Cough challenge in the assessment of cough reflex

Morice, Alyn H.; Kastelik, Jack A.; Thompson, Rachel H.

doi:10.1046/j.0306-5251.2001.01475.x

Cited by 107 publications

(82 citation statements)

References 94 publications

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“…Herein, it is demonstrated that a b 2 -agonist attenuates the cough response induced by capsaicin and citric acid. These tussive agents are commonly used in humans [19] and pre-clinical in vivo models, and this inhibitory effect of a b 2 -agonist is in accordance with previous results observed in a similar model [20,21].…”

Section: Discussionsupporting

confidence: 80%

2-Agonists block tussive responses in guinea pigs via an atypical cAMP-dependent pathway

Freund-Michel

Birrell²,

Giembycz³

et al. 2009

European Respiratory Journal

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b 2 -Adrenoceptor agonists are the most effective bronchodilators currently available, and are used for symptom management in asthmatics. However, whether b 2 -agonists are also antitussive is controversial. Identifying an antitussive role for b 2 -agonists and dissecting the possible mechanism of action may help to explain the inconsistencies in the clinical literature and lead to the development of novel therapeutic agents. The aim of the present study was to determine whether or not b 2 -agonists attenuate the tussive response in guinea pig and human models, and, if so, to identify the mechanism(s) involved.Depolarisation of vagal sensory nerves (human and guinea pig) was assessed as an indicator of sensory nerve activity. Cough was measured in a conscious guinea pig model.A b 2 -agonist, terbutaline, dose-dependently inhibited the cough response to tussive agents in conscious guinea pigs. Terbutaline and another b 2 -agonist, fenoterol, blocked sensory nerve activation in vitro. Using these mechanistic models, it was established that b 2 -agonists suppress the tussive response via a nonclassical cyclic adenosine monosphosphate-dependent pathway that involves the activation of protein kinase G and, subsequently, the opening of largeconductance calcium-activated potassium channels.In conclusion, b 2 -adrenoceptor agonists are antitussive, and this property occurs due to a direct inhibition of sensory nerve activation. These findings may help to explain the confusion that exists in the clinical literature, and could be exploited to identify novel therapies for the treatment of cough, which is a significant unmet medical need.

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Section: Discussionsupporting

confidence: 80%

2-Agonists block tussive responses in guinea pigs via an atypical cAMP-dependent pathway

Freund-Michel

Birrell²,

Giembycz³

et al. 2009

European Respiratory Journal

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“…The two main methods of capsaicin and citric acid delivery during cough challenge testing are the single-dose and doseresponse methods [25]. In the former method, a single concentration of capsaicin or citric acid is employed.…”

Section: Administration Of Capsaicin and Citric Acidmentioning

confidence: 99%

“…Therefore, only coughs occurring within 15 s of capsaicin and citric acid delivery should be counted [10,25,30,31]. Coughs that occur beyond this time period may not be capsaicin or citric acid induced.…”

Section: Placebo Inhalationsmentioning

confidence: 99%

“…In order to increase cough challenge blindness, inhalations of physiological saline (placebo) should be randomly interspersed between incremental concentrations of capsaicin and citric acid [25,29]. This strategy may reduce the effects of voluntary suppression or conditioned responses in subjects who would otherwise be anticipating progressively higher concentrations of tussive agent.…”

Section: Placebo Inhalationsmentioning

confidence: 99%

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ERS guidelines on the assessment of cough

Morice¹,

Fontana²,

Belvisi³

et al. 2007

European Respiratory Journal

588

619

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“…Cough challenges may provide an index of cough severity and can assess the strength of the reflex in patients with neurological disorders [94][95][96], but the presence of increased cough reflex is not disease-specific.…”

Section: Cough Challengesmentioning

confidence: 99%