title: Effects of Adding Tiotropium or Aclidinium as Triple Therapy Using Impulse Oscillometry in COPD.
abstract: BACKGROUND
  Long-acting muscarinic antagonists confer improvements in spirometry when used in addition to inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) in COPD. The dual objectives of this proof of concept study were to evaluate trough effects of tiotropium (TIO) or aclidinium (ACL) when used as triple therapy and to assess if impulse oscillometry (IOS) might be more sensitive than spirometry in detecting subtle differences in bronchodilator response.
  
  
  METHODS
  Patients with moderate to severe COPD already taking ICS/LABA were randomized to receive add-on therapy in cross-over fashion with either TIO 18 µg od or ACL 322 µg bid for 2-3 weeks each. Measurements of IOS, spirometry, 6-min walk test, St George's Respiratory Questionnaire (SGRQ) and Baseline/Transition Dyspnoea Index (TDI) were made at baseline and after chronic dosing at trough (12 h for ACL and 24 h for TIO), in addition to domiciliary diurnal spirometry.
  
  
  RESULTS
  13 patients were completed: mean age 69 years, FEV1 52 % predicted, FEV1/FVC 0.48, and R5 202 % predicted. There were no differences in any visit-based trough IOS or spirometry outcomes comparing TIO versus ACL. Resonant frequency but not total airway resistance at 5 Hz (R5) significantly improved from baseline with both treatments while peripheral airway resistance (R5-R20) significantly improved with ACL. Visit-based FEV1, and forced and relaxed vital capacity were also significantly improved from baseline with both treatments. There were no significant differences in diurnal FEV1 and FEV6 profiles between treatments. 6-min walk distance and post-walk fatigue significantly improved from baseline with ACL, while post-walk dyspnea improved with TIO. SGRQ symptom score significantly improved to a similar degree with both treatments. TDI significantly improved with ACL versus TIO by 1.54 units.
  
  
  CONCLUSIONS
  We observed comparable bronchodilator efficacy at trough with TIO and ACL when used as triple therapy in COPD, while IOS was no more sensitive than spirometry.
authors.affiliation: Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK.
authors.forename: Arvind
authors.initials: A
authors.lastname: Manoharan
authors.affiliation: Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Morrison
authors.affiliation: Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, UK. b.j.lipworth@dundee.ac.uk.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000403:Airway Resistance; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D009991:Oscillometry / Q000379:methods*; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D020127:Recovery of Function; D012606:Scotland; D013147:Spirometry; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014326:Tropanes / Q000009:adverse effects / Q000627:therapeutic use*; D014797:Vital Capacity
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D014326:Tropanes; C542859:aclidinium bromide; D000069447:Tiotropium Bromide
keywords: Aclidinium; COPD; Impulse oscillometry; Spirometry; Tiotropium