Extraesophageal Manifestations of Gastroesophageal Reflux Disease: Real or Imagined?

John M. Moore; Michael F. Vaezi


Curr Opin Gastroenterol. 2010;26(4):389-394. 

In This Article

Abstract and Introduction


Purpose of review Extraesophageal reflux disease is a common clinical presentation to gastroenterology as well as ear, nose and throat, allergy, and asthma clinics. The diagnosis and management of this condition is challenging. We review the current dilemma in this area and discuss the latest studies which help guide our therapies for patients with suspected extraesophageal reflux.
Recent findings Diagnostic approach to patients with extraesophageal reflux disease involved the use of insensitive tools, which have hampered the ability to correctly identify patients at risk. Empiric trial using proton pump inhibitors is still the recommended initial approach to those suspected of having reflux as the cause for extraesophageal symptoms such as asthma, chronic cough, or laryngitis. Diagnostic testing should be reserved to those unresponsive to therapy. Most recent studies suggest that ambulatory impedance/pH monitoring performed on therapy may be most likely to help exclude reflux as the cause for persistent symptoms. Recent randomized placebo-controlled studies on chronic laryngitis, cough, and asthma have been disappointing in showing benefit of acid suppressive therapy.
Summary Gastroduodenal reflux may cause symptoms such as chronic cough, asthma, or laryngitis. However, we are currently limited in our diagnostic ability to identify the subgroup of patients who might respond to acid suppressive therapy. Impedance/pH monitoring may be a step in the right direction; however, outcome studies are needed to better understand the role of acid or nonacid reflux in patients with extraesophageal symptoms.


Gastroesophageal reflux disease (GERD) is defined as a condition that develops when reflux of stomach contents causes troublesome symptoms and/or complications.[1] The manifestations of GERD are classically described as heartburn and reflux, which are often referred to as 'typical GERD.' However, GERD may also present atypically and is referred to as extraesophageal syndrome by the Montreal definition.[1] Common extraesophageal manifestations include reflux cough syndrome, reflux asthma syndrome, and reflux laryngitis syndrome.

Potential ways that gastroesophageal reflux may contribute to these symptoms involve both direct (aspiration) and indirect (neurally mediated) mechanisms.[2–5] A disturbance of the normal protective mechanisms may allow direct contact of gastroduodenal contents with the larynx or airway. This reflux may cause symptoms by irritation directly, or reflux may stimulate a vagal reflex arc producing cough and/or bronchospasm. Animal studies have documented that substantial laryngeal injuries may be caused by both exposure to noxious agents present in gastric and duodenal juice.[5–8] Injury secondary to acid and pepsin is a known causative factor in reflux esophagitis. However, trypsin and conjugated and unconjugated bile acids can cause histologic change in the absence of acid as well.[4] The reflux of nonacidic material may produce symptoms and tissue injury that may not be effectively treated with proton pump inhibitors (PPIs).

In this monograph, we will discuss the relevant studies in the past year in the area of extraesophageal reflux syndrome with respect to diagnostic testing and therapeutics.