free days; an increased value indicates improvement from baseline.~Definitions:~Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3, Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0)." (NCT03084796)
Timeframe: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period

Change From Baseline in Pre-dose Morning FEV1 at Week 3 and Week 6

"Change from baseline in FEV1 at treatment visit 3 (Week 3) and treatment visit 4 (Week 6) of treatment. Spirometry, used to measure FEV1, was performed according to internationally accepted standards.~Definitions:~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second;" (NCT03084796)
Timeframe: Baseline, Week 3, Week 6

Change From Baseline in Pre-Dose Morning Inspiratory Capacity (IC) at Week 3 and Week 6

"Change from baseline in IC at treatment Visit 3 (Week 3) and treatment Visit 4 (Week 6). Spirometry was used to measure IC and was performed according to internationally accepted standards.~Definitions:~Baseline: value of the measurement recorded at 45 mins pre-dose at Visit 2 (Week 0); IC=Inspiratory capacity;" (NCT03084796)
Timeframe: Baseline, Week 3, Week 6

Transition Dyspnea Index (TDI) Focal Score at Week 3 and Week 6

"Transitional Dyspnea Index (TDI) focal score at treatment visit 3 (Week 3) and treatment visit 4 (Week 6).~TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement), with a total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important.~Definitions:~Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index;" (NCT03084796)
Timeframe: Baseline, Week 3, Week 6

Transition Dyspnea Index (TDI) Response (Focal Score ≥1) at Week 3 and Week 6

"Number of subjects achieving TDI focal score ≥1, at treatment visit 3 (Week 3) and at treatment visit 4 (Week 6).~TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement); total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important.~Definitions:~Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index;" (NCT03084796)
Timeframe: Baseline, Week 3, Week 6

Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)

"Vital signs -- Systolic blood pressure (SBP), Diastolic blood pressure (DBP) were measured at prespecified times, using a 12-Lead single ECGs were recorded at all study visits (pre-dose at V1 (Week -2) and V3 (Week 3), as well as at pre-dose and 1.5 hours post-dose at Visit 2 (Week 0) and Visit 4 (Week 6).~Results are shown by treatment group, as change from baseline (in mmHg) for representative timepoints.~Definitions:~Baseline=Values recorded pre-dose (Visit 2, Week 0); Day 1=Day of the first dose of randomized study drug (Visit 2, Week 0);" (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

24-hour Holter ECG - Prolonged QTcF - Change From Baseline

"24-hour Holter ECG - Prolonged QTcF - Change from baseline.~Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.~Results are presented as the number of subjects who had a change from baseline in QTcF of: > 30 msec, > 60 msec, and no prolongation (by > 30 msec or > 60 msec)." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

24-hour Holter ECG - Prolonged QTcF - Female Subjects

"24-hour Holter ECG - Prolonged QTcF - Female subjects.~Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

24-hour Holter ECG - Prolonged QTcF - Male Subjects

"24-hour Holter ECG - Prolonged QTcF - Male subjects.~Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h." (NCT03084796)
Timeframe: Baseline, Day 1, Week 6

Length of Stay

Time to discharge eligibility (hours) (NCT00410150)
Timeframe: Hospital discharge

Number of Subjects With a Change From Baseline Serum Lactate Following a One Hour Albuterol Nebulizer Treatment.

We powered our study to detect a difference of 0.5 mmol/L between pre and post-treatment lactate levels, but hypothesize that the difference will be greater than 1.0 mmol/L. (NCT02073747)
Timeframe: Change in serum lactate from baseline to 1 hour

Intervention	FEV1: L; ΔFVC: L; ΔIC: L (Least Squares Mean)
	ΔFEV1	ΔFVC	ΔIC
Placebo	-0.004	-0.052	-0.024
Symbicort pMDI	0.187	0.259	0.256

Intervention	Litres (Least Squares Mean)
Treatment A	0.070
Treatment B	0.118
Treatment C	0.153
Treatment D	0.147
Treatment E	0.002
Treatment F	0.213

Intervention	minutes (Mean)
Treatment A	45.1
Treatment B	32.6
Treatment C	29.5
Treatment D	27.3
Treatment E	240.1
Treatment F	28.1

Intervention	msec (Mean)
	QTcF, Day 1, 5 min post dose	QTcF, Day 1, 55 min post dose	QTcF, Day 1, 2.5 h post dose	QTcF, Day before Week 6, 5 min post dose	QTcF, Day before Week 6, 55 min post dose	QTcF, Day before Week 6, 2.5 h post dose
Treatment A	3.62	8.37	7.15	1.61	2.38	4.13
Treatment B	5.37	5.41	8.65	1.14	0.09	0.85
Treatment C	6.81	6.72	7.20	-0.60	1.41	-0.97
Treatment D	6.25	9.90	5.45	1.67	4.15	1.73
Treatment E	3.59	6.04	4.81	-3.56	1.02	0.14
Treatment F	5.56	5.43	6.77	1.41	3.19	2.50

