Continuing Education Activity

Laryngopharyngeal reflux (LPR) represents a disorder in which gastric contents, including acid and pepsin, reflux beyond the esophagus into the larynx and pharynx, producing irritation of the upper aerodigestive tract. Symptoms frequently differ from those associated with gastroesophageal reflux disease, as many affected individuals lack classic heartburn and instead experience chronic cough, throat clearing, hoarseness, dysphonia, or globus sensation. Diagnosis often relies on clinical assessment, supported by laryngoscopic findings or, when available, ambulatory pH monitoring. Persistent mucosal irritation may contribute to vocal dysfunction, airway inflammation, and reduced quality of life, underscoring the importance of early recognition. Effective management generally involves lifestyle and dietary modification, pharmacologic therapy such as proton-pump inhibitors, and, for refractory presentations, surgical intervention aimed at restoring standard reflux control. A comprehensive understanding of symptom patterns and contributing factors supports accurate diagnosis and timely treatment.

Participants in this course gain enhanced competence in identifying variable presentations of LPR, interpreting diagnostic findings, and differentiating LPR from allergy, infection, vocal strain, and other laryngeal disorders. Instruction focuses on evidence-based strategies for implementing lifestyle counseling, optimizing pharmacologic therapy, and determining when surgical evaluation becomes appropriate. Collaboration among interprofessional team members—including otolaryngologists, gastroenterologists, speech-language pathologists, and primary care clinicians—promotes consistent communication, coordinated treatment planning, and more efficient escalation of care. This team-based approach strengthens diagnostic accuracy, improves treatment effectiveness, and supports sustained symptom resolution, ultimately enhancing overall patient outcomes and quality of life.

Objectives:

• Identify the signs and symptoms of laryngopharyngeal reflux, such as hoarseness, globus sensation, dysphagia, and chronic cough.
• Develop strategic approaches for the assessment and diagnosis of laryngopharyngeal reflux.
• Select appropriate medical and surgical treatment approaches in the management of laryngopharyngeal reflux.
• Collaborate with otolaryngologists, gastroenterologists, speech-language pathologists, and dietitians in an interprofessional team to develop strategies to enhance care coordination and improve clinical outcomes in patients with laryngopharyngeal reflux.

Introduction

The otolaryngologic manifestations of gastroesophageal reflux disease (GERD) or extraesophageal reflux in patients, including primarily hoarseness, cough, globus sensation, and throat clearing, constitute an increasingly significant portion of an otolaryngologist's practice.[1] Various descriptions and terminology have been employed to delineate laryngopharyngeal reflux (LPR), including supraesophageal GERD, extraesophageal complications of GERD, and atypical GERD. Patients and clinicians often confuse and conflate the signs and symptoms of GERD and LPR. However, current research suggests that, although there may be some overlap, GERD and LPR may represent 2 distinct conditions with different management approaches. The underlying premise remains that reflux of gastric contents is a primary cause of laryngeal pathology, even in the absence of GERD symptoms.[2]

Patients presenting with chronic laryngeal symptoms or a persistent cough pose diagnostic challenges. Although visible reflux-related injuries to the upper airway may be identified, many of these patients report no heartburn, regurgitation, chest pain, nausea, or vomiting, supporting the idea that GERD and LPR may be separate conditions. Acid-pepsin injury from direct contact might only be part of the explanation for LPR. Additionally, LPR could also result from a vagal reflex arc between the esophagus and the upper aerodigestive tract, triggered by acid reflux, leading to symptoms such as globus, throat clearing, and chronic cough.[3]

Four barriers prevent reflux from reaching the larynx: the lower esophageal sphincter, the upper esophageal sphincter, esophageal peristalsis, and epithelial resistance factors. Dysfunction in any of these areas can cause symptoms of LPR. The upper esophageal sphincter acts as the final gatekeeper against refluxed gastric contents. The distal pharynx and upper esophageal sphincter should open only during specific physiological states, such as swallowing, and remain closed otherwise. The muscle group forming this acid barrier includes the cricopharyngeus, thyropharyngeus, and proximal cervical esophageal muscles, which create a C-shaped sling attached to the cricoid cartilage. However, the tonic pressure from these muscles can decrease during general anesthesia, sleep, and cigarette smoking. Research suggests that a deficiency of epithelial cadherin, the intercellular junctional complex protein, and carbonic anhydrase isoenzyme III, in relation to the presence of intracellular pepsin in laryngeal epithelium, may occur in patients with LPR.[4]

