Socio-economic determinants

1. Grazie per aver scelto di utilizzare a scopo didattico questo materiale delle Guidelines 2011 libra.Le ricordiamo che questo materiale è di proprietà dell’autore e fornito come supporto didattico per uso personale.

2. Is a uniform definition of severity, control and risk possible in chronic diseases ?1- A novel concept of chronic diseases2- The example of asthma3- Tentative uniform definition4- Needs for a uniform definition

3. Is a uniform definition of severity, control and risk possible in chronic diseases ?1- A novel concept of chronic diseases2- The example of asthma3- Tentative uniform definition4- Needs for a uniform definition

4. Socio-economic determinants Life style - environment Risk and protective factors Tobacco smoking, Pollutants Allergens, Nutrition, Infections Physicalexercise, Others

5. Socio-economic determinants Life style - environment Risk and protective factors Tobacco smoking, Pollutants Allergens, Nutrition, Infections Physicalexercise, Others Genes

6. Socio-economic determinants Life style - environment Risk and protective factors Tobacco smoking, Pollutants Allergens, Nutrition, Infections Physicalexercise, Others Genes Biological expression of chronicdiseases Transcripts, proteins, metabolites Target organ local inflammation Systemic inflammation Cell and tissue remodelling Clinical expression of chronicdiseases Co-morbidities Severity of co-morbidities Persistence, remission Long-termmorbidity Responsiveness - sideeffects to treatment

7. Socio-economic determinants Life style - environment Risk and protective factors Tobacco smoking, Pollutants Allergens, Nutrition, Infections Physicalexercise, Others Genes Biological expression of chronicdiseases Transcripts, proteins, metabolites Target organ local inflammation Systemic inflammation Cell and tissue remodelling Ageing Clinical expression of chronicdiseases Co-morbidities Severity of co-morbidities Persistence, remission Long-termmorbidity Responsiveness - sideeffects to treatment

8. Socio-economic determinants Life style - environment Risk and protective factors Tobacco smoking, Pollutants Allergens, Nutrition, Infections Physicalexercise, Others Genes Systems biology on precisephenotypes Biological expression of chronicdiseases Transcripts, proteins, metabolites Target organ local inflammation Systemic inflammation Cell and tissue remodelling Ageing Clinical expression of chronicdiseases Co-morbidities Severity of co-morbidities Persistence, remission Long-termmorbidity Responsiveness - sideeffects to treatment

9. Socio-economic determinants Life style - environment Risk and protective factors Tobacco smoking, Pollutants Allergens, Nutrition, Infections Physicalexercise, Others Health promotion Primary prevention Genes Systems biology on precisephenotypes Biological expression of chronicdiseases Transcripts, proteins, metabolites Target organ local inflammation Systemic inflammation Cell and tissue remodelling • Personalized medicine • Primary prevention • Secondary prevention • Tertiary prevention • Treatment Ageing Clinical expression of chronicdiseases Co-morbidities Severity of co-morbidities Persistence, remission Long-termmorbidity Responsiveness - sideeffects to treatment

10. Classical phenotypes Novel phenotypes Hypothesis-driven Discovery driven Patient with chronic disease Co-morbidities (standardized assessment) CVD COPD Diabetes Assessment of co-morbities and severity Severity of co-morbidities (standardized assessment) Classical phenotypes in patients with severe defined diseases and co-morbidities Novel phenotypes in individual patients with severe co-morbidities of chronic diseases Responsiveness to treatment Follow up Responsiveness to treatment Follow up

11. Classical phenotypes Novel phenotypes Hypothesis-driven Discovery driven Patient with chronic disease Co-morbidities (standardized assessment) CVD COPD Diabetes Assessment of co-morbities and severity Severity of co-morbidities (standardized assessment) Classical phenotypes in patients with severe defined diseases and co-morbidities Novel phenotypes in individual patients with severe co-morbidities of chronic diseases Responsiveness to treatment Follow up Responsiveness to treatment Follow up

12. Classical phenotypes Novel phenotypes Hypothesis-driven Discovery driven Patient with chronic disease Co-morbidities (standardizedassessment) CVD COPD Diabetes Assessment of co-morbities and severity Severity of co-morbidities (standardized assessment) Classical phenotypes in patients with severe defined diseases and co-morbidities Novel phenotypes in individual patients with severe co-morbidities of chronic diseases Responsiveness to treatment Follow up Responsiveness to treatment Follow up

13. Is a uniformdefinition of severity, control and risk possible in chronicdiseases ?1- A novel concept of chronicdiseases2- The example of asthma

14. Asthma severity - GINA 2002 Asthmaseverity • Control • Symptoms • Functional limitation • over 2-4 weeks • Exacerbations over 6-12 mo

15. Classification of asthma: GINA 1998 Current treatment step Step 1 No controller Step 2 <500 BDP Step 3 200–1000 BDP + LABA Step 4 >1000 BDP + LABA + other Clinical features Severe persistent Moderate persistent Step 1 Symptoms <1 x week Nocturnal symptoms ≤2x month Lung function normal between episodes Intermittent Mild persistent Step 2 Symptoms >1 x week Nocturnal symptoms <1 x week Lung function normal between episodes Severe persistent Severe persistent Moderate persistent Mild persistent Step 3 Symptoms daily Nocturnal symptoms ≥1 x week FEV1 60–80% predicted Moderate persistent Severe persistent Severe persistent Severe persistent Severe persistent Severe persistent Step 4 Symptoms daily Frequent nocturnal symptoms FEV1 <60% predicted Severe persistent Severe persistent

16. Asthma control - GINA 2006 Asthma control • Control • Symptoms • Functional limitation • over 2-4 weeks • Exacerbations over 6-12 mo