Intervention	bpm (Mean)
	HR, Day 1, 5 min post dose	HR, Day 1, 55 min post dose	HR, Day 1, 2.5 h post dose	HR, Day before Week 6, 5 min post dose	HR, Day before Week 6, 55 min post dose	HR, Day before Week 6, 2.5 h post dose
Treatment A	-8.85	-7.19	-7.57	-1.72	-1.52	-2.30
Treatment B	-6.62	-8.29	-6.75	-1.06	0.41	-0.01
Treatment C	-7.78	-8.28	-9.20	-1.61	-1.10	-1.13
Treatment D	-7.64	-9.59	-7.46	-1.85	-1.40	-0.73
Treatment E	-4.84	-7.44	-6.12	3.92	1.12	2.49
Treatment F	-5.54	-7.19	-8.96	1.70	1.22	-1.47

Intervention	msec (Mean)
	PR Interval, Day 1, 5 min post dose	PR Interval, Day 1, 55 min post dose	PR Interval, Day 1, 2.5 h post dose	PR Interval, Day before Week 6, 5 min post dose	PR Interval, Day before Week 6, 55 min post dose	PR Interval, Day before Week 6, 2.5 h post dose
Treatment A	7.24	7.20	8.48	0.44	0.88	2.50
Treatment B	6.53	6.89	9.38	1.36	2.37	3.01
Treatment C	6.08	8.21	7.58	-0.11	1.91	0.16
Treatment D	6.71	6.77	6.16	3.88	0.82	0.84
Treatment E	3.06	4.38	5.84	-1.36	-1.13	-1.22
Treatment F	4.90	4.77	4.25	0.82	-1.66	-1.94

Intervention	msec (Mean)
	QRS Interval, Day 1, 5 min post dose	QRS Interval, Day 1, 55 min post dose	QRS Interval, Day 1, 2.5 h post dose	QRS Interval, Day before Week 6, 5 min post dose	QRS Interval, Day before Week 6, 55 min post dose	QRS Interval, Day before Week 6, 2.5 h post dose
Treatment A	1.18	0.97	1.38	0.61	1.12	1.49
Treatment B	0.05	1.19	2.40	-1.76	-0.09	0.74
Treatment C	1.50	1.21	1.80	0.43	0.85	0.30
Treatment D	1.99	1.56	1.50	2.00	2.38	2.18
Treatment E	0.45	0.14	0.64	0.45	0.77	1.14
Treatment F	1.50	1.70	0.86	0.69	0.42	1.35

Intervention	score on a scale (Least Squares Mean)
	Inter-visit period 1	Inter-visit period 2	Entire treatment period
Treatment A	-1.681	-2.030	-1.855
Treatment B	-1.539	-1.840	-1.689
Treatment C	-1.941	-2.147	-2.044
Treatment D	-1.663	-2.077	-1.870
Treatment E	-0.714	-0.681	-0.698
Treatment F	-1.280	-1.505	-1.393

Intervention	Litres (Least Squares Mean)
	Day 1	Week 6
Treatment A	0.101	0.116
Treatment B	0.115	0.157
Treatment C	0.173	0.198
Treatment D	0.190	0.204
Treatment E	0.030	0.024
Treatment F	0.194	0.253

Intervention	Litres (Least Squares Mean)
	Week 3	Week 6
Treatment A	0.059	0.020
Treatment B	0.080	0.088
Treatment C	0.122	0.107
Treatment D	0.111	0.130
Treatment E	0.000	-0.012
Treatment F	0.122	0.112

Intervention	Participants (Count of Participants)
	Week 3 Focal Score ≥ 1	Week 6 Focal Score ≥ 1
Treatment A	70	74
Treatment B	78	83
Treatment C	75	82
Treatment D	84	91
Treatment E	67	55
Treatment F	74	80

