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Laryngopharyngeal Reflux and Chronic Cough Disclosure Brett MacFarlane Laryngopharyngeal reflux and chronic cough A therapeutic dilemma 1 Disclosure I have received honoraria, speaker fees, consultancy fees, travel support, am a member of advisory boards or have appeared on expert panels for: Reckitt Benkiser, Bayer, Blackmores Produce education material for AJP, Retail Pharmacy, ITK, ACP 2 Disclaimer The information contained herein has not been independently verified, confirmed, reviewed or endorsed by Reckitt Benckiser. No consideration, in any form, has been provided or promised by Reckitt Benckiser in connection with or arising out of this presentation, and all findings are based on my own independent research, experience and expert opinion. The information contained herein is for guidance only and pharmacists are encouraged to conduct their own enquiries. No representation warranty, express or implied, is made as to the accuracy, reliability or correctness of the information contained herein and all liability is disclaimed arising out of or in connection with any reliance on this presentation or the information contained herein. 3 Learning objectives After completing this activity, pharmacists should be able to: 1. Describe laryngopharyngeal reflux (LPR) and how it relates to chronic cough 2. Describe the challenges of diagnosing LPR 3. Outline the management of LPR 4 What does reflux mean to you? Heartburn Acid Burning Rising into the oesophagus 5 What does chronic cough mean to you? Respiratory Asthma COPD Infection Smoking Cancer 6 Reflux is more than just acid Refluxate also contains: Pepsin (stomach) Trypsin (duodenum) Bile salts 7 Causes of chronic cough 29% asthma 33% reflux Li X, et al. Gastroesophageal Reflux Disease and Chronic Cough: A Possible Mechanism Elucidated by Ambulatory pH‐impedance‐pressure Monitoring. Neurogastroenterol Motil. 2009 Dec; 31 (12), e13707. 8 What is laryngopharyngeal reflux (LPR)? LPR is an inflammatory aerodigestive disorder AKA: Silent reflux Supra‐reflux Extra‐oesophageal reflux, and Reflux laryngitis syndrome 9 What is laryngopharyngeal reflux (LPR)? 4‐10% of patients visiting ENT departments Ultimately 50% of laryngeal complaints referred to ENT services diagnosed as LPR 75% of refractory ENT symptoms 80% of patients treated by specialist voice centres Heavy economic burden Lechien JR et al. Clinical Outcomes of Laryngopharyngeal Reflux Treatment: A Systematic Review and Meta‐Analysis. 2019. Laryngoscope 129 (5), 1174‐1187. 10 The dilemma Is it an extra‐oesophageal manifestation of GORD? OR A distinctly different condition? 11 The dilemma Montreal GORD classification describes: • Reflux Cough Syndrome • Reflux Laryngitis Syndrome • Reflux Asthma Syndrome, and • Reflux Dental Erosion Syndrome • ~ 1/3 GORD patients have extra‐oesophageal symptoms BUT, 30% of the general population have LPR regardless of a GORD diagnosis LPR is prevalent, yet underdiagnosed and undertreated Ghisa M, et al. Updates in the Field of Non‐Esophageal Gastroesophageal Reflux Disorder. 2019 Sept. Expert Rev Gastroenterol Hepatol, 13 (9), 827‐838. 12 Pharynx Aerodigestive tract Epiglottis Larynx (voice box) Trachea Oesophagus 13 LPR symptoms GORD LPR Heartburn Voice changes (chronic or intermittent hoarseness –presenting Regurgitation as reduced vocal quality, power, clarity, or stamina) Globus sensation (persistent lump in the throat, tightness, discomfort/soreness) Constant throat clearing (mucous is difficult to clear) Persistent cough Pulmonary manifestations including pneumonia, apnoea etc Dysphagia (mildly difficult swallowing) Marked absence of heartburn and regurgitation Disorders of the oral cavity including halitosis, dental erosions, oral burning and hypersensitivity Fraser‐Kirk, K. Laryngopharyngeal Reflux: A Confounding Cause of Aerodigestive Dysfunction. 2017. Aust Fam Physician, 46 (1), 34‐39. 14 Symptoms of LPR Occur when patient is upright Compared to GORD –often when supine < 50% experience actual heartburn 15 Direct and indicated causes of LPR Direct Indirect Protective mechanisms against Bronchial tree and oesophagus damage present in the embryonically related oesophagus largely absent from Share same neural innervation the laryngopharynx • Lower and upper oesophageal Reflex arc sphincters • Gravity • Peristalsis • Mucous • Aqueous bicarbonate layer • Oesophageal mucosal resilience 16 Indirect LPR causes Stimulation of Vagally mediated • Increased receptors in lower reflex arc laryngeal mucous oesophagus by secretions gastroduodenal • Cough contents (refluxate) • Globus sensation • Throat clearing 17 LPR diagnosis Challenging Non‐specific symptoms Overlap: URTI, rhinitis, asthma, smoking effects, vocal overuse, allergy No definitive diagnostic criteria for LPR Take patient history, symptoms, assess reflux and larynx 18 LPR diagnosis Some commonality with GORD < 50% experience actual heartburn Difficult to convince patients they have reflux “I have a cough” Potential for non‐adherence to acid suppressive therapy Fraser‐Kirk, K. Laryngopharyngeal Reflux: A Confounding Cause of Aerodigestive Dysfunction. 