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Original Research |

A Randomised Clinical Trial Comparing the Effects of Antitussives on Respiratory Centre Output in Patients with Chronic Cough

Claudia Mannini, M.D.; Federico Lavorini, M.D; Alessandro Zanasi, M.D; Federico Saibene, M.D; Luigi Lanata, M.D; Giovanni Fontana, M.D
Author and Funding Information

Conflicts of interest

All Authors filled out the ICMJE uniform disclosure form on http://icmje.org/coi_disclosure.pdf. FL reports in the last 36 months personal fees for speaking outside the present work from the following pharma companies: AstraZeneca, Chiesi, Cipla, Boehringer Ingelheim, Teva. GAF reports in the last 36 months personal fees for speaking outside the present work from the following pharma companies: Edmond Pharma, Mundipharma, Menarini, Dompè. CM, and AZ have nothing to disclose; FB and LL are employees of Dompè SpA Medical Department. Dompé SpA is the company that manufactures and commercializes Levodropropizine

This trials was registered in the European Union Clinical Trials Register on 2014, May 27 (EudraCT number: 2013-004735-68)

1Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

2Pneumology Unit, University of Bologna, S. Orsola Malpighi Hospital, Bologna, Italy

3Medical Department Dompè SPA, Milan, Italy

Correspondence: Prof. Giovanni A. Fontana, MD, FRCP Department of Experimental and Clinical Medicine University of Florence, Italy Largo Brambilla 3, 50134 Florence, Italy.


Copyright 2017, . All Rights Reserved.


Chest. 2017. doi:10.1016/j.chest.2017.02.001
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Abstract

Background  Cough is produced by the same neuronal pool implicated in respiratory rhythm generation and antitussive drugs acting at the central level, such as the opioids, may depress ventilation. Levodropropizine is classified as a non-opioid, peripherally-acting antitussive drug acting at the level of airway sensory nerves. However, the lack of a central action by Levodropropizine remains to be fully established. We set out to compare the effects of Levodropropizine and the opioid antitussive agent Dihydrocodeine on the respiratory responses to a conventional CO2 re-breathing test in patients with chronic cough of any origin.

Methods  Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60 mg Levodropropizine, or 15 mg Dihydrocodeine or matching placebo. Subsequently, patients breathed, for 5 min, a mixture of 93% oxygen and 7% CO2. Fractional end-tidal CO2 (FETCO2) and inspiratory minute ventilation (VI) were continuously monitored. Changes in breathing pattern variables were also assessed.

Results  At variance with Dihydrocodeine, Levodropropizine and placebo did not affect respiratory responses to hypercapnia (P<0.01). The ventilatory increases by hypercapnia were mainly accounted for by a rise in the volume components of the breathing pattern.

Conclusion  The results are consistent with a peripheral action by Levodropropizine; the assessment of ventilatory responses to CO2 may represent a useful tool to investigate the central respiratory effects of antitussives.


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