INVITED REVIEW ARTICLE

https://doi.org/10.5005/jp-journals-10001-1519
International Journal of Head and Neck Surgery
Volume 13 | Issue 1 | Year 2022

Laryngopharyngeal Reflux

Anagha A Joshi1, Bhagyashri Chiplunkar2

1ENT, LTM Medical College & General Hospital, Consultant ENT Surgeon at HN Reliance Hospital and Joshi Clinic, Mumbai, Maharashtra, India

2Department of ENT, GMC Akola, Maharashtra, India

Corresponding Author: Anagha A Joshi, ENT, LTM Medical College & General Hospital, Consultant ENT Surgeon at HN Reliance Hospital and Joshi Clinic, Mumbai, Maharashtra, India, Phone: +91 9820298027, e-mail: anagha_5@rediffmail.com

How to cite this article: Joshi AA, Chiplunkar B. Laryngopharyngeal Reflux. Int J Head Neck Surg 2022;13(1):8-17.

Source of support: Nil

Conflict of interest: None

Keywords: LPR, LPRD, RSI, RFS

INTRODUCTION

Laryngopharyngeal reflux (LPR) is a disease that, today, on account of pathophysiological, diagnostic, and therapeutic characteristics, directly involves the ENT specialist. The signs and symptoms of the disease are non-specific, and can be manifestations of other diseases such as infection, vocal abuse, allergy, smoking, or nonpathologic alterations. However, when these signs and symptoms present together, they can be a strong indicator of reflux.

DEFINITIONS

Laryngopharyngeal reflux (LPR): LPR is the backflow of gastric contents into the laryngopharyngeal area.

Laryngopharyngeal reflux disease (LPRD): It is the symptoms, signs and tissue abnormalities of the pharynx, larynx, and other associated respiratory organs, resulting from damage caused by gastric content in the upper aerodigestive tract. LPR is often confused with gastroesophageal reflux (GER).

Gastroesophageal reflux (GER): GER is defined as the backflow of stomach contents into the esophagus.

Gastroesophageal reflux disease (GERD): Refers to GER that is excessive, and that causes tissue damage and/or clinical symptoms.

Extraesophageal reflux: Extraesophageal reflux disease (EERD) is gastroesophageal reflux disease (GERD) with symptoms appearing outside the stomach and esophagus. This includes laryngopharynx, lower respiratory tract, nasopharynx, sinuses, and middle ear.

The symptoms of LPR are different from the GERD-associated symptoms of heartburn, regurgitation, and esophagitis, although one-third of LPR patients have concomitant GERD.1 It has been reported in up to 10% of patients presenting to an otolaryngologist’s office, and more than 50% of patients with hoarseness have been found to have reflux-related disease.2 It is also one of the most difficult disorders to diagnose because of its nonspecific symptomatology and vague signs.

Numerous synonyms for LPR have been defined. The first known term was “Reflux-related laryngeal disease” (reflux laryngitis), reported by Cherry in 1968.3 Currently, the most widely used term is LPR. This term was first proposed by Koufman in 1996. It was adopted by the American Academy Otolaryngology and Head and Neck Surgery in its 2002 Position Statement.4

PATHOPHYSIOLOGY

Pathophysiology of Gastroesophageal Reflux

The primary barrier to GER is the lower esophageal sphincter, which is located at the level of the diaphragmatic hiatus and acts as the main deterrent to reflux.5 Other structures that may be involved in preventing reflux are the intra-abdominal segment of the esophagus, the gastroesophageal angle, the diaphragmatic crura, and the phrenoesophageal ligament. Gastric motility also plays a role, with delayed emptying predisposing the patient to GERD. Thus, the mechanisms involved in preventing reflux are both anatomical and physiological as follows (Fig. 1):

Fig. 1: Anatomical and physiological barriers involved in preventing reflux

Anatomical

  • Lower esophageal sphincter

  • Intra-abdominal segment of esophagus

  • Angle of His

  • Mucosal rosette in the lower esophagus

  • Phreno-esophageal membrane

  • Pinch-cock effect of the diaphragmatic crura

Physiological

  • Effective peristaltic clearance of contents from distal esophagus

  • Prompt gastric emptying

Pathophysiology of Laryngopharyngeal Reflux

LPR disease is usually multifactorial. The association between LPR and GERD is yet to be established, and not all patients with GERD will develop LPR, and vice versa. Anatomical proximity provides the basis for assuming a causal association between acid reflux and LPR. LPR might result from direct injury or by a secondary mechanism.

