Biomedical Engineering Reference
In-Depth Information
studies of the effects of these two long acting
b
2-
agonists on mucus clearance
in COPD are required.
Anti-inflammatory Drugs
Suppression of inflammation should indirectly suppress mucus hypersecre-
tion. Anti-inflammatory drugs also directly affect the mucus hypersecretory
phenotype. For example, in experimental systems glucocorticosteroids inhi-
bit mucus secretion, MUC gene expression, mucus synthesis, and goblet cell
hyperplasia (88). However, in contrast to asthma where they are clinically
effective (89), in part due to an antihypersecretory action, glucocorticoids
have limited effectiveness in stable COPD (3). This limited effectiveness
appears to be due to a relative lack of effect of corticosteroids on the
pulmonary inflammation in COPD (90). A limited effect on pulmonary
inflammation will, therefore, hinder suppression of the component of hyper-
secretion that is inflammation driven (for example, by neutrophil elastase).
In addition, it may be that the COPD-specific aspects of mucus hypersecre-
tion (for example, increased proportion of gland mucous cells) are similarly
limited in their response to corticosteroids. In contrast to the lack of effect
of corticosteroids, inhalation of the nonsteroidal anti-inflammatory drug
indomethacin, a cyclooxygenase (COX) inhibitor with no obvious clinical
benefit in asthma, markedly reduced mucus output in patients with chronic
bronchitis (91). Clinical trials of selective COX-2 inhibitors in COPD, for
example rofecoxib, celecoxib, and eterocoxib which have reduced gastroin-
testinal activity, would be of great interest. The difference in efficacy of con-
ventional anti-inflammatory drugs between COPD and asthma highlights
the need to define the differences in inflammatory profile and hypersecretory
phenotype between the two conditions.
Combination Therapy
The combination of a long-acting
b
2-
agonist and glucocorticosteroid has
greater efficacy in asthmatic patients than merely increasing the dose of ster-
oid (92). Consequently, combination therapy with long-acting
b
2
-agonists
and glucocorticosteroids is now recommended in clinical management of
asthma (89). There is now evidence that the combination of a long-acting
b
2
-agonist and glucocorticosteroid has greater clinical benefit in COPD than
either drug alone, in particular in reducing exacerbations (93), Whether or
not any beneficial effect of this drug combination in COPD is due to effects
on airway mucus is not reported. Theoretically, the steroid would inhibit
mucus synthesis and mucus secretion, whilst the
b
2
-agonist would have
beneficial effects on mucus clearance (see above). Studies measuring these
parameters are required to address these issues. Similarly, the effects of
other combination therapies, for example long-acting
b
2
-agonists with either
anticholinergics or theophylline (94), on mucus hypersecretory parameters
need to be assessed.
