Detecting the &lt;i&gt;other&lt;/i&gt; reflux disease

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Applied Evidence

Detecting the other reflux disease

J Fam Pract. 2010 February;59(2):102-107

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References

1. Koufman JA, Aviv JE, Casiano RR, et al. Laryngopharyngeal reflux: position statement of the Committee on Speech, Voice, and Swallowing Disorders of the American Academy of Otolaryngology–Head and Neck Surgery. Otolaryngol Head Neck Surg. 2002;127:32-35.

2. Karkos PD, Thomas L, Temple RH, et al. Awareness of general practitioners towards treatment of laryngopharyngeal reflux: a British survey. Otolaryngol Head Neck Surg. 2005;133:505-508.

3. Morrison MD. Is chronic gastroesophageal reflux a causative factor in glottic carcinoma? Otolaryngol Head Neck Surg. 1988;99:370-373.

4. Ward PH, Hanson DG. Reflux as an etiologic factor of carcinoma of the laryngopharynx. Laryngoscope. 1988;98:1195-1199.

5. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope. 1991;101(4 pt 2 suppl 53):S1-S78.

6. Koufman JA, Amin MR, Panetti M. Prevalence of reflux in 113 consecutive patients with laryngeal and voice disorders. Otolaryngol Head Neck Surg. 2000;123:385-388.

7. Ford CN. Evaluation and management of laryngopharyngeal reflux. JAMA. 2005;294:1534-1540.

8. Aviv JE, Liu H, Parides M, et al. Laryngopharyngeal sensory deficits in patients with laryngopharyngeal reflux and dysphagia. Ann Otol Rhinol Laryngol. 2000;109:1000-1006.

9. Johnston N, Bulmer D, Gill GA, et al. Cell biology of laryngeal epithelial defenses in health and disease: further studies. Ann Otol Rhinol Laryngol. 2003;112:481.-

10. Gill GA, Johnston N, Buda A, et al. Laryngeal epithelial defenses against laryngopharyngeal reflux: investigations of E-cadherin, carbonic anhydrase isoenzyme III, and pepsin. Ann Otol Rhinol Laryngol. 2005;114:913-921.

11. Okamura H, Sugai N, Kanno T, et al. Histochemical localization of carbonic anhydrase in the trachea of the guinea pig. Histochem Cell Biol. 1996;106:257-260.

12. Johnston N, Knight J, Dettmar PW, et al. Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease. Laryngoscope. 2004;114:2129-2134.

13. Johnston N, Dettmar PW, Bishwokarma B, et al. Activity/stability of human pepsin: implications for reflux attributed laryngeal disease. Laryngoscope. 2007;117:1036-1039.

14. Axford SE, Sharp N, Ross PE, et al. Cell biology of laryngeal epithelial defenses in health and disease: preliminary studies. Ann Otol Rhinol Laryngol. 2001;110:1099-1108.

15. Toros SZ, Toros AB, Yüksel OD, et al. Association of laryngopharyngeal manifestations and gastroesophageal reflux. Eur Arch Otorhinolaryngol. 2009;266:403-409.

16. Koufman JA. Laryngopharyngeal reflux is different from classic gastroesophageal reflux disease Ear Nose Throat J. 2002;81(9 suppl 2):S7-S9.

17. Book DT, Rhee JS, Toohill RJ, et al. Perspectives in laryngopharyngeal reflux: an international survey. Laryngoscope. 2002;112(8 Pt 1):1399-1406.

18. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the Reflux Symptom Index (RSI). J Voice. 2002;16:274-277.

19. Ulualp SO, Roland PS, Toohill RJ, et al. Prevalence of gastroesophagopharyngeal acid reflux events: an evidence-based systematic review. Am J Otolaryngol. 2005;26:239-244.

20. Merati AL, Lim HJ, Ulualp SO, et al. Meta-analysis of upper probe measurements in normal subjects and patients with laryngopharyngeal reflux. Ann Otol Rhinol Laryngol. 2005;114(3):177-82.

21. Vaezi MF, Schroeder PL, Richter JE. Reproducibility of proximal probe pH parameters in 24-hour ambulatory esophageal pH monitoring. Am J Gastroenterol. 1997;92:825-829.

22. Vincent DA, Jr., Garrett JD, Radionoff SL, et al. The proximal probe in esophageal pH monitoring: development of a normative database. J Voice. 2000;142:247-254.

23. Reavis KM, Morris CD, Gopal DV, et al. Laryngopharyngeal reflux symptoms better predict the presence of esophageal adenocarcinoma than typical gastroesophageal reflux symptoms. Ann Surg. 2004;239:849-858.

24. Gupta R, Sataloff RT. Laryngopharyngeal reflux: current concepts and questions. Curr Opin Otolaryngol Head Neck Surg. 2009;17:143-148.

25. Tsunoda K, Ishimoto S, Suzuki M, et al. An effective management regimen for laryngeal granuloma caused by gastro-esophageal reflux: combination therapy with suggestions for lifestyle modifications. Acta Otolaryngol. 2007;127:88-92.

26. Hopkins C, Yousaf U, Pedersen M. Acid reflux treatment for hoarseness [protocol]. Cochrane Database Syst Rev. 2006;(1):CD005054.-

27. Kahrilas PJ, Falk GW, Johnson DA, et al. The Esomeprazole Study Investigators Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. Aliment Pharmacol Ther. 2000;14:1249-1458.

28. Park W, Hicks DM, Khandwala F, et al. Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response. Laryngoscope. 2005;115:1230-1238.

