Skip to main content
SpringerLink
Log in

Pathogenesis of Asthma

Mediators and Mechanisms

  • Chapter
Bronchial Asthma

Abstract

Asthma is a common lung disease defined by reversible airway obstruction, airway inflammation, and increased airway responsiveness to a wide variety of stimuli. It is characterized by paroxysmal bronchospasm, hypersecretion of mucus, airway wall edema, and bronchial hyperreactivity. There is substantial evidence for the role of inflammation in asthma and bronchial hyperreactivity. Early autopsy studies of patients who had died in status asthmaticus showed epithelial denudation, mucosal edema, glandular hypertrophy, and dense eosinophilic infiltration. More recently, bronchoalveolar lavage (BAL) studies in patients challenged with aeroallergens consistently reveal increased numbers of BAL fluid eosinophils, mast cell mediators, and products of other inflammatory cells (1,2). Furthermore, transbronchial biopsies, even of patients with mild, well-controlled disease, have shown significant inflammatory changes. Biopsies have not only shown inflammation, but also an association between the degree of inflammatory changes and measurements of nonspecific bronchial hyperresponsiveness (3,4). Finally, therapy directed toward airway inflammation has been most effective in the treatment of chronic asthma and in attenuating bronchial hyperreactivity.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Diaz P, Gonzalez MC, Galleguillos FR, Ancic P, Cromwell O, Shepherd D, Duram SR, Gleich GJ, and Kay AB. Leukocytes and mediators in bronchoalveolar lavage during allergen-induced late-phase asthmatic reactions. Am. Rev. Resp. Dis. 1989; 139:1383–1389.

    Article  PubMed  CAS  Google Scholar 

  2. De Monchy JGR, Kauffman HF, Venge P, Koëter GH, Jansen HM, Sluiter HJ, and DeVries K. Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. Am. Rev. Resp. Dis. 1985; 131:373–376.

    PubMed  Google Scholar 

  3. Beasley R, Roche WR, Roberts JA, and Holgate ST. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am. Rev. Resp. Dis. 1989; 139:806–817.

    Article  PubMed  CAS  Google Scholar 

  4. Jeffery PK, Wardlaw AJ, Nelson FC, Collins JV, and Kay AB. Bronchial biopsies in asthma: an ultrastructural, quantitative study and correlation with hyper-reactivity. Am. Rev. Resp. Dis. 1989; 140:1745–1753.

    Article  PubMed  CAS  Google Scholar 

  5. Casale TB. Mast cell mediators and their effects on airway smooth muscle, in Inflammatory Cells and Mediators in Bronchial Asthma (Agrawal DK and Townley RG, eds.), CRC, Boca Raton, FL, 1991; pp. 57–76.

    Google Scholar 

  6. Casale TB, Wood D, Richerson HB, Zehr B, Zavala D, and Hunninghake GW. Direct evidence of a role for mast cells in the pathogenesis of antigen-induced bronchoconstriction. J. Clin. Invest. 1987; 80:1507–1511.

    Article  PubMed  CAS  Google Scholar 

  7. Cavanah DK and Casale TB. Histamine, in The Role of the Mast Cell in Health and Disease (Kaliner M and Metcalfe D, eds.), Marcel Dekker, NY, 1993; pp. 321–342.

    Google Scholar 

  8. Farmer SG. Role of kinins in airway diseases. Immunopharmacology 1991; 22:1–20.

    Article  PubMed  CAS  Google Scholar 

  9. Lundgren JD and Shelhamer JH. Pathogenesis of airway mucus hypersecretion. J. Allergy Clin. Immunol. 1990; 85:399–419.

    Article  PubMed  CAS  Google Scholar 

  10. Holtzman MJ. Arachidonic acid metabolism: implications of biological chemistry for lung function and disease. Am. Rev. Resp. Dis. 1991; 143:188–203.

    Article  PubMed  CAS  Google Scholar 

  11. Dahlén S-E, Hansson G, Hedqvist P, Björck T, Granström E, and Dahlén B. Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc. Natl. Acad. Sci. USA 1983; 80:1712–1716.

    Article  PubMed  Google Scholar 

  12. Busse WW and Rubin P. The clinical importance of leukotrienes and platelet-activating factor in allergic respiratory disease. Am. Rev. Resp. Dis. 1991; 143:S85–S107.

