You are on page 1of 51

ASMA GRAVE E ACOS NEL DOCUMENTO GINA 2014

ASMA GRAVE E ACOS NEL DOCUMENTO GINA 2014 Università degli Studi di Pisa Pierluigi Paggiaro Azienda

Università degli Studi di Pisa

ASMA GRAVE E ACOS NEL DOCUMENTO GINA 2014 Università degli Studi di Pisa Pierluigi Paggiaro Azienda

Pierluigi Paggiaro

ASMA GRAVE E ACOS NEL DOCUMENTO GINA 2014 Università degli Studi di Pisa Pierluigi Paggiaro Azienda

Azienda

Ospedaliera

Pisana

GINA International Executive Committee, Chairman GINA ITaly Cardio-Thoracic and Vascular Department, University of Pisa

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

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

GINA 2014, draft

Main objectives in asthma

treatment: control vs future risk

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

ATS Statement, AJRCCM 2009

Symptom control vs future risk

Symptom control vs future risk GINA 2014, draft
Symptom control vs future risk GINA 2014, draft
Symptom control vs future risk GINA 2014, draft
Symptom control vs future risk GINA 2014, draft

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

Different asthma phenotypes
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
Bousquet et al, JACI 2010

Bousquet et al, JACI 2010

Asthma control in severe asthmatic patients

Asthma control in severe asthmatic patients 68.8% of patients had at least one exacerbation in the
Asthma control in severe asthmatic patients 68.8% of patients had at least one exacerbation in the

68.8% of patients had at least one exacerbation in the last year

Novelli et al, ERS 2013

Prevalence of comorbidities

Prevalence of comorbidities Novelli et al, ERS 2013

Novelli et al, ERS 2013

Chronic rhinosinusitis with nasal

polyps

ACT score

Poorly controlled, %

Exacerbation in the last year, %

AQLQ score

Sputum eosinophils, %

Pre-BD FEV1, %

Sputum eosinophils ≥3%

21 (10-24)

8 (38.1)

66.7

  • 4.63 (2.69-6.56)

71.0±17.5 *

81.1±17.7

  • 89.5 *

  • 22.3 (0.4-95.6)

10.6 (0-84.1)

63.9

  • 4.92 (3.03-6.75)

69.8

  • 23 (53.5)

  • 20 (7-25)

(N=21) Nasal polyps (N=43) No nasal polyps
(N=21) Nasal polyps (N=43) No nasal polyps
(N=21)
Nasal polyps
(N=43)
No nasal polyps
ACT score Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, %
ACT score Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, %
ACT score Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, %

Novelli et al, ERS 2013

Obesity

ACT

Poorly controlled, %

Exacerbation in the last year, %

AQLQ score

Sputum eosinophils, %

Pre-BD FEV1, %

Sputum eosinophils ≥3%

16.5 (7-25) *

  • 72.7 *

77.3

  • 4.47 (3.03-6.16)

77.7±23.5

77.9±14.8

63.2

8.3 (0-71.2)

17.4 (0-95.6)

77.8

  • 5.31 (2.69-6.75)*

64.3

35.7

21 (12-25)

Obese (N=22) (N=42) Normal weight
Obese (N=22) (N=42) Normal weight
Obese
(N=22)
(N=42)
Normal weight
ACT Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, % Pre-BD
ACT Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, % Pre-BD
ACT Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, % Pre-BD

Novelli et al, ERS 2013

GERD

ACT

Poorly controlled, %

Exacerbation in the last year, %

AQLQ score

Sputum eosinophils, %

Pre-BD FEV1, %

Sputum eosinophils ≥3%

19 (7-25)

56.0

76.0

  • 4.42 (2.69-6.16) *

77.4±16.5

78.1±19.3

  • 59.1 §

14.9 (0-82.8)

15.8 (0-95.6)

81.8

  • 5.28 (3.19-6.75)

64.1

43.6

21 (10-25)

(N=25) GERD (N=39) No GERD
(N=25) GERD (N=39) No GERD
(N=25)
GERD
(N=39)
No GERD
ACT Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, % Pre-BD
ACT Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, % Pre-BD
ACT Poorly controlled, % Exacerbation in the last year, % AQLQ score Sputum eosinophils, % Pre-BD

