Effects of Tiotropium With and Without Formoterol on Airflow Obstruction and Resting Hyperinflation in Patients With COPD

• Published in: Chest Vol. 129; no. 3; pp. 509 - 517
• Main Authors: van Noord, Jan A., Aumann, Joseph L., Janssens, Eduard, Verhaert, Jan, Smeets, Joseph J., Mueller, Achim, Cornelissen, Piet J.G.
• Format: Journal Article
• Language: English
• Published: Northbrook, IL Elsevier Inc 01.03.2006; American College of Chest Physicians; Elsevier B.V
• Subjects: Adrenergic beta-Agonists - therapeutic use; Aged; ATS = American Thoracic Society; Biological and medical sciences; Bronchodilator agents; Bronchodilator Agents - therapeutic use; Cardiology. Vascular system; Cholinergic Antagonists - therapeutic use; Chronic obstructive pulmonary disease; Circadian Rhythm; COPD; Cross-Over Studies; Drug dosages; Drug therapy; Drug Therapy, Combination; Ethanolamines - therapeutic use; Evaluation; Female; Forced Expiratory Volume; formoterol; Formoterol Fumarate; GOLD = Global Initiative for Chronic Obstructive Lung Disease; Humans; hyperinflation; IC = inspiratory capacity; LABA = long-acting β2-agonist; long-acting anticholinergic; long-acting β2-agonist; Lung diseases; Lung diseases, Obstructive; Male; Medical sciences; Middle Aged; Parasympatholytic agents; PEFR = peak expiratory flow rate; Pharmacodynamics; Pneumology; Pulmonary Disease, Chronic Obstructive - drug therapy; Scopolamine Derivatives - therapeutic use; Spirometry; tiotropium; Tiotropium Bromide; Treatment Outcome; Vital Capacity; United States; long-acting β2-agonist; GOLD = Global Initiative for Chronic Obstructive Lung Disease; long-acting anticholinergic; LABA = long-acting β2-agonist; PEFR = peak expiratory flow rate; hyperinflation; ATS = American Thoracic Society; formoterol; IC = inspiratory capacity; COPD; tiotropium; Human; Agonist; Hyperinflation; Respiratory disease; Tiotropium bromide; Cardiovascular disease; Patient; Obstruction; Chronic; Air flow; Formoterol; Parasympatholytic
• ISSN: 0012-3692; 1931-3543
• DOI: 10.1378/chest.129.3.509

The combination of short-acting β2-agonists and anticholinergics in the treatment of COPD has been well documented, but data on combination of long-acting agents are lacking. A randomized, open-label, placebo-controlled, three-way crossover study was conducted comparing 2-week treatment periods of tiotropium alone to tiotropium plus formoterol once or twice daily following a 2-week pretreatment period with tiotropium. Lung function (FEV1, FVC, and resting inspiratory capacity [IC]) serially over 24 h was measured in 95 patients with stable COPD at baseline and after 2 weeks of each treatment. Mean baseline FEV1 was 1.05 L (38% of predicted). There was a circadian variation in FEV1, FVC, and IC at baseline that was maintained during all treatment periods. Average FEV1 (0 to 24 h) improved by 0.08 L with tiotropium, by 0.16 L with tiotropium plus formoterol once daily, and by 0.20 L with tiotropium plus formoterol twice daily (p < 0.01 for all comparisons). Compared with tiotropium alone, add-on formoterol in the morning produced improvement in FEV1, FVC, and IC for > 12 h. The second add-on dose of formoterol in the evening caused further improvement in FEV1 for 12 h, but in FVC and IC for < 12 h. Peak increase in FEV1 was 0.23 L (22% of baseline) with tiotropium and 0.39 L (37% of baseline) with tiotropium plus formoterol (p < 0.0001). Compared with tiotropium alone, add-on formoterol once and twice daily reduced the use of rescue salbutamol during the daytime (p < 0.01) and with add-on formoterol twice daily also during the nighttime (p < 0.05). The combination of tiotropium and formoterol was well tolerated. In the treatment of COPD, there is benefit from adding formoterol once or twice daily to tiotropium once daily in terms of improvement in airflow obstruction, resting hyperinflation, and the use of rescue salbutamol.