Practical Methods for Assessing Emphysema Severity Based on Estimation of Linear Mean Intercept (Lm) in the Context of Animal Models of Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency is typified by panacinar emphysema in humans. Whilst animal models of (α1A-TD) that more accurately reflect the histology and molecular pathology of α1A-TD are in development, it is timely to discuss methods to assess emphysema severity. Several methods exist to quantify emphysema from histologic sections, including linear mean intercept (Lm), equivalent diameters (D) or their statistical derivatives (D2), and more recently probability models of D2 (“severity index”). Given proper attention to lung inflation, reference volume, and random sampling, Lm determined by intersect point counting provides a robust analytical tool to quantify emphysema severity. Details of lung preparation, processing for random sampling, and batch processing of prescreened images are provided herein.