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