?

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

E Wouters

• The hypothesis of systemic inflammation as spill-over of the local inflammatory process.

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).

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).

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.

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)

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!

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!

• Poze