Advertisement

Pathophysiology in the Lung

  • Chris Ward
  • Rhys Jones
  • Mellissa Friel
  • Eoin Hunt
  • Des Murphy
Chapter

Abstract

This chapter discusses selected aspects of reflux, aspiration and pathophysiology in the lung. It is complimented by reviews that exist in this broad area dealing with adult [1–3] and paediatric patients [4–6].

References

  1. 1.
    Harding SM, Allen JE, Blumin JH, Warner EA, Pellegrini CA, Chan WW. Respiratory manifestations of gastroesophageal reflux disease. Ann N Y Acad Sci. 2013;1300:43–52.CrossRefPubMedGoogle Scholar
  2. 2.
    Morehead RS. Gastro-oesophageal reflux disease and non-asthma lung disease. Eur Respir Rev. 2009;18(114):233–43.CrossRefPubMedGoogle Scholar
  3. 3.
    Sweet MP, Patti MG, Hoopes C, Hays SR, Golden JA. Gastro-oesophageal reflux and aspiration in patients with advanced lung disease. Thorax. 2009;64(2):167–73.CrossRefPubMedGoogle Scholar
  4. 4.
    Trinick R, Johnston N, Dalzell AM, McNamara PS. Reflux aspiration in children with neurodisability – a significant problem, but can we measure it? J Pediatr Surg. 2012;47(2):291–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Blake K, Teague WG. Gastroesophageal reflux disease and childhood asthma. Curr Opin Pulm Med. 2013;19(1):24–9.PubMedGoogle Scholar
  6. 6.
    Mousa HM, Woodley FW. Gastroesophageal reflux in cystic fibrosis: current understandings of mechanisms and management. Curr Gastroenterol Rep. 2012;14(3):226–35.CrossRefPubMedGoogle Scholar
  7. 7.
    Hu X, Lee JS, Pianosi PT, Ryu JH. Aspiration-related pulmonary syndromes. Chest. 2015;147(3):815–23.CrossRefPubMedGoogle Scholar
  8. 8.
    Ward C, Forrest IA, Brownlee IA, Johnson GE, Murphy DM, Pearson JP, et al. Pepsin like activity in bronchoalveolar lavage fluid is suggestive of gastric aspiration in lung allografts. Thorax. 2005;60(10):872–4.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    DeMeester TR, Wang CI, Wernly JA, Pellegrini CA, Little AG, Klementschitsch P, et al. Technique, indications, and clinical use of 24 hour esophageal pH monitoring. J Thorac Cardiovasc Surg. 1980;79(5):656–70.PubMedGoogle Scholar
  10. 10.
    Zerbib F, des Varannes SB, Roman S, Pouderoux P, Artigue F, Chaput U, et al. Normal values and day-to-day variability of 24-h ambulatory oesophageal impedance-pH monitoring in a Belgian-French cohort of healthy subjects. Alimentary Pharmacol Ther. 2005;22(10):1011–21.CrossRefGoogle Scholar
  11. 11.
    Huxley EJ, Viroslav J, Gray WR, Pierce AK. Pharyngeal aspiration in normal adults and patients with depressed consciousness. Am J Med. 1978;64(4):564–8.CrossRefPubMedGoogle Scholar
  12. 12.
    McNally P, Ervine E, Shields MD, Dimitrov BD, El Nazir B, Taggart CC, et al. High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations. Thorax. 2011;66(2):140–3.CrossRefPubMedGoogle Scholar
  13. 13.
    Stovold R, Forrest IA, Corris PA, Murphy DM, Smith JA, Decalmer S, et al. Pepsin, a biomarker of gastric aspiration in lung allografts: a putative association with rejection. Am J Respir Crit Care Med. 2007;175(12):1298–303.CrossRefPubMedGoogle Scholar
  14. 14.
    Gleeson K, Eggli DF, Maxwell SL. Quantitative aspiration during sleep in normal subjects. Chest. 1997;111(5):1266–72.CrossRefPubMedGoogle Scholar
  15. 15.
    Gleeson K, Reynolds HY. Pneumonia in the intensive care unit setting. J Intensive Care Med. 1992;7(1):24–35.CrossRefPubMedGoogle Scholar
  16. 16.
    Shah NH, LePendu P, Bauer-Mehren A, Ghebremariam YT, Iyer SV, Marcus J, et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One. 2015;10(6):e0124653.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Abraham NS. Proton pump inhibitors: potential adverse effects. Curr Opin Gastroenterol. 2012;28(6):615–20.CrossRefPubMedGoogle Scholar
  18. 18.
