Biomedical Engineering Reference
In-Depth Information
whereas the collections of B lymphocytes in the adventitial compartment of
the peripheral airways that had a tendency to aggregate into lymphoid fol-
licles (Fig. 5C) in mild to moderate COPD. Kuwano et al. (42) showed that
the walls of the small airways became thick in COPD and a recent compre-
hensive study of resected lung tissue from 169 cases over the full range of the
GOLD classification confirmed and extended many of these earlier reports
(36). These studies established that progression of COPD is associated with
a greater number of small airways containing each inflammatory cell type as
well as an absolute increase in the accumulated volume of CD8 and B-cell
lymphocytes and the number of lymphoid follicles, however, a multiple
regression analysis indicates that a decline in FEV
1
was more closely asso-
ciated with a repair and remodeling process that thickened the walls of
the small airways and an accumulation of inflammatory exudates containing
mucus in their lumen (36). Collectively, these data suggests that small airway
obstruction in COPD is based on an innate inflammatory immune response
that is associated with an exudation of fluid and cells into the wall and
lumen and an active repair and remodeling process that thickens the walls
of these airways (36). The progressive increase in lymphoid follicles with
active germinal centers also suggests that an adaptive immune response in
the later stages of COPD when the peripheral lung is known to become
colonized and infected with a variety of organisms (43).
IV. THE INNATE AND ADAPTIVE HOST DEFENSE SYSTEM
A.
Innate Immunity
The first line of the innate defense system of the lung is the mucus producing
and clearance system that physically removes foreign material deposited on
the airway surface (44). When this system fails plugs of exudates containing
mucus accumulate in the airway lumen, interfere with the clearance of micro-
bes from the lower airways and predispose the lung to infection. Although, it
is easy to demonstrate this type of airway occlusion in postmortem studies
it is not easy to separate the chronic disease from the effects of bronchopneu-
monia near the end of life. Cosio et al. (39) study of surgically resected lung
specimens suggested that the occlusion of the small airways could be reliably
estimated but did not correlate with a decline in lung function. But a recent
study of a much larger number of cases over the full range of COPD severity
suggests that there is an association between occlusion of the airway lumen
with inflammatory exudates containing mucus and the development of flow
limitation (36).
The second line of the innate defense system is provided by the tight
junctions that join the airway epithelial cells beneath the mucociliary layer
and provide protective barrier that is breached by chronic cigarette smoke
exposure (45). Cytokines released by macrophages and epithelial cells during