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

0.4 (0.1-1.5) 0.6 (0.2-1.8) 1.8 (0.6-5.8) GERD OR (CI 95%) OR (CI 95%) OR (CI 95%)
  • 0.4 (0.1-1.5)

  • 0.6 (0.2-1.8)

1.8 (0.6-5.8)

GERD
GERD
OR (CI 95%) OR (CI 95%) OR (CI 95%) Poor control Lower lung function (Post-BD 5.5
OR (CI 95%) OR (CI 95%) OR (CI 95%) Poor control Lower lung function (Post-BD 5.5

OR (CI 95%)

OR (CI 95%)

OR (CI 95%)

Poor control

Lower lung function (Post-BD

  • 5.5 (1.1-27.8) *

  • 3.6 (1,2-11.3) *

phenotype

  • 0.4 (0.1-1.5)

  • 0.6 (0.2-1.9)

1.7 (0.6-5.3)

  • 5.3 (1.5-18.2) *

FEV1<80%)

Eosinophilic

Nasal polyps

Obesity

0.4 (0.1-1.5) 0.6 (0.2-1.8) 1.8 (0.6-5.8) GERD OR (CI 95%) OR (CI 95%) OR (CI 95%)
0.4 (0.1-1.5) 0.6 (0.2-1.8) 1.8 (0.6-5.8) GERD OR (CI 95%) OR (CI 95%) OR (CI 95%)

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

Different asthma phenotypes
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

Current smokers with asthma have greater rate of exacerbations, despite ICS or ICS/LABA treatment Pedersen et

Pedersen et al, JACI 2007

Different asthma phenotypes

Different asthma phenotypes
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

Different asthma phenotypes Haldar et al, AJRCCM 2008

Haldar et al, AJRCCM 2008

Acute ozone exposure in laboratory induces

in mild-moderate asthmatics a prominent

neutrophilic inflammatory response, which is blunted by inhaled budesonide

Acute ozone exposure in laboratory induces in mild-moderate asthmatics a prominent neutrophilic inflammatory response, which is

Vagaggini et al., AJRCCM 2001

Asthma inflammatory phenotypes do not correlate with clinical findings
Asthma inflammatory phenotypes
do not correlate with clinical
findings
Asthma inflammatory phenotypes do not correlate with clinical findings Simpson et al, Respirology 2006
Simpson et al, Respirology 2006
Simpson et al, Respirology 2006

Absence of sputum eosinophilia

in corticosteroid”naive” asthmatics

predicts a poor short-term response to ICS

Absence of sputum eosinophilia in corticosteroid”naive” asthmatics predicts a poor short-term response to ICS Bacci et

Bacci et al, Chest 2006

Steroid-naif symptomatic noneosinophilic asthma

may remain stable over 6 months

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

Bacci et al, Respirology 2012

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 ?)

The control of sputum eosinophilia is associated

with a reduction in asthma exacerbations, but only for eosinophilic exacerbations

The control of sputum eosinophilia is associated with a reduction in asthma exacerbations, but only for
The control of sputum eosinophilia is associated with a reduction in asthma exacerbations, but only for

Green et al, Lancet 2002

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

Control of asthma in severe asthmatics treated with omalizumab Novelli et al, ERS 2013

Novelli et al, ERS 2013

Asthma control in severe

asthmatics treated with omalizumab

Aspirin intolerance, n (%)

Obesity, n (%)

Nasal polyps, n (%)

Chronic rhinosinusitis, n (%)

Rhinitis, n (%)

Months of OT

Mental disorders, n (%)

Gastro-oesophageal reflux, n(%)

Smoke, Y/Ex/No %

Gender, M/F %

Age, yrs

Number of patients

Pre-BD FEV1, % del predetto 78,3±19,7* 64,1±19,8
Pre-BD FEV1, % del predetto 78,3±19,7* 64,1±19,8
Pre-BD FEV1, % del predetto 78,3±19,7* 64,1±19,8
Pre-BD FEV1, % del predetto 78,3±19,7* 64,1±19,8
Pre-BD FEV1, % del predetto 78,3±19,7* 64,1±19,8

