1. Supraesophageal manifestations of GERD

3. Symptoms and signs of LPR
Hoarseness %
Chronic cough %
Globus pharyngeus %
Heart burn/regurgitation %
Chronic throat clearing %
Difficulty swallowing %
Cummings(III) ch.126 Gastroesophageal reflux disease P2426

4. Chronic Throat Symptoms
Treatment of Chronic Throat Symptoms with PPIs Should Be Preceded by pH Monitring Am J Gastroenterol 2006;101:6-11
Chronic Throat Symptoms
pH Monitoring
Empiric treatment with PPIs

5. PRO:Empiric treatment with PPIs is not appropriate without testing
PPIs are not innocent drugs
Side effects: Headache, diarrhea, constipation, flatulence, abdominal pain, dry mouth.
Less common: anaphylactic shock, Stevens-Johnson syn., pancreatitis, nephritis, toxic epidermal necrolysis.
Predispose treated individuals to pneumonia

6. PPIs are not innocent drugs
PPIs interfere with neutrophil function by increasing intracellular calcium leading to immunoedeficiency.
In hospitalized patients more CD enteritis.
Mask and delay the diagnosis of esophageal AdenoCa.

7. PPIs are not innocent drugs
Rebound and hypersecretion after PPIs withdrawal.
Hypergastrinemia
Increased parietal cell mass
Increase ECL cells activity
Rebound might last more than 2 months ( Fossmark et al. )

8. A successful empirical trial with PPIs does not necessarily confirm the diagnosis of reflux
Meta-analysis by Numans et al:
Sensitivity – 78%
Specificity -54%
Predictive value in LPR should be even lower

9. PPI trial in LPR has the predictive value of a coin flip
PPIs are overused
Placebo effect in LPR is high
Steward et al:
Rabeprazole bid + lifestyle modification
53% response
Vs. Placebo bid + lifestyle modification
50% response
Noordzij et al: placebo response of 50%
PPI trial in LPR has the predictive value of a coin flip
We are creating PPI addicts

10. Ambulatory pH testing complemented by laryngoscopy
Dual-probe pH testing is the gold standard for LPR
The proximal pH sensor is placed 1cm above the UES in the hypopharyngs
Proximal esophageal acid exposure can not be relied upon to diagnose extraesophageal disease!!!

11. Ambulatory pH testing
Merati et al. Meta-analysis of 790 extraesophageal pH reports in 16 studies for LPR
Hypopharyngeal pH study does appear to be able to discriminate LPR patients from normal.
Sensitivity of 80%

12. Laryngoscopy as adjunct test
Laryngoscopy alone cannot be relied upon to make the diagnosis of LPR
Tobacco, environmental pollutants, infections, excessive voice use and allergy can all cause laryngeal inflammation.
Combination of laryngoscopy and dual-probe pH testing should be considered the gold standard in the diagnosis of LPR

13. Treatment with PPIs should not preceded with pH monitoring in suspected LPR
Prolonged pH monitoring is considered the gold standard in the diagnosis of GERD However
pH monitoring is not likely to help in the diagnosis or treatment of LPR

14. The important questions:
Does the presence of esophageal acid reflux suggest a casual association between throat symptoms and GERD?
Does the absence of abnormal acid exposure in the esophagus or even in the hypopharyngs suggest lack of such an association?
Should the pH test be performed on or off therapy and does it matter?
NO!!!

15. pH monitoring
The overall pre-therapy prevalence of an abnormal pH test us 53%
The prevalence of excessive distal, proximal and hypopharyngeal acid exposure is 42%, 44% and 38%
No established casual relationship
Number and duration of hypopharyngeal reflux events are similar between controls and LPR patients ( Bilgen et al)

16. pH testing is a poor predictor of response to therapy
28/39 patients with posterior laryngitis were found to have abnormal pharyngeal reflux
However, both groups had improvement in symptoms and laryngeal findings with PPIs. (Ulualp et al)

17. The dichotomy in the literature regarding pH monitoring is a result of:
Probe positioning
Lack of consensus regarding duration and amount of reflux to denote abnormal acid reflux
Poor sensitivity of pH monitoring: 70%, 55% and 40% for distal, proximal and hypopharyngeal probes.
Intermittent nature of reflux events

18. pH testing in patients under treatment
Was not found to be clinically helpful
Among 115 pts with extraesophageal symptoms while on BID therapy only 2% had abnormal acid exposure.
Impedance studies did not reveal a significant role for non-acid reflux.