Intervention	mmHg (Mean)
	SBP, Day 1, 30 min post dose	DBP, Day 1, 30 min post dose	SBP, Day 1, 1,5 h post dose	DBP, Day 1, 1,5 h post dose	SBP, Day 1, 11 h post dose	DBP, Day 1, 11 h post dose	SBP, Week 6, pre-dose	DBP, Week 6, pre-dose	SBP, Week 6, 30 min post dose	DBP, Week 6, 30 min post dose	SBP, Week 6, 1,5 h post dose	DBP, Week 6, 1,5 h post dose	SBP, Week 6, 11 h post dose	DBP, Week 6, 11 h post dose
Treatment A	-1.4	-0.7	0.3	-0.7	1.1	-0.9	0.4	0.4	-1.6	-0.7	-1.3	-1.0	0.2	-0.9
Treatment B	-0.4	-0.6	-1.1	-1.8	2.0	0.3	0.8	0.5	-0.9	-0.9	-0.6	-2.7	1.5	-2.0
Treatment C	-2.0	-2.1	-0.6	-1.7	-0.0	-1.6	0.4	-0.3	-0.5	-1.5	-0.5	-2.0	0.5	-2.3
Treatment D	-1.9	-1.4	-1.8	-1.6	1.7	-1.4	-1.0	-1.0	-2.5	-2.0	-2.3	-2.3	2.2	-1.4
Treatment E	-0.9	-0.8	0.2	-1.7	1.9	-1.0	1.6	0.0	0.5	-0.8	0.1	-1.1	3.2	-1.0
Treatment F	-1.2	0.1	-1.5	-1.5	0.9	-1.2	1.3	-0.2	0.1	-1.2	0.5	-0.6	2.0	-0.7

Intervention	Participants (Count of Participants)
	QTcF, Any post dose time point72488794			QTcF, Any post dose time point72488795	QTcF, Any post dose time point72488796	QTcF, Any post dose time point72488797	QTcF, Any post dose time point72488798	QTcF, Any post dose time point72488793	QTcF, Day 1, 5 min post dose72488793	QTcF, Day 1, 5 min post dose72488795	QTcF, Day 1, 5 min post dose72488796	QTcF, Day 1, 5 min post dose72488797	QTcF, Day 1, 5 min post dose72488798	QTcF, Day 1, 5 min post dose72488794	QTcF, Day 1, 55 min post dose72488793	QTcF, Day 1, 55 min post dose72488794	QTcF, Day 1, 55 min post dose72488796	QTcF, Day 1, 55 min post dose72488797	QTcF, Day 1, 55 min post dose72488798	QTcF, Day 1, 55 min post dose72488795	QTcF, Day 1, 2.5 h post dose72488793	QTcF, Day 1, 2.5 h post dose72488795	QTcF, Day 1, 2.5 h post dose72488796	QTcF, Day 1, 2.5 h post dose72488797	QTcF, Day 1, 2.5 h post dose72488798	QTcF, Day 1, 2.5 h post dose72488794	QTcF, Day before Week 6, 5 min post dose72488793	QTcF, Day before Week 6, 5 min post dose72488794	QTcF, Day before Week 6, 5 min post dose72488795	QTcF, Day before Week 6, 5 min post dose72488796	QTcF, Day before Week 6, 5 min post dose72488797	QTcF, Day before Week 6, 5 min post dose72488798	QTcF, Day before Week 6, 55 min post dose72488793	QTcF, Day before Week 6, 55 min post dose72488794	QTcF, Day before Week 6, 55 min post dose72488796	QTcF, Day before Week 6, 55 min post dose72488797	QTcF, Day before Week 6, 55 min post dose72488798	QTcF, Day before Week 6, 55 min post dose72488795	QTcF, Day before Week 6, 2.5 h post dose72488794	QTcF, Day before Week 6, 2.5 h post dose72488796	QTcF, Day before Week 6, 2.5 h post dose72488797	QTcF, Day before Week 6, 2.5 h post dose72488798	QTcF, Day before Week 6, 2.5 h post dose72488793	QTcF, Day before Week 6, 2.5 h post dose72488795
	Change from baseline: > 60 msec	No change from baseline (> 30 msec or > 60 msec)	Change from baseline: > 30 msec
Treatment A	19
Treatment B	20
Treatment C	21
Treatment D	20
Treatment E	16
Treatment F	18
Treatment A	0
Treatment B	1
Treatment C	0
Treatment D	2
Treatment E	2
Treatment F	1
Treatment A	102
Treatment B	102
Treatment C	100
Treatment D	101
Treatment E	103
Treatment F	104
Treatment A	2
Treatment B	4
Treatment C	9
Treatment E	3
Treatment F	4
Treatment D	0
Treatment E	0
Treatment A	119
Treatment B	119
Treatment C	112
Treatment D	121
Treatment E	118
Treatment F	119
Treatment A	8
Treatment C	5
Treatment D	6
Treatment E	4
Treatment F	5
Treatment A	113
Treatment C	116
Treatment D	116
Treatment E	116
Treatment F	118
Treatment A	5
Treatment B	12
Treatment C	6
Treatment D	5
Treatment E	6
Treatment F	8
Treatment B	0
Treatment D	1
Treatment E	1
Treatment F	0
Treatment A	116
Treatment B	111
Treatment C	115
Treatment D	117
Treatment E	114
Treatment F	115
Treatment B	3
Treatment D	3
Treatment F	3
Treatment C	121
Treatment D	120
Treatment E	121
Treatment F	120
Treatment C	7
Treatment D	7
Treatment B	123
Treatment C	114
Treatment A	6
Treatment B	6
Treatment C	3
Treatment F	7
Treatment A	115
Treatment B	117
Treatment C	118
Treatment F	116

