Laryngopharyngeal reflux in adults: Evaluation, diagnosis, and management

INTRODUCTION — Laryngopharyngeal reflux (LPR) refers to the backflow of gastric contents into the pharynx via the esophagus. Although the concept of LPR was first introduced in the late 1960s and early 1970s through a series of clinical papers and experiments that described a variety of head and neck manifestations of gastroesophageal reflux disease (GERD) [1-7], the term “laryngopharyngeal reflux” was not coined until the 1990s [8,9]. There is growing consensus that LPR is responsible for a variety of disorders affecting the upper aerodigestive tract, including dysphonia, oropharyngeal dysphagia, globus, and benign laryngeal lesions [8-12]. LPR is also felt to play a role in some lower airway disorders such as asthma, pneumonia, and bronchiectasis [9,13], and our understanding of LPR continues to evolve.

This article will cover the pathophysiology, clinical manifestations, diagnosis, and treatment of LPR in adults. The evaluation and management of gastroesophageal reflux and related conditions in adult and pediatric populations are reviewed in detail elsewhere:

●(See "Pathophysiology of reflux esophagitis".)

●(See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults".)

●(See "Medical management of gastroesophageal reflux disease in adults".)

●(See "Approach to refractory gastroesophageal reflux disease in adults".)

●(See "Complications of gastroesophageal reflux in adults".)

●(See "Non-acid reflux: Clinical manifestations, diagnosis, and management".)

●(See "Gastroesophageal reflux in infants".)

●(See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents".)

●(See "Management of gastroesophageal reflux disease in children and adolescents".)

PATHOPHYSIOLOGY — Laryngopharyngeal reflux (LPR) is defined by the reflux of gastric contents into the laryngopharynx (figure 1). While the manifestations of gastroesophageal reflux disease (GERD) and LPR are different, there is an underlying link between the two, since the refluxate must traverse the esophagus to reach the laryngopharynx (figure 2). While both GERD and LPR are related to inappropriate reflux of gastric contents, it is the damage to the tissues and the triggering of specific clinical symptoms that differentiates them.

Anything that increases the quantity or frequency of reflux increases the likelihood that refluxate will reach and injure extraesophageal tissues. For example, the presence of esophageal dysmotility has been linked to more severe LPR and GERD symptoms and findings [14,15]. Similar to GERD, the role of Helicobacter pylori in the pathophysiology of LPR is unclear, though its presence has been noted in several studies [16]. (See "Helicobacter pylori and gastroesophageal reflux disease".)

Refluxed gastric contents have direct effects upon the tissues of the larynx and pharynx (picture 1); refluxate contains various digestive enzymes, acid, and depending upon the function of the duodenal sphincter, bile. Pepsin, a potent proteolytic enzyme present in the refluxate, is most active at or below pH 4.0 [17] (see "Physiology of gastric acid secretion", section on 'Pepsin'). Following reflux, however, pepsin can remain in the laryngeal/pharyngeal tissues for hours; it has been demonstrated in in vitro studies that pepsin can be endocytosed, existing intercellularly where it can cause cellular damage even in a non-acidic environment [18]. Bile, if present, increases the pH of the refluxate but also contains additional enzymes/agents that can damage tissue.

While the esophagus has several mechanisms to protect it from reflux-related injury, such tissue defenses are lacking in laryngeal/pharyngeal tissues. Esophageal epithelium secretes a layer of mucus, alkaline secretions, and other protective substances that help prevent injury to the underlying tissue layers. In addition, esophageal epithelium contains tight junctions and is layered (stratified squamous) to reduce entry of acid and enzymes into the surface cells or deeper layers. There are also active cellular mechanisms to clear intraepithelial hydrogen and neutralize acid with bicarbonate [19].

By contrast, the laryngeal epithelium (with the exception of the true vocal folds) consists of pseudostratified columnar epithelium, which is more susceptible to acidic and enzyme injury. When laryngeal/pharyngeal tissues are exposed to pepsin, particularly in an acidic environment, mucosal tissue is damaged (picture 1). This explains why patients may have severe tissue damage from LPR while demonstrating little or no abnormalities in the esophagus [20].

