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Coughing Precipitated by Bordetella pertussis Infection

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Abstract

Infections with the gram-negative bacteria Bordetella pertussis (B. pertussis) have long been recognized as a significant threat to children and are increasingly recognized as a cause of cough in adolescents and adults. Antibiotic therapy, when administered during the virulent stages of the disease, can reduce the duration and severity of symptoms. Unfortunately, there are no effective treatments for the persistent coughing that accompanies and follows the infection. The pathogenesis of B. pertussis infection is briefly reviewed. Also discussed is the evidence supporting the hypothesis that the inflammatory peptide bradykinin may be responsible for the persistent, paroxysmal coughing associated with B. pertussis-initiated illness.

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References

  1. Hewlett EL, Edwards KM (2005) Clinical practice. Pertussis—not just for kids. N Engl J Med 352(12):1215–1222

    Article  CAS  PubMed  Google Scholar 

  2. Crowcroft NS, Pebody RG (2006) Recent developments in pertussis. Lancet 367(9526):1926–1936

    Article  PubMed  Google Scholar 

  3. Singh M, Lingappan K (2006) Whooping cough: the current scene. Chest 130(5):1547–1553

    Article  PubMed  Google Scholar 

  4. Brooks DA, Clover R (2006) Pertussis infection in the United States: role for vaccination of adolescents and adults. J Am Board Fam Med 19(6):603–611

    Article  PubMed  Google Scholar 

  5. Halperin SA (2007) The control of pertussis—2007 and beyond. N Engl J Med 356(2):110–113

    Article  CAS  PubMed  Google Scholar 

  6. Gogol EB, Cummings CA, Burns RC, Relman DA (2007) Phase variation and microevolution at homopolymeric tracts in Bordetella pertussis. BMC Genomics 8:122

    Article  PubMed  CAS  Google Scholar 

  7. Kallonen T, He Q (2009) Bordetella pertussis strain variation and evolution postvaccination. Expert Rev Vaccines 8(7):863–875

    Article  CAS  PubMed  Google Scholar 

  8. Altunaiji S, Kukuruzovic R, Curtis N, Massie J (2007) Antibiotics for whooping cough (pertussis). Cochrane Database Syst Rev (3):CD004404

  9. Paddock CD, Sanden GN, Cherry JD, Gal AA, Langston C, Tatti KM, Wu KH, Goldsmith CS, Greer PW, Montague JL, Eliason MT, Holman RC, Guarner J, Shieh WJ, Zaki SR (2008) Pathology and pathogenesis of fatal Bordetella pertussis infection in infants. Clin Infect Dis 47(3):328–338

    Article  PubMed  Google Scholar 

  10. Braman SS (2006) Postinfectious cough: ACCP evidence-based clinical practice guidelines. Chest 129(1 Suppl):138S–146S

    Article  PubMed  Google Scholar 

  11. Pillay V, Swingler G (2003) Symptomatic treatment of the cough in whooping cough. Cochrane Database Syst Rev (4):CD003257

  12. Carbonetti NH (2007) Immunomodulation in the pathogenesis of Bordetella pertussis infection and disease. Curr Opin Pharmacol 7(3):272–278

    Article  CAS  PubMed  Google Scholar 

  13. Relman DA, Domenighini M, Tuomanen E, Rappuoli R, Falkow S (1989) Filamentous hemagglutinin of Bordetella pertussis: nucleotide sequence and crucial role in adherence. Proc Natl Acad Sci USA 86(8):2637–2641

    Article  CAS  PubMed  Google Scholar 

  14. Luker KE, Collier JL, Kolodziej EW, Marshall GR, Goldman WE (1993) Bordetella pertussis tracheal cytotoxin and other muramyl peptides: distinct structure–activity relationships for respiratory epithelial cytopathology. Proc Natl Acad Sci USA 90(6):2365–2369

    Article  CAS  PubMed  Google Scholar 

  15. Joseph K, Kaplan AP (2005) Formation of bradykinin: a major contributor to the innate inflammatory response. Adv Immunol 86:159–208

    Article  CAS  PubMed  Google Scholar 

  16. Leeb-Lundberg LM, Marceau F, Müller-Esterl W, Pettibone DJ, Zuraw BL (2005) International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 57(1):27–77

