Bacterial infections

The effect of respiratory infections on the inception and exacerbation of asthma

Discussion ideas

Bisgaard: bacterial infections in early life->

Discussion ideas:

-asthmatics airways provide an environment in which Gram- bacteria easily live or then there is just resistance to antibiotics

- S.pneumoniae -> good or bad?

-Limitations of the studies

-should common colds be dealt with more vigorously if there is a genetic disposition for asthma?

-Vaccinations against pneumonias

Introduce all the research groups first!!

S. pneumoniae:

• Iikura and Kloepfer: Significant correlation between S.pneumoniae and the exacerbation of asthma

M. catarrhalis:

• Kloepfer: when detected alongside rhinovirus increased the likelihood of experiencing cold symptoms, asthma symptoms, or both compared with isolated detection of rhinovirus. Thus shown to contribute to severity of respiratory tract illnesses, including asthma exacerbations
• Hentschke: was detected more frequently in asthmatics as compared to control children.

H.influenzae :

• Hentschke: Gram negative colonization of H.influenzae and/or M.catarrhalis had the highest IFN beta among the children analyzed
• colonization with H. influenzae or M. catarrhalis was higher after antibiotic treatment in asthmatic children.-> hint that bacteria of asthmatic children are either often resistant to common antibiotic treatment with macrolide or cephalosporine antibiotic due to frequent treatment in the individuals, or that an asthmatic airway provides further options for Gram negative bacteria to survive and modify immune response.

C.pneumoniae (atypical bacteria):

• Smith-Norowitz

- Th-cell memory and development

- is the immunity damaged or modified in some way?

-Th-cells as a target of future therapy?

Drug development

Bacteria on the exacerbation of asthma

Age of primary infection

-TH-cells

-Interferone genes

1. Culley et al. 2002: effect of the age at which mice were exposed to RSV in correlation to the development of asthma later in life

2. Kusel et al. 2007: early-life viral infections and the probability of asthma development in children (especially focusing on RSV and RV)

3. Sigurs et al. 2004: RSV bronchiolitis in infancy is a strong risk

factor for IgE-mediated asthma

Hansbro et al. 2004

Age of primary viral infection

Edwards:deficiency in type I interferon-beeta and type III interferon-gamma in response to RV in asthmatic subjects

Parsons: impaired TLR3 and MDA5 signalling in response to RV-> inability to activate types I and III interferon immune responses to RV infection, potentially increasing susceptibility to the effects of RV infection

Wark and Baraldo: less significant increases in IFN-lambda and IFN-beta mRNA levels in response to RV, in asthmatic patients

Wagener: double stranded RNA from RV caused changes in gene expression of primary nasal and bronchial epithelial cells. Induction of IFN related genes were impaired in patients with asthma.

Gill:

• Purified pDCs from allergic asthma patients secrete less IFN- alfa upon exposure to influenza viruses
• Plasmacytoid dendritic cells from patients with allergic asthma express increased surface FceRIa and this correlates inversely with influenza-induced IFN-a secretion
• IgE cross-linking inhibits influenza-induced secretion of IFN-a in pDCs
• IgE cross-linking interferes with influenza-induced maturation of pDCs

Sykes and Sykes:

• 13:No difference was observed in TLR induced interferon or proinflammatory
• cytokine production between asthmatic and non-asthmatic subjects from either cell typ
• 14: IFN-lambda and, to a lesser degree, IFN-beta are the major IFN subtypes induced by RV infection of HBECs. Neither defective IFN induction by RV nor increased RV replication was observed in the HBECs from subjects with well controlled asthma reported in this study.

Spann: not distinsic defect in the production of IFN-β or -λ, however, this response is influenced by the infecting virus. Higher viral load is associated with atopy and wheeze suggesting an impaired antiviral response to RSV and hMPV that is not influenced by production of IFNs

Patel:(influenza A and RSV) IFN response to these viruses in airway epithelial cells is

remarkably similar between subjects with and without asthma

Deficient anti-viral immunity

Bacterial infections

RV:

• Denlinger:
• Aab
• Akoto
• Iikura
• Bjerregaard

RSV:

• Iikura

Influenza:

• Chirkova

HMPV:

• Iikura:
• Bjerregaard

Viral infections

Viruses and asthma exacerbation

Effect of endotoxins (LPS) on the development and exacerbation of asthma

1.Thorne: how re-exopsure to LPS causes the inflammation of the lungs, leading to asthma exacerbation

2.Ueda: how re-exopsure to LPS causes the inflammation of the airways leading to asthma exacerbation

3. Braun-Fahrländer :Instead of inducing asthmatic tendencies, this study’s results presented the possibility that they would opposingly even prevent asthma

1.Marri: There are differences in the bacterial composition between asthmatics and non-asthmatics.

2.Huang: Airway bacterial composition was more diverse in asthmatic patients

3.Hentschke: Moraxella catarrhalis, Haemophilus influenza and Staphylococcus aureus were predominant in asthmatics

4.Bisgaard: Colonization early in life on the development of asthma

5.Ege: Wide range microbial exposure on the development of asthma-> refutes that the exposure to

great amounts of bacteria would in fact increase the prevalence of

asthma

Bacterial colonization and infections in general