The clinical diagnosis of LPR mainly depends on the patient's history of chronic laryngitis symptoms such as globus, throat clearing, cough, and hoarseness.[5] The physical exam may include nasopharyngoscopy, fiberoptic laryngoscopy, and, more recently, videostroboscopy of the larynx. Clinicians look for signs like erythema and edema of the posterior commissure, as well as cobblestoning. Often, patients present with pseudosulcus vocalis or infraglottic edema extending from the anterior commissure to the posterior larynx, especially in patients with pH-confirmed LPR.[5]

Workup may include barium esophagography, but its utility may be limited.[3] More useful procedures include laryngoscopy, esophageal endoscopy, and ambulatory 24-hour pharyngoesophageal pH monitoring. Some advocate flexible endoscopic evaluation of swallowing with sensory testing.[6]

Management can be individualistic and involve multiple factors. Medical treatment usually begins with an empirical trial of proton pump inhibitors, histamine-2 receptor antagonists (H2 blockers), prokinetic agents, and mucosal cryoprotectants. Patients who need ongoing or increasing acid suppression may be good candidates for Nissen fundoplication, especially if long-term medication negatively impacts their quality of life. Lifestyle modifications include dietary changes, regular exercise, elevating the head during sleep, and avoiding tobacco and alcohol. Some patients may also benefit from swallowing therapy administered by a speech-language pathologist. Most patients benefit from long-term follow-up, repeat laryngoscopy or testing, and lifestyle prevention.

Etiology

While GERD is among the most common gastrointestinal complaints, the direct link with LPR has caused confusion among researchers, clinicians, and patients.[7] GERD is caused by the excessive backward flow of acid and bile from the stomach and duodenum into the esophagus, usually due to frequent, transient relaxation or a weak lower esophageal sphincter. Possible triggers include, but are not limited to, fatty meals, coffee, chocolate, alcohol, citrus fruits, and medications such as beta-agonists, nitrates, calcium channel blockers, anticholinergics, bisphosphonates, doxycycline, ferrous sulfate, ascorbic acid, aspirin/nonsteroidal anti-inflammatories, chemotherapeutic agents, nitroglycerin, aminophyllines, benzodiazepines, progesterone, and nicotine.[8] 

The assumption is that the etiologies of LPR may be similar. The same triggers that cause GERD may cause similar direct injury to the larynx and surrounding tissues.[9] A lower pH may impede protective mechanisms, such as ciliary function, in the airways.[10] Nevertheless, the etiology of LPR may be more complex and may involve acid in the distal esophagus, which stimulates vagal-mediated reflexes. Consequently, these reflexes can lead to chronic cough, throat clearing, laryngeal lesions, and bronchoconstriction, even in the absence of typical heartburn symptoms.[3][11] 

Direct injury from gastric acid and vagally mediated reflexes can coincide. In some patients, voice overuse, smoking, and chronic throat clearing may contribute to laryngeal inflammation. Both GERD and LPR may be comorbid with other inflammatory diseases, including asthma, sinusitis, allergic rhinitis, and nasal polyposis.[12] Determining whether LPR contributes to these comorbidities or whether the comorbid conditions precipitate LPR remains challenging.

Epidemiology

Approximately 10% of patients visiting otolaryngology clinics experience symptoms of LPR, and LPR contributes to or causes hoarseness in up to 55% of affected patients.[1] In patients with LPR, nearly 100% report hoarseness at presentation, even in the absence of other classic reflux-associated symptoms.[13] LPR appears to have no racial preference but may be more frequently seen in older patients and men.

Pathophysiology

The retrograde flow of gastric acid and pepsin damages the laryngeal mucosa and impairs mucociliary clearance. While this can occur on its own, symptoms may worsen if LPR is exacerbated by vocal abuse, mucosal lesions, or a chronic cough, in which acid in the lower esophagus stimulates the vagus nerve, triggering a cough response.[14] One theory for why many patients experience LPR symptoms without GERD is that pepsin in nonacidic refluxate can harm hypopharyngeal epithelial cells.[15] Chronic LPR is also a risk factor for symptomatic subglottic stenosis, laryngeal malacia, laryngeal stenosis, and laryngeal carcinoma.[16]

Histopathology

Histologic findings reveal hyperplasia of the squamous epithelium in the posterior larynx, accompanied by a chronic submucosal infiltrate. Chronic LPR may cause submucosal ulcerations with fibrin deposits, granulation tissue, and fibrosis. In one study, postcricoidectomy epithelial cells from patients with LPR were examined and found to contain pepsin, while cells in the control group did not. Even when the refluxate's pH is neutral, inactivated pepsin at pH 7 is taken into cells and later reactivated, leading to mitochondrial and overall cell damage.[14] 

History and Physical

LPR can cause various symptoms that may prompt a patient to seek evaluation. Hoarseness is the most common of these, occurring in nearly 100% of patients with LPR, whereas in patients with GERD, virtually none report hoarseness.[13] The clinical presentation can be ambiguous when patients have both GERD and LPR.

