Over 215,000 people will be diagnosed in 2008 with bronchial carcinoma in the U.S. according to the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. Currently, asthma afflicts 22.9 million people in the U.S., and tracheomalacia is believed to afflict 3 million people in the U.S. In addition to these chronic or deadly conditions, intervention into the bronchial passageways with bronchoscopic procedures can cause bronchial granulation tissue that obstructs airflow. These diseases of the bronchi each may potentially be treated with local, direct infusion of medications into the bronchial wall and adventitia (the tissue between smooth muscle layers and cartilage). In fact, data suggests that diseases of the bronchi arise in the sub-epithelial bronchial wall, and thus local treatment beyond the epithelium is warranted. Despite the magnitude of these problems, and the potential for a simple solution, there exists no device useful to deliver safely and reliably into the bronchial wall. Mercator MedSystems has developed a vascular adventitial infusion catheter that has FDA 510(k) clearance to market for use in humans. This is an endovascular balloon catheter which extrudes a single needle through the vessel wall when the balloon is inflated, thus allowing direct therapeutic access to the adventitia. It has been discovered that vascular adventitial delivery leads to cylindrical deposition of drugs around the vessel, creating a natural drug-eluting reservoir. In this proposal, we hypothesize that by tailoring the Mercator Micro-Infusion Catheter for bronchial use, we can show that local infusion into the bronchial wall is safe and can result in an appropriate pharmacokinetic profile. We intend to verify that the device can be sized up from its current 8 mm diameter to 16 mm diameter for bronchial use while remaining compatible with the 2.8 mm working channel of bronchoscopes (Specific Aim 1). After this, we will test simple saline infusion into pig bronchial adventitia and analyze the tissue for damage at different volume infusions from 0.05 ml to 1.0 ml (Specific Aim 2). Finally, we will establish the pharmacokinetic and toxicity profile of paclitaxel, a drug that may be used for local chemotherapy or to reduce the buildup of granulation tissue, at doses ranging from 1 to 100
Public Health Relevance Statement: RELEVANCE The relevance of this proposal lies in its potential to reduce morbidity and mortality associated with occlusive diseases of the bronchi, due to a lack of effective therapies for this important clinical problem.
Project Terms: Adventitia; Adventitial Tissues; Adventitious Tissue; Albumins; Anzatax; Ar element; Argon; Asotax; Aspiration, Respiratory; Asthma; Azul de Metileno; Benign; Binding; Binding (Molecular Function); Blood Plasma; Blood Vessels; Blu di Metilene; Body Tissues; Breathing; Bristaxol; Bronchi; Bronchial Asthma; Bronchiogenic Carcinoma; Bronchogenic Carcinoma; Bronchogenic Lung Carcinoma; Bronchoscopes; Bronchoscopy; CI Basic Blue 9; Caliber; Carcinoma in Situ; Carcinoma, Bronchial; Carcinoma, Intraepithelial; Carcinoma, Preinvasive; Cartilage; Cartilagenous Tissue; Catheters; Chronic; Clinical; Clinical Research; Clinical Study; Clinical Trials, Phase II; Clotting; Coagulation; Coagulation Process; Cold Therapy; Coloring Agents; Colour Index No. 52015; Cryotherapy; Data; Deposit; Deposition; Development; Devices; Diagnosis; Diagnostic; Diameter; Diffusion; Disease; Disorder; Dose; Drug Delivery; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Drug Targeting; Drug Targetings; Drugs; Dyes; Electrocautery; Electrocoagulation; Electromagnetic, Laser; Endocavitary Fulguration; Epithelial; Epithelium; FLR; Failure (biologic function); Family; Family suidae; Forcep; Formulation; Formulations, Drug; Fulguration; Galvanocautery; Granulation Tissue; Human; Human, General; INFLM; Inflammation; Infusion; Infusion procedures; Inhalation; Inhaling; Injectable; Inspiration, Respiratory; Intervention; Intervention Strategies; Kinetic; Kinetics; Lasers; Learning; Liquid substance; Lung; Lung Parenchyma; Lung Tissue; Man (Taxonomy); Man, Modern; Marketing; Measures; Medication; Methylene Blue N; Methylene blue; Methylenum Caeruleum; Methylthionine Chloride; Methylthioninii Chloridum; Methylthioninium Chloride; Microscopic; Modeling; Molecular Interaction; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Muscle, Involuntary; Muscle, Smooth; NCI; NCI Organization; National Cancer Institute; Necrosis; Necrotic; Needles; Operation; Operative Procedures; Operative Surgical Procedures; Paclitaxel; Paclitaxel (Taxol); Patients; Pattern; Pharmaceutic Preparations; Pharmaceutical Preparations; Pharmacokinetics; Phase 2 Clinical Trials; Phase II Clinical Trials; Phenothiazin-5-ium, 3,7-bis(dimethylamino)-, chloride; Pigs; Pilot Projects; Plasma; Pneumology; Pneumonology; Praxel; Prevention; Procedures; Process; Pulmonary Disease (Specialty); Pulmonary Medicine; Pulmonology; RF ablation; Radiation, Laser; Radio Frequency Ablation; Radiofrequency Ablation; Radiofrequency Interstitial Ablation; Research; Respiratory System, Lung; Reticuloendothelial System, Serum, Plasma; SEER Program; SEER Program (National Cancer Institute (U.S.)); SEER-Surveillance, Epidemiology, and End Results; SYS-TX; Safety; Saline; Saline Solution; Schultz No. 1038; Serum, Plasma; Shunt; Shunt Device; Site; Smooth muscle (tissue); Solutions; Stents; Structure of parenchyma of lung; Suidae; Surgical; Surgical Diathermy; Surgical Interventions; Surgical Procedure; Surveillance, Epidemiology, and End Results Program; Swine; Swiss Blue; System; System, LOINC Axis 4; Systemic Therapy; Taxol; Taxol (Old NSC); Taxol A; Taxol Konzentrat; Technology; Testing; Tetramethylthionine Chloride Trihydrate; Therapeutic; Therapeutic Cold; Thermocoagulation; Time; Tissues; Toxic effect; Toxicities; Tracheal Stenosis; Translating; Translatings; Translations; Tunica Adventitia; Work; base; bronchial cancer; chemotherapy; clinical relevance; clinically relevant; commercialization; design; designing; disease/disorder; drug/agent; effective therapy; experiment; experimental research; experimental study; failure; fluid; improved; in situ cancer; innovate; innovation; innovative; inspiration; interventional strategy; language translation; liquid; local drug delivery; lung volume; meetings; nano particle; nanoparticle; novel; phase 2 study; phase 2 trial; phase II trial; pilot study; porcine; protocol, phase II; pulmonary; research study; response; restenosis; shunts; study, phase II; success; suid; surgery; tool; trend; tumor; vascular
