Laryngopharyngeal and Gastroesophageal Reflux Disorders Sarah K. Wise, M.D.

1. Laryngopharyngeal and Gastroesophageal Reflux Disorders Sarah K. Wise, M.D.

2. Acknowledgement John M. DelGaudio, MD Professor Otolaryngology – Head and Neck Surgery Emory University Atlanta, GA

3. Objectives • Understand the pertinent history and physical findings of LPR and GERD • Learn work-up for acid reflux disorders in otolaryngology • Learn medical and surgical treatment options for LPR and GERD

4. Case presentation 46 y/o man CC: “sinus drainage” HPI: 18 month history of intermittent post-nasal drainage, thick phlegm in the throat, frequent throat clearing, intermittent hoarseness, occasional heartburn. Symptoms unresponsive to antibiotics x2, fluticasone nasal spray, fexofenadine, and saline nasal sprays.

5. Physiologic barriers to reflux: LES • Lower esophageal sphincter • Smooth muscle • 3-5 cm long • Tonic at rest • Reflex relaxation • Abnormalities • Hiatal hernia: loss of intra-abdominal portion • Neurologic impairment

6. Physiologic barriers to reflux: UES • Upper esophageal sphincter • Cricopharyngeus • Skeletal muscle • 2 cm long • Tonic at rest • Reflex relaxation • Abnormalities • Cause short acid exposure events • Neurologic issues • Inappropriate relaxation

7. Theories for development of upper airway problems due to reflux • Direct gastric acid and/or pepsin exposure • Mucociliary function decreases with small amounts of acid exposure • Defense mechanisms against acid in upper airway are not as robust compared to esophageal defense mechanisms • Distal esophageal acid exposure causes increased UES pressure • Neurally-mediated upper airway mucosal inflammation

8. Pepsin in the upper airway • Pepsin • Produced in the stomach by gastric chief cells • May be detected in the laryngeal mucosa following reflux events • Causes mucosal injury by • Depletion of carbonic anhydrase isoenzyme III and squamous epithelial stress protein Sep70 • Breakdown of intercellular junctions • Pepsin activity • pH 2.0 – maximum activity • >pH 6.5 or higher – inactivated • pH 7.0-8.0 – stable for 24 hours Repeat acid reflux events may reactivate pepsin in upper airway. Johnston N, et al. Laryngoscope 2007;117:1036-9.

9. Pepsin in the upper airway • Ozmen et al. (2008) • 33 CRS pts (medically refractory) vs. 20 controls • Dual monitor pH probe • Pepsin assay from nasal lavage • 100% of pts with (+) pepsin assays had (+) pharyngeal reflux • Pepsin assays (-) in only 3 LPR pts • Pepsin assay for detecting LPR • 100% sensitive • 92.5% specific Ozmen et al. Laryngoscope 2008;118:890-94.

10. GERD: symptoms • Heartburn • Regurgitation • Indigestion • Nausea • Worse after meals • Aggravated by change in position • Relieved promptly by antacids Many classic GERD symptoms may be absent in LPR.

11. GERD: associated conditions • Hiatal hernia • Obesity • Reactive airway disease • Pregnancy • Smoking

12. LPR: symptoms Halitosis Cough Airway reactivity Bronchospasm, wheezing, Laryngospasm Choking/gagging Ear fullness, pain Dental caries • Throat irritation • Fullness, soreness, tickle, globus, phlegm, clearing • Vocal complaints • Hoarseness, raspiness, loss of vocal range • Post-nasal drip* • Dysphagia • Sour taste *Wise SK, Wise JC, DelGaudio JM. Am J Rhinol 2006;20:283-89.

13. LPR: symptoms • Less than half of LPR patients have classic esophageal symptoms (heartburn, indigestion, etc.) • LPR is a distinct subtype of reflux • Symptoms • Treatment regimen • Timing of response to medical therapy • Many symptoms attributed to other diseases and organ systems (i.e. sinus infections, allergies, pulmonary)

14. LPR: associated conditions • Vocal process granuloma • Subglottic stenosis • Reactive airway disease • Lymphoid hypertrophy* • Lingual tonsils • Waldeyer’s ring *DelGaudio JM, Naseri I, Wise JC. Otolaryngol Head Neck Surg 2008;138:473-78.