Two hypotheses exist about how gastric acid precipitates extraesophageal pathologic response.6 The first purports direct acid-pepsin injury to the larynx and surrounding tissues via esophago-pharyngeal reflux (the microaspiration theory). The second hypothesis suggests that acid in the distal esophagus stimulates vagal-mediated reflexes (the esophagobronchial reflex theory), that result in bronchoconstriction and chronic throat clearing and coughing, eventually leading to mucosal lesions. These two mechanisms may act in combination to produce the pathologic changes seen in LPR (Table 1).7

Table 1: Pathophysiology

Unlike the esophagus, the laryngeal structures are not rinsed with saliva, so small amounts of gastric contents are probably capable of producing injury in the respiratory epithelium. While the esophagus succeeds in neutralizing those physiological episodes of reflux, the pharyngo-laryngeal region is extremely vulnerable to every single episode of reflux, especially in the presence of an already inflamed mucosa due to concomitant inflammatory episodes of the upper aerodigestive tract. Cell damage occurs in the epithelium of the esophagus when the pH is below 4, but occurs in the laryngeal epithelium at a higher pH and with short-term exposure.8 For this reason, LPR should be treated more aggressively and for longer than GERD.

The following four physiological barriers protect the upper aerodigestive tract from reflux injury:

  • The lower esophageal sphincter

  • Esophageal motor function with acid clearance

  • Esophageal mucosal tissue resistance

  • The upper esophageal sphincter

The delicate ciliated epithelium of the respiratory tract is sensitive to damage when these mechanisms fail. Dysfunction in the cilia leads to mucus stasis. The accumulation of mucus produces sensations that provoke chronic throat clearing. Direct irritation of the upper airway by gastric refluxate can cause laryngospasm, producing symptoms of chronic coughing and choking.

The combination of direct injury by refluxate and symptoms such as chronic laryngospasm and throat clearing can lead to vocal cord edema, contact ulcers, and granulomas that cause other LPR-associated symptoms such as hoarseness, globus pharyngeus, and sore throat.

Evidence suggests that in both healthy and patient populations, the refluxed gastric acid may come into contact with structures as high as the pharynx. Furthermore, several signs of laryngeal irritation, which are generally considered to be signs of LPR, were found to be present in a high percentage of asymptomatic individuals on laryngoscopic examination.9

These findings suggest the existence of inter-individual variability in terms of mucosal resistance to acid exposure, both in the esophagus and pharyngolarynx. Currently, the understanding of the pharyngolaryngeal defense mechanisms against refluxed acid is limited, and the natural history of the disease is unknown. This problem is further magnified by the fact that pharyngolaryngeal lesions may have multiple etiologies with similar appearance and presentation.

More recent investigation into defense mechanisms against refluxed acid in the larynx and surrounding tissues suggests a possible mechanism of increased susceptibility in some patient populations. Defense mechanisms in the epithelium of the esophagus and larynx are known to differ. Active bicarbonate production is pumped into the extracellular space in the esophagus but not into the larynx. Recent investigations suggest that laryngeal tissues are protected from reflux damage by a carbonic anhydrase in the mucosa of the posterior larynx. The carbonic anhydrase enzyme catalyzes hydration of carbon dioxide to produce bicarbonate, which neutralizes the acid in refluxate. Carbonic anhydrase isoenzyme III, expressed at high levels in normal laryngeal epithelium, was shown to be absent in 64% of biopsy specimens from laryngeal tissues of LPR patients.10

LPR is most commonly characterized by chronic intermittent symptoms, and is not necessarily present constantly or even daily in an individual patient.

