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!
18/12/2015
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