The main function of the lung is gas exchange. This function is essential for life and optimized by combining a large surface area in contact with air and a thin barrier for gas (O2/CO2) diffusion. An array of conductive tubes (conductive airways: trachea and bronchi) leads atmospheric air through convection to the distal (alveolar) side of the lung, where gas exchange happens by diffusion (through a pressure gradient). At the alveoli level, many physical forces also play a vital role during the respiratory cycle. To the elastic recoil of the lung, due to the pleura and chest recoil forces, elastic properties of the connective tissue of the alveolar septa should also be taken into account. In addition, alveoli should also overcome interfacial forces from the air-liquid interface they are exposed to. This is mainly the surface tension at the liquid lining layer or hypophase. This force is primarily counteracted by lung surfactant, a specific mix of lipids and proteins synthesized and secreted by specialized cells, the alveolar epithelial type 2 cell (AE2C). On the other hand, the focus of this work is a specific lung disease, lung fibrosis. is a severe disease characterized by chronic inflammation, myofibroblast accumulation, and excessive extracellular matrix deposition, resulting in the damage of lung structure and respiratory failure. In Europe alone, approximately 40,000 new cases are diagnosed each year; however, its prognosis is overall poor, with a median survival of 3–4 years. We hypothesized that: 1) surfactant dysfunction contributes to the early stages and progression of the disease and; 2) we could target lung surfactant dysfunction as a therapeutic approach. With the use of animal models, we concluded that lung surfactant dysfunction is an early event, where AE2C injury plays a key role and alveolar macrophages play an important role during the progression of the disease. In addition, knowing the timing of lung surfactant dysfunction, we performed surfactant replacement therapies in order to prevent or slow down the onset or progression of the disease. From the results presented in this work, we can conclude that exogenous surfactant has an anti-fibrotic effect, increasing the surface area of opened alveoli and reducing the septal wall thickness. We could observe the same effect when transplanting healthy AE2C in diseased animal lungs, in order to replace the inactivated lung surfactant with healthy synthesizing cells.