29. Qadeer MA, Phillips CO, Lopez AR, et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol. 2006;101:2646-2654.

30. Karkos PD, Wilson JA. Empiric treatment of laryngopharyngeal reflux with proton pump inhibitors: a systematic review. Laryngoscope. 2006;116:144-148.

31. Fackler WK, Ours TM, Vaezi MF, et al. Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough. Gastroenterology. 2002;122:625-632.

32. Ours TM, Fackler WK, Richter JE, et al. Nocturnal acid breakthrough: clinical significance and correlation with esophageal acid exposure. Am J Gastroenterol. 2003;98:545-550.

33. Sato K. Laryngopharyngeal reflux disease with nocturnal gastric acid breakthrough while on proton pump inhibitor therapy. Eur Arch Otorhinolaryngol. 2006;263:1121-1126.

34. Mainie I, Tutuian R, Castell DO. Addition of a H2 receptor antagonist to PPI improves acid control and decreases nocturnal acid breakthrough. J Clin Gastroenterol. 2008;42:676-679.

35. Koufman JA, Rees CJ, Frazier WD, et al. Office-based laryngeal laser surgery: a review of 443 cases using three wavelengths. Otolaryngol Head Neck Surg. 2007;137:146-151.

Tell patients that weight loss, as needed, is likely to bring some symptom relief. Using wooden blocks to elevate the head of the bed about 4 to 6 inches may also be helpful, particularly for patients who suffer from both LPR and GERD.^7,25,26

TABLE 2
Dietary management of LPR: What to tell patients^7,14,24

Avoid*	Enjoy†
Caffeine	Meat
Alcohol	Poultry
Spicy foods	Seafood
Tomatoes	Milk
Chocolate	Fresh vegetables‡
Fats
Citrus fruits
Carbonated beverages
Jams/jellies
Barbecue sauces
Salad dressings
Hot mustard
Curry
Hot peppers
*Other acidic foods.
†Other foods and beverages that are neither spicy nor acidic.
‡ Except tomatoes.

Drug therapy: Straightforward, but not without controversy
Acid suppression with proton pump inhibitors (PPIs) is the primary treatment for LPR, as it is for GERD. But because the larynx is extremely susceptible to injury from acid reflux, LPR typically requires more aggressive and prolonged treatment, compared with GERD.^1,5

FAST TRACK

For maximum benefit, patients with LPR should continue taking PPIs twice daily for 4 to 6 months.

Clinical trials have shown that PPIs do not inhibit acid production to an intragastric pH of >4 for more than 16.8 hours.^1,27 Thus, most patients need twice-daily dosing (although once-a-day dosing or conservative management may be sufficient for those with mild and intermittent symptoms).^27,28 Regardless of dosing, PPIs should be taken on an empty stomach, 30 minutes before a meal to increase bioavailability. For maximum benefits, patients should continue the twice-daily regimen for 4 to 6 months, although the optimal duration is unknown.²⁶

One study found 4 months of therapy to be effective;²⁸ others suggest that while symptom relief should begin after 6 to 8 weeks of treatment, 6 months of PPI therapy is needed for laryngeal lesions and edema to resolve.^1,8 Despite the time frame, patients should be weaned gradually to prevent the delayed rebound effect associated with abrupt cessation of PPIs.

The PPI controversy. Not only the length of treatment is controversial, however, but the efficacy of PPIs for LPR. Many studies, including several prospective cohort studies and 9 RCTs, have reported significant improvement in laryngeal symptoms, but evidence that PPIs are significantly better than placebo is weak.^25,29,30 In fact, a systematic review and 2 meta-analyses concluded that not only is there a lack of sufficient evidence to draw reliable conclusions about the efficacy of PPIs vs placebo for the treatment of LPR, but there seems to be a significant response to placebo among patients with this condition, as well.^25,29,30

FAST TRACK

H2 blockers may be considered as adjuvant therapy to the PPI regimen to further reduce acid production in patients with more severe symptoms.

The role of adjunctive therapy. Histamine type 2 (H2) blockers have been shown to be helpful in the treatment of GERD. But data showing their efficacy for LPR, either as a single agent or in combination with a PPI, are limited. Indeed, 3 clinical trials have found that H2 blockers do not provide any added benefit to PPI therapy for LPR. All 3 were cohort studies that compared the treatment outcomes of PPI alone vs PPI and H2 blockers, and found no statistically significant difference (P>.05).^28,31,32 Despite these findings, recent studies suggest that 300 mg ranitidine twice a day provides added benefit (P<.01).^33,34 Given these mixed findings, H2 blockers may be considered as adjuvant therapy to the PPI regimen to further reduce acid production in patients with more severe symptoms. Ant-acids and prokinetic agents are sometimes used for this purpose, as well.

When medical management fails
Surgery has a limited, but useful, role in the treatment of LPR.

Nissen fundoplication—a procedure in which the fundus of the stomach is passed posteriorly behind the esophagus to encircle it and provide mechanical obstruction to the retrograde movement of acid—may be considered for patients with a confirmed diagnosis, severe symptoms, and little response to treatment. However, there is little evidence that this procedure will result in long-term improvement in LPR symptoms. Laryngeal surgery can be used to treat vocal fold sequelae of LPR, such as granulomas—with a higher likelihood of success.³⁵

CORRESPONDENCE Kevin Fung, MD, FRCSC, FACS, University of Western Ontario, London Health Sciences Center-Victoria Hospital, 800 Commissioners Road East, Room B3-427, London, Ontario, Canada, N6A 4G5; kevin.fung@lhsc.on.ca