Idiopathic chronic cough: Real disease or wrong diagnosis? Dr Surinder Birring MD Consultant Respiratory Physician King s College Hospital, London

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1 Idiopathic chronic cough: Real disease or wrong diagnosis? Dr Surinder Birring MD Consultant Respiratory Physician King s College Hospital, London

2 Chronic cough terminology Idiopathic Unexplained Refractory Persistent

3 Idiopathic chronic cough: clinical characteristics Cough >8 weeks duration Non-smoker Not taking ACE-Inhibitor Normal CXR/spirometry Treatment trial Investigations -high dose PPI (3 months) -Inhaled/oral steroids -Nasal steroids/antihistamine -24 Hr Oes ph (on PPI) -Methacholine/Induced Sputum

4 What is idiopathic chronic cough? Wrong Diagnosis (unrecognised asthma, GOR, rhinitis) Psychogenic Separate entity

5 Prevalence of idiopathic cough Morice et al, ERJ 2004; 24:481-92

6 Idiopathic cough: Missed asthma/eosinophilic bronchitis? Poor response to inhaled steroids: -compliance -inhaler-technique -dose/duration -small airways Second line tests for asthma infrequently used Missed asthma/eb- small number of cases -methacholine challenge -induced sputum -trial of oral prednisolone

7 Idiopathic chronic cough (ICC): Missed GOR? ipost-prandial cough frequency not increased in ICC Raj A et al, Thorax 2007; 62(Supp 3): P116 iacid reflux not important: PPIs ineffective inon-acid volume reflux not abnormal in ICC (oesophageal impendence studies) Decalmer S et al, Thorax 2007; 62(Supp 3): P114 itemporal relationship between cough and GOR?

8 ICC- no gastric aspiration Lung Transplantation Stovold R et al, AJRCCM 2007; 175:

9 BMJ 2006;332:11-17 GOR treatment failure BMJ Header BMJ Chang AB et BMJ 2006; 332:11-4 Primary outcome fig1

10 Idiopathic cough: Missed rhinitis? ino! iresponse to antihistamine not always indicative of rhinitis cough irhinitis-cough not considered an entity amongst many ENT physicians

11 Idiopathic cough- Are they mad?

12 Depressive symptoms in chronic cough Asthma Chronic cough Severe COPD Heart Failure Diabetes IHD Hypertension CES-D Score > 16 (%) Dicpinigaitis P et al, Chest 2006; 130:1839

13 Therapy for cough reduces psychological symptoms 7 *p=0.003 *p<0.001 *p=0.03 n=23, ICC LCQ Domain Score Before After Chest Physiotherapy 0 Physical Psychological Social Watkin G et al; Thorax 2006;61(suppl II):ii92

14 Idiopathic chronic cough - unique entity i180 patients ( ) ihighest incidence in 5th - 7th decade ionset around menopause i80% Female predominance idry cough with heightened cough reflex isome evidence of lower airway inflammation ipoor Quality of Life Yousaf N et al, Thorax 2007; 62(Supp 3): P118

15 Idiopathic Cough and Autoimmune Disease Autoimmune disorder Controls Idiopathic Cough (n=65) (n=22) Hypothyroidism 2 5 Hyperthyroidism 3 0 Diabetes mellitus type1 2 3 Pernicious anaemia 0 2 Coeliac disease 1 1 Vitiligo/premature menopause 0 1 Vitiligo & chronic hepatitis 0 1 Total 8 (12%) 13 (59%) Odd ratio 8.8; p<0.001 (4% in explained cough; 3-8% in general population) Birring et al, Resp Med 2004; 98: 242-6

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17 HYPOTHESIS - Idiopathic cough may have an autoimmune basis - Homing of activated lymphocytes from primary sites of autoimmune inflammation to the lung

18 BAL lymphocytosis in idiopathic cough BAL lymphocyte count % **p= 0.01 ANOVA History of autoimmune disease or positive autoantibodies Mean (SEM) 10 0 Normal (n=11) Idiopathic Cough (n=19) Explained Cough (n=14) Birring et al, Thorax 2003;58:

19 Airway lymphocytosis in idiopathic chronic cough BAL McGarvey et al. ERJ 1999;13:59-65 Mund et al. CHEST 2005;127: Bronchial biopsy Boulet et al. AJRCCM 1994;149:482-9 Lee et al. CHEST 2001;120:

20 Altered BAL T-cell phenotype after menopause Mund et al. Thorax 2001;56:450-5

21 Organ-specific autoimmunity Low grade airway inflammation Menopause associated change in lung immunity Amplified inflammatory response Clinical problem

22 3.5 Heightened cough reflex in chronic cough LogC2 µmol/l Healthy -0.5 LogC5 µmol/l Healthy CVA GORD PND ICC Others Prudon B et al, Chest 2005; 127:550-7

23 Cough Reflex Hypersensitivity CRH Idiopathic

24 Recently identified causes of cough Eosinophilic bronchitis Tonsillar Enlargement Obstructive Sleep Apnoea Hereditary Cough Gibson P, Lancet 1989; 1: 1346 Birring S, ERJ 2004;2 3: 199 Birring S, Cough 2007; 3: 7 Spring AH, Brain 2005; 128: 2797

25 ICC treatment: Improved QOL with Morphine **p< n=27 4 weeks 15.5 LCQ Score Baseline Placebo MST Treatment Morice AH et al; AJRCCM 2007; 175:312-5

26 Summary hidiopathic cough is a common condition haffects predominantly middle aged women hcough reflex hypersensitivity hassociation with autoimmune disease hneed better antitussive therapies

27 Acknowledgements htracey Fleming hclaire Wood hdaniel Cox hcatherine George hian Pavord handy Wardlaw hchris Brightling hdebbie Parker hben Prudon hsally Singh hbeverly Hargadon hsergio Matos hdavid Evans hanita Raj hgillian Watkin