Document Type

Dissertation

Date of Degree

2011

Degree Name

PhD (Doctor of Philosophy)

Degree In

Pharmacy

First Advisor

Jennifer Fiegel

Abstract

Airborne infectious diseases remain a major global health threat. The primary vector for their transmission is coarse and fine droplets, known as bioaerosols, exhaled from infected individuals during natural respiratory maneuvers, such as breathing, coughing and sneezing. Unfortunately, our current knowledge of the mechanisms by which these exhaled bioaerosols are formed in the lungs is in its infancy. In particular, progress in this field has been hindered by the complex structure of the respiratory fluid and the resulting lack of understanding of the biophysical properties of the fluid.

In this thesis, a series of in vitro mimetics of conducting airway mucus were developed to enable in depth studies of mucus properties and bioaerosol formation from mucus-like surfaces. These mucus mimetics overcome major limitations of currently available models by matching the primary chemical composition and key physical properties of the mimetic to that of native tracheal mucus. Three mimetics were chosen to facilitate the study of highly viscoelastic (diseased) mucus and non-diseased mucus under low shear conditions, such as breathing, or high shear conditions, such as cough.

To study bioaerosol formation in vitro, an enhanced simulated cough machine (SCM) was developed to generate bioaerosols from mucus mimetic surfaces during cough. By controlling the temperature and relative humidity within the SCM, the detectability of bioaerosols generated from the mimetic surfaces was improved due to limited aerosol drying. The size distribution of the bioaerosols was multimodal, with four to five modes being observed for all surfaces probed. While varying the composition of surfactant at the air-mucus interface had a significant impact on surface viscoelastic properties, the size distribution of bioaerosols generated from these surfaces did not differ significantly. However, the ability to generate bioaerosols from different surfaces was highly dependent on surface properties of the mimetic, with highly viscoelastic surfaces generating bioaerosols in only half the experiments. This research will enhance our knowledge of bioaerosol formation in the respiratory tract and ultimately guide the development of alternative strategies to suppress bioaerosol formation.

Keywords

Bioaerosols, Bulk rheology, DPPC, Infasurf, Mucus, Surface rheology

Pages

xxiii, 291 pages

Bibliography

Includes bibliographical references (pages 281-291).

Copyright

Copyright 2011 Rania Hamed

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