Current Allergy and Asthma Reports

, Volume 3, Issue 2, pp 166–171 | Cite as

Physiopathology of airway hyperresponsiveness

  • Louis-Philippe Boulet
Article

Abstract

Airway hyperresponsiveness (AHR), the tendency of the airways to narrow too much and too easily in response to various stimuli, is a universal feature of asthma, although it is not exclusive to this disease. Airway responsiveness shows a unimodal distribution in the general population and might vary with time, increasing after exposure to allergens, industrial substances, or infectious agents in predisposed individuals, or decreasing for variable time periods after environmental or pharmacologic interventions. Airway inflammation and structural airway changes can lead to this heightened airway response, but the mechanisms by which they modify airway function are still unclear. They might be associated with increased contractile properties of the airways—from an increase in contractile elements, a change in smooth muscle mechanical properties, or a reduction of forces opposing bronchoconstriction, such as reduced airway-parenchymal interdependence. Other factors, such as neurohumoral influences and “geometric factors” (eg, airway caliber), can modulate the degree of AHR.

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References and Recommended Reading

  1. 1.
    Woolcock AJ: What is bronchial hyperresponsiveness from the clinical standpoint? In Airway Hyperresponsiveness: Is It Really Important for Asthma? Edited by Page CP, Gardiner PJ. Oxford: Blackwell Scientific Publication; 1993:1–9.Google Scholar
  2. 2.
    Cockcroft DW: Airway responsiveness. In Asthma. Edited by Barnes PJ, Grunstein MM, Leff AR, Woolcock AJ. Philadelphia: Lippincott-Raven; 1997.Google Scholar
  3. 3.
    Sterk PJ, Bel EH: Bronchial hyperresponsiveness: the need for a distinction between hypersensitivity and excessive airway narrowing. Eur Respir J 1989, 2:267–274.PubMedGoogle Scholar
  4. 4.
    Cockcroft DW, Berscheid BA, Murdock KY: Unimodal distribution of bronchial responsiveness to inhaled histamine in a random human population. Chest 1983, 83:751–754. One of the initial reports suggesting that airway responsiveness has a unimodal distribution.PubMedGoogle Scholar
  5. 5.
    Rijcken B, Schouten JP, Weiss ST, et al.: Long-term variability of bronchial responsiveness to histamine in a random population sample of adults. Am Rev Respir Dis 1993, 148:944–949.PubMedGoogle Scholar
  6. 6.
    Jansen DF, Timens W, Kraan J, et al.: (A)Symptomatic bronchial hyper-responsiveness and asthma. Respir Med 1997, 91:121–134. An excellent review of asymptomatic airway responsiveness and why it is not associated with symptoms.PubMedCrossRefGoogle Scholar
  7. 7.
    Cockcroft DW, Murdock KY, Berscheid BA: Relationship between atopy and bronchial responsiveness to histamine in a random population. Ann Allergy 1984, 54:26–29.Google Scholar
  8. 8.
    Cockcroft DW, Killian DN, Mellon JJ, Hargreave FE: Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy 1977, 7:235–243.PubMedCrossRefGoogle Scholar
  9. 9.
    Josephs LK, Gregg I, Holgate ST: Does non-specific bronchial responsiveness indicate the severity of asthma? Eur Respir J 1990, 3:220–227.PubMedGoogle Scholar
  10. 10.
    Cockcroft DW, Murdock KY, Berscheid BA, Gore BP: Sensitivity and specificity of histamine PC20 determination in a random selection of young college students. J Allergy Clin Immunol 1992, 89:23–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Laprise C, Boulet LP: Asymptomatic airway hyperresponsiveness: a three-year follow-up. Am J Respir Crit Care Med 1997, 156:403–409. One of the few studies showing how airway responsiveness changes in asymptomatic subjects over time (more marked than in asthmatic and normal subjects).PubMedGoogle Scholar
  12. 12.
    Burdon JG, Juniper EF, Killian KJ, et al.: The perception of breathlessness in asthma. Am Rev Respir Dis 1982, 126:825–828.PubMedGoogle Scholar
  13. 13.
    Van Schoor J, Joos GF, Pauwels RA: Indirect bronchial hyperresponsiveness in asthma: mechanisms, pharmacology and implications for clinical research. Eur Respir J 2000, 16:514–533.PubMedCrossRefGoogle Scholar
  14. 14.
    De Meer G, Heederik D, Postma DS: Bronchial responsiveness to adenosine 5’-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV1. Am J Respir Crit Care Med 2002, 165:327–331.PubMedGoogle Scholar
  15. 15.
    Busse WW: Mechanisms and advances in allergic diseases. J Allergy Clin Immunol 2000, 105:S593-S598.PubMedCrossRefGoogle Scholar
  16. 16.
