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1 Department of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina 27710; 2 Johns Hopkins University School of Hygiene, Baltimore, Maryland 21205; and 3 Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543
The objective of the study was to develop a
scintigraphic method for measurement of airway mucociliary clearance in
small laboratory rodents such as the mouse. Previous investigations have characterized the secretory cell types present in the mouse airway, but analysis of the mucus transport system has been limited to
in vitro examination of tissue explants or invasive in vivo measures of
a single airway, the trachea. Three methods were used to deposit
insoluble, radioisotopic colloidal particles: oropharyngeal aspiration,
intratracheal instillation, and nose-only aerosol inhalation. The
initial distribution of particles within the lower respiratory tract
was visualized by 
-camera, and clearance of particles was followed
intermittently over 6 h and at the conclusion, 24 h
postdelivery. Subsets of mice underwent lavage for evidence of tissue
inflammation, and others were restudied for reproducibility of the
methods. The aspiration and instillation methods of delivery led to
greater distributions of deposited activity within the lungs, i.e.,
~60-80% of the total respiratory tract radioactivity, whereas
the nose-only aerosol technique attained a distribution of 32% to the
lungs. However, the aerosol technique maximized the fraction of
particles that cleared the airway over a 24-h period, i.e, deposited
onto airway epithelial surfaces and cleared by mucociliary function
such that lung retention at 24 h averaged 57% for delivery by
aerosol inhalation and 
80% for the aspiration or intratracheal
instillation techniques. Particle delivery methods did not cause lung
inflammation/injury with use of inflammatory cells and chemoattractant
cytokines as criteria. Scintigraphy can discern particle deposition and
clearance from the lower respiratory tract in the mouse, is noninvasive
and reproducible, and includes the capability for restudy and lung
lavage when time course or chronic treatments are being considered.
99mTc-labeled sulfur colloid; airway mucus; nose-only aerosol inhalation
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