Response of the Tracheobronchial Mucociliary Clearance System to Repeated Irritant Exposure: Effect of Sulfuric Acid Mist on Function and Structure

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Abstract
This study was designed to determine quantitative and temporal alterations in tracheobronchial mucociliary clearance function and structure due to repeated inhalation exposures to a common irritant, sulfuric acid mist. Rabbits were exposed to 250 μg/m3 sulfuric acid (0.3 μ) for 1 h/day, 5 days/week, for up to 1 year, with some animals allowed a 3-month recovery period following the end of the acid exposures. Control animals received temperature- and humidity-conditioned water vapor. At intervals of 2 to 4 weeks, animals inhaled a radioactively tagged tracer aerosol (ferric oxide microspheres, 4.5 μ.m), and its clearance via mucociliary transport from the thorax was monitored by external serial counting. Clearance became slower during the first month of acid exposure, and this slowing became progressive with time through the end of the 12-month exposure period. After cessation of acid exposure, clearance became extremely slow and did not return to normal by the end of the follow-up period. To assess specific histological changes in the tracheobronchial tree, groups of rabbits were killed after 4, 8, or 12 months of exposure and after the follow-up period. Tissue samples from each lung were embedded in plastic, sectioned at 3 μm, and stained with hematoxylin and eosin or alcian blue/periodic acid-Schiff (AB/PAS). Acid exposure changed the airway diameter distribution compared to the control; except for the follow-up group, all acid-exposed animals had a shift to smaller airways. Acid inhalation also caused an increase in epithelial secretory cell density and a shift from PAS to AB staining of glycoprotein within secretory cells, both of which were unresolved by 3 months after the exposures ceased. No evidence of inflammation was found in any of the animals. Thus, repeated exposures to H2S04 resulted in a slowing of mucociliary clearance that was associated with alterations in airway morphometry and morphology. Such changes may be involved in the early pathogenesis of chronic airway disease.