17. GINA 2002 (severity)- 2006 (control)

18. Control of asthma: GINA 2006

19. Asthma severity- NAEPP3 (NHLBI) Asthmaseverity • Control • Symptoms • Functional limitation • over 2-4 weeks • Exacerbations over 6-12 mo • Future risks • Asthma exacerbations • Lung functionloss • Lung growth in children • Adverse reactionsfrommedications) Responsiveness to treatment

20. GINA 2002 - 2010

21. Definition of severe asthma (Geneva, 6-7 April 2009)

22. Asthma severity WHO definition Bousquet J et al, J Allergy Clin Immunol 2010 Asthmaseverity • Control • Symptoms • Functional limitation • over 2-4 weeks • Exacerbations over 6-12 mo • Future risks • Asthma exacerbations • Lung function loss • Lung growth in children • Adverse reactions from medications) • Level of treatment • Inhalation technique • Compliance Responsiveness to treatment

24. Is a uniformdefinition of severity, control and risk possible in chronicdiseases ?1- A novel concept of chronicdiseases2- The example of asthma3- Tentative definition

25. WP 6 Epigenetics and targetedproteomics

26. Uniform severity of chronic diseases Diagnosis of chronic disease Underdiagnosis Short-term (eg exacerbation) Long-term (eg remodelling) Assess and regularlyreview CONTROL RISK Risks due to co-morbidities Side effects from treatment

27. Uniform severity of chronic diseases

28. Uniform severity of chronic diseases Diagnosis of chronic disease Underdiagnosis Patient with uncontrolled chronic disease NO Is treatment/prevention effective ? Short-term (eg exacerbation) Long-term (eg remodelling) Assess and regularlyreview CONTROL RISK Risks due to co-morbidities Side effects from treatment

29. Uniform severity of chronic diseases

30. Uniform severity of chronic diseases Diagnosis of chronic disease Underdiagnosis Patient with uncontrolled chronic disease NO Is treatment/prevention effective ? Short-term (eg exacerbation) Untreated severe disease Is treatment available and affordable ? Long-term (eg remodelling) Assess and regularly review CONTROL RISK Risks due to co-morbidities Side effects from treatment

31. Uniform severity of chronic diseases

32. Uniform severity of chronic diseases Diagnosis of chronic disease Underdiagnosis Patient with uncontrolled chronic disease NO Is treatment/prevention effective ? Short-term (eg exacerbation) Untreated severe disease Is treatment available and affordable ? Long-term (eg remodelling) Treat according to guidelines Assess and regularly review CONTROL RISK Possible risk due to other disease Check if diagnosis is correct OR if there are other associated diseases Risks due to co-morbidities Side effects from treatment

33. Re-check asthma diagnosis No asthma OR Asthma PLUS another condition causing current symptoms NO Diagnosis Severe asthma due to occupational expoure to isocyanates

34. Re-check asthma diagnosis No asthma OR Asthma PLUS another condition causing current symptoms NO Visit for coarse voice due to high dose ICS (and dyspnea) in a severe asthmatic FEV1: 1.78 l (72%), post-ß2: 1.92 (+5%), FEV1/FVC: 66%

35. Uniform severity of chronic diseases

36. Uniform severity of chronic diseases Diagnosis of chronic disease Underdiagnosis Patient with uncontrolled chronic disease NO Is treatment/prevention effective ? Short-term (eg exacerbation) Untreated severe disease Is treatment available and affordable ? Long-term (eg remodelling) Treat according to guidelines Assess and regularly review CONTROL RISK Possible risk due to other disease Check if diagnosis is correct OR if there are other associated diseases Risks due to co-morbidities Check co-morbidies, risk factors compliance and/or treatment administration Difficult-to-treat disease Side effects from treatment

37. Uniform severity of chronic diseases

38. Uniform severity of chronic diseases Diagnosis of chronic disease Underdiagnosis Patient with uncontrolled chronic disease NO Is treatment/prevention effective ? Short-term (eg exacerbation) Untreated severe disease Is treatment available and affordable ? Long-term (eg remodelling) Treat according to guidelines Assess and regularly review CONTROL RISK Possible risk due to other disease Check if diagnosis is correct OR if there are other associated diseases Risks due to co-morbidities Check co-morbidies, risk factors compliance and/or treatment administration Difficult-to-treat disease Side effects from treatment Treat to the highest recommended dose Severe disease controlled with optimal treatment

39. Uniform severity of chronic diseases

40. Uniform severity of chronic diseases Diagnosis of chronic disease Underdiagnosis Patient with uncontrolled chronic disease NO Is treatment/prevention effective ? Short-term (eg exacerbation) Untreated severe disease Is treatment available and affordable ? Long-term (eg remodelling) Treat according to guidelines Assess and regularly review CONTROL RISK Possible risk due to other disease Check if diagnosis is correct OR if there are other associated diseases Risks due to co-morbidities Check co-morbidies, risk factors compliance and/or treatment administration Difficult-to-treat disease Side effects from treatment Treat to the highest recommended dose Severe disease uncontrolled despite optimal treatment Severe disease controlled with optimal treatment

41. Uniform severity of chronic diseases

42. Is a uniformdefinition of severity, control and risk possible in chronicdiseases ?1- A novel concept of chronicdiseases2- The example of asthma3- Tentative uniformdefinition4- Needs for a uniformdefinition

43. Applicability of the definition • Public health: to improve the quality of allergy care, • but also to optimize health care planning and policies. • Clinical practice: simplicity for physicians • Clinical trials • Research: Well characterized approved phenotypes • Epidemiologic studies: Well characterized approved phenotypes • Drug development • Applicable to developed and developing countries • Registries

44. One step in the phenotype complexity By courtesy from J Kiley

45. One step in the phenotype complexity By courtesy from J Kiley