Interactions between viral infections and allergy in exacerbating asthma

1
Interactions between viral infections and allergy
in exacerbating asthma
2
Asthma exacerbations The tip of the iceberg

• Evident
• Dangerous
• Consequences
• Therapeutic target

• Sensitization
• Inflammation
• Remodeling
• Signal transduction
• Genes

3
Viruses induce most exacerbations
Johnston et al. BMJ (1995) 3101225 Nicholson et
al. BMJ (1993) 307982
4
Virus-induced exacerbations
Johnston et al. AJRCCM (1996) 154654 Nicholson
et al. BMJ (1993) 307982
5
Allergens exacerbate asthma

• Pollen, pet allergy
• Soya, storm epidemics
• Allergen challenges

6
Individual factors in a complicated Universe

• Viral infections
• Atopy
• Pollution
• Food allergy
• Aspirin
• Stress
• Exercise
• Weather changes
• of asthma exacerbations explainable

60 - 85 40 - 80 5 - 20 2 - 9 4 -
28 4 - 12 7 - 18 1 - 4 123 -
256 (!)
7
Viral infectionspredispose to an altered
response to non-specific and specific stimuli
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Virus-induced hyperresponsiveness

• Increase in non-specific hyperresponsiveness
• Preferential increase in allergic subjects and
  subjects with decreased FEV1
• Increased response to allergen

Calhoun et al. Am Rev Respir Dis (1991)
1441267 Gern et al Am J Respir Crit Care Med
(1997) 1551872 Calhoun et al. JCI (1994) 942200
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Mechanisms of hyperresponsiveness

• Epithelial damage
• Inflammatory mediators
• Cells recruited
• Neural reflexes
• Immunological mechanisms (eg IgE)

10
Allergy may lead to an abnormal response to
viruses
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Th1
Flu
Th2
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Virus-specific CD8 cells

• In an atopic environment, virus-specific CD8
  cells can switch to Th2 cytokine production and
  induce eosinophilia

Coyle AJ et al. J Exp Med (1995) 1811229
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An allergic response to virus
IFN-g
IFN-?/IL-4
IL-10
NG Papadopoulos et al. Thorax (2002) 57328
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Defective costimulation
NG Papadopoulos et al. Clin Exp Allergy (2002)
32537
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Outcome of RV infection
DE Parry et al. J Allergy Clin Immunol (2000)
105692
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Eosinophilia persists in atopics

• Experimental infection with RV
• Increase in bronchial hyperreactivity
• Infiltration with lymphocytes and eosinophils

Fraenkel DJ et al Am J Respir Crit Care Med
(1995) 151879
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Virus-induced hyperresponsiveness persists in
atopics
Xepapadaki, Papadopoulos et al. unpublished
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Could allergens protect from colds ?!
Avila PC et al. JACI (2000) 105923
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Natural historycombined effects
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Colds pollution allergy

• 57 asthmatics - diary cards for 1 year
• Colds, pollution and pollen/spore levels
• Comparison of the days with coldasthma vs either
  alone
• Asthmacold more SO2, NO, than asthma alone
• No correlation of pollen/spore counts with asthma
  exacerbations or colds

Tarlo SM et al JACI (2001) 10852
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Viruses and mites in asthma exacerbations

• Synergistic interaction between
• allergen sensitization
• allergen exposure
• virus infection

OR for asthma admission

Sensitized - - -
Exposed - - -
Virus - - -
Green, Custovic, Johnston, Woodcock et al. BMJ
(2002) 324763
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Exacerbations in seasonal asthma
NG Papadopoulos et al. XXI EAACI proceedings
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Conclusions

• Viruses induce hyperresponsiveness
• Atopy is a risk factor
• In the allergic environment, virus-induced
  inflammation persists
• A vicious circle