1. Tiotropium Bromide Step-Up Therapy for Adults with Uncontrolled Asthma Stephen P. Peters, M.D., Ph.D., Susan J. Kunselman, M.A., Nikolina Icitovic, M.A.S., Wendy C. Moore, M.D., Rodolfo Pascual, M.D., Bill T. Ameredes, Ph.D., Homer A. Boushey, M.D., William J. Calhoun, M.D., Mario Castro, M.D., Reuben M. Cherniack, M.D N Engl J Med 2010;363:1715-26 R2. Son Jung-il/ Prof. Park Myung-jae

2. Background Many adults with asthma have inadequate control of symptoms when receiving a low-to-medium dose of an inhaled glucocorticoid Treatment options –leukotriene modifier –long-acting beta-agonist (LABA) –increased dose of an inhaled glucocorticoid Safety ??? Any other medication?? Tiotropium !!

3. TALC study : Tiotropium Bromide as an Alternative to Increased Inhaled Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled Corticosteroid Two hypotheses were tested 1.Addition of tiotropium bromide would be superior to a doubling of the dose of an inhaled glucocorticoid 2.Addition of tiotropium would not be inferior to the addition of a LABA. Background

4. Method

5. Methods Inclusion criteria –Age of at least 18 years –History of asthma confirmed by bronchodilator –FEV1 of more than 40% of the predicted value, –Nonsmoker Exclusion criteria –Use of any prohibited drug including other asthma medications or medica tions contraindicated in the study –Significant medical illnesses or lung diseases other than asthma –Vocal cord dysfunction –Respiratory tract infection –Significant asthma exacerbation in the previous 4 weeks –History of life ‐ threatening asthma in the past 5 years, –Pregnant or not using acceptable birth control methods if of childbearing p otential

6. Methods

7.  Outcome measures Primary outcome Morning PEF Secondary outcome –FEV1 before bronchodilation –the number of asthma-control days –the number of asthma symptoms, –the number of rescue-bronchodilator use, asthma exacerbations –the number of use of health care services, –biomarkers of airway inflammation –Results of validated questionnaires

8. Results

11. 31.3% of patients had a two-dimensional response to all three treatment regimens, whereas 9.4% had no such response to any of them. Two-dimensional responses occurred in –66.3% in tiotropium, 53.1% in double-glucocorticoid, 70.6% in salmeterol group.

12. Conclusion 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