Many extraesophageal manifestations of reflux disease are due to the reflux triggering of vagal reflexes. For example, studies have demonstrated that acid infused into the distal esophagus can trigger airway hyperresponsiveness [21,22]. This is the basis for the relationship between asthma and GERD. In the larynx, this type of triggered vagal reflex may have several manifestations, including cough, laryngospasm, and paradoxical vocal fold motion disorder. (See "Causes and epidemiology of subacute and chronic cough in adults", section on 'Laryngopharyngeal reflux' and "Inducible laryngeal obstruction (paradoxical vocal fold motion)", section on 'Laryngopharyngeal reflux'.)

EVALUATION — The diagnosis of laryngopharyngeal reflux (LPR) should be suspected based upon the patient’s clinical presentation.

Clinical manifestations — Patients with LPR may present with a variety of symptoms based upon the effects on the upper aerodigestive tract; LPR symptoms may be nonspecific and overlap with other conditions that may cause similar symptoms. (See 'Differential diagnosis' below.)

The most frequently reported symptoms of LPR include hoarseness, recurrent or persistent throat clearing, excess throat mucus, dysphagia, postprandial or recumbent cough, and globus or persistent foreign-body sensation. Although many of these symptoms are nonspecific, they should trigger concern for LPR, particularly if these symptoms are experienced together and/or the patient has associated gastroesophageal reflux disease (GERD) symptoms (heartburn, dyspepsia) or occasional sour taste in the mouth.

Although both LPR and GERD involve the reflux of gastric contents, patients with LPR and GERD have different clinical manifestations. Patients with LPR typically have throat and voice complaints, while GERD patients primarily report chest and abdominal symptoms. Since LPR and GERD are related disorders, patients with GERD symptoms should be asked about LPR symptoms. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Clinical manifestations'.)

●Airway symptoms – Patients may experience airway symptoms related to the following disorders, all of which have been linked to LPR [23-26]:

•Subglottic stenosis – Patients with subglottic stenosis experience persistent, biphasic (inspiratory and expiratory) stridor, which is related to narrowing of the airway immediately inferior to the vocal folds (picture 2). This disorder has been linked to LPR, which may be a contributory factor even among patients diagnosed with idiopathic subglottic stenosis [12]. Treatment of subglottic stenosis often requires surgical management [12].

•Paradoxical vocal fold motion disorder – Patients with paradoxical vocal fold motion disorder (movie 1 and figure 3) typically experience intermittent episodes of dyspnea, which may be accompanied by inspiratory stridor and a feeling of air hunger. They may also experience episodic throat tightness, dysphonia, cough, or dysphagia [27,28]. Symptoms are generally triggered by episodes of reflux. (See "Inducible laryngeal obstruction (paradoxical vocal fold motion)", section on 'Laryngopharyngeal reflux'.)

•Recurrent laryngospasm – Patients with recurrent laryngospasm often experience intermittent complete upper airway obstruction related to reflux episodes, resulting in short periods of biphasic stridor and aphonia (inability to vocalize) [29,30]. Episodes may be triggered by direct effect of the refluxate on the laryngeal sensory receptors, causing reflex firing of the intrinsic laryngeal adductor muscles, resulting in closure of the glottis to protect the lower airways.

•Chronic cough – Chronic cough can be triggered by direct effects of the refluxate in the laryngopharynx, through microaspiration into the lungs, or through vagal reflexes, causing airway hyperresponsiveness. (See "Causes and epidemiology of subacute and chronic cough in adults", section on 'Laryngopharyngeal reflux'.)

●Voice and dysphagia – LPR can be associated with hoarseness, dysphonia, and, in some patients, dysphagia. There are no reliable statistics as to the prevalence of these symptoms in the LPR population, as the definition of LPR varies in many studies and these symptoms are fairly nonspecific. It is important to note, however, that these symptoms should not always be attributed to LPR without further evaluation, as there are other potentially serious causes of these symptoms that warrant further evaluation. (See 'Differential diagnosis' below and "Hoarseness in adults", section on 'Referral' and "Oropharyngeal dysphagia: Clinical features, diagnosis, and management".)

