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GASTROESOPHAGEAL REFLUX DISEASES

CHRONIC COUGH. due to. GASTROESOPHAGEAL REFLUX DISEASES. MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine. A cute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks. Chronic Cough. Lasting more than 8 weeks.

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GASTROESOPHAGEAL REFLUX DISEASES

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  1. CHRONIC COUGH due to GASTROESOPHAGEAL REFLUX DISEASES MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine

  2. Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S

  3. PNDS 12 ASTHMA 16 13 12 6 4 10 GERD 1.Gastroesophageal reflux disease(21-41%) 2. Cough variant asthma (24-59%) 3.Postnasal drip syndrome(41-58%) Chest 1999;116:279-284

  4. Percentage of Cases Presenting 1,2,3, and 4 Causative Factors Chest 1999;116:279-281

  5. Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough • İmmunocompetent patients • Not exposed to enviromental irritants • Chest radiograph is normal • Not taking an ACE inhibitor • Nonsmoker Harding SM .Chest 2003;123:659-660

  6. Cough the most common complaint for seeking medical care In the USA  Ist (1993) GERD the most common chronic disease ın the USA! R. C. Orlando

  7. Journal of the best Sabah. January 2004: 7

  8. GASTROESOPHAGEAL REFLUX The backflow of stomach contentsinto the esophagus (gastric acid, pepsin, bile, pancreatic enzymes) Heartburn (pyrosis) and regurgitation At least weekly symptoms manifested by either by extraesophageal reflux symptoms and/or esophageal mucosal damage GASTROESOPHAGEAL REFLUX DISEASE (GERD) Irwin SR. Chest 2006:129:80S-94S

  9. What happens during nonpathologic reflux? Kahrilas PJ.CCJM 70(5):S4-19,2003

  10. ANTIREFLUX BARRIERS Diaphragma Intrathoracic -5 mmHg Intraabdominal +5 mmHg LES +25mmHg Expiration Inspiration

  11. GERD ? Decreased saliva Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure Katzka & DiMarino 1995

  12. Causative Factors in GERD 1.Gastroesophageal barrier function impairment Hiatal hernia İmpaired diyaphragmatic crus Transient LES relaxations 2.Delayed esophageal clearance Low amplitude or simultaneous contractions Reduced salivation 3.Exogen factors Alcohol, smoking, drugs, hot drinks , hypertonic foods, aging 4.Gastric factors Acid hypersecretion ? Delayed gastric emptying Abnormal antropyloroduodenal motility (Alkalen reflux) 5.Impaired mucosal resistance

  13. Izmir, Türkiye (630) S.Bor et al. DDW 2000 Olmsted, USA (2073) Locke et al. Gastroenterology,1997 Gastroesophageal Reflux Diseasesİzmir - Olmsted Prevalance 20 18 16 14 12 15.6 10 20 17.8 19.8 Weekly symptoms % 8 10 6 4 6.3 2 0 Heartburn Regurgitation Pyrozis/ Regurgitation

  14. Menderes (Ege ÜTF) Olmsted (Mayo) Symptom GERD (+)% GERD (-) % GERD (+) % GERD (-) % Dysphagia 35,7 7,9 * 29,4 13,5 * NCCP 44,4 18,7 * 37 23,1 * Odynophagia 10,3 2,4 * Globus 23,8 8,1 * 14,2 10,6 * Regurgitation 24,6 13,8 * Hiccup 9,5 2,4 * Cough 19,8 10,3 * Hoarseness 28,6 13,1 * Asthma 0,8 2,2 11,6 9,3 GERD Related Symptoms

  15. GERD SPECTRUM Physiologic Typical Extraesophageal NERD Atypical Complications Chronic cough Hoarseness Asthma Laryngitis Aspiration pneumonia Dental erosions Snoring Noncardiac chest pain Chest pain Hiccup Dyspepsia Night sweats Globus Sleep disturbances Stricture Bleeding Barrett Adenocarcinoma Esophagitis

  16. Edema and hyperemia of larynx • Vocal cord erythema, polyps, granulomas, ulcers • Hyperemia and lymphoid hyperplasia • of posterior pharynx • Interarytenoid changes • Subglottic stenosis FLR Signs

  17. GERD-related cough incidence 5 - 41% ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 Irwin RS. Chest 2006;129:80S-94S May be the sole presenting symptom Association between cough andreflux is important • Esophageal-tracheal-bronchial reflex • Microaspiration Pathogenesis Nonacid factors? Esophageal dysmotility? Thorax 2003:58;1092-1095) Chest 1997; 111: 1389-1402 Irwin RS. Chest 2006;129:80S-94S

