Beyond heartburn: a systematic review of the extra-oesophageal spectrum of reflux-induced disease

Fam Pract. 2005 Dec;22(6):591-603. doi: 10.1093/fampra/cmi061. Epub 2005 Jul 15.


Background: Gastro-oesophageal reflux disease (GORD) is a chronic condition affecting up to one-quarter of the Western population. GORD is characterized by heartburn and acid regurgitation, but is reported to be associated with a spectrum of extra-oesophageal symptoms.

Objective: The aim of this systematic review was to critically evaluate postulated extra-oesophageal symptoms of GORD.

Methods: Extra-oesophageal symptoms were identified from population-based studies evaluating their association with GORD (either defined as heartburn and/or acid regurgitation, or diagnosed in general practice). The response of these symptoms to acid-suppressive therapy was investigated using randomized, double-blind, placebo-controlled studies. Pathogenic mechanisms were evaluated using clinical and preclinical studies.

Results: An association between GORD and symptoms or a diagnosis of chest pain/angina, cough, sinusitis and gall-bladder disease was evident from three eligible population-based studies of GORD. Randomized placebo-controlled studies (n=20) showed that acid-suppressive therapy provides symptomatic relief of chest pain, asthma and, potentially, chronic cough and laryngitis. Mechanistic models, based on direct physical damage by refluxate or vagally mediated reflexes, support a causal role for GORD in chest pain and respiratory symptoms, but not in gall-bladder disease.

Conclusion: GORD is likely to play a causal role in chest pain and possibly asthma, chronic cough and laryngitis. Further investigation is desirable, particularly for other potential extra-oesophageal manifestations of GORD such as chronic obstructive pulmonary disease, sinusitis, bronchitis and otitis. Acid-suppressive therapy is likely to benefit patients with non-cardiac chest pain, but further placebo-controlled studies are needed for other symptoms comprising the extra-oesophageal spectrum of GORD.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Asthma / etiology
  • Chest Pain / etiology
  • Cough / etiology
  • Double-Blind Method
  • Epidemiologic Studies
  • Family Practice
  • Gastric Juice
  • Gastroesophageal Reflux / complications*
  • Gastroesophageal Reflux / drug therapy
  • Heartburn*
  • Humans
  • Laryngitis / etiology
  • Randomized Controlled Trials as Topic
  • State Medicine
  • United Kingdom