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)