Estimation of alveolar number in the lung has traditionally been done by assuming a geometric shape and counting alveolar profiles in single, independent sections. In this study, we used the unbiased disector principle to estimate the Euler characteristic (and thereby the number) of alveolar openings in rat lungs and rhesus monkey lung lobes and to obtain robust estimates of average alveolar volume. The estimator of total alveolar number was based on systematic, uniformly random sampling using the fractionator sampling design. The number of alveoli in the rat lung ranged from 17.3 ⅐ 10 6 to 24.6 ⅐ 10 6 , with a mean of 20.1 ⅐ 10 6 . The average number of alveoli in the two left lung lobes in the monkey ranged from 48.8 ⅐ 10 6 to 67.1 ⅐ 10 6 with a mean of 57.7 ⅐ 10 6 . The coefficient of error due to stereological sampling was of the order of 0.06 in both rats and monkeys and the biological variation (coefficient of variance between individuals) was 0.15 in rat and 0.13 in monkey (left lobe, only). Between subdivisions (left/right in rat and cranial/caudal in monkey) there was an increase in variation, most markedly in the rat. With age (2Ϫ13 years) the alveolar volume increased 3-fold (as did parenchymal volume) in monkeys, but the alveolar number was unchanged. This study illustrates that use of the Euler characteristic and fractionator sampling is a robust and efficient, unbiased principle for the estimation of total alveolar number in the lung or in well-defined parts of it. Anat Rec Part A 274A: 216 -226, 2004.

Hyde DM, Blozis SA, Avdalovic MV, Putney LF, Dettorre R, Quesenberry NJ, Singh P, Tyler NK. Alveoli increase in number but not size from birth to adulthood in rhesus monkeys.

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SummaryBackground-Accumulation of immune cell populations and their cytokine products within tracheobronchial airways contributes to the pathogenesis of allergic asthma. It has been postulated that peripheral regions of the lung play a more significant role than proximal airways with regard to inflammatory events and airflow obstruction.

The extrapolation to humans of studies of infectious or toxic agents injurious to the respiratory system using animal models assumes comparability in the structure and function of animal models and humans. Measurement of conducting airways and parenchyma yields quantitative data for parameters like volume, surface area, length, cell number and cell size. Over the past few decades, there has been an evolution of rigorous uniform sampling designs of stereology that ensure unbiased estimates of number, length, surface area, and volume. This approach has been termed 'design-based' stereology because of the reliance on sampling design rather than geometric model-based stereology that makes assumptions. The aim of this paper is to define new design-based stereological approaches for the direct estimation of anatomical structures and epithelial, interstitial and endothelial cells of specific regions of the lung independent of the sampling, size, orientation and reference traps. An example is provided using wildtype and transgenic mice expressing transforming growth factor-α to show the importance of the reference trap in stereologic estimates of postnatal lung growth.