1. Centrale rol van wetenschappelijk onderzoek bij betere behandeling van chronische longziekten Prof. Dirkje Postma Netherlands Respiratory Society Groningen research Institute for asthma and COPD

2. To him who devotes his life to science, nothing can give more happiness than increasing the number of discoveries, but his cup of joy is full when the results of his studies immediately find practical applications -Louis Pasteur- Background of all our research

3. Optimisatie Selectie Formulering Productie Veiligheid 5000 chemische stoffen De trechter van geneesmiddelontwikkeling

4. 5 mogelijke medicamenten 2 % van patiënten Optimisatie Selectie Formulering Productie Veiligheid 5000 chemische stoffen

5. De trechter van geneesmiddelontwikkeling 5 mogelijke medicamenten 2 % van patiënten 5000 chemische stoffen Klinisch onderzoek Fase I Fase II Fase III 1 Medicijn!

6. The Research Enterprise Basic Research Applied Research Clinical Investigations and Trials Demonstration and Education Research Knowledge Acquisition Knowledge Validation Knowledge Transfer Knowledge Dissemination Health of the Nation

7. Examples in respiratory medicine

8. Helping Newborns Breathe Tens of thousands of babies died annually from a mysterious respiratory ailment. Clinical investigators characterized the patients and studied infant respiration and human lung physiology. Separately, basic studies of surface tension and pulmonary physiology allowed researchers to identify and characterize pulmonary surfactant. With this information in mind, clinical and basic scientists determined that the deaths were due to a lack of surfactant, causing the alveoli, or air sacs in the lungs, to collapse. Treatments were then developed in the lab and tested in and applied to patients with great clinical success.

9. Discovery of the ∆F508 CFTR Mutation 1989: Research teams led by Lap-Chee Tsui, Jack Riordan, and Francis Collins Newborn screening

10. 21st Century: a new era for children with CF Early diagnosis A paradigm shift in therapeutic strategy No longer dominated by intervention in ill children But prevention in presymptomatic patients -early deaths –salt depletion –malnutrition and growth failure –“cross-infection” –chronic Pseudomonas aeruginosa –hospitalizations –severe lung disease

11. Asthma No.1 chronic disease in childhood Great impact on individual’s life family society health economics

12. Inflammation and epithelial remodelling in asthma Asthma Normal Jeffery P. Asthma. 1998. Am Rev Resp Dis1985 Mar;131(3):373-6. De Monchy et al. Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. Asthma pre Asthma post ICS treatment Laitinen. JACI. 1992

13. Improvement of hyperresponsiveness and lung function with inhaled corticosteroids 0.13 1.00 0.25 0.50 2.00 061218 24 Follow-up (maand) 55 60 75 65 70 80 0 3 9 15 21 PC 20 histamine mg/mlFEV 1 % voorspeld Kerstjens et al New Engl J Med 1992 Becotide 800µg Placebo Atrovent160 µg SGO Nederlands onderzoek

14. Mortality due to asthma reduced Tabak, Smit et al 2002

15. COPD unmet needs There is a huge opportunity to get better approaches and help our COPD patients more

16. Garcia-Aymerich et al., Thorax 2011 Identification of clinically relevant COPD subtypes Airway morphology Lung density Cardiovascular problems Group1 Group2 Group 3 Quality of life Symptoms Lung function Systemic inflammation Nutritional status Less impairment More impairment

17. Patient reported Clinical Functional Cellular Molecular ‘Systems Medicine’ Auffray et al Chest 2010

18. New Pathways to Discovery and Biomedical phenotyping Clinical Research Enterprise Research Teams of the Future Roadmap for Dutch Respiratory Research