Abstract
The presentations of laryngopharyngeal reflux (LPR) are diverse and include chronic hoarseness, sensation of foreign body in the throat, sore throat etc. 24 h pH monitoring considered the gold standard of investigation for LPR is costly, cumbersome and not readily available at all centers. Empirical trial of Proton pump inhibitor (PPI) as a diagnostic tool after assessment by Reflux Symptom Index (RSI) and Reflux Findings Score (RFS) is a cheaper, simple and readily available alternative. The objectives of the study were to determine clinical manifestations in patients presenting with LPR and to evaluate the role of empirical treatment with PPI as a diagnostic tool in LPR. 100 patients were divided into experimental group (RSI ≥ 13 and RFS ≥ 7) and control group (RSI < 13 and RFS < 7). Omeprazole trial was given to experimental group and assessed for RSI and RFS at 04 and 08 weeks. Statistical analysis was done within the group and between the groups. (1) The response rate to Omeprazole at 04 and 08 weeks interval (RSI<13 and/or RFS<7) was 60% and 76% respectively. (2) The response to Omeprazole given to the experimental group with RSI≥13 and RFS≥7 was significant at 04 weeks and 08 weeks duration (P<0.0001). RSI and RFS are good clinical tools to assess and diagnose patients with Laryngopharyngeal reflux. Based on the clinical diagnosis an empirical trial of a proton pump inhibitor (PPI) can be given to patients for duration of 02 months resulting in a good response.
Keywords: Laryngopharyngeal reflux, Reflux symptom index (RSI), Reflux finding score (RFS), Proton pump inhibitor, Omeprazole
Introduction
Of all of the causes of laryngeal inflammation, gastroesophageal reflux disease (GERD) is the most common cause, and as many as 10–50% of patients with laryngeal complaints have a GER-related underlying cause. When refluxed material escapes the esophagus and enters the laryngopharynx above, the event is termed laryngopharyngeal reflux (LPR) [1].
Laryngopharyngeal reflux affects both children and adults and may be associated with an acute, chronic, or intermittent pattern of laryngitis, with or without granuloma formation [2–4].
Patients with “reflux laryngitis” (LPR) present with hoarseness, but almost two-thirds deny ever having heartburn. Other throat symptoms such as globus pharyngeus, dysphagia, chronic throat clearing and cough are often associated with LPR. A nine-item reflux symptom index (RSI) has been developed and validated to quantify patient symptoms of LPR and evaluate treatment efficacy. This outcome instrument has displayed excellent reproducibility and criterion-based validity [5].
Physical findings of LPR can range from mild, isolated edema and/or erythema of the area of the arytenoid cartilages to diffuse laryngeal edema and hyperemia with granuloma formation and airway obstruction. An eight-item reflux finding score (RFS) has been validated to document the severity of the clinical findings of LPR. Use of the RFS not only helps physicians identify subtle findings of reflux, it also assists in evaluating the severity of laryngeal tissue injury, as well as documenting treatment efficacy [6].
Ambulatory 24-hour double-probe pH monitoring is the gold standard for the diagnosis of LPR. The distal probe is placed 5 cm above the lower esophageal sphincter (LES), and the proximal probe is placed in the hypopharynx 1 cm above the upper esophageal sphincter (UES), just behind the laryngeal inlet. In general, the most important parameter used to evaluate the presence of GERD at the distal probe is the percentage of time that the pH is less than 4. This measurement is usually recorded for time in the upright position, time in the supine position, and the total time of the study. For the upright period, the upper limit of normal is approximately 8.0%, and for the supine period, approximately 2.5% [7].
The proximal pharyngeal probe is invaluable in patients with LPR because it is placed behind the larynx just above the cricopharyngeus; thus, reflux recorded by it is diagnostic of LPR. In addition, it has been found that without the proximal (pharyngeal) probe, the diagnosis of LPR will be missed in approximately 30–50% of patients. Although the prevalence of esophagitis in patients with LPR is only 20%, the percentage of other esophageal abnormalities such as Barrett’s metaplasia may be high [7].
Objectives
To determine various clinical manifestations in patients presenting to ENT outpatient department with Laryngopharyngeal Reflux.
To evaluate the role of empirical treatment with proton pump inhibitor (Omeprazole) as a diagnostic tool in Laryngopharyngeal Reflux.
Review of Literature
Laryngopharyngeal reflux (LPR) is the retrograde movement of gastric contents in laryngopharynx leading to symptoms. Possible mechanisms for LPR are micro aspiration of gastric contents or vagally mediated mechanism. Acidification of distal esophagus can stimulate acid sensitive receptors resulting in cough, broncho-constriction and asthma [8–10].