  18. Central Nervous System Esophagus Tracheobronchial Tree Airway REFLUX Microaspiration .Mediator Release . Inflammation . Edema .Mucus . Smooth Muscle Airway Vagal Afferents Esophageal Vagal Afferents CNS Airway Vagal Efferents Bronchial Hyperreactivity Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402

  19. Diagnostic TestsinGERD History PPI test Impedans Endoscopy Bernstein test Bilier scintigraphy Esophagography Aspiration methods Bilier scintigraphy Reflux scintigraphy Esophageal biopsy Esophageal manometry Standardized acid reflux test High magnificated endoscopy 24-h intraesophageal impedance and pH Telemetric esophageal pH monitorization 24-h intraesophageal pH monitoring

  20. Oesophagus Stomach

  21. The most sensitive and specific test for GERD is 24-h esophageal pH monitoring DeMeester score Distal DeMeester score >14.7 -Total time below pH 4 - Fractional of total time 4.2%  - Fractional time of upright position 6.3%  - Fractional time of supine position 1.2%  -Total reflux events 50  - Length of time 9.2 min.  -Total time below pH 4 - Fractional of total time 1.1%  - Fractional time of upright position 1.7%  - Fractional time of supine position 0.6%  -Total reflux events 5 - Length of time 3 min.  Proximal Richter JE, DeMeester TR.Gastroenterology 1990;98:122

  22. Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701

  23. Reflux symptoms in chronic cough patients are associated with pathologic reflux in proximal esophagus Ayık SÖ,Erdinç M,Bor S

  24. Esophageal-pulmonary Reflux • Lipid-laden macrophages in BAL • Adding indicators to feedings • Glucose oksidase test • Scintigraphic monitoring • Exhaled breath condensate (EBC) • Esophageal pH monitoring • Symptoms • Empiric PPI therapy Effros RM.Am J Med 2003;115:137S-143S

  25. 90 30 28 DLCO ml/min/mmHg 85 FEV1/FVC %   26   80 24  22  75 20 70 18 GER (-) Grade 1 İntermittent GER Grade 2 Severei GER Grade 3 GER (-) Grade 1 İntermittent GER Grade 2 Severei GER Grade 3 GER severity GER severity DLCO decrease in severe GER Schachter LM.Chest 2003;123:1932-38

  26. The empiric trial of medical therapy is appropiate when pHmonitoring cannot be done or is not available American College of Chest Physicians Chest 1998; 114(suppl1) :133S-181S The empiric trial of medical therapy should be considered even in cases pHmonitoring can be done Thorax 2003 ;58:901-907 Poe RH.Chest 2003;123:679-684 Chest 2003 ;123:650-660

  27. 24 hour pHmetry Empiric PPI therapy • GERD the most common cause of chronic cough • Empiric PPI therapy is not only practical • but is also ‘cost-effective’ • 3. Consensus should be reconsidered • 4. pHmetry should be done in nonresponsive • to empiric therapy Harding SM. Chest 2003 ;123:650-660

  28. pHmetry, High sensitive in typical symptoms however diagnostic value in extraesophageal symptoms 50 - 80% Symptom / reflux association is more important in atypical symptoms Empiric PPI therapy sensitivity  62.5 - 81% -Patients presented with laryngeal symptoms and cough-

  29. Respiratory symptoms prevalance with GERD symptoms Roka R.Digest.2005:92-96

  30. 17 cm 15 cm 9 cm 7 cm pH - 5 cm 5 cm 6 impedance channels 3 cm + 1 pH electrode Multichannel intraluminal impedance-pH catheter Adult Standard Model ZAN-S61C01E

  31. Symptoms No symptoms 50 40 Percentage of subjects 30 Oesophageal dysmotility ? 20 10 0 Abnormal Manometry alone Abnormal manometry and 24-h pH Abnormal 24-h pH alone Normal investigations Results of oesophageal manometry and 24 hour ambulatory pH monitoring in patients with chronic cough with (n=34) and without (n=9) symptoms of gastro-oesophageal reflux Kastelik JA. Thorax 2003;58:699-702

  32. Weakly acidic reflux with chronic cough Sifrim D.Gut 2005;54:449-54

  33. In patients with chronic cough who had failed to respond very intensive medical therapy, the improvement or elimination of cough in all subjects 12 months following surgery Irwin RS.Chest 2002;121:1132-1140 The term acid reflux disease when applied to chronic cough due to GERD, can be misnomer Irwin RS. Chest 2006;129:80S-94S

  34. Therapetic Options Antacids/ alginates Life-styles PPIs H2RB GERD Prokinetic agents Fundoplication Endoscopic Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–406.