    Article  CAS  PubMed  Google Scholar 

  17. Abraham WM, Scuri M, Farmer SG (2006) Peptide and non-peptide bradykinin receptor antagonists: role in allergic airway disease. Eur J Pharmacol 533(1–3):215–221

    Article  CAS  PubMed  Google Scholar 

  18. Proud D (1998) The kinin system in rhinitis and asthma. Clin Rev Allergy Immunol 16(4):351–364

    Article  CAS  PubMed  Google Scholar 

  19. Proud D, Togias A, Naclerio RM, Crush SA, Norman PS, Lichtenstein LM (1983) Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen. J Clin Invest 72(5):1678–1685

    Article  CAS  PubMed  Google Scholar 

  20. Christiansen SC, Proud D, Cochrane CG (1987) Detection of tissue kallikrein in the bronchoalveolar lavage fluid of asthmatic subjects. J Clin Invest 79(1):188–197

    Article  CAS  PubMed  Google Scholar 

  21. Christiansen SC, Proud D, Sarnoff RB, Juergens U, Cochrane CG, Zuraw BL (1992) Elevation of tissue kallikrein and kinin in the airways of asthmatic subjects after endobronchial allergen challenge. Am Rev Respir Dis 145(4 Pt 1):900–905

    CAS  PubMed  Google Scholar 

  22. Mansour E, Ahmed A, Cortes A, Caplan J, Burch RM, Abraham WM (1992) Mechanisms of metabisulfite-induced bronchoconstriction: evidence for bradykinin B2-receptor stimulation. J Appl Physiol 72(5):1831–1837

    CAS  PubMed  Google Scholar 

  23. Ricciardolo FL, Nadel JA, Graf PD, Bertrand C, Yoshihara S, Geppetti P (1994) Role of kinins in anaphylactic-induced bronchoconstriction mediated by tachykinins in guinea-pigs. Br J Pharmacol 113(2):508–512

    CAS  PubMed  Google Scholar 

  24. Coyle AJ, Ackerman SJ, Burch R, Proud D, Irvin CG (1995) Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation. J Clin Invest 95(4):1735–1740

    Article  CAS  PubMed  Google Scholar 

  25. Yoshihara S, Geppetti P, Hara M, Linden A, Ricciardolo FL, Chan B, Nadel JA (1996) Cold air-induced bronchoconstriction is mediated by tachykinin and kinin release in guinea pigs. Eur J Pharmacol 296(3):291–296

    Article  CAS  PubMed  Google Scholar 

  26. Grünberg K, Kuijpers EA, de Klerk EP, de Gouw HW, Kroes AC, Dick EC, Sterk PJ (1997) Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo. Am J Respir Crit Care Med 155(3):833–838

    PubMed  Google Scholar 

  27. Ricciardolo FL, Rado V, Fabbri LM, Sterk PJ, Di Maria GU, Geppetti P (1999) Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of tachykinins, bradykinin, and nitric oxide. Am J Respir Crit Care Med 159(2):557–562

    CAS  PubMed  Google Scholar 

  28. Scuri M, Forteza R, Lauredo I, Sabater JR, Botvinnikova Y, Allegra L, Abraham WM (2000) Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism. J Appl Physiol 89(4):1397–1402

    CAS  PubMed  Google Scholar 

  29. Folkerts G, Vlieger JW, de Vries A, Faas S, van Der Linde H, Engels F, de Jong JC, Verheyen FA, Van Heuven-Nolsen D, Nijkamp FP (2000) Virus- and bradykinin-induced airway hyperresponsiveness in guinea pigs. Am J Respir Crit Care Med 161(5):1666–1671

    CAS  PubMed  Google Scholar 

  30. Turner P, Dear J, Scadding G, Foreman JC (2001) Role of kinins in seasonal allergic rhinitis: icatibant, a bradykinin B2 receptor antagonist, abolishes the hyperresponsiveness and nasal eosinophilia induced by antigen. J Allergy Clin Immunol 107(1):105–113

    Article  CAS  PubMed  Google Scholar 

  31. Effros RM, Dunning MB 3rd, Biller J, Shaker R (2004) The promise and perils of exhaled breath condensates. Am J Physiol Lung Cell Mol Physiol 287(6):L1073–L1080