While upto 51 reflux episodes per day are considered normal in the esophagus, even a single pharyngeal episode of pH < 4 is considered pathological.8

It is seen that patients with gastrointestinal symptoms are night time refluxers as they have reflux in the supine position whereas patients with LPR show daytime reflux.

While heartburn forms the main symptom of patients with GERD, it does not form a part of symptoms complex of LPR, hence LPR patients are also called “silent refluxers”. Differences between GERD and LPR are listed in Table 2.

Table 2: Difference between LPR and GERD
GERD LPRD
Backflow of gastric contents into esophagus Backflow of gastric contents into hypopharynx, larynx
Prolonged esophageal clearance, esophageal dysmotility No prolonged esophageal clearance, no esophageal dysmotility
Significant esophagitis and heartburn No esophagitis
>45 reflux episodes/day One or two episodes/week
Supine (nocturnal) reflux Upright (daytime) reflux
Lower esophageal dysfunction Upper esophageal sphincter dysfunction

As reflux of the acid contents occur from the upper esophageal sphincter, the larynx which is sensitive to acid, pepsin and pancreatic enzymes gets severely affected. The posterior laryngeal components, i.e., the arytenoid cartilages and posterior commissure are affected the earliest due to their proximity to the cricopharyngeal sphincter.

DIAGNOSTIC EVALUATION

History

The diagnosis of LPR has become more common over the last few years, 4–10% of patients presenting to ear-nose-throat physicians have complaints related to GERD. A good case history is very critical to both diagnosis and treatment in patients with extraesophageal reflux (EER). The clinician must identify not only symptoms but also behavioral and medical risk factors. Factors that may predispose a patient to esophageal reflux should be discussed, e.g.:

  • Tobacco use

  • Diet (e.g., soda, spicy foods, fatty foods)

  • Alcohol use

  • Certain drugs (calcium channel blockers, nitrates, steroids).

Common symptoms described in association with EER are listed below (Listed in order of frequency)

  • Hoarseness/dysphonia (episodic or chronic)

  • Globus sensation

  • Chronic throat clearing

  • Vocal fatigue

  • Voice breaks

  • Sore throat

  • Neck pain

  • Excessive throat mucus

  • Chronic or night time cough

  • Dysphagia

  • Odynophagia

  • Postnasal drip

  • Halitosis

  • Ear pain

  • Laryngospasm

  • Asthma exacerbation

  • Loss of upper singing range

  • Prolonged warm up time in singers

  • Heartburn/regurgitation

The most common symptoms of LPR are excessive throat clearing, coughing, hoarseness, and globus pharyngeus (“lump in the throat sensation”). In Kaufman’s study including 899 patients, throat clearing was observed in 87% of patients with LPR versus 3% of patients with GERD.8 On the other hand, only 20% of the patients with LPR reported heartburn or a burning sensation compared with 83% in the group with GERD. Hoarseness is generally a fluctuating symptom that occurs in the morning and improves during the day. It is important for physicians to appreciate the potential significance of hoarseness and the relative nonspecificity of laryngitis. Laryngitis is a nonspecific designation of laryngeal inflammation. Often, it is mild and resolves spontaneously. When persistent, laryngitis must be further defined based on probable etiologic factors: viral bacterial infection, allergy, vocal trauma, postnasal discharge, or LPR (Table 3). Persistent or progressive hoarseness lasting beyond 2–3 weeks requires examination of the laryngopharynx to rule out any laryngeal pathology. This is generally considered good practice; however, laryngeal examination is particularly important in suspected LPR because of the apparent known association of LPR and upper aerodigestive tract cancer.