Transient lower oesophageal sphincter relaxations (tLOSRs) are both a dominant mechanism of reflux and an element of the belch reflex. Upper oesophageal sphincter relaxation was usually preceded by a pressure change in the oesophagus; however, some relaxations (16%) occurred without a discernable increase in pressure or before the pressure increase began. Acid reflux did not appear to play a role in determining UOS response to tLOSRs [11].
The larynx, pharynx and proximal airway are more sensitive to reflux than esophagus. Poor clearance of refluxate, less mucosal thickness, diminished mucosal bicarbonate production and absence of salivary clearance and buffering with salivary bicarbonate, all make this region uniquely sensitive to reflux [12].
Gastroesophageal reflux disease (GERD) may manifest as laryngitis, asthma, cough, or non-cardiac chest pain. Diagnosing these extra esophageal manifestations may be difficult for primary care physicians because most patients do not have heartburn or regurgitation. Diagnostic tests have low specificity, and a cause-and-effect association between GERD and extra esophageal symptoms is difficult to establish. Response to aggressive acid suppression is often the best indication of GERD etiology in a patient with extra esophageal symptoms. Multi-probe ambulatory pH monitoring is currently the diagnostic tool of choice, but the level of sensitivity for supra esophageal manifestations of reflux disease are uncertain. It has a poor sensitivity of 70–80%. False negative rate ranges from 20 to 50%. A negative test may not exclude LPR. Also a positive test does not confirm the diagnosis. Usually cause and effect relationship is best established with sustained response to acid suppressive therapy. Clinical response rate with twice daily proton pump inhibitor ranges from 60 to 98%. Empiric treatment with a proton pump inhibitor is a recommended diagnostic strategy [13, 14].
In a study by Wang WH and colleagues the overall sensitivity and specificity of a PPI test were 80% and 74% respectively, compared with 19% and 77% respectively in the placebo group. The use of PPI treatment as a diagnostic test for detecting GERD has an acceptable sensitivity and specificity and could be used as an initial approach by primary care physicians to detect GERD [15].
Reflux symptom index (RSI) is a nine-item index to quantify patients’ symptoms of LPR and evaluate treatment efficacy. RSI is an easily administered, highly reproducible and exhibits excellent construct and criterion based validity. Reflux finding score (RFS) is an eight-item score to document the severity of clinical findings of LPR [16].
Twenty-four-hour pH monitoring has come to be considered the most sensitive and specific test in the diagnosis of GORD, but a significant proportion of patients (about 25%) have symptoms compatible with GORD and have 24-h pH monitoring results that can be considered normal. Besides, demonstrating the presence of acid reflux alone does not prove that it is the cause of suspected GORD-related signs or symptoms. Despite 24-h oesophageal pH testing being an excellent diagnostic tool, it has no utility in routine clinical settings and hence its availability should be limited to tertiary care settings. The use of PPIs both as a diagnostic test (1–2 weeks) and as a diagnostic-therapeutic test (1–4 months) has a moderate usefulness and may be used especially in those environments in which there are difficulties in performing the objective test [17].
In the study conducted by Schenk BE and colleagues it was observerd that using pH monitoring as a gold standard, the omeprazole test had positive and negative predictive values of 68 and 63%, respectively. If the omeprazole test was used as the gold standard, pH monitoring had positive and negative predictive values of 68 and 63%, respectively. The authors concluded that symptomatic response to omeprazole 40 mg each day for 14 days is a simple and inexpensive tool in the diagnosis of GERD, with a sensitivity and specificity similar to 24-h pH monitoring [18].
Laryngeal signs are not pathognomonic for laryngopharyngeal reflux because many of these signs can be found in healthy volunteers. A combination of signs and symptoms should be sought before suspecting this diagnosis. Multidisciplinary trials are needed to establish the optimal combination of sign and symptom scores, reflux monitoring results, and empiric treatment trials for the most accurate diagnosis of laryngopharyngeal reflux [19].
There is no pathognomonic symptom or finding, but characteristic symptoms and laryngoscopic findings provide the basis for validated assessment instruments (the RSI and RFS) useful in initial diagnosis. Laryngopharyngeal reflux should be suspected when the history and laryngoscopy findings are suggestive of the diagnosis. Failure to respond to a 3-month trial of behavioral change and gastric acid suppression by adequate doses of proton pump inhibitor medication dictates need for confirmatory studies [20].