Patients may also experience a variety of other symptoms, including globus sensation, chronic throat clearing, postnasal drip, Eustachian tube dysfunction, heartburn, other voice changes, and regurgitation.[3][17] Patients with LPR typically experience upright, or daytime, reflux and maintain healthy esophageal motility function.[18] On the other hand, patients with esophageal dysmotility typically experience symptoms while lying down or at night.[19] Patients with GERD may experience symptoms similar to those with LPR, except for hoarseness. Still, their anatomical dysfunction occurs at the lower esophageal sphincter rather than the upper esophageal sphincter, as in LPR.[20] For patients with LPR, the Reflux Symptom Index (RSI) questionnaire can be used to monitor therapy results.

Reflux Symptom Index

The RSI is a validated, patient-reported outcome measure that accurately evaluates the severity of LPR.[21] This index consists of a 9-item questionnaire completed by patients, in which they rate each symptom on a scale of 0 to 5, with 5 indicating the most severe. An RSI score above 10 indicates a high probability of reflux pathology, though the maximum score is 45. The 9 domains are:

• Hoarseness
• Throat clearing
• Mucus or postnasal drip
• Dysphagia
• Coughing after eating or lying down
• Breathing difficulties or choking episodes
• Chronic cough
• Globus sensation
• Heartburn, indigestion, or regurgitation [21]

During a physical exam, laryngoscopy and/or videostroboscopy can be very helpful in raising suspicion of LPR in patients with hoarseness and other symptoms that fit the diagnosis. Thickening and pachydermia of the posterior laryngeal commissure and postcricoid mucosa have been associated with LPR.[22] Granulomas of the vocal processes of the arytenoid cartilages are also strongly linked to LPR.[23] Other physical signs of LPR include edema of the false and true vocal cords, with or without ventricular obliteration, along with diffuse swelling of the larynx and pharynx. Severe cases may also show erythema, hyperemia, thickened mucus, mucosal ulcers, and even subglottic stenosis.

Edema on the underside of the vocal fold, extending from the anterior to the posterior commissure, is also commonly observed in LPR.[19] This swelling pushes the mucosa medially and upward over the free margin of the vocal fold, creating a ripple and a groove known as pseudosulcus vocalis, which is essentially pathognomonic for LPR.[5] However, distinguishing this from a true sulcus vocalis, which involves a visible groove caused by scarring that tethers the mucosa to the vocal ligament below, is essential. Common causes of sulcus vocalis include trauma, surgery, infection, and cyst rupture.

Evaluation

The typical patient with LPR presents with globus sensation, throat clearing, cough, hoarseness, intermittent sore throat, and vague symptoms of dysphagia. Some have a history of vocal overuse, smoking, environmental allergies, or recent infection. Many individuals do not experience GERD symptoms and are often confused when informed about LPR, especially when no abnormalities are detected during the initial physical examination. They are even more confused when prescribed empiric antireflux medications. The workup may include the following, along with the corresponding findings:

• Laryngoscopy (mirror, flexible fiberoptic laryngoscopy, rigid laryngoscopy, and videostroboscopy)

  • Posterior laryngeal edema, erythema, or ulceration
  • Granulation
  • Pseudosulcus vocalis [5]
• Flexible endoscopic evaluation of swallowing with sensory testing [24]

  • Sensory testing of the laryngopharynx using varying degrees of calibrated air pulse delivery to the arytenoids
  • Sensory deficits may be measured in mm Hg air pulse pressure
  • Formally assess both airway protection and bolus transport [25]
• Esophagoscopy

  • The presence of esophagitis does not confirm LPR.
  • Treating GERD adequately and LPR inadequately is possible.
• Ambulatory 24-hour pharyngoesophageal pH monitoring

  • Three probes are used with a nasal catheter.

