Evaluation and Management of Laryngopharyngeal

Reflux
Charles N. Ford
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 CLINICAL REVIEW CLINICIAN’S CORNER

Evaluation and Management

of Laryngopharyngeal Reflux
Charles N. Ford, MD Context Laryngopharyngeal reflux (LPR) is a major cause of laryngeal inflammation

L
ARYNGOPHARYNGEAL REFLUX and presents with a constellation of symptoms different from classic gastroesopha-
geal reflux disease.
(LPR) is the result of retro-
grade flow of gastric contents to Objective To provide a practical approach to evaluating and managing cases of LPR.
the laryngopharynx, where it Evidence Acquisition The PubMed database and the Ovid Database of System-
comes in contact with tissues of the up- atic Reviews were systematically searched for laryngopharyngeal reflux, laryngopha-
per aerodigestive tract. It has been re- ryngeal reflux fundoplication, laryngopharyngeal reflux PPI treatment, and gastro-
ported in up to 10% of patients pre- esophageal reflux AND laryngitis. Pertinent subject matter journals and reference lists
senting to an otolaryngologist’s office,1 of key research articles were also hand-searched for articles relevant to the analysis.
and more than 50% of patients with Evidence Synthesis Reflux of gastric contents is a major cause of laryngeal pathol-
hoarseness have been found to have re- ogy. The pathophysiology and symptom complex of LPR differs from gastroesophageal
flux-related disease.2 There is a dan- reflux disease. Laryngeal pathology results from small amounts of refluxate—typically
ger in failing to recognize LPR, while occurring while upright during the daytime—causing damage to laryngeal tissues and
producing localized symptoms. Unlike classic gastroesophageal reflux, LPR is not usu-
overdiagnosis of LPR can lead to un- ally associated with esophagitis, heartburn, or complaints of regurgitation. There is no
necessary costs and missed diagnoses. pathognomonic symptom or finding, but characteristic symptoms and laryngoscopic find-
When a medical practitioner fails to rec- ings provide the basis for validated assessment instruments (the Reflux Symptom Index
ognize LPR, patients have prolonged and Reflux Finding Score) useful in initial diagnosis. There are 3 approaches to confirm-
symptoms and delayed healing.3 In- ing the diagnosis of LPR: (1) response of symptoms to behavioral and empirical medical
flamed laryngeal tissues are more eas- treatment, (2) endoscopic observation of mucosal injury, and (3) demonstration of re-
ily damaged from intubation, have a flux events by impedance and pH-monitoring studies and barium swallow esophagram.
greater risk of progressing to forma- While pH monitoring remains the standard for confirming the diagnosis of gastroesopha-
geal reflux, the addition of multichannel intraluminal impedance technology improves
tion of contact ulcers and granulo-
diagnostic accuracy for describing LPR events. Ambulatory multichannel intraluminal im-
mas, and often evolve to symptomatic pedance assessment allows for identification of gaseous as well as liquid refluxate and
subglottic stenosis4 and lower airway detection of nonacid reflux events that are likely significant in confirming LPR. Al-
disease. In a recent report, LPR symp- though some patients respond to conservative behavioral and medical management, as
toms were found to be more prevalent is the case with gastroesophageal reflux, most require more aggressive and prolonged
in patients with esophageal adenocar- treatment to achieve regression of symptoms and laryngeal tissue changes. Surgical in-
cinoma than were typical gastroesopha- tervention such as laparoscopic fundoplication is useful in selected recalcitrant cases with
geal reflux symptoms, and they often laxity of the gastroesophageal sphincter.
represented the only sign of disease.5 Conclusions Laryngopharyngeal reflux should be suspected when the history and
Heightened awareness of LPR can lead laryngoscopy findings are suggestive of the diagnosis. Failure to respond to a 3-month
to overdiagnosis of the condition be- trial of behavioral change and gastric acid suppression by adequate doses of proton
cause the typical LPR symptoms (ex- pump inhibitor medication dictates need for confirmatory studies. Multichannel intra-
luminal impedance and pH-monitoring studies are most useful in confirming LPR and
cessive throat clearing, cough, hoarse-
assessing the magnitude of the problem.
ness, and globus pharyngeus [a
JAMA. 2005;294:1534-1540 www.jama.com
sensation of a lump in the throat]) are
nonspecific6 and can also be caused by Author Affiliation: Department of Surgery, Division of
EVIDENCE ACQUISITION
infections, vocal abuse, allergy, smok- Otolaryngology, University of Wisconsin, Madison.
The PubMed database was systemati- Corresponding Author: Charles N. Ford, MD, Univer-
ing, inhaled environmental irritants, sity of Wisconsin Clinical Science Center, 600 High-
cally searched using the natural lan-
and alcohol abuse.7 land Ave, K4/714, Madison, WI 53792 (ford@surgery
guage phrases laryngopharyngeal .wisc.edu).
reflux, laryngopharyngeal reflux fundo- Clinical Review Section Editor: Michael S. Lauer, MD.
CME available online at plication, and laryngopharyngeal re- We encourage authors to submit papers for con-
www.jama.com sideration as a “Clinical Review.” Please contact
flux PPI treatment. These phrases were Michael S. Lauer, MD, at [email protected].

