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Review
. 2020 Sep;177(18):4096-4112.
doi: 10.1111/bph.15197. Epub 2020 Aug 7.

Cough as an adverse effect on inhalation pharmaceutical products

Rachel Yoon Kyung Chang  1 , Philip Chi Lip Kwok  1 , Sussan Ghassabian  1 , John D Brannan  2 , Heikki O Koskela  3   4 , Hak-Kim Chan  1
Affiliations
Review

Cough as an adverse effect on inhalation pharmaceutical products

Rachel Yoon Kyung Chang et al. Br J Pharmacol. 2020 Sep.

Abstract

Cough is an adverse effect that may hinder the delivery of drugs into the lungs. Chemical or mechanical stimulants activate the transient receptor potential in some airway afferent nerves (C-fibres or A-fibres) to trigger cough. Types of inhaler device and drug, dose, excipients and formulation characteristics, including pH, tonicity, aerosol output and particle size may trigger cough by stimulating the cough receptors. Release of inflammatory mediators may increase the sensitivity of the cough receptors to stimulants. The cough-provoking effect of aerosols is enhanced by bronchoconstriction in diseased airways and reduces drug deposition in the target pulmonary regions. In this article, we review the factors by which inhalation products may cause cough.

Keywords: adverse effect; aerosol; cough; inhalation; pharmaceutical products.

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Conflict of interest statement

J.D.B. receives a 10% portion of royalties for the sale of Aridol™/Osmohaler™ that are paid to his prior employer, Royal Prince Alfred Hospital. He holds a minimum number of shares in the manufacturer Pharmaxis Ltd. In the past, he has acted as a consultant to Pharmaxis Ltd and the North American distributor of Aridol, Methapharm Pty Ltd.

Figures

FIGURE 1
FIGURE 1
The cough reflex arc
FIGURE 2
FIGURE 2
Common stimulants of airway sensory vagal fibres. RAR, rapidly adapting receptor; SAR, slowly adapting receptor
FIGURE 3
FIGURE 3
Factors that influence cough in pulmonary drug delivery
See this image and copyright information in PMC

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