diagnosis and treatment of extraesophageal … and treatment of extraesophageal reflux disease ......
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Diagnosis and Treatment ofExtraesophageal Reflux
DiseaseRachel Rosen, MD
Aerodigestive Center (ADC) Center for Motility and Functional
Gastrointestinal Disorders
Sinusitis 4.2%
Otitis 2.1%
Dental erosion 40.2°/o
Apparent lifethreatening event 20%Asthma 13.2%
Pneumonia 6.3%
Bronchiectasis 1%
General respiratorysymptoms 57.7%
Making the diagnosis
• Total reflux burden? Acid vs. non-acid?• Symptom correlation?• Distal Reflux Burden?• Proximal Reflux burden?• Esophagitis?• Lung biomarkers?
100
80
60
40
20
0>10% pHDrop <5.5
pH pH pH<5.0 <4.5 <4.0
No Corresponding MII-pH event Assoc w/ Non-Acid GER
Assoc w/ Acid GER
Correlation of Changes in Oropharyngeal pHwith MII Events
Chiou et al Neurogastro 2011
Multi Channel Intraluminal Impedance (MII)
• pH independent method of measuringreflux
• 7 sensors throughout the esophagus• 1 distal pH sensor• Advantages:
– Height of the refluxate,– Non-acid burden– Composition of reflux (liquid,gas)
Non Acid Reflux in PediatricsVandenplas et al Acta Paediatr. 2007
Percent of nonacid reflux episodes recorded(relative to total number of reflux episodes recorded)
Sifrim (n = 22) Rosen (n = 28) Mousa (n = 25) Wenzl (n = 22)
40 45 49 89
Del Buono (n =20) Corvaglia (n= 5)
69 78
Wenzl (n = 14) 55Condino (n = 24) 51
Condino (n =34) Lopez-Alonso (n= 21) Lopez-Alonso
(n = 7)
46 53 73
Del Buono (n = 16) 56Mattioli ( > 1 yr) (n = 50) 49Mattioli ( < 1 yr) (n = 50) 53
0 20 40 60 80 100
and MIIRosen et al, Clinical Gastro and Hepatol 2006
pH probe MII P Value
Sensitivity in Untreated Patients
80.6±18.2% 76.1±13.5% 0.41
Sensitivity in Treated Patients
47.2±36.0% 80.3±21.1% 0.005
Normal Values?
Shay S, et al. Am J Gastroenterol. 2008Rosen et al JPGN 2008
Lopez-Alonso M, et al. Pediatrics. 2006 Peter et al., J. Pediatrics 2002
Acid Weakly Non- pH only Acid Acid
55 26 1 3
58 13 35
52 98
Total Events
Adults 73
Children 69
Preterm Infants
100
Full Column Reflux MattersJadcherla et al Am J Gastro 2008
SSI: Number of Reflux Events associated with SymptomsTotal Number of Reflux Events
Predictors of SymptomAssociation
Rosen and Nurko, Am J Gastro, 2004
Variable OR P Value
Non-Acid 1.70 (1.03-2.82) 0.04Proximal Reflux 1.31 (1.01-1.69) 0.04Liquid 0.63 (0.42-0.92) 0.02BCT (sec) 1.00 (0.98-1.00) 0.36
p g pOutcome?
Rosen et al JPGN 2010
Improved (N=22)
Not Improved (N=12)
P value
# acid events 13 (5, 25) 18 (5, 72) 0.36# non-acid events 19 (10, 29) 15 (2, 23) 0.21# pH-only events 18 (8, 30) 16 (8, 24) 0.71% full column
reflux38±23 17±14 0.005
% time pH<4 7.9±7.7 13.7±13.8 0.12
So much is unknown…
• How much full column reflux is too much?• How much full column reflux is too much in
the child that aspirates?• Can we treat full column reflux, other than
fundoplication?
30 sec
cough
peristalsis
pH
coughcough
Pres
sure
C
hann
els
Addition of manometry increases cough detectionby 100%
Sifrim, Gut 2005Rosen et al JPGN 2013
10000
lm0
10000
lm100
100
Pr0
0
pJOO
p Ro ...................................................................................................................................................................................................................................................................................................................................................................................................................·········································-·····································································································-································-···································································-································-·····································································································-··················
0
Sul>ine .................................................................................................................................................................................................................................................................................................................................................................................................................. .
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Lipid Laden Macrophage Index (LLMI): No relationship with Esophagitis
Chang et al Respiratory Research 2005
Pepsin in Patients With GERD
1Starosta V, et al. Chest. 2007
Pepsin Sensitivity and Specificity
• 63% sensitivity; 92%specificity if reflux indistal esophagus2
• 75% sensitivity; 91% specificity if reflux in the proximal esophagus2
Peps
inin
BAL
(n
g/m
L)1
2500
1500
500200
100
0
Reflux indexproximal ≥ 2%
Reflux indexproximal < 2%
Peps
inin
BAL
flu
id(n
g/m
L)1
0 25 50 75 100 125 150 175Number of proximal reflux episodes
r = 0.51
P < 0.0001
P = 0.034
Rosen et al Neurogastro 2011
Sensitivity of
Pepsin
Specificity
of PepsinIf Abnormal EGD 67% 59%
If Abnormal pH probe 45% 56%
If Abnormal MII 71% 60%
If Any Abnormal Test (pH/MI/EGD) 57% 65%
Pepsin in the Lung and other ManifestationsRosen et al Neurogastro 2011
Pepsin Negative
n=28
Pepsin Positive
n=22
P Value
Ear Infections 11/28 3/19 0.4
Ear Tubes 4/28 5/22 0.4
Tonsillectomy 6/28 7/22 0.3
Sinus Infection 6/26 6/17 0.3
Pneumonia 6/26 8/19 0.4
Croup 5/27 4/20 0.9
Asthma 25/28 12/19 0.03
Cough 24/28 13/22 0.5
pReflux Events
Blondeau et al J Heart Lung Transpl 2009
Bile in bronchoscopy fluid has been
associated with increased lung
rejection
Chang et al, BMJ, 2005
Gatta et al, Alim Pharm Ther, 2007
PPI on laryngeal or pharyngeal symptoms
PPI on Cough
Macrolides
• Increase antral contractility– Improvement in gastric emptying?– Improvement in reflux?
• Anti-inflammatory effect• Antimicrobial effect
RCT of Emycin (12.5 mg/kg/dose Q6)
Ng et al Gastro 2007
Prior efficacy data with conflicting results with feeding tolerance
readmissions?Golden et al, Pediatrics, 2006
RRE: Reflux related eventsARP: Anti‐reflux procedure
22 % of all patients had more reflux related hospitalizations post surgery than pre-surgery
rate divided by pre-fundoplication rate), with 95% CIs, for refluxrelated hospital admissions (RRH).
Srivastava R et al. BMJ 2009
hour during feed (JF) and non-feed (NF) periods
Rosen et al, JPGN 2011
JF NF p Value
# Acid Events/hr 0.9±1.0 0.4±0.8 0.02
# Non-Acid Events/hr
1.3±1.3 0.7±1.1 0.04
# pH-Only Events/hr
0.5±0.8 0.3±0.6 0.3
# total MII/hr 2.2±1.4 1.1±1.2 0.003
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