Chapter 60

Pulmonary surfactant lines the inner layer of the lung and serves to lower surface tension at the air–liquid interface, thereby maintaining alveolar stability. In the absence of surfactant, the work of breathing increases markedly ultimately resulting in respiratory failure secondary to atelectasis, alveolar flooding, and severe hypoxemia. The clinical correlate of surfactant deficiency is the neonatal respiratory distress syndrome (NRDS) in preterm infants, which before the mid-1980s was a devastating and fatal disease. Since the advent of exogenous surfactant replacement therapy, however, newborn mortality from NRDS has decreased approximately 56% from 1987 to 1995.1 The primary surfactant deficiency of NRDS is now a well-characterized condition, and does not appear as complex as the various surfactant changes occurring during acute lung injury (ALI) and/or the acute respiratory distress syndrome (ARDS). Alterations of the endogenous surfactant system in the mature lungs of patients with these disorders are not as well understood, but currently represent an area of intense investigation. This complexity has resulted in inconsistent results of clinical trials evaluating exogenous surfactant administration in this patient population.

This chapter reviews surfactant metabolism and function in the mature lung and its role in maintaining normal lung homeostasis, including its more recently described host defense functions. The metabolism and function of surfactant in the injured lung is also outlined, with particular reference to the effects of mechanical ventilation on the alveolar surfactant system. Subsequently, the status of clinical trials evaluating exogenous surfactant administration in patients with ALI or ARDS is addressed, as are the various factors that may influence a host’s response to this therapy. Future research directions relevant to the understanding of the role of surfactant both in ALI and ARDS and other lung diseases conclude the chapter.

### Composition

The composition of surfactant is remarkably similar among mammalian species, consisting of approximately 80% phospholipids, 10% surfactant-associated proteins,24 and approximately 10% neutral lipids, among which cholesterol is the most abundant (80% to 90% by weight).5,6 The major phospholipid component is phosphatidylcholine, half of which is the disaturated species, dipalmitoylphosphatidylcholine (DPPC).4 This latter molecule is the major surface-active component responsible for lowering surface tension at the air–liquid interface, and is an essential component of all exogenous surfactant preparations currently available for clinical use. Other lipids include phosphatidylglycerol and a few minor lipid species, which are thought to be important in the generation and maintenance of the surface film. The surfactant-associated proteins have been designated as SP-A, SP-B, SP-C, and SP-D.7,8 SP-B and SP-C are small, hydrophobic proteins closely associated with the phospholipids, where they play a major role in generating and maintaining the surface tension-reducing surface film.911 SP-B is an 18-kDa dimer, whereas SP-C is a 4-kDa monomer, the latter being the more hydrophobic of these two proteins.12,13 The most clinically effective exogenous surfactant preparations currently in use contain at least one of these natural ...

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