Deposition, retention, and clearance of inhaled particles.

Abstract

The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles > 2 ,um that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air.For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from the alveolar region in a series of temporal phases. The earliest, lasting several weeks, appears to include the clearance of phagocytosed particles via the bronchial tree. The terminal phases appear to be related to solubility at interstitial sites. While the mechanisms and dynamics of particle deposition and clearance are reasonably well established in broad outline, reliable quantitative data are lacking in many specific areas. More information is needed on: (1) normal behaviour, (2) the extent of the reserve capacity of the system to cope with occupational exposures, and (3) the role of compensatory changes in airway sizes and in secretory and transport rates in providing protection against occupational exposures, and in relation to the development and progression of dysfunction and disease.

Desensitization of PKA‐Stimulated Ciliary Beat Frequency in an Ethanol‐Fed Rat Model of Cigarette Smoke Exposure

“…This was consistent across all ethanol concentrations in the rat diet. One possible explanation is that elevated particle exposure from the inhalation of cigarette smoke results in CBF elevation as previously reported (Lippmann et al, 1980;Wolff, 1986). It remains unclear why the presence of isoproterenol under these conditions would abrogate smoke-induced elevated baseline beating.…”

Comparison of twenty three nebulizer/compressor combinations for domiciliary use

“…However, it is likely that these values for deposition will differ depending on the nebulizer used. Where particles are greater than 5 µm, greater quantities of the drug will be deposited in the buccal cavity and the nasopharynx [18][19][20][21]. To be of use, the particles of nebulized bronchodilators must then be absorbed systematically or swallowed.…”

Comparative analysis of inhaled particles contained in human bronchoalveolar lavage fluids, lung parenchyma and lymph nodes.

“…Deposition curves show that 10 to 60% of the inhaled particles within the range 0.1 to 5.0 pm reach the lung (1). The larger fraction of these particles undergoes rapid clearance, but a significant percentage remains trapped in the lungs.…”