Effect of salbutamol on smoking related cough Siobhan Mulrennan a , Caroline Wright a , Rachel Thompson a , Peter Goustas b , Alyn Morice a, * a Division of Academic Medicine, University of Hull, Castle Hill Hospital, Cottingham, East Yorkshire, UK b GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, England UK Received 1 July 2003; revised 17 December 2003; accepted 6 January 2004 Abstract Smokers have an increased prevalence of chronic cough and may complain of exacerbation of cough when attempting smok We investigated the use of smokers cough as a model for testing anti-tussive agents. The effect of salbutamol was compared healthy adult smokers. In a randomised double blind crossover study the effect of 400 mg salbutamol via MDI plus spacer versus placebo was studi assessed before and after the first cigarette of the day (received at 20 mintes) and throughout the day. Cough frequency, citr 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 ðp , 0:05Þ: reduction in cough followed cigarette consumption in those on placebo. Mean pre-cigarette 6 compared to 3.9 post-cigarette ð citric acid concentration causing two coughs (C2) at 60 min increased on salbutamol. Geometric mean 278.8 compared to 190.4 mM on placebo ðp , 0:03Þ: Cough frequency is reduced in smokers following a cigarette. The reduction in cough frequency and evoked cough after salbutamol suggests that b agonists have modest activity in smoking related cough and that smokers cough represents a sensitive mode tussive activity. q 2004 Elsevier Ltd. All rights reserved. Keywords: Cough; Smoking; b Agonists; Anti-tussives 1. Introduction Chronic cigarette smoking leads to a dose related cough and smokers cough is typically productive [1 – 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 isan increasein non-specificbronchial hyperresponsiveness, even in subjects with normalung 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 modelto testanti-tussive activity which would be of relevance in clinical practice. b Agonists have a marked bronchoprotective effect on non-specific bronchial hyperresponsiveness but have little or no effecton the cough reflex in healthy individuals. Salbutamol has no effecton 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. 2. Methods A two way cross over study was performed to determine the efficacy of salbutamol via inhalerversus 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. 1094-5539/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.pupt.2004.01.002 Pulmonary Pharmacology & Therapeutics 17 (2004) 127–131 www.elsevier.com/locate/ypupt * Correspondingauthor.Tel.: þ 44-1482-624067; fax: þ 44-1482- 624068. E-mail address: a.h.morice@hull.ac.uk (A. Morice).