15. LPR: associated conditions • Chronic laryngitis/sinusitis* • Cricopharyngeal spasm • Zenker’s diverticulum • Serous otitis media** • Laryngeal carcinoma *DelGaudio. Laryngoscope 2005;115:946-57. **Tasker et al. Laryngoscope 2002;112:1930-4.

16. Protective mechanisms Larynx Pharynx Saliva – neutralizes acid Swallow – occurs less often while asleep • Reflex vocal fold closure • No acid neutralization or clearance mechanisms • Very small amounts of acid may have deleterious effects

17. LPR and GER: exacerbating factors • Foods • Caffeine • Carbonated beverages • Chocolate • Citrus fruits • Fried food • Fatty food • Tomato products • Dairy products • Mint flavoring • Garlic

18. LPR and GER: exacerbating factors • Habits • Smoking • Alcohol • Lifestyle • Eating within 2-3 hours of bedtime • Eating large meals late in the day

19. LPR and GER: exacerbating factors • Medications • Decrease LES pressure • Ca channel blockers • Nitrates • Anticholinergics • Theophylline • Injure mucosa • Aspirin • NSAIDS • Tetracycline • Quinidine

20. LPR and GER: initial work-up • History • Symptoms • Frequency, duration, intermittent vs. constant • Daytime vs. nighttime • Associated with meals? • Weight gain? • Exacerbating factors? (foods, medications, tobacco, etc.) • Prior treatment for reflux? • PMH • Ulcers, hiatal hernia?

21. LPR and GER: initial work-up • Physical examination • Thorough head and neck exam • Indirect laryngoscopy • Consider chest auscultation • Flexible fiberoptic laryngoscopy (if indicated)

22. Physical findings • Some physical findings have been associated with acid reflux • Lingual tonsil hypertrophy* • Vocal process granuloma • Pseudosulcus vocalis • Posterior laryngitis • Diffuse laryngeal irritation & mucosal thickening *DelGaudioJM, Naseri I, Wise JC. OtolaryngolHead Neck Surg 2008;138:473-78.

23. Physical findings Despite some physical findings being associated with reflux, there are no pathognomonic physical findings for GER or LPR that can be identified on routine ENT exam/scope.

24. Initial treatment • Benign history, examination, and upper airway endoscopy: • Begin lifestyle changes and medical therapy for reflux • Any concern for malignancy or other pathology: • Radiologic work-up • Referral as necessary

25. Initial treatment: lifestyle modifications • Avoid exacerbating foods & beverages • Avoid eating late at night • Elevate head-of-bed with wood blocks (6 in.) • Stop smoking • Lose weight • Eat small meals • Avoid tight-fitting clothing

26. Initial treatment: pharmacotherapy • Antacids • Combinations of basic salts (Ca, Mg, Al) with hydroxide or bicarbonate to neutralize acid • Side effects: constipation (Ca, Al) or diarrhea (Mg) • Foaming agents – coat stomach

27. Initial treatment: pharmacotherapy • H2 blockers – decrease acid production • Short term relief • Effective for approx. 50% • Examples: • Cimetidine • Famotidine • Ranitidine

28. Initial treatment: pharmacotherapy • Proton pump inhibitors – inhibit acid production • More effective than H2 blockers • Heal esophageal lining • Typically first choice for LPR • Examples • Omerazole • Lansoprazole • Pantoprazole • Esomeprazole

29. Initial treatment: pharmacotherapy • DelGaudio & Waring. Empiric esomeprazole in the treatment of laryngopharyngeal reflux. (Laryngoscope 2003) • 30 patients with suspected LPR • Stepwise approach: Qday esomeprazole – BID esomeprazole – pH study if no response after BID dosing • At least 8 weeks of therapy necessary to improve laryngeal symptoms of LPR • Treatment for LPR often requires higher dose & longer duration of PPI therapy vs. GERD

