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.

-Aging is associated with morphometric changes in the lung that lead to decreased lung function. The nonhuman primate lung has been shown to have similar architectural, morphological, and developmental patterns to that of humans. We hypothesized that the lungs of rhesus monkeys age in a pattern similar to human lungs. Thirty-four rhesus monkeys from the California National Primate Research Center were euthanized, necropsied, and the whole lungs sampled. Stereological analysis was performed to assess the morphological changes associated with age. The number of alveoli declined significantly from age 9 to 33 yr with a greater decline in females compared with males. Lungs of females contained roughly 20% more alveoli at age 9 yr than males, but by ϳ30 yr of age, females had 30% fewer alveoli than males. The volume of alveolar air also showed a significant linear decrease in females relative to age, while males did not. The numberweighted mean volume of alveoli showed a significant positive correlation with age in females but not in males. The volume of alveolar duct showed a significant positive correlation with age in females, but not in males. Structural decrements due to aging in the lung were increased in the female compared with male rhesus monkey. stereology; alveolar loss; alveolar duct enlargement OVER THE LAST SEVERAL decades, the median age of the US population has increased by 20 yr. The number of people age 65 yr and over is projected to increase from 35 million in 2000 to an estimated 71 million in 2030, with the largest increase in individuals age 80 yr and above (US Census 2005; http://www. census.gov/#). Numerous diseases are more frequently diagnosed in the aging lung including chronic obstructive pulmonary disease, pulmonary fibrosis, pneumonia, and lung cancer. Emphysema occurs more frequently in aged individuals and implies greater susceptibility of the aged lung to this disease (2). With the costs associated with maintaining an aging population that is increasing, it has become important to understand the process of aging in the lung and the diseases that can be associated with the aging process. An appropriate research model needs to be identified and characterized, both structurally and functionally, to understand the role of the aging process and how diseases exploit that process.Landmark work by Fletcher and Peto (4) demonstrated that the forced expiratory flow in 1 s (FEV 1 ) declines with age and that this decline is accelerated in active smokers with associated lung disease. In addition to accelerated decline of FEV 1 , there is an age-related loss of elastic recoil and decreased dynamic compliance with an increase in air flow resistance (1). The aging lung in humans is associated with numerous changes both functionally and structurally. The structural changes include an increase in alveolar duct volume, mean linear intercept, and the number of interalveolar pores (7, 23). However, a lack of representation of the oldest humans in physiological studies limits our understanding of pulmonar...

In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in lung parenchyma would be permanent following a long-term recovery in filtered (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O3) or HDMA/ozone (HDMA + O3) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compare with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O3 alters the development process in lung alveoli.

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