6 Approach to unproductive cough recap & recent updates.pptx

Approach to unproductive cough recap & recent updates

1. Approach to unproductive cough recap & recent updates A2C cough symposium Dr. Kamal Kishore MD Consultant Physician Geetanjali Multi Speciality Hospital Hisar

2. contents Case discussion Overview of cough Newer antitussives Levocloperastine Recent updates [NEW study in Indian population] Clinical evidences Summary and take home message 2

3. 3 Cough- as a symptom 3 Not a disease in itself It is an indication that something is wrong with systems like respiratory, cardiovascular & gastrointestinal One of the most common reasons to consult a doctor

4. Cough Reflex Arc 4

5. Cough Reflex Arc Afferent pathway: Sensory nerve fibers (branches of the vagus nerve) located in the ciliated epithelium of the upper airways (pulmonary, auricular, pharyngeal, superior laryngeal, gastric) and cardiac and esophageal branches from the diaphragm.   Efferent pathway: Via the vagus , phrenic, and spinal motor nerves to diaphragm, abdominal wall and muscles. The nucleus retroambigualis , by phrenic and other spinal motor nerves, sends impulses to the inspiratory and expiratory muscles; and the nucleus ambiguus , by the laryngeal branches of the vagus to the larynx. 5

6. 6 Classifying cough: based on duration Based on sputum production : Dry cough Wet cough/productive cough Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest 2006; 129:1S.

7. Trigger factors 7

8. 8 Causes of acute cough Kalpesh B Vaishnav. Diagnostic Approach to Cough. Supplement to Journal of the association of physicians of india • MAY 2013 • VOL. 61

9. 9 Causes of Sub-acute cough Kalpesh B Vaishnav. Diagnostic Approach to Cough. Supplement to Journal of the association of physicians of india • MAY 2013 • VOL. 61

10. Causes of chronic cough Respiratory conditions Postnasal drip syndrome Post-infectious cough, Pulmonary TB Asthma / COPD Allergic or vasomotor rhinitis Interstitial lung disease (ILD) Primary or metastatic lung tumors Drug induced cough (ACE inhibitors, beta blockers, NSAIDS) ACE inhibitors induced- usually within a week but may be delayed till 6months; maybe due to accumulation of bradykinins/ substance P Non respiratory conditions Gastroesophageal reflux disease Recurrent aspiration Left ventricular failure Psychological response Pulmonary infarction Aortic aneurysm 10 Huliraj N. Diagnosis and Management of Dry Cough: Focus on Upper Airway Cough Syndrome and Postinfectious Cough. Indian Journal of Clinical Practice, Vol. 24, No. 9, February 2014 Chronic cigarette smoking is the most common cause of chronic cough

11. Etiology Cough occurs when there is inflammation, constriction, infiltration or compression of the airways Inflammation : viral/ bacterial bronchitis or bronchiectasis Constriction : Asthma Infiltration : With granulomas as in tuberculosis, neoplasms Compression : Lymph node masses, mediastinal tumours , aortic aneurysm 11

12. Current management options for cough 12

13. 13 MANAGEMENT OF COUGH Type of Cough Class of Ingredient Examples Dry Cough Anti- tussives Codeine
Dextromethorphan Levocloperastine Antihistamines Fexofenadine Chlorpheniramine maleate Productive Cough Expectorants Guaiphenesin Mucolytic agents Ambroxol Carboxymethylcysteine Bronchodilators Theophylline, Levosalbutamol Terbutaline Decongestants Phenylephrine
Pseudoephedrine 13

14. 14 14 Expectorants

15. 15 Dry cough therapy – Antitussives 15

16. 16 16 Centrally acting Anti- tussives

17. Anti- tussive drugs : Types and sites of action De Blasio F et al. Cough. 2011 Oct 10;7(1):7 17 Antitussive Drugs Central action Peripheral action Codeine, Pholcodeine +++ - Noscapine , Dextromethorphan +++ - Diphenhydramine, Chlorpheniramine - ++++ Levodropropizine - +++ Levocloperastine +++++ +++++

18. 18 Limitations of current therapy

19. Limitations of current therapy 19 Current antitussive agents at effective doses have adverse events such as sedation, nausea and constipation that limit their use 1 Dependence and addiction liabilities are a concern 2 Therefore, there is a therapeutic need for effective and better tolerated agents in dry cough management 19 Online J. Med. Med. Sci. Res. ;2013. 2 (1), 1-5 2. Multidisciplinary Respiratory Medicine (2015) 10:19

20. What is Levocloperastine? Non-opioid antitussive Centrally as well as peripherally acting Levorotatory isomer of DL- cloperastine Advantages of Levocloperastine NO Sedation NO Dependence or addiction liability NO significant drug-drug interactions 20 Clin drug invest., 2002;22(4):209-220

