title: Indacaterol and tiotropium combination therapy in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Combination therapy with a long-acting antimuscarinic agent and a long-acting β2-agonist are recommended in chronic obstructive pulmonary disease (COPD) if control is not adequate with one long-acting bronchodilator alone. We evaluated the effects of indacaterol and tiotropium combination therapy, including the effects of adding indacaterol to tiotropium (indacaterol add-on group) and adding tiotropium to indacaterol (tiotropium add-on group).
  
  
  METHODS
  We recruited 79 patients with COPD already treated with tiotropium or indacaterol. We undertook pulmonary function tests, the COPD assessment test (CAT), and the multi-frequency forced oscillation technique (to measure respiratory resistance and reactance) before and after 8 weeks of indacaterol and tiotropium combination therapy.
  
  
  RESULTS
  The median age was 72.1 years and the mean forced expiratory volume in 1 s (FEV1) as a proportion of predicted was 57.2 ± 18.3%. After 8 weeks of combination therapy, FEV1 and %predicted FEV1 had increased significantly. There was no change in CAT score. For respiratory impedance, combination therapy improved resistance at 5 Hz (R5) and resistance at 20 Hz (R20) in the whole-breath, inspiratory and expiratory phases, and resonant frequency (Fres) in the inspiratory phase. The indacaterol add-on group (43 patients) and tiotropium add-on group (36 patients) showed improvements in FEV1 and %predicted FEV1 over monotherapy, although the CAT score fell significantly in the indacaterol add-on group (p = 0.005).
  
  
  CONCLUSIONS
  Indacaterol and tiotropium combination therapy improved airflow limitation and respiratory resistances. Adding indacaterol to tiotropium, or tiotropium to indacaterol, had similar effects on airflow limitation.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Sayomi
authors.initials: S
authors.lastname: Matsushima
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan; Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. Electronic address: inui@hama-med.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kono
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Respiratory Medicine, Hamamatsu Rosai Hospital, 25 Shougen-cho, Hamamatsu 430-8525, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Toyoshima
authors.affiliation: Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1 Kita-ando, Shizuoka 420-0881, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shirai
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000627:therapeutic use*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D007189:Indans; D015363:Quinolones; D012602:Scopolamine Derivatives; C510790:indacaterol; D000069447:Tiotropium Bromide
keywords: Chronic obstructive pulmonary disease; Combination therapy; Forced oscillation technique; Indacaterol; Tiotropium