Lung surfactant has additional beneficial properties:^{78 79}

•  Acts as physical barrier to inhaled particles and noxious agents
•  Enhances particle clearance
•  Provides host defense against infection
•  Possesses anti-inflammatory properties

Surfactants are a complex mixture of phospholipids and proteins. Phospholipids are the primary surface tension-lowering component of pulmonary surfactants. The surfactant proteins play a critical role in a variety of functions related to respiratory health and development. Currently, researchers have identified four distinct surfactant-associated proteins designated as: SP-A; SP-B; SP-C; and SP-D. The role of each of these proteins in surfactant function and pulmonary function has been clarified in various in vivo and in vitro studies. One of the key differentiating factors among these proteins is their respective affinity for water. SP-A and SP-D proteins are hydrophilic -- they have a strong affinity to water and have been shown to be involved in the innate immunity of the lungs. SP-B and SP-C are both hydrophobic -- they have no affinity to water molecules, which supports their ability to interact with phospholipids and lower surface tension.

Over the past 25 years, since surfactant replacement therapy was first used, it has become commonly accepted that both SP-B and SP-C, when combined with surfactant phospholipids, produce exogenous replacement surfactants that possess the properties needed to promote the formation and stability of the surfactant film leading to lowering of surface tension in the lungs.¹ Studies have shown that SP-B is the most important for the lowering of surface tension. SP-B gene-knockout mice (i.e., mice lacking the SP-B protein) die of respiratory failure soon after birth, whereas those mice lacking SP-C (i.e., SP-C gene-knockout) survive the neonatal period, but may develop various forms of interstitial lung disease much later in life. This same lethal respiratory failure has been documented in human newborns that lack SP-B. ^{80 81}

There are many respiratory diseases associated with the absence of surfactant or loss of its function. These diseases affect both infant and adult populations, and include: ^{43 82 83 84 85}

Many of these diseases are the result of surfactant deficiency or degradation. The goal of Surfactant Replacement Therapy (SRT) is to replace and restore surfactant function.

Currently, exogenous therapeutic surfactants are approved only for use as prophylactic (prevention) or rescue treatment for RDS in premature infants. Commercially available surfactants predominantly in use today are derived from animal sources. Animal-derived surfactants contain low levels of SP-B relative to human surfactant. Concentration of this protein varies considerably between lots of the animal derived surfactants. There is also a theoretical risk of transmitting known and yet to be discovered animal-borne disease. Additionally, cultural or other sensitivities become an important consideration when using animal derived products. Finally, despite many years of research with animal-derived surfactants, the only currently approved administration approach in the United States and Europe entails invasive mechanical ventilation. ^{39 40 44}