3. GJ Braunstahl
• Impaired nasal function affects the lower airways of
asthmatic patients.
• Various alternative mechanisms play a role in
nasobronchial interactions:
– Aspiration of nasal contents
– Neural reflexes
– Systemic inflammation
• Most human and animal data point towards a systemic
pathway linking the upper and lower airways, involving
both bloodstream and bone-marrow.
importance of an integrated approach involving both
ends of the respiratory tract
4. E Wouters
• The hypothesis of systemic inflammation
as spill-over of the local inflammatory
process.
5. S.Holgate
• In asthma there is evidence that both structural
and functional aspects of the airway epithelium
are defective.
• Epithelial cells cultured from asthmatic airways
fail to develop fully functional tight junctions
enhanced permeability (as a consequence of
altered cell cycling with nuclear translocation of
P21Waf and related cell cycle inhibitors).
6. S.Holgate
• Asthmatic epithelium from children with asthma
is defective in its ability to repair after injury or to
generate primary interferons when exposed to
common cold viruses.
(a defective signaling through toll-like receptor 3
to activate interferon regulatory functions that
induce the production of IFNβ and λ).
7. S Hirst
• Functional ( vasodilatation, hyper-
perfusion, increased microvascular
permeability, oedema formation,
inflammatory cell recruitement) and
• Angiogenic structural changes in airway
blood vessels in asthma have potentially
important therapeutic implication for
targering these alterations.
8. R. Gosens
• Inflammation is important but.. it is not the
whole story!!!
• (maybe is just a marker of the remodeling
of the airway smooth muscle bundle)
9. P.Barnes
• Low concentrations of theophylline
specifically inhibit oxidant-activated PI3-
kinase-σ and have the capacity to reverse
corticosteroid resistance in severe asthma
and smoking asthmatics
targe the epigenome in the treatment
of asthma!
10. Dirkje Postma
• Gender differences in: asthma prevalence, risk
of asthma by age, physiology (bronchial eNO, air
trapping), response to treatment etc
• There exist sex-specific genetic influences on
asthma for IL-9R, IL-1-beta, COX-2, CXCR-3
and ESR-1
• Gender differentiatic therapy could be common
in the future!