●Additional symptoms – LPR has been linked to chronic sinusitis, chronic otitis media, and asthma, although the evidence supporting causality is lacking [31-33].

Physical examination — Many of the physical findings of LPR involve the pharynx and larynx and cannot be adequately evaluated upon routine bedside examination. However, lymphoid hypertrophy along the pharyngeal walls may be identified.

DIAGNOSIS

Our approach — There are two competing approaches to the diagnosis of laryngopharyngeal reflux (LPR). The first uses empiric treatment and relies upon the patient’s response to therapy; the second approach involves specific LPR testing prior to initiation of therapy. There is no consensus on the best approach for all patients.

There are few studies comparing the different diagnostic approaches to diagnosing LPR [34,35]. The testing-first approach allows for a more personalized approach to treatment, avoids unnecessary medications, and in some cases may be more cost-effective. Conversely, empiric treatment avoids uncomfortable testing, and further, there are no widely accepted testing criteria for the definitive diagnosis of LPR. A survey of otolaryngology practitioners demonstrated that most tend to use the empiric approach [36].

While it is reasonable to offer empiric treatment in patients who present with a constellation of LPR symptoms including hoarseness, recurrent throat clearing, excess throat mucus, postprandial or recumbent cough, and globus sensation, we agree with guidelines from the American Academy of Otorhinolaryngology-Head and Neck Surgeons (AAOHNS), which make a strong recommendation against empiric LPR treatment for patients with isolated hoarseness without visualization of the larynx [37]. This is due to the concern over missing significant laryngeal pathology that can cause dysphonia. Several studies demonstrate a high rate of missed pathology, including laryngeal cancers, in patients initially diagnosed with LPR [38-40]. Of note, in these studies, more specific laryngeal pathology was identified when patients were referred to specialty voice clinics, even when patients had prior laryngeal examinations.

The empiric treatment approach tends to be most appropriate for patients with nonsevere symptoms and in young, otherwise healthy patients. In patients with more severe symptoms and those with more complex medical histories, we typically prefer testing prior to initiating therapy, as it can offer information that can help to individualize treatment. For example, in a patient taking multiple medications and who only has mild reflux on testing, we may be able to avoid treatment with proton pump inhibitors (PPIs), thus minimizing the potential risks of adverse effects and medication interactions. We may also be able to tailor the treatment regimen (eg, to specifically control nighttime versus daytime reflux).

In our practice, we generally offer both options to patients and engage in shared clinical decision-making to determine the preferred approach. The majority of patients opt for the empiric approach, as the testing for LPR can be uncomfortable and can often be associated with increased out-of-pocket costs.

In addition, the decision to use empiric treatment rather than the testing-first approach may be influenced by the availability of reliable reflux testing. Reflux testing requires expertise in performing and interpreting the test results and may not be widely available.

Empiric treatment — Empiric treatment relies upon the ability of the clinician to diagnose LPR through the clinical history and physical examination, with confirmation based upon the patient’s response to treatment.

In addition, the clinician can use available standardized instruments, such as the Reflux Symptom Index (RSI) to aid in the diagnosis and to determine the severity of symptoms [41,42]. The RSI is a nine-item questionnaire that focuses on common reflux symptoms and rates them in an ordinal scale that is added up to create a score. Scores greater than 13 are considered abnormal [42]. Although fairly nonspecific, the RSI is typically sensitive enough to capture most cases of LPR.

LPR testing

Laryngoscopy — For more specificity and to rule out other pathology, particularly in patients in whom the diagnosis is uncertain based upon clinical evaluation, laryngoscopy (typically done by an otolaryngologist) is usually performed (see "Hoarseness in adults", section on 'Referral'). The clinician may use a tool known as the reflux finding score (RFS) to quantify the presence and severity of laryngoscopic abnormalities. The RFS is an eight-item severity scale created to quantify the endoscopic findings of LPR. In initial validation studies, the RFS demonstrated 95 percent accuracy in diagnosing LPR (given a score of ≥7 out of a possible 26) and accurately correlated with treatment efficacy [41].

