Dataset Information

Theophylline inhibits the cough reflex through a novel mechanism of action.

ABSTRACT:

Background

Theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. In addition to bronchodilator and anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. Cough is the most frequent reason for consultation with a family doctor, and treatment options are limited. Determining how theophylline inhibits cough might lead to the development of optimized compounds.

Objective

We sought to investigate the inhibitory activity of theophylline on vagal sensory nerve activity and the cough reflex.

Methods

Using a range of techniques, we investigated the effect of theophylline on human and guinea pig vagal sensory nerve activity in vitro and on the cough reflex in guinea pig challenge models.

Results

Theophylline was antitussive in a guinea pig model, inhibited activation of single C-fiber afferents in vivo and depolarization of human and guinea pig vagus in vitro, and inhibited calcium influx in airway-specific neurons in vitro. A sequence of pharmacological studies on the isolated vagus and patch clamp and single-channel inside-out experiments showed that the effect of theophylline was due to an increase in the open probability of calcium-activated potassium channels. Finally, we demonstrated the antitussive activity of theophylline in a cigarette smoke exposure model that exhibited enhanced tussive responses to capsaicin.

Conclusion

Theophylline inhibits capsaicin-induced cough under both normal and "disease" conditions by decreasing the excitability of sensory nerves through activation of small- and intermediate-conductance calcium-activated potassium channels. These findings could lead to the development of optimized antitussive compounds with a reduced side effect potential.

SUBMITTER: Dubuis E

PROVIDER: S-EPMC4048545 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Theophylline inhibits the cough reflex through a novel mechanism of action.

Dubuis Eric E Wortley Michael A MA Grace Megan S MS Maher Sarah A SA Adcock John J JJ Birrell Mark A MA Belvisi Maria G MG

The Journal of allergy and clinical immunology 20140107 6

<h4>Background</h4>Theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. In addition to bronchodilator and anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. Cough is the most frequent reason for consultation with a family doctor, and treatment options are limited. Determining how theophylline inhibits cough might lead to the development of optimized compounds.<h4>Objective< ...[more]

PMID: 24406072

Similar Datasets

Project description:RationaleSpeech language pathology is an effective management intervention for chronic cough that persists despite medical treatment. The mechanism behind the improvement has not been determined but may include active cough suppression, reduced cough sensitivity or increased cough threshold from reduced laryngeal irritation. Objective measures such as cough reflex sensitivity and cough frequency could be used to determine whether the treatment response was due to reduced underlying cough sensitivity or to more deliberate control exerted by individual patients. The number of treatments required to effect a response was also assessed.ObjectiveThe aim of this study was to investigate subjective and objective measures of cough before, during and after speech language pathology treatment for refractory chronic cough and the mechanism underlying the improvement.MethodsAdults with chronic cough (n = 17) were assessed before, during and after speech language pathology intervention for refractory chronic cough. The primary outcome measures were capsaicin cough reflex sensitivity, automated cough frequency detection and cough-related quality of life.ResultsFollowing treatment there was a significant improvement in cough related quality of life (Median (IQR) at baseline: 13.5 (6.3) vs. post treatment: 16.9 (4.9), p = 0.002), objective cough frequency (Mean +/- SD at baseline: 72.5 +/- 55.8 vs. post treatment: 25 +/- 27.9 coughs/hr, p = 0.009), and cough reflex sensitivity (Mean +/- SD log C5 at baseline: 0.88 +/- 0.48 vs. post treatment: 1.65 +/- 0.88, p < 0.0001).ConclusionsThis is the first study to show that speech language pathology management is an effective intervention for refractory chronic cough and that the mechanism behind the improvement is due to reduced laryngeal irritation which results in decreased cough sensitivity, decreased urge to cough and an increased cough threshold. Speech language pathology may be a useful and sustained treatment for refractory chronic cough.Trial registrationAustralian New Zealand Clinical Trials Register, ACTRN12608000284369.

Dataset Information

Theophylline inhibits the cough reflex through a novel mechanism of action.

Background

Objective

Methods

Results

Conclusion

Publications

Theophylline inhibits the cough reflex through a novel mechanism of action.

Similar Datasets

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