1534 JAMA, September 28, 2005—Vol 294, No. 12 (Reprinted) ©2005 American Medical Association. All rights reserved.

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 MANAGEMENT OF LARYNGOPHARYNGEAL REFLUX

Table. Clinical Clues to Distinguish LPR From Other Causes of Hoarseness

Rhinosinusitis Benign Malignant
LPR Infection (Postnasal Drip) Allergy Vocal Fold Lesion Vocal Fold Lesion
Hoarseness Fluctuates Acute, resolves Acute/chronic or Fluctuates Constant Progressive
characteristic recurrent
Throat pain Common (with Yes Uncommon No From secondary Late (local and
cough, throat muscle tension referred)
clearing)
Laryngeal Edema, Erythema, edema Secretions (thick, Edema, clear Nodules, polyps, Ulcerative or exophytic
findings granuloma, discolored), secretions, cysts, scars (red-white mass),
erythema, edema bluish mucosa stiff
pseudosulcus
Aggravating Smoking, obesity, Systemic infection, LPR, allergy, Environment, Smoking, vocal Smoking (common),
factors diet/lifestyle immunosuppression smoking seasonal trauma, LPR LPR, ethanolism
Abbreviation: LPR, laryngopharyngeal reflux.

used individually, with no language or tecting the upper aerodigestive tract ryngeal epithelium,wass absent in 64%
date restrictions. PubMed was then from reflux injury: the lower esopha- (47/75) of biopsy specimens from la-
searched using the Medical Subject geal sphincter, esophageal motor func- ryngeal tissues of LPR patients.11
Heading terms gastroesophageal reflux tion with acid clearance, esophageal
and laryngitis. These terms were com- mucosal tissue resistance, and the up- Diagnosis
bined using the AND operator and were per esophageal sphincter.1 The deli- History. It is important for physicians
limited by language to English, by date cate ciliated respiratory epithelium of to appreciate the potential signifi-
range to 2001-2005, and by publica- the posterior larynx that normally func- cance of hoarseness and the relative
tion type to randomized controlled tions to clear mucus from the tracheo- nonspecificity of laryngitis. Laryngitis
trial OR clinical trial. The Ovid ver- bronchial tree is altered when these bar- is a nonspecific designation of laryn-
sion of the Cochrane Database of riers fail, and the resultant ciliary geal inflammation.12 Often, it is mild
Systematic Reviews was also searched dysfunction causes mucus stasis.9 The and resolves spontaneously. When per-
using the key-word combination of subsequent accumulation of mucus sistent, laryngitis must be further de-
laryngitis.mp and reflux.mp. produces postnasal drip sensation and fined based on probable etiologic fac-
All retrieval sets generated by the provokes throat clearing. Direct reflux- tors: viral or bacterial infection, allergy,
PubMed and Ovid searches were re- ate irritation can cause coughing and vocal trauma, postnasal discharge, or
viewed for relevant citations address- choking (laryngospasm) because sen- LPR (TABLE). Persistent or progres-
ing core issues of diagnosis, assess- sitivity in laryngeal sensory endings is sive hoarseness lasting beyond 2 to 3
ment, and management. The reference up-regulated by local inflammation.9 weeks requires examination of the la-
lists of all relevant citations were re- This combination of factors can lead to ryngopharynx to rule out cancer and
viewed for further material describing vocal fold edema, contact ulcers, and other serious conditions. This is gen-
validation of diagnostic instruments and granulomas that cause other LPR- erally considered good practice; how-
basic science addressing pathogenesis associated symptoms: hoarseness, glo- ever, laryngeal examination is particu-
and evolving technology. References in bus pharyngeus, and sore throat.1 larly important in suspected LPR
the Cochrane Database of Systematic Recent investigations suggest that because of the apparent known asso-
Reviews protocol for reviewing acid re- vulnerable laryngeal tissues are pro- ciation of LPR and upper aerodiges-
flux treatment of hoarseness were par- tected from reflux damage by the pH- tive tract cancer.5,13
ticularly useful. regulating effect of carbonic anhy- Laryngopharyngeal reflux should be
drase in the mucosa of the posterior suspected when clinical history and ini-
EVIDENCE SYNTHESIS larynx. 10 Carbonic anhydrase cata- tial findings are suggestive. Failure to
Pathogenesis lyzes hydration of carbon dioxide to appreciate LPR as different from GERD
Laryngopharyngeal reflux differs from produce bicarbonate; this protects tis- has been a major source of skepticism
gastroesophageal reflux disease (GERD) sues from acid refluxate. In the esopha- about the diagnosis in the past. Kouf-
in that it is often not associated with gus, there is active production of bi- man1 was the first to clearly distin-
heartburn and regurgitation symp- carbonate in the extracellular space that guish LPR from GERD, noting that in
toms.8 The larynx is vulnerable to gas- functions to neutralize refluxed gas- a combined reported series of 899 pa-
tric reflux, so patients often present with tric acid. There is no active pumping tients, throat clearing was a complaint
laryngopharyngeal symptoms in the ab- of bicarbonate in laryngeal epithelium of 87% of LPR patients vs 3% of those
sence of heartburn and regurgitation.8 and carbonic anhydrase isoenzyme III, with GERD, while only 20% of LPR pa-
There are 4 physiological barriers pro- expressed at high levels in normal la- tients complained of heartburn vs 83%
©2005 American Medical Association. All rights reserved. (Reprinted) JAMA, September 28, 2005—Vol 294, No. 12 1535

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MANAGEMENT OF LARYNGOPHARYNGEAL REFLUX

