Laryngopharyngeal Reflux

Laryngopharyngeal reflux (LPR) is the retrograde flow of gastric contents (acid, pepsin, bile acids, and nonacid components) into the larynx and pharynx. It causes inflammation of the laryngeal, pharyngeal and upper aerodigestive tract mucosa. It accounts for 10 percent of otolaryngology clinic visits.

LPR differs from gastro oesophageal reflux disease (GERD):

• Most patients with LPR do not have heartburn or oesophagitis (up to 75 percent have no classic GERD symptoms).
• Reflux events are brief and usually occur in the upright position and in the daytime (rather than supine and nocturnal).
• The laryngeal epithelium is more susceptible to injury than the oesophagus (lack of the acid clearance mechanisms and the protective mucus, lower pepsin tolerance and carbonic anhydrase III deficiency).

Pepsin deposited in the laryngeal tissue is activated by weakly acidic pH. It causes injury through intracellular uptake in laryngeal epithelium. Mechanisms of injury include the direct chemical effect, and vagally mediated reflex mechanisms (chronic cough and throat clearing).

Contributing factors: incompetent upper oesophageal sphincter, transient lower oesophageal sphincter relaxation, hiatus hernia, obesity, high fat diet, caffeine, alcohol, tobacco, carbonated beverages, large meals, late night eating, and vocal use (singers, teachers).

Prevalence is difficult to define (laryngeal symptoms in 10 to 30 percent of the population).

LPR is associated with vocal fold granuloma, Reinke oedema, subglottic stenosis, laryngeal leukoplakia and, though debated, laryngeal cancer. It is also associated with laryngospasm, chronic cough, asthma and sleep apnoea.

• Chronic throat clearing (the commonest), persistent hoarseness (dysphonia, with voice fatigue and voice breaks), sensation of a lump in the throat (globus), postnasal drip, chronic cough (dry, particularly after meals, or at night), and difficulty swallowing (dysphagia, feeling of food sticking).
• Throat pain or burning, bad taste in the mouth, halitosis, and sometimes laryngospasm and choking episodes.
• Symptoms are scored by the Reflux Symptom Index (nine items, scored 0 to 5; a total above 13 is abnormal).
• Laryngoscopic findings are scored by the Reflux Finding Score, with a total above 7 indicating likely reflux, but with limited specificity.
• Findings: erythema and oedema of the arytenoids and posterior commissure, posterior commissure hypertrophy (pachydermia), infraglottic oedema (pseudosulcus), ventricular obliteration, thick endolaryngeal mucus, vocal fold oedema, granulation tissue and granulomas (contact ulcer), and diffuse laryngeal oedema.
• Findings are non-specific and also found in healthy individuals.
• Heartburn and regurgitation absent in many.

• Diagnosis is largely clinical, based on symptoms and laryngoscopy (flexible laryngoscopy or videostroboscopy), and often confirmed by a therapeutic trial of proton pump inhibitors for 2 to 3 months (response of symptoms).
• Hypopharyngeal oesophageal multichannel intraluminal impedance with pH monitoring (HEMII-pH): the most sensitive test, identifying acid and non-acid events. Abnormal pharyngeal sensor findings are more than one pharyngeal reflux event in 24 hours, or a pharyngeal acid exposure time above 0.1 percent.
• Oropharyngeal pH monitoring (Restech Dx-pH probe; at pH below 5.5 in the upright position, and below 5.0 in the supine position, with a Ryan score of above 9.41 upright or 6.79 supine) is also used.
• Both tests are used in refractory cases or before surgery, for patients not responding to proton pump inhibitors.
• Salivary pepsin detection (Peptest, a lateral flow device; a positive result at 16 ng/mL or above on at least one of 3 samples, after symptoms), with moderate sensitivity.
• Upper gastrointestinal endoscopy: for patients with dysphagia, alarm symptoms (weight loss, anaemia, vomiting, bleeding), failure to respond to therapy, age above 50 with long standing symptoms, or risk factors for Barrett oesophagus, to look for oesophagitis, hiatus hernia and malignancy.
• Oesophageal manometry (to exclude achalasia and motility disorders before anti-reflux surgery) and barium swallow when dysphagia exists.
• Exclusion of other causes of laryngeal symptoms: allergic rhinitis and chronic rhinosinusitis, asthma, smoking related laryngitis, voice misuse, infection, tumour (laryngoscopy in patients with persistent hoarseness over 3 weeks), and medications (angiotensin converting enzyme inhibitors).

• Lifestyle and dietary modification:
  • avoid late meals (no eating within 3 hours of bedtime)
  • avoid trigger foods (fatty and fried foods, spicy foods, citrus, tomatoes, chocolate, peppermint, caffeine, alcohol, carbonated drinks)
  • reduce portion size
  • weight loss (if overweight)
  • smoking cessation
  • avoid tight clothing
  • elevate the head of the bed (15 to 20 cm), and left lateral sleeping
  A Mediterranean diet with plant based and alkaline water (pH above 8) may decrease reflux. A plant based Mediterranean diet has efficacy similar to proton pump inhibitors in some studies.
• Alginate antacid (sodium alginate 500 mg with sodium bicarbonate and calcium carbonate, 10 to 20 mL after meals and at bedtime, four times daily), forming a raft barrier, which is used alone or as an adjunct for non-acid and pepsin reflux.
• Proton pump inhibitors: omeprazole 20 to 40 mg twice daily (or esomeprazole 40 mg, lansoprazole 30 mg, or pantoprazole 40 mg twice daily) taken 30 to 60 minutes before breakfast and dinner, for a trial of 8 to 12 weeks.
• Twice daily dosing is traditionally recommended in LPR, as the effect is slower than in GERD, with symptom improvement at 2 to 3 months, and laryngeal signs at 4 to 6 months.
• Then step down to once daily or on demand, and stop if no response. Evidence for benefit over placebo is limited, and the response rate is around 50 percent.
• Potassium competitive acid blockers (vonoprazan 20 mg daily; tegoprazan 50 mg daily) are alternatives.
• Add an H2-receptor antagonist at night (famotidine 20 to 40 mg at bedtime) for nocturnal symptoms.
• Use prokinetics (domperidone 10 mg three times daily; metoclopramide 10 mg three times daily with caution, short term) in delayed gastric emptying.
• Baclofen 5 to 20 mg three times daily reduces transient lower oesophageal sphincter relaxation in refractory cases (side effects include drowsiness).
• Treatment of cough or throat clearing: voice therapy and behavioural techniques (to break the habit), hydration, and neuromodulators (gabapentin 100 to 300 mg three times a day, amitriptyline 10 to 25 mg at night) for neurogenic cough after reflux is controlled.
• Long term proton pump inhibitor use should be regularly reviewed, with the potential adverse effects (hypomagnesaemia, vitamin B12 deficiency, fracture, Clostridioides difficile infection, and pneumonia).
• Surgical management: laparoscopic fundoplication (Nissen or Toupet) or magnetic sphincter augmentation or transoral incisionless fundoplication in carefully selected patients. Selection requires objective confirmation of reflux, a good response to proton pump inhibitors, and documented abnormal pharyngeal reflux testing.
• Benefit is limited in those with no response to medical therapy, with a success of about 70 percent in selected patients. Repair hiatus hernia when present.
• Complications and monitoring: follow up laryngoscopy at 3 to 6 months to confirm resolution of laryngeal signs, with biopsy of persistent leukoplakia or suspicious lesions; long term follow up.
• Prognosis: many patients improve with lifestyle and drug therapy, though relapse on discontinuation is common.