Biomedical Engineering Reference
In-Depth Information
Figure 9
Inhibition of cholinergic airway mucus secretion. ACh, acetylcholine; M,
muscarinic receptor; VPAC
1
, vasoactive intestinal peptide (VIP) receptor; m and
d
opioid receptors; BK
Ca
, large conductance calcium-activated potassium channel.
by radioaerosol clearance (77-80). However, stimulation is more dramatic in
healthy individuals compared with patients with respiratory disease (81).
b
2-
Agonists may mediate these effects through an increase in intracellular
cyclic adenosine monophosphate (cAMP) levels, which increases ciliary beat
frequency (82,83). Methylxanthines have been shown to promote mucus
secretion, augment airway epithelial ion transport, with consequent
increases in luminal water flux, and stimulate ciliary beat frequency, with
net enhancement of mucociliary clearance (84). However, interpretation of
the mucus clearance effects of
b
2
-agonists and methylxanthines in clinical
studies could be hindered by the bronchodilator action of these agents,
which may allow greater penetration of the radioaerosol into the smaller
bronchi where mucociliary clearance is slower. However, a placebo con-
trolled study in healthy individuals treated with salbutamol or theophylline
found no such effect (85), indicating that, at least in this subject group, ben-
eficial effects on clearance were unrelated to effects on airway calibre.
Long-Acting
b
2
-Agonists
Salmeterol and formoterol are the two inhaled long-acting
b
2-
agonists cur-
rently available for treatment of COPD. They have a duration of action
of at least 12 hr and can be administered twice-daily. Both drugs appear
to exhibit anti-inflammatory activity, with consequent reduction in mucus
hypersecretion. In terms of specific beneficial effects on the mucus hyperse-
cretory phenotype, salmeterol increases ciliary beat frequency in cultured
human bronchial epithelial cells (83) and improves mucociliary transport
compared with placebo in asthmatic patients (86). Similarly, formoterol
improves mucociliary clearance in 10 patients with bronchitis (87). Larger