Table 3: Clinical clues of distinguish LPR from other causes of hoarseness
LPR Infection Rhinosinusitis Allergy Benign
Vocal cord Lesion		 Malignant vocal cord lesion
Hoarseness characteristics Fluctuates Acute, resolves Acute/chronic or recurrent Fluctuates Constant Progressive
Throat pain Common (with cough, throat cleaning) Yes Uncommon No From secondary muscle tension Late (local and referred)
Laryngeal findings Edema, granuloma, erythema, pseudosulcos Erythema, edema Secretions (thick discolored edema) Edema, clear secretions, bluish mucosa Nodules, polyps, cysts, scars Ulcerative or exophytic (red white mass) stiff
Aggravating factors Smoking, obesity, diet/lifestyle Systemic infection, immunosuppression LPR, Allergy, smoking Environment seasonal Smoking, vocal trauma, LPR Smoking (common) LPR, ethanolism

LPR, laryngopharyngeal reflux

Reflux Symptom Index (RSI)

Belafsky and colleagues11-13 developed the reflux symptom index (RSI), a self-administered survey of nine questions used to assess patients with LPR. The questionnaire for RSI is not time consuming, and can be completed in less than one minute. The scale for each individual item ranges from 0 (no problem) to 5 (severe problem), with a maximum total score of 45 (Table 4). The 95% upper confidence limit for the RSI in controls was 13.6. Thus, they consider an RSI greater than 13 to be abnormal14 (Table 4). They demonstrated that this instrument is reliable and that it provides reproducible and valid findings. They prospectively evaluated 40 patients with EER documented by dual pH probe studies and 2 months of medical management. The RSI was noted to show improvement before changes were seen in physical findings. The mean RSI at initiation of the study was 19.3, which improved to a mean of 13.9 after 2 months.12

Table 4: Reflux symptom index
Symptom No problem, 5-severe problem
1 Hoarseness or a problem with your voice 0 1 2 3 4 5 Total
2 Clearing your throat
3 Excess throat mucus or postnasal drip
4 Difficulty swallowing food, liquids, or pills
5 Coughing after you ate or after lying down
6 Breathing difficulties or choking episodes
7 Troublesome or annoying cough
8 Sensations of something sticking in your throat or a lump in your throat
9 Heartburn, chest pain, indigestion, or stomach acid coming up

Physical Examination and Laryngeal Endoscopy

The physical examination can yield several clues to EER. Observations of the quality of the voice, frequent throat clearing, cough or stridor, muscle tension in extralaryngeal musculature, and general body habitus are important to the evaluation. The larynx can be evaluated with indirect laryngoscopy along with rigid and/or flexible laryngoscopy.

Reflux Finding Score (RFS)

Belafsky et al. (2001) developed an eight-item reflux finding score (RFS).11 This score is based on objective findings observed during fiberoptic nasoendoscopy of the larynx. This aims to facilitate the standardization of the clinical findings of LPR so that clinicians may improve on diagnosis, quantify symptom severity, and measure therapeutic effectiveness of patients with this disorder. The score ranges from a minimum of zero (no abnormal findings) to a maximum of 26 (worst score possible). It is essential to note that the RFS is simply a clinical scale of laryngeal inflammation. The independent items on RFS are not designed to individually forecast the presence or absence of LPR. Other factors such as infection, allergy, neoplasia, autoimmune disorders, and environmental toxins may add to the inflammation and hence contribute to an abnormal RFS. In a study of 40 patients with LPR and 40 normal control individuals, it was found that mean RFS for the normal individual was 5.2, while the mean RFS for patients with confirmed LPR was 11.5. The authors concluded that RFS of six should be considered normal and RFS of greater than seven is statistically associated with LPR in 95% of individuals.11

The RFS was developed to standardize the laryngeal findings of LPR so that clinicians may better diagnose, evaluate clinical improvement, and assess therapeutic efficacy of patients with LPR (Table 5). This outcome instrument successfully documents treatment efficacy and thus displays good criterion-based validity. The most frequent finding of persons with LPR was posterior laryngeal hypertrophy, which was documented in 85% of all patients before the initiation of treatment.11