greater than 13 is considered abnor- cal fold edema, diffuse laryngeal edema,
Figure 1. Reflux-Induced Granulomas and
Pseudosulcus mal. When hoarseness is a prominent posterior commissure hypertrophy,
symptom, acoustic voice analysis mea- granuloma, and thick endolaryngeal
suring frequency, intensity, perturba- edema. The results could range from 0
tion, and signal-to-noise ratio pro- (normal) to 26 (worst possible score).
vides an objective way to document Based on their analysis, one can be 95%
symptom severity and progress of the certain that a patient with a Reflux Find-
disease.2 ing Score of 7 or more will have LPR.
Laryngoscopy. Nonspecific signs of Confirming Reflux. There are 3 ap-
laryngeal irritation and inflammation are proaches to confirming the diagnosis:
usually seen, but several findings are response of symptoms to behavioral and
highly suggestive of LPR. Although not empirical medical treatment, endo-
pathognomonic, thickening, redness, scopic observation of mucosal injury,
and edema concentrated in the poste- and demonstration of reflux events by
rior larynx—“posterior laryngitis”—is multichannel impedance and pH-
a common finding.7 Based on a color monitoring studies. Additional stud-
analysis, Hanson and Jiang9 quantified ies, including radiography, esophageal
This rigid telescopic view shows a larynx with large
the degree of erythema as a measure of manometry, spectrophotometric mea-
bilateral granulomas based on the medial surfaces of posterior laryngitis. Other laryngo- surement of bile reflux, and mucosal bi-
the arytenoids (top). A prominent pseudosulcus is iden- scopic findings have a strong associa- opsy, can provide information useful in
tified (arrowhead), representing typical infraglottic
edema associated with laryngopharyngeal reflux. tion with LPR. Contact granuloma was targeting therapy.
found to be associated with pH moni- Because many patients respond well
toring–confirmed cases of LPR in 65% to behavioral modification and initial
in the GERD group. An international to 74% of patients.16,17 Frequently, the medical management, an acid suppres-
survey of American Bronchoesophago- medial edge of the vocal fold appears to sion trial is a frequently used ap-
logical Association members revealed have a linear indentation due to diffuse proach to initial diagnosis.22 The main-
that the most common LPR symptoms infraglottic edema (F IGURE 1). Al- stay of empirical treatment is proton
were throat clearing (98%), persistent though this gives the illusion of a patho- pump inhibitor (PPI) medication for at
cough (97%), globus pharyngeus logical condition of the vocal fold called least 3 months.
(95%), and hoarseness (95%).14 Based sulcus vocalis, in which there is a me- Endoscopic examination should in-
on a careful study of pH probe– dial edge concavity of the vocal fold clude flexible or rigid laryngoscopy in
confirmed LPR cases, Belafsky et al15 de- (sulcus) due to fibrosis and tissue loss, all suspected cases. Transnasal esopha-
veloped a useful self-administered tool, it lacks the fibrotic changes of patho- goscopy and esophagogastroduodenos-
the Reflux Symptom Index, that can logical sulcus vocalis.18 This finding is copy (EGD) are useful in detecting char-
help clinicians assess the relative de- termed pseudosulcus and has been re- acteristic associated mucosal injury,
gree of LPR symptoms during initial ported in as much as 90% of LPR esophagitis, and Barrett esophagus.
evaluation and after treatment. Pa- cases.19 In a comparison of 30 LPR pa- Overall, EGD and 24-hour pH-
tients are asked to use a 0- to 5-point tients and 30 controls, those with pseu- monitoring studies have proven less
scale to grade the following symp- dosulcus were 2.5 times more likely to useful in detecting LPR than in identi-
toms: (1) hoarseness or voice prob- have pH testing–confirmed LPR fying GERD. While EGD reveals esoph-
lem, (2) throat clearing, (3) excess (P⬍.001).20 Although the sensitivity ageal lesions in 50% of typical GERD
throat mucus or postnasal drip, (4) dif- and specificity of finding pseudosul- patients, it is abnormal in less than 20%
ficulty swallowing, (5) coughing after cus in LPR patients were only 70% and of LPR laryngitis patients.23
eating or lying down, (6) breathing dif- 77%, respectively, pseudosulcus re- Demonstration of reflux events is best
ficulties or choking spells, (7) trouble- mains highly suggestive of LPR. achieved with ambulatory multichan-
some or annoying cough, (8) sensa- Since there is no pathognomonic LPR nel intraluminal impedance (MCII) and
tion of something sticking or a lump in finding, Belafsky et al21 developed an pH-monitoring studies. 24 This ap-
the throat, and (9) heartburn, chest 8-item clinical severity scale for judg- proach is based on changes in resis-
pain, indigestion, or stomach acid com- ing laryngoscopic findings, the Reflux tance to alternating current between a
ing up. The Reflux Symptom Index Finding Score, which appears to be use- series of metal electrodes produced by
score in untreated LPR patients was sig- ful for assessment and follow-up of LPR intraluminal gas, liquid, or bolus. When
nificantly higher than in controls (21.2 patients. They rated 8 LPR-associated combined with pH transducers, it
vs 11.6; P⬍.001). Since the 95% up- findings on a variably weighted scale makes it possible to give a more com-
per confidence limit for controls was from 0 to 4: subglottic edema, ventricu- plete description of reflux events.25 Not
13.6, a Reflux Symptom Index score lar obliteration, erythema/hyperemia, vo- only can acid and nonacid reflux events
1536 JAMA, September 28, 2005—Vol 294, No. 12 (Reprinted) ©2005 American Medical Association. All rights reserved.

