LINEE GUIDA DELL ASMA: UP TO DATE

Transcription

1 LINEE GUIDA DELL ASMA: UP TO DATE Azienda Ospedaliera Pisana Università degli Studi di Pisa Pierluigi Paggiaro GINA International Executive Committee, Chairman GINA ITaly Cardio-Thoracic and Vascular Department, University of Pisa XXX Congresso Sezione SIAIC Toscana Firenze, ottobre 2014

2 Bronchial Asthma heterogeneity in clinical presentation Large difference in clinical manifestations, related to: Severity of the disease Heterogeneity of inducers and/or triggers Level of adherence to therapeutic plan Existance of different phenotypes Clinical and functional Biological Difference in: Strategy of asthma treatment

3 A new definition of asthma (GINA 2014): a heterogeneous disease GINA 2014, draft

4 Main objectives in asthma treatment: control vs future risk ATS Statement, AJRCCM 2009

5 Symptom control vs future risk GINA 2014

6 Bronchial Asthma heterogeneity in clinical presentation Large difference in clinical manifestations, related to: Severity of the disease Heterogeneity of inducers and/or triggers Level of adherence to therapeutic plan Existance of different phenotypes Clinical and functional Biological Difference in: Strategy of asthma treatment

7 Different asthma phenotypes

8 Different asthma phenotypes

9 Asthma phenoypes Eosinophilic vs non-eosinophilic asthma Eosinophilic phenotype Allergen-induced asthma, children asthma Severe asthma with frequent exacerbations (CSdependent asthma) Non eosinophilic phenotype Specific triggers (pollutants, endotoxins, chemicals, viruses) In all asthma severity levels

10 Absence of sputum eosinophilia in corticosteroid naive asthmatics predicts a poor short-term response to ICS Bacci et al, Chest 2006

11 Steroid-naif symptomatic noneosinophilic asthma may remain stable over 6 months Bacci et al, Respirology 2012

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13 Initial controller treatment GINA 2014

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15 Role of combination therapy GINA 2014

16 Maintenance and reliever strategy reduces asthma exacerbations, as well as or better than traditional strategies Humbert et al, Allergy 2008

17 Extrafine BDP/F as maintenance and reliever therapy - significantly prolonged time to first severe exacerbation - 36% reduction in the risk of experiencing a severe exacerbation Papi et al, The Lancet Respiratory Medicine, 2013

18 When and how stepping up GINA 2014

19 When and how stepping down GINA 2014

20 When and how stepping down GINA 2014

21 When and how stepping down GINA 2014

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26 Anticholinergics in asthma Short-acting anticholinergics in asthma Less effective than short-acting beta2-agonists Recommended only in acute severe asthma attack Tiotropium: Recent studies on tiotropium in asthma Largely used in COPD Since 2007 Large RCTs with Tiotropium in Asthma (TinA)

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28 First coprimary endopoint (FEV1) Kerstjens et al, NEJM 2012

29 Third coprimary endopoint (severe exacerbations) Severe exacerbation rate - 21% Time to first ex: + 56 days NNT: 15 Minor changes in symptoms - ACQ in trial 1 (n.s.) in trial 2 (p=0.06) - AQLQ in trial 1 (n.s.) in trial 2 (p=0.02) Kerstjens et al, NEJM 2012

30 Triple therapy in asthma Combination of ICS, LAMA, LAMA Different inhalers Single inhaler (once daily vs twice daily) Current position LAMA in addition to ICS/LABA Which patients?

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32 The control of sputum eosinophilia is associated with a reduction in asthma exacerbations, but only for eosinophilic exacerbations Green et al, Lancet 2002 Jayaram et al, ERJ 2006

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34 Multiple Levels to Target Novel Therapies 1. Antigen presentation 2. Th-2 cell stimulation and release of Th-2 cytokines 3. Mast cell activation (IgE) 4. Eosinophil recruitment and activation. 5. Upregulation of adhesion molecule expression in blood vessels and epithelium. 6. Activation of resident cells such as fibroblasts.

35 Italian multicentre observational study in patients under treatment with Omalizumab 24 Italian pulmonary and allergology centres More than 300 patients under treatment Aims: Evaluation of the level of asthma control (symptoms, pulmonary function, exacerbations) Factors related to poor asthma control Relationship «duration of treatment / level of control»

36 Control of asthma in severe asthmatics treated with omalizumab Novelli et al, Pulm Pharm Ther 2014

37 Asthma control in severe asthmatics treated with omalizumab Poorly controlled Number of patients Age, yrs Gender, M/F % Smoke, Y/Ex/No % Rhinitis, n (%) Chronic rhinosinusitis, n (%) Nasal polyps, n (%) Aspirin intolerance, n (%) Obesity, n (%) Gastro-oesophageal reflux, n(%) Mental disorders, n (%) Months of OT Pre-BD FEV1, % del predetto 75 53,4±13,5 34,7/65,3 4,0/25,3/70,7 51(68,9) 28(38,4) 20(27,8) 24(33,8) 25(33,3) 35(47,3) 8(11,3) 29,5(4-96) 64,1±19,8 Well-partially controlled ,5±13,9 38/62 3,6/28,1/67,4 142(65,1) 70(33) 51(23,6) 39(18,6)* 43(19,5)* 69(32,5)* 15(7,1) 33(4-120) 78,3±19,7* * p<0.05 Novelli et al, Pulm Pharm Ther 2014

38 Exacerbations in severe asthmatics treated with omalizumab Number of patients Age, yrs Gender, M/F Smoke, Y/Ex/No Rhinitis, % Chronic rhinosinusitis, % Nasal polyps, % Aspirin intolerance, % Obesity, % Gastro-oesophageal reflux, % Mental disorders, % Months of omalizumab Pre-BD FEV1, % del predetto ACT score * p<0.05 No exacerbations Exacerbations ,6±13,2 39,5/60,5 3,6/28,1/67,1 108(65,9) 43 (27) 30 (18,5) 25(15) 28(16,9) 47 (29,4) 10(6,3) 32 (5-79) 77,8±18,6 22 (10-25) ,5±14,4 34,4/65,6 3,2/25,6/71,2 80(64,5) 52 (43,3)* 43 (35,2) 3 * 35(29,4) 5* 38 (30,4)* 55(45,1)* 11 (9,2) 36 (4-120) 70,6±22,4* 20 (6-25)* Novelli et al, Pulm Pharm Ther 2014

39 Asthma control in patients without comorbidities Novelli et al, Pulm Pharm Ther 2014

40 Duration of omalizumab treatment may be associated with a better asthma control * * p=0.003 Novelli et al, Pulm Pharm Ther 2014

41 Different targets for intervention on the «inflammatory cascade» Gallelli et al, Biomed Res Int 2013

42 Pelaia et al, Nature Rev 2012

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45 Castro et al, AJRCCM 2010

46 Asthma: a heterogeneous disease Identification of different phenotypes According to etiology According to pathogenesis According to severity Implication for treatment With current drugs With biologic drugs With allergen-immunotherapy