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Principles of Molecular Medicine pp 319–327Cite as

Asthma

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Abstract

Asthma is often defined as a lung disease with three characteristics: reversible airway obstruction, increased airway responsiveness (hyperreactivity) to inhaled stimuli, and airway inflammation. The disease is generally a chronic condition, and it affects between 7 and 20 million Americans, 2 to 5 million of whom are children. The impact of asthma on any individual is highly dependent on the control of the disease that can be achieved by elimination of precipitating factors and the effective use of medical therapy. Despite improved understanding of these factors and the availability of more effective drugs for treatment of the condition, the prevalence of asthma, the numbers of hospitalizations for asthma, and deaths attributed to the disease have all been increasing, especially among minority and inner-city populations. At least some of the increases in mortality and morbidity are based on poor use of medication and, in particular, inadequate long-term treatment with antiinflammatory drugs. Nonetheless, the marked increases in frequency and severity of asthma during the past decade serve to underscore the need for a better understanding of the molecular basis for the disease.

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Selected References

  • Ben-Baruch A, Michiel DF, Oppenheim JJ. Signals and receptors involved in recruitment of inflammatory cells. J Biol Chem 1995;270:11, 703–11, 706.

    Google Scholar 

  • Bentley AM, Durham SR, Robinson DS, et al. Expression of endothelial and leukocyte adhesion molecules intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in the bronchial mucosa in steady-state and allergen-induced asthma. J Allergy Clin Immunol 1993; 92: 857–868.

    Article  PubMed  CAS  Google Scholar 

  • Bleecker ER, Postma DS, Meyers DA. Genetic susceptibility to asthma in a changing environment. Ciba Found Symp 1997; 206: 90–99.

    PubMed  CAS  Google Scholar 

  • Bousquet J, Chanez P, Lacoste JY, et al. Eosinophilic inflammation in asthma. N Engl J Med 1990; 323: 1033–1039.

    Article  PubMed  CAS  Google Scholar 

  • Bradding P, Roberts JA, Britten KM, et al. Interleukin-4, -5, and -6 and tumor necrosis factor-a in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 1994; 10: 471–480.

    Article  PubMed  CAS  Google Scholar 

  • Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 1989; 320: 271–277.

    Article  PubMed  CAS  Google Scholar 

  • Cippitelli M, Sica A, Viggiano V, et al. Negative transcriptional regulation of the interferon-y promoter by glucocorticoids and dominant negative mutants of c-Jun. J Biol Chem 1995;270:12, 548–12, 556.

    Google Scholar 

  • The Collaborative Study on the Genetics of Asthma (CSGA). A genomewide search for asthma susceptibility loci in ethnically diverse populations. Nat Genet 1997; 15: 389–392.

    Article  Google Scholar 

  • Cookson WOCM, Sharp A, Faux JA, Hopkin JM. Linkage between immunoglobulin E responses underlying asthma and rhinitis and chromosome l lq. Lancet 1989; 1: 1292–1295.

    Article  PubMed  CAS  Google Scholar 

  • Dixon RAF, Diehl RE, Opas E, et al. Requirement of a 5–lipoxygenaseactivating protein for leukotriene synthesis. Nature 1990; 343: 282–284.

    Article  PubMed  CAS  Google Scholar 

  • Hamilos DL, Leung DYM, Wood R, et al. Evidence for distinct cytokine expression in allergic versus nonallergic chronic sinusitis. J Allergy Clin Immunol 1995; 96: 537–544.

    Article  PubMed  CAS  Google Scholar 

  • Heiss LN, Lancaster JR Jr, Corbett JA, Goldman WE. Epithelial autotoxicity of nitric oxide: role in the respiratory cytopathology of pertussis. Proc Natl Acad Sci USA 1994; 88: 3681–3685.

    Google Scholar 

  • Holgate ST. Asthma Genetics: waiting to exhale. Nat Genet 1997; 15: 227–229.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Holtzman MJ, Brody SL, Look DC. Does gene therapy call for “STAT” immunity and inflammation at the epithelial barrier? Am J Respir Cell Mol Biol 1995; 12: 127–129.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman MJ, Fabbri LM, O’Byrne PM, et al. Importance of airway inflammation for hyperresponsiveness induced by ozone in dogs. Am Rev Respir Dis 1983; 127: 686–690.

    PubMed  CAS  Google Scholar 

  • Holtzman MJ, Sampath D, Castro M, Look DC, Jayaraman S. The one-two of T helper cells: does interferon-y knockout the Th2 hypothesis for asthma? Am J Respir Cell Mol Biol 1996; 14: 316–318.

    Article  PubMed  CAS  Google Scholar 

  • Hou J, Schindler U, Henzel WJ, et al. An interleukin-4–induced transcription factor: IL-4 Stat. Science 1994; 265: 1701–1706.

    Article  PubMed  CAS  Google Scholar 

  • Huang S-K, Marsh DG. Genetics of allergy. Ann Allergy 1993; 70: 347–358.

    PubMed  CAS  Google Scholar 

  • Iademarco MF, Barks JL, Dean DC. Regulation of vascular cell adhesion molecule-1 expression by IL-4 and TNF-a in cultured endothelial cells. J Clin Invest 1995; 95: 264–271.

    Article  PubMed  CAS  Google Scholar 

  • Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K, Silvennoinen O. Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol 1995; 13: 369–398.

