Editorial: The effect of heterogeneity of the network of alveolar wall tissue on airflow, interstitial flow and lung biology.

Over inhalation, oxygen-rich air is drawn into the alveolar cavity by the expansion of the alveolar volume. The volume expansion results in an increase in the alveolar surface area. Because septal tissue is essentially incompressible, stretching of the alveolar surface area results in a thinning of the alveolar wall thickness. The reverse process happens over exhalation; that is, the surface area decreases and the wall thickness increases. The cyclic motion of the alveolar walls plays an important role in influencing the motion of fluid in the interstitial space (i.e., the space between the alveolar epithelium and vascular endothelium). The capillary network surrounding the alveoli is extensive but it does not provide a continuous, uniform, layer. Hence, the thickness and mechanical properties of the alveolar walls are not uniform. On the thin side (Figure 1), the epithelium and endothelium share one common basal lamina. This structural arrangement maximizes gas diffusion, and helps prevent fluid accumulation. On the thick side (Figure 1), extracellular matrix structurally stabilizes the septa, contributing to the mechanical properties of the alveolar walls. Dickie et al. (2007), Dickie et al. (2009) and Tsuda et al. (2019) showed that the structure of the alveolar wall changes over time. Specifically, they found that the alveolar barrier of developing lungs is more easily compromised and susceptible to foreign material influx than that of adult lungs. Interstitial fluid delivers nutrients and oxygen to cells and transports organic wastes, damaged cells, and foreign invaders (nano particles, bacteria, viruses, etc.) from the interstitial space (Choi et al., 2010). Fluid enters the interstitium from the capillaries at the arterial end of the capillary bed and leaves at the venous end. The pressure gradient driving this flow varies along the interstitium, and is a combination of hydrostatic and plasma oncotic pressure between the capillaries and the interstitium. Albumin is responsible for the majority the plasma oncotic pressure (Waddell, 2009). The variation of flow along the interstitium provides another element to the heterogeneity in the alveolar wall. Another source of heterogeneity in the alveolar wall is that the alveolar epithelium is composed of flat and thin Type I pneumocytes, and cuboidal Type II pneumocytes (Figure 1). The former covers most of the alveolar surface and is ideal for gas exchange and the latter plays a crucial role in producing and secreting pulmonary surfactant, which OPEN ACCESS