Many clinicians utilize the RSI and RFS to presumptively diagnose LPR and begin empiric treatment. However, subsequent studies assessing the validity of the RSI and RFS scores have demonstrated these tools to have limited inter-rater reproducibility and poor correlation with each other [43-47]. Further, the RFS can be elevated in asymptomatic individuals and correlation with pH studies is variable [48-50].

Laryngoscopy is particularly useful in evaluating for the presence of other concerning pathology in patients with LPR symptoms. (See 'Differential diagnosis' below.)

pH impedance testing — The gold standard for the diagnosis of LPR is pH impedance testing. This test utilizes a transnasal catheter to record reflux events over a 24-hour period and monitors the flow of refluxate, including the pH, up to the pharynx (see "Esophageal multichannel intraluminal impedance testing"). Theoretically, the refluxate can be measured within the pharynx as well, but this is less reliable. However, there are no uniformly accepted criteria for the diagnosis of LPR and they vary between institutions. Additionally, the catheter is uncomfortable for patients, and they may produce excess saliva, swallow more frequently, or change their diet in response to the presence of the catheter, altering the results of the study and rendering them unreliable. Another monitoring option is a wireless probe that is clipped to the distal esophagus during endoscopy [51,52]. This device can deliver data for 48 hours before detaching and harmlessly passing through the digestive tract. However, the device only measures refluxate in the distal esophagus, so it is less useful in evaluating patients with laryngopharyngeal symptoms.

However, it is not clear what level of refluxate (eg, pepsin and acid) exposure in the pharynx and larynx is abnormal; some studies suggest that more than a single episode of pharyngeal reflux may be abnormal [53,54]. It is also not clear how extensive the exposure to reflux must be during a given episode of reflux to cause injury.

Role of esophagoscopy — Esophagoscopy is an important adjunctive test that may be helpful in the management of patients with LPR, although it cannot be used to diagnose LPR. Since acid exposure to refluxate may affect esophageal and laryngeal/pharyngeal tissues differentially, many patients with LPR may not have findings of esophagitis or other esophageal findings of reflux injury [20]. Therefore, although esophagoscopy cannot eliminate the possibility of LPR, it can provide visual confirmation of injury related to frequent reflux into the esophagus, if present. In addition, esophagoscopy can diagnose esophageal adenocarcinoma or esophageal changes that may lead to the development of esophageal adenocarcinoma (eg, Barrett’s esophagus) [55] and can also rule out other abnormalities that may be contributing to the patient’s symptoms. (See 'Differential diagnosis' below and "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Upper gastrointestinal endoscopy' and "Barrett's esophagus: Epidemiology, clinical manifestations, and diagnosis", section on 'Upper endoscopy with biopsy'.)

Other testing — Other tests have been studied to assess patients with possible LPR, including refluxate pepsin testing and pharyngeal aerosolized pH testing [56-60]. Pepsin testing has the theoretical advantage of being able to specifically measure the composition of refluxate; although refluxate pH can be altered by variables such as saliva production and medications, pepsin is specific to gastric contents and can be quantified. However, pepsin testing is not widely available and normative data on quantitative refluxed pepsin levels are lacking; thus, the clinical utility of this test is limited. Aerosolized pH testing can directly measure pH in the pharynx, which is more relevant to the diagnosis of LPR and eliminates the issues with esophageal testing. However, confounding variables may affect pharyngeal pH and, like refluxed pepsin levels, normative data are lacking.

TREATMENT — Treatment of laryngopharyngeal reflux (LPR) is typically multipronged, involving a combination of dietary and lifestyle modifications and medications.

