Non-absorptive clearance from airways

Abstract

The lung is protected by multiple mechanisms, but the primary defense is mucociliary clearance (MCC). MCC is responsible for removing noxious particulates that may reduce lung health, but it can also clear inhaled pharmaceuticals. Effective MCC relies on the correct ciliary structure and pattern of movement, combined with mucus rheology characteristics, that together facilitate particle capture and transport. Abnormalities in these result in muco-obstructive disease. The ability to accurately measure MCC is vital for understanding airway dysfunction, and for evaluating inhaled pharmaceutical performance. MCC measurements have been performed in humans for more than a century, and today most still rely on measuring the transit time of marker particles, with the gold standard technique utilizing radiolabeled technetium sulfur colloid. Similar assessment methods for tracking the mass-transit of particles have also been used in animal models. More recent methods designed to assess local individual particle clearance via computed tomography or synchrotron imaging have enabled the MCC behavior of individual particles to be better understood. These new methods have been augmented by airway clearance models and by micro-optical coherence tomography, which can assess MCC directly without the addition of marker particles. Although our understanding of non-absorptive clearance has improved, further technical advances are required to properly understand the key role these mechanisms play in drug design and delivery.