Symposium: Gastroesophageal Reflux Disease
Extraesophageal Manifestations of GERD

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ABSTRACT

The association between gastroesophageal reflux disease (GERD) and extraesophageal disease is often referred to as extraesophageal reflux (EER). This article reviews EER, discussing epidemiology, pathogenesis, diagnosis, and treatment with a focus on the most studied and convincing EER disorders—asthma, cough, and laryngitis. Although EER comprises a heterogeneous group of disorders, some general characterizations can be made, as follows. First, although GERD's association with extraesophageal diseases is well-established, definitive evidence of causation has been more elusive, rendering epidemiological data scarce. Secondly, regarding the pathogenesis of EER, 2 basic models have been proposed: direct injury to extraesophageal tissue by acid and pepsin exposure or injury mediated through an esophageal reflex mechanism. Third, because heartburn and regurgitation are often absent in patients with EER, GERD may not be suspected. Even when GERD is suspected, the diagnosis may be difficult to confirm. Although endoscopy and barium esophagram remain important tools for detecting esophageal complications, they may fail to establish the presence of GERD. Even when GERD is diagnosed by endoscopy or barium esophagram, causation between GERD and extraesophageal symptoms cannot be determined. Esophageal pH is the most sensitive tool for detecting GERD, and it plays an important role in EER. However, even pH testing cannot establish GERD's causative relationship to extraesophageal symptoms. In this regard, effective treatment of GERD resulting in significant improvement or remission of the extraesophageal symptoms provides the best evidence for GERD's pathogenic role. Finally, EER generally requires more prolonged and aggressive antisecretory therapy than typical GERD requires.

Section snippets

Epidemiology

Asthma is a prevalent condition affecting 5 to 10% of the world's population,6 and its incidence has been increasing worldwide over the past several decades.7 Accumulated epidemiologic evidence has clearly established an association between GERD and asthma, and some evidence supports a causative role, adding GERD to the list of important triggers in asthma.

Epidemiology

Chronic cough, defined as the persistence of cough for more than 3 to 8 weeks,60 is among the leading symptoms for which medical attention is sought and accounts for 30 million physician visits per year.60 For at least 3 decades, GERD has been recognized as an important contributor to chronic cough. Multiple studies have identified GERD as among the 3 most common causes of chronic cough in all age groups60 contributing to cough in up to 40% of cases.61

In 1981, Irwin et al62 prospectively studied

Other Pulmonary Diseases and GERD

Whereas asthma and chronic cough are the most widely studied of the pulmonary disorders associated with GERD, there is a large and growing list of claimed pulmonary-GERD associations (see Table 1).

Epidemiology

Although many ear, nose, and throat (ENT) conditions have been associated with GERD, the most predominant ENT manifestation of EER is probably laryngitis. Because of the various descriptions of the inflamed larynx, and proposed mechanisms of injury, GERD-related laryngitis has gone by many different names, including posterior laryngitis, acid laryngitis, peptic laryngitis, and the currently favored term, reflux laryngitis. Although the prevalence of reflux laryngitis is unknown, it is estimated

Other Otolaryngeal Diseases and GERD

Laryngeal injury (such as inflammation, edema, contact ulcer formation, and contact granuloma formation) and laryngeal symptoms (such as hoarseness and globus) are the most studied of the otolaryngeal disorders associated with GERD. However, there is a large and growing list of claimed otolaryngeal disease associations with GERD (see Table 1). Interest in the association between several diseases such as subglottic stensosis,113 vasomotor rhinitis,114 and laryngospasm115 has arisen.

Yellen et al

Conclusions

Extraesophageal associations with GERD include common illnesses and complaints such as asthma, chronic cough, laryngitis, and many others. Although EERs are a heterogeneous group of disorders, some general characterizations can be made.

Many patients with EER do not have classic symptoms of GERD, such as heartburn and regurgitation. Owing partly to the high prevalence of “silent GERD” in this population, diagnosing EER can be difficult. Traditional tests, such as endoscopy and barium esophagram,

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