Table 5: Reflux finding score (RFS)
Findings Grading Pt score
1 Subglottic edema 0 Absent
2 Present
2 Ventricular obliteration 2 Partial
4 Complete
3 Erythema/hyperemia 2 Arytenoids
4 Diffuse
4 Vocal fold edema 1 Mild
2 Moderate
3 Severe
4 Polypoid
5 Diffuse laryngeal edema 1 Mild
2 Moderate
3 Severe
4 Obstructing
6 Posterior commissure
hypertrophy		 1 Mild
2 Moderate
3 Severe
4 Obstructing
7 Granuloma/granulation tissue 0 Absent
2 Present
8 Thick endolaryngeal mucus 0 Absent
2 Present

Koufman first described subglottic edema, also called pseudosulcus vocalis, in 1995. It refers to subglottic edema that extends from the anterior commissure to the posterior larynx (Fig. 2). It can be differentiated from sulcus vergeture, which is caused by adherence of the vocal fold epithelium to the vocal ligament secondary to the absence of the superficial layer of lamina propria. While true sulcus stops at the vocal process and is in the mid portion of the vocal fold striking zone, pseudosulcus vocalis extends all the way to the back of the larynx. Its presence contributes 2 points to the RFS.

Fig. 2: Comparison of pseudosulcus versus true sulcus vocalis. (A) Bilateral pseudosulcus vocalis (arrow). Notice the subglottic edema extends past the vocal process all the way to the posterior larynx. Also present are posterior commissure hypertrophy and partial ventricular obliteration. (B) True sulcus vocalis of the right vocal fold (arrow). Notice that the sulcus is present in the midportion of the striking zone and stops at the vocal process of the arytenoid

Ventricular obliteration (Fig. 3) is a relatively frequent finding in patients with LPR (80%). Swelling of the true and false vocal folds causes this space to be poorly visualized (obliterated). With partial ventricular obliteration the ventricular space is reduced and the false fold edge is indistinct. With complete ventricular obliteration, the true and false folds appear to touch and there is no true ventricular space. This finding is noticeably reversed with successful antireflux treatment. Partial obliteration contributes 2 points and complete obliteration contributes 4 points to the RFS.

Fig. 3: Ventricular obliteration. (A) Open laryngeal ventricles. Note the sharp ventricular bands and the open space between the true and false vocal folds. (B) Ventricular obliteration. Both the true and false vocal folds are swollen, thus obliterating the ventricles

Laryngeal erythema/hyperemia (Fig. 4) is a relatively nonspecific finding that is significantly dependent on the videoendoscopic equipment. Subtle changes in erythema are difficult to quantify and vary depending on the quality of the fiberscope, video monitor, and light source. Nonetheless, isolated erythema of the arytenoids contributes 2 and diffuse laryngeal erythema contributes 4 points to the RFS.

Fig. 4: Diffuse laryngeal erythema

True vocal fold edema is graded as mild (1 point) if only slight swelling exists and moderate (2 points) when it becomes more perceptible (Figs 5A and B). Edema is graded as severe (3 points) when swelling of the cord becomes sessile. Finally, polypoid degeneration of the true vocal fold contributes 4 points to the RFS.

Figs 5A and B: Vocal fold edema. (A) Mild vocal fold edema. (B) Polypoid degeneration of the true vocal folds. Also present are posterior commissure hypertrophy, total ventricular obliteration

Diffuse laryngeal edema is judged by the size of the airway relative to the size of the larynx. It is graded as mild (1 point) to obstructing (4 points).

Hypertrophy of the posterior commissure is a frequent finding in LPR. It is graded as mild (1 point) (Fig. 6A) when there is a moustache-like appearance of the posterior commissure mucosa and moderate (2 points) (Fig. 6B) when the posterior commissure mucosa is swollen enough to create a straight line across the back of the larynx. Posterior commissure hypertrophy is graded as severe (3 points) (Fig. 6C) when there is bulging of the posterior larynx into the airway and obstructing (4 points) (Fig. 6D) when a significant portion of the airway is obliterated.

