Growth of alveoli during postnatal development in humans based on stereological estimation

Abstract

Alveolarization in humans and nonhuman primates begins during prenatal development. Advances in stereological counting techniques allow accurate assessment of alveolar number; however, these techniques have not been applied to the developing human lung. Based on the recent American Thoracic Society guidelines for stereology, lungs from human autopsies, ages 2 mo to 15 yr, were fractionated and isometric uniform randomly sampled to count the number of alveoli. The number of alveoli was compared with age, weight, and height as well as growth between right and left lungs. The number of alveoli in the human lung increased exponentially during the first 2 yr of life but continued to increase albeit at a reduced rate through adolescence. Alveolar numbers also correlated with the indirect radial alveolar count technique. Growth curves for human alveolarization were compared using historical data of nonhuman primates and rats. The alveolar growth rate in nonhuman primates was nearly identical to the human growth curve. Rats were significantly different, showing a more pronounced exponential growth during the first 20 days of life. This evidence indicates that the human lung may be more plastic than originally thought, with alveolarization occurring well into adolescence. The first 20 days of life in rats implies a growth curve that may relate more to prenatal growth in humans. The data suggest that nonhuman primates are a better laboratory model for studies of human postnatal lung growth than rats.

Functional evidence for continued alveolarisation in former preterms at school age?

“…Whether the association of minute ventilation with Scond indicates an adaptive mechanism upon increased Scond, or a primary regulatory response cannot be answered by our data [15]. The mechanism for this pattern of ventilation inhomogeneity could be explained by the fact that these children were born during the late canalicular-early saccular period of lung development, when the peripheral conducting airways are already developed and thus vulnerable, while the alveolar regions develop later and continue to grow after birth [35]. Thus, our findings indicate a mismatch in the growth of peripheral conducting airways and lung parenchyma in children born preterm, supporting the concept of a "dysanaptic" lung growth [36,37], related to prematurity.…”

“…Recent advances in imaging techniques [38] and stereological counting methods [35] have provided new evidence for continued alveolarisation beyond infancy up to young adulthood in the healthy lung. Of particular interest, a recent study using helium magnetic resonance showed evidence of continued alveolarisation at school age both in healthy adolescent [38] and former preterm children [39], half the latter diagnosed with BPD.…”

A review of recent developments and applications of morphometry/stereology in lung research

“…Three papers on the postnatal development and aging of the rat, the nonhuman primate, and the human lung will be addressed (48,49,147). All of the three papers used state-of-the-art stereology and present a portfolio of detailed methods to assess lung alveolarization or age-associated loss of alveoli.…”

Modeling human lung development and disease using pluripotent stem cells

“…In humans, exponential growth takes place in the first two years, and a slower increase in alveolar number continues into puberty. In rodents, exponential growth occurs in the first 20 days of life, and stops more abruptly (Herring et al, 2014).…”