Laryngopharyngeal Reflux (LPR) and Asthma
Turkish Thoracic Society 26/04/08
Ronald A. Simon, MDHead, Division of Allergy, Asthma and Immunology
Scripps Clinic
Adjunct MemberDept. Molecular & Experimental Medicine
The Scripps Research Institute
La Jolla, CaliforniaUSA
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Definition of Terms
• GastroEsophageal Reflux Disease (GERD)– Heartburn– Regurgitation
• LaryngoPharyngeal Reflux (LPR)
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Synonyms for Laryngopharyngeal Reflux (LPR)• Atypical reflux• Extraesophageal reflux• Gastropharyngeal reflux• Laryngeal reflux• Pharyngoesophageal reflux• Reflux laryngitis• “Silent” reflux
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Clinical Presentation
• Hoarseness• Chronic cough• Throat Clearing• Globus• Chronic/intermittent
laryngitis• Vocal cord granuloma• Postnasal drip
• Dysphonia• Sore or burning throat• Otalgia• Dysphagia• Apnea• Laryngospasms• Neoplasms
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Definition of Terms
• GastroEsophageal Reflux Disease (GERD)– Heartburn– Regurgitation
• LaryngoPharyngeal Reflux (LPR)
• SupraEsophageal Reflux Disease (SERD)– All LPR symptoms + rhinosinusitis & asthma
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Patterns and Mechanism of LPR and GERD
LPR• No heartburn• Daytime (“upright”) refluxers• Normal esophageal motility• Normal acid clearance• Majority without esophagitis• 1 defect - UES• Clinical presentations
GERD• Heartburn• Nocturnal (“supine”) refluxers• Esophageal dysmotility• Prolonged acid clearance• Can present with esophagitis• 1 defect – LES• Clinical presentations
Koufman et al. Laryngoscopy 2002;112:1606-9 Koufman et al. Ear, Nose and Throat 2002;81(Suppl 2):7-9
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Reflux and Laryngitis
• Dr L.A Coffin was first to associate GER with laryngeal disorders in 1903– “eructation of gases from the stomach”
associated with postnasal catarrh• Cherry and Marguiles in 1968 reported 3-
individuals with granular lesions of the larynx.
Cherry and Marguiles. Laryngoscope 1968;78:1937-40
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Epidemiology/ Prevalence
• Using objective tests, studies suggest concomitant GERD in – 80% of patients with hoarseness – 50% with globus sensation– Small group with cancer of the larynx
Gaynor EB. Am J Gastroenterol. 1991;86:801-805.
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Limitations of Prevalence Data• Control population for comparison• Small # of patients from highly selected
referral populations• Prevalence of GERD studied in population
with single laryngopulmonary disease• Varied prevalence data (50%-80%)• Studies likely included combination
GERDSERD patients• Far fewer studies done with SERD/LPR
alone
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Pathophysiology• “Reflux” theory:
– Direct contact with gastric contents: Acid/Pepsin)– Direct contact with duodenal contents: Bile acids/Pancreatic
enzymes (trypsin)– Irritation of oropharynx/larynx: SERD– Aspiration into lungs: asthma
• “Reflex” theory: – Vagal mediated reflexes initiate a protective response
• Other possible mechanisms include:– Defective UES pressure– Esophageal dysmotility– Poor acid clearance
Vaezi M.Current Perspectives in Gastroenterology Nov/Dec 2002:324-28.
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Modified from: Goldman, Motility. 1990;10:4.
Direct Contact Model of Tracheopulmonary GERD Complications
TracheaTrachea
GEJGEJ
GE refluxGE reflux Stomach
Bronchus
Esophagus
Micro-aspirationof refluxate
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Modified from: Goldman, Motility. 1990;10:4.
Vago-vagal Reflex Model of Tracheopulmonary GERD Complications
Vagal nerves cause Vagal nerves cause
increased bronchospasmincreased bronchospasm
Chemoreceptors in esophagus
GE refluxGE reflux
StomachStomach
Vagal afferent loopVagal afferent loop
Vagal efferent loop
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Diagnosis
• Symptom questionnaire• Laryngeal examination / Laryngoscopy• Therapeutic trial• Endoscopy – limited utility• Ambulatory 24-hr esophageal pH monitoring
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Diagnosis
• Symptom questionnaire• Laryngeal examination / Laryngoscopy• Therapeutic trial• Endoscopy – limited utility• Ambulatory 24-hr esophageal pH monitoring
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Symptom Questionnaire:Reflux Symptom Index
Belafski et al. ENT 2002;81 (9):10-13
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Diagnosis
• Symptom questionnaire• Laryngeal examination / Laryngoscopy• Therapeutic trial• Endoscopy – limited utility• Ambulatory 24-hr esophageal pH monitoring
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Laryngeal Abnormalities
Most common laryngeal abnormalities include erythema and edema of the cricoarytenoid folds and posterior portion of true vocal cords
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Supraesophageal complications of reflux disease (a)
Normal Larynx
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Supraesophageal complications of reflux disease (b)
Interarytenoid edema
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Use of Laryngoscopy to Diagnose LPR
• Interobserver variability in interpreting laryngeal findings – Evaluated laryngeal photos from 250
consecutive videos– Photos scored in blinded fashion– Evaluated aspiration changes, arytenoid
erythema and edema and cord lesions Considerable interobserver variability
Vaezi, MF Laryngoscope 2006;116:1718.
