Standards and recommendations for quantitative assessment of lung structure in research

recently, a task force of experts in lung morphology have published an excellent document on recommended methods for quantitative studies of lung structure (1). This report represents input from many experienced and talented scientists who, for many years, have done research on lung structure and its relationship to pulmonary function both in the normal and the abnormal lung. The task force was supported by the American Thoracic Society and the European Respiratory Society to critically review state-of-the-art methods for studies of lung structure in order to provide practical guidelines for the use of these methods in basic, translational, and clinical lung research.

For quantitative assessment of lung structure, the only effective way to avoid bias and to ensure accuracy is by rigorous experimental design and standardization of each step of tissue fixation, processing, sampling, and analysis. With what the authors describe as an “efficient study design,” the number of samples, sections, images, and measurements at each analytical stage can be maintained at a reasonably low level without compromising accuracy and while still achieving reasonable global precision for the studies. Furthermore, the authors conclude that the principles of design-based stereology can also be applied to the sampling and morphometric analysis of structural data obtained by in vivo imaging modalities including computed tomography, magnetic resonance imaging, and positron emission tomography. There are 208 references in this article (1), one of the main contributions of this report.

The task force has provided considerable detail regarding the principles for standardization of study design, including methods for inflation and perfusion of the lung as well as the appropriate use of fixatives and processing procedures that will minimize tissue distortion. The article also recommends how to select tissue blocks or image fields using established unbiased sampling schemes to guarantee that all parts of the lung or the portion being imaged have an equal chance for being sampled. There are several excellent figures that illustrate the recommendations from experts in the field. There are also specific guidelines regarding sampling of human tissues with endobronchial and transbronchial biopsies as well as thorascopic and open lung biopsies.

Because of limited resources, some investigators will not be able to support studies that involve detailed morphometric methods. This article may, however, provide investigators with a list of potential investigators to collaborate with for detailed studies of lung structure. However, even investigators with limited resources should benefit from the recommendations of this report in order to make their morphological studies of the lung more efficient and focused on achieving the goals of their research as well as making their morphological studies more representative, more quantitative, and less biased.

This document will be an outstanding resource for investigators who wish to carry out high-quality morphological studies of the lung. I believe that this publication should be of major value to investigators who wish to study morphological aspects of acute and chronic pulmonary diseases.

GRANTS

This work was supported by National Institutes of Health Grants 2P01-AI-053194, HL-51856, and HL-51854.

DISCLOSURES

No conflicts of interest are declared by the author(s).