Intervention	Participants (Count of Participants)
	QTcF, Day -1, 5 min72488795			QTcF, Day -1, 5 min72488798	QTcF, Day -1, 5 min72488793	QTcF, Day -1, 5 min72488794	QTcF, Day -1, 5 min72488796	QTcF, Day -1, 5 min72488797	QTcF, Day -1, 55 min72488795	QTcF, Day -1, 55 min72488797	QTcF, Day -1, 55 min72488798	QTcF, Day -1, 55 min72488793	QTcF, Day -1, 55 min72488794	QTcF, Day -1, 55 min72488796	QTcF, Day -1, 2.5 h72488794	QTcF, Day -1, 2.5 h72488797	QTcF, Day -1, 2.5 h72488795	QTcF, Day -1, 2.5 h72488793	QTcF, Day -1, 2.5 h72488796	QTcF, Day -1, 2.5 h72488798	QTcF, Any post dose time point72488794	QTcF, Any post dose time point72488795	QTcF, Any post dose time point72488797	QTcF, Any post dose time point72488798	QTcF, Any post dose time point72488793	QTcF, Any post dose time point72488796	QTcF, Day 1, 5 min post dose72488798	QTcF, Day 1, 5 min post dose72488795	QTcF, Day 1, 5 min post dose72488793	QTcF, Day 1, 5 min post dose72488794	QTcF, Day 1, 5 min post dose72488796	QTcF, Day 1, 5 min post dose72488797	QTcF, Day 1, 55 min post dose72488793	QTcF, Day 1, 55 min post dose72488798	QTcF, Day 1, 55 min post dose72488797	QTcF, Day 1, 55 min post dose72488794	QTcF, Day 1, 55 min post dose72488795	QTcF, Day 1, 55 min post dose72488796	QTcF, Day 1, 2.5 h post dose72488795	QTcF, Day 1, 2.5 h post dose72488793	QTcF, Day 1, 2.5 h post dose72488794	QTcF, Day 1, 2.5 h post dose72488796	QTcF, Day 1, 2.5 h post dose72488797	QTcF, Day 1, 2.5 h post dose72488798	QTcF, Day before Week 6, 5 min post dose72488798	QTcF, Day before Week 6, 5 min post dose72488793	QTcF, Day before Week 6, 5 min post dose72488794	QTcF, Day before Week 6, 5 min post dose72488795	QTcF, Day before Week 6, 5 min post dose72488796	QTcF, Day before Week 6, 5 min post dose72488797	QTcF, Day before Week 6, 55 min post dose72488798	QTcF, Day before Week 6, 55 min post dose72488793	QTcF, Day before Week 6, 55 min post dose72488794	QTcF, Day before Week 6, 55 min post dose72488795	QTcF, Day before Week 6, 55 min post dose72488796	QTcF, Day before Week 6, 55 min post dose72488797	QTcF, Day before Week 6, 2.5 h post dose72488798	QTcF, Day before Week 6, 2.5 h post dose72488793	QTcF, Day before Week 6, 2.5 h post dose72488794	QTcF, Day before Week 6, 2.5 h post dose72488795	QTcF, Day before Week 6, 2.5 h post dose72488796	QTcF, Day before Week 6, 2.5 h post dose72488797
	Actual value > 470 msec	Actual value > 500 msec	No prolongation (> 470 msec or > 500 msec)
Treatment B	64
Treatment C	67
Treatment E	0
Treatment A	3
Treatment F	1
Treatment A	55
Treatment F	0
Treatment F	57
Treatment A	2
Treatment B	3
Treatment A	56
Treatment B	65
Treatment C	0
Treatment F	56
Treatment A	1
Treatment A	57
Treatment B	2
Treatment A	0
Treatment B	0
Treatment D	0
Treatment A	58
Treatment B	66
Treatment D	65
Treatment E	52
Treatment B	1
Treatment D	1
Treatment B	67
Treatment D	64

