ABSTRACT
The major function of the human neonatal lung is to rapidly clear fluid from the airways and to begin to exchange gas. The gas diffusion surface of the mature human neonatal lung has a honeycomb-like structure, comprising extensively branched, perfectly matched ducts for air and blood. This configuration maximizes the gas exchange surface area between air and blood, and facilitates maximally efficient packing within the chest cavity. In humans, the gas exchange membrane, which is about 1-mm thick, consists of type I alveolar epithelial cells (AECI), basement membrane, and endothelial cells, with a total surface area that increases in the adult to about 70 m2. This vast and complex structure is developed sequentially by early epithelial tube branching and late septation of terminal air sacs. Perturbation of this developmental process results in abnormal lung structure and, hence, deficiency of the gas exchange function. Thus, premature human delivery interrupts this developmental process, resulting in an injury response phenotype that depends on the stage of lung maturity at the time of delivery. Northway et al. (1) coined the term bronchopulmonary dysplasia (BPD) to label the clinical, radiographic, and pathological features of chronic airway obstruction (broncho) and interstitial lung disease (pulmonary) with emphysema-like alveolar destruction and abnormal peripheral lung development (dysplasia). In those now far-off days respiratory distress syndrome (RDS) due to a combination of delayed fluid clearance, structural immaturity, and surfactant deficiency of the premature lung with the radiographic appearance of hyaline membrane disease were recognized as the major etiological factors from about 32 up to 36 weeks’ gestation. Supportive treatment (oxygen plus pressure plus time) (2) plus fluid overload and left-to-right shunting through a patent ductus arteriosus (3) were recognized early on as the key postnatal, mostly iatrogenic, factors. With the widespread implementation of prophylactic artificial surfactant therapy, coupled with improvements in neonatal care including control of thermoregulation, judicious fluid therapy, gentler ventilation, and so on, the threshold for survival in human prematurity moved steadily downward toward 24 weeks’ gestation. In these extremely premature infants, alveolarization has barely started, and accordingly, the critical feature of the “new BPD” was recognized to be alveolar hypoplasia (4). This chapter provides an overview of the
integrated genetic and molecular processes that drive lung development and discusses concisely how lung injury, repair, and regeneration impact them in the context of BPD.
