Intra-bronchial valves (IBV) Spiration Inc. are being evaluated as palliative treatment for patients with advanced emphysema. Minimal tissue response around this non-stent device is highly desirable to maintain the valve function as well as allow for removal. In order to evaluate the tissue response to IBV devices, histological evaluation of implanted airways was performed in two species.
IBV devices were implanted in 8 sheep and 8 dogs. The animals were bronchoscopically observed at 1, 3 and 6-months. A scheduled number of devices were removed at each time-point from all but 2 of each species. At 1 and 3 months, 2 of each species were sacrificed; the remaining 6 animals were sacrificed at 6-months. For this analysis tissue samples were taken from the airways implanted with valves and from airways where devices had been removed in previous procedures. Each sample was graded on a 5-point scale (0-normal, 1-minimal, 2-mild, 3-moderate, 4-marked) for 8 response categories including mucosal changes (epithelial hyperplasia, cilia loss, metaplasia, ulceration), submucosal changes (edema, fibrosis, glandular hyperplasia) and inflammation. Average tissue response grades were calculated for each category and plotted against time and location to show trends. An average of all response category grades for the implanted airways was calculated for both species to determine the comparative level of tissue reaction for implant sites and removed device sites.
The comparative level of tissue reaction reached a plateau approximately 1 month after implant (1-month: 2.1 ±0.8; 3-month: 2.26 ±0.81; 6-month: 2.39 ±0.85). After removal, resolution of changes occurred quickly, returning to near normal in 2-5 months (1-month removals: 0.45 ±0.53 at 3-months, 0.61 ±0.86 at 6-months; 3-month removals: 0.69 ±0.74 at 6-months).
In these animal models, the average histological response to IBV implants was mild to moderate, preserving tissue and device functionality. Near complete resolution was observed after removal.
In patients, limited tissue response may be a distinctive advantage of the IBV system to preserve function, facilitate removal and allow tissue recovery post-removal.
D.H. Dillard, Spiration Inc.