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Effect of Reflux on Cough Sensitivity and Bronchial Responsiveness

  • Peter V. Dicpinigaitis
Chapter

Abstract

Gastroesophageal reflux is an extremely common condition often associated with chronic cough, dyspnea, laryngeal discomfort, and other extraesophageal symptoms. A considerable body of evidence has established an association of reflux with the presence of cough reflex hypersensitivity and/or bronchial hyperresponsiveness. However, the demonstration of such airway hyperreactivity does not uniformly predict the presence of underlying pathology nor the occurrence of symptoms. Furthermore, treatment aimed at suppressing cough reflex sensitivity or bronchial responsiveness, even when successful, often fails to ameliorate associated symptoms. Given that reflux, cough, and asthma are all very common conditions, the association of reflux with cough reflex hypersensitivity and bronchial hyperresponsiveness is likely causal in some individuals and coincidental in others. Adequately performed clinical trials evaluating the presence of pathological reflux, its effect on cough reflex sensitivity, airway responsiveness and pulmonary symptoms, as well as objective and symptomatic response to therapeutic interventions, will be most useful in elucidating the pathophysiologic manifestations of reflux on the respiratory system.

References

  1. 1.
    Faruqi S, Molyneux ID, Fathi H, Wright C, Thompson R, Morice AH. Chronic cough and esomeprazole: a double-blind placebo-controlled parallel study. Respirology. 2011;16:1150–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Shaheen NJ, Crockett SD, Bright SD, Madanick RD, Buckmire R, Couch M, et al. Randomised clinical trial: high-dose acid suppression for chronic cough-a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;33:225–34.CrossRefPubMedGoogle Scholar
  3. 3.
    American Lung Association Asthma Clinical Research Centers, Mastronarde JG, Anthonisen NR, Castro M, Holbrook JT, Leone FT, Teague WG, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360:1487–99.CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Chan WW, Chiou E, Obstein KL, Tignor AS, Whitlock TL. The efficacy of proton pump inhibitors for the treatment of asthma in adults: a meta-analysis. Arch Intern Med. 2011;171:620–9.CrossRefPubMedGoogle Scholar
  5. 5.
    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;181:1042–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Smid SD, Page AJ, O’Donnell T, Langman J, Rowlan R, Blackshaw LA. Oesophagitis-induced changes in capsaicin-sensitive tachykininergic pathways in the ferret lower oesophageal sphincter. Neurogastroenterol Motil. 1998;10:403–11.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhang S, Liu Z, Heldsinger A, Owyang C, Yu S. Intraluminal acid activates esophageal nodose C fibers after mast cell activation. Am J Physiol Gastrointest Liver Physiol. 2014;306:G200–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Yu X, Hu Y, Yu S. Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus. Am J Physiol Gastrointest Liver Physiol. 2014;307:G471–8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Morice AH, Fontana GA, Belvisi MG, Birring SS, Chung KF, Dicpinigaitis PV, Kastelik JA, McGarvey LP, Smith JA, Tatar M, Widdicombe J. European Respiratory Society Task Force. ERS guidelines on the assessment of cough. Eur Respir J. 2007;29:1256–76.CrossRefPubMedGoogle Scholar
  10. 10.
    Javorkova N, Varechova S, Pecova R, Tatar M, Balaz D, Demeter M, et al. Acidification of the esophagus acutely increases the cough sensitivity in patients with gastro-oesophageal reflux and chronic cough. Neurogastroenterol Motil. 2008;20:119–24.PubMedGoogle Scholar
  11. 11.
    Wu DN, Yamauchi K, Kobayashi H, Tanifuli Y, Kato C, Suzuki K, et al. Effects of esophageal acid perfusion on cough responsiveness in patients with bronchial asthma. Chest. 2002;122:505–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Ferrari M, Olivieri M, Sembenini C, Benini L, Zuccali V, Bardelli E, et al. Tussive effect of capsaicin in patients with gastroesophageal reflux without cough. Am J Respir Crit Care Med. 1995;151:557–61.CrossRefPubMedGoogle Scholar
  13. 13.
    Qiu Z, Yu L, Xu S, Liu B, Zhao T, Lu H, et al. Cough reflex sensitivity and airway inflammation in patients with chronic cough due to non-acid gastro-esophageal reflux. Respirology. 2011;16:645–52.CrossRefPubMedGoogle Scholar