Pre-BD FEV1, % del predetto

78,3±19,7* 64,1±19,8
78,3±19,7*
64,1±19,8
Aspirin intolerance, n (%) Obesity, n (%) Nasal polyps, n (%) Chronic rhinosinusitis, n (%) Rhinitis,
Aspirin intolerance, n (%) Obesity, n (%) Nasal polyps, n (%) Chronic rhinosinusitis, n (%) Rhinitis,
35(47,3) Poorly controlled Well-partially controlled 75 34,7/65,3 53,4±13,5 51,5±13,9 3,6/28,1/67,4 4,0/25,3/70,7 38/62 221 25(33,3) 43(19,5)* 20(27,8)
35(47,3)
Poorly controlled
Well-partially
controlled
75
34,7/65,3
53,4±13,5
51,5±13,9
3,6/28,1/67,4
4,0/25,3/70,7
38/62
221
25(33,3)
43(19,5)*
20(27,8)
69(32,5)*
8(11,3)
29,5(4-96)
33(4-120)
15(7,1)
51(68,9)
142(65,1)
28(38,4)
70(33)
51(23,6)
24(33,8)
39(18,6)*
Aspirin intolerance, n (%) Obesity, n (%) Nasal polyps, n (%) Chronic rhinosinusitis, n (%) Rhinitis,

* p<0.05

Novelli et al, ERS 2013

Exacerbations in severe asthmatics treated with omalizumab

Gender, M/F No exacerbations Exacerbations ≥1 Number of patients 167 125 Age, yrs 51,6±13,2 52,5±14,4 34,4/65,6

Gender, M/F

 

No exacerbations

Exacerbations ≥1

Number of patients

167

125

Age, yrs

51,6±13,2

52,5±14,4

34,4/65,6

39,5/60,5

Rhinitis, % 108(65,9) 80(64,5) Chronic rhinosinusitis, % 43 (27) 52 (43,3)* Nasal polyps, % 30 (18,5)

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*

Pre-BD FEV1, % del predetto

77,8±18,6

70,6±22,4*

ACT score

22 (10-25)

20

(6-25)*

Mental disorders, %

10(6,3)

11 (9,2)

Months of omalizumab

32

(5-79)

36

(4-120)

Obesity, %

28(16,9)

38

(30,4)*

Gastro-oesophageal reflux, %

47

(29,4)

55(45,1)*

3,2/25,6/71,2

3,6/28,1/67,1

Smoke, Y/Ex/No

Gender, M/F No exacerbations Exacerbations ≥1 Number of patients 167 125 Age, yrs 51,6±13,2 52,5±14,4 34,4/65,6
Gender, M/F No exacerbations Exacerbations ≥1 Number of patients 167 125 Age, yrs 51,6±13,2 52,5±14,4 34,4/65,6

* p<0.05

Novelli et al, ERS 2013

Asthma control in patients without comorbidities

Asthma control in patients without comorbidities Novelli et al, ERS 2013

Novelli et al, ERS 2013

Duration of omalizumab treatment may be

associated with a better asthma control

* * p=0.003
*
* p=0.003

Novelli et al, ERS 2013

Castro et al, AJRCCM 2010
Castro et al, AJRCCM 2010
Castro et al, AJRCCM 2010

Castro et al, AJRCCM 2010

Asthma-COPD overlap syndrome

Asthma-COPD overlap syndrome GINA 2014, draft
Asthma-COPD overlap syndrome GINA 2014, draft

GINA 2014, draft

Prevalence of self-reported physician-

diagnosed asthma and COPD

Prevalence of self-reported physician- diagnosed asthma and COPD De Marco et al, PlosOne 2013

De Marco et al, PlosOne 2013

GINA 2014, draft
GINA 2014, draft
GINA 2014, draft

GINA 2014, draft

GINA 2014, draft
GINA 2014, draft
GINA 2014, draft

GINA 2014, draft

Check different features of asthma and COPD

Check different features of asthma and COPD GINA 2014, draft

GINA 2014, draft

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