UNCERTAINTIES PAGE Are persistent throat symptoms atypical features of gastric reflux and should they be treated with proton pump inhibitors? Jason Powell research fellow 1 , James O’Hara consultant otolaryngologist, head and neck surgeon 2 , Janet A Wilson professor of otolaryngology, head and neck surgery 3 1 Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; 2 Freeman Hospital, Newcastle upon Tyne, UK; 3 Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK This is one of a series of occasional articles that highlight areas of practice where management lacks convincing supporting evidence. The series adviser is David Tovey, editor in chief, the Cochrane Library. This paper is based on a research priority identified and commissioned by the National Institute for Health Research’s Health Technology Assessment programme on an important clinical uncertainty. To suggest a topic for this series, please email us at uncertainties@thebmj.com Persistent throat symptoms are common in adults. Globus pharyngeus (a feeling of a lump in the throat), dysphonia, throat clearing, cough, excessive phlegm, throat pain, and postnasal secretions are present in up to 25% of primary care attenders, and more than 60 000 people are referred to secondary otolaryngological care annually. 1 Treating persistent throat symptoms with gastric acid suppression has been in vogue for more than a decade, on the basis that they represent “atypical” manifestations of gastro-oesophageal reflux disease (GORD). 2 So called extraoesophageal reflux or laryngopharyngeal reflux is internationally acknowledged as a separate GORD subcategory from “typical” oesophageal reflux disease. 3 However, the relation between gastric reflux and persistent throat symptoms, and the role of proton pump inhibitor (PPI) treatment remains controversial. 45 More than half of UK otolaryngologists prescribe PPIs for persistent throat symptoms. 6 The message has also filtered through to primary care that PPIs are a reasonable “empirical” treatment. PPI treatment is a substantial expense for healthcare systems and increasingly treatment of persistent throat symptoms is adding to this. The cost of PPI treatment to the National Health Service in England for all conditions, including persistent throat symptoms, was £425m (€540m; $694m) in 2006 and the global bill was £7bn. 7 What is the evidence of uncertainty? On 25 June 2014 we searched Medline and Embase databases and the Cochrane Library for studies dealing with persistent throat symptoms, gastric reflux, and treatment with PPIs. We used the search terms “throat symptoms” or “laryngopharyngeal reflux” or “extra-oesophageal reflux” or “extra-esophageal reflux” or “gastro-oesophageal reflux disease” or “gastro-esophageal reflux disease” or “proton pump inhibitors”. Are persistent throat symptoms atypical features of gastric reflux? The pathogenesis of persistent throat symptoms in gastric reflux is hypothesised to be through retrograde flow of gastric contents (particularly acid, bile, and pepsin) that affect the laryngopharynx by direct mucosal contact, or by a secondary mechanism. 8 Persistent throat symptoms, 1 and endoscopic evidence of gastro-oesophageal reflux, 9 are common in the population. This implies that they will coexist in a considerable proportion of people, however, a causal link between the two has not been convincingly shown. Some evidence shows that gastric contents enter the laryngopharynx. Using 24 hour ambulatory pH monitoring, significantly more reflux events and greater pharyngeal acid exposure times were recorded in the laryngopharynx of people with throat symptoms compared with asymptomatic controls in a meta-analysis (n=793). 10 In vivo experiments have demonstrated tissue damage and cellular changes in response to individual and combination components of gastric juice on laryngopharyngeal cells, 11 with genetic changes, immunohistochemical effects, and changes in molecular regulator activity. 12 Some of these cellular changes have also been shown in laryngeal samples taken from patients with persistent throat symptoms. 12 Correspondence to: J Powell jason.powell@doctors.org.uk For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe BMJ 2014;349:g5813 doi: 10.1136/bmj.g5813 (Published 9 October 2014) Page 1 of 4 Practice PRACTICE