Skip to main content

Reflux and Aspiration: Their Presumed Role in Chronic Cough and the Development of End-Stage Lung Disease

  • Chapter
  • First Online:
Reflux Aspiration and Lung Disease

Abstract

Amongst patients with end-stage lung disease (ESLD), symptoms and diagnostic evidence of gastroesophageal reflux disease (GERD) are extremely common. In fact, roughly two-thirds of all patients with ESLD have documentable gastroesophageal reflux [1]. The presence of significant reflux is not limited to one pulmonary disease, but is seen in patients with ESLD secondary to COPD, cystic fibrosis and idiopathic pulmonary fibrosis (IPF) [2] (Gasper et al. 2007). While the pathophysiology of COPD and cystic fibrosis are well understood, it remains unknown what leads to the eventual development of IPF. Interestingly, evidence has continued to mount over the last 20 years that reflux is not just prevalent in patients with IPF, but may in fact be contributing to its development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. D’Ovidio F, Singer L, Hadjiliadis D, et al. Prevalence of gastroesophageal reflux in end-stage lung disease candidates for lung transplant. Ann Thorac Surg. 2005;80:1254–61.

    Article  PubMed  Google Scholar 

  2. Sweet M, Herbella F, Leard L, et al. The prevalence of distal and proximal gastroesophageal reflux in patients awaiting lung transplantation. Ann Surg. 2006;244:491–7.

    PubMed  PubMed Central  Google Scholar 

  3. Gasper W, Sweet M, Golden J, et al. Lung transplantation in patients with connective tissue disorders and esophageal dysmotility. Dis Esophagus. 2008;21:650–5.

    Article  PubMed  Google Scholar 

  4. Reid K, McKenzie F, Menkis A, et al. Importance of chronic aspiration in recipients of heart-lung transplants. Lancet. 1990;336:206–8.

    Article  CAS  PubMed  Google Scholar 

  5. Rinaldi M, Martinelli L, Volpato G, et al. Gastroesophageal reflux as a cause of obliterative bronchiolitis: a case report. Transplant Proc. 1995;27:2006–7.

    PubMed  CAS  Google Scholar 

  6. Hartwig M, Anderson D, Onaitis M, et al. Fundoplication after lung transplantation prevents the allograft dysfunction associated with reflux. Ann Thorac Surg. 2011;92:462–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Birring S. Controversies in the evaluation and management of chronic cough. Am J Respir Crit Care Med. 2010;183:709–15.

    Google Scholar 

  8. Fathi H, Wright C, Thompson R, et al. Chronic cough and esomeprazole: a double-blind placebo-controlled parallel study. Respirology. 2011;16:1150–6.

    Article  PubMed  Google Scholar 

  9. Mastronarde J, Anthonisen N, Castro M, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360:1487–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Irwin R, Baumann M, Bolser D, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006;129:1S–23S.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Patti M, Tedesco P, Golden J, et al. Idiopathic pulmonary fibrosis: how often is it really idiopathic? J Gastrointest Surg. 2005;9:1053–8.

    Article  PubMed  Google Scholar 

  12. Raghu G. The role of gastroesophageal reflux in idiopathic pulmonary fibrosis. Am J Med. 2003;115:60S–4S.

    Article  PubMed  Google Scholar 

  13. Glauser FL, Millen JE, Falls R, et al. Increased alveolar epithelial permeability with acid aspiration: the effects of high-dose steroids. Am Rev Respir Dis. 1970;120:1119–23.

    Google Scholar 

  14. Salley S, Santo G, Barnhart M, et al. Immediate histopathology of hydrocholoric acid aspiration. Scan Electron Microsc. 1970;3:911–20.

    Google Scholar 

  15. Schwartz D, Wynne J, Gibbs C, et al. The pulmonary consequences of aspiration of gastric contents at pH values greater than 2.5. Am Rev Respir Dis. 1980;121:119–26.

    PubMed  CAS  Google Scholar 

  16. el-Serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans. Gastroenterology. 1997;113:755–60.

    Article  CAS  PubMed  Google Scholar 

  17. Mays E, Dubois J, Hamilton G, et al. Pulmonary fibrosis associated with tracheobronchial aspiration: a study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology. Chest. 1976;69:512–5.

    Article  CAS  PubMed  Google Scholar 

  18. Sweet M, Patti M, Leard L, et al. Gastroesophageal reflux in patients with idiopathic pulmonary fibrosis referred for lung transplantation. J Thorac Cardiovasc Surg. 2007;133:1078–84.

    Article  PubMed  Google Scholar 

  19. Beck-Schimmer B, Bonvini J. Bronchoaspiration: incidence, consequences and management. Eur J Anaesthesiol. 2011;28:78–84.

    Article  PubMed  Google Scholar 

  20. Hu X, Lee J, Pianosi P, et al. Aspiration-related pulmonary syndromes. Chest. 2015;147:815–23.

    Article  PubMed  Google Scholar 

  21. Marik P. Pulmonary aspiration syndromes. Curr Opin Pulm Med. 2011;17:148–54.

    Article  PubMed  Google Scholar 

  22. Kennedy T, Johnson K, Kunkel R, et al. Acute acid aspiration lung injury in the rat: biphasic pathogenesis. Anesth Analg. 1989;69:87–92.

