Biomedical Engineering Reference
In-Depth Information
Macrolide Antibiotics
Antibiotic treatment against acute infections is recommended in clinical
management of COPD (3). Erythromycin, clarithromycin, and flurythromy-
cin are macrolide antibiotics that have a variety of beneficial effects on air-
way mucus, for example inhibition of mucin secretion in a variety of
experimental preparations including human airways in vitro (19,102). Anec-
dotally, erythromycin reduces excessive sputum production in patients with
airway mucus hypersecretion (103,104). The mechanism of action of ery-
thromycin is relatively unexplored, but may involve anti-inflammatory
effects (105,106) as well as direct inhibitory effects on MUC gene expression,
mucin synthesis and mucin secretion (107). Formal clinical studies of its
effects on the pathophysiology of mucus hypersecretion, for example
sputum production and lung function, in COPD would be of interest.
B. Novel Pharmacotherapy
The clinical symptoms of cough and sputum production, coupled with a per-
ception of the importance of mucus hypersecretion in the pathophysiology
of a number of severe lung conditions, including COPD, has prompted
renewed interest in research into airway hypersecretion and, in concert, in
development of drugs targeting mucus and the hypersecretory phenotype
in COPD. These drugs and their purported targets have been discussed in
detail recently (10,19,94,108,109), and will only be briefly highlighted herein
(Table 3). It should be noted that the activity of many of these compounds is
not as selective for the target as may be thought and, in any event, whether
or not any beneficial activity of the drug is due to activity at the target is, for
the most part, substantially unproven.
Epoxygenase Inducers
Cytochrome P-450 enzymes (epoxygenases) metabolise arachidonic acid and
regulate inflammation (110). Benzafibrate, an inducer of epoxygenase, inhi-
bits airway goblet cell hyperplasia in a rat model of chronic bronchitis (111).
The mechanisms underlying the inhibition include production of anti-
inflammatory mediators and reduction in amount of 'available' arachidonic
acid. Epoxygenase inducers, or of selective eopxyeicosanoids, would be
potential therapy for both the inflammation and mucus hypersecretion of
COPD.
Inhibitors of Reactive Gases
Oxidant stress is considered a pathophysiological feature of COPD f(112)
and exhaled nitric oxide (NO) is elevated in COPD (113). Oxidants and
NO have marked effects on airway mucus and goblet cells (114,115).
Consequently, antioxidants and inhibitors of inducible NO synthase (iNOS)
may have therapeutic benefit for mucus hypersecretion in COPD.
