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Diapositiva 1
XX Anniversario SIMeR Belgirate, 19 dicembre 2014 20 anni di asma bronchiale Stefano Centanni Clinica di Malattie dell’ Apparato Respiratorio Università degli Studi di Milano Ospedale San Paolo di Milano Drugs for asthma Adrenaline Oral steroids Theophylline, 2011 PDE4i Short-acting B2 Disodium Cromoglycate -Nedocromil Inhaled corticosteroids Anticholinergics Long – acting B2 LTR antagonists Long- acting anticholinergic Anti IgE Ultra- long acting steroid and B2 1960 1970 1980 1990 2000 2004 2006 2013 Definizione di asma bronchiale • IERI • OGGI Patologia infiammatoria cronica Malattia caratterizzata da dispnea, ad insorgenza a crisi parossistiche, determinate da stenosi bronchiale per spasmo della muscolatura liscia, edema ed ipersecrezione, nella cui patogenesi può avere importanza il meccanismo allergico delle vie aeree nella quale giocano un ruolo molte cellule, in particolare i mastociti, gli eosinofili, i linfociti T, e numerosi mediatori chimici, in grado di provocare alterazioni strutturali delle vie aeree e rimodellamento, a loro volta responsabili di una riduzione della funzione respiratoria Asthma Inflammation: Cells and Mediators Source: Peter J. Barnes, MD Definition of asthma Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation. NEW! 11/08/2016 GINA 2014 © Global Initiative for Asthma A possible new definition of asthma: clinical syndrome or heterogeneous disease GINA 2014, draft Il gomitolo dell’asma L. Allegra, tanti anni fa… Asthma : defining of the persistent phenotypes S. Wenzel 2006; 368 : 804 Different asthma phenotypes Wenzel, Lancet 2007 Inflammatory phenotypes Paucigranulocytic asthma Neutrophyliceosinophylic asthma 31% Neutrophylic asthma 20% 8% Eosinophylic asthma 41% Main comorbidities in asthma Boulet, ERJ 2009 © 2010 PROGETTO LIBRA • www.ginasma.it 24 Current smokers with asthma have greater rate of exacerbations, despite ICS or ICS/LABA treatment Pedersen et al, JACI 2007 Main comorbidities in asthma Boulet, ERJ 2009 © 2010 PROGETTO LIBRA • www.ginasma.it 26 United Airways Disea therapeutic aspects . Passalacqua G., Ciprandi G Canonica GW. THORAX gw41298 Prevalence of comorbidities Novelli et al, ERS 2013 Predictors of poor control, lower lung function and eosinophilic phenotype Poor control Lower lung function (Post-BD FEV1<80%) Eosinophilic phenotype OR (CI 95%) OR (CI 95%) OR (CI 95%) Obesity 5.3 (1.5-18.2) * 1.7 (0.6-5.3) 0.6 (0.2-1.9) Nasal polyps 0.4 (0.1-1.5) 3.6 (1,2-11.3) * 5.5 (1.1-27.8) * GERD 1.8 (0.6-5.8) 0.6 (0.2-1.8) 0.4 (0.1-1.5) Novelli et al, ERS 2013 Asthma: a heterogeneous disease • Symptoms – Non specific – Blunted by bronchodilators or poor perception • Risk factors – Atopic vs non atopic – Young vs older patients • Mechanisms – Dfferent pattern of airway inflammation – Different mechanisms (non-inflammatory ?) • Importance of functional assessment – Reversible obstruction – Bronchial hyperresponsiveness – Wide variability over time of pulmonary function Primary role of lung function variability for diagnosis GINA 2014, draft GINA guidelines Main points for clinical application • Definition and assessment of asthma – Clinical and functional assessment – Severity vs control • Main outcomes in asthma management – Reach and maintain asthma control – Consider future risk – The value of maintaining asthma control » Impact on natural history • Strategies for maintaining asthma control – Role of ICS/LABA combination – Flexible dose according » Control: Step-up vs step-down » Phenotypes: high vs