    Ghebremariam YT, Cooke JP, Gerhart W, Griego C, Brower JB, Doyle-Eisele M, et al. Pleiotropic effect of the proton pump inhibitor esomeprazole leading to suppression of lung inflammation and fibrosis. J Transl Med. 2015;13:249.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Raghu G, Amatto VC, Behr J, Stowasser S. Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review. Eur Respir J. 2015;46(4):1113–30.CrossRefPubMedGoogle Scholar
  20. 20.
    Mays EE, Dubois JJ, Hamilton GB. 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(4):512–5.CrossRefPubMedGoogle Scholar
  21. 21.
    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.CrossRefPubMedGoogle Scholar
  22. 22.
    Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C, Hayes J, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;27(1):136–42.CrossRefPubMedGoogle Scholar
  23. 23.
    Aseeri A, Brodlie M, Lordan J, Corris P, Pearson J, Ward C, et al. Bile acids are present in the lower airways of people with cystic fibrosis. Am J Respir Crit Care Med. 2012;185(4):463.CrossRefPubMedGoogle Scholar
  24. 24.
    Griffin SM, Robertson AG, Bredenoord AJ, Brownlee IA, Stovold R, Brodlie M, et al. Aspiration and allograft injury secondary to gastroesophageal reflux occur in the immediate post-lung transplantation period (prospective clinical trial). Ann Surg. 2013;258(5):705–11. Discussion 11-2.CrossRefPubMedGoogle Scholar
  25. 25.
    Lee JS, Ryu JH, Elicker BM, Lydell CP, Jones KD, Wolters PJ, et al. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;184(12):1390–4.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lee JS, Song JW, Wolters PJ, Elicker BM, King TE Jr, Kim DS, et al. Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J. 2012;39(2):352–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Tcherakian C, Cottin V, Brillet PY, Freynet O, Naggara N, Carton Z, et al. Progression of idiopathic pulmonary fibrosis: lessons from asymmetrical disease. Thorax. 2011;66(3):226–31.CrossRefPubMedGoogle Scholar
  28. 28.
    Savarino E, Carbone R, Marabotto E, Furnari M, Sconfienza L, Ghio M, et al. Gastro-oesophageal reflux and gastric aspiration in idiopathic pulmonary fibrosis patients. Eur Respir J. 2013;42(5):1322–31.CrossRefPubMedGoogle Scholar
  29. 29.
    Allaix ME, Fisichella PM, Noth I, Herbella FA, Borraez Segura B, Patti MG. Idiopathic pulmonary fibrosis and gastroesophageal reflux. Implications for treatment. J Gastrointest Surg. 2014;18(1):100–4. Discussion 4-5.CrossRefPubMedGoogle Scholar
  30. 30.
    Allaix ME, Fisichella PM, Noth I, Mendez BM, Patti MG. The pulmonary side of reflux disease: from heartburn to lung fibrosis. J Gastrointest Surg. 2013;17(8):1526–35.CrossRefPubMedGoogle Scholar
  31. 31.
    Ghatol A, Ruhl AP, Danoff SK. Exacerbations in idiopathic pulmonary fibrosis triggered by pulmonary and nonpulmonary surgery: a case series and comprehensive review of the literature. Lung. 2012;190(4):373–80.CrossRefPubMedGoogle Scholar
  32. 32.
    Key AL, Holt K, Hamilton A, Smith JA, Earis JE. Objective cough frequency in idiopathic pulmonary fibrosis. Cough. 2010;6:4.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lee JS, Collard HR, Raghu G, Sweet MP, Hays SR, Campos GM, et al. Does chronic microaspiration cause idiopathic pulmonary fibrosis? Am J Med. 2010;123(4):304–11.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Eryuksel E, Dogan M, Olgun S, Kocak I, Celikel T. Incidence and treatment results of laryngopharyngeal reflux in chronic obstructive pulmonary disease. Eur Arch Otorhinolaryngol. 2009;266(8):1267–71.CrossRefPubMedGoogle Scholar
  35. 35.
    Pacheco-Galvan A, Hart SP, Morice AH. Relationship between gastro-oesophageal reflux and airway diseases: the airway reflux paradigm. Arch Bronconeumol. 2011;47(4):195–203.CrossRefPubMedGoogle Scholar
  36. 36.