Article	Year
Improving the quality of life in patients with chronic obstructive pulmonary disease: focus on indacaterol. International journal of chronic obstructive pulmonary disease, 2013, Volume: 8 Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Bronchodilator Agents; Clinical Trials as Topic; Dys	2013
Ten years of tiotropium: clinical impact and patient perspectives. International journal of chronic obstructive pulmonary disease, 2013, Volume: 8 Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Bronchodilator Agents; Dyspnea; Ethanolamines; Formo	2013
Clinical Practice. Mild asthma. The New England journal of medicine, 2013, Aug-08, Volume: 369, Issue:6 Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Algorithms; Anti-Asthmatic Agents;	2013
Efficacy of indacaterol 75 μg versus fixed-dose combinations of formoterol-budesonide or salmeterol-fluticasone for COPD: a network meta-analysis. International journal of chronic obstructive pulmonary disease, 2012, Volume: 7 Topics: Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combi	2012
Effects of long-acting bronchodilators in COPD patients according to COPD severity and ICS use. Respiratory medicine, 2013, Volume: 107, Issue:2 Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Bronchodila	2013
[Dyspnea and quality of life in chronic obstructive pulmonary disease]. Archivos de bronconeumologia, 2002, Volume: 38, Issue:10 Topics: Albuterol; Bronchodilator Agents; Clinical Trials as Topic; Dyspnea; Emotions; Exercise; Follow-Up S	2002
[The beta2-adrenergic receptor agonists in the treatment of chronic obstructive pulmonary disease]. Przeglad lekarski, 2005, Volume: 62, Issue:7 Topics: Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Delayed-Action Preparation	2005
[Fire-eater's lung. Two cases and review of the literature]. Deutsche medizinische Wochenschrift (1946), 2006, Feb-17, Volume: 131, Issue:7 Topics: Administration, Inhalation; Adult; Albuterol; Anti-Bacterial Agents; Bronchodilator Agents; Chest Pa	2006
Improving dyspnea in chronic obstructive pulmonary disease: optimal treatment strategies. Proceedings of the American Thoracic Society, 2006, Volume: 3, Issue:3 Topics: Adrenergic beta-Agonists; Albuterol; Cholinergic Antagonists; Dyspnea; Humans; Pulmonary Disease, Ch	2006
The role of patient-centered outcomes in the course of chronic obstructive pulmonary disease: how long-term studies contribute to our understanding. The American journal of medicine, 2006, Volume: 119, Issue:10 Suppl 1 Topics: Acute Disease; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; B	2006
A paradoxical effect of bronchodilators. Chest, 1997, Volume: 111, Issue:6 Topics: Acidosis, Lactic; Acute Disease; Adrenergic beta-Agonists; Albuterol; Asthma; Bronchodilator Agents;	1997

