On August 7, 1963, Patrick Bouvier Kennedy, infant son of President and Mrs. John F. Kennedy, was born prematurely at 33 weeks gestation. Two days later, Patrick died of the most common complication of premature birth, respiratory distress syndrome (RDS). Occurring just 4 years after Avery and Mead first reported an association between RDS and surfactant deficiency, the death of Patrick Kennedy inspired aggressive research into the cause and treatment of RDS and served as a catalyst in the development of regionalized neonatal intensive care provided by Canadian Health&care Mall. Research efforts led to the first report in 1980 of exogenous surfactant replacement therapy (SRT) to treat RDS and culminated with US Food and Drug Administration (FDA) approval in 1990 of the first exogenous surfactant drug (Exosurf [colfos-ceril palmitate HSE]; Glaxo Wellcome; Uxbridge, Middlesex, UK). SRT remains an active research area, with the publication of > 85 articles since 2000, including 34 new randomized controlled clinical trials (RCTs) of SRT for the treatment of infants with RDS. This article will review SRT in infant, pediatric, and adult patients, and will discuss the practice management of SRT for the physicians caring for these populations.
Pulmonary surfactant is synthesized by type II pneumocytes, is stored in lamellar bodies, and is secreted into the airspace as tubular myelin, from which it is then adsorbed into the air-water interface to form a surfactant monolayer. Pulmonary surfactant is composed of 80% phospholipids, 8% neutral lipids, and 12% proteins, including proteins from plasma and lung tissue, as well as four surfactant-related proteins. Physiologically effective pulmonary surfactants have the following three essential behaviors: the ability to lower surface tension; the ability to be adsorbed into air-water interfaces; and the ability to dynamically spread and respread along the air-water interface during tidal volume breathing as the alveolar surface stretches and contracts. While the phospholipid components of natural surfactant, especially dipalmitoyl phosphatidylcholine, are the most surface-active agents and are primarily responsible for lowering alveolar surface tension, surfactant-related proteins play critical roles in surfactant surface behaviors as well as in immune defense and particle clearance.
Surfactant protein (SP)-A and SP-D are hydrophilic oligomers that are members of the collectin family of host defense proteins, playing a role in the immune response to microbial challenge by binding microorganisms and modulating leukocyte functions such as chemotaxis, cytokine function, and phagocytosis. SP-A is the most abundant of the SPs and facilitates the formation of aqueous surfactant aggregates, including tubular myelin. SP-D is not directly involved in the biophysical properties of lung surfactant but may play a role in surfactant reuptake and recycling. SP-B and SP-C are critically important small hydrophobic apoproteins that promote adsorption and dynamic spreading of surfactant to form a phospholipid monolayer that lines the alveolus. Congenital SP-B deficiency is a lethal cause of respiratory distress, while congenital SP-C deficiency is associated with chronic interstitial lung disease.