Pharmacological ablation of the airway smooth muscle layer-Mathematical predictions of functional improvement in asthma.

Physiological Reports
Graham M DonovanP B Noble

Abstract

Airway smooth muscle (ASM) plays a major role in acute airway narrowing and reducing ASM thickness is expected to attenuate airway hyper-responsiveness and disease burden. There are two therapeutic approaches to reduce ASM thickness: (a) a direct approach, targeting specific airways, best exemplified by bronchial thermoplasty (BT), which delivers radiofrequency energy to the airway via bronchoscope; and (b) a pharmacological approach, targeting airways more broadly. An example of the less well-established pharmacological approach is the calcium-channel blocker gallopamil which in a clinical trial effectively reduced ASM thickness; other agents may act similarly. In view of established anti-proliferative properties of the macrolide antibiotic azithromycin, we examined its effects in naive mice and report a reduction in ASM thickness of 29% (p < .01). We further considered the potential functional implications of this finding, if it were to extend to humans, by way of a mathematical model of lung function in asthmatic patients which has previously been used to understand the mechanistic action of BT. Predictions show that pharmacological reduction of ASM in all airways of this magnitude would reduce ventilation heterogeneity in a...Continue Reading

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Citations

Mar 29, 2021·Pharmacology & Therapeutics·Gang LiuPhilip M Hansbro

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Methods Mentioned

BETA
sedation
biopsy

Software Mentioned

SigmaPlot
Stereo Investigator
NFA
Systat

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