Laryngopharyngeal reflux testing.
Reflux testing is still evolving as new technology. New criteria for determination of clinical and subclinical laryngopharyngeal reflux are surfacing. The technique and interpretation of pH monitoring, the current gold standard, are still somewhat controversial. The authors' experience and opinions are presented herein.
Testing for laryngopharyngeal reflux (LPR) can involve six different modalities: (1) the laryngeal examination, (2) ambulatory 24-hour double-probe (simultaneous esophageal and pharyngeal) pH monitoring, (3) esophageal manometry, (4) esophagoscopy or esophagography, (5) laryngeal sensory testing, and (6) intraluminal impedance monitoring. These modalities are not equally important. Impedance monitoring is still new enough that its value is as yet undetermined.
When a patient has symptoms that suggest LPR, the clinician should perform a complete otolaryngologic examination and fiberoptic laryngoscopy. The clinician should also consider pH monitoring and a screening examination of the esophagus.
LPR is best diagnosed by ambulatory 24-hour double-probe pH monitoring. (1,2) Barium esophagography, radionucleotide scanning, the Bernstein acid perfusion test, and esophagoscopy with biopsy are often negative in LPR patients. This is probably because most LPR patients do not develop esophagitis, which is typically observed in gastroenterology patients with gastroesophageal reflux disease (GERD). Traditional diagnostic tests for GERD are often falsely negative in LPR. (1,2)
Ambulatory 24-hour double-probe pH monitoring (pH-metry) is both highly sensitive and specific for LPR. (2-5) In fact, it is superior to any other diagnostic modality, including barium swallow, endoscopy, and single-probe esophageal pH testing, in the diagnosis of LPR. Furthermore, pH-metry reveals the pattern of reflux (figure 1) 50 that subsequent treatment can be custom-tailored to each patient. (2) For example, if a patient does not have supine nocturnal reflux, elevation of the head of the bed need not be recommended. Yet, despite the fact that pH-metry is considered the gold standard for LPR testing in otolaryngologic practice, there is no consensus with respect to the number of pH sensors, their location, or the interpretation of results. (2)
Importance of the pharyngeal probe. The importance of the pharyngeal sensor cannot be overemphasized. When the pharyngeal probe is positive, it is diagnostic for LPR. (1,2) Katz showed in a small number of LPR patients that reliance on only an esophageal probe can result in false-negative results. (6)
A review of a consecutive series of 334 pharyngeal-positive pH studies at our center demonstrated that 126 (38%) had normal esophageal acid exposure times in the esophageal probe. (5) In other words, the esophageal exposure times were in the normal range, but some esophageal reflux reached the pharynx. Therefore, if only a single-probe esophageal study had been performed in that group, 38% would have been falsely assumed not to have LPR. Similarly in the pediatric population, Little et al showed that 78 of 168 children (46%) with pH-documented LPR had normal esophageal acid exposure times. (7) It is clear that measuring esophageal acid exposure does not allow us to make any assumptions concerning the presence or absence of pharyngeal reflux.
One point of clarification for the reader is needed here. In the studies cited above, pharyngeal reflux occurred in the face of normal esophageal parameters. However, by definition, each pharyngeal reflux event was preceded by an esophageal reflux event. After all, the refluxate must traverse the esophagus to reach the pharynx. But in the situation described above, the percentage of time of esophageal acid exposure and/or the total number of esophageal reflux events fell within the normal range. If, for example, a 24-hour study showed a total of just 25 esophageal reflux events, that would be considered normal (in our laboratory, up to 51 reflux events per 24 hours is normal). But if some of those esophageal reflux events reached the pharyngeal probe, the patient would be diagnosed as having LPR--that is, reflux into the pharynx. Abnormal esophageal reflux by pH monitoring does not imply LPR; conversely, normal esophageal reflux by pH monitoring does not rule it out.
