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
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. - PowerPoint PPT Presentation
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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
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
7
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
8
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.
9
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
10
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
• 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
Pharyngeal probe– 2 cm above UESProximal esoph. probe- below UESDistal esoph. probe–5 cm above LES
32
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.
33
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
34
Problems With GERD/LPR and Asthma Treatment Studies
• Not placebo controlled• Inadequate treatment• Not administered long enough• Improper endpoints
35
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.
37
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
39
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)