Figs 6A to D: Posterior commissure hypertrophy. (A) Mild posterior commissure hypertrophy. Slight moustache-like configuration of posterior commissure. (B) Moderate posterior commissure hypertrophy. Straight line across the posterior larynx. (C) Severe posterior commissure hypertrophy. (D) obstructing posterior commissure hypertrophy

The final two items on the RFS are granuloma/granulation tissue (Fig. 7) and thick endolaryngeal mucus (Fig. 8). Patients get 2 points when these entities are present and 0 points otherwise.

Fig. 7: Granuloma

Fig. 8: Thick endolaryngeal mucus

Dual-Sensor pH Probe

The 24-hour dual-sensor pH probe (simultaneous esophageal and pharyngeal) is considered the gold standard in the diagnosis of GERD, with sensitivity of 93.3% and specificity of 90.4%, when using a cut-off value of 4.5% of total time with pH < 4 during a 24-hour period.15 Ambulatory pH probe monitoring is often applied to evaluate the efficacy of drug treatment in cases of LPR;4 however, it is considered a less reliable test for confirming LPR.16,2 This is primarily due to the difficulties involved in interpreting pH-monitoring data and a lack of consensus on normal pH limits, number of events, and probe placement.16-18 Another concern with pH probe monitoring is its inability to detect gaseous and/or nonacid refluxate, which are potentially harmful to the laryngopharynx. As a result, intraluminal impedance testing is generally regarded as a superior approach.2

Multichannel Intraluminal Impedance-pH Monitoring (MII)

MII is able to detect esophageal bolus movement by measuring changes in electrical resistance, and it is associated with pH monitoring. The single use 2 mm width MII-pH catheter contains ring electrodes that are usually positioned 3, 5, 7, 9, 15, and 17 cm from the tip and combined with at least 1 pH electrode at the tip. MII-pH is the most reliable means to precisely diagnose acid, nonacid, or mixed reflux. Addition of impedance testing improves the sensitivity (70–80%) and the false-negative rate (20–50%) of classical pH monitoring, which is unable to detect nonacid reflux or some aerosolized molecules.19

However, MII-pH too has several limitations. The number and characteristics of reflux episodes may vary from day to day, and the results can be associated with false-positive and false-negative rates. There is no standardization of interpretation for results at the proximal sensor. It is costly, inconvenient to the patient, and not available in all centers.

Oropharyngeal pH Monitoring

It consists of a single hypopharyngeal probe designed to measure pH of aerosolized droplets. Studies have suggested that the oropharyngeal probe may have higher positive predictive capability than that of esophageal measurement, but these findings are based on low numbers of patients and remain preliminary.20 The severity of EER is assessed with the help of the Ryan Score. This comprises the total time of pH < 5.5 in the upright position or pH < 5.0 in the supine position, as well as the number and length of each reflux period. A positive Ryan Score means severe reflux, whereby higher values are associated with a greater acid exposure in the throat.21 However, a negative Ryan Score does not exclude moderate, mild, neutral or alkaline LPR, as well as no reflux.

Empirical Therapeutic Trial

Patients with suspected LPR with RSI >13 and/or RFS >7 are put on dietary recommendations and proton pump inhibitors (PPIs) for 3 months and then reassessed. A patient is considered to have improved if there is 50% improvement of symptoms score after treatment, both a ≥3-point RFS reduction and a ≥5-point or ≥6-point RSI reduction, or a reduction of scores to RSI <13 and RFS <7 after 3 or 6 months of treatment.19

There are several limitations to this method of diagnosis. Refractory reflux or nonacid reflux may be present in nonresponders; this cannot be excluded on the basis of empiric treatment, and patients without LPR are subjected to unnecessary medication, and are assigned reflux diagnosis falsely.

