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Parasympathetic efferent innervation of the lung is the primary source of lung acetylcholine. Inhaled long-acting anticholinergics improve lung function and symptoms in patients with chronic obstructive pulmonary disease. Targeted lung denervation (TLD), a bronchoscopic procedure intended to disrupt pulmonary parasympathetic inputs, is an experimental treatment for chronic obstructive pulmonary disease. The physiologic and histologic effects of TLD have not previously been assessed. Eleven sheep and two dogs underwent circumferential ablation of the main bronchi with simultaneous balloon surface cooling using a lung denervation system (Nuvaira, Inc., Minneapolis, MN). Changes in pulmonary air flow resistance were monitored before and following TLD. Four animals were assessed for the presence or abolishment of the sensory axon-mediated Hering-Breuer reflex before and following TLD. Six sheep were histologically evaluated 30 days post-TLD for the extent of lung denervation (axonal staining) and effect on peribronchial structures near the treatment site. No adverse clinical effects were seen in any treated animals. TLD produced a ~30% reduction in pulmonary resistance and abolished the sensory-mediated Hering-Breuer reflex. Axonal staining was consistently decreased 60% at 30 days after TLD. All treated airways exhibited 100% epithelial integrity. Damage to other peribronchial structures was minimal. Tissue 1 cm proximal and distal to the treatment was normal, and the esophagus and periesophageal vagus nerve branches were unaffected. TLD treatment effectively denervates the lung while protecting the bronchial epithelium and minimizing effects on peribronchial structures.NEW & NOTEWORTHY The feasibility of targeted lung denervation, a new minimally invasive therapy for obstructive lung disease, has been demonstrated in humans with preliminary clinical studies demonstrating improvement in symptoms, pulmonary function, and exercise capacity in patients with chronic obstructive pulmonary disease. This preclinical animal study demonstrates the ability of targeted lung denervation to disrupt vagal inputs to the lung and details its physiologic and histopathologic effects.

Purpose: A wireless tumor localization and tracking system using three implanted AC electromagnetic transponders is in clinical trials for use in prostate cancer (Calypso® Medical). Phantom‐based studies have shown sub‐millimeter spatial localization accuracy in static tests. Accuracy has not been evaluated for dynamic motion found in lung tumors. This study was designed to determine the feasibility of using this patient positioning system for real‐time tumor‐tracking. Materials and Methods: A 4‐dimensional (4D) stage capable of arbitrary multidimensional motion with speeds up to 10 cm/sec was constructed. Two elliptical trajectory paths were created with peak‐to‐peak motion of 1cm × 2cm × 1cm and 2cm × 4cm × 2cm in the x, y and z directions. Each trajectory was operated with periods of 15 – 20 cycles per minute. The Calypso System was operated using one and two transponders with radiofrequency signal integration times of 33 ms 100 ms. The transponders were mounted on the 4D‐stage, with the ellipse centroids positioned 14 cm from the array. The effects of ellipse size, speed, number of transponders and signal integration time on transponder localization accuracy were evaluated by comparing the intended and measured trajectories. Results: The root mean square (RMS) position difference was less than 1 mm for all tested combinations. While small, the RMS error was largest for the large ellipse at 20 cycles per minute compared with the small ellipse at 15 cycles per minute. The single‐transponder system with 67 ms integration time had the smallest overall error, with a maximum single‐point error of 1.3mm. Conclusions Use of a wireless electromagnetic implanted transponder system for real‐time tumor‐tracking is feasible, with RMS errors less than 1mm for high‐speed multidimensional ellipses. This compares favorably with continuous fluoroscopic tracking methods without an ionizing radiation burden. This work is currently being expanded to patient‐derived tumor trajectories.

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