Article	Year
Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial. Pediatrics, 2022, 09-01, Volume: 150, Issue:3 Topics: Albuterol; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Dyspnea; Fluticasone	2022
Sensory-mechanical effects of a dual bronchodilator and its anticholinergic component in COPD. Respiratory physiology & neurobiology, 2018, Volume: 247 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Airway Resistance; Albuterol; Benzyl Alcohols; Bronchodil	2018
Intravenous magnesium sulfate for acute wheezing in young children: a randomised double-blind trial. The European respiratory journal, 2018, Volume: 51, Issue:2 Topics: Acute Disease; Administration, Intravenous; Albuterol; Asthma; Bronchodilator Agents; Child, Prescho	2018
Effect of fluticasone/salmeterol combination on dyspnea and respiratory mechanics in mild-to-moderate COPD. Respiratory medicine, 2013, Volume: 107, Issue:5 Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Cross-Over Studies; Double-Blind	2013
Perception of bronchoconstriction: a complementary disease marker in children with asthma. The Journal of asthma : official journal of the Association for the Care of Asthma, 2013, Volume: 50, Issue:6 Topics: Adolescent; Albuterol; Androstadienes; Anti-Allergic Agents; Asthma; Bronchial Hyperreactivity; Bron	2013
A pilot study assessing the effect of bronchodilator on dynamic hyperinflation in LAM. Respiratory medicine, 2013, Volume: 107, Issue:11 Topics: Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Bronchodilator Agents; Cross-Over Studies; Do	2013
Effects of long-acting bronchodilators and prednisolone on inspiratory lung function parameters in stable COPD. Pulmonary pharmacology & therapeutics, 2014, Volume: 28, Issue:2 Topics: Administration, Oral; Aged; Aged, 80 and over; Albuterol; Bronchodilator Agents; Delayed-Action Prep	2014
Comparing dynamic hyperinflation and associated dyspnea induced by metronome-paced tachypnea versus incremental exercise. COPD, 2014, Volume: 11, Issue:1 Topics: Aged; Albuterol; Albuterol, Ipratropium Drug Combination; Bronchodilator Agents; Cross-Over Studies;	2014
Repeated dyspnea score and percent FEV1 are modest predictors of hospitalization/relapse in patients with acute asthma exacerbation. Respiratory medicine, 2014, Volume: 108, Issue:9 Topics: Acute Disease; Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Asthma; Bronchodilator Agents;	2014
Immediate salbutamol responsiveness does not predict long-term benefits of indacaterol in patients with chronic obstructive pulmonary disease. BMC pulmonary medicine, 2017, 01-31, Volume: 17, Issue:1 Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Dose-Response Rela	2017
A randomized controlled trial of intravenous magnesium sulphate as an adjunct to standard therapy in acute severe asthma. Iranian journal of allergy, asthma, and immunology, 2008, Volume: 7, Issue:4 Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Drug Therapy, Combination; Dyspnea; Female	2008
Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD. Respiratory medicine, 2009, Volume: 103, Issue:4 Topics: Administration, Inhalation; Aged; Albuterol; Bronchodilator Agents; Double-Blind Method; Drug Admini	2009
Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD. The European respiratory journal, 2009, Volume: 33, Issue:4 Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; beta-Endorphin; Bronchodilator Agents;	2009
Efficacy and safety of nebulized formoterol as add-on therapy in COPD patients receiving maintenance tiotropium bromide: Results from a 6-week, randomized, placebo-controlled, clinical trial. Drugs, 2009, Jun-18, Volume: 69, Issue:9 Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Area Under Curve; Broncho	2009
Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study. Respiratory medicine, 2010, Volume: 104, Issue:3 Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Combined Modality Therapy; Drug Administrati	2010
Combining tiotropium and salmeterol in COPD: Effects on airflow obstruction and symptoms. Respiratory medicine, 2010, Volume: 104, Issue:7 Topics: Adult; Airway Obstruction; Albuterol; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method	2010
Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison. The European respiratory journal, 2011, Volume: 37, Issue:2 Topics: Adrenal Cortex Hormones; Aged; Albuterol; Bronchodilator Agents; Drug Administration Schedule; Dyspn	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respiratory medicine, 2011, Volume: 105, Issue:6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Double-Blind Method; Dyspnea; Ethanolamines; F	2011
Improved respiratory system conductance following bronchodilator predicts reduced exertional dyspnoea. Respiratory medicine, 2011, Volume: 105, Issue:9 Topics: Aged; Aged, 80 and over; Albuterol; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method;	2011
Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients. International journal of chronic obstructive pulmonary disease, 2011, Volume: 6 Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Androstadienes; Beclomethasone; Bronchodilator	2011
Randomized controlled trial of a breath-activated nebulizer in patients with exacerbation of COPD. Respiratory care, 2012, Volume: 57, Issue:9 Topics: Aged; Aged, 80 and over; Albuterol; Bronchodilator Agents; Dyspnea; Female; Humans; Inspiratory Capa	2012