    Article  PubMed  CAS  Google Scholar 

  • Jacobson NG, Szabo SJ, Weber-Nordt RM, et al. Interleukin 12 signaling in T helper type 1 (Thl) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (STAT)3 and Stat4. J Exp Med 1995; 181: 1755–1762.

    Article  PubMed  CAS  Google Scholar 

  • Kamijo R, Harada H, Matsuyama T, et al. Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 1994; 263: 1612–1615.

    Article  PubMed  CAS  Google Scholar 

  • Kips JC, Tavernier JH, Joos GF, Peleman RA, Pauwels RA. The potential role of tumour necrosis factor alpha in asthma. Clin Exp Allergy 1993; 23: 247–250.

    Article  PubMed  CAS  Google Scholar 

  • Li JT. Mechanism of asthma. Curr Opin Pulm Med 1997;3:10–16. Lobb RR, Hemler ME. The pathophysiologic role of a4 integrins in vivo. J Clin Invest 1994; 94: 1722–1728.

    Google Scholar 

  • Look DC, Pelletier MR, Holtzman MJ. Selective interaction of a subset of interferon-y response element binding proteins with the intercellular adhesion molecule-1 (ICAM-1) gene promoter controls the pattern of expression on epithelial cells. J Biol Chem 1994; 269: 8952–8958.

    PubMed  CAS  Google Scholar 

  • Marsh DG, Neely JD, Breazeale DR, et al. Linkage analysis of IL4 and other chromosome 5g31.1 markers and total serum immunoglobulin E concentrations. Science 1994; 264: 1152–1156.

    CAS  Google Scholar 

  • McEver RP, Moore KL, Cummings RD. Leukocyte trafficking mediated by selectin-carbohydrate interactions. J Biol Chem 1995;270:11, 02511, 028.

    Google Scholar 

  • Nakajima S, Look DC, Roswit WT, Bragdon MJ, Holtzman MJ. Selective differences in vascular endothelial-vs. airway epithelial-T cell adhesion mechanisms. Am J Physiol 1994; 267: L422–L432.

    PubMed  CAS  Google Scholar 

  • Nakajima S, Roswit WT, Look DC, Holtzman MJ. A hierarchy for integrin expression and adhesiveness among T cell subsets that is linked to TCR gene usage and emphasizes VSl* yS T cell adherence and tissue retention. J Immunol 1995; 155: 1117–1131.

    PubMed  CAS  Google Scholar 

  • Postma DS, Bleecker ER, Amelung PJ, et al. Genetic susceptibility to asthma-bronchial hyperresponsiveness coinherited with a major gene for atopy. New Engl J Med 1995; 333: 894–900.

    Article  PubMed  CAS  Google Scholar 

  • Raulet DH, Held W. Natural killer cell receptors: the offs and ons of NK cell recognition. Cell 1995; 82: 697–700.

    Article  PubMed  CAS  Google Scholar 

  • Robinson DS, Hamid Q, Bentley A, et al. Activation of CD4* T cells, increased TH2–type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol 1993; 92: 313–324.

    Article  PubMed  CAS  Google Scholar 

  • Ruffilli A, Bonini S. Susceptibility genes for allergy and asthma. Allergy 1997; 52: 256–273.

    Article  PubMed  CAS  Google Scholar 

  • Schindler C, Darnell JEJ. Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem 1995; 64: 621–651.

    Article  PubMed  CAS  Google Scholar 

  • Sears MR, Burrows B, Flannery EM, et al. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 1991; 325: 1067–1071.

    Article  PubMed  CAS  Google Scholar 

  • Seminario M-C, Gleich GJ. The role of eosinophils in the pathogenesis of asthma. Curr Opin Immunol 1994; 6: 860–864.

    Article  PubMed  CAS  Google Scholar 

  • Shirakawa T, Li A, Dubowitz M, et al. Association between atopy and variants of the ß subunit of the high-affinity immunoglobulin E receptor. Nat Genet 1994; 7: 125–130.

    Article  CAS  Google Scholar 

  • Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994; 76: 301–314.

    Article  PubMed  CAS  Google Scholar 

  • Stahle-Backdahl M, Inoue M, Giudice GJ, Parks WC. 92 kDa gelatinase is produced by eosinophils at the site of blister formation in bullous pemphigoid and cleaves the extracellular domain of the 180 kDa bullous pemphigoid autoantigen. J Clin Invest 1994; 93: 2202–2230.

    Article  Google Scholar 

  • Ying S, Durham SR, Corrigan CJ, Hamid Q, Kay AB. Phenotype of cells expressing mRNA for TH2–type (interleukin 4 and interleukin 5) and TH1–type (interleukin 2 and interferon y) cytokines in bronchoalveolar lavage and bronchial biopsies from atopic asthmatic and normal control subjects. Am J Respir Cell Mol Biol 1995; 12: 477–487.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Michael J. Holtzman
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  2. Dwight C. Look
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  3. Michael F. Iademarco
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  4. Douglas C. Dean
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  5. Deepak Sampath
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  6. Mario Castro
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Editor information

Editors and Affiliations

  1. Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, IL, USA

    J. Larry Jameson MD, PhD

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© 1998 Springer Science+Business Media New York

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Holtzman, M.J., Look, D.C., Iademarco, M.F., Dean, D.C., Sampath, D., Castro, M. (1998). Asthma. In: Jameson, J.L. (eds) Principles of Molecular Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-726-0_36

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  • DOI: https://doi.org/10.1007/978-1-59259-726-0_36

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-6272-3

  • Online ISBN: 978-1-59259-726-0

  • eBook Packages: Springer Book Archive

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