Extra-Oesophageal Reflux (EOR)

EOR - background
Causes
Prevalence and statistics
Symptoms
Use of alginate reflux suppressant in management of EOR symptoms
Complications
Respiratory conditions associated with EOR
EOR in children

EOR - background

EOR is the retrograde movement of the stomach contents all the way up the oesophagus and into the laryngopharyngeal area (Figure 1), resulting in symptoms, including globus, hoarseness and persistent throat clearing. Respiratory symptoms are also common in EOR, such as chronic cough and those typical in asthma, for example, wheezing.

EOR is also known by many different names:

• Laryngopharyngeal Reflux
• 'Silent' reflux
• Atypical reflux
• Gastro-pharyngeal reflux
• Laryngeal reflux
• Pharyngo-oesophageal reflux
• Reflux laryngitis
• Supra-oesophageal reflux

Causes

The larynx and pharynx do not have the protective features of the oesophagus (eg, local bicarbonate production, salivation and clearance mechanisms) that guard against refluxed activated pepsin and low pH.

The laryngeal epithelium is therefore more sensitive to reflux-related injury than the oesophagus.[Axford SE, 2001; Bulmer DM, 2002, Johnston N, 2003] Damage to the epithelium can occur at pH levels up to 7.0,[Johnston N, 2003] 70% of maximal peptic activity is still present at pH 4.5, and pepsin is irreversibly activated at pH 8.0,[Piper DW, 1965, Johnston N,2003] which means that even a single reflux event in this area may be of clinical significance.

The primary defect in EOR may be upper oesophageal sphincter (UOS) dysfunction,[Sataloff RT, 1999] in contrast with GORD, in which the LOS is implicated.

Prevalence and statistics

EOR is a relatively recently recognised disease, and therefore its true prevalence is unknown. It is likely that EOR is mis- or under-diagnosed, as up to 50% of patients presenting with extra-oesophageal symptoms do not report heartburn and other symptoms typical of GORD.[Paterson WG, 2001]

In one prospective study of 113 patients with laryngeal and voice disorders, at least 50% were found to have pH-documented EOR.[Koufman JA, 2001]

In a community-based study, EOR was found in 64% of 100 adults over 40 years of age, though they had no history of previous voice disorders, which is a common symptom in EOR.[Reulbach TR, 2001]

Symptoms

EOR is not usually accompanied by the symptoms associated with GORD, such as heartburn, probably because the laryngeal epithelium is more sensitive to reflux related injury, the refluxate does not remain in the oesophagus long enough to cause irritation, or because the volume of the refluxate is lower.

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

Intermittent dysphonia

Vocal fatigue

Voice breaks

Chronic throat clearing

Excessive throat mucus

Postnasal drip

Chronic cough

Dysphagia

Globus pharyngeus

Heartburn

Regurgitation

Airway obstruction

Paroxysmal laryngospasm

Wheezing

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

Differential diagnosis of EOR from GORD

Use of alginate reflux suppressant in management of EOR symptoms

A study carried out to investigate the improvement in symptom score and clinical findings in LPR achieved with liquid alginate suspension (Gaviscon Advance) compared with control (no treatment) showed Gaviscon Advance statistically significantly improved both symptom scores and clinical findings compared with the control group.

Complications

Persistent presence of gastro-oesophageal reflux in the larynx may lead to more serious long-term complications, including:

• Subglottic stenosis
• Carcinoma of the larynx
• Contact ulcers and granulomas
• Endotracheal intubation injury
• Paroxysmal laryngospasm
• Arytenoid fixation
• Globus pharyngeus
• Vocal nodules
• Laryngomalacia
• Pachydermia larynges
• Recurrent leukoplakia

Respiratory conditions associated with EOR

Cough

It has been estimated that 70% of patients’ cough will be due to an underlying reflux disease, and almost 50% of all coughs and wheezes in asthmatics are related to gastric reflux episodes,[Avidan B, 2001] thereby implying a strong association between the cough and reflux diseases.

The clinical features that distinguish reflux-related cough when typical symptoms of GORD are absent are as follows:[Irwin RS, 2002]

• Cough of 2-months' duration or longer
• Patient is not a present smoker or not exposed to other environmental irritants
• Patient is not taking an angiotensin-converting enzyme (ACE) inhibitor
• Chest radiograph normal or near-normal
• Symptomatic asthma has been ruled out
• Post-nasal drip syndrome due to rhinosinus diseases has been ruled out
• Eosinophilic bronchitis has been ruled out
• Cough has not improved with corticosteroids

Mechanism of cough in EOR

Two current hypotheses exist regarding the exact mechanical association between cough and gastro-oesophageal reflux:

• Vagally mediated nervous reflex (the oesophageal-tracheo-bronchial reflex): persistent coughing may then cause damage to the larynx.
• Direct-contact damage, where the refluxate comes into direct contact with the larynx and causes damage

The cough threshold in patients with GORD has been found to be lower than normal, and the patients more sensitive to protussive stimuli.[Benini L, 2000] This implies that the acid within the laryngeal area induces cough, and thus supports the direct-contact theory.

Other studies show that there is impaired clearance of acid within the oesophagus in patients with chronic cough, which may suggest a role for dysmotility.[Ing AJ, 1992]

Asthma

There is an 80% association between asthma and GORD.[Harding SM, 1999] However, for a large percentage of asthma patients, GORD is silent (asymptomatic, considering the typical symptoms of GORD).[Kiljander TO, 1999]

Mechanism of asthma in EOR

Two current hypotheses are:

1. Gastric refluxate in the oesophageal lumen causes reflex bronchoconstriction
2. Microaspiration of small volumes of gastric contents occurs causing injury to the bronchial tree

EOR in children

Extra-oesophageal manifestations of reflux are more common in children than in adults, particularly respiratory symptoms. In infants, transient lower oesophageal sphincter relaxations are abnormally common and the main contributory factor in the pathophysiology of EOR.[Omari TI, 2002]

Symptoms include:

• Benign postprandial vomiting in first year of life
• Failure to thrive
• Oesophagitis
• Airway disturbances

Gastric reflux will contribute to morphological and inflammatory symptoms seen in infants, resulting in:

• Voice abnormalities [Nedzielska G, 2000]
• Recurrent laryngotracheitis [Contencin P, 1992]
• Glue ear [Tasker A, 2003]
• Sleep apnoea [Page M, 2000]
• Sudden infant death syndrome [Page M, 2000]
• Chronic sinus disease refractory to aggressive medication [Phipps CD, 2000]

Investigation of the genetics of paediatric GORD has localised a putative GORD gene to chromosome 13q14.[Hu FZ, 2000]

Generally, improvements are seen within the first year of life, as soon as solid foods are introduced. However, symptoms can be persistent and children older than 3 years may require medical and/or surgical intervention to avoid long-term complications.[Treen WR, 1991]

Antireflux therapy can be effective in reducing or eliminating GORD-related lesions of the laryngeal area in children.[Zalesska-Krecicka M, 2002]

Laryngopharyngeal reflux

More to reflux than Acid

Heartburn in Pregnancy