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2 results on '"Joseph A. Nero"'

1. Aerosolization of Second-generation Triazoles: In Vitro Evaluation and Application in Therapy of Invasive Airway Aspergillosis

Author

Carlo J. Iasella, Shahid Hussain, Christopher R. Ensor, Harisudhan Thanukrishnan, Joseph A. Nero, M. Hong Nguyen, Matthew R. Morrell, Raman Venkataramanan, Timothy E. Corcoran, John F. McDyer, and Cody A. Moore

Subjects
Adult, medicine.medical_specialty, Posaconazole, Antifungal Agents, 030230 surgery, Aspergillosis, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, Galactomannan, 0302 clinical medicine, Internal medicine, Administration, Inhalation, Bronchoscopy, medicine, Humans, Respiratory Tract Infections, Aerosolization, Voriconazole, Aerosols, Transplantation, medicine.diagnostic_test, business.industry, Triazoles, medicine.disease, Regimen, Bronchoalveolar lavage, chemistry, Feasibility Studies, 030211 gastroenterology & hepatology, Female, Caspofungin, business, Invasive Fungal Infections, medicine.drug, Lung Transplantation
Abstract

BACKGROUND A lung transplant patient with invasive aspergillosis (IA) manifested symptoms of voriconazole-induced transaminitis with systemic voriconazole and progression of IA after switching to oral posaconazole. With limited options for standard triazole therapy, aerosolized delivery with one of the second-generation triazoles was considered. METHODS Feasibility for aerosolized delivery was evaluated using cascade impactor and analysis of physicochemical characteristics of voriconazole (10 mg/mL) and posaconazole (6, 12 mg/mL) solutions. RESULTS Both triazoles showed favorable characteristics for aerosol delivery with mass median aerodynamic diameter, geometric standard deviation, respirable fraction (

Published
2019

2. Quantitative imaging of airway liquid absorption in cystic fibrosis

Author

Joseph M. Pilewski, Matthew R. Markovetz, Lawrence Weber, Thomas J. Harding, Landon W. Locke, Michael M. Myerburg, Timothy E. Corcoran, Michael Czachowski, Robert S. Parker, Stefanie L. Brown, and Joseph A. Nero

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Spirometry, Osmosis, Pathology, medicine.medical_specialty, Cystic Fibrosis, Mucociliary clearance, Absorption (skin), Pharmacology, Cystic fibrosis, Article, Young Adult, In vivo, Image Processing, Computer-Assisted, Humans, Medicine, Child, Radionuclide Imaging, Cells, Cultured, Aerosols, medicine.diagnostic_test, business.industry, Middle Aged, Pentetic Acid, respiratory system, Fluid transport, medicine.disease, Mucus, Hypertonic saline, Treatment Outcome, Case-Control Studies, Mutation, Technetium Tc 99m Sulfur Colloid, cardiovascular system, Female, Radiopharmaceuticals, business, circulatory and respiratory physiology
Abstract

New measures are needed to rapidly assess emerging treatments for cystic fibrosis (CF) lung disease. Using an imaging approach, we evaluated the absorptive clearance of the radiolabeled small molecule probe diethylene triamine penta-acetic acid (DTPA) as an in vivo indicator of changes in airway liquid absorption. DTPA absorption and mucociliary clearance rates were measured in 21 patients with CF (12 adults and nine children) and nine adult controls using nuclear imaging. The effect of hypertonic saline on DTPA absorption was also studied. In addition, in vitro studies were conducted to identify the determinants of transepithelial DTPA absorption. CF patients had significantly increased rates of DTPA absorption compared with control subjects but had similar mucociliary clearance rates. Treatment with hypertonic saline resulted in a decrease in DTPA absorption and an increase in mucociliary clearance in 11 out of 11 adult CF patients compared with treatment with isotonic saline. In vitro studies revealed that ∼ 50% of DTPA absorption can be attributed to transepithelial fluid transport. Apically applied mucus impedes liquid and DTPA absorption. However, mucus effects become negligible in the presence of an osmotic stimulus. Functional imaging of DTPA absorption provides a quantifiable marker of immediate response to treatments that promote airway surface liquid hydration.

Published
2014

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