unlock-01 paggiaro asma
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ASMA GRAVE E ACOS
NEL DOCUMENTO GINA 2014
Pierluigi Paggiaro
GINA International Executive Committee, Chairman GINA ITaly
Cardio-Thoracic and Vascular Department, University of Pisa
Università degli
Studi di Pisa
Azienda
Ospedaliera
Pisana
1° Convegno Pneumologia 2.0
Firenze Villa Castiglione, 8-10 maggio 2014
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 therapeutical plan
• Existance of different phenotypes
–Clinical and functional
–Biological
• Difference in:
–Strategy of asthma treatment
–Strategy in asthma management
A new definition of asthma: a heterogeneous disease
GINA 2014, draft
Main objectives in asthma treatment: control vs future risk
ATS Statement, AJRCCM 2009
Symptom control vs future risk
GINA 2014, draft
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 therapeutical plan
• Existance of different phenotypes
–Clinical and functional
–Biological
• Difference in:
–Strategy of asthma treatment
–Strategy in asthma management
Bronchial Asthma examples of special cases
• According to severity
– Mild-moderate vs severe («difficult to treat»)
– Frequent exacerbators vs chronic airway obstruction
• According to comorbidities or concominat situations:
– Obesity
– Pregnancy
• According to risk factors:
– Smoking habit
– Occupational sensitizers
• According to biological mechanisms:
– Non eosinophilic asthma
Different asthma phenotypes
Clinical asthma phenotypes Severity
• Assessment of severity
– Intensity and frequency of symptoms
– Level of treatment needed to control asthma
• Severity (first examination) vs control (under treatment)
– Large variability in moving from different levels of severity or control
• Implication for treatment
– Only for «difficult-to-treat» asthma
– «Steroid-resistant» asthma: biologic basis (?)
Bousquet et al, JACI 2010
Asthma control in severe asthmatic patients
68.8% of patients had at least one exacerbation in the last year
Novelli et al, ERS 2013
Prevalence of comorbidities
Novelli et al, ERS 2013
Chronic rhinosinusitis with nasal polyps
Nasal polyps
(N=21)
No nasal polyps
(N=43)
Pre-BD FEV1, % 71.0±17.5 * 81.1±17.7
Sputum eosinophils, % 22.3 (0.4-95.6) 10.6 (0-84.1)
Sputum eosinophils ≥3% 89.5 * 63.9
ACT score 21 (10-24) 20 (7-25)
Poorly controlled, % 8 (38.1) 23 (53.5)
Exacerbation in the last year, % 66.7 69.8
AQLQ score 4.63 (2.69-6.56) 4.92 (3.03-6.75)
Novelli et al, ERS 2013
Obesity
Obese
(N=22)
Normal weight
(N=42)
Pre-BD FEV1, % 77.7±23.5 77.9±14.8
Sputum eosinophils, % 8.3 (0-71.2) 17.4 (0-95.6)
Sputum eosinophils ≥3% 63.2 77.8
ACT 16.5 (7-25) * 21 (12-25)
Poorly controlled, % 72.7 * 35.7
Exacerbation in the last year, % 77.3 64.3
AQLQ score 4.47 (3.03-6.16) 5.31 (2.69-6.75)*
Novelli et al, ERS 2013
GERD
GERD
(N=25)
No GERD
(N=39)
Pre-BD FEV1, % 77.4±16.5 78.1±19.3
Sputum eosinophils, % 14.9 (0-82.8) 15.8 (0-95.6)
Sputum eosinophils ≥3% 59.1 § 81.8
ACT 19 (7-25) 21 (10-25)
Poorly controlled, % 56.0 43.6
Exacerbation in the last year, % 76.0 64.1
AQLQ score 4.42 (2.69-6.16) * 5.28 (3.19-6.75)
No difference in prevalence of obesity beetween the two groups
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
Clinical asthma phenotypes Exacerbations vs FEV1 decline vs age of
onset
• Exacerbation-prone phenotype («frequent exacerbators»)
– 50% of severe and 30% of moderate asthmatics (SARP study)
– Related to risk factors
– Different susceptibility to viral infections ?
• Progressive decline in FEV1 («decliners»)
– 25% of mild-moderate asthmatics (CAMP study)
– Persistent airflow limitation in 60% of severe asthmatics (TENOR study)
– Risk factors: male, age, smoking, asthma duration, airway inflammation
– Genetic predisposition (ADAM33) (?)
• Age of onset
– Early-onset asthma: more atopic, lower severity (?)
