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Determinants of reflux-induced chronic cough
  1. Thomas V K Herregods1,
  2. Ans Pauwels2,
  3. Jafar Jafari3,
  4. Daniel Sifrim3,
  5. Albert J Bredenoord1,
  6. Jan Tack2,
  7. André J P M Smout1
  1. 1Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
  2. 2Translational Research Centre for Gastrointestinal Disorders, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium
  3. 3Barts and the London School of Medicine, Queen Mary University of London, London, UK
  1. Correspondence to Dr Thomas V K Herregods, Department of Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, Meibergdreef 9, Room A3-246, Amsterdam-Zuidoost 1105 AZ, The Netherlands; t.v.herregods{at}


Objective Gastro-oesophageal reflux is considered to be an important contributing factor in chronic unexplained cough. It remains unclear why some reflux episodes in the same patient causes cough while others do not. To understand more about the mechanism by which reflux induces cough, we aimed to identify factors which are important in triggering cough.

Design In this multicentre study, 49 patients with reflux-associated chronic cough were analysed using 24-hour pH-impedance-pressure monitoring. The characteristics of reflux episodes that were followed by cough were compared with reflux episodes not associated with cough.

Results The majority (72.4%) of the reflux episodes were acidic (pH<4). Compared with reflux episodes that were not followed by cough, reflux episodes that were followed by a cough burst were associated with a higher proximal extent (p=0.0001), a higher volume clearance time (p=0.002) and a higher acid burden in the preceding 15 min window (p=0.019) and higher reflux burden in the preceding 30 min window (p=0.044). No significant difference was found between the two groups when looking at the nadir pH, the pH drop, the acid clearance time or the percentage of reflux episodes which were acidic.

Conclusions The presence of a larger volume of refluxate and oesophageal exposure to reflux for a longer period of time seems to play an important role in inducing cough, while the acidity of the refluxate seems to be less relevant. This helps explain the observation that most patients with chronic cough tend not to benefit from acid inhibitory treatment.


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  • Contributors TVKH designed the study, collected data, analysed and interpreted data, drafted the manuscript, and critically revised the article for important intellectual content; AJB and AJPMS designed the study, interpreted data and critically revised the manuscript for important intellectual content; AP and JJ collected data, interpreted data, and critically revised the article for important intellectual content. DS and JT interpreted data and critically revised the article for important intellectual content.

  • Funding TVKH is funded by the European Union's Seventh Framework Programme under REA grant agreement no. 607652 (NeuroGut).

  • Competing interests AJB received research funding from Endostim, Medical Measurement Systems, Danone and Given and received speaker and/or consulting fees from MMS, Astellas, AstraZeneca and Almirall; DS received a research grant from Sandhill Sc USA.

  • Ethics approval Review board of the Academic Medical Centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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