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• AIRWAY Reflux in IPF
  Ahmed Fahim, Simon Hart and Alyn Morice
  Published on: 16 April 2019

• Published on: 16 April 2019

  AIRWAY Reflux in IPF

  • Ahmed Fahim, Consultant Respiratory Physician New Cross Hospital, Wolverhampton.
  • Other Contributors:
    • Simon Hart, Consultant Respiratory Physician and Honorary Clincial Lecturer
    • Alyn Morice, Professor of Respiratory Medicine

  We read with interest this article by Dutta et al evaluating the feasibility of proton pump inhibitor (PPI) therapy in Idiopathic Pulmonary Fibrosis (IPF). We congratulate the authors for successfully conducting this first ever double blind, randomised, placebo-controlled pilot trial of PPI in IPF despite the challenges to the recruitment in this disease with high prevalence of gastroesophageal reflux. Furthermore, we agree with the authors that cough is a neglected but important outcome measure in IPF trials and they should be praised for pursuing this.
  The role of gastro-oesophageal reflux in IPF has long been debated and its prevalence has been evaluated in a number of studies (1,2). However, the value of anti-acid therapy in relation to clinically meaningful outcomes has lacked true prospective randomised and controlled evaluation in previous trials/analyses. Furthermore, a pooled analysis (3) of 3 randomised controlled trials (RCTs) of Pirfenidone in IPF showed no clinical benefit of antacid use in terms of disease progression, mortality or markers of functional assessment with a signal towards increased infection rate in those with advanced disease and receiving antacids.
  Though airway reflux has been implicated in the exacerbation and pathophysiology of chronic cough in IPF, the aspect of oesophageal dysmotility/ non-acid reflux has largely been ignored. Dutta and colleagues had a small fraction of patients completing oesophageal manometry in the trial (...

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  We read with interest this article by Dutta et al evaluating the feasibility of proton pump inhibitor (PPI) therapy in Idiopathic Pulmonary Fibrosis (IPF). We congratulate the authors for successfully conducting this first ever double blind, randomised, placebo-controlled pilot trial of PPI in IPF despite the challenges to the recruitment in this disease with high prevalence of gastroesophageal reflux. Furthermore, we agree with the authors that cough is a neglected but important outcome measure in IPF trials and they should be praised for pursuing this.
  The role of gastro-oesophageal reflux in IPF has long been debated and its prevalence has been evaluated in a number of studies (1,2). However, the value of anti-acid therapy in relation to clinically meaningful outcomes has lacked true prospective randomised and controlled evaluation in previous trials/analyses. Furthermore, a pooled analysis (3) of 3 randomised controlled trials (RCTs) of Pirfenidone in IPF showed no clinical benefit of antacid use in terms of disease progression, mortality or markers of functional assessment with a signal towards increased infection rate in those with advanced disease and receiving antacids.
  Though airway reflux has been implicated in the exacerbation and pathophysiology of chronic cough in IPF, the aspect of oesophageal dysmotility/ non-acid reflux has largely been ignored. Dutta and colleagues had a small fraction of patients completing oesophageal manometry in the trial (9 patients out of 45 at the baseline and 6 at the end of treatment). We propose that high resolution manometry may provide an invaluable adjunct to future larger RCTs of investigating airway reflux in IPF with the measurement of gastro-esophageal pressure gradient (4). Furthermore, Hull Airway Reflux Questionnaire (5) would be a useful adjunct to the subjective assessment incorporating the acid and non-acid reflux symptoms as a measure of airway reflux when conducting future clinical trials of either acid suppression or pro-kinetic agents in IPF.
  Hence, we believe that future clinical trials of reflux in IPF should focus on non-acid reflux/ oesophageal dysmotility with a special emphasis on high resolution oesophageal manometry for comprehensive assessment of airway reflux as it is likely to be a significant contributor to chronic cough in IPF and the fact that acid suppression does not work in non-IPF chronic cough.

  References:

  1- Tobin RW, Pope CE 2nd, Pellegrini CA, Emond MJ, Sillery J, Raghu G. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;158(6):1804-8.

  2- Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C, Hayes J, Sillery JK, Pope CE 2nd, Pellegrini CA. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006 Jan;27(1):136-42.

  3- Kreuter M, Wuyts W, Renzoni E, Koschel D, Maher TM, Kolb M, Weycker D, Spagnolo P, Kirchgaessler KU, Herth FJ, Costabel U. Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: a pooled analysis. Lancet Respir Med. 2016;4(5):381-9. doi: 10.1016/S2213-2600(16)00067-9.

  4- Burke JM, Jackson W, Morice AH. The role of high resolution oesophageal manometry in occult respiratory symptoms. Respir Med 2018: 138: 47-49.

  5- Morice AH, Faruqi S, Wright CE, Thompson R, Bland JM. Cough hypersensitivity syndrome: a distinct clinical entity. Lung. 2011;189(1):73-9. doi: 10.1007/s00408-010-9272-1.

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  Conflict of Interest:
  None declared.

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