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.

Keywords: alveolar growth; developmental biology; stereology.

Fig. 1.

The log of the number of alveoli in the lung (N_alv,lung) vs. age (yr) is plotted according to a 2-parameter power function (Table 1).

Fig. 2.

The log of the number of alveoli in the right lung (circles and solid line) and the left lung (triangles and broken line) vs. age (yr) is plotted according to a 2-parameter power function (Table 1).

Fig. 3.

Log N_alv,lung vs. length (cm) is plotted according to a linear function (Table 1).

Fig. 4.

N_alv,lung vs. weight (kg) is plotted according to a 2-parameter power function (Table 1).

Fig. 5.

Radial alveolar counts vs. age (yr) are plotted according to a 2-parameter power function (Table 1).

Fig. 6.

N_alv,lung vs. percentage of life lived based on life expectancy for the species for human (circles and solid line), rhesus (triangles and dotted line), and rat (stars and dotted-broken line) are plotted according to a 2- or 3-parameter function (Table 1). Rhesus data were based on previous reports (14, 19) and rat alveoli numbers (3, 24, 25).

Fig. 7.

The log of the lung volume (Log Lv) vs. percentage of life lived based on life expectancy for the species for human (circles and solid line), rhesus (triangles and dotted line), and rat (stars and dotted-dashed line) are plotted according to a 2- or 3-parameter function (Table 1). Rhesus data were based on previous reports (14, 19) and rat alveoli numbers (3, 24, 25).

Fig. 8.

Lung log Lv vs. the log of the number of alveoli in the lung (Log N_alv,lung) for human (circles and solid line), rhesus (triangles and broken line), and rat (stars and dotted-dashed line) are plotted according to a linear function (Table 1). Rhesus data were based on previous reports (14, 19) and rat alveoli numbers (3, 24, 25).