LINEE GUIDA DELLASMA: UP TO DATE Azienda Universit degli - - PowerPoint PPT Presentation

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LINEE GUIDA DELLASMA: UP TO DATE Azienda Universit degli - - PowerPoint PPT Presentation

Jun 28, 2023 436 likes •918 views

LINEE GUIDA DELLASMA: UP TO DATE Azienda Universit degli Ospedaliera Studi di Pisa Pisana Pierluigi Paggiaro GINA International Executive Committee, Chairman GINA ITaly Cardio-Thoracic and Vascular Department, University of Pisa XXX

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LINEE GUIDA DELL’ASMA: UP TO DATE

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

XXX Congresso Sezione SIAIC Toscana Firenze, 10-11 ottobre 2014

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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 therapeutic plan

  • Existance of different phenotypes

– Clinical and functional – Biological

  • Difference in:

– Strategy of asthma treatment

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A new definition of asthma (GINA 2014): a heterogeneous disease

GINA 2014, draft

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Main objectives in asthma treatment: control vs future risk

ATS Statement, AJRCCM 2009

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Symptom control vs future risk

GINA 2014

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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 therapeutic plan

  • Existance of different phenotypes

– Clinical and functional – Biological

  • Difference in:

– Strategy of asthma treatment

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Different asthma phenotypes

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Different asthma phenotypes

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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

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Bacci et al, Chest 2006

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

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Bacci et al, Respirology 2012

Steroid-naif symptomatic noneosinophilic asthma may remain stable over 6 months

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Initial controller treatment

GINA 2014

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Role of combination therapy

GINA 2014

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“Maintenance and reliever” strategy reduces asthma exacerbations, as well as or better than traditional strategies

Humbert et al, Allergy 2008

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Extrafine BDP/F as maintenance and reliever therapy

Papi et al, The Lancet Respiratory Medicine, 2013

  • significantly prolonged time to first severe exacerbation
  • 36% reduction in the risk of experiencing a severe exacerbation
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When and how stepping up

GINA 2014

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When and how stepping down

GINA 2014

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When and how stepping down

GINA 2014

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When and how stepping down

GINA 2014

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Anticholinergics in asthma

  • Short-acting anticholinergics in asthma

– Less effective than short-acting beta2-agonists – Recommended only in acute severe asthma attack

  • Tiotropium:

– Largely used in COPD

  • Recent studies on tiotropium in asthma

– Since 2007

  • Large RCTs with Tiotropium in Asthma (TinA)
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First coprimary endopoint (FEV1)

Kerstjens et al, NEJM 2012

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Severe exacerbation rate

  • 21%
  • Time to first ex: + 56 days
  • NNT: 15

Minor changes in symptoms

  • ACQ7
  • -0.09 in trial 1 (n.s.)
  • -0.13 in trial 2 (p=0.06)
  • AQLQ
  • -0.04 in trial 1 (n.s.)
  • -0.18 in trial 2 (p=0.02)

Kerstjens et al, NEJM 2012

Third coprimary endopoint (severe exacerbations)

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Triple therapy in asthma

  • Combination of ICS, LAMA, LAMA

– Different inhalers – Single inhaler (once daily vs twice daily)

  • Current position

– LAMA in addition to ICS/LABA – Which patients ?

Future perspectives

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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

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1. Antigen presentation 2. Th-2 cell stimulation and release of Th-2 cytokines 3. Mast cell activation (IgE) 4. Eosinophil recruitment and activation. 5. Upregulation of adhesion molecule expression in blood vessels and epithelium. 6. Activation of resident cells such as fibroblasts.

Multiple Levels to Target Novel Therapies

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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»

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Control of asthma in severe asthmatics treated with omalizumab

Novelli et al, Pulm Pharm Ther 2014

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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, Pulm Pharm Ther 2014

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Exacerbations in severe asthmatics treated with

  • malizumab

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, Pulm Pharm Ther 2014

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Asthma control in patients without comorbidities

Novelli et al, Pulm Pharm Ther 2014

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Duration of omalizumab treatment may be associated with a better asthma control

*

* p=0.003

Novelli et al, Pulm Pharm Ther 2014

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Different targets for intervention on the «inflammatory cascade»

Gallelli et al, Biomed Res Int 2013

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Pelaia et al, Nature Rev 2012

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Castro et al, AJRCCM 2010

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Asthma: a heterogeneous disease

  • Identification of different phenotypes

– According to etiology – According to pathogenesis – According to severity

  • Implication for treatment

– With current drugs – With biologic drugs – With allergen-immunotherapy – With thermoplasty