  14. 14.
    Xu X, Yang Z, Chen Q, Yu L, Liang S, Lu H, et al. Comparison of clinical characteristics of chronic cough due to non-acid and acid gastroesophageal reflux. Clin Respir J. 2015;9:196–202.CrossRefPubMedGoogle Scholar
  15. 15.
    Varechova S, Mikler J, Murgas D, Dragula M, Banovcin P, Hanacek J. Cough reflex sensitivity in children with suspected and confirmed gastroesophageal reflux disease. J Physiol Pharmacol. 2007;58(Suppl 5;Pt 2):717–27.PubMedGoogle Scholar
  16. 16.
    Ferrari M, Benini L, Brotto E, Locatelli F, De Iorio F, Bonella F, et al. Omeprazole reduces the response to capsaicin but not to methacholine in asthmatic patients with proximal reflux. Scand J Gastroenterol. 2007;42:299–307.CrossRefPubMedGoogle Scholar
  17. 17.
    Benini L, Ferrari M, Sembenini C, Olivieri M, Micciolo R, Zuccali V, et al. Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oespophageal damage. Gut. 2000;46:762–7.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    O’Connell F, Thomas VE, Pride NB, Fuller RW. Capsaicin cough sensitivity decreases with successful treatment of chronic cough. Am J Respir Crit Care Med. 1994;150:374–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Torrego A, Cimbollek S, Hew M, Chung KF. No effect of omeprazole on pH of exhaled breath condensate in cough associated with gastro-esophageal reflux. Cough. 2005;1:10.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Nieto L, de Diego A, Perpina M, Compte L, Garrigues V, Martinez E, et al. Cough reflex testing with inhaled capsaicin in the study of chronic cough. Respir Med. 2003;97:393–400.CrossRefPubMedGoogle Scholar
  21. 21.
    Herrera-Lopez JA, Mejia-Rivas MA, Vargas-Vorachkova F, Valdovinos-Diaz MA. Capsaicin induction of esophageal symptoms in different phenotypes of gastroesophageal reflux disease. Rev Gastroenterol Mex. 2010;75:396–404.PubMedGoogle Scholar
  22. 22.
    Kindt S, Vos R, Blondeau K, Tack J. Influence of intra-oesophageal capsaicin instillation on heartburn induction and oesophageal sensitivity in man. Neurogastroenterol Motil. 2009;21:1032–e82.CrossRefPubMedGoogle Scholar
  23. 23.
    Rodriguez-Stanley S, Collings KL, Robinson M, Owen W, Miner PB. The effects of capsaicin on reflux, gastric emptying and dyspepsia. Aliment Pharmacol Ther. 2000;14:129–34.CrossRefPubMedGoogle Scholar
  24. 24.
    Grossi L, Cappello G, Marzio L. Effect of an acute intraluminal administration of capsaicin on oesophageal motor pattern in GORD patients with ineffective oesophageal motility. Neurogastroenterol Motil. 2006;18:632–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Dariusz Z, Wojciech J, Jozef D, Andrzej K, Jacek C, Jan C, et al. Assessment of cough threshold in patients with gastroesophageal reflux disease [article in Polish]. Pneumonol Alergol Pol. 2003;71:221–9.PubMedGoogle Scholar
  26. 26.
    Ziora D, Jarosz W, Dzielicki J, Ciekalski J, Krzywiecki A, Dworniczak S, et al. Citric acid cough threshold in patients with gastroesophageal reflux disease rises after laparoscopic fundoplication. Chest. 2005;128:2458–64.CrossRefPubMedGoogle Scholar
  27. 27.
    Ebihara S, Ebihara T, Yamasaki M, Asada M, Yamanda S, Niu K, et al. Contribution of gastric acid in elderly nursing home patients with cough reflex hypersensitivity. J Am Geriatr Soc. 2007;55:1686–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Stein MR. Possible mechanisms of influence of esophageal acid on airway hyperesponsiveness. Am J Med. 2003;115(Suppl 3A):55S–9S.CrossRefPubMedGoogle Scholar
  29. 29.
    Allen GB, Leclair TR, von Reyn J, Larrabee YC, Cloutier ME, Irvin CG, et al. Acid aspiration-induced airways hyperresponsiveness in mice. J Appl Physiol. 2009;107:1763–70.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Herve P, Denjean A, Jian R, Simonneau G, Duroux P. Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects. Am Rev Respir Dis. 1986;134:986–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Chakrabarti S, Singh K, Singh V, Nain CK, Jindal SK. Airway response to acid instillation in esophagus in bronchial asthma. Indian J Gastroenterol. 1995;14:44–7.PubMedGoogle Scholar
  32. 32.
    Wu DN, Tanifuji Y, Kobayashi H, Yamauchi K, Kato C, Suzuki K, et al. Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma. Chest. 2000;118(6):1553.CrossRefPubMedGoogle Scholar
