1. Opiate Therapy in Chronic Cough Alyn H. Morice, Madhav S. Menon, Siobhan A. Mulrennan, Caroline F. Everett, Caroline Wright, Jennifer Jackson and Rachel Thompson - Am J. Resp. and Crit. Care of Med. Vol 175. 2007-

2. Background Chronic cough - most common complaint symptom - prevalence : 7% by questionnaire survey “chronic cough can be both physically and mentally debilitating ” Opiate therapy - have long been advocated for the suppression of cough - single-dose studies of codeine in chronic bronchitis have shown some benefit : recent trial suggested an effect similar to that of placebo

3. Aim To determine whether low-dose opiates in the form of slow- release morphine has a role in the management of patients with idiopathic cough or in those resistant to conventional treatments

4. Methods(1) Subjects - adult patients attending the Hull Cough Clinic - who had a chronic, persistent cough of greater than 3 months - excludes patients with significant lung disease - enrolled who failed to respond to trials of specific antitussive therapy

5. Methods(2) Data collections - randomized into a double-blind placebo-controlled crossover study - 4 weeks of slow-release morphine sulfate (MST) 5 mg twice daily - 4 weeks of matched placebo - three visits to the clinical trials unit : filled in the Leicester Cough Questionnaire -- the impact of chronic cough on activities of daily living -- the 19-item questionnaire based on physical, social, and psychological effects of cough

6. Methods(3) Assessment of outcomes - spirometry with reversibility to 2.5 mg of nebulized salbutamol - citric acid cough challenge test - cough severity : scale of 0 to 9 and recorded on a daily diary Primary end point - change in the Leicester Cough Questionnaire (LCQ)

7. RESULTS

8. Result Core study - Study enroll & method : 27 pts, morphine sulfate 5mg bid - LCQ score change : improvement of 3.2 points over baseline ( p<0.01) - Daily cough score : rapid and significant reduction by 40% (p<0.01) - Objective testing of citric acid cough challenge test : no change Extension study - Study enroll & method : 18 pts, morphine sulfate 10mg bid - 3month later  similar improvement in cough between the 5mg and 10mg group

9. Figure 1. Daily cough severity scores on a scale of 0 to 9. MST = slow- release morphine sulfate

10. TABLE 1. Analysis of varuence-tukey post hock test for multiple comparision on subdomains of the Leicester Cough Questionnaire

11. Figure 2. Mean of daily diary cough scores

12. Discussion (1) Chronic cough - be similar to that seen in severe chronic obstructive pulmonary disease - need for symptomatic treatment Codeine - the archetypical antitussive opiate - noncontrolled drug status : metabolized to morphine by cytochrome P450–2D6, and so plasma levels depend on the acetylator status

13. Discussion(2) antitussive action of morphine - due to sedation - clear benefit was demonstrated in severity and frequency of cough - the average improvement in total LCQ score : higher than 2.56, to be clinically significant - response : rapidly, with maximum benefit being achieved by Day 5 - optimum dose : between 5 and 10 mg twice daily

14. Discussion(3) The limitations of this study - cannot be completely blinded - not addressed the long-term effects of low-dose morphine

15. Conclusion Morphine sulfate is an effective antitussive in intractable chronic cough at the doses of 5 to 10 mg twice daily