PARTICLE RETENTION AND CLEARANCE

Inhaled particulate substances such as cigarette smoke, viruses, bacteria, pollen and occupational or environmental pollutants are pivotal pathogenetic factors for the development of lung disease. Nowadays an increasing number of different therapeutic aerosols are also delivered to the respiratory tract. The impact of the particles on health depends critically on their retention and clearance, which begins at the moment of their interaction with surfactant at the air-liquid interface. The major clearance mechanisms for soluble substances are absorptive processes completed within minutes, such as transepithelial diffusion and transcellular endocytosis. The most effective clearance mechanism for insoluble particles deposited in the alveolar region is phagocytosis by alveolar macrophages and subsequent transport to the mucociliary ''escalator'' in the conducting airways. Submicrometric particles and fibres can be translocated directly from the alveoli to the interstitial space. There is evidence that particulate material which is insoluble in aqueous solution may be dissolved gradually in the lung, once it has been phagocytosed. The alveolar elimination of insoluble particles may take months or years. In the conducting, i.e. ciliated, airways the backbone of the clearance of insoluble particles is the continuous transport of the mucus blanket towards the larynx. This clearance pathway, which can be accelerated by coughing, is normally completed within 24-36 hours. For clinical investigations, 72-hour retention remains a useful functional parameter. There is growing evidence, however, that retention in the conducting airways may last considerably longer, depending on particle size. Due to promotion by surfactant, particles may be retained below the mucus blanket in between the cilia, and be phagocytosed by airway macrophages.