Deposition, retention, and clearance of inhaled particles.

Abstract

Relation between concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after inhalation depended on their patterns of deposition and rates and pathways for their clearance from deposition sites. Distribution of deposition sites of inhaled particles depended on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles .gtorsim. 2 .mu.m that deposited in conducting airways by impaction were concentrated onto a small fraction of the surface. Cigarette smoking and bronchitis produced a proximal shift in deposition pattern. The major factor affecting deposition of smaller particles was their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake was relatively complete for all deposition patterns and there was local toxic or irritant effects. Slowly soluble particles depositing in conducting airways were carried on the surface to the glottis and swallowed within 1 day. Mucociliary transport rates were highly variable along ciliated airways of a given individual and between individuals. Changes in clearance rates produced by drugs, cigarette smoke and other environmental pollutants could increase or decrease these rates. Particles deposited in non-ciliated airways had large surface-to-volume ratios and clearance by dissolution occurred for materials generally considered insoluble. They could also be cleared as free particles by passive transport along surface liquids or after phagocytosis by transport within alveolar macrophages. If particles penetrated epithelium, bare or within macrophages, they could be sequestered within cells or entered lymphatic circulation and were carried to pleural, hilar and more distant lymph nodes. Non-toxic insoluble particles were cleared from alveolar region in a series of temporal phases. The earliest, lasting several weeks, included the clearance of phagocytozed particles via bronchial tree. Terminal phases were related to solubility at interstitial sites. While the mechanisms and dynamics of particle deposition and clearance were well established in broad outline, reliable quantitative data were lacking in specific areas. More information was needed on: normal behavior, extent of system reserve capacity to cope with occupational exposures and role of compensatory changes in airway sizes and in secretory and transport rates in providing protection against occupational exposures and in relation to development and progression of dysfunction and disease.