Pepsin and Bile Salt Detection

The detection of pepsin, bile salts, and probably trypsin on saliva and pharyngeal or laryngeal mucosa is a promising diagnostic approach.22 A recent meta-analysis of 11 studies suggested that sensitivity and specificity of salivary pepsin detection would be 64 and 68%, respectively.23Lately, a new pepsin rapid test (Peptest-Biomed) is also being used as a convenient, office based, noninvasive, quick, and inexpensive technique in LPR diagnosis. The clinical value of this test in patients with LPR has insufficient evidence and is the subject of ongoing studies.

In summary, there is no gold standard for the LPR diagnosis. However, it is accepted that patients with LPR symptoms, signs, and ≥1 proximal esophageal reflux episodes at the MII-pH can be considered to have LPR. In case of doubt or in case of symptoms, signs, but negative MII-pH, pepsin detection could be useful for the diagnosis.19 MII-pH and pepsin detection are not available in all centers. We follow the following protocol as given in Figure 9. Future technologies are needed to improve the LPR diagnosis.

Fig. 9: Algorithm for Assessment and Management of LPR

TREATMENT

Lifestyle modification: The role of lifestyle modification in patients with GERD cannot be underestimated. Following are the instructions that can be given to the patients to help regularize their lifestyle.

Role of Antireflux Therapy

Along with advice on lifestyle and dietary modifications, most of the patients will require some form of medical therapy. The aim of the medical management of LPR is neutralization of the gastric juice acidity and the enhancement of gastrointestinal tract motility.

  • Proton Pump Inhibitors (PPI): Proton pump inhibitors are considered the mainstay of medical treatment, although there is some controversy regarding their efficacy.24 A 3-month empirical trial is a cost-effective approach to initial assessment and management.25,26 Responders can be weaned, while non-responders should undergo further studies to confirm LPR.

Symptom resolution of straightforward LPR usually takes place within two months of therapy with PPI. Nonetheless, the objective findings of LPR recover more slowly and continue to get better for the period of 6 months of treatment12,27 Voice disorders may have numerous causes. Therefore, the lack of ability of proton pump inhibitors to entirely resolve the symptoms or physical findings is likely. Treatment of LPR of more than 6 months may be indicated to attain a full resolution of physical findings and to reduce the risk of the return of symptoms.27 Termination of treatment based on the presumption that LPR symptoms are getting better alone may be premature. This conclusion concurs with the view of the Consensus Conference Report on LPR (1997)28 that the suggested twice daily PPI treatment be continued for a minimum period of 6 months.

In one prospective, placebo-controlled, randomized, double-blind study, the laryngoscopic findings and laryngopharyngeal symptoms in reflux laryngitis showed improvement through antireflux treatment with omeprazole.29 Besides the nature of treatment, the dosage and duration of treatment is also of great interest. A considerable number of patients on twice daily PPIs do not have satisfactory acid suppression for curing the LPR. As a consequence, this group of patients may need a higher dosage of PPI or replacement by H2-receptor antagonists. Lifelong treatment with PPI in some patients may be inevitable.

  • H2-receptor antagonist: Ranitidine has proven to be a more potent inhibitor of gastric secretion than cimetidine and is the H2-receptor antagonist of choice,30 although it has been found to be of limited value in treating LPR.31

  • Prokinetic agents: They accelerate esophageal clearance and increase lower esophageal sphincter pressure, but have fallen out of favor because of reported adverse effects of ventricular arrhythmias and diarrhea.32 Cisapride has been discontinued because of such serious adverse effects. Tegaserod is a prokinetic agent that was recently demonstrated to decrease reflux and lower esophageal sphincter relaxation events,33 and has been found useful in treating some LPR cases with associated esophageal dyskinesia.