    Andersen LI, Jensen G. Prevalence of benign oesophageal disease in the Danish population with special reference to pulmonary disease. J Intern Med. 1989;225(6):393–402.CrossRefPubMedGoogle Scholar
  37. 37.
    Casanova C, Baudet JS, del Valle Velasco M, Martin JM, Aguirre-Jaime A, de Torres JP, et al. Increased gastro-oesophageal reflux disease in patients with severe COPD. Eur Respir J. 2004;23(6):841–5.CrossRefPubMedGoogle Scholar
  38. 38.
    Tottrup A, Forman A, Madsen G, Andersson KE. The actions of some beta-receptor agonists and xanthines on isolated muscle strips from the human oesophago-gastric junction. Pharmacol Toxicol. 1990;67(4):340–3.CrossRefPubMedGoogle Scholar
  39. 39.
    Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12):1128–38.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Perng DW, Chang KT, Su KC, Wu YC, Wu MT, Hsu WH, et al. Exposure of airway epithelium to bile acids associated with gastroesophageal reflux symptoms: a relation to transforming growth factor-beta1 production and fibroblast proliferation. Chest. 2007;132(5):1548–56.CrossRefPubMedGoogle Scholar
  41. 41.
    Ward C, Ryan V, Pearson J. Susceptibility to exacerbation in COPD. N Engl J Med. 2010;363(27):2671. Author reply.PubMedGoogle Scholar
  42. 42.
    Jung YH, Lee DY, Kim DW, Park SS, Heo EY, Chung HS, et al. Clinical significance of laryngopharyngeal reflux in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulm Dis. 2015;10:1343–51.Google Scholar
  43. 43.
    Jarjour NN, Erzurum SC, Bleecker ER, Calhoun WJ, Castro M, Comhair SA, et al. Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. Am J Respir Crit Care Med. 2012;185(4):356–62.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    American Lung Association Asthma Clinical Research C, Mastronarde JG, Anthonisen NR, Castro M, Holbrook JT, Leone FT, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360(15):1487–99.CrossRefGoogle Scholar
  45. 45.
    Kiljander TO, Junghard O, Beckman O, Lind T. Effect of esomeprazole 40 mg once or twice daily on asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2010;181(10):1042–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Blondeau K, Dupont LJ, Mertens V, Verleden G, Malfroot A, Vandenplas Y, et al. Gastro-oesophageal reflux and aspiration of gastric contents in adult patients with cystic fibrosis. Gut. 2008;57(8):1049–55.CrossRefPubMedGoogle Scholar
  47. 47.
    Hallberg K, Fandriks L, Strandvik B. Duodenogastric bile reflux is common in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2004;38(3):312–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Mertens V, Blondeau K, Van Oudenhove L, Vanaudenaerde B, Vos R, Farre R, et al. Bile acids aspiration reduces survival in lung transplant recipients with BOS despite azithromycin. Am J Transpl. 2011;11(2):329–35.CrossRefGoogle Scholar
  49. 49.
    Parikh S, Brownlee IA, Robertson AG, Manning NT, Johnson GE, Brodlie M, et al. Are the enzymatic methods currently being used to measure bronchoalveolar lavage bile salt levels fit for purpose? J Heart Lung Transpl. 2013;32(4):418–23.CrossRefGoogle Scholar
  50. 50.
    Brodlie M, Aseeri A, Lordan JL, Robertson AG, McKean MC, Corris PA, Griffin SM, Manning NJ, Pearson JP, Ward C. Bile acid aspiration in people with cystic fibrosis before and after lung transplantation. Eur Respir J. 2015;46(6):1820–3.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Fathi H, Moon T, Donaldson J, Jackson W, Sedman P, Morice AH. Cough in adult cystic fibrosis: diagnosis and response to fundoplication. Cough. 2009;5:1.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Boesch RP, Acton JD. Outcomes of fundoplication in children with cystic fibrosis. J Pediatr Surg. 2007;42(8):1341–4.CrossRefPubMedGoogle Scholar
  53. 53.
