Interspecies comparisons of particle deposition and mucociliary clearance in tracheobronchial airways

Abstract

Inhaled insoluble particles that deposit along normal healthy tracheobronchial airways of humans and other mammals are transported on the proximally moving mucous lining to the larynx, where they are swallowed. The transit time from the most distal ciliated airways varies from 0.1 to 1 d, with each individual having a relatively constant, characteristic time. The exact time course of clearance depends on the distributions of both particle deposition and mucus velocities along the airways. There are too few data on intrabronchial deposition and mucociliary transport rates for laboratory animals to permit a thorough intercomparison among species. However, enough is known about the relative lung sizes and anatomical differences among the various species to make some preliminary, but important, distinctions. As compared to commonly used experimental animals, humans have larger lungs and a more symmetric upper bronchial airway branching pattern. In addition, humans do considerable oral breathing, thus bypassing the effective air cleaning capability of the nasal airways. These differences contribute to a greater amount of upper bronchial airway particle deposition in humans, as well as to greater concentrations of deposition on localized surfaces near airway bifurcations. Airborne irritants that deposit in small ciliated airways may produce marked changes in mucociliary transport. Such materials include cigarette smoke, submicrometer-sized sulfuric acid mist, nitrogen dioxide, and ozone. For cigarette smoke and sulfuric acid, which have been studied for transient effects following single brief exposures in both humans and animals, the responses are similar. Upon repetitive exposures in animals, both of these irritants produce persistant alterations in clearance rates and airway morphometry. Studies of the effects of ozone on mucociliary clearance have, up to now, been limited to tests of the responses of rats to single exposures. The similarities between the known effects of various irritants suggests a nonspecific response.

RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol

“…There was very little overlap between the lethal and 'safe' doses, and the estimated LD 50 of ricin in mice was approximately 4 μg/kg, in agreement with the published value of 3-5 μg/kg [ 9 ]. Histopathological analysis of the lungs (including the trachea and alveoli) from the mice showed necrosis of alveolar cells, indicating that the aerosol particles were small enough (1-2 μm) to penetrate to the aveolar region of the lung [ 20 ] (data not shown).…”

“…It has been suggested that hepatocellular and renal lesions are the result of toxin induced vascular damage rather than organ damage per se [ 3 ], but we rarely observe such lesions. We postulate that death is more likely due to severe hypoglycemia, as reported by Pincus et al [ 20 ]. With regard to the toxicity of aerosolized ricin, it is not entirely clear how death is caused, though it is likely to be related to a large extent to damage in the lung [ 3 ].…”

In vivo animal models for drug delivery across the lung mucosal barrier☆

“…differences in breathing patterns, obligate nose-breathing and the physics of the aerosols delivered [74]. Overall it would appear that the airway anatomy and oral breathing of humans tends to lead to a greater amount of upper bronchial airway particle deposition and to greater deposition on localized surfaces near airway bifurcations compared to smaller mammals [75]. Table 4 shows the morphometric characteristics of cells in the alveolar region of the lungs of rats, dogs, baboons and humans [76] .…”

Sidestream tobacco smoke exposure acutely alters human nasal mucociliary clearance.

“…Small changes in NMC related to cyclic changes in nasal passage volume are also unlikely to account for the effects seen. Upper respiratory responses to numerous toxicants are qualitatively similar between humans and many experimental animals (10,20,21), and the mechanisms of mucociliary clearance are thought to be similar in humans and most other mammals. Animal studies have shown that low-level irritant exposure accelerates mucociliary clearance.…”