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 MANAGEMENT OF LARYNGOPHARYNGEAL REFLUX

be detected but, also, liquid (de- versy regarding their efficacy. A 3-month cant decrease in pharyngeal reflux (7.9
creased impedance) as well as gaseous empirical trial is a cost-effective ap- to 1.6 episodes per 24 hours; P⬍.05)
(increased impedance) events can be proach to initial assessment and man- and esophageal acid exposure (7.5% to
identified. Although controversy ex- agement.29,30 Responders can be weaned, 2.1%; P⬍.05) following basic laparo-
ists, an LPR event is evident when pH while nonresponders should undergo scopic Nissen fundoplication surgery.
in the proximal sensor abruptly drops studies to confirm LPR. Fundoplication appears superior to
to less than 4 during or immediately af- Other drugs have been used to treat medical management in preventing Bar-
ter distal acid exposure (exposure near LPR. Ranitidine has proven a more rett metaplasia.39 Although there is in-
the lower esophageal sphincter) and potent inhibitor of gastric secretion than terest in recent nonfundoplication en-
LPR is confirmed when total acid ex- cimetidine and is the H2-receptor antago- doscopic techniques (Bard EndoCinch
posure time (percentage of time dur- nist of choice,31 although it has been System for endoluminal plication, C. R.
ing 24-hour monitoring when the sen- found to be of limited value in treating Bard, Murray Hill, NJ; Stretta System for
sor detects pH levels ⬍4) is more than LPR.32 Prokinetic agents that accelerate radiofrequency-induced thermal in-
1%.24 Reflux is often associated with esophageal clearance and increase lower jury, Curon Medical, Fremont, Calif;
esophageal dysmotility, including non- esophageal sphincter pressure have fallen and Enteryx liquid polymer injection,
progressive (tertiary) contractions, in- out of favor because of reported adverse Boston Medical, Natick, Mass) to im-
creased amplitude and duration of effects of ventricular arrhythmias and prove lower esophageal sphincteric
contractions, and increased tone.1 Mul- diarrhea.33 Cisapride has been discon- function, there are no controlled stud-
tichannel intraluminal impedance soft- tinued because of such serious adverse ies and there is no long-term fol-
ware technology combined with ma- effects. Tegaserod is a prokinetic agent low-up evidence to support their use.40
nometry allows for graphic displays of that was recently demonstrated to
simulated esophageal motility, sphinc- decrease reflux and lower esophageal CONTROVERSIES
ter competence, and bolus transport, so sphincter relaxation events34 and that we While there is an increased apprecia-
the use of barium swallow studies is have found useful in treating some LPR tion of LPR as distinct from GERD, con-
more limited in LPR assessment. cases with associated esophageal dyski- troversy remains regarding how to con-
nesia. Sucralfate is a polysulfated salt of firm the diagnosis and what comprises
Treatment sucrose that may be helpful as an adjunct appropriate medical management. In
Patient Education and Behavioral in protecting injured mucosa from mild LPR cases, symptoms and physi-
