Biomedical Engineering Reference
In-Depth Information
Figure 8
Cholinergic airway mucus pathophysiology in COPD. Cholinergic nerves
are activated directly and indirectly to induce mucin, water, and albumin secretion
with consequent mucus hypersecretion. X,
inhibition by anticholinergic drugs.
Dotted lines, pathways uncertain.
receptors over the M2 (auto-inhibitory) receptor. There are no current
reports of its effects on cholinergic mucus secretion output. In one clinical
study, tiotropium did not significantly improve tracheobronchial clearance
compared with placebo, despite improving airway patency (74).
There are novel options for inhibiting the effects of cholinergic nerves
(68), none of which are used clinically. These include inhibition of neuro-
transmitter (acetylcholine) release by activation of prejunctional receptors,
for example opioid m and
d
receptors, cannabinoid CB
2
receptors, or vasoac-
tive intestinal peptide VPAC1 receptors, and activation of large conduc-
tance calcium-activated potassium (BK
Ca
) channels (Fig. 9). There is also
the possibility that sensory nerve activation may mediate mucus output in
COPD (75). These nerves can also be inhibited in a similar fashion to
cholinergic nerves (see above), and also by inhibition of the effects of their
tachykinin neurotransmitters, including substance P and neurokinin A, by
tachykinin antagonists (76).
Short-Acting
b
2
-Agonists and Methylxanthines
Short-acting
b
2-
agonists and methylxanthines stimulate mucus clearance in
healthy subjects and patients with chronic bronchitis or asthma, as assessed
