How to treat cough associated with common cold

Transcription

1 How to treat cough associated with common cold Professor Ron Eccles Common Cold Centre Cardiff School of Biosciences Cardiff University Pneumology around the clock Alberobello October

2 Common Cold Centre Part of Cardiff University, Wales, UK Main interest is in understanding mechanisms of symptoms and symptomatic treatments Common Cold centre established 1988 to conduct clinical trials on new treatments for common cold and flu 2

3 Cough ---- a vital protective reflex cerebral cortex Urge to cough Voluntary control sensation of irritation NTS respiratory area of brainstem +ve / -ve MECHANICAL OSMOTIC ph vagus nerve Aspirated food and fluid respiratory muscles cough! 3

4 Acute cough due to common cold is the most common type of cough and one of the most common symptoms Defined as cough < 3weeks Boujaoude ZC, Pratter MR. Clinical approach to acute cough. Lung. 2010;188 Suppl 1:S Pratter MR. Cough and the common cold: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):72S-74S. Acute cough is caused by respiratory viral infection which causes hypersensitivity of airway receptors 4

5 1976 Empey DW et al. Mechanisms of bronchial Hyperreactivity in normal subjects after upper respiratory tract infection. Am Rev Respir Dis. 1976;113(2): Our study demonstrates that spontaneous, presumably viral, upper respiratory tract infections cause striking increases in bronchial reactivity to inhaled histamine and citric acid aerosols in otherwise normal subjects. This bronchial hyperreactivity was present during infection and for several weeks after recovery, but all the subjects returned to normal within 7 weeks. 5

6 2016 Zaccone EJ, Lieu T, Muroi Y, Potenzieri C, Undem BE, Gao P, et al. Parainfluenza 3- Induced Cough Hypersensitivity in the Guinea Pig Airways. PLoS One. 2016;11(5):e In summary, PIV3 infection leads to elevations in TRPV1 expression in the two key cough evoking nerve subtypes in the guinea pig trachea, and this is associated with a hypertussive state with respect to various TRPV1 activating stimuli. 6

7 Acute cough cerebral cortex Urge to cough Voluntary control sensation of irritation NTS respiratory area of brainstem +ve / -ve hypersensitivity vagus nerve TRPV1 INFECTION airway inflammation and irritation respiratory muscles cough! 7

8 Treatments for acute cough can work at three levels cerebral cortex (psychological)r brainstem (cough control) peripheral actionsr 8

9 Treatments for acute cough peripheral actionsr 9

10 1 peripheral actionsr NORMAL COUGH (reflex?) ACUTE HYPERSENSITIVE COUGH (voluntary?) INCREASED TRPV1 EXPRESSION VIRAL INFECTION MECHANICAL CHEMICAL ph inflammatory mediators bradykinin, prostaglandins, cytokines, Substance P etc. 10

11 Peripherally acting treatments ACUTE COUGH EFFECT ON NERVE ENDINGS guaifenesin levodropropozine EFFECT ON MEDIATORS NSAID s corticosteroids leukotriene antagonists HYPERSENSITIVITY 11

12 Efficacy of levodropropizine This analysis indicates that levodropropizine is an effective antitussive drug in children and adults Zanasi A, Lanata L, Fontana G, Saibene F, Dicpinigaitis P, De Blasio F. Levodropropizine for treating cough in adult and children: a meta-analysis of published studies. Multidisciplinary respiratory medicine. 2015;10(1):19. 12

13 Cough scores over 3 evenings, honey and milk, dextromethorphan, levodropropizine Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. Miceli Sopo S, Greco M, Monaco S, Varrasi G, Di Lorenzo G, Simeone G, et al. Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review. Allergol Immunopathol (Madr). 2015;43(5):

14 Treatments for acute cough brainstem (cough control) 14

15 TREATMENTS acting on brainstem codeine dextromethorphan antihistamines Urge to cough sensation of irritation Voluntary control sweet syrups NTS respiratory area of brainstem +ve / -ve vagus nerve INFECTION airway irritation respiratory muscles cough! 15

16 codeine placebo Mean cough frequency before and after treatment with a single dose of codeine syrup B.P (30mg/10ml) n= 46 and placebo syrup vehicle n = 45 Eccles, R., Morris, S. & Jawad, M. (1992) Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection. Journal of Clinical Pharmacy and Therapeutics, 17,

17 Subjective scores for cough placebo versus 30mg codeine Eccles R, Morris S, Jawad M Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection. J Clin Pharm Ther. 1992;17:

18 Severity scores over 3 days for cough, placebo versus 30mg codeine Eccles R, Morris S, Jawad M Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection. J Clin Pharm Ther. 1992;17:

19 Lack of effect of codeine as an antitussive BOLSER, D. C. & DAVENPORT, P. W. (2007) Codeine and cough: an ineffective gold standard. Current opinion in allergy and clinical immunology, 7, Recent placebo-controlled studies have shown that codeine is no more effective than placebo in suppressing cough caused by either upper respiratory disorders or chronic obstructive pulmonary disease. These recent reports are not consistent with several older placebo-controlled studies that demonstrated the efficacy of codeine. 19

20 Most cough medicines are viscous sweet syrups Sweet taste may modulate cough by generation of endogenous opioid compounds in brainstem. This mechanism is accepted for analgesic effects of sweet substances ECCLES, R. (2006) Mechanisms of the placebo effect of sweet cough syrups. Respiratory physiology & neurobiology, 152,

21 Antitussive effect of sweet taste ECCLES, R. (2006) Mechanisms of the placebo effect of sweet cough syrups. Respiratory physiology & neurobiology, 152,

22 Effect of taste sensation on cough Rinsing mouth with sweet solution inhibited capsaicin induced cough but rinsing with bitter tasting solution had no effect Wise PM, Breslin PA, Dalton P. Effect of taste sensation on cough reflex sensitivity. Lung. 2014;192(1):

23 Treatments for acute cough cerebral cortex (psychological)r 23

24 TREATMENTS acting on cerebral cortex Urge to cough Voluntary control Placebo effect sensation of irritation of ALL cough treatments NTS respiratory area of brainstem +ve / -ve vagus nerve INFECTION airway irritation respiratory muscles cough! 24

25 Placebo The placebo is the most effective medication known to science, subjected to more clinical trials than any other medicine yet nearly always does better than anticipated O Donnel M, Monitor Weekly

26 Placebo versus no treatment No treatment Received only a glass of water cough 30 frequency 15 minutes minutes placebo Received a glass of water and a capsule of vitamin E 0 pre pre treatment post post treatment Patients were told that the study was designed to investigate the effects of vitamin E on cough associated with common cold Lee et al 2005 Psychosomatic Medicine

27 Factors influencing psychological effects of cough medicine Side effects of medicine Environment Doctor-patient interaction Culture Advertising and branding Conditioned response Formulation and dose Physiological effect Personality of patient Faith, hope, belief 27

28 Treatments for acute cough can work at three levels cerebral cortex (psychological)r brainstem (cough control) peripheral actionsr 28

29 ALL SWEET SYRUPS ARE EFFECTIVE ANTITUSSIVES FOR ACUTE COUGH Sweet placebo syrups containing honey etc. are effective antitussives and until we have a safe and effective pharmacological treatment to reverse cough hypersensitivity associated with viral infection sweet syrups are still my preferred treatment for pediatric and adult acute cough 29

30 THANK YOU Cardiff bay 30