Change. Patients with LPR should be harmful effects of pepsin and acid.35,36 cal findings lack sufficient specificity;
educated as to the nature of the prob- Antacids (sodium bicarbonate–, alumi- similar symptoms can result from smok-
lem and counseled on helpful behav- num-, and magnesium-containing ing, toxic inhalants, allergies, and post-
ioral and dietary changes.26 Important over-the-counter antacids) may relieve nasal discharge. Assessing treatment
behavioral changes include weight loss, GERD symptoms but do not play a role regimens is complicated because clini-
smoking cessation, and alcohol avoid- in LPR management.26 cal trials are vulnerable to placebo effect,
ance. Ideal dietary changes would re- Surgery. When medical manage- uncontrolled behavioral changes, and
strict chocolate, fats, citrus fruits, car- ment fails, patients with demon- the variable natural history of LPR.23,41,42
bonated beverages, spicy tomato- strable high-volume liquid reflux and Apparently, 25% of LPR patients expe-
based products, red wines, caffeine, and lower sphincter incompetence are of- rience spontaneous resolution of symp-
late-night meals. Such behavioral ten candidates for surgical interven- toms and 50% have a chronic course of
changes appear to be an indepen- tion. Fundoplication, either complete disease, with intermittent exacerba-
dently significant variable in determin- (Nissen or Rossetti) or partial (Toupet tions and remissions.1
ing response to medical therapy.27 Edu- or Bore), is the most common proce-
cation should include the optimal dure performed, and the laparoscopic Physical Findings
schedule for taking PPI medications approach is preferred.2 The goal of sur- Laryngoscopic findings can be mislead-
(omeprazole, esomeprazole, rabepra- gery is to restore competence of the ing, as shown in several studies in which
zole, lansoprazole, and pantoprazole), lower esophageal sphincter, and the asymptomatic participants revealed
which work best when taken 30 to 60 outcome measures for LPR include findings similar to those seen in LPR-
minutes before meals. demonstration of reduced pharyngeal proven patients. Lundy et al43 found
Medical Management. There are 4 reflux episodes. Excellent results have posterior erythema in 73% of asymp-
categories of drugs used in treating LPR: been reported in 85% to 95% of reflux tomatic singing students and Hicks
PPIs, H2-receptor antagonists, proki- cases37 but results with LPR are not as et al41 found tissue changes associated
netic agents, and mucosal cytopro- impressive.22 Focusing on a carefully with LPR in a group of more than 100
tectants. Proton pump inhibitors are screened group of patients with demon- asymptomatic volunteers. Lack of a reli-
considered the mainstay of medical treat- strable extraesophageal reflux (LPR), able clinical marker has confounded
ment,28 although there is some contro- Oelschlager et al38 reported a signifi- progress in the diagnosis and treat-
©2005 American Medical Association. All rights reserved. (Reprinted) JAMA, September 28, 2005—Vol 294, No. 12 1537