  33. 33.
    Dal Negro RW, Tognella S, Micheletto C, Sandri M, Guerriero M. A MCh test pre-post esophageal acidification in detecting GER-related asthma. J Asthma. 2009;46:351–5.CrossRefPubMedGoogle Scholar
  34. 34.
    Vincent D, Cohen-Jonathan AM, Leport J, Merrouche M, Geronimi A, Pradalier A, et al. Gastro-oesophageal reflux prevalence and relationship with bronchial reactivity in asthma. Eur Respir J. 1997;10:2255–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Bagnato GF, Gulli S, Giacobbe O, De Pasquale R, Purello D’Ambrosio F. Bronchial hyperresponsiveness in subjects with gastroesophageal reflux. Respiration. 2000;67:507–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Moote DW, Lloyd DA, McCourtie DR, Wells GA. Increase in gastroesophageal reflux during methacholine-induced bronchospasm. J Allergy Clin Immunol. 1986;78:619–23.CrossRefPubMedGoogle Scholar
  37. 37.
    Zerbib F, Guisset O, Lamouliatte H, Quinton A, Galmiche JP, Tunon-De-Lara JM. Effects of bronchial obstruction on lower esophageal sphincter motility and gastroesophageal reflux in patients with asthma. Am J Respir Crit Care Med. 2002;166:1206–11.CrossRefPubMedGoogle Scholar
  38. 38.
    Ekstrom T, Tibbling L. Esophageal acid perfusion, airway function, and symptoms in asthmatic patients with marked bronchial hyperreactivity. Chest. 1989;96:995–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Singh V, Aggarwal V, Bansal S, Nijhawan S, Chaudhary N. Effect of intraesophageal acid instillation on airway reactivity in patients with asthma. J Assoc Physicians India. 2000;48:601–2.PubMedGoogle Scholar
  40. 40.
    Agarwal A, Rishi JP, Gupta AN, Bhandari VM. Histamine bronchoprovocation tests in subjects with gastro-oesophageal reflux disease. J Assoc Physicians India. 1990;38:159–61.PubMedGoogle Scholar
  41. 41.
    Compte L, Garrigues V, Perpina M, Ponce J. Prevalence of gastroesophageal reflux in asthma. J Asthma. 2000;37:175–82.CrossRefPubMedGoogle Scholar
  42. 42.
    DiMango E, Holbrook JT, Simpson E, Reibman J, Richter J, Narula S, et al. Effects of asymptomatic proximal and distal gastroesophageal reflux on asthma severity. Am J Respir Crit Care Med. 2009;180:809–16.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Emilsson OI, Bengtsson A, Franklin KA, Toren K, Benediktsdottir B, Farkhoov A, et al. Nocturnal gastro-oesophageal reflux, asthma and symptoms of OSA: a longitudinal, general population study. Eur Respir J. 2013;41:1347–54.CrossRefPubMedGoogle Scholar
  44. 44.
    Jiang SP, Liang RY, Zeng ZY, Liu QL, Liang YK, Li JG. Effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease. World J Gastroenterol. 2003;9(5):1123.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sato A, Tanifuji Y, Kobayashi H, Inoue H. Effects of proton pump inhibitor on airway hyperresponsiveness in asthmatics with gastroesophageal reflux. Arerugi. 2006;55:641–6.PubMedGoogle Scholar
  46. 46.
    Khoshoo V, Mohnot S, Haydel R, Saturno E, Edell D, Kobernick A. Bronchial hyperreactivity in non-atopic children with asthma and reflux: effect of anti-reflux treatment. Pediatr Pulmonol. 2009;44:1070–4.CrossRefPubMedGoogle Scholar
  47. 47.
    Kiljander TO, Salomaa ER, Hietanen EK, Ovaska J, Helenius H, Liippo K. Gastroesophageal reflux and bronchial responsiveness: correlation and the effect of fundoplication. Respiration. 2002;69:434–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Karbasi A, Ardestani ME, Ghanei M, Harandi AA. The association between reflux esophagitis and airway hyper-reactivity in patients with gastro-esophageal reflux. J Res Med Sci. 2013;18:473–6.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Boeree MJ, Peters FT, Postma DS, Kleibeuker JH. No effects of high-dose omeprazole in patients with severe airway hyperesponsiveness and (a)symptomatic gstro-oesophageal reflux. Eur Respir J. 1998;11:1070–4.CrossRefPubMedGoogle Scholar
  50. 50.
    Kiljander T, Rantanen T, Kellokumpu I, Koobi T, Lammi L, Nieminen M, et al. Comparison of the effects of esomeprazole and fundoplication on airway responsiveness in patients with gastro-oesophageal reflux disease. Clin Respir J. 2013;7:281–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Peter V. Dicpinigaitis
    • 1
  1. 1.Albert Einstein College of Medicine and Montefiore Medical CenterBronxUSA

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