New Positions

Introduction

The terminal respiratory units of our lungs are spherical  air-sacs called alveoli. These alveoli are lined by pulmonary surfactant which reduces our work of breathing. The mechanism of action of pulmonary surfactant is a reduction of the surface tension at the air-liquid interface of the alveoli to near zero levels during expiration.

What is pulmonary surfactant?

Figure depicts the composition of pulmonary surfactant

Lung surfactant is a complex mixture of phospholipids, neutral lipids and proteins. The main constituent is dipalmitoyl phosphatidylcholine (DPPC) and is responsible for achieving low surface tensions. Presence of surfactant specific proteins SP-A, SP-B, SP-C and SP-D,  unsaturated phosphatidyl cholines (PC) and phosphatidylglycerol (PG) help in the adsorption of lung surfactant to the interface.

 
Surfactant Replacement therapy in Neonatal Respiratory Distress Syndrome (NRDS)

Neonatal Respiratory Distress Syndrome (NRDS) is a fatal disease of the premature newborn. The cause of the disease is deficiency of natural lung surfactant. Instillation of artificial lung surfactant at the air/alveolar interface is the treatment of prime importance in this disease. The commercially available artificial lung surfactants are either synthetic phospholipid mixtures or are derived from animals, which are to be instilled intratracheally. They are costly; and those derived from animals, pose a danger of immunogenic reaction. We are interested in studying this fascinating system responsible for normal respiration in details, both at the level of understanding more of the physiological processes involved, the functions of individual components as well as for development of surfactant replacements in diseases where the surfactant is dysfunctional, notable amongst which is the Neonatal Respiratory Distress Syndrome. An effort has been made to develop an artificial lung surfactant for the treatment of NRDS using various natural and artificial biomaterials.

 
Surfactant Inhibition in Adult Respiratory Distress Syndrome (ARDS)

Adult Respiratory Distress Syndrome (ARDS) is characterized by high permeability pulmonary edema and intrapulmonary shunting caused by endothelial cell damage, which results in refractory hypoxemia. Blood and its components flood the alveoli and may be responsible for the inhibition of lung surfactant in trauma based ARDS. The aim is to develop a surfactant specially tailor-made to this condition.  We have established the role of hematological inhibitors in case of trauma based ARDS, and found a graded susceptibility of different lung surfactant components to inhibition. Our findings have positive implications for the future development of an effective protein-free surfactant that can overcome inhibition and would be promising for trauma based ARDS.

Figure shows the effect of plasma proteins on liposomes of model lung surfactant lipids

Drug Loaded Pulmonary Surfactants in Tuberculosis

In spite of centuries of struggle tuberculosis continues to be a killer disease world wide with 8 million new cases and about 2 million deaths a year. Even with the advent of newer chemotherapeutic drugs and decades of BCG vaccination the disease remains far from being under control. Most cases of tuberculosis begin due to the active mycobacteria in the alveoli of the lungs. Here they interact with a specialized substance called lung surfactant. The presence of the cell wall components of the mycobacteria alters the function of the surfactant system. This project involves study of the interactions between the mycobacterial cell wall and the lung surfactant system and the development of anti-tubercular drug loaded surfactants as inhalable delivery in this disease. The drug loaded surfactant can have dual benefits of acting both as drug carriers as well as anti-atelectatic agents allowing a more homogenous distribution of the drugs in the alveoli.

Figure compares the capillary opening in a capillary surfactometer of a drug loaded surfactant and suitable controls

Miscellaneous Applications

We have been evaluating the dysfunction of pulmonary surfactant in several conditions due to presence of inhibitory agents. These include acids in case of acid lung injury, biofuel emissions and vehicular exhausts in case of the effect of environmental pollutants and meconium in case of meconium aspiration syndrome.

Figure shows the effect of biofuel emissions on the surface activity of three different model and commercial pulmonary surfactants