Emphysema of the lungs – first described by Laennec (1) – is a manifestation of chronic obstructive lung disease, and is almost always caused by smoking (2). Rare causes of emphysema are hypersensitivity pneumonitis (3) and human immunodeficiency virus (HIV) infection (4). Histologically, emphysema is characterized by loss of alveolar septal cells, and it can be centrilobular or panlobular. In extreme cases, the lung is literally vanishing. Modern imaging technology allows both a regional and quantitative assessment of emphysema. Although traditionally thought of as chronic progressive airway disease involving proteolytic injury to lung extracellular matrix, Liebow already recognized in 1959 that the lung vessels were involved (5) as well. Recent data on human emphysema, and in animal studies, demonstrate structural alterations of small precapillary arterioles and endothelial cell (EC) dysfunction (6–9). In addition, there is evidence by Tunel staining for EC apoptosis in these small arterioles (10).

THE INVOLVEMENT OF THE ENDOTHELIUM

EC dysfunction had been demonstrated by exposing small pulmonary arteries from patients with emphysema who underwent lung resection to acetylcholine and observing impaired vasodilation when compared with normal lung artery segments of comparable diameter. This test is consistent with EC dysfunction; however, whether this ex vivo test reflects in vivo pulmonary vascular EC dysfunction remains unknown. The cause or causes of this EC dysfunction are also not understood (8,9). Subsequently, Kasahara and colleagues (10) showed increased apoptosis of ECs in lungs from patients with emphysema, as well as a decrease in the overall lung tissue expression of vascular endothelial growth factor (VEGF) and the VEGF receptor 2 (VEGFR2/FLK-1/KDR).