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1 Asthmatx Inc., Mountain View, California, USA
2 Department of Pathology, Stanford University , El Camino Hospital, Mountain View, California, USA
3 Department of Pathology, Microbiology, and Immunology, University of California at Davis, Davis, California, USA
4 St. Joseph's Healthcare and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
5 Broncus Technologies Inc., Mountain View, California, USA
6 St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
7 Departments of Medicine, Neurobiology, Pharmacology and Physiology, Universtiy of Chicago, Chicago, Illinois, USA
* To whom correspondence should be addressed. E-mail: cdanek{at}asthmatx.com.
We delivered controlled radiofrequency (RF) energy to the airways of anesthetized, ventilated dogs to examine the effect of this treatment on reducing airway narrowing caused by a known airway constrictor. The airways of 11 dogs were treated with a specially designed bronchial catheter in 3 of 4 lung regions. Treatments in each of the 3 treated lung regions were controlled to a different temperature (55°C, 65°C, and 75°C); the untreated lung region served as a control. We measured airway responsiveness to local methacholine chloride (MCh) challenge before and after treatment and examined post-treatment histology to 3 years. Treatments controlled to 65°C as well as 75°C persistently and significantly reduced airway responsiveness to local MCh challenge (p 
0.022). Airway responsiveness (mean percent decrease in airway diameter following MCh challenge), averaged from 6 months to 3 years post-treatment, was 79% ± 2.2% in control airways vs. 39% ± 2.6% (p 0.001) for airways treated at 65°C, and 26% ± 2.7% (p 0.001) for airways treated at 75°C. Treatment effects were confined to the airway wall and the immediate peri-bronchial region on histologic examination. Airway responsiveness to local MCh challenge was inversely correlated to the extent of altered airway smooth muscle (ASM) observed in histology (r = -0.54, p<0.001). We conclude that the temperature controlled application of RF energy to the airways can reduce airway responsiveness to MCh for at least 3 years in dogs by reducing ASM contractility.
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