  • Alginates: They are polysaccharides found in algae and convert into a gel form when they combine with cations. In particular, they form a physical barrier for gastroduodenal contents, and have the advantage of being a nonsystemic medication. In a prospective, randomized controlled study, liquid alginate preparations (taken four times daily) have been shown to be effective in treatment of LPR symptoms and signs.34 Alginates should be given after each meal and last thing at night, and nothing should be taken by mouth after the nocturnal dose.35

  • Mucosal cytoprotectants: Sucralfate is a polysulfated salt of sucrose that may be helpful as an adjunct in protecting injured mucosa from harmful effects of pepsin and acid.36,37 Antacids (sodium bicarbonate, aluminum, and magnesium-containing over-the-counter antacids) may relieve GERD symptoms but do not play a role in LPR management.38

  • Neuromodulators: Patients with persistent reflux–refractory to PPI (nonacid or weakly acid), assessed with ambulatory 24-h MII-pH monitoring, could benefit from reflux-reducing agents.39 Reflux-reducing agents such as GABAB agonists (Baclofen) have been shown to decrease acid reflux occurrence, esophageal acid exposure, and improved reflux-related symptoms.40 However, their use in clinical practice is limited by a poor tolerability profile.

Surgery-Nissen Fundoplication

When medical management fails, patients with demonstrable high-volume liquid reflux and lower sphincter incompetence are often candidates for surgical intervention, often done using a laparoscopic surgical technique. The goal of surgery is to restore competence of the lower esophageal sphincter, and the outcome measures for LPR include demonstration of reduced pharyngeal reflux episodes.

Speech Therapy and Rehabilitation Techniques

Eherer and colleagues41 in a randomized controlled study, showed that actively training the diaphragm muscle by breathing exercise, can improve reflux disease.

Exercises to relieve pharyngolaryngeal tension, voice exercises, and vocal tract voice hygiene to relieve discomfort and tension have provided significant results in reducing persistent globus symptoms.42

RECOMMENDATIONS

The algorithm in Figure 9 summarizes an approach to assessment and management of LPR-induced hoarseness. It begins with clinical evaluation and progresses to an empirical trial of lifestyle and dietary changes and initiation of PPI therapy. Although most patients can experience symptomatic improvement in 3 months, it often takes at least 6 months for the laryngeal symptoms and related physical findings to resolve.43 Unlike GERD, treatment for LPR must be more aggressive and prolonged in many cases to achieve28,44resolution. Patients whose LPR has resolved should have drugs titrated off, while others who show signs of improvement should be treated with omeprazole, 40 mg (or an equivalent PPI), twice daily 30–60 minutes before meals.

Cases that fail to substantially improve with aggressive medical management over 3 months require definitive assessment. Ambulatory MCII with pH monitoring is currently the most effective way to demonstrate LPR. Where such technology is not available, multichannel pH monitoring remains a well-tested option. Mucosal injury, hiatal hernia, and other esophageal pathology such as Barrett esophagus should be documented by esophagoscopy (transnasal esophagoscopy or EGD). Barium swallow esophagoscopy, manometry, and MCII with manometry can be helpful in demonstrating pathology, describing dysmotility problems, and guiding the surgeon in planning fundoplication surgery. Recent studies suggest that those with moderate to severe reflux detected during EGD and/or pH monitoring with concomitant typical symptoms may be more likely to have reflux as the cause for their extraesophageal symptoms. Patients whose LPR fails to resolve after definitive medical or surgical treatment must be followed indefinitely with careful examination of the upper aerodigestive tract for signs of complications and malignancy.45

CONCLUSION

The diagnosis of extraesophageal reflux is difficult due to the lack of gold standard diagnostic criteria for extraesophageal symptoms of GERD. Esophagogastroduodenoscopy and esophageal pH and impedance monitoring are inadequate diagnostic tools for definitively establishing a causal link between reflux and patients’ chronic symptoms. Therefore, markers for LPR and reflux-associated laryngitis, such as RSI and RFS may be useful parameters, and can be easily included in the daily clinical care of patients suspected of having LPR and are helpful in identifying patients who have a high likelihood of a favorable response during PPI treatment. Empirical PPI therapy is recommended as an initial approach to diagnose and treat LPR symptoms. Diagnostic testing with EGD, 24-hour esophageal pH and/or impedance monitoring is usually reserved for those who continue to be symptomatic despite initial empiric trial of PPI therapy. Though PPIs are the main-stay in the treatment of LPR, lifestyle modifications are essential for its success.

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