    Article  CAS  PubMed  Google Scholar 

  32. Fox AJ, Lalloo UG, Belvisi MG, Bernareggi M, Chung KF, Barnes PJ (1996) Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough. Nat Med 2(7):814–817

    Article  CAS  PubMed  Google Scholar 

  33. Tom B, Dendorfer A, de Vries R, Saxena PR, Jan Danser AH (2002) Bradykinin potentiation by ACE inhibitors: a matter of metabolism. Br J Pharmacol 137(2):276–284

    Article  CAS  PubMed  Google Scholar 

  34. Dicpinigaitis PV (2006) Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines. Chest 129(1 Suppl):169S–173S

    Article  CAS  PubMed  Google Scholar 

  35. Jacoby DB (2002) Virus-induced asthma attacks. JAMA 287(6):755–761

    Article  PubMed  Google Scholar 

  36. Kaneko T, Stearns-Kurosawa DJ, Taylor F Jr, Twigg M, Osaki K, Kinasewitz GT, Peer G, Kurosawa S (2003) Reduced neutrophil CD10 expression in nonhuman primates and humans after in vivo challenge with E. coli or lipopolysaccharide. Shock 20(2):130–137

    Article  CAS  PubMed  Google Scholar 

  37. Casey L, Krieger B, Kohler J, Rice C, Oparil S, Szidon P (1981) Decreased serum angiotensin converting enzyme in adult respiratory distress syndrome associated with sepsis: a preliminary report. Crit Care Med 9(9):651–654

    Article  CAS  PubMed  Google Scholar 

  38. Choudry NB, Fuller RW, Pride NB (1989) Sensitivity of the human cough reflex: effect of inflammatory mediators prostaglandin E2, bradykinin, and histamine. Am Rev Respir Dis 140(1):137–141

    CAS  PubMed  Google Scholar 

  39. Canning BJ, Mazzone SB, Meeker SN, Mori N, Reynolds SM, Undem BJ (2004) Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs. J Physiol 557(Pt 2):543–558

    Article  CAS  PubMed  Google Scholar 

  40. El-Hashim AZ, Amine SA (2005) The role of substance P and bradykinin in the cough reflex and bronchoconstriction in guinea-pigs. Eur J Pharmacol 513(1–2):125–133

    Article  CAS  PubMed  Google Scholar 

  41. Mazzone SB, Mori N, Canning BJ (2005) Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea-pigs. J Physiol 569(Pt 2):559–573

    Article  CAS  PubMed  Google Scholar 

  42. Arndt PG, Young SK, Poch KR, Nick JA, Falk S, Schrier RW, Worthen GS (2006) Systemic inhibition of the angiotensin-converting enzyme limits lipopolysaccharide-induced lung neutrophil recruitment through both bradykinin and angiotensin II-regulated pathways. J Immunol 177(10):7233–7241

    CAS  PubMed  Google Scholar 

  43. Johnson AR, Ashton J, Schulz WW, Erdös EG (1985) Neutral metalloendopeptidase in human lung tissue and cultured cells. Am Rev Respir Dis 132(3):564–568

    CAS  PubMed  Google Scholar 

  44. Sunday ME, Hua J, Torday JS, Reyes B, Shipp MA (1992) CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation. J Clin Invest 90(6):2517–2525

    Article  CAS  PubMed  Google Scholar 

  45. Johnson AM, Alper CA, Rosen FS, Craig JM (1971) C1 inhibitor: evidence for decreased hepatic synthesis in hereditary angioneurotic edema. Science 173(996):553–554

    Article  CAS  PubMed  Google Scholar 

  46. Stoppa-Lyonnet D, Tosi M, Laurent J, Sobel A, Lagrue G, Meo T (1987) Altered C1 inhibitor genes in type I hereditary angioedema. N Engl J Med 317(1):1–6

    Article  CAS  PubMed  Google Scholar 

  47. Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A (1998) Plasma bradykinin in angio-oedema. Lancet 351(9117):1693–1697