Methodology
Research Design
Where: ME(1): RSI and RFS in patients presenting to ENT out-patient department and assigned to experimental group. T: Empirical trial with proton pump inhibitor (Omeprazole). ME(2): RSI and RFS at 04 weeks Post treatment with Omeprazole in the experimental group. ME(3): RSI and RFS at 08 weeks Post treatment with Omeprazole in the experimental group. MC(1): RSI and RFS in patients presenting to ENT out-patient department and assigned to control group.MC(2): RSI and RFS at 04 weeks in the control group. MC(3): RSI and RFS at 08 weeks in the control group.
Setting of the Study
The study was conducted in ENT Department of tertiary care hospital.
Variables
- Dependent
RSI and RFS in patients presenting in ENT out-patient department
- Independent
Proton pump inhibitor (Omeprazole)
Population
The population comprised of all the patients visiting the outpatient department of Otorhinolaryngology.
Sample Size
The sample size consisted of 100 patients. The 100 samples were divided into 02 equal groups of 50 each based on RSI and RFS for the purpose of control.
Sampling Technique
The technique used was non-probability convenience method of sampling (Random sampling).
Criteria for Selection of Sample
Inclusion Criteria
Patients who present to ENT outpatient department with clinical features of Laryngopharyngeal Reflux and having a Reflux Symptom Index of ≥ 13 and Reflux Finding Score ≥ 7 were included in the Experimental group.
Patients having a Reflux Symptom Index < 13 and Reflux Finding Score < 7 were included in the Control Group.
Patients in the age group 18–60 years.
Exclusion Criteria
Patients with any other organic cause for presentation to the ENT outpatient department.
Patients < 18 years and > 60 years.
Technique and Tool
Patients who satisfied the criteria of selection were taken as subjects of the study.
A brief history of past 1 month related to the symptoms of Laryngopharyngeal Reflux was taken and each symptom was scored on the self-assessment scale of 0–5. The symptoms and the scoring were based on Reflux Symptom Index (RSI).
Reflux Symptom Index
| Finding | ||||||
|---|---|---|---|---|---|---|
| Within the last MONTH, how did the following problems affect you? | 0 = no problem 5 = severe problem |
|||||
| Hoarseness or a problem with your voice | 0 | 1 | 2 | 3 | 4 | 5 |
| Clearing your throat | 0 | 1 | 2 | 3 | 4 | 5 |
| Excess throat mucus or postnasal drip | 0 | 1 | 2 | 3 | 4 | 5 |
| Difficulty swallowing food, liquids, or pills | 0 | 1 | 2 | 3 | 4 | 5 |
| Coughing after you ate or after lying down | 0 | 1 | 2 | 3 | 4 | 5 |
| Breathing difficulties or choking episodes | 0 | 1 | 2 | 3 | 4 | 5 |
| Troublesome or annoying cough | 0 | 1 | 2 | 3 | 4 | 5 |
| Sensations of something sticking in your throat or a lump in your throat | 0 | 1 | 2 | 3 | 4 | 5 |
| Heartburn, chest pain, indigestion, or stomach acid coming up | 0 | 1 | 2 | 3 | 4 | 5 |
| Total | ||||||
Complete Otolaryngological examination of the patient was done. Patients who had any obvious organic cause for the various clinical presentations were treated accordingly and excluded from the study. Patients with Indirect Laryngoscopy findings and the findings confirmed with Fibreoptic Laryngoscopy were given the Reflux Finding Score (RFS).
Reflux Finding Score
| Finding | Score |
|---|---|
| Subglottic edema | 2 = present 0 = absent |
| Ventricular obliteration | 2 = partial 4 = complete |
| Erythema/hyperemia | 2 = arytenoids only 4 = diffuse |
| Vocal cord edema |
1 = mild 2 = moderate 3 = severe 4 = polypoid |
| Diffuse laryngeal edema |
1 = mild 2 = moderate 3 = severe 4 = obstructing |
| Posterior commissure hypertrophy |
1 = mild 2 = moderate 3 = severe 4 = obstructing |
| Granuloma/granulation | 2 = present 0 = absent |
| Thick endolaryngeal mucus/other | 2 = present 0 = absent |
| TOTAL | |
The Reflux Symptom Index and Reflux Finding Score were then taken into consideration together with other Otorhinolaryngological examination and a clinical diagnosis of Laryngopharyngeal Reflux was made in patients with RSI ≥ 13 and RFS ≥ 7.
Empirical trial with proton pump inhibitor was given to the experimental group for a period of 04 weeks and then the RSI and RFS recorded at the end of 04 weeks treatment. The proton pump inhibitor was continued for a period of another 04 weeks and the RSI and RFS was recorded again at the end of 08 weeks.
