Adaptation of an amphibian mucociliary clearance model to evaluate early effects of tobacco smoke exposure

Abstract

Rationale: Inhaled side-stream tobacco smoke brings in all of its harmful components impairing mechanisms that protect the airways and lungs. Chronic respiratory health consequences are a complex multi-step silent process. By the time clinical manifestations require medical attention, several structural and functional changes have already occurred. The respiratory system has to undergo an iterative process of injury, healing and remodeling with every exposure. Methods:To have a better understanding of the initial changes that take place when first exposed to environmental tobacco smoke, we have developed an exposure model, using the frog palate that closely represents the features of obstructive airways where ciliary dysfunction and mucus hypersecretion occur.Results: Mucus transport was significantly reduced, even after exposure to the smoke of one cigarette (p < 0.05) and even further with 4-cigarettes exposure (p < 0.001). Morphometric and ultrastructural studies by SEM show extensive areas of tissue disruption. Gelatinase zymography shows activation of MMP9 in mucus from palates exposed to tobacco smoke. Conclusions:The clearance of mucus on the frog palate is significantly reduced after exposure to environmental tobacco smoke. Cilia and the extracellular matrix are anatomically disrupted. Tobacco smoke triggers an increased activity of matrix metalloproteinases associated with a substantial defoliation of ciliated epithelium. These studies enhance the knowledge of the changes in the mucociliary apparatus that occur initially after exposure to environmental tobacco smoke, with the goal of understanding how these changes relate to the genesis of chronic airway pathologies in humans.

The diagnosis and management of rhinitis: An updated practice parameter

“…171,172 Tobacco smoking of 1 or more cigarettes in an in vitro frog palate model results in a reduction of mucus clearance and disruption and defoliation of the ciliated epithelium. 831 Although it is often assumed that similar effects occur in human beings, 1 study using saccharin clearance time demonstrated normal mucociliary clearance in healthy smokers, although the average clearance time was longer than in nonsmokers. 173 Likewise, there was no significant difference in mean nasal ciliary beat frequency when comparing healthy smokers with nonsmokers.…”

“…173 It has been suggested that tobacco smoking leads to the dysfunction of the normal metachronal waves that drive mucus over nonciliated areas and that prolonged, sustained exposure to cigarettes may produce loss of ciliated epithelium secondary to activation of matrix metalloproteinases. 831 However, even this ciliary dysfunction shows at least partial recovery within 30 minutes of cigarette smoke avoidance in pure air. 174 Evaluation of rhinitis History 35.…”

In vitro assessment of reproductive toxicity of tobacco smoke and its constituents

“…Ciliary beat frequency is of interest in smokerelated studies because cilia clear mucus from the respiratory tract, which is the first site of smoke exposure in humans, as well as move OCC into and through the oviduct. Cigarette smoke contains chemicals that inhibit ciliary beating in a variety of mammalian and nonmammalian models (Wang, 1963;Dalhamm, 1970;Battista, 1974;Zayas et al, 2004). Ciliary beat frequency has been measured from video recordings using the hamster infundibular bioassay before, during, and after exposure to solutions containing whole smoke, particulate smoke, or the gas phase of smoke (Knoll et al, 1995).…”

Symmetrical-Waveform High-Frequency Oscillation Increases Artificial Mucus Flow Without Changing Basal Mucus Transport in In Vitro Ovine Trachea

“…21 Wills et al also found that some of the responses of mammalian airway were contrary to those of amphibian palate, 22 which has been the classical model for mucociliary transport. 23,24 Taken together, the above studies indicate that the in vitro mammalian trachea may be a sensitive model with which to assess the effects of exogenous factors on mucociliary function.…”