Assessing Treatment Options for Smokers With Asthma.

The study is designed as an open label cross-over study. Ethical approval will be obtained from both the University of Alberta Health Research Ethics Board and the University of Saskatchewan Health Research Ethics Board.

Following informed consent, we will obtain pulmonary function testing in all subjects. If subject is currently prescribed a long acting beta agonist (LABA) it will be stopped before continuing with the study and the subject, as with all subjects, will be re-assessed after two weeks. We will also measure exhaled NO (eNO) using standards established by the American Thoracic Society. Additionally we will obtain a urine sample which will be frozen and stored for subsequent metabolite profiling by NMR spectroscopy. Subjects currently prescribed LABA's will have testing done two weeks after stopping medication.

We will obtain routine demographic information including age, sex, and usual asthma medication usage. We will also obtain health related quality of life status using generic (15D) and disease specific (Asthma Quality of Life) questionnaires. Subjects will be instructed regarding use of peak flow meters and the typical symptoms associated with loss of asthma control. They will be instructed regarding accessing a dedicated asthma website (the Virtual Asthma Clinic) that incorporates the above questions. There is also a place for subjects to enter twice daily peak flow measurements. The website is password protected and each subject can access only their own individualized data entry pages. A research coordinator is able to access any subject data again using a unique password. We will use this internet-based program to monitor daily PEF, daily asthma symptoms and asthma-related quality of life. Patients will be instructed to access the website daily and will be re-assessed at two weeks. Subjects will be instructed to continue with their usual asthma management and to log on to the asthma website daily to record symptoms and twice daily peak flows. Peak flows will consist of pre-bronchodilator peak expiratory flow taken in the morning and in the evening. Only subjects meeting criteria for well controlled asthma (GOAL criteria) along with objective compliance with study protocols over the two weeks will then be enrolled in the next phase of the study.

For the next two weeks of the study, subjects will be randomly allocated to take either their regularly prescribed inhaled corticosteroid (ICS) and a long acting beta agonist (LABA) or their regularly prescribed ICS and tiotropium. At the end of this period all subjects will return for spirometry, urine sampling and for measurement eNO. This will be followed by a two week wash-out period when all subjects will take only their inhaled corticosteroid (ICS). For the subsequent two weeks the subject will take the treatment they did not receive in the first two weeks. At the end of this period all subjects will again return for spirometry, urine sampling and for measurement of eNO. During a fifth period of two weeks duration, subjects will take both the LABA and tiotropium. Subjects will then return for final measurement of spirometry, urine sampling and eNO.

Subjects showing variability of symptoms consistent with poor asthma control, will be referred back to their treating physicians with their clinical information. All subjects will be instructed to return to their medication regimen that was initiated by their physician prior to the study.