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MANAGEMENT OF LARYNGOPHARYNGEAL REFLUX

ment of LPR.23 Some trials based on depletion of carbonic anhydrase isoen- related to the wide-open pharynx and
clinical diagnosis have been misinter- zyme III in documented LPR cases.45 intermittent probe drying. The re-
preted because of lax inclusion crite- cently developed Bravo wireless pH-
ria. The symptoms and physical find- pH Monitoring monitoring system (Medtronic Inc,
ings of mild LPR can be confused with Hydrogen ion concentration monitor- Shoreview, Minn) allows for precise en-
other laryngeal inflammations and non- ing is considered the gold standard in doscopic placement of the pH trans-
pathological variations. Since patients detecting GERD, but it is less reliable in ducer at the upper esophageal sphinc-
with advanced LPR and obvious pos- confirming LPR.46 Variability in testing ter. A pinch of esophageal mucosa is
terior laryngitis probably differ from methods and lack of agreement on nor- used to secure the Bravo capsule, and the
patients with milder cases that might mative values have raised questions patient wears a pager-sized monitor dur-
have alternative etiologies; future effi- about the sensitivity of pH-monitoring ing 48 hours of normal activity. The cap-
cacy studies should be rigorous in their studies for detecting LPR.44,47,48 In some sule passes in 3 to 5 days with the su-
exclusion criteria and/or stratify patients studies, the proximal probe was placed perficial sloughing of mucosa. This has
in the treatment group. 44 A break- below the upper esophageal sphincter been proven more effective in children
through in LPR diagnosis may evolve and in others in the hypopharynx, where and some adults who fail to tolerate an
from recent immunohistochemical it is considered closer to the site of in- external catheter.50
studies of laryngeal biopsy specimens jury.49 High placement of the proximal Disagreement about normative val-
showing concentration of pepsin and probe is subject to spurious drops in pH ues adds to the controversy. An abrupt
decrease in pH to less than 4 in the proxi-
mal probe following or synchronous with
Figure 2. Algorithm for Assessment and Management of LPR a drop at the lower esophageal sphinc-
ter is considered a default cutoff value,51
Initial Assessment
Patient With Possible LPR but this is largely based on lower esoph-
ageal standards applied to GERD. In the
Reflux Symptom Index (History, Symptoms) >13 hypopharynx, a drop to less than 5 is
and probably a more reliable indicator of
Reflux Finding Score (Laryngoscopy) >7
proximal reflux because neutralizing fac-
tors such as saliva and airway secre-
Empirical Therapeutic Trial
Lifestyle tions can raise pH values.52 Failure to
Diet
PPI Therapy
demonstrate clinical correlation in pH
studies can result from not recognizing
3-mo Follow-up Assessment
the minimal amount of gastric reflux-
ate necessary to cause laryngeal inflam-
mation (in patients with LPR) or from
Symptoms Resolved Symptoms Improved Symptoms Unchanged or Worse
not considering alternative sources of la-
ryngeal inflammation in control groups.48
Titrate PPI Therapy Increase Dose of PPI
An important recent meta-analysis of
Continue Lifestyle and 16 double pH-probe studies showed
Diet Modifications
consistency and accuracy in distinguish-
ing healthy persons vs those with LPR
6-mo Follow-up Assessment
where techniques were tightly con-
trolled.51 Upper probe placement at 2 cm
above the upper esophageal sphincter
Symptoms Symptoms
Resolved not Resolved was considered critical; higher place-
ment reduces contact of the sensor with
Titrate PPI Definitive Assessment (Perform 1 or More Studies) mucosa, drying, and false-positive read-
Therapy Multichannel Impedance and pH Monitoring (Demonstrate Reflux) ings, whereas events at or below the
TNE or EGD (Document Pathology)
sphincter fail to correlate with LPR
Manometry (Assess Etiology)
Barium Swallow symptoms. This study affirmed that
while healthy persons experienced some
When the history and clinical examination are suggestive of laryngopharyngeal reflux (LPR), patients are reflux events, the acid exposure time per-
instructed in lifestyle and dietary changes. Proton pump inhibitor (PPI) therapy is started and the patient centage is very reliable in differentiat-
is reassessed 3 months later. Failure to respond dictates a pathway to definitive assessment and continued
monitoring. Those showing improvement proceed with more medical treatment, whereas those with resolu- ing persons with and without LPR. Us-
tion of symptoms have PPI treatment tapered. TNE indicates transnasal esophagoscopy; EGD, ing a mixed-effects model, LPR was
esophagogastroduodenoscopy.
found to be a statistically significant risk
1538 JAMA, September 28, 2005—Vol 294, No. 12 (Reprinted) ©2005 American Medical Association. All rights reserved.

