Asthma is a major health problem in the United States affecting over 22 million individuals. 20 to 30% of asthmatics smoke and smoking asthmatics are relatively resistant to standard treatments. Paradoxically, asthmatics who smoke are routinely excluded from studies of asthma drug therapy. Treatment of asthmatics who are currently smoking is, therefore, an important but understudied area. There are unique aspects of the biology of smoking in asthma that impact treatment and suggest treatment alternatives. The use of inhaled corticosteroids (ICS) is the recommended first step in treating patients with persistent asthma. The combination of an ICS and a long-acting beta agonist (ICS/LABA) is the preferred action when ICS alone fails to achieve adequate control. What to do if control is not achieved with ICS/LABA is problematic. Smokers have a demonstrated resistance to ICS, montelukastand theophyllinemay be more effective in smoking asthmatics compared to non-smokers. Tiotropium is effective as add-on treatment of asthma but its role in smoking asthmatics is unknown. The relative benefits of these treatments have not been studied nor have they been compared to increasing ICS dose in smoking asthmatics with poorly controlled asthma symptoms. As a result, a definitive understanding of the best therapeutic approach to smoking asthmatics that are not adequately controlled with ICS/LABA alone has not been determined. The ultimate goal of the Smoking Asthmatics Pilot Study (SAPS) is a successful completion of the Theophylline/Tiotropium or Montelukast as Add-On Therapy in Smokers with Asthma Not Controlled with Combination ICS/LABA (TOM Trial). This proposed clinical trial will utilize the recruiting potential of the American Lung Association's Asthma Clinical Research Centers (ALA-ACRC) to directly compare four competing approaches to add-on therapy in smoking asthmatics with mild to moderate persistent asthma who are not adequately controlled by the currently recommended asthma treatments, i.e., ICS/LABA, in terms of symptomatic and physiologic endpoints of asthma management. SAPS consists of two protocols, the Network Protocol and the Vanguard Protocol, that will utilize the 19 Clinical Centers of the ALA-ACRC to assess recruitment, retention and compliance of smoking asthmatics and pilot a full-scale TOM Trial protocol at the UCSD ALA-ACRC Clinical Center. It will specifically assess the availability of adequate numbers of subjects for the study, test the performance characteristics of the proposed outcome measures in smoking asthmatics, test the feasibility of the study design and develop the infrastructure, including drug acquisition, necessary for timely initiation of recruitment of a ful-scale study.

Public Health Relevance

Asthma is a major problem in this country affecting 18 million adults, an estimated 20 to 30% of whom smoke. Smoking asthmatics are at increased risk for serious disease and do not respond to usual treatments as well as non-smokers, yet they are systematically excluded from most asthma treatment studies. This study will test the feasibility of a major clinical trial to clearly define the best approach to treating smoking asthmatics whose symptoms are not well controlled by simple inhaled corticosteroids, a long-acting beta agonist and rescue albuterol.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Planning Grant (R34)
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Clinical Trials Review Committee (CLTR)
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Freemer, Michelle M,
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University of California San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
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