19. Posterior laryngitis

21. Specificity of laryngoscopy
The laryngeal signs are nonspecific.
In a study o 105 healthy subjects without any symptoms, the majority had abnormal laryngeal findings.
91/105 (87%) had at least one abnormal finding
3 abnormal findings have been identified:
Posterior cricoid awall erythema
Vocal cord erythema and edema
Arytenoid medial wall erythema and edema

27. The role of empiric therapy
Aggressive acid suppression would identify those whose laryngeal signs and symptoms are related to GERD
An overall response rate of 50-70% could be expected.
The lack of response among the remaining patients is most likely related to an overlap between GERD and other causes
The suggestion that PPI therapy is not safe even for a short time period is not based on any solid data.

28. Medical antireflux treatment of reflux laryngitis: placebo-controlled studies
Symptoms Laryngoscopy
L: 43%; P: 54%
L: 35%; P: 33%
Lansoprazole 30 mg b.d. × 3 months 15
Havas et al
No a priori predictors of response
L: 58%
P: 30%
L: 50% P: 10%* 20
El-Serag et al.
Mild hoarseness and throat clearing better with omeprazole
O: NC;
P: NC
O: 48%; P: 19%
Omeprazole 40 mg b.d. × 2 months 30
Noordzij et al.
Patients on placebo did as well as pantoprazole
Pan: N.S.
P: N.S.
Pan: 43%; P: 41%
Pantoprazole 40 mg b.d. × 3 months 14
Eherer et al.
Enrolled patients had either no or minimal classic GERD symptoms
Eso: N.S.; P: N.S.
Eso: 42%; P: 46%
Esomerprazole 40 mg b.d. × 4 months
145
Vaezi et al.

31. תודה רבה

33. אפידמיולוגיה של תופעות על וושטיות ב-GERD
בנבדקים עם צרבת קלה
ב- 80% נמצאה לפחות תופעה על-ושטית אחת
בנבדקים ללא צרבת
ב-49% נמצאו תופעות על ושטיות
במחקר VA על 101,366 נבדקים
ב-17% מהנבדקים עם אזופגיטיס היו תופעות על- ושטיות
Lock GR et al. Gastroenterology. 1997

34. 6215 נבדקים עם GERD ס"ה ב-32.8% תופעות ע"ו
Prevalence of extra-oesophageal manifestations in GERD: an analysis based on the ProGERD Study.
6215 נבדקים עם GERD
ס"ה ב-32.8% תופעות ע"ו
עם אזופגיטיס- 34.9%
ללא אזופגיטיס – 30.5% %
Aliment Pharmacol Ther Jaspersen D et al

35. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. (2200 individuals) %
Lock GR et al. Gastroenterology. 1997

42. Introduction
Comparision of the GERD Symptoms of the Typical Esophagitis Patient, the “Atypical” Otolaryngology Patient, and Pediatric Patient.
Typical (%) 83 23 40 47 16 12 3
Atypical
(%) 20 - 12 26 44 87
Pediatric
(%) 16 68 30 - 36
Symptoms
Heartburn
Regurgitation
Dysphagia
Cough
Pulmonary infection
Hoarseness
Throat irritation (soreness, clearing)
Koufman JA, Laryngoscope 1991

