Transcript 슬라이드 제목 없음 - Tel-Aviv Sourasky Medical Center

Supraesophageal manifestations
of GERD
Symptoms and signs
Symptoms and signs of LPR

Hoarseness
71%

Chronic cough
51%

Globus pharyngeus
47%

Heart burn/regurgitation
43%

Chronic throat clearing
42%

Difficulty swallowing
35%
Cummings(III) ch.126 Gastroesophageal reflux disease P2426
Treatment of Chronic Throat Symptoms with PPIs Should
Be Preceded by pH Monitring
Am J Gastroenterol 2006;101:6-11
Chronic Throat Symptoms
Empiric
treatment with
PPIs
pH Monitoring
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
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.
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. )
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
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
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!!!
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%
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 dualprobe pH testing should be considered the
gold standard in the diagnosis of LPR
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
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!!!
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)
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)
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
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.
Posterior laryngitis
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
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.
Medical antireflux treatment of reflux laryngitis: placebo-
controlled studies
Symptoms Laryngoscopy
Havas et al
15
Lansoprazole
30 mg
L: 35%;
P: 33%
L: 43%;
L: 50%
No a priori
predictors of
P: 10%*
L: 58%
P: 30%
O: 48%;
O: NC;
Mild hoarseness
and throat
clearing better
b.d. × 3 months
20
El-Serag et al.
Lansoprazole
30 mg
b.d. × 3 months
.
Noordzij et al
30
Omeprazole
40 mg
b.d. × 2 months
Eherer et al.
14
Pantoprazole 40 mg
b.d. × 3 months
P: 19%
P: 54%
P: NC
response
with omeprazole
Pan: 43%;
P: 41%
Pan: N.S.
P: N.S.
Patients on
placebo did as
well as
pantoprazole
Vaezi et al.
145
Esomerprazole
40 mg
b.d. × 4 months
Eso: 42%;
P: 46%
Eso: N.S.;
P: N.S.
Enrolled patients
had either no or
minimal classic
GERD symptoms
‫תודה רבה‬
‫אפידמיולוגיה של תופעות על וושטיות‬
‫ב‪GERD-‬‬
‫‪‬‬
‫בנבדקים עם צרבת קלה‬
‫• ב‪ 80% -‬נמצאה לפחות תופעה על‪-‬ושטית אחת‬
‫‪‬‬
‫בנבדקים ללא צרבת‬
‫• ב‪ 49%-‬נמצאו תופעות על ושטיות‬
‫במחקר ‪ VA‬על ‪ 101,366‬נבדקים‬
‫ב‪ 17%-‬מהנבדקים עם אזופגיטיס היו תופעות על‪-‬‬
‫ושטיות‬
‫‪Lock GR et al. Gastroenterology. 1997‬‬
Prevalence of extra-oesophageal manifestations in GERD:
an analysis based on the ProGERD Study.
GERD ‫ נבדקים עם‬6215
‫ תופעות ע"ו‬32.8%-‫ס"ה ב‬
35
30
34.9% -‫• עם אזופגיטיס‬
30.5% – ‫• ללא אזופגיטיס‬
25
20
15
10
5
ta
l
N
ch CC
.C P
la
ry oug
ng
h
ea
ld
i
as s.
th
m
a
0
To
%
Jaspersen D 2003 .Ther Aliment Pharmacol
et al


Prevalence and clinical spectrum of gastroesophageal
reflux: a population-based study in Olmsted County,
Minnesota. (2200 individuals)
25
20
15
10
5
us
Gl
ob
ma
As
th
itis
Br
on
ch
s
rsn
es
Ho
a
NC
CP
eu
mo
nia
0
Pn
%
Lock GR et al. Gastroenterology. 1997
Introduction
Comparision of the GERD Symptoms
of the Typical Esophagitis Patient, the “Atypical” Otolaryngology
Patient, and Pediatric Patient.
Symptoms







Heartburn
Regurgitation
Dysphagia
Cough
Pulmonary infection
Hoarseness
Throat irritation (soreness,
clearing)
Typical
(%)
Atypical
(%)
Pediatric
(%)
83
23
40
47
16
12
20
12
26
44
16
68
30
36
-
3
87
-
Koufman JA, Laryngoscope 1991
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)
Otolaryngology Pt. Esophagitis Pt.
A. Symptoms

Heartburn and/or regurgitation
6%
89%

Hoarseness, dysphagia, globus, throat
100%
0%
clearing and cough
B. Laryngeal Examination
50%
100%

Normal
25%
0%

Erythema
25%
0%

Contact ulcer or granulation
C. Diagnostic Studies

Upper esophageal sphincter pressure
144±121
71±40
(mmHg)
68%
100%

Positive standard acid reflux test
5%
89%

Positive Bernstein acid perfusion test
10%
8%

Abnormal esophageal manometry
60%
10%

Esophageal dysmotility
78%
80%

Abnormal esophageal acid clearance
Koufman JA, Laryngoscope 1991
Upper GI Endoscopy
Left Vocal Fold Granuloma:
Pre and Post anti-acid therapy
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.
Abnormal acid reflux linked
to asthma
Patients with abnormal acid reflux
(%)
100
90
82
80
70
61
60
55
40
53
33
20
0
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.
f
Sontag SJ, O'Connell S, Khandelwal
S, et al. Asthmatics
a
with gastroesophageal reflux:r long term results of a
randomized trial of medical and
a surgical anti-reflux
therapies. Am J Gastroenterol
n 2003; 98: 987–99.
d
o
m
i
z
e
d
t
r
i
a
l
o
Mucosal healing
Poe RH, Kalloy MC. Chronic cough and gastroesophageal
reflux disease. Experience with specific therapy for
.
diagnosis and treatment. Chest 2003; 123 84–679 :
.Cumulative Response to GERD Therapy
Weeks of anti-reflux Rx
Patients Responding, No
(%)
2
4
6
8
)41( 16
)86( 38
)95( 42
)99( 43
12
(100( 44
Diagnosis
24hr double probe pH-metry
Management of LPRD
dietary & life style modification plus
ranitidine 1 tablet(150mg) twice daily
After 8weeks
improve (-)
ranitidine 300mg bid or tid
After 8weeks
improve (+)
persistent medication for
6 months
After 6 months
improve (-)
Consider surgical management
Cummings(III) ch.126 Gastroesophageal reflux disease P2419
Cummings(III) ch.126 Gastroesophageal reflux disease P2426
Range of presentations of GERD
Typical symptoms
(Heartburn/regurgitation)
With
oesophagitis
Atypical symptoms
Chest pain
(visceral
hyperalgesia)
Without
oesophagitis
Complications
Oesophageal
erosions
and/or ulcers
Stricture
Hoarseness
)‘reflux
laryngitis’(
Asthma,
chronic cough,
wheezing
Dental erosions
Barrett’s
oesophagus
Oesophageal
adenocarcinoma
Nathoo, Int J Clin Pract 2001; 55: 465–9.
Table 1. Ear, nose and throat (ENT) signs in
normal volunteers
Common signs
%
• Interarytenoid bar
• Arytenoid medial wall edema
• Posterior pharyngeal wall
cobblestoning
• Intererytenoid bar erythema
• Posterior cricoid wall edema
• True vocal cord edema
70
29
21
15
10
10