21. Pharmacodynamics Antitussive action Levocloperastine acts centrally on receptors in the bulbar cough centre 50% effective dose values were less for Levocloperastine vs codeine Highly selective CNS action: does not cause sedation like codeine Anti-spasmolytic Antihistaminic action demonstrated in the respiratory tract (in-vitro and in-vivo) 21 21 Aliprandii P. Clin drug invest., 2002;22(4):209-220 Effective Dose range: 60-120mg/day

22. Contraindications & Precautions 22 CONTRAINDICATIONs Hypersensitivity Productive cough Severe liver impairment Pregnancy and lactation PRECAUTIONS Hypertension, cardiovascular disease, Uncontrolled diabetes mellitus, Hyperthyroidism Seizures 22

23. Tolerability 23 Selective CNS action 1 No sedation – does not interfere with ability to drive or use machinery No dependence liability Does not interfere with mucociliary clearance – more physiological Does not interfere with peristalsis 1 - Less chances of constipation Does not interact with other drugs and hence can be taken by patients who are on medication for other conditions Mild and transient nausea was the only adverse event reported in clinical trials 23 Miliani M. Online J. Med. Med. Sci. Res. ; Volume 2, Issue 1, pp. 1-5; January 2013 Levocloperastine is well tolerated with no central adverse effects

24. Recent updates [NEW study in Indian population ] 24 First of its kind – prospective, multicentre, observational study on Levocloperastine in 100 Indian patients across different age groups with cough!

25. Publication details Original study published in JAPI in May 2018 JAPI is one of the premier medical journals in India. It is published on behalf of Association of Physicians of India (API) which has approximately 13,000 membership consisting of consultant physicians and specialists in various branches of internal medicine. They are considered as trend setters in prescribing habits in the country. 25

26. Purpose/Aim: To evaluate effectiveness and safety of Levocloperastine in the treatment of dry cough in adult Indian patients. 26

27. Methods: patient details prospective, observational study patients aged 18-60 years, presenting with dry cough and prescribed with Levocloperastine at baseline or a day prior to enrolment, as per standard clinical practice, were recruited These patients were enrolled over a period of approximately 2 months (Nov to Dec 2017) from 3 centres (one each at Karnataka, Delhi, and Maharashtra) in India. 27

28. Methods: Study design This was a prospective, multicentre, observational study consisting of 2 visits (baseline visit and on Day 14) Patients were followed up telephonically on Days 2, 5 and 7 of enrolment and the data regarding: patient compliance with treatment, study requirements (daily completion of the patient diary) and adverse drug reactions (ADRs), if any, were collected 28

29. Methods: Study assessment tools Cough severity was measured on 100 mm VAS scale Cough frequency since last 24 h (7-point Likert scale) Sleep disruption due to night-time awakenings(10 cm VAS) 29

30. Methods: Study assessment tools The QoL was assessed using 19-item patient-reported Leicester Cough Questionnaire (LCQ). LCQ comprises of 3 health domains: physical psychological and social Each item assesses symptoms or the impact of symptoms on a 7-point Likert scale. 30

31. Methods: Study outcomes measured Primary outcome mean change in cough severity score from baseline to Day 14. Secondary outcome mean changes in cough frequency score, sleep disruption score based on night time awakenings, and LCQ scores from baseline to Day time (in days) for achieving minimal important difference (MID) in cough severity and physician-reported effectiveness of treatment with Levocloperastine . 31

32. Methods: Study outcomes measured Safety outcome nature and frequency of ADRs and Proportion of patients reporting sedation and other central nervous system side effects (dizziness, drowsiness, drug dependence etc.) while on treatment with Levocloperastine 32

33. Results: The mean scores of cough severity, cough frequency and sleep disruption due to night-time awakening were significantly reduced from baseline to Day 14 (p<0.0001) A significant improvement in QoL scores was noted from baseline to Day 14 (p<0.0001) Disappearance of cough was reported in 44% of patients; 54% patients reported improvement of cough by Day 14. No ADRs, cases of sedation or other side-effects were reported in the study. 33

34. Summary of Results 34

35. Summary of Results 35 of the patients showed improvement in cough within Mean reduction in severity of cough by within Sleep disruption reduced by of the patients had complete disappearance of cough Mean reduction in Frequency of cough by

36. Levocloperastine was found to be effective and safe in the management of dry cough. A significant reduction in severity scores, frequency of cough and sleep disruption was reported, with an overall improvement in patient’s QoL . 36

37. Other supporting studies A quick recap 37 37