43. Introduction
Comparision of History, Laryngeal Examination, and Diagnostic Testing in Otolaryngology Patient With Cervical Symptoms(n=63) or Esophagitis(n=36), and in Controls(n=10)
A. Symptoms
Heartburn and/or regurgitation
Hoarseness, dysphagia, globus, throat
clearing and cough
B. Laryngeal Examination
Normal
Erythema
Contact ulcer or granulation
C. Diagnostic Studies
Upper esophageal sphincter pressure (mmHg)
Positive standard acid reflux test
Positive Bernstein acid perfusion test
Abnormal esophageal manometry
Esophageal dysmotility
Abnormal esophageal acid clearance
Otolaryngology Pt.
Esophagitis Pt. 6%
100%
50%
25%
144±121
68% 5%
10%
60%
78%
89% 0%
100%
71±40 8%
10%
80%
Koufman JA, Laryngoscope 1991

52. Upper GI Endoscopy

55. Left Vocal Fold Granuloma: Pre and Post anti-acid therapy

72. 54 patients with chronic persistent cough possibly due to reflux
GORD in patients with pulmonary symptoms
54 patients with chronic persistent cough possibly due to reflux
Normal
22%
(n=12)
Reflux
78%
(n=42)
Schnatz et al., Am J Gastroenterol 1996; 91: 1715–18.

73. Patients with abnormal acid reflux (%)
Abnormal acid reflux linked to asthma
100 90 82 80 70 61 60 55 53
Patients with abnormal acid reflux (%) 40 33 20
Ducolone
et al.
(n=51)
Nagel
et al.
(n=44)
Giudicelli
et al.
(n=140)
Sontag
et al.
(n=104)
DeMeester
et al.
(n=77)
Larrain
et al.
(n=105)
Kiljander
et al.
(n=107)
Harding & Sontag, Am J Gastroenterol 2000; 95(Suppl): S23–32.

76. Asthmatics with gastroesophageal reflux
Long term results of a randomized trial of medical and surgical antireflux therapies
Asthmatics with gastroesophageal reflux
Long term results of a randomized trial of medical and surgical antireflux therapies
Asthmatics with gastroesophageal reflux
Long term results of a randomized trial of medical and surgical antireflux therapies
Sontag SJ, O'Connell S, Khandelwal S, et al. Asthmatics with gastroesophageal reflux: long term results of a randomized trial of medical and surgical anti-reflux therapies. Am J Gastroenterol 2003; 98: 987–99.

78. Mucosal healing

84. Poe RH, Kalloy MC. Chronic cough and gastroesophageal reflux disease
Poe RH, Kalloy MC. Chronic cough and gastroesophageal reflux disease. Experience with specific therapy for diagnosis and treatment. Chest 2003; 123: 679–84.

85. Patients Responding, No (%) Weeks of anti-reflux Rx
. Cumulative Response to GERD Therapy
Patients Responding, No (%)
Weeks of anti-reflux Rx
16 (41) 2
38 (86) 4
42 (95) 6
43 (99) 8
(44 (100 12

88. 24hr double probe pH-metry
Diagnosis
24hr double probe pH-metry

89. Management of LPRD dietary & life style modification plus
ranitidine 1 tablet(150mg) twice daily
After 8weeks improve (-)
After 8weeks improve (+)
ranitidine 300mg bid or tid
persistent medication for 6 months
After 6 months
improve (-)
Consider surgical management
Cummings(III) ch.126 Gastroesophageal reflux disease P2419

91. Cummings(III) ch.126 Gastroesophageal reflux disease P2426

93. Range of presentations of GERD
Typical symptoms
(Heartburn/regurgitation)
Atypical symptoms
Complications
With oesophagitis
Chest pain (visceral hyperalgesia)
Oesophageal erosions and/or ulcers
Without oesophagitis
Hoarseness
(‘reflux laryngitis’)
Stricture
Barrett’s oesophagus
Asthma, chronic cough, wheezing
Oesophageal adenocarcinoma
Dental erosions
Nathoo, Int J Clin Pract 2001; 55: 465–9.

95. Common signs 70 Interarytenoid bar 29 Arytenoid medial wall edema 21
Table 1. Ear, nose and throat (ENT) signs in normal volunteers
Common signs 70
 Interarytenoid bar 29
 Arytenoid medial wall edema 21
 Posterior pharyngeal wall cobblestoning 15
Intererytenoid bar erythema 10
 Posterior cricoid wall edema
 True vocal cord edema %