Diagnosis of Extra Oesophageal Reflux (EOR)

There is a lack of specificity and sensitivity in the test methodologies available for diagnosing EOR. There is no consensus or standardisation of tests or diagnostic criteria, there is large inter-clinical variability, and often the same tests are used for EOR as for GORD.

Differential diagnosis of EOR from GORD

Currently, the diagnosis of EOR involves a combination of methods:

1. Symptoms
2. 24-hour dual-probe pH monitoring
3. Laryngoscopy
4. Reflux Symptom Index (RSI)
5. Reflux Finding Score (RFS)
6. Anatomic diagnostic protocol
7. Other

1. Symptoms

The most commonly reported symptoms specific to EOR are listed in Table 1 in approximate order of incidence.

Table 1 – Common symptoms of EOR (in approximate order of incidence, according to Belafsky PC, et al, 2002)

Chronic dysphonia	Dysphagia
Intermittent dysphonia	Globus pharyngeus
Vocal fatigue	Heartburn
Voice breaks	Regurgitation
Chronic throat clearing	Airway obstruction
Excessive throat mucus	Paroxysmal laryngospasm
Postnasal drip	Wheezing
Chronic cough

The Reflux Symptom Index (RSI) can be given to patients to assess the presence and degree of symptoms.

2. 24-hour dual probe pH monitoring

The most commonly used and most sensitive test for detection of acid reflux is ambulatory 24-hour pH monitoring. This measures the number of times (or overall percentage of time) period that the pH in the oesophagus is below 4 during a 24-hour. However, this may not be adequate or relevant for the diagnosis of EOR, as it is the gastric refluxate that comes into contact with the larynx, which causes the damage.

The larynx may be more sensitive to the pepsin found in gastric contents than to the low pH. This is particularly relevant as pepsin is active at pH 5.0,[Dobhan R, 1993] and is not irreversibly inactivated until subjected to pH 6.5 [Panetti M, 2001] and can be as high as pH 8.0 [Piper DW, 1965]. A more relevant diagnostic test should include measurements at pH 5 in the pharynx.[Panetti M, 2001]

Pharyngeal pH monitoring has been assessed and was considered to be an accurate diagnostic method for EOR.[Oeschlager BK, 2002]

The most recent development in diagnosis is the use of dual-probe pH monitoring, with one probe in the oesophagus, and one in the pharynx. In this way, the temporal relationship between the two events can be accurately recorded.

Accurate placement of the pharyngeal probe is essential to achieve more consistent results and avoid false-positives.

In patients with severe, life-threatening EOR, pH monitoring should be performed because:

• It confirms the diagnosis of EOR
• It determines the severity of EOR and establishes a baseline
• It allows treatment to be individualized
• The results might justify early fundoplication.[Postma GN, 2002]

However, pH-monitoring equipment is not available everywhere and it is an expensive and invasive procedure.

3. Laryngoscopy

This is the examination of the interior of the larynx with either the aid of a small mirror held against the back of the palate (indirect) or a rigid or flexible (fibreoptic) viewing tube called a laryngoscope (direct).

Fibreoptic laryngoscopy is complimentary to pharyngeal pH monitoring in establishing laryngeal injury induced by reflux.[Oeschlager BK, 2002]

In a survey of the American Broncho-Esophagological Association, 76% of members considered fibreoptic laryngoscopy the preferred diagnostic visualization procedure.[Book DT, 2002]

A score can be assigned to the degree of laryngeal findings using the Reflux Finding Score (RFS).

4. Reflux Symptom Index (RSI)

This is a self-administered 9-item questionnaire for patients that can help practitioners assess the presence and degree of EOR symptoms. The instrument is validated and highly reproducible.[Belafsky PC, 2002]

Each item is scored on a scale of 0-5, and out of a maximum score of 45, an RSI above 10 is abnormal.[Reulbach TR, 2001]

The Reflux Symptom Index

Within the past month, how did the following 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, liquid, 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
Sensation 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

5. Reflux Finding Score (RFS)

This is a validated, 8-item clinical severity scale that assesses EOR findings during fibreoptic laryngoscopy.[Belafsky PC, 2002] 

The maximum score is 26, but an RFS of more than 5 is considered abnormal.[Reulbach TR, 2001]

The Reflux Finding Score (based on most common laryngeal findings in EOR patients according to Belafsky PC, et al, 2002)

Laryngeal finding	Scale	Score
Pseudosulcus (infraglottic edema)	0 = Absent 2 = Present
Ventricular obliteration	0 = Absent 2 = Present 4 = Complete
Erythema/hyperemia	0 = None 2 = Arytenoids only 4 = Diffuse
Vocal fold edema	0 = None 1 = Mild 2 = Moderate 3 = Severe 4 = Polypoid
Diffuse laryngeal edema	0 = None 1 = Mild 2 = Moderate 3 = Severe 4 = Obstructing
Posterior commissure hypertrophy	0 = None 1 = Mild 2 = Moderate 3 = Severe 4 = Obstructing
Granuloma/graulation	0 = Absent 2 = Present
Thick endolaryngeal mucus	0 = Absent 2 = Present
Total

6. Anatomic diagnostic protocol

For chronic cough relating to GORD, a systematic method of treatment was devised based on specific diagnostic examinations, called the anatomic diagnostic protocol.[Irwin RS, 2002]

First, the clinician reviews the patient history. This is followed by a physical examination, a chest X-ray and 24-h pH monitoring or barium oesophagography. If none of these tests reveals the cause, empiric pharmacotherapy should be attempted for 3–6 months. Whichever therapy the patient responds to will determine the cause.

7. Other

Alternative diagnostic criteria include bronchoscopy, patient questionnaires [Hollenz M, 2002] and sinus radiographs.

The future prospects for diagnosis include dual- or multi-channel intraluminal impedance pH monitoring, or an immunoassay for human pepsin (currently in development). These all aim to be more 'user-friendly', cost-effective, non-invasive, more specific and sensitive in measuring the effects of reflux on the laryngeal area.

Differential diagnosis of EOR from GORD

EOR is not usually accompanied by the symptoms associated with GORD, such as heartburn, probably because the refluxate does not remain in the oesophagus long enough to cause irritation or because the volume of the refluxate is lower. Hence, EOR is sometimes referred to as ‘silent reflux’.

The typical symptoms, findings and test results of GORD and EOR differ significantly (Table 2).

TABLE 2 – Differences between main symptoms of GORD and EOR

GORD	EOR
SYMPTOMS
Intermittent / lifestyle-related	Usually chronic
Mainly supine reflux	Mostly daytime, upright reflux
Heartburn and/or regurgitation common	Heartburn and/or regurgitation unusual
Hoarseness, cough, dysphagia, globus not usually present	Hoarseness, cough, dysphagia, globus normally present
FINDINGS
Oesophagitis common	Oesophagitis uncommon
Laryngeal inflammation uncommon	Laryngeal inflammation common
Dysfunction of the lower oesophageal sphincter	Dysfunction of the upper oesophageal sphincter
TEST RESULTS
Erosive or Barrett’s oesophagus can be present	Erosive or Barrett’s oesophagus uncommon
Abnormal oesophageal pH monitoring	Usually normal oesophageal pH monitoring
Normal pharyngeal pH monitoring	Abnormal pharyngeal pH monitoring
Dysmotility	Good gastrointestinal motility
Abnormal oesophageal acid clearance	Normal oesophageal acid clearance

Laryngopharyngeal reflux

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Heartburn in Pregnancy