We believe that the proximal probe should be placed in the pharynx and not in the upper esophagus (figure 2), as has been suggested by some. Proximal esophageal reflux does not necessarily correlate with LPR. (8-10) To measure the gastric pH and extrapolate those data to imply GERD is clearly invalid. Similarly, using esophageal pH data (even at a proximal esophageal location) to prove the presence or absence of LPR is invalid, because the upper esophageal sphincter (UES) functions as the final barrier against LPR. In normals and GERD patients, experimental acid instillation into the esophagus increases the UES resting pressure, thereby enhancing its effectiveness as a barrier to LPR. (11)
Esophageal manometry. Esophageal manometry is the preferred method of guiding pH probe placement. It is our contention that the use of manometry rather than direct visual placement is vital to ensuring accurate placement of pH probes. (1,2,12) The available normative data for reflux in the esophagus are derived from standard distal probe placement 5 cm above the lower esophageal sphincter (LES). Even small degrees of variance from this position can result in significant changes in the results obtained from the esophageal pH probe. If the probe is not in the proper position, no reliable conclusions regarding esophageal acid exposure data can be made.
Using visual placement to position the proximal probe in the hypopharynx (just above the UES) is an accurate method (figure 3). (12,13) However, when one does so, the fixed distance between the proximal and distal sensors of the probe means that the distal probe is placed in an unknown position in reference to the LES. (12) Therefore, the esophageal acid exposure data cannot be interpreted as normal or abnormal.
Manometry not only accurately locates the UES and LES, but it also allows for evaluation of pharyngo-esophageal function. UES/pharyngeal manometric information is especially important in patients with dysphagia and globus pharyngeus. Finally, manometry is used to evaluate esophageal body motor function.
Definition of pharyngeal reflux
In the 1980s, the reliability of pH-metry with a pharyngeal probe was occasionally hampered by the occurrence of "pseudopharyngeal reflux" events. (1,14-16) In the early days of pH-metry, the pharyngeal probe was placed 2cm above the UES. When the pharyngeal sensor was too high in the hypopharynx, it was not in contact with the mucosa and it dried out. This led to false-positive readings. However, the pattern of pseudopharyngeal reflux events is different from that of true pharyngeal reflux events. The former are not preceded by an esophageal reflux event, and the pH drops slowly as the probe dries out. True pharyngeal reflux events are characterized by a precipitous drop in pH immediately following an esophageal reflux event. Nowadays, pseudopharyngeal reflux is not a problem. The technique in current use calls for placement of the pharyngeal probe just above the UES behind the laryngeal inlet.
We have established four criteria that must be met in order for an event to be defined as a pharyngeal reflux episode:
* a decrease in the pH level to less than 4.0 (or <5.0; see below)
* a decrease in the pharyngeal pH level immediately following distal esophageal acid exposure
* no decrease in the pH level during eating or swallowing
* a rapid and sharp decrease in the proximal sensor pH level rather than a gradual one
Work regarding the function and stability of human pepsin shows that it is active at a pH level of 5.0. Although controversial, the use of this pH level threshold as a defining point for LPR might be more valid than a threshold of 4.0. (8,17) Using a pH level of 5.0 as indicative of reflux in the proximal esophagus might also be valid, because proximal acid exposure times are short and the dilutional and neutralizing factors present in saliva are greater at this level. (8)
What is normal acid exposure in the pharynx? The nature of the larynx, pharynx, and upper airway make them highly susceptible to reflux-induced injury. Unlike the esophagus, the laryngopharynx does not have effective defense mechanisms to resist acid- and pepsin-induced injury once the UES is breached. (18) It is clear that in the setting of laryngeal or subglottic injury, a single LPR event has great clinical significance. However, is occasional LPR in an asymptomatic individual abnormal?
As a result of work by Little et al (19) in the injured canine subglottis and work by Delahunty and Cherry, (20) it has been assumed that any extraesophageal acid contact was pathologic in nature. Koufman tested 20 asymptomatic controls and also reported no evidence of LPR. (1) Eubanks et al studied 10 healthy controls and found only a single episode of LPR in the entire group. (21) On the other hand, other studies have found laryngopharyngeal acid contact in entirely asymptomatic individuals. (22-24) In fact, Toohill et al reported that pharyngeal acid reflux events occurred in as many as 20% of normal controls. (23) Smit et al reported that perhaps as many as three LPR events over a 24-hour period might be normal. (13) However, their brief report did not mention laryngeal examinations or whether symptoms were present.
In our opinion, a single reflux event into the pharynx indicates extraesophageal reflux--that is, LPR. However, this does not prove causality. Judgments as to whether a given patient's LPR is significant must be made on an individual basis. For example, in patients with subglottic stenosis, laryngeal edema, leukoplakia, or a recurrent granuloma, a single episode of LPR would probably be considered highly significant. Conversely, one or two pharyngeal reflux events in an entirely asymptomatic person with a normal laryngeal examination might be of little importance.
