Recent advances in our understanding of the mechanisms of late lung development and bronchopulmonary dysplasia

Abstract

The objective of lung development is to generate an organ of gas exchange that provides both a thin gas diffusion barrier and a large gas diffusion surface area, which concomitantly generates a steep gas diffusion concentration gradient. As such, the lung is perfectly structured to undertake the function of gas exchange: a large number of small alveoli provide extensive surface area within the limited volume of the lung, and a delicate alveolo-capillary barrier brings circulating blood into close proximity to the inspired air. Efficient movement of inspired air and circulating blood through the conducting airways and conducting vessels, respectively, generates steep oxygen and carbon dioxide concentration gradients across the alveolo-capillary barrier, providing ideal conditions for effective diffusion of both gases during breathing. The development of the gas exchange apparatus of the lung occurs during the second phase of lung development-namely, late lung development-which includes the canalicular, saccular, and alveolar stages of lung development. It is during these stages of lung development that preterm-born infants are delivered, when the lung is not yet competent for effective gas exchange. These infants may develop bronchopulmonary dysplasia (BPD), a syndrome complicated by disturbances to the development of the alveoli and the pulmonary vasculature. It is the objective of this review to update the reader about recent developments that further our understanding of the mechanisms of lung alveolarization and vascularization and the pathogenesis of BPD and other neonatal lung diseases that feature lung hypoplasia.

Estimation of absolute number of alveolar epithelial type 2 cells in mouse lungs: a comparison between stereology and flow cytometry

“…The stereological analysis of lung structure has gained much momentum over the past years (Weibel, ), where stereology is increasingly appreciated as a means to study pathological disturbances to lung structure that accompany disease (Mühlfeld & Ochs, ; Ochs & Mühlfeld, ; Mühlfeld et al ., ; Surate Solaligue et al ., ; Weibel, ). Similarly, stereology is appreciated as a means to quantify the parenchymal (Hyde et al ., ; Ochs et al ., , Knust et al ., ; Wulfsohn et al ., ; Herring et al ., ; Pozarska et al ., ; Hoang et al ., ) and vascular (Knust et al ., ; Willführ et al ., ; Mühlfeld et al ., ) structure of healthy immature, as well as adult lungs.…”

“…The stereological analysis of lung structure has gained much momentum over the past years (Weibel, 2013), where stereology is increasingly appreciated as a means to study pathological disturbances to lung structure that accompany disease Mühlfeld et al, 2015;Surate Solaligue et al, 2017;Weibel, 2017). Similarly, stereology is appreciated as a means to quantify the Fig.…”

Human lung development: recent progress and new challenges

“…It is immediately obvious that human developmental biology will provide insight into lung conditions experienced by premature neonates whose lungs are still going through embryonic developmental stages at the time of birth (Surate Solaligue et al, 2017). However, a recent study revealed the surprising finding that some of the most tightly linked genetic variants that predispose a person to chronic adult lung disease were predicted to function in lung development (Hobbs et al, 2017).…”

Autophagy inducers restore impaired autophagy, reduce apoptosis, and attenuate blunted alveolarization in hyperoxia‐exposed newborn rats

“…In contrast to severe lung injury and fibrosis manifest in old BPD, new BPD primarily manifests as mild lung injury as well as simplified pulmonary alveoli and blood vessels. The lungs of these premature infants are in transition from the canalicular phase to the vesicular phase and this process that can be interrupted by oxygen inhalation or mechanical ventilation …”