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

Adrenaline Drugs for asthma Oral steroids Theophylline, 2011 PDE4i Short-acting B 2 Disodium Cromoglycate -Nedocromil Inhaled corticosteroids Anticholinergics Long – acting B 2 LTR antagonists Long- acting anticholinergic Anti IgE Ultra- long acting steroid and B 2 1960 1970 1980 1990 2000 2004 2006 2013

Definizione di asma bronchiale

• IERI

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

• OGGI

Patologia infiammatoria cronica 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!

26/04/2020

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 31% Neutrophylic eosinophylic asthma 8% Neutrophylic asthma 20% Eosinophylic asthma 41%

Main comorbidities in asthma

Boulet, ERJ 2009

© 2010 PROGETTO LIBRA • www.ginasma.it

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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

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gw41298 United Airways Disease : therapeutic aspects .

Passalacqua G., Ciprandi G., Canonica GW.

THORAX 2000

Prevalence of comorbidities

Novelli et al, ERS 2013

Predictors of poor control, lower lung function and eosinophilic phenotype

Obesity Nasal polyps GERD

Poor control

OR (CI 95%) 5.3 (1.5-18.2) * 0.4 (0.1-1.5) 1.8 (0.6-5.8)

Lower lung function (Post-BD FEV1<80%)

OR (CI 95%) 1.7 (0.6-5.3) 3.6 (1,2-11.3) * 0.6 (0.2-1.8)

Eosinophilic phenotype

OR (CI 95%) 0.6 (0.2-1.9) 5.5 (1.1-27.8) * 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 STEP 4 Grave Persistente STEP 3 Moderato Persistente STEP 2 Lieve Persistente STEP 1 Intermittente CLASSIFICAZIONE DI GRAVITÀ Caratteristiche cliniche in assenza di terapia Sintomi Continui Attività fisica limitata < 1 volta/settimana  Sintomi notturni Frequenti Quotidiani Attacchi che limitano L’attività > 1 volta Alla settimana > 1 volta/settimana > 2 volte al mese ma < 1 volta / giorno 2 volte al mese FEV 1 o PEF FEV1  60% predetto Variabilità PEF> 30% FEV1 60 - 80% predetto Variabilità PEF > 30% FEV1  80% predetto Variabilità PEF 20-30% 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: TO STEP 4 TREATMENT, ADD EITHER Shaded green - preferred controller options

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 STEP 2 STEP 3 STEP 4 STEP 5

Opzione principale

Altre opzioni (in ordine decrescente di efficacia)

β 2 -agonisti a breve azione al bisogno CSI a bassa dose CSI a bassa dose + LABA

Cicli di CSI o CSI+LABA?

Anti-leucotrieni * Cromoni CSI+LABA a basso dosaggio ?

CSI a bassa dose + anti-leucotrieni * CSI a bassa dose + teofilline-LR CSI a dose medio-alta

CSI a media dose + LABA

aggiungere 1 o più:

Anti-leucotrieni Teofilline-LR

CSI a alta dose + LABA

aggiungere 1 o più:

Anti-leucotrieni Anti-IgE (omalizumab) ** Teofilline-LR CS orali

β 2 -agonisti a breve azione al bisogno

Programma di educazione Dose aggiuntiva di CSI+LABA Controllo ambientale e Immunoterapia quando indicata

CSI = corticosteroidi inalatori; LABA = long-acting β 2 -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

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