The RSI and RFS of the control group were recorded at the time of entry into the study and thereafter at 04 weeks and 08 weeks of the study.
The data collected was subjected to appropriate statistical analysis.
Results
Method of Statistical Analysis
Statistical analysis was done by using the following methods:-
Paired t test for comparison of Reflux symptom index within the experimental group.
Paired t test for comparison of Reflux finding score within the experimental group.
Paired t test for comparison of Reflux symptom index within the control group.
Paired t test for comparison of Reflux finding score within the control group.
t test between the experimental and control group for Reflux symptom index.
t test between the experimental and control group for Reflux finding score.
SPSS was used to perform the statistical tests.
Frequency and Percentage Distribution of Sample
In the experimental group Females were 28 (56%) and males 22 (44%) whereas in the control group females 34 (68%) and males 16 (32%).
The average RSI and RFS in the experimental group are as mentioned in Table 1.
Table 1.
Average RSI and RFS in Experimental group
| RSI | ME1 | ME2 | ME3 |
|---|---|---|---|
| Average | 16.44 | 11.7 | 9.94 |
| SD | 1.70 | 2.08 | 2.53 |
| RFS | ME1 | ME2 | ME3 |
| Average | 7.26 | 5.88 | 4.62 |
| SD | 1.61 | 1.45 | 1.40 |
The average RSI and RFS in the control group are as mentioned in Table 2.
Table 2.
Average RSI and RFS in Control group
| RSI | MC1 | MC2 | MC3 |
|---|---|---|---|
| Average | 10.6 | 9.06 | 7.78 |
| SD | 1.07 | 1.49 | 1.45 |
| RFS | MC1 | MC2 | MC3 |
| Average | 3.94 | 3.68 | 2.64 |
| SD | 1.19 | 1.28 | 1.01 |
The average score of various symptoms as per RSI in the experimental group are as mentioned in Table 3.
Table 3.
Average score of various symptoms according to RSI in Experimental group
| Symptom | Average Score |
|---|---|
| Hoarseness or a voice problem | 0.76 |
| Throat clearing | 3.14 |
| Excess throat mucus or postnasal drip | 1.76 |
| Difficulty swallowing food, liquids, or pills | 0.82 |
| Cough after eating or after lying down | 0.52 |
| Breathing difficulties or choking episodes | 0.48 |
| Troublesome or annoying cough | 3.36 |
| Sensations of something sticking in the throat or a lump in the throat | 3.24 |
| Heartburn, chest pain, indigestion, or stomach acid coming up | 2.34 |
The average score of various signs according to RFS in the experimental group are as mentioned in Table 4.
Table 4.
Average score of various signs according to RF Score in Experimental Group
| Findings | Average score |
|---|---|
| Subglottic edema | 0.4 |
| Ventricular obliteration | 0.32 |
| Erythema/hyperemia | 1.92 |
| Vocal cord edema | 1.56 |
| Diffuse laryngeal edema | 1.16 |
| Posterior commissure hypertrophy | 1.1 |
| Granuloma/granulation | 0.2 |
| Thick endolaryngeal mucus/other | 0.6 |
The response to Omeprazole in the experimental group at 04 weeks is as shown in Fig. 1.
Fig. 1.
Percentage distribution of response to Omeprazole in experimental group at 04 weeks
Experimental Group (n = 50)
The response to Omeprazole in the experimental group at 08 weeks is as shown in Fig. 2.
Fig. 2.
Percentage distribution of response to Omeprazole in experimental group at 08 weeks
Experimental Group (n = 50)
Paired t Test Comparison of Reflux Symptom Index Within the Experimental Group
In the study, there was a significant change in Reflux symptom index in the Experimental group receiving Omeprazole at 4 weeks and 8 weeks duration (P < 0.0001).
Paired t Test Comparison of Reflux Finding Score Within the Experimental Group
In the study, there was a significant change in Reflux finding score in the Experimental group receiving Omeprazole at 4 weeks and 8 weeks duration (P < 0.0001).
Paired t Test Comparison of Reflux Symptom Index Within the Control Group
In the study, there was a significant change in Reflux symptom index in the Control group receiving at 4 weeks and 8 weeks duration (P < 0.0001).
Paired t Test Comparison of Reflux Finding Score Within the Control Group
In the study, there was a significant change in Reflux finding score in the Control group at 4 weeks and 8 weeks duration (P < 0.0001).
t Test for Reflux Symptom Index Between Experimental and Control Group
In the study, there was a significant difference in the improvement in Reflux symptom index in the Experimental group as compared to the Control group at 4 weeks and 8 weeks duration (P < 0.0001). This is shown in Table 5.