    Vos R, Blondeau K, Vanaudenaerde BM, Mertens V, Van Raemdonck DE, Sifrim D, et al. Airway colonization and gastric aspiration after lung transplantation: do birds of a feather flock together? J Heart Lung Transpl. 2008;27(8):843–9.CrossRefGoogle Scholar
  54. 54.
    Gregson AL, Wang X, Weigt SS, Palchevskiy V, Lynch JP 3rd, Ross DJ, et al. Interaction between Pseudomonas and CXC chemokines increases risk of bronchiolitis obliterans syndrome and death in lung transplantation. Am J Respir Crit Care Med. 2013;187(5):518–26.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    McShane PJ, Naureckas ET, Tino G, Strek ME. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2013;188(6):647–56.CrossRefPubMedGoogle Scholar
  56. 56.
    Mandal P, Morice AH, Chalmers JD, Hill AT. Symptoms of airway reflux predict exacerbations and quality of life in bronchiectasis. Respir Med. 2013;107(7):1008–13.CrossRefPubMedGoogle Scholar
  57. 57.
    Tsang KW, Lam WK, Kwok E, Chan KN, Hu WH, Ooi GC, et al. Helicobacter pylori and upper gastrointestinal symptoms in bronchiectasis. Eur Respir J. 1999;14(6):1345–50.CrossRefPubMedGoogle Scholar
  58. 58.
    Noth I, Zangan SM, Soares RV, Forsythe A, Demchuk C, Takahashi SM, et al. Prevalence of hiatal hernia by blinded multidetector CT in patients with idiopathic pulmonary fibrosis. Eur Respir J. 2012;39(2):344–51.CrossRefPubMedGoogle Scholar
  59. 59.
    Bredenoord AJ, Pandolfino JE, Smout AJ. Gastro-oesophageal reflux disease. Lancet. 2013;381(9881):1933–42.CrossRefPubMedGoogle Scholar
  60. 60.
    McDonnell MJ, Ahmed M, Das J, Ward C, Mokoka M, Breen DP, et al. Hiatal hernias are correlated with increased severity of non-cystic fibrosis bronchiectasis. Respirology. 2015;20(5):749–57.CrossRefPubMedGoogle Scholar
  61. 61.
    McDonnell MJ, O’Toole D, Rutherford R, De Soyza A, Lordan J, Pearson J, Ward C, Laffey JG. Bile acids cause direct inflammation and injury and worsen acid induced injury in the pulmonary epithelium. Am J Respir Crit Care Med. 2015;191:A1292.Google Scholar
  62. 62.
    McDonnell MJ, Ward C, Rutherford RM, Verdon B, Pearson JP, Aldhahrani A, Lordan J, De Soyza A, Laffey JG, O Toole D. Azithromycin attenuates release of bile acid-mediated neutrophilic and remodeling factors in bronchiectasis airway epithelial cells. Am J Respir Crit Care Med. 2018;197:A2841.Google Scholar
  63. 63.
    Robertson AG, Griffin SM, Murphy DM, Pearson JP, Forrest IA, Dark JH, et al. Targeting allograft injury and inflammation in the management of post-lung transplant bronchiolitis obliterans syndrome. Am J Transpl. 2009;9(6):1272–8.CrossRefGoogle Scholar
  64. 64.
    Hartwig MG, Anderson DJ, Onaitis MW, Reddy S, Snyder LD, Lin SS, et al. Fundoplication after lung transplantation prevents the allograft dysfunction associated with reflux. Ann Thorac Surg. 2011;92(2):462–8. Discussion 8-9.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Jones RT, Krishnan A, Zeybel GL, Pearson JP, Simpson AJ, Griffin SM, et al. P276 characterisation of reflux and aspiration in idiopathic pulmonary fibrosis; an integrated approach. Thorax. 2014;69(Suppl 2):A194.CrossRefGoogle Scholar
  66. 66.
    Krishnan A, Perry A, Robertson A, Brodlie M, Perry J, Corris P, et al. Identical biofilm forming strains of pseudomonas aeruginosa occur in lung allograft BAL and gastric juice from CF patients with gastro oesophageal reflux. J Heart Lung Transpl. 2013;32(4):S28.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Chris Ward
    • 1
  • Rhys Jones
    • 2
  • Mellissa Friel
    • 3
  • Eoin Hunt
    • 4
  • Des Murphy
    • 4
  1. 1.Institute of Cellular MedicineNewcastle UniversityNewcastle upon TyneUK
  2. 2.Northern Oesophago-Gastric UnitRoyal Victoria InfirmaryNewcastle upon TyneUK
  3. 3.Department of Respiratory MedicineGalway University HospitalsGalwayIreland
  4. 4.Department of Respiratory MedicineCork University HospitalsCorkIreland

Personalised recommendations