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Respiratory disease and the oesophagus: reflux, reflexes and microaspiration

  • Review Article
  • Published:

From Nature Reviews Gastroenterology & Hepatology

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Key Points

  • The prevalence of gastro-oesophageal reflux and sometimes its proximal extent is high in respiratory disease, suggesting the association between reflux and respiratory disease to be more than coincidence

  • Gastrointestinal factors that can influence gastro-oesophageal reflux include delayed gastric emptying, increased intra-abdominal pressure, lower oesophageal sphincter (LES) pressure plus LES misalignment with the crural diaphragm, transient LES relaxation and disordered oesophageal motility

  • Respiratory factors that might also influence the likelihood of gastro-oesophageal reflux include changes in lung volume that compromise the oesophageal-gastric junction, reduced lung compliance, breathlessness and possibly coughing

  • Gastro-oesophageal refluxate aggravates respiratory disease by either stimulating the sensitized oesophageal-bronchial neuronal pathway (for example, in chronic cough or asthma) or aspirating into the airways (microaspiration)

  • For aspiration, numerous oesophagopharyngolaryngeal protective reflexes must be overcome as well as the additional defence mechanisms of the cough reflex and mucociliary barrier; whether these are defective in respiratory disease is unknown

  • Understanding how these complex processes in the gastrointestinal tract and respiratory system truly interact and become dysfunctional in individual patients with respiratory disease remains challenging

Abstract

Gastro-oesophageal reflux is associated with a wide range of respiratory disorders, including asthma, isolated chronic cough, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cystic fibrosis. Reflux can be substantial and reach the proximal margins of the oesophagus in some individuals with specific pulmonary diseases, suggesting that this association is more than a coincidence. Proximal oesophageal reflux in particular has led to concern that microaspiration might have an important, possibly even causal, role in respiratory disease. Interestingly, reflux is not always accompanied by typical reflux symptoms, such as heartburn and/or regurgitation, leading many clinicians to empirically treat for possible gastro-oesophageal reflux. Indeed, costs associated with use of acid suppressants in pulmonary disease far outweigh those in typical GERD, despite little evidence of therapeutic benefit in clinical trials. This Review comprehensively examines the possible mechanisms that might link pulmonary disease and oesophageal reflux, highlighting the gaps in current knowledge and limitations of previous research, and helping to shed light on the frequent failure of antireflux treatments in pulmonary disease.

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Figure 1: Diagram showing the shared neuronal innervation of the oesophagus, stomach and airways.
Figure 2: Pathophysiological and structural abnormalities linking reflux and respiratory disease.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, 32224, Florida, USA

    Lesley A. Houghton, Kenneth R. DeVault & Jaclyn A. Smith

  2. Centre for Gastrointestinal Sciences, University of Manchester, University Hospital of South Manchester, Southmoor Road, M23 9LT, Manchester, UK

    Lesley A. Houghton

  3. Division of Pulmonology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, 32224, Florida, USA

    Augustine S. Lee

  4. Centre for Respiratory Medicine and Allergy, University of Manchester, University Hospital of South Manchester, Southmoor Road, Manchester, M23 9LT, UK

    Huda Badri & Jaclyn A. Smith

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L.A.H., A.S.L. and J.A.S. researched data for the article, contributed to discussion of content, wrote and reviewed/edited the manuscript. H.B. researched data for the article and contributed to writing. K.R.D reviewed/edited the manuscript.

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Houghton, L., Lee, A., Badri, H. et al. Respiratory disease and the oesophagus: reflux, reflexes and microaspiration. Nat Rev Gastroenterol Hepatol 13, 445–460 (2016). https://doi.org/10.1038/nrgastro.2016.91

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