Effect of levalbuterol on prehospital patient parameters. The American journal of emergency medicine, 2002, Volume: 20, Issue:5 Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Bronchodilator Agents; Dyspne	2002
Effects of exercise and beta 2-agonists on lung function in chronic obstructive pulmonary disease. Journal of applied physiology (Bethesda, Md. : 1985), 2002, Volume: 93, Issue:6 Topics: Adrenergic beta-Agonists; Aged; Albuterol; Bronchoconstriction; Cross-Over Studies; Dyspnea; Exercis	2002
Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD. The European respiratory journal, 2003, Volume: 21, Issue:1 Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Bronchodilator Agents; Cross-	2003
Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax, 2003, Volume: 58, Issue:5 Topics: Administration, Inhalation; Albuterol; Bronchodilator Agents; Double-Blind Method; Dyspnea; Female;	2003
A comparison of the effects of salbutamol and ipratropium bromide on exercise endurance in patients with COPD. Chest, 2003, Volume: 123, Issue:6 Topics: Adrenergic beta-Agonists; Aged; Aged, 80 and over; Albuterol; Bronchodilator Agents; Cholinergic Ant	2003
The reversibility of increased airways resistance in chronic heart failure measured by impulse oscillometry. Journal of cardiac failure, 2004, Volume: 10, Issue:2 Topics: Aged; Airway Resistance; Albuterol; Bronchodilator Agents; Case-Control Studies; Double-Blind Method	2004
A short-term comparison of fluticasone propionate/salmeterol with ipratropium bromide/albuterol for the treatment of COPD. Treatments in respiratory medicine, 2004, Volume: 3, Issue:3 Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; And	2004
Relief of dyspnoea by beta2-agonists after methacholine-induced bronchoconstriction. Respiratory medicine, 2004, Volume: 98, Issue:9 Topics: Adolescent; Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Bronchoconstriction; Bronchodilator	2004
Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease. Thorax, 2005, Volume: 60, Issue:4 Topics: Administration, Inhalation; Albuterol; Analysis of Variance; Androstadienes; Bronchodilator Agents;	2005
Responsiveness of continuous ratings of dyspnea during exercise in patients with COPD. Medicine and science in sports and exercise, 2005, Volume: 37, Issue:4 Topics: Aged; Albuterol; Bronchodilator Agents; Computers; Double-Blind Method; Dyspnea; Exercise Test; Fema	2005
Beneficial effects of albuterol therapy driven by heliox versus by oxygen in severe asthma exacerbation. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2005, Volume: 12, Issue:9 Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Bronchodilator Agents; Double-Blind Method; Dy	2005
[Clinical and functional benefits of adding theophylline to a standard treatment with short acting bronchodilators in patients with COPD]. Revista medica de Chile, 2005, Volume: 133, Issue:10 Topics: Administration, Inhalation; Administration, Oral; Aged; Albuterol; Bronchodilator Agents; Double-Bli	2005
Addition of salmeterol to existing treatment in patients with COPD: a 12 month study. Thorax, 2006, Volume: 61, Issue:2 Topics: Albuterol; Bronchodilator Agents; Double-Blind Method; Dyspnea; Exercise Tolerance; Female; Forced E	2006
Additional clinical benefit of enoxaparin in COPD patients receiving salmeterol and fluticasone propionate in combination. Pulmonary pharmacology & therapeutics, 2006, Volume: 19, Issue:6 Topics: Aged; Albuterol; Androstadienes; Anticoagulants; Blood Gas Analysis; Bronchodilator Agents; Double-B	2006
Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD. Chest, 2006, Volume: 130, Issue:3 Topics: Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Dose-Response Rela	2006
The effect of bronchodilators and oxygen alone and in combination on self-paced exercise performance in stable COPD. Respiratory medicine, 2007, Volume: 101, Issue:4 Topics: Aged; Albuterol; Bronchodilator Agents; Combined Modality Therapy; Cross-Over Studies; Dyspnea; Exer	2007
The additive effect of theophylline on a combination of formoterol and tiotropium in stable COPD: a pilot study. Respiratory medicine, 2007, Volume: 101, Issue:5 Topics: Aged; Albuterol; Bronchodilator Agents; Drug Administration Schedule; Drug Interactions; Drug Therap	2007
Onset of relief of dyspnoea with budesonide/formoterol or salbutamol following methacholine-induced severe bronchoconstriction in adults with asthma: a double-blind, placebo-controlled study. Respiratory research, 2006, Dec-04, Volume: 7 Topics: Adolescent; Adult; Albuterol; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconst	2006
Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial. Clinical therapeutics, 2007, Volume: 29, Issue:2 Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Bronchodilator Agents; Dose-R	2007
Endurance shuttle walking test: responsiveness to salmeterol in COPD. The European respiratory journal, 2008, Volume: 31, Issue:3 Topics: Aged; Albuterol; Bronchodilator Agents; Cohort Studies; Cross-Over Studies; Double-Blind Method; Dys	2008
Inhaled corticosteroids as additional treatment in alpha-1-antitrypsin-deficiency-related COPD. Respiration; international review of thoracic diseases, 2008, Volume: 76, Issue:1 Topics: Administration, Inhalation; Aged; Albuterol; alpha 1-Antitrypsin Deficiency; Beclomethasone; Broncho	2008