Different asthma phenotypes
Asthma phenotypes according to triggers
• Allergens («allergic asthma»)
– Prevalent in children and in mild-moderate asthmatic adults
– Typical Th2-driven inflammation
– Target for Immunotherapy
• Occupational and environmental factors
– Up to 15% of asthma is related to occupation
– Work-related asthma: occupational asthma + work-aggravated asthma
• Exercise
– In children and elite athletes («exercise-induced bronchospasm»)
Asthma phenotypes Smoke
• High risk for asthma developing
• Prevalence in asthmatics: 20% smokers
• Characteristics of asthma in smokers – Lower eosinophilic inflammation
– Lower response to ICS
– Greater FEV1 decline over time
Current smokers with asthma have greater rate of exacerbations, despite
ICS or ICS/LABA treatment
Pedersen et al, JACI 2007
Different asthma phenotypes
Asthma phenoypes Eosinophilic vs non-eosinophilic asthma
• Eosinophilic phenotype – Allergen-induced asthma, children asthma
– Severe asthma with frequent exacerbations (CS-dependent asthma)
• Non eosinophilic phenotype – Specific “triggers” (pollutants, endotoxins, chemicals,
viruses)
– In all asthma severity levels
– Stable over time ?
– Lower response to ICS
different therapeutic strategies ?
Different asthma phenotypes
Haldar et al, AJRCCM 2008
Vagaggini et al., AJRCCM 2001
Acute ozone exposure in laboratory induces in mild-moderate asthmatics a prominent neutrophilic inflammatory response, which
is blunted by inhaled budesonide
Asthma inflammatory phenotypes do not correlate with clinical
findings
Simpson et al, Respirology 2006
Bacci et al, Chest 2006
Absence of sputum eosinophilia in corticosteroid”naive” asthmatics
predicts a poor short-term response to ICS
Bacci et al, Respirology 2012
Steroid-naif symptomatic noneosinophilic asthma may remain stable over 6 months
Asthma phenotypes Implications for treatment
• With current available drugs – High dose vs low dose ICS (non eosinophilic, smokers)
– Eosinophil-driven strategies
– LTRA (exercise asthma, aspirin-inuced asthma, asthma + rhinitis)
– Heterogeneity of the response also in unselected asthmatics
• With new therapeutic targets – Anti-IgE, anti-IL5, anti-IL13, …..
– Allergic and eosinophilic allergic asthmatics
• With new treatments (thermoplasty) – Severe uncontrolled patients (which phenotype ?)
Green et al, Lancet 2002
The control of sputum eosinophilia is associated with a reduction in asthma exacerbations,
but only for eosinophilic exacerbations
Jayaram et al, ERJ 2006
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»
Control of asthma in severe asthmatics treated with omalizumab
Novelli et al, ERS 2013
Asthma control in severe asthmatics treated with omalizumab
Poorly controlled Well-partially controlled
Number of patients 75 221
Age, yrs 53,4±13,5 51,5±13,9
Gender, M/F % 34,7/65,3 38/62
Smoke, Y/Ex/No % 4,0/25,3/70,7 3,6/28,1/67,4
Rhinitis, n (%) 51(68,9) 142(65,1)
Chronic rhinosinusitis, n (%) 28(38,4) 70(33)
Nasal polyps, n (%) 20(27,8) 51(23,6)
Aspirin intolerance, n (%) 24(33,8) 39(18,6)*
Obesity, n (%) 25(33,3) 43(19,5)*
Gastro-oesophageal reflux, n(%) 35(47,3) 69(32,5)*
Mental disorders, n (%) 8(11,3) 15(7,1)
Months of OT 29,5(4-96) 33(4-120)
Pre-BD FEV1, % del predetto 64,1±19,8 78,3±19,7* * p<0.05
Novelli et al, ERS 2013
Exacerbations in severe asthmatics treated with omalizumab
No exacerbations Exacerbations ≥1
Number of patients 167 125
Age, yrs 51,6±13,2 52,5±14,4
Gender, M/F 39,5/60,5 34,4/65,6
Smoke, Y/Ex/No 3,6/28,1/67,1 3,2/25,6/71,2
Rhinitis, % 108(65,9) 80(64,5)
Chronic rhinosinusitis, % 43 (27) 52 (43,3)*
Nasal polyps, % 30 (18,5) 43 (35,2) 3 *
Aspirin intolerance, % 25(15) 35(29,4) 5*
Obesity, % 28(16,9) 38 (30,4)*
Gastro-oesophageal reflux, % 47 (29,4) 55(45,1)*
Mental disorders, % 10(6,3) 11 (9,2)
Months of omalizumab 32 (5-79) 36 (4-120)
Pre-BD FEV1, % del predetto 77,8±18,6 70,6±22,4*
ACT score 22 (10-25) 20 (6-25)*
* p<0.05 Novelli et al, ERS 2013
Asthma control in patients without comorbidities
Novelli et al, ERS 2013
Duration of omalizumab treatment may be associated with a better asthma control
*
* p=0.003
Novelli et al, ERS 2013
Castro et al, AJRCCM 2010
Asthma-COPD overlap syndrome
GINA 2014, draft
Prevalence of self-reported physician-diagnosed asthma and COPD
De Marco et al, PlosOne 2013
GINA 2014, draft
GINA 2014, draft
Check different features of asthma and COPD
GINA 2014, draft
GINA 2014, draft
Asthma: a heterogeneous disease
• Identification of different phenotypes – According to etiology
– According to pathogenesis
– According to severity
• Implication for treatment – With current drugs
– With biolgoic drugs
– With allergen-immunotherapy
– With thermoplaty
• «tailoring» asthma approach