Alveolar type I

Alveolar gas exchange

Alveolar type II

Surfactant secretion; differentiation into type I cell

Alveolar macrophage

Pulmonary defense



Source: Refs. 100-102.

Source: Refs. 100-102.

converge on the larger, more central airways, whose mucus clearance rate would have to be greater to accommodate the large volumes of mucus being delivered by the smaller distal airways. This process of the movement of mucus up the pulmonary tree, known as the mucociliary escalator, serves the defensive function of clearing from the lung inhaled particles that become trapped in the mucus.

The significance of mucous trapping of aerosolized particles is emphasized by the fact that radiolabeled aerosols have been used in the measurement of mucociliary transport [11]. Mucus clearance from the airways is also enhanced by coughing, which rapidly propels the mucus toward the pharynx. Failure to clear mucus from the airways as a result of ciliary dysfunction or mucus hypersecretion (as may occur in cystic fibrosis or chronic bronchitis) can result in airway obstruction and infection. Such a situation may adversely affect the therapeutic activity of an inhaled drug by increasing the thickness of the mucus layer through which the drug must diffuse to reach its site of action and retard penetration of the aerosolized particles throughout the airways as a result of mucus plugging of the airway lumen. Goblet cells (and mucous glands) are not present in airways distal to the bronchi [12], and therefore a mucus layer does not line the peripheral airways.

Alveolar type I cells represent the principal cell type lining the lumenal surface of the alveoli [10,13], and it is through these cells that gases must diffuse for oxygen and carbon dioxide exchange to occur with blood in the pulmonary capillaries. Alveolar type II cells are also present in the alveoli. Cuboidal in nature, these cells possess microvilli and serve the important function of secreting surfactant [10], a mixture of carbohydrates, proteins, and lipids essential in reducing alveolar surface tension, which diminishes the work of alveolar expansion during inspiration. In addition, type II cells serve as progenitor cells in the regeneration of the alveolar epithelium. For example, type II cells differentiate into type I cells after type I cell damage [10,14].

Epithelium of the central and peripheral airways have the capacity to produce and release proinflammatory mediators, such as arachidonic acid metabolites, nitric oxide, cytokines, and growth factors, and thereby modulate the progression of airway diseases [15]. In addition, substances released from central airway epithelium can influence the ability of adjacent smooth muscle to contract [16].

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