PURPOSE: Bronchial diseases may potentially be treated with local, direct infusion of medications into the bronchial wall and adventitia. The safety of deploying a microneedle and infusing liquids into the bronchial adventitia has not been tested. The aim of this study was to characterize injury, inflammation, epithelial damage and hemorrhage, fibrin or thrombus (HFT) one week after broncho-adventitial infusion.
METHODS: The transbronchoscopic micro-infusion catheter (Blowfish(tm), Mercator MedSystems, Inc.) uses balloon inflation to deploy a single, 0.9 mm long 35Ga needle perpendicularly into the bronchial wall. Three pigs underwent flexible bronchoscopy with the catheter advanced through the working channel and received infusions of 20% contrast medium (IsoVUE(r) 370, Bracco Diagnostics, Inc.) in saline. Three infusion volumes (0.3ml, N=10; 1.0ml, N=10; 3.0ml, N=6) were tested. X-ray fluoroscopy and bronchoscopy were used to confirm infusion success. Subjects were sacrificed seven days after delivery. Formalin-fixed bronchi and surrounding parenchymal tissues were cross-sectioned at 2-4 mm intervals. Injury, inflammation, epithelial loss and HFT were each scored (0=none, 1=mild, 2=moderate, 3=severe) to determine broncho-adventitial infusion safety.
RESULTS: Findings of mild to moderate injury, inflammation and HFT were typically focal (2/26 bronchi had findings of injury or HFT in two serial tissue sections and 1/26 bronchi had inflammation in four serial tissue sections). Mild epithelial loss was noted in only 1/126 tissue sections. Averages of the highest scores for each infused segment yielded injury scores of 0±0, 0.30±0.20 and 0±0, inflammation scores of 0.60±0.16, 1.0±0.15 and 0.67±0.21, epithelial loss scores of 0±0, 0.10±0.10 and 0±0, and HFT scores of 0.30±0.21, 0.70±0.30 and 0.33±0.21 with infusion volumes of 0.3ml, 1.0ml and 3.0ml, respectively.
CONCLUSION: Broncho-adventitial infusion of 0.3 to 3.0ml resulted on average in mild injury, inflammation and HFT seven days after infusion of 20% contrast in saline. Mild to moderate damage is expected to heal over time and 21-day studies are planned.
CLINICAL IMPLICATIONS: Safety of broncho-adventitial drug delivery may allow the development of local drug therapies to treat a substantial and growing number of bronchial diseases.
DISCLOSURE: Armin Ernst, Grant monies (from sources other than industry) The project described was supported by Award Number R41CA141907 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.; Shareholder Dr. Kirk Seward is a shareholder of Mercator MedSystems, Inc.; Employee Dr. Kirk Seward is President and Chief Technology Officer of Mercator MedSystems, Inc.; Fiduciary position (of any organization, association, society, etc, other than ACCP Dr. Kirk Seward is on the Board of Directors of Mercator MedSystems, Inc.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The Blowfish Micro-Infusion Catheter is not yet approved by the FDA.