low airway inflammation Classificazione di Gravità prima dell’inizio del trattamento CLASSIFICAZIONE DI GRAVITÀ Caratteristiche cliniche in assenza di terapia Sintomi Sintomi notturni FEV1 o PEF STEP 4 Grave Persistente Continui Attività fisica limitata STEP 3 Moderato Persistente Quotidiani Attacchi che limitano L’attività > 1 volta Alla settimana FEV1 60 - 80% predetto Variabilità PEF > 30% STEP 2 Lieve Persistente > 1 volta/settimana ma < 1 volta / giorno > 2 volte al mese FEV1 80% predetto Variabilità PEF 20-30% < 1 volta/settimana 2 volte al mese STEP 1 Intermittente Frequenti FEV1 60% predetto Variabilità PEF> 30% FEV1 80% predetto Variabilita PEF < 20% La presenza di almeno uno dei criteri di gravità è sufficiente per classificare un paziente in un determinato livello di gravità TO STEP 3 TREATMENT, SELECT ONE OR MORE: Shaded green - preferred controller options TO STEP 4 TREATMENT, ADD EITHER Main objectives in asthma treatment: control vs future risk ATS Statement, AJRCCM 2009 Main objectives in asthma treatment: control vs future risk ATS Statement, AJRCCM 2009 Future risk • Expressed by – – – – – Low FEV1 Persistent exposure to allergen or irritants (smoke) Comorbidities Persistent sputum or blood eosinophilia Specific phenotypes (?) • Consequences – Maintenance treatment vs step-down – Choise in the drugs/devices Assessment of overall asthma control GINA 2014, draft GINA guidelines Main points for clinical application • Definition and assessment of asthma – Clinical and functional assessment – Severity vs control • Main outcomes in asthma management – Reach and maintain asthma control – Consider future risk – The value of maintaining asthma control » Impact on natural history • Strategies for maintaining asthma control – Role of ICS/LABA combination – Flexible dose according » Control: Step-up vs step-down » Phenotypes: high vs low airway inflammation ICS/LABA combination therapy • First choice in a large part of asthmatic patients » From step 3 » Sometimes associated with other drugs » Effective on all “outcomes” of the disease • Simptoms, pulmonary function, exacerbations • Complementary and/or synergic • Safety demonstrated by several studies – Cochrane Database Syst Rev, apr & jul 2009, jan 2010 • Effective also in step-down as single daily dose • Effective also as rescue medication APPROCCIO PROGRESSIVO ALLA TERAPIA DELL’ASMA NELL’ADULTO STEP 1 Opzione principale Altre opzioni (in ordine decrescente di efficacia) STEP 2 STEP 3 β2-agonisti a breve azione al bisogno CSI a bassa dose Cicli di CSI o CSI+LABA? Anti-leucotrieni * Cromoni CSI+LABA a basso dosaggio ? STEP 4 STEP 5 CSI a bassa dose + LABA CSI a media dose + LABA CSI a alta dose + LABA CSI a bassa dose + anti-leucotrieni * CSI a bassa dose + teofilline-LR CSI a dose medio-alta aggiungere 1 o più: Anti-leucotrieni Teofilline-LR aggiungere 1 o più: Anti-leucotrieni Anti-IgE (omalizumab) ** Teofilline-LR CS orali β2-agonisti a breve azione al bisognoDose Programma di educazione Controllo ambientale e Immunoterapia quando indicata CSI = corticosteroidi inalatori; LABA = long-acting β2-agonisti; LR = a lento rilascio * nei pazienti con asma e rinite rispondono bene agli anti-leucotrieni ** nei pazienti allergici ad allergeni perenni e con livelli di IgE totali sieriche compresi tra 30 e 700 U/ml aggiuntiva di CSI+LABA How to improve asthma control ? • Frequent assessment of control – Regular use of ACT – Periodic assessment (APPs) • «Tailoring» asthma treatment – In selected phenotypes » «heterogeneity» of asthma – Balance between ICS and LABA