LPR2002

Laryngopharyngeal reflux 2002: a new paradigm of airway disease. (Introduction).
Our purpose in writing this supplement is to provide an overview of laryngopharyngeal reflux (LPR). This supplement is not all-encompassing; some of the material presented is controversial; and we recognize that it does represent the bias of physicians at the Center for Voice Disorders of Wake Forest University. Furthermore, we understand that we raise as many questions as we answer. Still, we hope that this supplement will serve as a useful summary of LPR for clinicians, and that it will stimulate others in the research arena.
Background
It is likely that gastroesophageal reflux disease (GERD) was recognized in antiquity.
In 1618, Fabricius described the gastroesophageal junction, which he referred to as cardia, a term he attributed to Galen (ca. 200 AD). (1) Galen had coined the term because symptoms arising from the gastroesophageal junction could mimic those arising from the heart. (1) It was not until the 20th century, however, that the relationship between symptoms and gastroesophageal reflux (GER) was established. (2,3)
Even though the distally lighted esophagoscope had been invented by Chevalier Jackson in 1890, (1) for the first half of the 20th century he and his contemporaries did not understand GER. For example, they thought that esophageal strictures were caused by inflammatory diseases (e.g., tuberculosis) that arose in the mediastinum or below the diaphragm. In 1935, Winkelstein first described peptic esophagitis in adults.
(2) It was not until 1950 that GERD was first described in children. (3)
In 1968, laryngopharyngeal reflux (LPR)--that is, GERD that affects the larynx and pharynx--was described in relationship to contact ulcers and granulomas of the larynx. (4,5) However, relatively few reports of LPR/ GERD were published in the otolaryngology literature between 1970 and the mid-1980s. (6-20) GERD patients who did not have heartburn were considered to have atypical GERD, and it was the prevailing belief that laryngopharyngeal symptoms were not the result of actual reflux of gastric contents into the throat, but rather the result of vagally mediated reflexes.
To document the presence of acid in the pharynx of presumed LPR patients, Wiener
et al used both an esophageal pH probe and a pH probe placed in the pharynx just above the upper esophageal sphincter. (21) Patients actually wore two pH boxes, and the two pH probes were piggy-backed together with small dental rubber bands. Published in 1987, preliminary data from patients with clinical LPR who had undergone ambulatory 24-hour double-probe (simultaneous pharyngeal and esophageal) pH monitoring documented that acid was present in the pharynx of most of these patients. (21)
In 1989, Wiener et al reported the results of double-probe pH monitoring in a series of 32 otolaryngology patients with clinical LPR; 78% of them had pH-documented LPR.
(22) Analysis of the pH tracings made it apparent that the pattern of reflux in LPR was different from that usually seen in GERD; the LPR patients had predominantly upright (daytime) reflux. (22) This finding was new and surprising, because most patients with GERD had been previously shown to be predominantly supine (nocturnal) refluxers. (1) In addition, fewer than one-third of the LPR patients had esophagitis (by esophagoscopy with biopsy). (22) Thus, it appeared early on that the patterns and mechanisms of LPR might be different from those of classic GERD (figure). But the reason LPR patients were upright refluxers without heartburn or esophagitis was still unknown.
Areas of ongoing research
Much of the subsequent LPR research has been focused on seven areas: (1) associations with other diseases, (2) symptoms and findings, (3) mechanisms, (4) neurophysiologic reflexes, (5) diagnostic tests, (6) treatment outcomes, and (7) cell biology.
LPR association data. The goal of this type of research is to show the association between certain medical conditions and the presence of LPR by clinical and
reflux-testing criteria. (1,23-49)
Defining the symptoms and findings of LPR. Many studies have sought to define the clinical parameters of LPR. (1,50,51)
LPR mechanisms. (52-54) Why is LPR different from GERD? Why do LPR patients have upright reflux and not esophagitis or heartburn? How are the mechanisms of LPR different from those of GERD?
Neurophysiologic (vagal) reflexes. Using experimental animal models, investigators have begun to examine the neurophysiologic mechanisms and pathophysiology of LPR, reflux-related laryngospasm, asthma, and sudden infant death snydrome. (55-59)
New diagnostic tests for LPR. Although double-probe pH testing is an excellent diagnostic test, it has its limitations. Since 1997, our laboratory has been working to develop sensitive immunoassays for human pepsin. Our goal is to develop noninvasive, inexpensive tests for LPR. Other new diagnostic methods (e.g., impedance measurement) are also on the horizon. (60-62)
Treatment outcomes. Outcomes data have become increasingly important in clinica l medicine. Outcomes studies have been and still are being conducted in LPR. (51)
Cell biology. Investigations of the impact of reflux on a cellular level are being
conducted. In 1998, an international collaborative research network of basic scientists and clinicians was established. Preliminary data suggest that laryngeal epithelium is far more sensitive to reflux-related injury than is esophageal epithelium and that peptic injury can occur at a pH level of 5.0 or more. (63,64)
LPR is not GERD
Despite discoveries that have yielded a better understanding of LPR and how it differs from GERD, much is still not known. LPR remains controversial, partly because the gastroenterology model of reflux disease (i.e., GERD) does not seem to apply to patients with LPR. The term laryngopharyngeal reflux itself was coined because otolaryngologists wanted a new diagnostic term to designate reflux in otolaryngology patients. The clinical dichotomy of reflux patients who are seen by gastroenterologists and those who are seen by otolaryngologists warrants the use of two different diagnostic designations. Several other terms have been used for LPR in the medical literature (table).
