Chapter 121: Pulmonary Clearance of Infectious Agents

Introduction

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, the lung is repeatedly challenged with microbes via aspiration of secretions from the upper respiratory tract, particularly during sleep. The lung must defend itself against this potentially hostile environment while maintaining the alveolar architecture required for adequate gas exchange. This group of nonrespiratory functions has been collectively termed pulmonary host defenses.¹

Mechanical Defenses

Mechanical defenses include those present in the nasopharynx and conducting airways of the lung.

Nasopharyngeal 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 cleared from the throat.^2–4

Conducting Airways

Defense mechanisms within the conducting airways include the so-called “mucociliary escalator” and a number of constituents of airway secretions.

Mucociliary Escalator

Most particulates larger than 2 μm in diameter affect the conducting airways. Mucociliary clearance and coughing are the principal means of mechanical defense.³ The mucosa of the conducting airways is lined with mucus secreted by goblet cells, bronchial glands, and Clara cells. The mucus blanket is composed of two distinct layers: a watery sublayer, in which most ciliary movement takes place, and an upper viscous layer that is just penetrated by the ciliary tip.^2,4,5 Mucus is propelled cephalad within the respiratory tract by the 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. Particulates can be cleared from the trachea and distal airways within minutes to hours.

Airway Secretions

Airway epithelial cells secrete a broad array of antimicrobial molecules.^6,7 Iron is essential for survival of many microbes.⁸ Iron is sequestered in cells or firmly complexed to transport proteins. Microbes compete for this iron with their own transport proteins, known as siderophores. Lactoferrin, transferrin, and lipocalin-2 are host-derived molecules that effectively complex free iron in mucosal secretions, suppressing bacterial growth by limiting iron required for bacterial replication.⁹

Lysozyme is secreted in abundant quantities in human airways (10–20 mg per day). This enzyme catalyzes the hydrolysis of peptidoglycan constituents of the ...