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.