Diagnosis and Treatment of Extraesophageal Reflux Disease · 2016-11-21 · Diagnosis and Treatment...
Transcript of Diagnosis and Treatment of Extraesophageal Reflux Disease · 2016-11-21 · Diagnosis and Treatment...
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Diagnosis and Treatment ofExtraesophageal Reflux
DiseaseRachel Rosen, MD
Aerodigestive Center (ADC) Center for Motility and Functional
Gastrointestinal Disorders
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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%
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The uphill battle…….Goldski et al Pediatrics 2010
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symptomsNelson et al J Med Economic 2009
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Mechanisms of Reflux RelatedRespiratory Disease
• Neurally Mediated• Microaspiration
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Making the diagnosis
• Total reflux burden? Acid vs. non-acid?• Symptom correlation?• Distal Reflux Burden?• Proximal Reflux burden?• Esophagitis?• Lung biomarkers?
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pH probe
•Pharyngeal pH monitoring
•pH-MII
•Cough catheters
•Cough microphone
•Biomarkers
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Pharyngeal pH Monitoring
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MII‐pHwith corresponding Restech event
Oropharyngeal pH drop >10% corresponds with MII‐pH changes
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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
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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)
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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
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pH SensorImpedance
Sensors
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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
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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
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Full Column Reflux MattersJadcherla et al Am J Gastro 2008
SSI: Number of Reflux Events associated with SymptomsTotal Number of Reflux Events
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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
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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
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p g gevaluation have abnormal testing by
EGD or pH-MIIRosen et al Peds Pulm 2014
7% have EoE
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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?
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Impedance: The nextgeneration…
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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
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10000
lm0
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pJOO
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Sul>ine .................................................................................................................................................................................................................................................................................................................................................................................................................. .
I2/09 :53:30
I2/09 :54:00
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I2/09 :55:00
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microphones
Impedance Sensors
Pressure sensors
(manometry)
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Acoustic coughrecording is as
sensitive as esophageal
pressurerecording
Rosen et al NGM 2014
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to
Predict Aspiration Risk:Swallow Risk
IndexOmari et al Gastro 2011
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Biomarkers
• LLMI• Pepsin• Bile• Bacteria??
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Lipid Laden Macrophage Index (LLMI): No relationship with Esophagitis
Chang et al Respiratory Research 2005
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Reflux by ImpedanceRosen et al Pediatrics 2008
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AspirationReiley et al Laryngoscope 2011
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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
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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%
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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
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SalivaryPepsin in
GERDpatients
andControls
Hayat et al Gut 2014
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pReflux Events
Blondeau et al J Heart Lung Transpl 2009
Bile in bronchoscopy fluid has been
associated with increased lung
rejection
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SurvivalMertens et al, American J Transplantation 2011
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You made the diagnosis: Nowwhat?
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Acid Suppression
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Esomeprazole does not improve asthma
outcomeNEJM 2009
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RCT of Omeprazole in Treatment of AsthmaStordal et al Arch Dis Child 2005
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AsthmaALA Clinical Research Centers, JAMA 2012
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Chang et al, BMJ, 2005
Gatta et al, Alim Pharm Ther, 2007
PPI on laryngeal or pharyngeal symptoms
PPI on Cough
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Esomeprazole for CoughShaheen et al APT 2010
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Lansoprazole for Postnasal DripVaezi et al Gastro 2010
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PPI Therapy and RefluxVela et al., Gastroenterology, 2001
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Motility Agents
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Reglan
Cisapride
Tagaserod
DomperIdone
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Macrolides
• Increase antral contractility– Improvement in gastric emptying?– Improvement in reflux?
• Anti-inflammatory effect• Antimicrobial effect
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in preterm infantsNg et al JPGN 2003
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RCT of Emycin (12.5 mg/kg/dose Q6)
Ng et al Gastro 2007
Prior efficacy data with conflicting results with feeding tolerance
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RefluxMertens et al Dig Dis Sci 2009
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Azithromycin and its effect
on refluxRohof et al Gut 2012
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InjuryWalkey and Weiner Chest 2011
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Fundoplication
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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
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Hospitalization after FundoplicationLee et al J Peds Surg 2008
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Fundoplication does not reduce hospitalizations
Barnhart et al JAMAPeds 2013
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rate divided by pre-fundoplication rate), with 95% CIs, for refluxrelated hospital admissions (RRH).
Srivastava R et al. BMJ 2009
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g yFrancis et al Laryngoscope 2011
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Transpyloric Feeding
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before and after Initiation of Transpyloric Feeds.
Malcolm et al J Perinatol 2009
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pPneumonia free period
Sirvastava et al Pediatrics 2009
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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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Summary
• Full column reflux matters• Acid suppression in the aerodigestive
patient requires thought and close followup
• Macrolides may be useful beyond their motility effect
• Fundoplication in the aerodigestive patientneeds thought (and a detailed consent)