Biomedical Engineering Reference
In-Depth Information
axonemes and cilia with intracytoplasmic microtubule doublets (43). These
abnormalities coupled with mucus hypersecretion are associated with
reduced mucus clearance and airway obstruction (44). However, differences
in methodology (45) and patient selection, especially, exclusion of patients
with asthma (46), can confuse overall interpretation of the results of these
studies. Lung clearance is significantly reduced in heavy smokers (47) and
in patients with chronic bronchitis (48). However, it should be noted that
forced expirations and cough, compensate relatively and effectively for
decreased mucus clearance in patients with chronic bronchitis, although
they are much less effective in patients with emphysema where lung elastic
recoil is impaired (49,50).
V.
EPIDEMIOLOGY OF MUCUS HYPERSECRETION IN COPD
The perception of the role of airway mucus hypersecretion in pathophysiol-
ogy and clinical symptoms in COPD has shifted from being a condition inde-
pendent of disease progression to now being positively associated with
morbidity and mortality (4,19). Epidemiological studies sampling hundreds
to thousands of subjects in the late 1970s to early 1990s found scant evidence
for the involvement of mucus in either the mortality or accelerated age-related
decline in lung function associated with COPD (1,2,51-55). In all studies, spu-
tum production, assessed by standardized questionnaire, was the index of
mucus hypersecretion. However, the relationship between sputum production
and mucus hypersecretion, particularly in the small airways, the main site of
airflow obstruction in COPD (56), is unclear. It is also noteworthy that these
studies were primarily in occupational cohorts, and were exclusively in men.
Nevertheless, the consensus of these studies was that airflow obstruction and
mucus hypersecretion were largely independent disease processes.
In contrast, a number of studies over the last 18 years, again with large
sample numbers, and with an emphasis on general population samples
rather than occupational cohorts, found positive associations between
sputum production and decline in lung function, hospitalization and death
(57-65). Some of these reports were re-examinations of the same patients,
now older, reported previously (57). Of note is the observation that inci-
dence of death was related to increased risk of patients with phlegm produc-
tion to die of respiratory infection (5). Additionally, the association between
chronic mucus hypersecretion and frequency of lower respiratory illness
extends to an association with an accelerated decline in lung function with
successive bouts of pulmonary infection (66). In summary, although not
associated with disease progression in all cases, mucus hypersecretion
contributes to morbidity and mortality in many patients with COPD,
particularly those prone to infection, those with low lung function (58)
and, possibly, as patients age. This highlights the importance of developing
drugs that inhibit mucus hypersecretion in these patients.
