title: Tiotropium bromide step-up therapy for adults with uncontrolled asthma.
abstract: BACKGROUND
  Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed.
  
  
  METHODS
  In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison).
  
  
  RESULTS
  The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthma-control days, with a difference of 0.079 (P=0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P=0.004); and daily symptom scores, with a difference of -0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P=0.003).
  
  
  CONCLUSIONS
  When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.).
authors.affiliation: Wake Forest University Health Sciences, Center for Genomics and Personalized Medicine Research, Medical Center Blvd., Winston-Salem, NC 27157, USA. sppeters@wfubmc.edu
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kunselman
authors.forename: Nikolina
authors.initials: N
authors.lastname: Icitovic
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pascual
authors.forename: Bill T
authors.initials: BT
authors.lastname: Ameredes
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Reuben M
authors.initials: RM
authors.lastname: Cherniack
authors.forename: Timothy
authors.initials: T
authors.lastname: Craig
authors.forename: Loren
authors.initials: L
authors.lastname: Denlinger
authors.forename: Linda L
authors.initials: LL
authors.lastname: Engle
authors.forename: Emily A
authors.initials: EA
authors.lastname: DiMango
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Nizar
authors.initials: N
authors.lastname: Jarjour
authors.forename: Shamsah D
authors.initials: SD
authors.lastname: Kazani
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Njira
authors.initials: N
authors.lastname: Lugogo
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Joe
authors.initials: J
authors.lastname: Ramsdell
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.forename: E Rand
authors.initials: ER
authors.lastname: Sutherland
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Wasserman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walter
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D010366:Peak Expiratory Flow Rate; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000009:adverse effects / Q000627:therapeutic use*; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D005938:Glucocorticoids; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D001507:Beclomethasone; D000420:Albuterol; D000069447:Tiotropium Bromide