We offer a diverse array of capabilities for performing first in man Phase I clinical studies of novel therapeutic agents.
Contact Us- Our experts are available to answer questions about your needs.
- Lung
physiology/function in control and diseased patients
- Challenge
studies in normal, asthma/allergy and COPD patients
Novel Airway Surface Pharmacokinetics Techniques
Measurement of the pharmacokinetics of drugs on the airway surface is an important but difficult technique to make practical for drug development. The UNC Marsico Lung Insitute has an extensive experience in bronchoscopy of subjects post-drug delivery and direct (filter paper) and directed lavage techniques for making such measurements. More recently, much effort has been dedicated to developing a non-invasive technique that is suitable for repetitive PK measurements to generate accurate measurements of pharmacokinetic parameters. A technique that has generated much promise in this regard is the exhaled breath condensate (EBC) technique that harvests small quantities of aerosol droplets, presumably generated in small airways at inspiration, that can be analyzed with high sensitivity by mass spectroscopy approaches.
Measures of the Pulmonary Microbiome
We have developed the capacity to measure the respiratory microbiome with 16S-454 pyrosequencing technologies. This technique has already been applied to studies of acute exacerbations in CF and COPD and measurement of antibiotic effects.
The Marsico Lung Institute (MLI) has developed a number of novel biomarkers for measuring the pharmacodynamic and therapeutic effects of inhaled therapeutic agents in sputum. Much effort has been focused on the measurement of the proper vs. improper hydration of mucus in airway diseases. Consequently, the MLI has a spectrum of technologies designed to measure these parameters in induced or expectorated sputum, including measures of absolute mucin concentrations, mucin/mucus osmotic pressure/modulus, and measures of mucus adhesion. In parallel, the UNC CF Center has the capacity to measure a large number of classical biomarkers in sputum through our Sputum Core, including measures of cell counts, cytokines, and growth factors.
Samples: sweat, sputum, BAL, nasal lavage, exhaled
breath condensate, blood
Markers: cytokines,
mediators, proteins, nucleotides,
mucins,
% solids content,
protease biochemistry, mucus rheology, Westerns,
PCR, flow cytometry
(cell immunophenotyping; cell function), gene arrays, genotyping, isoraft
technology
Sputum
cell viability, total and differential
sputum cell analysis,
sputum cell enrichment/isolation
Scintigraphic evaluation of aerosol particle lung deposition (efficiency, distribution)
We have extensive experience measuring mucociliary clearance as a function of disease status and importantly, in response to therapeutic agents. More recently, these techniques have been extended so that analyses of the heterogeneity of mucus transport as a function of disease status and therapeutic intervention can now be measured.
In addition to classical CT imaging techniques, we have recently advanced the utilization of MRI for investigation of pulmonary disease and therapeutics directed towards restoration of pulmonary function. Novel techniques include state-of-the-art algorithms to generate detailed structural information about the lung from MRI, utilization of measurements of blood flow to generate insights into airway plugging, and soon, the ability to use hyperpolarized xenon to generate measurements of gas distribution to complete the characterization of the lung by this powerful, non-radiation exposing technique.
