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Mucociliary and Cough Clearance by Gamma Scintigraphy Core

$351,195P50FY2008HLNIH

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

The goal of Core E (Mucociliary and Cough Clearance (MCC/CC by Gamma Scintigraphy) is to assess[unreadable] MCC/CC in human subjects and mice in support of projects III-VI of the SCCOR application. Mucociliary and[unreadable] cough clearance, innate host defense mechanisms important for keeping the airways cleansed of bacteria[unreadable] and viruses, are impaired in chronic inflammatory airways diseases such as chronic bronchitis (CB) and[unreadable] cystic fibrosis (CF). MCC rates are measured in humans and animals by assuming that a non-permeating,[unreadable] inhaled marker depositing on the airway surface moves out of the lung at the same rate as the airway[unreadable] surface liquid in which it is immersed. For the human and mouse projects described in this SCCOR proposal[unreadable] we will use radiolabeled (Tc99m) sulfur colloid particles delivered to the lung under controlled inhalation[unreadable] conditions. The egress of these particles from the lung will be monitored by planar gamma scintigraphy. In[unreadable] the human studies, we will measure CC by incorporating a fixed number of controlled, voluntary coughs[unreadable] during the measures of radiolabeled particle clearance. As part of the phenotyping of each human subject to[unreadable] be studied in the clinical projects, we will measure baseline MCC and CC. The effects of inhaled endotoxin[unreadable] and experimental rhinovirus on MCC and CC will be assessed in healthy smokers and nonsmokers (Project[unreadable] IV). In addition, the Core will have the capacity to make measurements of MCC/CC in the UNC Hospitals[unreadable] Clinical Research Unit before and during acute exacerbations of CB (Project V) and CF subjects (Project VI).[unreadable] The ability of hypertonic saline (HS) to enhance rates of MCC/CC in CB and CF patients by rehydrating the[unreadable] airway surface will be evaluated as part of projects V and VI respectively. In addition, measures of airways[unreadable] obstruction (tracer distribution/skew) and the heterogeneity of these measures during repeat studies will be[unreadable] made available to Project investigators. Finally, similar methods used to monitor MCC in humans will be[unreadable] applied to phenotyping the mouse models of MCC dysfunction and assessing the effect of viral infection in[unreadable] the mice (Project III). A small field of view gamma camera with pin-hole collimator will be used to allow[unreadable] sufficient resolution to monitor MCC of the delivered marker to the mouse lung.

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