    Article  CAS  PubMed  Google Scholar 

  48. Han ED, MacFarlane RC, Mulligan AN, Scafidi J, Davis AE 3rd (2002) Increased vascular permeability in C1 inhibitor-deficient mice mediated by the bradykinin type 2 receptor. J Clin Invest 109(8):1057–1063

    CAS  PubMed  Google Scholar 

  49. Bork K, Frank J, Grundt B, Schlattmann P, Nussberger J, Kreuz W (2007) Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant). J Allergy Clin Immunol 119(6):1497–1503

    Article  CAS  PubMed  Google Scholar 

  50. Temino VM, Peebles RS Jr (2008) The spectrum and treatment of angioedema. Am J Med 121(4):282–286

    Article  PubMed  Google Scholar 

  51. Marr N, Luu RA, Fernandez RC (2007) Bordetella pertussis binds human C1 esterase inhibitor during the virulent phase, to evade complement-mediated killing. J Infect Dis 195(4):585–588

    Article  CAS  PubMed  Google Scholar 

  52. Kirimanjeswara GS, Agosto LM, Kennett MJ, Bjornstad ON, Harvill ET (2005) Pertussis toxin inhibits neutrophil recruitment to delay antibody-mediated clearance of Bordetella pertussis. J Clin Invest 115(12):3594–3601

    Article  CAS  PubMed  Google Scholar 

  53. Andreasen C, Carbonetti NH (2008) Pertussis toxin inhibits early chemokine production to delay neutrophil recruitment in response to Bordetella pertussis respiratory tract infection in mice. Infect Immun 76(11):5139–5148

    Article  CAS  PubMed  Google Scholar 

  54. Kenne E, Soehnlein O, Herwald H, Lindbom L (2009) Neutrophil-derived heparin binding protein (HBP) is an endogenous activator of the kallikrein-kinin system. FASEB J 23:762.3

    Google Scholar 

  55. Garcia JG, Wang P, Schaphorst KL, Becker PM, Borbiev T, Liu F, Birukova A, Jacobs K, Bogatcheva N, Verin AD (2002) Critical involvement of p38 MAP kinase in pertussis toxin-induced cytoskeletal reorganization and lung permeability. FASEB J 16(9):1064–1076

    Article  CAS  PubMed  Google Scholar 

  56. Camerer E, Regard JB, Cornelissen I, Srinivasan Y, Duong DN, Palmer D, Pham TH, Wong JS, Pappu R, Coughlin SR (2009) Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J Clin Invest 119(7):1871–1879

    CAS  PubMed  Google Scholar 

  57. Proud D, Vio CP (1993) Localization of immunoreactive tissue kallikrein in human trachea. Am J Respir Cell Mol Biol 8(1):16–19

    CAS  PubMed  Google Scholar 

  58. Tamaoki J, Takeyama K, Yamawaki I, Kondo M, Konno K (1997) Lipopolysaccharide-induced goblet cell hypersecretion in the guinea pig trachea: inhibition by macrolides. Am J Physiol 272(1 Pt 1):L15–L19

    CAS  PubMed  Google Scholar 

  59. Forteza R, Lauredo I, Abraham WM, Conner GE (1999) Bronchial tissue kallikrein activity is regulated by hyaluronic acid binding. Am J Respir Cell Mol Biol 21(6):666–674

    CAS  PubMed  Google Scholar 

  60. Yan F, Li W, Jono H, Li Q, Zhang S, Li JD, Shen H (2008) Reactive oxygen species regulate Pseudomonas aeruginosa lipopolysaccharide-induced MUC5AC mucin expression via PKC-NADPH oxidase-ROS-TGF-alpha signaling pathways in human airway epithelial cells. Biochem Biophys Res Commun 366(2):513–519

    Article  CAS  PubMed  Google Scholar 

  61. Herwald H, Mörgelin M, Olsén A, Rhen M, Dahlbäck B, Müller-Esterl W, Björck L (1998) Activation of the contact-phase system on bacterial surfaces—a clue to serious complications in infectious diseases. Nat Med 4(3):298–302

    Article  CAS  PubMed  Google Scholar 

  62. Lauredo IT, Forteza RM, Botvinnikova Y, Abraham WM (2004) Leukocytic cell sources of airway tissue kallikrein. Am J Physiol Lung Cell Mol Physiol 286(4):L734–L740