The prevalence of GERD and of LPR is unknown, but each has been estimated. Reportedly, 10% of the American population has heartburn on a daily basis, and as many as one-third has it less often. (1) In 1988, we estimated that approximately 10% of patients with laryngeal and voice disorders had LPR. (65) In 2000, a prospective study of 113 patients with laryngeal and voice disorders found that 57 (50%) had
pH-documented reflux. (46)
A study to determine the prevalence of LPR symptoms and findings in a
community-based cohort found that they were common in "normals." (66) The mean age of the 100 volunteers was 60 years, and none of them had a history of reflux disease or took any antireflux medication. However, 35% of these subjects reported one or more LPR symptoms, and 64% had one or more LPR findings on examination.
A host of controversies remains
LPR is ubiquitous. If one combines all the clinical and normative data, it would be easy to conclude that at least one-third of the American population older than 40 years has LPR. Although this is speculation, if one combines the potential size of the LPR and GERD populations, as many as 100 million Americans might have reflux. In truth, the epidemiology of LPR and GERD remains to be studied.
But who really has LPR? In fact, what is LPR? Is it simply a combination of certain symptoms and findings? How is the diagnosis made? Indeed, there has been controversy about how to diagnose LPR. At our center, we employ a reflux symptom index (RSI) as a clinical tool to compare groups of patients and to compare the symptoms of individual patients during the course of treatment. (50) We have also instituted a standardized method of grading the laryngeal findings of LPR, which we
call the reflux finding score (RFS). (51) This tool has proved to be very useful in the diagnosis and treatment of LPR. The RSI and the RFS are both validated outcomes instruments. Based on data obtained from normals, an RSI of more than 10 and an RFS of more than 5 are abnormal. (66)
Why is LPR controversial? Not only are the symptoms and findings of LPR not clearcut, more important is the fact that there is no ideal diagnostic test battery for evaluating LPR. Traditional diagnostic criteria for GERD simply do not apply to LPR. Why is a pH value of less than 4.0 defined as a significant reflux event? Do patients with LPR require esophageal screening for esophagitis and other complications? Why do LPR patients require relatively high-dose (twice-daily) treatment with
proton-pump inhibitors for many months? (67) What are the manifestations of
LPR--does it cause laryngeal cancer, subglottic stenosis, laryngospasm, and scarring complications following vocal fold surgery? The controversies surrounding LPR are grounded in uncertainty. The laryngopharyngeal symptoms and findings of LPR are nonspecific. Furthermore, there are no unambiguous diagnostic or treatment outcomes criteria.
LPR controversies can be summarized in five categories: (1) symptoms, (2) clinical findings, (3) diagnostic testing, (4) interpretation of findings, and (5) treatment.
Symptoms. There is no universal agreement on the symptoms of LPR. When is postnasal drip caused by a nasal or sinus problem, and when is it actually a red herring? Could the presence of too much mucus in the nose and throat be the result of direct irritation from LPR or the result of vagally mediated responses to throat irritation? What happens to patients with sinus symptoms and LPR when the LPR is effectively controlled?
Clinical findings. There is no clear consensus about the findings and clinical manifestations of LPR. Although an extremely high incidence of LPR has been reported in patients with subglottic stenosis, (1) the role of LPR in the development of subglottic stenosis remains controversial. (In my opinion, virtually all airway stenosis and complications following intubation are the result of LPR. If it were not for LPR, would mucosal abrasions and ulcers heal uneventfully? Is it not the inflammation of LPR that likely continues the nonhealing process?)
Diagnostic testing. Controversy surrounds diagnostic testing for LPR, including pH monitoring. How should it be performed? Should one use a single or double probe? Should manometry be performed first in order to ascertain sphincter location? Which patients should undergo pH monitoring? How is it interpreted? (At our center, we believe that full esophageal manometry of the pharynx and esophageal sphincter is essential in patients with LPR to ensure accurate pH data. (68) Furthermore, we feel that the proximal probe must be located in the pharynx. We perform ambulatory
24-hour double-probe simultaneous [esophageal and pharyngeal] pH monitoring, with
probe placement based on manometric measurement. (69)
Interpretation of findings. Interpretation of pharyngeal reflux events is controversial. Should we use a pH level of less than 4.0 as the pH threshold for determining reflux in the pharynx? Is laryngeal epithelium more sensitive to acid and peptic injury than is esophageal epithelium? Significant peptic injury to laryngeal epithelium has been reported in patients whose pH level was 5.0. (64) Would it...。