Table 5.
Test for RSI between experimental and control group
| RSI | ||
|---|---|---|
| ME1 VS MC1 | ME2 VS MC2 | ME3 VS MC3 |
| 1.45155E − 37 | 4.01533E − 11 | 4.74391E − 07 |
| P < 0.0001 | P < 0.0001 | P < 0.0001 |
t Test for Reflux Finding Score Between Experimental and Control Group
In the study, there was a significant difference in the improvement in Reflux finding score in the Experimental group as compared to the Control group at 4 weeks and 8 weeks duration (P < 0.0001). This is shown in Table 6.
Table 6.
t test for RFS between experimental and control group
| RFS | ||
|---|---|---|
| ME1 VS MC1 | ME2 VS MC2 | ME3 VS MC3 |
| 1.15642E − 20 | 1.12563E − 12 | 6.67714E − 13 |
| P < 0.0001 | P < 0.0001 | P < 0.0001 |
Discussion
In our study with 50 patients with laryngopharyngeal reflux, the sex distribution was females 56% (n = 28) and males 44% (n = 22). The common presentations of patients with laryngopharyngeal reflux seen in this study were annoying cough (100%), something sticking in the throat (100%), frequent throat clearing (100%), heartburn/chest pain/indigestion (96%) and excess throat mucus or post nasal drip (84%). Other less common symptoms were hoarseness of voice (50%), dysphagia (68%), cough after eating or lying (42%) and breathlessness or choking episodes (36%).
Carrau and colleagues in their study showed that patients with laryngopharyngeal reflux often reported multiple symptoms, most frequently, chronic throat-clearing (85.5%), globus (82.1%), and hoarseness (80.3%) [21].
In our study the common findings seen on laryngoscopy were erythema/hyperemia of the arytenoids (96%), vocal cord edema (96%), posterior commissure hypertrophy (96%), diffuse laryngeal edema (94%), Other less commonly seen are subglottic edema (20%), ventricular obliteration (16%), granuloma/granulation (10%) and thick endolaryngeal mucus (32%).
In a study by Jonaitis and colleagues it was seen that important significant changes in patients with LPR were mucosal lesions of IAN, vocal cord and edema of vocal cords. These 3 signs together distinguished patients from controls in 95.9% cases [22].
In our study it was observed that on treatment with twice daily Omeprazole for 04 weeks, the response rate was 60%, which on further evaluation after treatment for 08 weeks was 76%. In the control group there was a significant reduction in RSI and RFS after lifestyle modifications, however, on comparison with experimental group getting Omeprazole, the experimental group showed a significant improvement in RSI and RFS (P < 0.0001).
Issing WJ and colleagues in their study reported an improvement in 68% patients at 04 weeks and 95% at 08 weeks on treatment with PPIs [23].
In a study done by DelGaudio JM and colleagues after 04 weeks of treatment with once daily PPI, only 8 of 30 patients had significant improvement and at 08 weeks of treatment, 19 of 30 patients had significant improvement. 40% of non-responders improved further after increasing their dosage to twice a day [24].
Three approaches to confirm the diagnosis of LPR are (a) response of symptoms to empirical treatment with PPIs, (b) Endoscopic observation of mucosal injury and (c) demonstration of reflux events by impedence and pH monitoring studies and Barium swallow esophagogram. Multi-channel intraluminal impedance and 24 h pH monitoring considered to be gold standard for diagnosis of LPR are expensive, cumbersome and not readily available in all the centres. In clinical practice a reliable tool for diagnosis of LPR is a RSI and RFS and an empirical trial with PPIs for more than 08 weeks. An improvement in the symptoms and findings on laryngoscopy confirm the diagnosis of LPR.
Conclusion
Laryngopharyngeal reflux is a condition, which may present to the Otolaryngology outpatient department with varying symptoms. The Reflux symptom index and Reflux finding score are good clinical tools to assess and diagnose patients with Laryngopharyngeal reflux. Based on the clinical diagnosis an empirical trial of a proton pump inhibitor (PPI) can be given to patients for duration of 02 months or more resulting in a good response. The diagnostic role of PPI being a good response in terms of RSI and RFS evaluated at intervals.
Compliance with Ethical Standards
Conflict of interest
The author declares that there is no conflict of interest.
Ethical Approval
All procedures performed were in accordance and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and ethical approval was obtained from the ethical committee of the hospital where the study was conducted.
Informed Consent
Awritten informed consent was taken from all the individual participants who were included in the study.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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