In 1985, the National Heart, Lung, and Blood Institute defined emphysema as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis," Wayne Mitzner, Ph.D., wrote in an editorial accompanying the report by Mr. McDonough and colleagues. This study, however, challenges that definition by finding that patients with various degrees of COPD have a narrowing and almost total loss of terminal bronchioles, sometimes with minimal quantifiable damage in the distal parenchyma, Dr. Mitzner said.
Even though the authors suggest that small-airway damage probably occurs before emphysematous destruction, the study was cross-sectional and involved a limited number of subjects, so it is difficult to prove causality. For example, if alveolar walls weaken and become more distensible, they could contribute to narrowing of the inflamed bronchial arteries. Also, a seminal study by J.G. Leopold and J. Gough in 1957 found relatively few severely narrowed airways that led to emphysematous regions.
Whatever the initiating cause, it is difficult to determine how pathological changes affect the 3-D structure. For example, if terminal bronchioles disappear after being completely obstructed and degraded as dead tissue, how do the larger airways connect to the remaining distal acini? And, if the small airways just disappear, why do the larger upstream airways stay obstructed? This study was limited by the inability to identify airways with lumens below the resolution of the CT images (approximately 1-2 mm), so there may still be fibrous connections to the distal parenchyma.
A new definition of emphysema may be needed to reflect the involvement of small airways beyond the simple absence of obvious fibrosis. Permanent enlargement of the distal airspaces may serve only as a structural biomarker that is a secondary result of small-airway inflammation and destruction.
Dr. Mitzner is with the Program in Respiratory Biology and Lung Disease, Johns Hopkins University, Baltimore. He is on grant review panels for and receives travel expenses from the National Institutes of Health.
