Role of the physicochemical environment in lung development

Mechanical forces, exerted on lung tissue via alterations in lung expansion are a major determinant of fetal lung development, having a potent effect on the rate of cellular proliferation, the differentiated state of alveolar epithelial cells and the three-dimensional tissue structure. As a result, much research is currently focused on understanding the molecular mechanisms involved. Although it is likely that mechanical forces exert similar influences on lung development after birth, the types of forces applied to the air-filled lung are very different and more complex. For example, lung aeration causes surface tension to form, which greatly increases lung recoil, leading to a reduction in interstitial tissue and pleural pressures, as well as lung expansion. Because of the loss of the distending influence of lung liquid, the chest wall assumes the role of maintaining resting lung volumes after birth by acting as an external brace that opposes lung recoil. As a result, the distribution of force throughout lung tissue changes markedly. Little is known of how changing the mechanical environment of the lung influences its development after birth, but this has important implications for understanding the impact of assisted ventilation on patients, particularly very preterm infants, who are often ventilated using high positive pressures. Although the application of positive internal distending pressures may, in part, duplicate the fetal environment, the effect of gas versus liquid is unknown and high positive airway pressures are known to adversely affect cardiopulmonary physiology. Understanding the role of mechanical forces in regulating lung development as well as pulmonary physiology in the fetus and newborn is central to improving the care and management of infants suffering respiratory failure.