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 MANAGEMENT OF LARYNGOPHARYNGEAL REFLUX

factor for experiencing objective reflux therapy for LPR, Steward et al27 found well-tested option. Mucosal injury, hia-
events (odds ratio, 9.19; 95% confi- that lifestyle modification for 2 months, tal hernia, and other esophageal pa-
dence interval, 5.4-15.4; P⬍.001). with or without PPI therapy, signifi- thology such as Barrett esophagus
Another problem with standard pH cantly improved chronic laryngitis should be documented by esophagos-
probe–monitoring studies is failure to ac- symptoms. In a recent open-labeled, pro- copy (transnasal esophagoscopy or
count for bouts of potentially harmful spective cohort study, Park et al56 shed EGD). Barium swallow esophagos-
gaseous and/or nonacid refluxate. This some light on the controversy. They con- copy, manometry, and MCII with ma-
is where impedance testing is supe- cluded that twice-daily dosing of PPI re- nometry can be helpful in demonstrat-
rior.24 Gaseous reflux events associated sulted in significantly higher symptom ing pathology, describing dysmotility
with small pH drops (⬎1) have been relief than daily dosing (P = .03) and problems, and guiding the surgeon in
found with significantly greater fre- noted that nonresponders improved planning fundoplication surgery. Pa-
quency in patients with LPR than in when twice-daily dosage was extended tients whose LPR fails to resolve after
those with GERD or in healthy con- from 2 to 4 months. Like Fackler et al,32 definitive medical or surgical treat-
trols. The ability to detect gaseous and they found that the addition of H2- ment must be followed indefinitely with
mixed (gaseous-liquid) events is par- antagonist therapy at bedtime was of no careful examination of the upper aero-
ticularly important in patients with LPR added benefit. Further clarification is an- digestive tract for signs of complica-
because gases are more diffusible and can ticipated based on the Cochrane Data- tions and malignancy.5
reach higher laryngeal structures. Fur- base of Systematic Reviews protocol that Financial Disclosures: None reported.
thermore, impedance testing detects po- will focus on clinical trials with atten- Acknowledgment: I thank Eric A. Gaumnitz, MD, Gas-
troenterology Section, University of Wisconsin, for his
tentially harmful nonacidic reflux. Pel- tion to randomization, selection bias, careful reading of an early version of the manuscript
legrini et al53 called attention to alkaline blinding process, and outcome assess- and helpful suggestions.
gastroesophageal reflux long ago, and ment in reviewing acid reflux treat-
REFERENCES
Galli et al54 demonstrated laryngopha- ment of hoarseness.2
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