    Article  Google Scholar 

  13. Smith LJ, Rubin A-HE, and Patterson R. Mechanism of platelet activating factor-induced bronchoconstriction in humans. Am. Rev. Resp. Dis. 1988; 137:1015–1019.

    Article  PubMed  CAS  Google Scholar 

  14. Kay AB. Asthma and inflammation. J. Allergy Clin. Immunol. 1991; 87:893–910.

    Article  PubMed  CAS  Google Scholar 

  15. Broide DH, Gleich GJ, Cuomo AJ, Coburn DA, Federman EC, Schwartz LB, and Wasserman SI. Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway. J. Allergy Clin. Immunol. 1991; 88:637–648.

    Article  PubMed  CAS  Google Scholar 

  16. Samter M and Gleich GJ. The eosinophil, in Immunological Diseases, 4th ed. (Samter M, ed.), Little Brown and Co., Boston, MA, 1988; pp. 279–300.

    Google Scholar 

  17. Sheffer AL and Fink JN. Immunopharmacologic update. J. Allergy Clin. Immunol. 1991; 88:303–321.

    Article  Google Scholar 

  18. Holtzman MJ, Fabbri LM, O’Byrne PM, Gold PM, Aizawa H, Walters EH, Alpert SE, and Nadel JA. Importance of airway inflammation for hyper-responsiveness induced by ozone. Am. Rev. Resp. Dis. 1983; 127:686–690.

    PubMed  CAS  Google Scholar 

  19. Sheller JR. Effect of neutrophils on airway smooth muscle responsiveness, in Inflammatory Cells and Mediators in Bronchial Asthma (Agrawal DK and Townley RG, eds.), CRC, Boca Raton, FL, 1991; 77–87.

    Google Scholar 

  20. Barnes PJ. New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma. J. Allergy Clin. Immunol. 1989; 83:1013–1026.

    Article  PubMed  CAS  Google Scholar 

  21. Walker C, Kaegi MK, Braun P, and Blaser K. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J. Allergy Clin. Immunol. 1991; 88:935–942.

    Article  PubMed  CAS  Google Scholar 

  22. Bradley BL, Azzawi M, Jacobson M, Assoufi B, Collins JV, Irani AA, Schwartz LB, Durham SR, Jeffrey PK, and Kay AB. Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. J. Allergy Clin. Immunol. 1991; 88:661–674.

    Article  PubMed  CAS  Google Scholar 

  23. Plaut M, Pierce JH, Watson CJ, Hanley-Hyde J, Nordan RP, and Paul WE. Mast cell lines produce lymphokines in response to cross-linkage of FcεRI or to calcium ionophores. Nature 1989; 339:64–67.

    Article  PubMed  CAS  Google Scholar 

  24. Wodnar-Filipowicz A, Heusser CH, and Moroni C. Production of the haemopoietic growth factors GM-CSF and interleukin-3 by mast cells in response to IgE receptor-mediated activation. Nature 1989; 339:150–151.

    Article  PubMed  CAS  Google Scholar 

  25. Gordon JR and Galli SJ. Release of both preformed and newly synthesized tumor necrosis factor a (TNF-α)/cachectin by mouse mast cells stimulated via the FcεRI. A mechanism for the sustained action of mast cell-derived TNF-α during IgE-dependent biological responses. J. Exp. Med. 1991; 174:103–107.

    Article  PubMed  CAS  Google Scholar 

  26. Warringa RAJ, Koenderman L, Kok PTM, Kreukniet J, and Bruijnzeel PLB. Modulation and induction of eosinophil chemotaxis by granulocyte-macrophage colony-stimulating factor and interleukin-3. Blood 1991; 77:2694–2700.

    PubMed  CAS  Google Scholar 

  27. Broide DH and Firestein GS. Endobronchial allergen challenge in asthma: demonstration of cellular source of granulocyte macrophage colony-stimulating factor by in situ hybridization. J. Clin. Invest. 1991; 88:1048–1053.

    Article  PubMed  CAS  Google Scholar 

  28. Brown PH, Crompton GK, and Greening AP. Proinflammatory cytokines in acute asthma. Lancet 1991; 338:590–593.

    Article  PubMed  CAS  Google Scholar 

  29. Hamid Q, Azzawi M, Ying S, Moqbel R, Wardlaw AJ, Corrigan CJ, Bradley B, Durham SR, Collins JV, Jeffrey PK, Quint DJ, and Kay AB. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J. Clin. Invest. 1991; 87:1541–1546.

