Signs and Symptoms of Chest Diseases: Cough |

A Randomized Clinical Trial of Levodropropizine Effect on Respiratory Centre Output in Patients With Intractable Chronic Cough: Preliminary Results FREE TO VIEW

Claudia Mannini, MD; Federico Lavorini, MD; Federico Saibene, MD; Giovanni Fontana, MD; Luigi Lanata, MD
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Dompè, Milano, Italy

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A546. doi:10.1016/j.chest.2016.02.570
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: 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 an effective, well tolerated, non-opioid, peripherally-acting antitussive drug; the drug exerts its peripheral action by inhibiting the release of neuropeptides from airway sensory nerves, particularly C-fibers. Little evidence exists demonstrating that Levodropropizine is devoid of any significant action at the central level. The aim of the study was to investigate the effects of Levodropropizine on the respiratory response to a standard CO2 re-breathing testing in both normal subjects and in patients with intractable chronic cough of any origin. We also wished to compare the effects of Levodropropizine with those of codeine, a widely used opioid central acting antitussive agent.

METHODS: Eight outpatients (aged 20-70 yrs) with chronic cough, i. e a cough lasting for longer than 8 weeks, were studied according to an open- label, placebo controlled, cross-over design. On each different study days, at least 48 hours apart, each participant to the study were randomly administered a single dose of Levodropropizine (Levotuss ® 6% drops; 60 mg = 20 drops) or Codeine (Codeine 15 mg = 45 drops) or matching placebo (45 drops of a multivitamin compound). Subsequently, participants performed the Reid CO2 re-breathing test. With this technique, patients breathed, for 5 min, through a 2-way valve connected to a rebreathing bag filled with a mixture of 93% Oxygen and 7% CO2. During the test fractional end tidal CO2 (FETCO2) and inspiratory minute ventilation (I) were continuously monitored. With the rebreathing method, the CO2 sensitivity was calculated as the slope of the relationship between I and FETCO2.

RESULTS: In all patients administration of Codeine significantly (P<0,01) depressed the ventilatory response to hypercapnia compared with Levodropropizine and placebo. The ventilatory response to hypercapnic stimulus after administration of Levodropropizine completely overlapped that after Placebo.

CONCLUSIONS: These preliminary results show that Levodropropizine, at the recommended usual dose, does not affect the ventilatory response to CO2.

CLINICAL IMPLICATIONS: These preliminary results confirm the absence of any central action of Levodropropizine. The clinical study of the ventilatory response to CO2 may represent a useful tool to investigate the central respiratory effects of antitussives.

DISCLOSURE: Federico Saibene: Employee: Medical Department Luigi Lanata: Employee: Medical department The following authors have nothing to disclose: Claudia Mannini, Federico Lavorini, Giovanni Fontana

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