Variability of pH-metry
The typical pattern of LPR is chronic-intermittent, and therefore the diagnosis might not be straightforward because a negative pH study does not necessarily rule out LPR. (1,15) The difficulty in confirming the diagnosis of LPR by pH-metry was reported by Vaezi et al. (10) They studied 32 subjects on two occasions using ambulatory double-probe pH monitoring, with the esophageal probe placed 5 cm above the LES and the proximal probe placed just below the UES. The two tests were conducted within 20 days of each other. Vaezi et al found that there was a significant day-to-day variability in acid exposure in the proximal esophagus. Intrasubject reproducibility in the healthy subjects was good (91 to 100%). Reproducibility was not as good in those subjects who had distal reflux (70 to 90%) and proximal reflux (55%). This study demonstrated good specificity but poor sensitivity for the detection of proximal reflux during any single 24-hour test period.
Screening examination of the esophagus
It is advisable to obtain a barium-swallow esophagogram or to perform esophagoscopy in LPR patients, because either study allows the otolaryngologist to assess the integrity of the esophagus. Although barium esophagography is not a sensitive test for diagnosing LPR, it can demonstrate significant abnormalities that might otherwise be missed. (25) In a series of 128 patients, the results of barium studies revealed that 18% had esophagitis, 14% had a lower esophageal ring, and 3% had a peptic stricture. (1) Barium swallow, then, can be used as a screening test. Patients with abnormal findings on barium swallow should undergo esophagoscopy.
Recently, transnasal fiberoptic esophagoscopy was introduced. (26,27) This examination requires only topical nasal anesthesia; no sedation is necessary and the procedure is well tolerated by patients. In the future, this examination is likely to replace radiographic imaging for esophageal screening of LPR patients.
In view of the cost and lack of availability of pH-metry in many locations, empiric therapy is often undertaken. Based on the symptoms and physical findings of LPR, an experienced otolaryngologist can make a diagnosis of LPR with a reasonable degree of certainty. (28-30) This method of diagnosis, coupled with a therapeutic trial of prolonged acid suppression, might indeed be preferable to any other method in some patients.
Laryngeal sensory testing
Although laryngeal sensory testing has not been used as an isolated test for LPR, it is important to note that LPR patients appear to have laryngeal sensory deficits. Using sensory testing, Aviv et al studied LPR patients with dysphagia. (31) Sensation was tested before and after antireflux treatment. Prior to treatment, 19 of 35 patients had severe laryngeal sensory deficits; after treatment, sensory deficits improved in 15 of the 19 (79%; p < 0.01). Aviv et al also found that laryngeal edema and sensory deficits in LPR were correlated. In LPR patients who do not have neurologic disease, the results of this test might prove to be a valuable treatment endpoint--that is, a return of normal sensation might correlate well with symptom resolution.
Multichannel intraluminal impedance monitoring is a new diagnostic technology that allows for the detection of bolus movement in the esophagus regardless of the pH level. (32,33) It can demonstrate the height of bolus propagation in the esophagus, differentiate between acid and nonacid reflux if coupled with a pH probe, and quantify volume clearance time. When coupled with standard pH monitoring, impedance measurement might provide several other advantages, particularly in the evaluation of certain difficult-to-manage problems. These problems include: (1) persistent symptoms in patients who are on high-dose proton-pump inhibitor therapy or in those who have undergone fundoplication, (2) early postprandial or prandial symptoms, (3) paradoxical vocal fold motion, (4) chronic cough, and (5) pediatric/neonatal reflux. Important clinical questions about neutral-pH reflux and alkaline reflux are likely to be answered by impedance testing.
In our laboratory, we have developed an ultrasensitive immunoassay for human pepsin. Clinical testing of this assay is just beginning, but we hope that by detecting pepsin in airway secretions, we might be able to develop an inexpensive, noninvasive, clinical ("spit-in-a-cup") test for LPR. The concept of identifying other markers of LPR, such as inflammatory mediators, is also under development.
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|Author:||Koufman, James A.|
|Publication:||Ear, Nose and Throat Journal|
|Date:||Sep 1, 2002|
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