    Article  CAS  PubMed  Google Scholar 

  63. Imamura T, Kobayashi H, Khan R, Nitta H, Okamoto K (2006) Induction of vascular leakage and blood pressure lowering through kinin release by a serine proteinase from Aeromonas sobria. J Immunol 177(12):8723–8729

    CAS  PubMed  Google Scholar 

  64. Moss J, Hom BE, Hewlett EL, Tsai SC, Adamik R, Halpern JL, Price SR, Manganiello VC (1988) Mechanism of enhanced sensitivity to bradykinin in pertussis toxin-treated fibroblasts: toxin increases bradykinin-stimulated prostaglandin formation. Mol Pharmacol 34(3):279–285

    CAS  PubMed  Google Scholar 

  65. Fujimoto M, Sakata T, Tsuruta Y, Iwagami S, Teraoka H, Mihara S, Fukiishi Y, Ide M (1990) Enhancement of bradykinin-induced prostacyclin synthesis in porcine aortic endothelial cells by pertussis toxin. Possible implication of lipocortin I. Biochem Pharmacol 40(12):2661–2670

    Article  CAS  PubMed  Google Scholar 

  66. Wolsing DH, Rosenbaum JS (1993) The mechanism for the rapid desensitization in bradykinin-stimulated inositol monophosphate production in NG108-15 cells involves interaction of a single receptor with multiple signaling pathways. J Pharmacol Exp Ther 266(1):253–261

    CAS  PubMed  Google Scholar 

  67. Kozaki Y, Kambe F, Hayashi Y, Ohmori S, Seo H, Kumazawa T, Mizumura K (2007) Molecular cloning of prostaglandin EP3 receptors from canine sensory ganglia and their facilitatory action on bradykinin-induced mobilization of intracellular calcium. J Neurochem 100(6):1636–1647

    CAS  PubMed  Google Scholar 

  68. Morice AH, Lowry R, Brown MJ, Higenbottam T (1987) Angiotensin-converting enzyme and the cough reflex. Lancet 2(8568):1116–1118

    Article  CAS  PubMed  Google Scholar 

  69. Katsumata U, Sekizawa K, Ujiie Y, Sasaki H, Takishima T (1991) Bradykinin-induced cough reflex markedly increases in patients with cough associated with captopril and enalapril. Tohoku J Exp Med 164(2):103–109

    Article  CAS  PubMed  Google Scholar 

  70. Morice AH, Turley AJ, Linton TK (1997) Human ACE gene polymorphism and distilled water induced cough. Thorax 52(2):111–113

    Article  CAS  PubMed  Google Scholar 

  71. Wood N, McIntyre P (2008) Pertussis: review of epidemiology, diagnosis, management and prevention. Paediatr Respir Rev 9(3):201–211

    Article  PubMed  Google Scholar 

  72. Kajekar R, Proud D, Myers AC, Meeker SN, Undem BJ (1999) Characterization of vagal afferent subtypes stimulated by bradykinin in guinea pig trachea. J Pharmacol Exp Ther 289(2):682–687

    CAS  PubMed  Google Scholar 

  73. Carr MJ, Kollarik M, Meeker SN, Undem BJ (2003) A role for TRPV1 in bradykinin-induced excitation of vagal airway afferent nerve terminals. J Pharmacol Exp Ther 304(3):1275–1279

    Article  CAS  PubMed  Google Scholar 

  74. Kollarik M, Undem BJ (2004) Activation of bronchopulmonary vagal afferent nerves with bradykinin, acid and vanilloid receptor agonists in wild-type and TRPV1−/− mice. J Physiol 555(Pt 1):115–123

    CAS  PubMed  Google Scholar 

  75. Lee MG, Macglashan DW Jr, Undem BJ (2005) Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre activation. J Physiol 566(Pt 1):205–212

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the National Institutes of Health (HL083192).

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Correspondence to Brendan J. Canning.

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Hewitt, M., Canning, B.J. Coughing Precipitated by Bordetella pertussis Infection. Lung 188 (Suppl 1), 73–79 (2010). https://doi.org/10.1007/s00408-009-9196-9

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