    • A distal pH probe is located 5 cm above the lower esophageal sphincter (LES). 
    • A proximal pH probe is placed 20 cm above the LES, just below the upper esophageal sphincter.
    • A third pH probe is placed in the pharynx to simultaneously record changes associated with acid escape into the pharynx.
  • The pH readings are recorded for 24 hours, with the patient indicating the onset and end of meals, sleep, and symptom events.
  • Information provided includes the frequency, duration, and site of reflux events.
  • Lee et al demonstrated that the 24-hour window can be shortened to 6 to 10 hours while maintaining high sensitivity.[26]
  • Pathologic reflux is considered present when the pH is less than 4 for at least 1% of the study time.[27]
  • Intraluminal combined pH impedance testing (MII-pH) [28]

    • This helps determine whether GERD exists in patients with atypical symptoms unresponsive to proton pump inhibitor therapy.
    • This test also distinguishes between acid reflux, nonacid reflux, and gas reflux, which affects how it is managed.
• Fasting hypopharyngeal saliva pepsin levels 

  • Salivary pepsin concentration is a simple, noninvasive, convenient, and widely accepted diagnostic marker for LPR. However, the diagnostic threshold for salivary pepsin remains nonstandardized.[29]
  • The fasting hypopharyngeal salivary pepsin concentration test, with 1-time sampling, can be used with an optimal cutoff value of 29.62 ng/mL (sensitivity, 51.8%; specificity, 93.6%).[29]
• Barium esophagoscopy

  • A significantly greater degree of abnormal esophageal acid exposure occurs in patients who have either a hiatus hernia or spontaneous reflux.
  • The sensitivity and specificity of barium radiology for detecting severe acid reflux are insufficient to justify its use as a screening procedure.[3][30]
  • This offers very low utility in diagnosing pharyngolaryngeal complications

Treatment / Management

Lifestyle Modifications

Patients should be counseled on specific behavioral and dietary adjustments to minimize reflux symptoms and promote gastric health:

• Eat slowly and chew thoroughly.
• Consume smaller, more frequent meals rather than large portions.
• Avoid lying down for at least 2 to 3 hours after eating.
• Avoid trigger foods and substances, including:

  • Fried or fatty foods
  • Chocolate
  • Peppermint
  • Coffee and other caffeinated beverages
  • Citrus fruits and juices
  • Tomatoes and tomato-based products (eg, ketchup, sauces)
  • Mustard and vinegar
  • Tobacco
  • Alcohol

These changes can significantly reduce symptoms and complement medical or surgical management strategies.

Medications

Pharmacologic therapy remains the cornerstone of treatment for gastroesophageal and laryngopharyngeal reflux disease. Proton pump inhibitors (PPIs) are the most effective agents for managing GERD and are often required at higher doses and for longer durations to achieve optimal control in LPR.[31] H2 blockers can provide symptom relief, particularly for nocturnal acid suppression, though they are less potent than PPIs.[32] Prokinetic agents may be used as adjuncts in patients with documented motility disorders to enhance gastric emptying and lower esophageal sphincter tone.[33] Mucosal cytoprotectants offer an additional protective barrier to esophageal and laryngeal mucosa, reducing irritation and promoting healing.[34]

Surgery

Minimally invasive laparoscopic fundoplication remains the gold standard surgical treatment for refractory GERD.[35] This procedure restores lower esophageal sphincter competence and has demonstrated long-term efficacy, with an approximately 80% success rate at 20-year follow-up.[36] Surgical intervention, however, should not be considered first-line therapy for patients with suspected supraesophageal manifestations of GERD, such as laryngopharyngeal reflux, until medical management has failed. Exceptions may include patients with significant regurgitation, aspiration, or laryngospasm, as well as younger individuals with severe GERD who would otherwise require lifelong pharmacologic therapy.