With LPR, the focus is on treating throat symptoms and reducing the impact of LPR on associated disorders (see 'Clinical manifestations' above). Although treatment for gastroesophageal reflux disease (GERD) is also focused on relieving symptoms, it can also prevent progression to esophageal adenocarcinoma (see "Barrett's esophagus: Surveillance and management", section on 'Management of acid reflux'). However, no such causal relationship between LPR and cancer has been confirmed [61].

Management strategies for GERD and LPR differ in terms of medical therapy; GERD patients will generally experience symptom resolution within six weeks, while LPR patients will typically require longer treatment and may need higher doses of medication [62-66].

Dietary and lifestyle modification — For all patients with LPR, we suggest initial dietary and lifestyle modifications. These include:

●Avoidance or reduction of foods that may aggravate reflux, including spicy or fatty (including fried) foods, acidic foods (eg, tomato and citrus juices), chocolate, mints, coffee, tea, colas, and alcohol

●Avoidance of eating or drinking two to three hours before bedtime and lying down

●Elevation of the head of the bed

●Stopping smoking

●Eating smaller meals

●Avoidance of clothing with a constricting waistband

●Maintenance of ideal weight

●Avoidance of bending over after eating

We work with patients to identify and avoid the specific triggers that seem to worsen their symptoms. Even for patients with less severe symptoms, a period of 6 to 12 weeks of diet and lifestyle modification may be necessary to achieve symptom control.

Several studies have shown the benefits of dietary modifications on the signs and symptoms of LPR [67-70]. However, a subsequent systematic review found that there was insufficient evidence to support dietary changes in the management of LPR due to the lack of rigorous methodology of available studies [71]. Despite the lack of high-quality evidence demonstrating efficacy, we and most clinicians continue to prescribe these modifications, as they have low risk of harm and are likely beneficial in disease management.

Medications — For patients with LPR symptoms that are not controlled with a trial of dietary and lifestyle modification, and for patients with more severe symptoms or with evidence of severe LPR on testing, we suggest medication therapy.

Proton pump inhibitors — Proton pump inhibitors (PPIs) are the most commonly prescribed medications to treat LPR due to their inhibition of acid production by gastric parietal cells. They work to neutralize gastric contents, preventing activation of pepsin and other enzymes that require an acidic environment. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Pharmacology'.)

For most patients, we initiate once-daily PPI therapy 30 minutes before breakfast or dinner. Options include:

●Omeprazole 40 mg orally once daily

●Lansoprazole 30 mg orally once daily

There is no consensus on the optimal PPI dosing for the treatment of LPR. We prefer initiation of therapy with once-daily dosing, with the option of increasing to twice-daily dosing depending upon the patient’s response. Although twice-daily dosing has demonstrated superiority compared with once-daily dosing [72], it is not required for all patients, particularly those with less severe symptoms and those with evidence of nonsevere reflux on testing. In our clinical experience, once-daily PPI therapy is effective in the majority of patients.

All PPIs have similar efficacy in acid reduction, and the selection of a particular PPI may depend upon insurance coverage, concurrent medications, and patient cost. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Selecting a PPI'.)

Results of studies evaluating PPIs for the treatment of LPR are mixed:

●Randomized placebo controlled trials of PPIs have demonstrated mixed results, with some trials demonstrating efficacy [62,73,74] and others showing no benefit [63,68]. These variable trial results may in part be due to methodologic differences such as differing inclusion criteria and outcome measures.

●In a meta-analysis including 10 randomized controlled trials and 480 patients, treatment with PPI and dietary and lifestyle modifications were modestly effective in treating LPR (relative risk [RR] 1.31, 95% CI 1.03-1.67) [75]. However, in a preplanned subgroup analysis, PPI treatment without simultaneous dietary and lifestyle modifications were less effective and did not reach statistical significance (RR 1.42, 95% CI 0.96-2.09).

●In another meta-analysis including 13 randomized controlled trials and 831 patients, results evaluating the efficacy of PPIs were also mixed [76]. Among the included trials that reported patients with a >50 percent reduction in symptoms and in trials that used the Reflux Finding Score (RFS), PPI treatment was not found to be effective compared with placebo. However, when using the Reflux Symptom Index (RSI) for evaluation, PPI treatment was beneficial for reducing symptoms compared with placebo (standardized mean difference [SMD] 3.65; 95% CI 1.56-5.75).

Patients who have a definitive diagnosis of LPR and who show an initial positive response to empiric PPI therapy are treated for a total of three to six months. This duration of treatment allows for adequate mucosal healing and prevents early relapse.

We typically schedule patients for follow-up at three months to evaluate their response to treatment:

●For patients who are symptom-free, we discontinue the PPI (see 'Discontinuation of proton pump inhibitors' below) and advise indefinite continuation of lifestyle and dietary modifications.

●For patients who remain mildly symptomatic on once-daily PPI therapy, we perform laryngoscopy (if not already done), continue current PPI therapy for another two to three months, and then reattempt PPI discontinuation. (See 'Discontinuation of proton pump inhibitors' below.)

●For patients who remain moderately to severely symptomatic on once-daily PPI therapy, we perform laryngoscopy (if not already done), increase the PPI to twice daily (eg, omeprazole 40 mg orally twice daily 30 minutes before breakfast and dinner), and often add an additional medication, such as a histamine 2 (H2) blocker to be taken at bedtime (eg, ranitidine 300 mg). (See 'Histamine 2 blockers' below.)

Patients who require continuation of acid reducing medications are seen in follow-up in another two to three months; those who continue to have severe, refractory symptoms despite dietary and lifestyle modifications and medication treatment, as well as those who cannot successfully wean off medical therapy (eg, PPI or H2 blocker), are referred for consideration of interventional management. (See 'Interventional approaches for refractory symptoms' below.)

Discontinuation of proton pump inhibitors — Rebound acid hypersecretion may occur following abrupt cessation of PPI treatment [77] and can complicate the process of discontinuing therapy. We typically wean patients off the PPI over a period of several weeks, particularly if they have been on the medication for several months. For example, we will reduce twice-daily PPI therapy to once-daily dosing for one to two weeks and then switch to a once-daily H2 blocker (eg, ranitidine 150 to 300 mg once daily) for one to two weeks before stopping acid reducing medication entirely. (See 'Histamine 2 blockers' below.)

Care should be taken to prevent unnecessary, indefinite PPI use due to potential adverse effects including vitamin and mineral malabsorption (eg, calcium, vitamin B12, magnesium), increased risk of Clostridioides difficile infection, and kidney disease [62,78-81]. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Adverse effects'.)

Histamine 2 blockers — H2 blockers have been shown to reduce symptoms of chronic laryngitis in patients with LPR, although their efficacy is limited [82]. They are typically used in combination with PPIs or as “step-down” therapy when discontinuing a PPI [83]. H2 blockers provide basal acid suppression as opposed to PPIs, which suppress stimulated acid production. This mechanism of action is theoretically complementary to that of PPIs and can help with nighttime reflux when PPIs are less effective. (See "Physiology of gastric acid secretion" and "Antiulcer medications: Mechanism of action, pharmacology, and side effects" and "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Pharmacology'.)

Antacids — Antacids (eg, calcium carbonate) have a limited but important role; they are often used for patients with very mild LPR and for longer-term maintenance in patients who have been successfully weaned from PPIs to help prevent relapse. We advise patients to use antacids as needed when they can anticipate reflux events, perhaps when they may have eaten particularly fatty or acidic foods. (See "Antiulcer medications: Mechanism of action, pharmacology, and side effects", section on 'Antacids'.)

Other medications — Other medications that may be useful in the management of LPR include prokinetics and alginates.

●Alginates (eg, sodium alginate) are increasingly prescribed for management of LPR, as they may have some efficacy and have few known adverse effects. Alginates form a raft in the stomach after exposure to acid, creating a physical barrier to prevent refluxate from entering the esophagus. This theoretically addresses all the components of the refluxate, including the acid, bile, and enzymes. However, high quality evidence supporting the use of alginates in LPR is lacking, with mixed evidence of efficacy in clinical trials [84-86]. (See "Medical management of gastroesophageal reflux disease in adults", section on 'Surface agents and alginates'.)

●Prokinetics (eg, metoclopramide) have a more limited role, largely due to patient intolerance and the risk of serious adverse effects. They are typically prescribed for patients who have esophageal dysmotility to help to reduce reflux events. Side effects include depression, diarrhea, drowsiness, nausea, and tardive dyskinesia. (See "Functional dyspepsia in adults", section on 'Prokinetic agents'.)

Interventional approaches for refractory symptoms — Patients with LPR who have ongoing, severe refractory symptoms despite dietary and lifestyle modifications and medication treatment, as well as those who cannot be successfully weaned off medical therapy (eg, PPI or H2 blocker), are referred for consideration of interventional management. Candidates for interventional treatment should have correlation of symptoms and reflux events documented on reflux testing.

There are several available interventional options (surgical and endoscopic), including fundoplication, the Stretta procedure, and magnetic sphincter augmentation (MSA). However, none of these procedures have been studied adequately to make a specific recommendation on their use for patients with LPR; recommendations are based upon indirect evidence from the treatment of GERD. The techniques and evidence for their use in GERD are reviewed in detail elsewhere. (See "Surgical treatment of gastroesophageal reflux in adults", section on 'Operative techniques' and "Magnetic sphincter augmentation (MSA)".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis list for laryngopharyngeal reflux (LPR) is broad, as it includes most conditions that affect the upper airway.

Patients who present with LPR symptoms should be asked about heartburn, regurgitation, dysphagia, or weight loss. The presence and duration of these symptoms may indicate possible concerning esophageal disease that would benefit from esophagoscopy or other esophageal evaluation. (See 'Role of esophagoscopy' above and "Medical management of gastroesophageal reflux disease in adults", section on 'Are there indications for upper endoscopy?' and "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Evaluation in selected patients'.)

When evaluating and treating patients with suspected LPR, clinicians should always maintain a high level of suspicion that there may be an alternative diagnosis, especially if patients do not respond fully to LPR management. Such conditions include:

●Laryngeal and pharyngeal lesions (eg, vocal fold polyp, Reinke’s edema, malignancy) (see "Hoarseness in adults", section on 'Benign vocal fold lesions' and "Hoarseness in adults", section on 'Laryngeal cancer' and "Hoarseness in adults", section on 'Acute laryngitis')

●Presbylarynges (age-related dysphonia due to vocal fold bowing secondary to loss of muscle and collagen from the vocal folds)

●Oropharyngeal dysphagia (see "Oropharyngeal dysphagia: Clinical features, diagnosis, and management")

●Allergic pharyngitis (inflammation of the pharyngeal tissues and lymphoid patches within the pharynx due to environmental allergen exposure)

●Upper respiratory tract infections, including chronic sinusitis (see "The common cold in children: Clinical features and diagnosis", section on 'Other symptoms and signs' and "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis", section on 'Clinical manifestations')

●Chronic environmental irritation (eg, tobacco smoke, inhaled chemical fumes) (see "Hoarseness in adults", section on 'Irritants')

●Food allergies (see "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Oropharyngeal symptoms')

●Habitual throat clearing (behavioral)

●Asthmatic cough (see "Causes and epidemiology of subacute and chronic cough in adults", section on 'Asthma')

●Post-nasal drip (see "Causes and epidemiology of subacute and chronic cough in adults", section on 'Upper airway cough syndrome')

●Voice overuse/misuse (see "Hoarseness in adults", section on 'Polyps and nodules' and "Hoarseness in adults", section on 'Acute laryngitis')

●Laryngeal neuropathy (see "Hoarseness in adults", section on 'Neurologic dysfunction')

●Functional neurological symptom disorder (conversion disorder)(see "Hoarseness in adults", section on 'Functional neurological symptom disorder (conversion disorder)')

Many of these conditions can be diagnosed with an appropriate clinical history and physical examination, although several require specialty referral and testing to fully evaluate.

