Effect of salbutamol on smoking related cough

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Abstract

Smokers have an increased prevalence of chronic cough and may complain of exacerbation of cough when attempting smoking cessation. We investigated the use of smokers cough as a model for testing anti-tussive agents. The effect of salbutamol was compared with placebo in healthy adult smokers.

In a randomised double blind crossover study the effect of 400 μg salbutamol via MDI plus spacer versus placebo was studied. Cough was assessed before and after the first cigarette of the day (received at 20 mintes) and throughout the day. Cough frequency, citric acid cough challenge, change in cough symptoms and peak flow were recorded.

Salbutamol reduced the mean cough frequency between 0 and 20 min. A mean of 4.5 compared to 6 on placebo (p<0.05). A significant reduction in cough followed cigarette consumption in those on placebo. Mean pre-cigarette 6 compared to 3.9 post-cigarette (p<0.02). The citric acid concentration causing two coughs (C2) at 60 min increased on salbutamol. Geometric mean 278.8 compared to 190.4 mM on placebo (p<0.03).

Cough frequency is reduced in smokers following a cigarette. The reduction in cough frequency and evoked cough after salbutamol suggests that β agonists have modest activity in smoking related cough and that smokers cough represents a sensitive model to test anti-tussive activity.

Introduction

Chronic cigarette smoking leads to a dose related cough and smokers cough is typically productive [1], [2], [3]. Smoking is associated with airway inflammation manifested as an increase in macrophages and cells expressing interleukin and adhesion molecule receptors. The consequence of this inflammation is an increase in non-specific bronchial hyperresponsiveness, even in subjects with normal lung function [2]. This airway inflammation mimics many of the pathological features seen in disease states characterised by chronic cough. We hypothesised that smoking related cough could provide a useful model to test anti-tussive activity which would be of relevance in clinical practice.

β Agonists have a marked bronchoprotective effect on non-specific bronchial hyperresponsiveness but have little or no effect on the cough reflex in healthy individuals. Salbutamol has no effect on induced cough in normal subjects, but does alter cough response in asthmatics [4]. If smokers' cough does mirror disease related alterations in the cough reflex then salbutamol should have detectable activity in this model. We therefore performed a study to determine the anti-tussive effects of salbutamol in smoking related cough.

Section snippets

Methods

A two way cross over study was performed to determine the efficacy of salbutamol via inhaler versus placebo on natural (i.e. on waking, before contact with triggers) and evoked (following the first cigarette) cough in habituated smokers.

The primary efficacy endpoint was a reduction in cough frequency after waking on treatment day 1 over the following periods: 0–10, 10–20, 20–40, and 40–60 min. The secondary efficacy endpoints were a reduction in cough frequency on treatment days 2–5, nocturnal

Results

Males (31) and females (13) of age range 20–61 years were recruited. Mean FEV1 was 4.1 l (range 2.8–6) and mean pack years 20.4 (range 5–100). At screening mean salbutamol reversibility was 5% and mean PD10 was 0.67 mg.

Total cough frequency was reduced from 6 to 4.5 in the first 20 min after salbutamol inhalation (p<0.05, CI of difference 0.02 and 2.9). There was no statistically significant reduction in total cough frequency at the other time intervals. (Fig. 1 and Table 1, Table 2). On the

Discussion

Cough is a troublesome symptom in smokers and in those attempting smoking cessation. The cough associated with smoking is multifactorial, related to bronchoconstriction, alteration in cough threshold [8], airway inflammation [9], [10], and the fact that smoke is an irritant fume. Salbutamol appears to have anti-tussive properties in asthma due to bronchodilation and reduced bronchial hyperresponsiveness. We hypothesised that it may have a role in the treatment of smoking related cough as short

Acknowledgements

Funded by an unrestricted grant from GlaxoSmithKline.

References (17)

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