An early history of pulmonary surfactant
The concept of surfactant was first mooted by Kurt von Neergaard in 1929, a German physiologist working in a laboratory in Switzerland. He was the first person to demonstrate that reduced surface tension in the lungs plays an important role in respiratory physiology and should be investigated further[1, 2]. Almost 2 decades later, Peter Gruenwald demonstrated the use of a surface active substance that could be used to reduce the resistance required for aeration of the lungs in his experiments with stillborn infants[3].
In 1959, Mary Avery and Jere Mead published their seminal paper describing how children dying of hyaline membrane disease had increased alveolar surface tension. Avery and Mead further concluded that hyaline membrane disease was associated with the absence or late appearance of a substance, which in normal subjects render the internal surface capable of attaining a low surface tension when lung volume is decreased[4]. It was only 5 years later, following the demise of President John Fitzgerald Kennedy and Jackie Kennedy’s third child, Patrick Bouvier Kennedy who was born at 35 weeks gestation and died 2 days later, that the further study into surfactants, and the development of synthetic surfactants accelerated[5].
During the study of nerve warfare agents in the 1950s , Richard Pattle conducted a study on lung fluid and identified that it mainly constituted of lecithin, protein and gelatin. He also demonstrated that this property of lowering surface tension disappeared when exposed to pancreatin and trypsin[6]. The components of this lung fluid was further delineated by Clements et al into 3 distinct categories; unsaturated phospholipids, non-phosphorylated lipids and proteins[2]. Following this, Weibel and Gil were the first to be able to preserve the layer of surfactant and examine it under electron microscopy which further paved the way into the study of surfactant and surfactant proteins[7, 8].
Surfactant is important to lower the surface tension in alveoli of the lungs, it reduces the surface tension on the air/liquid interface down to a pressure of 1mN/m at low lung volumes[8], therefore surfactant is pivotal in not only lowering the work of breathing, but it also prevents end expiratory alveolar collapse which otherwise would lead to atelectasis[9].Besides lowering surface tension, surfactant also plays a role in the host defence mechanism within the lungs particularly in its’ ability to regulate neutrophils, macrophage, T cells and dendritic cells[10, 11]. Through the study and improved understanding of surfactant over the decades, there is increasing interest into the study of childhood interstitial lung diseases (chILD)[12]. Several mutations of surfactant related gene have been identified as a cause of chILD and the body of research continues to grow in this field.
This review article seeks to provide an overview of surfactant protein deficiency in the context of chILD.