    Article  PubMed  CAS  Google Scholar 

  30. Okudaira H and Miyamoto T. Interleukin-5 (IL-5) dependent accumulation of eosinophils in the lung. ACI News 1991; 3/4:117–121.

    Google Scholar 

  31. Vercelli D and Geha RS. Regulation of IgE synthesis in humans: a tale of two signals. J. Allergy Clin. Immunol. 1991; 88:285–295.

    Article  PubMed  CAS  Google Scholar 

  32. Ricci M and Rossi O. Dysregulation of IgE responses and airway allergic inflammation in atopic individuals. Clin. Exp. Allergy 1990; 20:601–609.

    Article  PubMed  CAS  Google Scholar 

  33. Kunkel SL, Standiford T, Kasahara K, and Strieter RM. Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp. Lung Res. 1991; 17:17–23.

    Article  PubMed  CAS  Google Scholar 

  34. Standiford TJ, Kunkel SL, Basha MA, Chensue SW, Lynch JP, Toews GB, Westwick J, and Streiter RM. Interleukin-8 gene expression by a pulmonary epithelial cell line: a model for cytokine networks in the lung. J. Clin. Invest. 1990; 86:1945–1953.

    Article  PubMed  CAS  Google Scholar 

  35. Carré PC, Mortenson RL, King TE, Jr., Noble PW, Sable CL, and Riches DWH. Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis: a potential mechanism for the recruitment and activation of neutrophils in lung fibrosis. J. Clin. Invest. 1991; 88:1802–1810.

    Article  PubMed  Google Scholar 

  36. Beutler B and Cerami A. Cachectin: more than a tumor necrosis factor. N. Eng. J. Med. 1987; 316:379–385.

    Article  CAS  Google Scholar 

  37. Huber M, Beutler B, and Keppler D. Tumor necrosis factor a stimulates leukotriene production in vivo. Eur. J. Immunol. 1988; 18:2085–2088.

    Article  PubMed  CAS  Google Scholar 

  38. Ming WJ, Bersani L, and Mantovani A. Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leukocytes. J. Immunol. 1987; 138:1469–1474.

    PubMed  CAS  Google Scholar 

  39. Stephens KE, Ishizaka A, Wu Z, Larrick JW, and Raffin TA. Granulocyte depletion prevents tumor necrosis factor-mediated acute lung injury in guinea pigs. Am. Rev. Resp. Dis. 1988; 138:1300–1307.

    Article  PubMed  CAS  Google Scholar 

  40. Spatafora M, Merendino A, Chiappara G, Gjomarkaj M, Melis M, Bellia V, and Bonsignore G. Lung compartmentalization of increased TNF releasing ability by mononuclear phagocytes in pulmonary sarcoidosis. Chest 1989; 96:542–549.

    Article  PubMed  CAS  Google Scholar 

  41. Casale TB. Neurogenic control of inflammation and airway function, in Allergy: Principles and Practice, 4th ed. (Middleton E, Jr., Reed CE, Ellis EF, Adkinson NF, Jr., and Yunginger JW, eds.) Mosby-Yearbook, St. Louis, MO, 1993;650–671.

    Google Scholar 

  42. Goldie RG. Receptors in asthmatic airways. Am. Rev. Resp. Dis. 1990; 141:S151–S156.

    Article  PubMed  CAS  Google Scholar 

  43. Barnes PJ. Asthma as an axon reflex. Lancet 1986; 1:242.

    Article  PubMed  CAS  Google Scholar 

  44. Makino S, Fukuda T, Motojima S, and Yukawa T. Eosinophils in airway hyper-responsiveness, in Inflammatory Cells and Mediators in Bronchial Asthma (Agrawal DK and Townley RG, eds.), CRC, Boca Raton, FL, 1991; p. 127.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Medicine and VA Medical Center, University of Iowa, Iowa City, IA, USA

    Stephen J. Smart

  2. College of Medicine and VA Medical Center, University of Iowa, Iowa City, IA, USA

    Thomas B. Casale

Authors
  1. Stephen J. Smart
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas B. Casale
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of California School of Medicine, Davis, CA, USA

    M. Eric Gershwin  & Georges M. Halpern  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Smart, S.J., Casale, T.B. (1994). Pathogenesis of Asthma. In: Gershwin, M.E., Halpern, G.M. (eds) Bronchial Asthma. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-0297-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-0297-4_2

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-6697-6

  • Online ISBN: 978-1-4612-0297-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation