INTRODUCTION — Laryngopharyngeal reflux (LPR) is the retrograde movement of gastric contents (acid and enzymes such as pepsin) into the laryngopharynx, leading to symptoms referable to the larynx/hypopharynx [1,2]. Typical LPR symptoms include dysphonia/hoarseness, globus pharyngeus, mild dysphagia, chronic cough, and nonproductive throat clearing [3].

Most patients are relatively unaware of LPR, with only 35 percent reporting heartburn. There are no unequivocal criteria that reliably demonstrate a causal link between acid reflux and laryngeal symptoms; results of esophageal pH testing, and response to proton pump inhibition therapy in controlled trials, are variable. (See 'Diagnosis' below.)

In fact, the validity of reflux as a cause of symptoms attributed to LPR, in the absence of esophageal symptoms associated with gastroesophageal reflux disease (GERD), has been called into question. Guidelines issued by specialty societies in laryngology [1] and gastroenterology [4] present differing perspectives. Both groups acknowledge that interpretation of existing studies is confounded by uncertain diagnostic criteria for LPR, differing measures of treatment response, and a significant placebo treatment effect.

Thus, it is likely that some patients are mistakenly diagnosed with LPR, and investigation of other causes of laryngeal symptoms (allergy, sinus, or pulmonary disease) should be considered for patients who fail to respond to LPR measures.

The clinical manifestations, diagnosis, and treatment of LPR are discussed here. GERD is discussed separately. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults" and "Medical management of gastroesophageal reflux disease in adults" and "Surgical management of gastroesophageal reflux in adults".)

EPIDEMIOLOGY — There are relatively limited data on the prevalence of laryngopharyngeal reflux (LPR) or the prevalence of findings consistent with LPR in healthy individuals.

One study of 105 healthy adults found that 86 percent had some findings on laryngoscopy associated with reflux [5]. In a meta-analysis of studies using pH probe measurements, 10 to 60 percent (mean 30 percent) of control patients demonstrated reflux [6]. In another study, 30 percent of healthy volunteers (n = 20) and 63 percent of subjects with symptoms of LPR (n = 43) had episodes of LPR detected by 24-hour dual pH probe examination [7]. Reflux episodes occurred more frequently in symptomatic subjects compared with controls (seven versus one episode daily). Local laryngopharyngeal factors, such as reflux severity and lack of local tissue protection, might account for the difference between the symptomatic patient and the asymptomatic control.

Without a clear diagnostic gold standard (see 'Diagnosis' below), it is difficult to determine the prevalence of LPR in the population.

PATHOPHYSIOLOGY

General issues — Laryngopharyngeal reflux (LPR) can cause laryngeal symptoms directly or indirectly. The direct mechanism involves irritation of laryngeal mucosa by refluxate through the action of the caustic materials (ie, acid, pepsin) on the tissues. The indirect mechanism involves irritation of other structures such as the esophagus by refluxate that does not reach the laryngeal tissues; this irritation evokes laryngeal reflexes that then cause a vagally mediated change (chronic cough, asthma-like symptoms though bronchoconstriction). Regardless of the pathway, factors such as the resting tone of the upper and lower esophageal sphincters and the duration and magnitude of increases in intraabdominal pressure are important to the creation of the refluxate bolus.

The primary function of the larynx is to act as a sphincter to protect the lower airways from the aspiration of material intended for the stomach. The larynx is endowed with a dense neural blanket, making it exquisitely sensitive and vigilant to the approaching materials. In an ideal system, refluxate would never make its way onto the larynx because it would be sensed in the laryngopharynx, and a protective cough would help keep it out of the laryngeal introitus. But refluxate does make it onto and through the vocal folds in some patients. Studies have helped elucidate the mechanism by which this can occur:

●Sensory changes may play a role in LPR. This was illustrated in a study that compared the results of laryngopharyngeal sensory testing (using adductor reflex response to standardized air-puff stimuli) in 54 patients with dysphagia and 25 healthy controls [8]. LPR was observed in 38 of the 54 patients with dysphagia and in one of the control patients; 48 of the 54 patients with dysphagia had edema of the posterior pharynx. Sensory deficits were found in 42 (78 percent) of the patients with dysphagia and in the one control patient with LPR. When 23 patients with LPR were reexamined after 90 days of treatment with a proton pump inhibitor (PPI), laryngeal edema had improved in 14 of 21 who had pretreatment edema and sensory deficits had resolved in 15 of 19 who had pretreatment deficits. When 11 patients with dysphagia but no observed LPR were reexamined after 90 days of treatment with an H2 blocker, laryngeal edema had not improved in any of the patients and sensory deficits had improved in one patient. Although this study evaluated patients with more severe problems including dysphagia, the reversibility of the sensory deficit is encouraging and reinforces the need for proper diagnosis and treatment of LPR.

●There may be mechanisms by which acid could affect laryngeal tissues even in patients with no objective swallowing problems. A pilot study that used immunohistochemical staining with monoclonal antibodies for both the alpha and beta subunits of the H+/K+ ATPase found strong staining in the serous cells and ducts of the minor seromucinous glands in the larynx of two fresh cadaveric specimens [9]. There was no positive staining in normal stomach cells unless they were parietal cells. This study raises the possibility that the larynges of LPR patients may in fact supply higher levels of their own acid via functional H+/K+ ATPase. Proton pumps have been found in the salivary glands of other organisms and are believed to play a role in acid-base homeostasis [10,11]. Thus, this may be an intended function that goes awry in symptomatic LPR patients.

●Heterotropic gastric mucosal patch (HGMP), a condition considered to be congenital in which ectopic acid-secreting gastric mucosa is present in the upper esophagus, may also cause LPR-type symptoms [12,13]. A 2010 study found HGMP patients experienced LPR symptoms more than non-HGMP patients (73 versus 26 percent) [13]. The endoscopic prevalence of HGMP is low and ranges from 0.1 to 10.0 percent with typical symptoms similar to LPR such as globus, cough, hoarseness, and dysphagia.

●There is growing belief that some patients with LPR may have alterations in laryngeal sensitivity (neuropathy of the superior and recurrent laryngeal nerves) that can create an symptomatic "irritable larynx" without an increase in the amount of refluxate [14-16].

●Helicobacter pylori infection may play a role. In a 2017 systematic review and meta-analysis of 14 clinical trials and observational studies, the prevalence of H. pylori among patients with LPR was 44 percent [17]. The study was unable to assess the effect of eradicating H. pylori on LPR symptoms due to heterogeneity of the included studies. (See "Bacteriology and epidemiology of Helicobacter pylori infection".)

More evidence is needed to examine the roles of these mechanisms in LPR as well as to look for additional etiologies.

Laryngophageal reflux versus GERD — Although stomach acid is common to both LPR and gastroesophageal reflux disease (GERD), there are many differences, making LPR a distinct clinical entity. The sine qua non of GERD is the presence of heartburn, something reliably seen in only about 40 percent of LPR patients. The majority of GERD patients have signs of esophagitis on biopsy, while only 25 percent of LPR patients do [1]. GERD is felt to be a problem of the lower esophageal sphincter and mainly occurs in a recumbent position. By contrast, LPR is seen as primarily an upper esophageal sphincter problem that mainly occurs in the upright position during periods of physical exertion (eg, bending over, Valsalva, exercise) [1,18]. There appears to be a lower incidence of esophageal dysmotility in LPR versus GERD [19].

Much less acid exposure is necessary to create LPR than GERD. An in vitro porcine study demonstrated that pepsin maintains its damaging activity up to a pH as high as 6. This means that when the laryngopharynx is exposed to pepsin after a reflux episode, it continues to injure the epithelium long after the acid has cleared. It is important to remember that reflux tests (dual pH probe) define a significant drop in pH as one that is less than a pH of 4, despite the fact that there is damage above 4.

There are dramatic differences between the epithelium and physiology of the esophagus and the laryngopharynx that account for many of the above-mentioned differences [20,21]:

●Although up to 50 events per day is considered the upper limit of normal for acid reflux events into the esophagus, more than four into the laryngopharynx is abnormal. Experimental topical application of acid to the larynx three times per week can lead to visible damage [1].

●The laryngopharynx lacks the effective stripping motion of esophageal peristalsis, and this allows acid and pepsin to remain in place longer, causing further irritation.

●The laryngeal epithelium is thin and is intrinsically poorly adapted to deal with caustic chemical injury from pepsin and acid [20].

The production of carbonic anhydrase (CAH), an important enzyme in maintaining proper pH balance by catalyzing the conversion of carbon dioxide and water into bicarbonate and hydrogen ions, appears to be different in the esophagus and larynx. One study found that one of the CAH isoenzymes, CAH III, was found in high levels in normal true folds but was not detectable in LPR patients [21]. Exposure to low pH caused a reversible decrease in laryngeal CAH III expression, while the addition of pepsin at a pH of 4 and 2 caused irreversible suppression of laryngeal CAH III expression. This suppression was not observed in the esophagus.

CLINICAL MANIFESTATIONS — In a series of patients with otolaryngologic symptoms who were found to have laryngopharyngeal reflux (LPR), the following symptoms were present [3,22]:

●Dysphonia or hoarseness (71 percent)

●Cough (51 percent)

●Globus (47 percent)

●Throat clearing (42 percent)

●Dysphagia (35 percent)

LPR has also been associated with nasal obstructive symptoms [23], vocal fold granulomas [24,25], laryngospasm [26,27], and Reinke's edema and vocal polyps [28]. Some believe that chronic laryngeal irritation may explain the development of laryngeal carcinoma in patients without a history of alcohol consumption or tobacco smoking [29,30], although this has not been substantiated.

Most patients are relatively unaware of LPR with only approximately 35 percent reporting heartburn. As noted above, LPR has been questioned as an etiology in the absence of symptomatic gastroesophageal reflux disease (GERD) [4]. (See 'Introduction' above.)

Differential diagnosis — Multifactorial elements may contribute to or explain symptoms in patients thought to have LPR. These factors may include:

●Postnasal drip

●Allergic rhinitis

●Nonallergic rhinitis

●Upper respiratory infections

●Habitual throat clearing

●Tobacco or alcohol use

●Excessive voice use

●Change in temperature or climate

●Emotional issues

●Environmental irritants

●Vagal neuropathy

DIAGNOSIS

General approach — There is significant controversy over the appropriate way to diagnose laryngopharyngeal reflux (LPR), and there is no test that is both easy to perform and highly reliable.

Most patients are diagnosed clinically based on symptoms associated with LPR. In patients who are seeing a specialist, the clinical history is generally augmented with a laryngoscopic examination. Laryngeal edema, of varying degrees, is typically seen with LPR (picture 1 and picture 2). We do not usually perform dual sensor pH probe studies to diagnose LPR.

Clinical diagnosis — Most commonly, the diagnosis of LPR is based on a combination of patient history related to common LPR complaints (hoarseness, excessive laryngeal mucus, throat clearing, globus sensation, cough) with laryngoscopic findings associated with LPR (posterior laryngeal edema, true vocal fold edema, and pseudosulcus) [31]. Critics of this strategy point to the high prevalence of these findings (up to 70 percent) in the general population [5].

The lack of standardized criteria for the diagnosis LPR and the relatively poor correlation between symptoms and endoscopic findings of LPR [32] have been cited as a rationale against the use of endoscopic techniques to diagnose LPR [33,34].

The reflux finding score (RFS), an eight-item validated clinical severity scale was introduced as a means of standardization for LPR diagnosis [35]. The RFS is a semi-objective measure of findings on laryngoscopic examination with good inter- and intraobserver reproducibility that may be used to document findings at initial diagnosis and to evaluate treatment response. A combination of the RFS and the reflux severity index (RSI) has been used to diagnose patients and monitor response to therapy with proton pump inhibitors (PPIs) [36,37]. One study of 104 symptomatic Taiwanese patients found a positive predictive value of 80 percent for pharyngeal acid reflux (diagnosis based upon 24-hour pH monitoring, endoscopic findings, and the RFS) in patients who had a combination of the following risk factors: classic reflux symptoms, hiatal hernia, and obesity [38].

Dual sensor pH probe — The 24-hour dual sensor pH probe is considered by many to be the gold standard for diagnosing LPR. Despite superior sensitivity and specificity for acid reflux events compared with physical examination findings, one study found that the dual pH probe could not predict the severity of patients' reflux symptoms or signs [39]. The authors of this study give several reasons for the lack of ability of the pH probe to separate normal patients from LPR patients. They postulate that so little acid exposure is needed to cause LPR that it may not register as positive during a limited 24-hour study. The 69 percent reproducibility of the pH tests may speak to the fact that a 24-hour testing period may be too short a sampling period to accurately estimate what is going on the rest of the time. The authors also consider that there may be another source for the irritation that is attributable to LPR. In another prospective study, 24-hour pH monitoring was abnormal in 27 of 49 patients (55 percent), with symptoms suggesting LPR [40].

A meta-analysis of trials came to more favorable conclusions about the utility of upper esophageal sphincter pH probe measurements [6]. The analysis concluded that acid exposure time reliably distinguishes patients with LPR from normal controls. However, sensitivity and specificity were not calculated.

Problems associated with pH testing include the lack of consensus on normal pH limits, number of events, and probe placement [41]. Pharyngeal reflux has been found in 16 to 21 percent of normal healthy controls, making the interpretation of pH monitoring data difficult. There has been discussion of redefining criteria for a positive pH probe test, given the known difference in acid tolerance between laryngeal and esophageal mucosa. One study found that when defining a positive test as pH below 5, rather than the present standard of pH below 4, LPR was detectable in 34 out of 44 symptomatic patients, compared with 29 with a pH threshold <4 [42].

Newer probes are being designed that may improve sensitivity or facilitate placement in the oropharynx with less invasive techniques [43,44].

Trial of therapy — Another method that has been proposed to diagnose LPR is an empiric trial of a PPI. However, controlled trials of PPIs have shown significant benefits in the placebo groups. In one study that measured response to PPI by the change in 24-hour pH studies in 27 LPR patients with baseline abnormal pH studies, four of the five patients in whom no measurable pH response to PPI was identified still reported symptom improvement [40]. (See 'Proton pump inhibitors' below.)

Molecular and histologic evaluation — Given the difficulty with present diagnostic methodology for LPR, alternative diagnostic techniques are being explored, including evaluating the concentration of salivary epidermal growth factor (EGF), immunologic markers, laryngeal mucosa gene expression, and histologic changes in patients with suspected LPR.

Lower concentrations of salivary EGF have been found in patients with LPR compared with control patients [45]. EGF is involved in the regeneration of epithelium due to physical or chemical trauma. An increase in the number of natural killer cells (NKT), as well as levels of the antigen-presenting molecule CD1d and the endogenous glycophospholipid iGb3, have been found in samples of laryngeal epithelium from patients with LPR compared with normal samples [46]. Increased levels of iGb3 and CD1d may act to stimulate the NKT system and maintain chronic inflammation. This may serve as a target system for future pharmacotherapy.

Changes in the expression of multiple genes (transforming growth factor [TGF] beta-1; vascular endothelial growth factor [VEGF]; fibroblast growth factor [FGF]-2; early growth response factor [EGR]-1; activating transcription factor [ATF]-3; connective tissue growth factor [CTGF]; matrix metalloproteinase [MMP]-1; MMP-2; and decorin) have been demonstrated by measurement of messenger RNA after exposure of laryngeal mucosa to acid [47]. These changes appear to be time-dependent and most significant within the first 60 seconds of exposure, and more vigorous with exposure to a combination of acid plus pepsin. Differences in gene expression may reflect different phenotypes of LPR [48].

Histologic changes in the larynx, similar to those seen in esophageal biopsies from gastroesophageal reflux disease (GERD) patients with acid damage, were found in patients with LPR, including dilation of intercellular spaces and occasional patients with numerous cytoplasmic vacuoles [49]. These changes, recognized as markers of acid damage in the esophagus, may prove useful as markers for LPR.

TREATMENT

General approach — Laryngopharyngeal reflux (LPR), like other extraesophageal manifestations of reflux, is initially treated with a combination of diet changes and behavior modifications. The role of medication is more controversial. (See 'Drug therapy' below.)

It is uncertain whether patients who are asymptomatic and are incidentally noted to have LPR findings require treatment. There are theoretical concerns that LPR could increase the risk of malignancy, but this has not been proven. We suggest treating asymptomatic LPR with diet and behavior modifications but not with medication.

Dietary modifications — Foods and beverages containing caffeine (coffee, tea, sodas, etc), alcohol, chocolate, and peppermints weaken the protective esophageal sphincters that normally hold stomach contents in the stomach and esophagus. There are caffeine-like substances within chocolates and peppermint that stimulate acid production and weaken the upper esophageal sphincter. It should be noted that decaffeinated teas and coffees still contain enough caffeine to cause problems with the sphincters. It is best to choose drinks that were never caffeinated.

Most foods have a pH range between 2.5 and 6.0 [50]. Low acid foods, with a pH above 4.6, include meat, poultry, seafood, milk, and fresh vegetables (except tomatoes). Acid foods (pH <4.6) include most fruits (especially citrus), tomatoes, jams and jellies, barbecue sauces, and most salad dressings. Acid foods and spicy foods (hot mustards, curry, hot peppers) directly irritate the throat lining and can cause inflammation. Pepsin is a stable molecule and can be reactivated whenever the pH drops into the proper zone. While many of these foods are otherwise healthy, they can exacerbate reflux at the level of the larynx and it is best to find less-acidic alternatives in patients with severe symptoms.

Carbonated beverages should be avoided. Many contain caffeine and loosen the sphincters, causing stomach contents to come up with each burp. Carbonated drinks with alcohol have similar effects. Even noncaffeinated carbonated beverages such as seltzer water will cause belching and can lead to stomach acid and enzymes coming into the laryngopharynx with each burp.

Behavior modifications — Common sense can limit the detrimental effects that LPR can have on the voice. Cigarette smoking (nicotine) stimulates acid production and should be avoided. The more the stomach is distended, the more chance there is that its contents will spill into the esophagus. When pressure is applied to the abdomen by bending over, performing exercise, lifting heavy objects, or singing, the probability of reflux increases dramatically.

●It is best to eat smaller meals throughout the day rather than large lunches and dinners.

●Vigorous exercise should be avoided for at least two hours after eating. Patients should also avoid overdistending the stomach with fluids during or soon before exercise, but will need to ingest adequate fluids as appropriate for the exercise.

●Patients should avoid eating or drinking for three hours prior to going to sleep. Although LPR does not routinely occur supine, some patients (particularly those who eat closer to bedtime) may also benefit from raising the head of the bed to allow gravity to help prevent reflux of stomach contents.

Drug therapy — Drug therapy for LPR typically involves acid suppression with proton pump inhibitors (PPIs). H2 blockers and antacids may provide additional benefits. For patients with symptoms that are not relieved by acid suppression, neuromodulators may be an option.

Acid suppression — There is controversy on the role of acid inhibition in the treatment of patients with symptoms suggesting LPR in the absence of esophageal irritation [1,2]. Evidence for the effectiveness of drug therapy, beyond placebo effect, is relatively weak. Guidelines from the American Gastroenterological Association recommend "against proton pump inhibitors (PPIs) or H2 blockers … in the absence of a concomitant esophageal GERD syndrome" [4]. By contrast, guidelines from the American Academy of Otolaryngology-Head and Neck Surgery recommend twice-daily PPI for no less than six months "for most patients with LPR."

Proton pump inhibitors — We suggest that patients with symptoms of LPR and symptomatic gastroesophageal reflux disease (GERD) be treated with PPIs. However, there is relatively weak evidence of efficacy in patients without concomitant GERD [51].

In the absence of symptomatic GERD, we suggest not treating with acid-blocking therapy. However, a minority of patients with LPR who have severe symptoms that significantly impact professional or social responsibilities (eg, singers, lecturers) may benefit from a trial of anti-acid therapy.

When treatment is indicated, we suggest initiating a low-dose PPI (eg, omeprazole 20 mg) once daily, one half-hour before a meal. If symptoms do not start to improve within six to eight weeks of use, the dose can be increased to twice a day or to a higher dose (eg, omeprazole 40 mg).

If there is no appreciable improvement in symptoms on the increased dose after an additional six to eight weeks, we wean the patient off the PPI slowly, decreasing both the dose and increasing the daily interval until he/she is using the medication once every third day without exacerbation of symptoms, eventually stopping the medication. (See 'Stopping therapy' below.)

For patients who do receive benefit, there are little data from clinical trials to guide treatment duration. Treatment of LPR with PPIs is believed to require at least six months of therapy [1]. This is based on results of endoscopic studies showing time needed to decrease laryngeal edema [36], as well as a recurrence of symptoms if PPIs are stopped after three months [52]. (See 'Stopping therapy' below.)

To achieve the best results, PPIs should be taken on an empty stomach one half-hour before a meal. The most effective dose is the morning dose because the stomach is relatively empty. Food intake is necessary 30 to 45 minutes after taking the pill, or the medication will not work as well. PPIs only work on activated proton pumps. Eating 30 minutes after taking the pill ensures that there are therapeutic levels of the medicine in the blood and that the maximum numbers of proton pumps have been activated (eating strongly stimulates activation of acid secretion).

The evidence of efficacy is mixed. Several randomized trials comparing PPI with placebo from two to four months found no significant difference in symptom outcomes [53-56]. One trial comparing omeprazole with placebo demonstrated no significant change in laryngoscopic appearance or clinical symptoms other than throat clearing [57]. By contrast, several small randomized trials comparing rabeprazole and esomeprazole with placebo have shown some symptom improvement [37,52]. Two studies have found that LPR symptoms were more likely to respond to treatment in patients who tested positive for Helicobacter pylori serum or stool antigen [58,59]. In an observational study, PPI treatment for LPR was associated with improvement in nasal obstructive symptoms [23].

H2 blockers — For the subset of patients who require drug therapy for LPR, H2 blockers can be added to a PPI regimen as a once at bedtime dose to help reduce overnight acid production.

Antacids — Antacids, such as those containing calcium, magnesium, or aluminum compounds, can be used 30 minutes after eating a very acidic meal. They can also be used in anticipation of reflux events to help neutralize acid that is already present in the stomach, such as prior to exercising. We routinely begin Gaviscon Advance (sold in Europe, but available in the United States via the internet). Because it is composed of alginate and potassium bicarbonate, it forms a “raft”, creating a barrier to stomach contents reaching the esophagus. We ask that patients take this 30 minutes after meals and 30 minutes prior to exercising or lying down to sleep. They can taper the frequency as symptoms allow.

Stopping therapy — When attempting to discontinue medications, a stepwise gradual decrease over the course of six to eight weeks with monitoring for the return of symptoms should be used. A rebound effect may be seen with abrupt cessation of medications.

For patients with symptomatic benefit, we suggest that patients be tapered off medication after six months. We continue the H2 blocker at night before bed (or Gaviscon Avance treatment) and reduce the PPI dose to once daily in the morning for eight weeks and then to every other morning for eight weeks. Patients whose symptoms remain controlled can then discontinue medication therapy. Many patients may find that symptoms return six to eight weeks after a reduction in the dose of medication.

Neuromodulating agents — Small case series suggest that tricyclic antidepressants, gabapentin, and pregabalin can provide benefit when laryngeal sensitivity (neuropathy) is thought to be contributing to symptoms of LPR [14,16,60]. These medications can be added if an initial trial of PPIs and H2 blockers has been unsuccessful.

We start nortriptyline in patients who have little or no response to other therapies (diet and behavioral modifications and acid suppression) or in patients whose exam does not show significant edema, erythema, or secretions. We also start nortriptyline if the exam shows consistent laryngeal asymmetry on examination, possibly indicating a laryngeal paresis. Nortriptyline can be started while the PPI is being weaned. We start at 10 mg at bedtime for three months. In patients with little or no response, we increase the dose to 20 mg at bedtime for an additional three months. If there is no response at 20 mg, the patient should be weaned over the course of six to nine weeks (eg, 10 mg every day for three weeks, then every other day for three weeks, then every three days for three weeks, then off).

Referral — Most patients with typical symptoms, and who are young, have dietary or behavioral risk factors for LPR, and are at low risk for malignancy, can be initially treated without evaluation by an otolaryngologist.

We suggest that the following are indications for initial referral:

●Age greater than 50

●Risk factors for head and neck cancer, such as tobacco use or excessive alcohol consumption

●Neck mass

●Dramatic hoarseness, dysphagia, or pain

Chronic hoarseness should not be assumed to be secondary to LPR. We suggest that patients who show no improvement be referred for visualization of the larynx and hypopharynx.

Some have suggested that patients with heartburn, significant dysphagia, or chest pain undergo esophagogastroduodenoscopy (EGD), as they may have Barrett's metaplasia or other esophageal GERD-related changes [49]. We do not recommend EGD for patients with LPR in the absence of dysphagia and heartburn unresponsive to PPI therapy.

Patients who do not respond to the behavioral and medical treatments above are sometimes treated with reflux surgery. A controlled trial suggested that surgery was not consistently effective in patients who were unresponsive to aggressive PPI therapy [61]. Other studies have demonstrated benefit for Nissen fundoplication but were not controlled trials [62,63]. (See "Surgical management of gastroesophageal reflux in adults".)

SUMMARY AND RECOMMENDATIONS

●Laryngopharyngeal reflux (LPR) is the retrograde movement of gastric contents (acid and enzymes such as pepsin) into the laryngopharynx, leading to symptoms referable to the larynx/hypopharynx. (See 'Introduction' above.)

●LPR is distinct from gastroesophageal reflux disease (GERD) in a number of ways. These include that LPR is primarily a disorder of the upper esophageal sphincter rather than the lower esophageal sphincter and that the laryngopharynx is less able than the esophagus to tolerate caustic refluxate. (See 'Laryngophageal reflux versus GERD' above.)

●Common clinical manifestation of LPR include dysphonia/hoarseness, cough, globus, throat clearing, and dysphagia. Multiple factors may contribute to or be responsible for symptoms suggesting LPR. (See 'Clinical manifestations' above.)

●There is significant controversy over the appropriate way to diagnose LPR, and there is no test that is both easy to perform and highly reliable. In the presence of symptoms, laryngoscopic findings of edema increase the likelihood of LPR. (See 'Diagnosis' above.)

●We suggest that patients with LPR be managed with dietary and behavioral changes (Grade 2C). These include avoiding caffeine, alcohol, chocolate, peppermints, carbonated beverages, and nicotine, and consuming acid and spicy foods only in moderation. Patients should eat smaller meals and avoid eating for several hours before exercise or sleep. (See 'Dietary modifications' above and 'Behavior modifications' above.)

●We suggest that patients with symptoms of LPR and a concomitant esophageal GERD syndrome be treated with proton pump inhibitors (PPIs; eg, omeprazole 20 mg once or twice daily) (Grade 2B). (See 'Drug therapy' above.)

●Except for the unusual patient with debilitating symptoms, in the absence of symptomatic GERD, we suggest NOT treating with acid-blocking therapy (Grade 2C). Patients with mild complaints should use antacids and medications that can form a temporary blockade from the stomach into the esophagus (such as Gaviscon Advance). A minority of patients with LPR have severe symptoms that significantly impact professional or social responsibilities; these patients are seen most often in a referral clinic.

We suggest that such patients be treated with PPIs, as well as with H2 blockers at bedtime and with antacids when reflux is anticipated (such as prior to exercise soon after eating) (Grade 2C). (See 'Drug therapy' above.)

●Patients requiring PPIs should be treated for six to eight weeks before evaluation for a response. If there is no response, the dose of the PPI should be increased. If there is no appreciable improvement in symptoms on the increased dose after an additional six to eight weeks, the medication can be tapered. If a patient has a response, the patient should be treated for a minimum of six months prior to gradually tapering therapy. (See 'Acid suppression' above and 'Stopping therapy' above.)

●Patients with persistent symptoms despite adequate antireflux treatment can be offered neuromodulating agents such as the tricyclic antidepressants, gabapentin, or pregabalin. (See 'Neuromodulating agents' above.)

●Patients who are over age 50, use tobacco or consume excessive alcohol, have a neck mass, or present with dramatic hoarseness, dysphagia, or pain should be referred for evaluation, as should patients who show no improvement after six weeks of therapy. (See 'Referral' above.)

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