SUMMARY AND RECOMMENDATIONS

●Pathophysiology of LPR – Laryngopharyngeal reflux (LPR) is defined by the reflux of gastric contents into the laryngopharynx (figure 1). Although there is an underlying link between gastroesophageal reflux disease (GERD) and LPR, since the refluxate must traverse the esophagus to reach the laryngopharynx (figure 2), it is the damage to the tissues and the triggering of specific clinical symptoms that differentiates them. (See 'Pathophysiology' above.)

●Clinical manifestations of LPR – The most frequently reported symptoms of LPR include hoarseness, recurrent or persistent throat clearing, excess throat mucus, dysphagia, postprandial or recumbent cough, and globus or persistent foreign-body sensation. Although many of these symptoms are nonspecific, they should trigger concern for LPR, particularly if these symptoms are experienced together and/or the patient has associated GERD symptoms (heartburn, dyspepsia) or occasional sour taste in the mouth. (See 'Clinical manifestations' above.)

●Diagnosis: Empiric treatment versus testing – There are two competing approaches to the diagnosis of LPR. The first uses empiric treatment and relies upon the patient’s response to therapy; the second approach involves specific LPR testing prior to initiation of therapy. There is no consensus on the best approach for all patients. The empiric treatment approach tends to be most appropriate for patients with nonsevere symptoms and in young, otherwise healthy patients. In patients with more severe symptoms and those with more complex medical histories, we typically prefer testing prior to initiating therapy, as it can offer information that can help to individualize treatment. We generally offer both options to patients and engage in shared clinical decision-making to determine the preferred approach. The majority of patients opt for the empiric approach, as the testing for LPR can be uncomfortable and can often be associated with increased out-of-pocket costs. (See 'Our approach' above.)

For more specificity and to rule out other pathology, particularly in patients in whom the diagnosis is uncertain based upon clinical evaluation, laryngoscopy is usually performed. (See 'Laryngoscopy' above.)

●Management

•For all patients with nonsevere LPR symptoms or mild LPR on testing, we suggest initial dietary and lifestyle modifications rather than medication therapy (Grade 2C). Despite the lack of high-quality evidence demonstrating efficacy, these interventions are likely beneficial in disease management and have low risk of harm. (See 'Dietary and lifestyle modification' above.)

•For patients with LPR symptoms that are not controlled with a trial of dietary and lifestyle modification, and for patients with more severe symptoms or with evidence of severe LPR on testing, we suggest the addition of proton pump inhibitor (PPI) rather than other medications (Grade 2C). Evidence supporting the efficacy of PPIs in the management of LPR is mixed, but many trials demonstrate symptom improvement with the addition of PPI therapy to dietary and lifestyle modifications. There is no consensus on optimal PPI dosing, but we prefer initiation of therapy with once-daily dosing with the option of an increasing to twice-daily dosing depending upon the patient’s response. Patients are seen in follow-up at three months to evaluate their response to treatment (see 'Medications' above):

-For patients who are symptom-free, we discontinue the PPI and advise indefinite continuation of lifestyle and dietary modifications. (See 'Discontinuation of proton pump inhibitors' above.)

-For patients who remain mildly symptomatic on once-daily PPI therapy, we perform laryngoscopy (if not already done), continue current PPI therapy for another two to three months, and then reattempt PPI discontinuation. (See 'Discontinuation of proton pump inhibitors' above.)

-For patients who remain moderately to severely symptomatic on once-daily PPI therapy, we perform laryngoscopy (if not already done), increase the PPI to twice daily, and often add a histamine 2 (H2) blocker to be taken at bedtime. (See 'Histamine 2 blockers' above.)

●Referral for interventional management – Patients who continue to have severe, refractory LPR symptoms on PPI therapy and those who are unable to wean off PPI therapy are referred for consideration of interventional management. (See 'Interventional approaches for refractory symptoms' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Ramon Franco, Jr, MD, who contributed to an earlier version of this topic review.