    Asher I, Boner A, Chuchalin A, et al.: Prevention of allergy and asthma: interim report. Allergy 2000, 55:1069–1088.PubMedCrossRefGoogle Scholar
  17. 17.
    Hopp RJ, Bewtra AK, Watt GD, et al.: Genetic analysis of allergic disease in twins. J Allergy Clin Immunol 1984, 73:265–270.PubMedGoogle Scholar
  18. 18.
    O’Byrne PM, Postma DS: The many faces of airway inflammation. Am J Respir Crit Care Med 1999, 159:S41-S66.PubMedGoogle Scholar
  19. 19.
    Sandford AJ, Weir TD, Paré PD: Genetics of asthma. In Evidence- based asthma management. Edited by Fitzgerald JM, Ernst P, Boulet LP, O’Byrne PM. Hamilton, Ontario: BC Dekker; 2001:13–26.Google Scholar
  20. 20.
    Van Eerdewegh P, Little RD, Dupuis J, et al.: Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 2002, 418:426–430.PubMedCrossRefGoogle Scholar
  21. 21.
    Busse WW, Lemanske RF Jr.: Asthma. N Engl J Med 2001, 344:350–362. Excellent review on asthma, particularly on the role of inflammatory mechanisms in its physiopathology.PubMedCrossRefGoogle Scholar
  22. 22.
    Bousquet J, Chanez P, Lacoste JY, et al.: Eosinophilic inflammation in asthma. N Engl J Med 1990, 323:1033–1039.PubMedCrossRefGoogle Scholar
  23. 23.
    Crimi E, Spanevello A, Neri M, et al.: Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med 1998, 157:4–9.PubMedGoogle Scholar
  24. 24.
    Gronke L, Kanniess F, Holz O, et al.: The relationship between airway hyper-responsiveness, markers of inflammation and lung function depends on the duration of the asthmatic disease. Clin Exp Allergy 2002, 32:57–63. An interesting study showing how the relationship between airway hyperresponsiveness and inflammation might change with the duration of asthma.PubMedCrossRefGoogle Scholar
  25. 25.
    Cockcroft DW: Airway responses to inhaled allergens. Can Respir J 1998, 5(Suppl A):14A-17A.PubMedGoogle Scholar
  26. 26.
    van Grunsven PM, van Schayck CP, Molema J, et al.: Effect of inhaled corticosteroids on bronchial responsiveness in patients with “corticosteroid naïve” mild asthma: a metaanalysis. Thorax 1999, 54:316–332. This study shows the temporal profile of the effects of corticosteroids on airway responsiveness.PubMedCrossRefGoogle Scholar
  27. 27.
    Elias JA, Zhu Z, Chupp G, Homer RJ: Airway remodeling in asthma. J Clin Invest 1999, 104:1001–1006.PubMedGoogle Scholar
  28. 28.
    Minshall EM, Leung DY, Martin RJ, et al.: Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 1997, 17:326–333.PubMedGoogle Scholar
  29. 29.
    Boulet LP, Laviolette M, Turcotte H, et al.: Bronchial subepithelial fibrosis correlates with airway responsiveness to methacholine. Chest 1997, 112:45–52.PubMedGoogle Scholar
  30. 30.
    Westergren-Thorsson G, Chakir J, Lafrenière-Allard MJ, et al.: Correlation between airway responsiveness and proteoglycan production by bronchial fibroblasts from normal and asthmatic subjects. Int J Biochem Cell Biol 2002, 34:1256–1267.PubMedCrossRefGoogle Scholar
  31. 31.
    Huang J, Olivenstein R, Taha R, et al.: Enhanced proteoglycan deposition in the airway wall of atopic asthmatics. Am J Respir Crit Care Med 1999, 160:725–729.PubMedGoogle Scholar
  32. 32.
    Sont JK, Willems LN, Bel EH, et al.: Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. Am J Respir Crit Care Med 1999, 159:1043–1051. This study not only suggests a possible role for the monitoring of AHR in the long-term management of asthma but also shows the beneficial effects of a good control of asthma on airway inflammation and remodeling.PubMedGoogle Scholar
  33. 33.
    Laitinen LA, Laitinen A: Remodeling of asthmatic airways by glucocorticosteroids. J Allergy Clin Immunol 1996, 97:153–158.PubMedCrossRefGoogle Scholar
  34. 34.
    James AL, Pare PD, Hogg JC: The mechanics of airway narrowing in asthma. Am Rev Respir Dis 1989, 139:242–246.PubMedGoogle Scholar
  35. 35.
    Richter A, Puddicombe SM, Lordan JL, et al.: The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma. Am J Respir Cell Mol Biol 2001, 25:385–391.PubMedGoogle Scholar
  36. 36.
    Fahy JV: Remodeling of the airway epithelium in asthma. Am J Respir Crit Care Med 2001, 164:S46-S51.PubMedGoogle Scholar
  37. 37.
    Holtzman MJ, Morton JD, Shornick LP, et al.: Immunity, inflammation, and remodeling in the airway epithelial barrier: epithelial-viral-allergic paradigm. Physiol Rev 2002, 82:19–46.PubMedGoogle Scholar
  38. 38.