Differential Diagnosis

Diagnosing LPR can be challenging due to a range of patient complaints, laryngeal issues, and swallowing problems. The following comprehensive list of clinical conditions should be considered potential diagnoses in patients with LPR:

• GERD 

  • Hiatal hernia
• Infectious 

  • Laryngitis 
  • Pharyngitis
  • Esophagitis (eosinophilic)
  • Sinusitis
• Allergic/nonallergic 

  • Vasomotor rhinitis
• Neuromuscular

  • Peripheral disorders due to diabetes
  • Primary disorders of the larynx or esophagus
  • Cerebrovascular accident (stroke)
  • Diffuse esophageal spasm
  • Multiple sclerosis
  • Parkinson disease
  • Paterson-Kelly syndrome [37][38]
  • functional voice disorders [39]
• Anatomic or injury

  • Laryngeal stenosis
  • Esophageal webs and rings
  • Chronic cough [40]
  • Zenker diverticulum [41]
  • Vagal injury
  • Congestive heart failure
  • Foreign body aspiration
  • Chronic aspiration
• Malignancy

  • Esophageal
  • Pharyngeal
  • Laryngeal
  • Lung
  • Bronchiogenic
  • Thyroid

Prognosis

The overall prognosis is favorable. Patient education plays a vital role in maintaining a healthy lifestyle alongside dietary modifications and appropriate pharmacologic interventions. Long-term follow-up, including larynx visualization, is recommended. Medication adjustments and doses may be required. In some instances, repeat ambulatory 24-hour pH monitoring is advised to assess the efficacy of acid suppression. 

Complications

Among the major long-term complications of LPR are bronchopulmonary issues, recurrent pneumonia, chronic cough, chronic or recurrent laryngitis, and oral cavity disorders.[42] Unmanaged long-term LPR can cause ongoing vocal damage, leading to scarring of the true vocal folds and hoarseness. Occasionally, LPR may result in subglottic stenosis or squamous cell carcinoma.[43] LPR may also be associated with untreated GERD, which, if left unaddressed, can develop into Barrett esophagitis and ultimately progress to malignant adenocarcinoma.[44] LPR has been recognized as a risk factor for laryngeal carcinoma, though this link remains uncertain.[42]

Consultations

Consultations may differ depending on LPR symptoms and associated conditions. Many patients benefit from seeing specialists in otolaryngology and gastroenterology, and sometimes in pulmonary, speech, and swallowing therapy.  

Deterrence and Patient Education

Patient education is a vital part of management. Teaching patients about the potential anatomical and physiological abnormalities linked to LPR, as well as how these may differ from or overlap with GERD signs and symptoms, is essential. The clinician must explain why patients might be experiencing LPR and what steps can be taken to improve their condition. Many patients are willing to make lifestyle and dietary changes. However, they may be skeptical about long-term medication, which could require higher doses—especially if they do not have GERD symptoms. Only some patients with LPR should be considered for fundoplication surgery.

Pearls and Other Issues

Although there may be some overlap, LPR and GERD are probably separate conditions with similar treatment approaches. Patient education, lifestyle changes, avoidance of voice abuse, and dietary modifications may be just as crucial as pharmacologic therapies in achieving positive outcomes when treating LPR, especially chronic cough, throat clearing, and vocal disorders. Comorbidities like sinusitis, nasal polyposis, asthma, allergies, and other immune disorders may be associated with LPR.

Enhancing Healthcare Team Outcomes

Optimal management of laryngopharyngeal reflux (LPR) requires a multidisciplinary, patient-centered approach that integrates the expertise of physicians, advanced practitioners, nurses, pharmacists, and speech-language pathologists. Physicians and advanced practitioners play a central role in identifying symptoms, performing diagnostic evaluations, and guiding individualized treatment plans that include lifestyle modification, pharmacotherapy, and, when indicated, surgical referral. Nurses contribute to patient education by reinforcing behavioral strategies—such as dietary changes, meal timing, and weight management—that are critical for symptom control. Pharmacists ensure appropriate medication selection, dosing, and adherence while counseling patients on potential adverse effects and interactions, especially in those requiring long-term acid suppression therapy.

Interprofessional communication and coordination enhance diagnostic accuracy and treatment adherence, ensuring that LPR is not misdiagnosed as chronic laryngitis, asthma, or other upper airway disorders. Collaborative case reviews and shared decision-making between gastroenterologists, otolaryngologists, and primary care clinicians optimize both diagnostic efficiency and continuity of care. Speech-language pathologists provide essential support for patients with chronic hoarseness or vocal strain through targeted voice therapy. Together, these coordinated efforts improve patient safety, minimize unnecessary medication use or invasive testing, and promote sustained symptom resolution and improved quality of life.

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Disclosure: Jens Brown declares no relevant financial relationships with ineligible companies.

Disclosure: Olivia Matz declares no relevant financial relationships with ineligible companies.

Disclosure: Andrew Sutton declares no relevant financial relationships with ineligible companies.

Disclosure: Carl Shermetaro declares no relevant financial relationships with ineligible companies.