Biomedical Engineering Reference
In-Depth Information
deficiency), whereas patchy centrilobular emphysema may have near normal
P
L
. Indeed, uniform ''microscopic'' emphysema might account for func-
tional 'pseudoemphysema' without any CT change.
In practice, a reduction in conductance or maximum flow that is com-
pletely explained by a reduction in P
L
is unusual, except in mild disease.
Retrograde catheter studies in excised lungs from patients with severe air-
flow obstruction due to COPD have all found large increases in peripheral
resistance at standard P
L
(35-37). But there are many other possible changes
in airway function due to emphysema which would result in an increased
resistance at a given P
L
, including abnormal angulation or compression of
normal airways by surrounding overdistended lung, loss of parallel airways
due to emphysematous destruction, or to functional loss of patent airways
supplying poorly ventilated areas of lung. The effects of emphysema may
not always reduce P
L
, e.g., a short stenosis caused by local loss of alveolar
attachments. Present analyses of airway morphology are not sufficient to
reveal the anatomical basis of the consistent physiological finding of an
increase in peripheral airflow resistance. Assuming that the increase is all
due to ''intrinsic'' disease of the peripheral airways underestimates the role
of emphysema. Emphysema may play a more prominent role in severe
disease as the decline in lung function accelerates.
D. Mucus Hypersecretion
The contribution of mucus hypersecretion to airflow limitation in COPD is
still uncertain. Although early studies supported the view that mucus hyper-
secretion was not associated with any physiological defect (38,39), more
recent studies have demonstrated that mucus hypersecretion may be a
potential risk factor for accelerated decline in lung function (40,41). The
early studies examined the early stages of COPD and also included an occu-
pational cohort. The most likely mechanism whereby chronic mucus hyper-
secretion contributes to progression of COPD may be due to the increased
risk of exacerbations that appear to accelerate loss of FEV
1
(42). Chronic
mucus hypersecretion may contribute little in the early phases of COPD
when exacerbations are infrequent. It is possible that chronic mucus hyper-
secretion may reflect the inflammatory process around submucosal glands
(43) and may reflect the intensity of inflammation in more peripheral air-
ways. Increased numbers of neutrophils and mast cells have also been found
around submucosal glands (43,44) and serine proteases and mast cell
chymase are potent mucus secretagogues (45-47). In severe COPD chronic
mucus hypersecretion is associated with mortality and this may also reflect
an increased risk of terminal infection (48-50). Chronic cough and mucus
production in smokers with normal lung function (GOLD Stage 0) do not
appear to predict the later development of COPD (51).
