HOST DEFENSES AGAINST RESPIRATORY-INFECTION

The lungs are remarkably resistant to infection. The alveolar membrane covers a surface area of over 140 m(2), nearly three fourths the size of a tennis court, and is exposed to the external environment with every breath.(37, 87) Each day, more than 10,000 L of ambient air pass in and out of the respiratory tract, air that is contaminated with viable particles shed by animals, plants, and soil. The air on a city street may contain more than 100 bacteria/m(3),(5) and indoor environments are often more polluted, containing hundreds to thousands of microorganisms per cubic meter, depending on the activities and ventilation in the room.(5, 110) Humans contribute to bacterial and viral airborne contamination by talking, coughing, sneezing, and releasing microbes from skin and clothing. A cough generates hundreds of respirable droplets, and sneezing releases up to 40,000 droplets, each of which may contain many microorganisms.(45,72) It has been estimated that a million bacteria-laden particles may be released into the air by a person undressing and dressing over a 2-minute period.(5) In addition to the hazard posed by airborne microorganisms, there is evidence that the aspiration of oropharyngeal bacteria is a common occurrence during sleep. Huxley et al(46) reported that 9 of 20 normal subjects aspirated a radiolabeled tracer deposited in the nasopharynx during sleep, and aspiration was observed in all subjects who slept soundly. Despite these onslaughts, the lower respiratory tract is kept nearly sterile, and pneumonia is a relatively infrequent event. The local defenses of the respiratory tract are sufficient to eliminate most microbial transgressions without clinical sequelae. Pneumonia occurs when the offending challenge overwhelms the resident defenses, leading to microbial replication, inflammation, and an immune response. The outcome of this battle depends on microbial virulence, infectious inoculum, and host susceptibility. A vigorous pathogen or legions of less robust invaders are required to triumph over intact host defenses, but a meager challenge may suffice when resistance is weak. This article reviews the local defense mechanisms of the respiratory tract and the pathways for the amplification of these defenses through the inflammatory and immune responses. Common defects in pulmonary defenses that predispose to infection as well as to opportunities to augment host resistance are considered.