title: Daily variation in lung function in COPD patients with combined albuterol and ipratropium: results from a 4-week, randomized, crossover study.
abstract: BACKGROUND
  The bronchodilator response to short-acting β2-agonist and short-acting muscarinic antagonist monotherapies varies on a day-to-day basis within individual patients. The objective of this study was to compare daily variation in bronchodilator response to the combined use of albuterol and ipratropium with monotherapies in patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  This was a 4-week, randomized, open-label, two-period crossover study in patients with COPD. Patients were randomized 1:1 to receive albuterol via metered dose inhaler followed by ipratropium or vice versa during treatment Period 1 (10-14 days). The order of treatments was then reversed during treatment Period 2 (10-14 days). Pre-defined efficacy endpoints were: forced expiratory volume in 1 s (FEV1), derived FEV1, inspiratory capacity (IC) and daily variability of FEV1 and IC as measured by coefficient of variation (CV).
  
  
  RESULTS
  Albuterol and ipratropium improved FEV1 when administered as the first bronchodilator, compared with pre-dose values (0.269 and 0.243 L, respectively). Administration of the second bronchodilator provided further improvements in lung function, but to a lesser magnitude than the first bronchodilator (0.094 L for both treatments). A statistically significant reduction in daily variability in FEV1 was observed for dual bronchodilator therapy compared with monotherapy (difference in CV = 0.007; p = 0.019) and pre-dose values (no treatment; difference in CV = 0.022; p < 0.001).
  
  
  CONCLUSIONS
  The free combination of albuterol and ipratropium resulted in greater improvements and lower day-to-day variability in FEV1 compared with either monotherapy or no bronchodilator therapy. The reduced daily variability may be an important therapeutic advantage of using different classes of bronchodilators in COPD.
  
  
  BACKGROUND
  NCT01691482.
authors.affiliation: University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK. Electronic address: dsingh@meu.org.uk.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: GlaxoSmithKline, Clinical Statistics (Respiratory), Stockley Park, UK.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhu
authors.affiliation: GlaxoSmithKline, Respiratory and Immuno-Inflammation, Research Triangle Park, NC, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sharma
authors.affiliation: GlaxoSmithKline, Respiratory and Immuno-Inflammation, Research Triangle Park, NC, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Church
authors.affiliation: GlaxoSmithKline, Respiratory and Immuno-Inflammation, Research Triangle Park, NC, USA.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Kalberg
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012129:Respiratory Function Tests
chemical_list: D001993:Bronchodilator Agents; D009241:Ipratropium; D000420:Albuterol
keywords: Bronchodilator; COPD; Short-acting muscarinic antagonist; Short-acting β(2)-agonist