Effects of salbutamol, ipratropium bromide and disodium cromoglycate on breathlessness induced by exercise in normal subjects. British journal of clinical pharmacology, 1981, Volume: 12, Issue:4 Topics: Adult; Albuterol; Atropine Derivatives; Cromolyn Sodium; Dyspnea; Humans; Ipratropium; Physical Exer	1981
The assessment of dyspnea in bronchial asthma. International journal of clinical pharmacology and therapeutics, 1995, Volume: 33, Issue:7 Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Bronchodilator Agents; Dyspnea; Female; Forced	1995
Terbutaline vs albuterol for out-of-hospital respiratory distress: randomized, double-blind trial. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 1995, Volume: 2, Issue:8 Topics: Administration, Inhalation; Adult; Aged; Albuterol; Bronchodilator Agents; Double-Blind Method; Dysp	1995
Is an anticholinergic agent superior to a beta 2-agonist in improving dyspnea and exercise limitation in COPD? Chest, 1995, Volume: 108, Issue:3 Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Aged; Alb	1995
Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine, 1996, Volume: 153, Issue:3 Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Bronchodilator Agents; Dyspne	1996
Salmeterol reduces dyspnea and improves lung function in patients with COPD. Chest, 1997, Volume: 112, Issue:2 Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Bronchodilator Agents; Cross-	1997
[Evaluation of the effectiveness and safety of salmeterol in children with nocturnal dyspnea]. Pneumonologia i alergologia polska, 1997, Volume: 65 Suppl 1 Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol	1997
Does inhaled albuterol improve diaphragmatic contractility in patients with chronic obstructive pulmonary disease? American journal of respiratory and critical care medicine, 1999, Volume: 160, Issue:6 Topics: Action Potentials; Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Bronchodil	1999
Immunohistochemically stained activated eosinophils in sputum in patients with asthma. Respiration; international review of thoracic diseases, 2000, Volume: 67, Issue:2 Topics: Administration, Inhalation; Adult; Albuterol; Antibodies, Monoclonal; Antibody Specificity; Asthma;	2000
The cumulative effect of long-acting bronchodilators, exercise, and inspiratory muscle training on the perception of dyspnea in patients with advanced COPD. Chest, 2000, Volume: 118, Issue:3 Topics: Administration, Inhalation; Albuterol; Bronchodilator Agents; Delayed-Action Preparations; Dyspnea;	2000
The spirometric efficacy of once-daily dosing with tiotropium in stable COPD: a 13-week multicenter trial. The US Tiotropium Study Group. Chest, 2000, Volume: 118, Issue:5 Topics: Aged; Albuterol; Bronchodilator Agents; Cholinergic Antagonists; Double-Blind Method; Dyspnea; Femal	2000
Effectiveness of salmeterol versus ipratropium bromide on exertional dyspnoea in COPD. The European respiratory journal, 2001, Volume: 17, Issue:6 Topics: Administration, Inhalation; Aged; Albuterol; Double-Blind Method; Dyspnea; Exercise Test; Female; Fo	2001
Unaltered perception of dyspnoea during treatment with long-acting beta2-agonists. The European respiratory journal, 2001, Volume: 18, Issue:2 Topics: Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Bronchial Provocation Tests; Bronchoconstriction	2001
Airway response to inhaled hypertonic saline in patients with moderate to severe chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine, 2001, Nov-15, Volume: 164, Issue:10 Pt 1 Topics: Administration, Inhalation; Aged; Airway Resistance; Albuterol; Bronchoconstriction; Bronchodilator	2001
Potential masking effect on dyspnoea perception by short- and long-acting beta2-agonists in asthma. The European respiratory journal, 2002, Volume: 19, Issue:2 Topics: Adolescent; Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Bronchial Hyperreactivity; Bronchial	2002
What is the optimal treatment strategy for chronic obstructive pulmonary disease exacerbations? The European respiratory journal, 2002, Volume: 19, Issue:5 Topics: Acute Disease; Aged; Albuterol; Bronchodilator Agents; Dyspnea; Female; Fenoterol; Glucocorticoids;	2002
Measuring functional status in chronic lung disease: conclusions from a randomized control trial. Respiratory medicine, 1991, Volume: 85 Suppl B Topics: Aged; Albuterol; Chronic Disease; Double-Blind Method; Dyspnea; Exercise Test; Female; Humans; Lung;	1991
Mechanism of bronchodilator effect in chronic airflow limitation. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 1991, Jan-01, Volume: 144, Issue:1 Topics: Activities of Daily Living; Aged; Albuterol; Drug Therapy, Combination; Dyspnea; Forced Expiratory V	1991
Acute response to bronchodilator. An imperfect guide for bronchodilator therapy in chronic airflow limitation. Archives of internal medicine, 1988, Volume: 148, Issue:9 Topics: Administration, Inhalation; Administration, Oral; Aged; Albuterol; Analysis of Variance; Clinical Tr	1988
Effects of beta-agonists on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease. Respiration; international review of thoracic diseases, 1986, Volume: 49, Issue:2 Topics: Aged; Albuterol; Clenbuterol; Clinical Trials as Topic; Dyspnea; Ethanolamines; Forced Expiratory Vo	1986
The treatment of acute transient cough: a placebo-controlled comparison of dextromethorphan and dextromethorphan-beta 2-sympathomimetic combination. European journal of respiratory diseases, 1986, Volume: 69, Issue:2 Topics: Acute Disease; Adult; Albuterol; Cough; Dextromethorphan; Double-Blind Method; Drug Combinations; Dy	1986