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Beyond heartburn: a systematic review of the extra-oesophageal spectrum of reflux-induced disease Hungin AP; Raghunath AS; Wiklund IFam Pract 2005[Dec]; 22 (6): 591-603BACKGROUND: 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.|*Heartburn[MESH]|Asthma/etiology[MESH]|Chest Pain/etiology[MESH]|Cough/etiology[MESH]|Double-Blind Method[MESH]|Epidemiologic Studies[MESH]|Family Practice[MESH]|Gastric Juice[MESH]|Gastroesophageal Reflux/*complications/drug therapy[MESH]|Humans[MESH]|Laryngitis/etiology[MESH]|Randomized Controlled Trials as Topic[MESH]|State Medicine[MESH]|United Kingdom[MESH] |