    Holgate ST, Davies DE, Lackie PM, et al.: Epithelial-mesenchymal interactions in the pathogenesis of asthma. J Allergy Clin Immunol 2000, 105:193–204. This is a review of a mechanism that could explain the development of asthma: altered impaired epithelial repair possibly leads to myofibroblast activation, excessive matrix deposition, and production of mediators that propagate and amplify the remodeling.PubMedCrossRefGoogle Scholar
  39. 39.
    Evans MJ, Van Winkle LS, Fanucchi MV, Plopper CG: The attenuated fibroblast sheath of the respiratory tract epithelialmesenchymal trophic unit. Am J Respir Cell Mol Biol 1999, 21:655–657.PubMedGoogle Scholar
  40. 40.
    Tomasek JJ, Gabbiani G, Hinz B, et al.: Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol May 2002, 3:349–363.CrossRefGoogle Scholar
  41. 41.
    Mitzner W, Brown RH: Potential mechanism of hyperresponsive airways. Am J Respir Crit Care Med 2000, 161:1619–1623.PubMedGoogle Scholar
  42. 42.
    Stephens NL: Airway smooth muscle. Lung 2001, 179:333–373.PubMedCrossRefGoogle Scholar
  43. 43.
    Schmidt D, Rabe KF: Immune mechanisms of smooth muscle hyperreactivity in asthma. J Allergy Clin Immunol 2000, 105:673–682.PubMedCrossRefGoogle Scholar
  44. 44.
    Brightling CE, Bradding P, Symon FA, et al.: Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med 2002, 346:1699–1705.PubMedCrossRefGoogle Scholar
  45. 45.
    Ward C, Pais M, Bish R, et al.: Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma. Thorax 2002, 57:309–316. This study examines the contribution of airway structural changes on AHR and shows that although interrelated, physiologic changes, airway inflammation, and remodeling changes in asthma following inhaled corticosteroids are not temporally concordant. Prolonged treatment is necessary for maximal benefit remodeling and AHR.PubMedCrossRefGoogle Scholar
  46. 46.
    Skloot G, Permutt S, Togias G: Airway hyperresponsiveness in asthma: a problem of limited smooth muscle relaxation with inspiration. J Clin Invest 1995, 96:2393–2403. One of the key studies showing the influence of inhibition of deep inspirations on methacholine responsiveness.PubMedCrossRefGoogle Scholar
  47. 47.
    Warner DO, Gunst SJ: Limitation of maximal bronchoconstriction in living dogs. Am Rev Respir Dis 1992, 145:553–560.PubMedGoogle Scholar
  48. 48.
    Fredberg JJ, Inouye D, Miller B, et al.: Airway smooth muscle, tidal stretches and dynamically determined contractile states. Am J Respir Crit Care Med 1997, 156:1752–1759.PubMedGoogle Scholar
  49. 49.
    Chakir J, Laviolette M, Boutet M, et al.: Lower airways remodeling in nonasthmatic subjects with allergic rhinitis. Lab Invest 1996, 75:735–744. This studies shows significant airway remodeling in atopic, nonasthmatic subjects with allergic rhinitis.PubMedGoogle Scholar
  50. 50.
    Laprise C, Laviolette M, Boutet M, Boulet LP: Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodeling. Eur Respir J 1999, 14:63–73. This study shows airway inflammatory/remodeling changes that occur when subjects with previously asymptomatic AHR develop symptomatic asthma.PubMedCrossRefGoogle Scholar
  51. 51.
    Thomson NC: Neurogenic and myogenic mechanisms of nonspecific bronchial hyperresponsiveness. Eur J Respir Dis Suppl 1983, 128:206–212.PubMedGoogle Scholar
  52. 52.
    Jartti T: Asthma, asthma medication and autonomic nervous system dysfunction. Clin Physiol 2001, 21:260–269.PubMedCrossRefGoogle Scholar
  53. 53.
    Boulet LP, Turcotte H, Carrier G, et al.: Increased maximal airway response to methacholine during seasonal allergic rhinitis in nonasthmatic subjects: relationships with airway wall thickness and inflammation. Eur Respir J 1995, 8:913–921.PubMedGoogle Scholar
  54. 54.
    Platts-Mills TA, Vaughan JW, Carter MC, Woodfolk JA: The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease. J Allergy Clin Immunol 2000, 106:787–804.PubMedCrossRefGoogle Scholar
  55. 55.
    Boulet LP, Turcotte H, Laviolette M, et al.: Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma: influence of inhaled corticosteroids. Am J Respir Crit Care Med 2000, 162:1308–1313.PubMedGoogle Scholar
  56. 56.
    O’Byrne PM: Asthma treatment: antileukotriene drugs. Can Respir J 1998, 5(Suppl A):64–70.Google Scholar
  57. 57.
    Boulet LP: Role of long-acting b2 adrenergic agents. In Evidence-based asthma management. Edited by Fitzgerald JM, Ernst PE, Boulet LP, O’Byrne PM. Hamilton, Ontario: BC Dekker; 2001:149–158.Google Scholar

Copyright information

© Current Science Inc. 2003

Authors and Affiliations

  • Louis-Philippe Boulet
    • 1
  1. 1.Hôpital Laval, 2725, chemin Sainte-FoySainte-Foy, QuébecCanada

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