chapter  15
26 Pages

Alveolar Epithelial Function in Ventilator-Injured Lungs

WithJames A. Frank, Michael A. Matthay

A healthy alveolar epithelium functions to maintain a surface for gas exchange, protect against invasion from airborne pathogens, regulate air-

space fluid content (including removing airspace edema fluid), synthesize

and secrete surfactants, and repair itself following injury. All of these func-

tions are potentially impaired as a consequence of injurious mechanical

ventilation (Table 1). Clinical studies have found that preservation of the

alveolar epithelial barrier correlates with better outcomes including mortal-

ity in patients with acute lung injury (ALI) and the acute respiratory distress

syndrome (ARDS) (1,2). For example, Ware and Matthay reported that ALI/ARDS patients with the most preserved epithelial fluid-transport rates

had a significantly lower death rate and a shorter duration of mechanical

ventilation compared with patients who had submaximal or absent alveolar

fluid transport capacity (2). Because mechanical ventilation induces abnor-

mal mechanical stresses on the alveolar epithelium, ventilator-induced alve-

olar epithelial injury could significantly affect outcomes in ARDS patients.

This hypothesis was supported by the recent ARDS Clinical Trials Net-

work study comparing ventilation with 12mL/kg tidal volumes and ventila-

tion with 6mL/kg tidal volumes (3). In this study, lower tidal volume

ventilation resulted in an absolute reduction in mortality of 9%, translating

into one life saved for every 11 ALI/ARDS patients managed with the low tidal volume strategy (3). This chapter primarily considers the effects of

mechanical ventilation on alveolar epithelial barrier function including lung

epithelial protein permeability and ion and fluid transport. The effects of

mechanical ventilation on epithelial-derived inflammatory mediators and

surfactant function are briefly reviewed; however, these topics are reviewed

in more detail in Chapters 7, 8, 9, and 19 of this text.