The primary function of the lungs is the exchange of gases at a rate required to support tissue metabolism. During gas exchange, the lung is continuously exposed to a varied burden of foreign substances, including infectious agents. In addition, microbes immigrate into the lower respiratory tract via subclinical microaspiration of oropharyngeal microbiota.1,2 The lung has the difficult task of defending itself against this potentially hostile environment while maintaining the alveolar architecture required for adequate gas exchange. This group of nonrespiratory antimicrobial functions has been collectively termed pulmonary host defenses.3
Mechanical defenses of the respiratory system include those in the nasopharyngeal airway as well as those in the conducting airways.
Nasal hairs remove most particulates larger than 10 μm. Brisk airflow and rapid changes in direction of the airstream within the nose promote inertial deposition of large particulates, which are cleared primarily by swallowing, sneezing, or coughing. Mucociliary clearance participates in the removal of particulates from the nasopharynx. Ciliated mucosa is present on the nasal septum and turbinates; mucociliary action sweeps mucus toward the posterior pharynx, where secretions are either swallowed or expelled from the throat.4–6
Important functional aspects of the conducting airway defense mechanisms include the mucociliary escalator and airway secretions, as discussed below.
Most particulates larger than 2 μm in diameter affect the conducting airways of the lower respiratory tract. Mucociliary clearance and coughing are the principal means of mechanical defense.5,7 The mucosa of the conducting airways is lined with mucus secreted by goblet cells, bronchial glands, and club cells (previously termed Clara cells). The mucous blanket is composed of two distinct layers: a watery periciliary layer, which provides lubrication for ciliary movement, and an upper more viscous layer that is just penetrated by the ciliary tip.4,6–9 Mucus is propelled cephalad within the respiratory tract by the terminally differentiated pseudostratified ciliated epithelium that lines the conducting airways. Each ciliated cell has approximately 200 cilia, which are approximately 5 to 6 μm in length and have a beat frequency of 12 to 14 beats per second. Beat frequency is regulated by both environmental factors and pharmacologic agents. Particulates can be cleared from the trachea and distal airways within minutes to hours.
Secretory cells of the airway epithelium, including serous, club, and goblet cells, secrete a broad array of antimicrobial molecules.10–13 Mucus is comprised of a complex mix of mucin glycoproteins, diverse antimicrobial peptides, and metabolites. Mucus functions to ensnare microbes for removal and protects the respiratory epithelium from microbial invasion. MUC5B and MUC5AC are the predominant mucins present in mucus, and MUC5B in particular is essential for effective ...