Laryngopharyngeal Reflux (LPR) and Asthma

Laryngopharyngeal Reflux (LPR) and Asthma Turkish Thoracic Society 26/04/08 Ronald A. Simon, MD Head, Division of Allergy, Asthma and Immunology Scripps Clinic Adjunct Member Dept. Molecular & Experimental Medicine The Scripps Research Institute La Jolla, California USA

Definition of Terms • GastroEsophageal Reflux Disease (GERD) • Heartburn • Regurgitation • LaryngoPharyngeal Reflux (LPR)

Synonyms for Laryngopharyngeal Reflux (LPR) • Atypical reflux • Extraesophageal reflux • Gastropharyngeal reflux • Laryngeal reflux • Pharyngoesophageal reflux • Reflux laryngitis • “Silent” reflux

Hoarseness Chronic cough Throat Clearing Globus Chronic/intermittent laryngitis Vocal cord granuloma Postnasal drip Dysphonia Sore or burning throat Otalgia Dysphagia Apnea Laryngospasms Neoplasms Clinical Presentation

Definition of Terms • GastroEsophageal Reflux Disease (GERD) • Heartburn • Regurgitation • LaryngoPharyngeal Reflux (LPR) • SupraEsophageal Reflux Disease (SERD) • All LPR symptoms + rhinosinusitis & asthma

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 Patterns and Mechanism of LPR and GERD Koufman et al. Laryngoscopy 2002;112:1606-9 Koufman et al. Ear, Nose and Throat 2002;81(Suppl 2):7-9

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

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.

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

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.

Micro-aspirationof refluxate Trachea Esophagus Bronchus GEJ GE reflux Stomach Direct Contact Model of Tracheopulmonary GERD Complications Modified from: Goldman, Motility. 1990;10:4.

Vagal efferent loop Vagal afferent loop Vagal nerves cause increased bronchospasm Chemoreceptors in esophagus GE reflux Stomach Vago-vagal Reflex Model of Tracheopulmonary GERD Complications Modified from: Goldman, Motility. 1990;10:4.

Diagnosis • Symptom questionnaire • Laryngeal examination / Laryngoscopy • Therapeutic trial • Endoscopy – limited utility • Ambulatory 24-hr esophageal pH monitoring

Symptom Questionnaire:Reflux Symptom Index Belafski et al. ENT 2002;81 (9):10-13

Laryngeal Abnormalities Most common laryngeal abnormalities include erythema and edema of the cricoarytenoid folds and posterior portion of true vocal cords

Supraesophageal complications of reflux disease (a) Normal Larynx

Supraesophageal complications of reflux disease (b) Interarytenoid edema

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.

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!

Diagnosis • Symptom questionnaire • Laryngeal examination / Laryngoscopy • Therapeutic trial • Endoscopy – limited utility • Ambulatory 24-hr esophageal pH monitoring • Distal esophageal • Proximal esophageal • Dual • Pharyngeal • Oropharyngeal

Ambulatory pH Monitoring Pharyngeal probe– 2 cm above UES Proximal esoph. probe- below UES Distal esoph. probe–5 cm above LES

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.

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

Problems With GERD/LPR and Asthma Treatment Studies • Not placebo controlled • Inadequate treatment • Not administered long enough • Improper endpoints

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

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.

Treatment Algorithm Katz et al.Am J Med 2000;108:170S-177S

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 alcohol • Elevate 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

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)

Laryngopharyngeal Reflux (LPR) and Asthma