30. Initial treatment: pharmacotherapy • Prokinetics – promote faster stomach emptying and increase LES strength • Example: metoclopramide • Side effects: sleepiness, fatigue, depression, anxiety • Due to differing mechanisms of action, various drugs may be used in combination to treat GERD and LPR

31. Additional work-up • When medications and lifestyle modifications fail to control GERD symptoms, consider additional testing… • Barium swallow • Detects anatomic abnormalities (strictures, hiatal hernias, dysmotility) • May not directly observe reflux unless it occurs during the test • Strongly consider for reflux with dysphagia

32. Additional work-up • Upper endoscopy or transnasal esophagoscopy • Visualization of mucosal surfaces • Biopsy of lesions • Koufman et al. (2002) • 58 pts with LPR on pH study • All underwent EGD and biopsy • 19% with esophagitis or metaplasia • Generally, EGD is not initial diagnostic test of choice for LPR Koufman et al. Laryngoscope, 2002;112:1606-9.

33. Additional work-up • Barrett’s esophagus – intestinal metaplasia of esophagus • Increased risk of Barrett’s esophagus with classic GER (heartburn 2x per week for 5 years) • Risk for esophageal adenocarcinoma in people with Barrett’s esophagus <1% per year Shaheen & Ransohoff. JAMA 2002;287:1982-6.

34. Additional work-up • Consider EGD for… • Longstanding heartburn • GER or LPR refractory to medical therapy • Dysphagia • Barium swallow with evidence of mass, mucosal lesion, or other abnormalities • Barrett’s esophagus monitoring Per J. Patrick Waring, gastroenterologist

35. Additional work-up • pH monitoring • Esophageal and pharyngeal probes may be placed to record pH changes over 24-48 hours • Abnormal LES: pH <4.0 for >4% of the time • Abnormal UES: no uniform criteria • Diary • PO intake • Upright vs. supine position • Symptoms (heartburn, cough, etc.)

36. pH Testing: GER vs. LPR • Abnormal distal (esophageal) reflux parameters on pH monitor are not necessary for LPR • LPR • Higher proportion of reflux episodes reach upper esophagus • Upright reflux more prevalent than in GER • pH study indications • Inadequate response to medical therapy • Verification of reflux diagnosis • Evaluation for reflux surgery Weiner et al. Am J Gastroenterol, 1989;84:1503-8. Shaker et al. Gastroenterol, 1995;109:1575-82.

37. Surgery for GER or LPR • Referral for reflux surgery may be indicated when medications fail to control symptoms • Fundoplication • Superior stomach wrapped around LES to strengthen LES and prevent reflux • Open vs. laproscopic • Predictors of good surgical outcome (EER) • Response to PPI’s • Proximal reflux on pH probe So et al. Surgery. 1998;124:28-32.

38. Surgery for GER or LPR • Endoscopic techniques • LES suturing • LES cautery • Long term outcomes not known

39. Surgery for GER and LPR • Potential indications for reflux surgery • Failure or intolerance of medical (PPI) therapy • Complications of GER • Barrett’s esophagus • Erosive esophagitis • Complications of LPR • Airway scarring/stenosis

40. Complications of Reflux • Esophagitis • Ulceration • GI bleed • Strictures • Barrett’s esophagus • Esophageal carcinoma • Pulmonary fibrosis

41. Summary • Reflux patients often present to the ENT clinic. Many have failed treatment for other allergies, sinus infections, etc. • A detailed history will often lead the provider to reflux symptoms and exacerbating factors. • Thorough laryngopharyngeal examination is imperative to rule out neoplasm and evaluate for other physical findings.

42. Summary • If there is no evidence of mass or lesion on examination, initial reflux treatment typically begins with dietary/behavioral changes and empiric medical therapy. • Consider additional radiologic or pH testing for inadequate response to medical therapy. • For patients unresponsive to medical therapy, referral for reflux surgery may be indicated.