S35 Randomised control trial quantifying the efficacy of low dose morphine in a responder group of patients with refractory chronic cough

The pathophysiology of chronic cough remains poorly understood and treatment options are limited. Morphine sulphate can improve quality of life in refractory chronic cough,1 but its mechanism of action and effect on objective cough frequency remain unknown. Here we report morphine’s influence on cough frequency and patient reported outcomes in a group of refractory chronic cough patients who responded favourably to morphine in our tertiary clinic. We recruited 22 patients (mean age 61.7 years, 18 female, mean cough duration 14 years) taking low dose morphine for refractory chronic cough into a double blinded, placebo controlled, crossover study. Volunteers withdrew their morphine therapy and were randomised to receive morphine (5–10 mg BD slow release)/matched placebo during two treatment period (5–7 days duration) separated by a 5–7 day washout. At baseline and at the end of each treatment period we assessed 24 hour cough recordings using a semi-automated cough counter (vitaloJAK), cough severity (visual analogue scales (VAS)) and the cough quality of life questionnaire (CQLQ) . For analysis we ran generalised estimating equations to compare morphine and placebo, adjusting for baseline measures and assessing any influence of treatment, sequence or period. Low dose morphine reduced objective cough frequency compared to placebo by 71.8% over 24 hours. Morphine significantly reduced cough frequency overnight as well as during the daytime (p<0.05) and responses were independent of baseline cough frequency. All patient reported outcomes were consistent with this effect (p<0.05). The treatment effect was not significantly influenced by period or sequence. Overall morphine was well tolerated. There was one serious adverse event, unrelated to the study treatment. This is the first study to demonstrate a substantial objective reduction in cough frequency with low dose morphine in a clinically responsive group. Importantly this was accompanied by improvements in patient reported outcomes despite the short treatment duration used. The data suggests this population would be suitable for further investigation of the mode of action of opioids in chronic cough. Morice AHet al. Opiate therapy in chronic cough. Am J Respir Crit Care Med 2007;175(4):312–5. Median values for efficacy markers at baseline, on morphine and placebo *mean values.