2017. Aust Fam Physician, 46 (1), 34‐39. 19 LPR diagnosis Otolaryngologist (ENT) History of non‐specific laryngopharyngeal symptoms that cannot be explained by another cause (after exclusion of red flags) Reflux assessment scales Laryngoscopy Barium swallow Technetium scan 24‐hour oesophageal pH testing (for acid reflux) Endoscopy (of very limited use) 20 LPR diagnosis Reflux Finding Score (RFS) –physician administered Reflux Symptom Index (RSI) –self‐administered 9 point questionnaire Reflux Symptom Score (RSS) –newly developed 24 hour oesophageal pH testing for acid reflux (pH<4.0) (low or non‐acid reflux pH 4.1‐7.0 is not captured) pH testing can be used to classify but not eliminate a diagnosis of LPR 21 LPR and chronic cough Persistent coughing > 8 weeks 4 most common causes • Reflux • Cough variant asthma • Non‐asthmatic eosinophilic bronchitis • Upper airway cough syndrome (post‐nasal drip) Also medicines (ACE inhibitors), environmental triggers, smoking, COPD 22 LPR and chronic cough Exact cause unknown Possibly • micro‐aspiration of gastroduodenal contents, plus • Activation of vagal oesophageal‐bronchial reflex Chronic cough patients tend to have more episodes of acid reflux at upper and lower oesophagus Ghisa M, et al. Updates in the Field of Non‐Esophageal Gastroesophageal Reflux Disorder. 2019 Sept. Expert Rev Gastroenterol Hepatol, 13 (9), 827‐838. Li X, et al. Gastroesophageal Reflux Disease and Chronic Cough: A Possible Mechanism Elucidated by Ambulatory pH‐impedance‐pressure Monitoring. Neurogastroenterol Motil. 2009 Dec; 31 (12), e13707. 23 Aspiration If refluxate makes it past the larynx Acute: pneumonia, respiratory failure Chronic (micro‐aspiration) contributes to fibrotic lung disease, asthma, and chronic cough Aspiration risk is low –must bypass the protective mechanisms 24 LPR Management 25 1. Diet and lifestyle Diet and lifestyle alone as good as PPI Diet and lifestyle + PPI, better than PPI alone • Meal times • Meal posture • Meal size • Eat slowly • Avoid food and beverage triggers • Quit smoking • Lose weight • Avoid throat clearing • Elevate the bed head Lechien JR et al. Evaluation and Management of Laryngopharyngeal Reflux Disease: State of the Art Review. Otolaryngol Head Neck Surg. 2019 May;160(5):762‐782. 26 2. PPIs Not licenced for LPR Lack of supporting evidence Consider potential long‐term PPI risks For patients with heartburn or regurgitation (discontinue if these symptoms of GORD are not present, or after 8 week trial with no improvement) Mechanism of PPI not suited to LPR. Why? Kahrilas PJ et al. American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease. Gastroenterology. 2008 Oct;135 (4), 1392‐1413. 27 2. PPIs ↧ Gastric acid (↥ gastric pH) Do NOT ↧ episodes of reflux Not effective for non-acid reflux (pepsin, trypsin, bile salts) Even low acid reflux can damage the laryngopharynx PPIs may ↥ pepsin production and promote bile salt activity PPIs found to be less effective for LPR compared to GORD (18-87%) Lechien JR, Muls V, Dapri G, et al. The management of suspected or confirmed laryngopharyngeal reflux patients with recalcitrant symptoms: A contemporary review. Clin Otolaryngol. 2019;44(5):784–800. 28 3. Alginate Gaviscon™ not licenced for LPR in Aus • Forms a physical barrier • Forms protective coat on oesophagus • Removes pepsin and bile from refluxate Prevents refluxate entering oesophagus (up to 4 hours) Useful for acid and non‐acid reflux Efficacy studies • Alginate = Alginate + PPI • + Alginate to PPI, improves efficacy of PPI McGlashan JA, Johnstone LM, Sykes J, Strugala V, Dettmar PW. The value of a liquid alginate suspension (Gaviscon Advance) in the management of laryngopharyngeal reflux. Eur Arch Otorhinolaryngol. 2009;266(2):243–251. Wilkie MD, Fraser HM, Raja H. Gaviscon® Advance alone versus co‐prescription of Gaviscon® Advance and proton pump inhibitors in the treatment of laryngopharyngeal reflux. Eur Arch Otorhinolaryngol. 2018;275(10):2515–2521 29 Summary 1. LPR and extra‐oesophageal manifestations of GORD (e.g. cough) are more common than you think 2. Difficult to identify 3. Start with diet and lifestyle 4. Trial PPI for 8 weeks (in heartburn and regurgitation ‐ GORD) 5. Deprescribe PPI if no GORD symptoms, or if 8 week trial ineffective 6. Alginate to prevent refluxate entering the aerodigestive tract, coat the mucosa, remove pepsin and bile 7. Surgery in some cases?? 30.
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