  35. Pharmacological Therapy in GERD • 1) Acid inhibition / neutralization • Antascides • H2 receptor blockers • Ranitidin • Famotidin • Nizatidin • Proton pump inhibitors • Omeprazol • Lansoprazol • Pantoprazol • Rabeprazol • Esomeprazol 2) Barrier Alginic acid 3) Cytoprotectives Sucralfat Mizoprostol 4) Prokinetics Cisapride Domperidon? Metoclopramid?

  36. Comparison of H2B with PPI Metaanalysis Study Risk ratio (95% CI) % Weight Bardhan 1995 0.26 (0.15,0.46) 5.0 Klinkenberg-Knol 1987 0.33 (0.16,0.69) 3.3 Havelund 1988* 0.42 (0.28,0.62) 7.1 Sandmark 1988 0.48 (0.33,0.69) 7.8 Bate 1990 0.59 (0.48,0.73) 11.1 Dehn 1990* 0.60 (0.37,0.98) 5.9 Bianchi Porro 1992 0.63 (0.42,0.94) 7.1 Koop 1995 0.72 (0.54,0.95) 9.5 IROSG 1991 0.61 (0.38,0.99) 5.9 Robinson 1995 0.37 (0.24,0.57) 6.6 Vantrappen 1988* 0.26 (0.10,0.67) 2.2 Farley 2000 0.64 (0.52,0.79) 11.0 Jansen 1999 0.35 (0.21,0.59) 5.5 Armbrecht 1997 0.59 (0.29,1.20) 3.5 Van Zyl 2000 0.52 (0.36,0.76) 7.6 Soga 1999 0.09 (0.01,0.62) 0.6 Overall (95% CI) 0.50 (0.43,0.58) .012003 1 83.3135 Risk ratio PPI H2RA Moayyedi. Health Care Needs Assessment, 2002

  37. Therapy in Esophageal-pulmonary reflux • Conservative and lifestyle measures • Pharmacological therapy: Proton pump inhibitors PPI x 2 / 3 months • Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry) GERD (+) High dose PPI Surgery, + H2 blocker agent Pulmonary and Crit Care Update 1994;Vol 9 Morice AH. ERJ 2004;24:481-492

  38. J. A.Koufman. ENT-Ear, Nose & Throat Journal, Sep 2002 Supp Morice AH.ERJ 24:481-492,2004

  39. Esophagus PPI PPI Stomach

  40. Specific therapy for diagnosis and treatment Results of therapy in treating cough due to GERD Poe RH.Chest 2003;123:679-684

  41. Cumulative Response to GERD Therapy Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 44 (100) Poe RH.Chest 2003;123:679-684

  42. Effect of the GABAB agonist baclofen on symptoms in patients with GERD Ciccaglione AF.Gut 2003;52:464-470

  43. Anti-Reflux Surgery Restore Intraabdominal esophagus Reduce Hiatal Hernia Approximate Diaphragmatic crurae Perform Fundoplication

  44. Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9

  45. Preop pH <4: %14.5 De Meester: 52.9 Postop pH <4: %3.8 De Meester: 14.2

  46. Clinical Profile That Chronic Cough İs Likely Due To‘Silent GERD’ 1.Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy 1st generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002

  47. Chronic Cough History and Physical Avoid irritants Discontinue ACE ihibitors Smoking cessation normal abnormal Chest radiograph Sputum cytology, HRCT scan Bronchoscopy Esophagography Cardiac evaluation GERD symptoms (-) (+) Ampiric PPI Three months b.i.d. Asthma, PNDS Spirometry (BPT) ENTevaluation Spesific diagnosis and treatment Spesific diagnosis and treatment Cough persists pHmetry ( surgery?) Psychogenic cough(?) Cough persists Cough persists

  48. Pharyngeal pHmetry - + Increase dose PPI + alginate Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Not improved İmproved Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance pHmetry under treatment Continue Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004

  49. EGE REFLUX WORKING GROUP KBB Faringolaringeal reflü Gastroenteroloji Erişkin-Çocuk Göğüs, Pulmoner reflü Kardiyoloji NCCP Psikiyatri, Halk sağlığı Patoloji Diş Hek. Cerrahi Erişkin, Çocuk www.gerd-turkey.org

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