    PubMed  CAS  Google Scholar 

  23. Madjdpour L, Kneller S, Booy C, et al. Acid-induced lung injury: role of nuclear factor-κB. Anesthesiology. 2003;99:1323–32.

    Article  CAS  PubMed  Google Scholar 

  24. Appel J, Lee S, Hartwig M, et al. Characterization of the innate response to chronic aspiration in a novel rodent model. Respir Res. 2007;8:87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tobin R, Pope C, Pellegrini C, et al. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;158:1804–8.

    Article  CAS  PubMed  Google Scholar 

  26. Raghu G, Freudenberger T, Yang S, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;27:136–42.

    Article  CAS  PubMed  Google Scholar 

  27. Lee J, Collard H, Raghu G, et al. Does chronic microaspiration cause idiopathic pulmonary fibrosis. Am J Med. 2010;123:304–11.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lee J, Ryu J, Elicker B, et al. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;184:1390–4.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Linden P, Gilbert R, Yeap B, et al. Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation. J Thorac Cardiovasc Surg. 2006;131:438–46.

    Article  PubMed  Google Scholar 

  30. Young L, Hadjiliadis D, Davis D, et al. Lung transplantation exacerbates gastroesophageal reflux disease. Chest. 2003;124:1689–93.

    Article  PubMed  Google Scholar 

  31. Li B, Hartwig M, Appel J, et al. Chronic aspiration of gastric fluid induces the development of obliterative bronchiolitis in rat lung transplants. Am J Transplant. 2008;8:1614–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Palmer S, Miralles A, Howell D, et al. Gastresophageal reflux as a reversible cause of allograft dysfunction after lung transplantation. Chest. 2000;118:1214–7.

    Article  CAS  PubMed  Google Scholar 

  33. Blondeau K, Mertens V, Vanaudenaerde B, et al. Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection. Eur Respir J. 2008;31:707–13.

    Article  CAS  PubMed  Google Scholar 

  34. Fisichella P, Davis C, Gagermeier J, et al. Laparoscopic antireflux surgery for gastroesophageal reflux disease after lung transplantation. J Surg Res. 2011;170:e279–86.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Fisichella P, Davis C, Lundberg P, et al. The protective role of laparoscopic antireflux surgery against aspiration of pepsin after lung transplantation. Surgery. 2011;150:598–606.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Stovold R, Forrest I, Corris P, et al. Pepsin, a biomarker of gastric aspiration in lung allografts. Am J Respir Crit Care Med. 2007;175:1298–303.

    Article  CAS  PubMed  Google Scholar 

  37. Shah N, Force S, Mitchell P, et al. Gastroesophageal reflux disease is associated with an increased rate of acute rejection in lung transplant allografts. Transplant Proc. 2010;42:2702–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ward C, Forrest I, Brownlee I, et al. Pepsin like activity in bronchoalveolar lavage fluid is suggestive of gastric aspiration in lung allografts. Thorax. 2005;60:872–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. D’Ovidio F, Mura M, Ridsdale R, et al. The effect of reflux and bile acid aspiration on the lung allograft and its surfactant and innate immunity molecules of SP-A and SP-D. Am J Transplant. 2006;6:1930–8.

    Article  CAS  PubMed  Google Scholar 

  40. Berkowitz N, Shulman L, McGregor C, et al. Gastroparesis after lung transplantation: potential role in postoperative respiratory complications. Chest. 1995;108:1602–7.

    Article  CAS  PubMed  Google Scholar 

  41. Bhashyam A, Mogayzel P, Cleary J, et al. Vagal control of mucociliary clearance in murine lungs: a study in a chronic preparation. Auton Neurosci. 2010;154:74–8.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Pazetti R, Pêgo-Fernandes P, Jatene F. Adverse effects of immunosuppressant drugs upon airway epithelial and mucociliary clearance: implications for lung transplant recipients. Drugs. 2013;73:1157–69.

    Article  CAS  PubMed  Google Scholar 

  43. Fisichella P, Davis C, Lowery E, et al. Pulmonary immune changes early after laparoscopic antireflux surgery in lung transplant patients with gastroesophageal reflux disease. J Surg Res. 2012;177:e65–73.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Cantu E, Appel J, Hartwig M, et al. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease. Ann Thorac Surg. 2004;78:1142–51.

    Article  PubMed  Google Scholar 

  45. Robertson A, Krishman A, Ward C, et al. Anti-reflux in lung transplant recipients: outcomes and effects on quality of life. Eur Respir J. 2012;39:691–7.

    Article  CAS  PubMed  Google Scholar 

  46. Hoppo T, Jarido V, Pennathur A, et al. Antireflux surgery preserves lung function in patients with gastroesophageal reflux disease and end-stage lung disease before and after lung transplantation. Arch Surg. 2011;146:1041–7.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matthew G. Hartwig .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Klapper, J.A., Gulack, B., Hartwig, M.G. (2018). Reflux and Aspiration: Their Presumed Role in Chronic Cough and the Development of End-Stage Lung Disease. In: Morice, A., Dettmar, P. (eds) Reflux Aspiration and Lung Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-90525-9_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-90525-9_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-90523-5

  • Online ISBN: 978-3-319-90525-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics