Airway Reflux: Is It Acid, Non-Acid, Something Else?

21 Sep 2022 16:00 18:00

Milwaukee

Nikki Johnston Host

Nikki Johnston Panelist

Perspectives from Laryngology, Gastroenterology, Respiratory Medicine, Surgery, and Research

Didactic Presentation: Pepsin – Molecular Pathophysiology and Diagnostic Utility

Tina Samuels, MS, Program Manager

Gastroesophageal and extraesophageal reflux are prevalent and costly diseases. Recognition of the pathogenicity of nonacid reflux has stimulated interest in alternatives to acid-targeting diagnostics and therapeutics. Pepsin is the most deleterious enzyme in refluxate, eliciting inflammatory and carcinogenic effects irrespective of acid. Its presence in all refluxate and detection in saliva have situated pepsin as the most widely researched biomarker for reflux today. A summary of the emerging findings regarding pepsin-mediated damage during reflux and developments in pepsin-targeting diagnostics will be presented.

Didactic Presentation: Fosamprenavir for the Treatment of Laryngopharyngeal Reflux (LPR)

Nikki Johnston, PhD

Given the paucity of data supporting efficacy of acid-suppression therapy for laryngopharyngeal reflux (LPR), the America Gastroenterology Association recommends against its use in the absence of classic gastro-esophageal reflux disease (GERD) symptoms. With compelling evidence of nonacid proximal reflux of pepsin and its association with laryngeal and pharyngeal symptoms and endoscopic findings, a new treatment which specifically targets pepsin could be of great value. Fosamprenavir was found to bind to and inhibit pepsin, abrogating pepsin-mediated laryngeal inflammation and mucosal damage in an LPR mouse model. Fosamprenavir has a good safety profile, is well-tolerated, and targets a foreign virus, making it an ideal drug to repurpose/reformulate, allowing a more expeditious and limited safety assessment in a clinical trial compared to a new molecule. Furthermore, this new approach would be amenable to local treatment of readily accessible airways affected by LPR allowing lower dosing, limiting systemic side effects. FDA/IND approval has been obtained for a 12-week, randomized, placebo-controlled, double-blind, phase III clinical trial to assess the efficacy of oral fosamprenavir for the treatment of LPR. Safety, tolerability, and pharmacokinetic parameters of fosamprenavir administered by dry powder inhaler is also being assessed.

Case 1: Chronic Cough, Proximal Reflux Events and Reflux Hypersensitivity

Presenter: Prof. Jonathan Bock

Medical College of Wisconsin

Patient: 46-year-old male
History: Many years of allergy and cough symptoms.
Previous Treatment: History of allergy shots.
PFTs: Variable inspiratory phase.
Respiratory Symptoms: Longstanding spells of sudden shortness of breath with exertion.
Other Symptoms: Cough, throat clearing, and globus specifically after meals.
Absent Symptoms: No dysphonia, no dysphagia, and no significant heartburn or reflux.
Reflux Testing: DeMeester score 9, but 98 proximal reflux impedance events and 2 pH-positive pharyngeal events.
Treatment Response: Did well on Gaviscon.
Surgical Consideration: Eventually referred for LINX procedure.

Case 2: Chronic Cough With Vocal Fold Paresis, Voice Change and GERD

Presenter: Prof. Thomas L. Carroll

Director, BWH Voice Program
Brigham and Women's Hospital
Harvard Medical School

Patient: 38-year-old female
History: Three years of chronic cough and voice change.
Initial Management: Underwent traditional empiric treatments for acidic reflux after negative allergy and asthma workup.
Reflux Testing: Testing off acid suppression confirmed distal acid reflux after BID PPI failed.
Laryngovideostroboscopy: Vocal fold paresis and glottic insufficiency appreciated.
Treatment: Vocal fold augmentation relieved the cough.

Case 3: Chronic Cough, GERD, Hiatal Hernia and Esophageal Diverticulum

Presenter: Prof. Alyn Morice

Head, Cardiorespiratory Studies
Castle Hill Hospital
Hull York Medical School, UK

Patient: 34-year-old female
1967: Born.
1988: Chronic dry cough.
2009: Gastro-oesophageal reflux with heartburn and cough.
2011: Manometry (St Elsewheres): Hypotonic LO(E)S. “Motility within normal limits”.
2012 (March): Nissen fundoplication (St Elswheres). Peptic symptoms improved, but coughing persisted.
2012 (October): Seen in the Hull Cough Clinic, HARQ score 45 out of 70.
Medical Treatment: Trials of promotility agents, azithromycin, metoclopramide, domperidone, and baclofen were unsuccessful. Initially, a good response was achieved to slow-release morphine and chlorpheniramine.
2014: Hiatus hernia on endoscopy.
2019: Referred back to Hull Cough Clinic. Prominent features included voice change, metallic taste, cough on phonation, and post-prandial cough at 10 minutes.
Drug Trials: Trials of P2X3 antagonists and NK1 antagonist without success.
Manometry: 100% ineffectual. Normal LO(E)S, but hiatal hernia.
DeMeester Score: 27.38.
Additional Findings: Esophageal diverticulum plus hiatal hernia and dysmotility.
Multidisciplinary Decision: Proceed to surgery.
2019 Surgery: Redo Nissen fundoplication, recurrent for large paraoesophageal hiatus hernia, no diverticulum. Extensive scarring. Repaired using Bio-A reinforcement.

Case 4: Laryngopharyngeal Reflux Symptoms With Negative Symptom Association

Presenter: Prof. Serhat Bor

Chair, Department of Gastroenterology
Ege University, School of Medicine
Izmir, Turkey

Patient: 27-year-old female referred for evaluation of anti-reflux surgery.
Clinical Presentation: Heartburn, acid regurgitation and especially hoarseness daily for three years.
Nocturnal Symptoms: Wakes up with heartburn and cough.
PPI Response: Less than 50% for all symptoms.
Alarm Symptoms: None.
Upper GI Endoscopy: LA-A esophagitis.
24-hour MII-pH Monitoring: Showed “weak acid reflux”.
Symptom Association: SAP and SI were negative.
High-Resolution Esophageal Manometry: Normal.

Psychiatric Assessment & Treatment

Psychiatric Consultation: The patient was also consulted by Psychiatry and was diagnosed with somatisation disorder.
Reflux Team Decision: Her strong desire for anti-reflux surgery was discussed during the reflux team meeting and refused.
Initial Treatment: She was put on alginate.
Neuromodulator: She initially refused neuromodulators but was later convinced. Amitriptyline 10 mg was started and increased to 20 mg.
Outcome: She is in a much better situation now.

Panel for Discussion