Tiotropium bromide step-up therapy for adults with uncontrolled asthma.
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.).
Peters
Stephen P
SP
Wake Forest University Health Sciences, Center for Genomics and Personalized Medicine Research, Medical Center Blvd., Winston-Salem, NC 27157, USA. sppeters@wfubmc.edu
Kunselman
Susan J
SJ
Icitovic
Nikolina
N
Moore
Wendy C
WC
Pascual
Rodolfo
R
Ameredes
Bill T
BT
Boushey
Homer A
HA
Calhoun
William J
WJ
Castro
Mario
M
Cherniack
Reuben M
RM
Craig
Timothy
T
Denlinger
Loren
L
Engle
Linda L
LL
DiMango
Emily A
EA
Fahy
John V
JV
Israel
Elliot
E
Jarjour
Nizar
N
Kazani
Shamsah D
SD
Kraft
Monica
M
Lazarus
Stephen C
SC
Lemanske
Robert F
RF
Lugogo
Njira
N
Martin
Richard J
RJ
Meyers
Deborah A
DA
Ramsdell
Joe
J
Sorkness
Christine A
CA
Sutherland
E Rand
ER
Szefler
Stanley J
SJ
Wasserman
Stephen I
SI
Walter
Michael J
MJ
Wechsler
Michael E
ME
Chinchilli
Vernon M
VM
Bleecker
Eugene R
ER
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
D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D005938:Glucocorticoids; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D001507:Beclomethasone; D000420:Albuterol; D000069447:Tiotropium Bromide