Mario Castro, MD, examines patient Marsha D. Mitchell.
Researchers at Washington University School of Medicine in St. Louis participated in the study, which found that adding the drug tiotropium bromide, currently approved for COPD but not asthma, to low doses of inhaled corticosteroids was more effective at controlling asthma than doubling inhaled corticosteroids alone, and as effective as adding the long-acting beta agonist salmeterol.
Results were published online Sept. 19 in the New England Journal of Medicine.
Increasing inhaled corticosteroids or supplementing them with long-acting beta agonists like salmeterol are the two preferred treatment options available for adults whose asthma is poorly controlled on low doses of inhaled corticosteroids.
However, higher doses of corticosteroids do not improve symptoms for all patients and can have significant side effects, while long-acting beta agonists have come under scrutiny for their risk of worsening asthma symptoms that could result in hospitalization and, rarely, death.
“Alternative treatments are needed,” says Mario Castro, MD, who led the study locally. Castro directs the Asthma and Airway Translational Research Unit at Washington University School of Medicine. “And these results show that adding tiotropium may expand options available to patients for controlling their asthma.”
Conducted by the National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network, the study compared three treatment methods: doubling the dose of inhaled corticosteroids alone, supplementing a low dose of inhaled corticosteroids with a long-acting beta agonist (salmeterol), and supplementing a low dose of inhaled corticosteroids with a long-acting anticholinergic drug (tiotropium bromide).
Anticholinergics block a part of the autonomic nervous system that can cause airway muscles to contract.
The study followed 210 adults whose asthma was not well controlled on low doses of inhaled corticosteroids alone. Forty of the patients participated in the Washington University study. Participants received each treatment for 14 weeks with two-week breaks in between, for a total of 48 weeks.
Tiotropium bromide was shown to be effective using several asthma control measurements, including patients’ day-to-day lung function as well as the number of days in which they had no asthma symptoms and did not need to use their albuterol rescue inhalers.
When patients began the trial, their average number of such “asthma control days” was 77 per year (extrapolated from the treatment period). Doubling corticosteroids gave patients another 19 symptom-free days on average, while adding tiotropium to low-dose corticosteroids gave them another 48.
“Because tiotropium works through a different mechanism than beta agonists such as salmeterol, it may help people who do not respond well to currently recommended treatments, and may be a good option as a second controller,” Castro says.
Castro says that further analysis of study data will identify which patients respond best to tiotropium. Longer-term studies will establish its safety for asthma patients and its effect on the frequency and severity of asthma exacerbations.
The research was supported by the National Heart, Lung, and Blood Institute (NHLBI), a unit of the National Institutes of Health, and conducted at the 10 member universities of the Asthma Clinical Research Network (ACRN). NHLBI established the network to conduct multiple, well-designed clinical trials for rapid evaluation of new and existing therapeutic approaches to asthma and to disseminate laboratory and clinical findings to the health-care community
Peters S, Kunselman S, Icitovic N, Moore W, Pascual R, Ameredes B, Boushey H, Calhoun W, Castro M, Cherniack R, Craig T, Denlinger L, Engle L, DiMango E, Fahy J, Israel E, Jarjour N, Kazani S, Kraft M, Lazarus S, Lemanske R, Lugogo N, Martin R, Meyers D, Ramsdell J, Sorkness C, Sutherland E, Szefler S, Wasserman S, Walter M, Wechsler M, Chinchilli V, Bleecker E. Tiotropium Bromide Step-Up Therapy for Adults with Uncontrolled Asthma. New England Journal of Medicine. Online Sept. 19, 2010.
More information about the trial—Tiotropium Bromide as an Alternative to Increased Inhaled Corticosteroid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid, or TALC (NCT00565266)—can be found at www.clinicaltrials.gov.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.