Biomedical Engineering Reference
In-Depth Information
are only a small percentage of smokers, they represent a significant health
and economic burden through hospital admission and absenteeism from
work. Lung specimens from patients undergoing lung volume reduction sur-
gery (LVRS) or lung transplantation for severe emphysema represent a
unique opportunity to examine lung pathology in living patients who
develop a severe stage of the disease. Moreover, the fact that these patients
perform pulmonary function tests before surgery allows investigation of the
relationship between lung pathology and measurements of pulmonary func-
tion. In COPD patients, as airflow obstruction progressively worsens, the
parenchymal inflammation enhances, as shown by the pioneering study by
Retamales et al. (15). The authors demonstrated that there is an increase
in the intensity of the inflammatory response in the alveolar walls and alveo-
lar spaces of these patients, and that this inflammatory process is character-
ized by an increased number of all the inflammatory cell types, including
neutrophils, macrophages, CD4 and CD8 T-lymphocytes, and eosinophils.
Moreover, a strong correlation was observed between the numbers of all
these inflammatory cells, with exclusion of eosinophils, and the amount of
emphysematous destruction as determined by computerized tomography
scan. A recent study extended these findings showing that, when the disease
progresses, there is an amplification of the inflammatory response even in
the peripheral airways and that this enhanced airway inflammatory process
is correlated with the degrees of airflow obstruction, lung hyperinflation, CO
diffusion impairment, and radiologic emphysema (60). Taken as a whole, all
these findings suggest a role for this enhanced inflammatory response in the
clinical progression of the disease. The observation that all the inflammatory
cell types contribute to the amplification of the inflammatory response in the
lung parenchyma of severe emphysema suggests that, as pointed out by Sha-
piro (61), our challenge now is more to find out how these inflammatory
cells interact and contribute to the disease than to detect the specific role
of a single cell type.
III. PARENCHYMAL DESTRUCTION
Although the pathogenesis of parenchymal destruction in smokers remains
enigmatic, increasing evidence suggests a role for alveolar wall inflammation
in the destructive process. The most common type of parenchymal destruc-
tion in smokers is that of centriacinar (or centrilobular) emphysema, which
is characterized by focal destruction restricted to respiratory bronchioli and
to the central portions of the acinus, surrounded by areas of grossly normal
lung parenchyma (62-64). These lesions occur more frequently in the upper
lobes of the lung. Microscopically, in the early classical lesion, the enlarged
destroyed respiratory bronchioles coalesce to produce sharply demarcated
emphysematous lesions separated from the acinar periphery by intact