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Diagnosis
• Symptom questionnaire• Laryngeal examination / Laryngoscopy• Therapeutic trial• Endoscopy – limited utility• Ambulatory 24-hr esophageal pH monitoring
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Therapeutic Trial for SERD
• H2 receptor blockers– Work great for GERD– Generally don’t work for SERD (even high/double
doses)• Proton pump inhibitors
– Generally work for SERD often require double dosing– Must use double dose PPI for therapeutic trial– Duration: 2 weeks – 6 months (one month should be
sufficient to see improvement– May still fail…
• Remember: Non-acid reflux!
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Diagnosis
• Symptom questionnaire• Laryngeal examination / Laryngoscopy• Therapeutic trial• Endoscopy – limited utility• Ambulatory 24-hr esophageal pH monitoring
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Diagnosis• Symptom questionnaire• Laryngeal examination / Laryngoscopy• Therapeutic trial• Endoscopy – limited utility• Ambulatory 24-hr esophageal pH monitoring
– Distal esophageal– Proximal esophageal– Dual– Pharyngeal– Oropharyngeal
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Ambulatory pH Monitoring
Pharyngeal probe– 2 cm above UESProximal esoph. probe- below UESDistal esoph. probe–5 cm above LES
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Prevalence and Treatment of LPR and Asthma
• 28 mild-moderate asthmatics• Symptom questionnaire and
videolaryngoscopy• Pantoprazole 40 mg/day x 3 months• 21/28 (75%) had LPR• Treatment improved both LPR (p<0.001)
and asthma symptoms (p=0.001)
Eryuksel E et al. J Asthma. 2006;437:539-42.
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Problems With GERD/LPR and Asthma Prevalence Studies
• Diagnostic criteria for asthma• Which asthmatic population
– All, Mild/moderate, nocturnal or severe• Diagnostic criteria for LPR &/or GERD
– Either/both (acid wash into oropharynx is which?), severity– Laryngoscopy (unreliable)– pH monitoring (distal/proximal/dual esophageal, pharyngeal
or oropharyngeal• Severity of GERD/LPR
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Problems With GERD/LPR and Asthma Treatment Studies
• Not placebo controlled• Inadequate treatment• Not administered long enough• Improper endpoints
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Suggestions for Future Studies• Enroll patients meeting ATS criteria for asthma• Assess severity & control according to NAEPP or
GINA guidelines• Enroll patients with and without LPR• Record both LPR scores (Scripps modified Belafsky)
and asthma symptom scores• Record FEV1/PEF baselines, intervals, end of study• Oropharyngeal pH monitor baseline, after treatment,
end of study• Double blind placebo controlled for 6 months
– Assessments weekly for one month then monthly
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Suggestions for Future Studies(continued)
• Double dose PPI 30-60 minutes before breakfast & dinner (or tailored to oropharyngeal pH monitor data)
• Lifestyle modifications (can be according to oropharyngeal pH monitor data)
• Compliance monitoring
• With all these design elements, incorporated into a single study (utilizing subgroup analysis) or with separate studies, we will answer many of the currently unanswered questions about SERD and asthma.
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Treatment Algorithm
Katz et al.Am J Med 2000;108:170S-177S
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Management of the SERD/Asthma Patient
Life-style changes: Diet: avoid large meals, spicy and/or acidic foods,
carbonated beverages or eating within 3 hours of going to bed
Weight-loss Eliminate nicotine, caffeine and alcoholElevate head of bed (not pillows) 2 -2.5 cm
Acid suppression therapeutic trial (PPI) Consider ambulatory pH monitoring (before or after
above) Cost/Benefit of medical versus surgical intervention Quality of life issues
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Suggested Reading
• Am J Med Vol.115 Supplement 3A; August 2003 (symposium on supraesophageal complications of reflux disease)
• Kiljander, TO, Am J Med 2003;115 (3A):65s-71s (Role of PPI’s in GERD related asthma and chronic cough)
• Kiljander (NOC asthma & GERD• Wong CH et al. Aliment Pharm Ther 2006; 23:1321-1327
Prevalence of GERD in difficult to control asthma & response to PPI treatment)
• Havermann BD et al. Gut 2007;56:1654-1664 (review of association between GERD and asthma)
• Eryuksel E et al. J Asthma. 2006;437:539-42 (Asthma & LPR)