1. Il ruolo dell’infiammazione nella BPCO1

2. Il ruolo centrale del’infiammazione cronica nella BPCO
Neutrophils
CD8+ T-lymphocytes
Macrophages
Key inflammatory cells
Smoke
Pollutants
Inflammation
Chronic inflammation
Structural changes
Speaker notes
Chronic inflammation of the airways, lung tissue and pulmonary blood vessels results from exposure to inhaled irritants such as tobacco smoke and other pollutants.
Inflammation of the airways is present from the onset of COPD1 and increases with disease severity.1,2
Inflammatory cells accumulate in the lung tissue and trigger an inflammatory cascade that results in airflow limitation and systemic inflammation outside the lung.
In COPD, these cells include neutrophils, CD8+ T-lymphocytes, and macrophages.1,3 They release inflammatory mediators such as tumour necrosis factor-α (TNFα), matrix-metalloproteinases (MMP-9), and interleukins (IL-1, IL-6, IL-8).3,4
An acute COPD exacerbation represents a further amplification of the inflammation that is present in the stable state. 5,6
References
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645–2653.
Saetta M. Airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:S17–S20.
Barnes PJ, Hansel TT. Prospects for new drugs for Chronic Obstructive Pulmonary Disease. Lancet 2004;364:985–996.
Barnes PJ. Chemokines in COPD. In: Stockley RA, Rennard SI, Rabe K, Celli B, editors. Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
Papi A, Bellettato CM, Braccioni F, et al. Infections and Airway Inflammation in Chronic Obstructive Pulmonary Disease Severe Exacerbations. Am J Respir Crit Care Med 2006;173:1114–1121.
Perera W, Hurst JR, Wilkinson TM, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J 2007;29:527–534.
Systemic inflammation
Bronchoconstriction, oedema, mucus, emphysema
Acute exacerbation
Airflow limitation
Barnes PJ. From: Stockley RA, Rennard SI, Rabe K, et al (Editors). Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860. 2

3. L’infiammazione nella BPCO 1
Increased total inflammatory cells
Increased CD8+ve T cells
Increased neutrophils in sputum
Increased B cells in severe disease
Increased mast cells
CD45
CD8
Speaker notes
Chronic inflammation of the airways, lung tissue and pulmonary blood vessels results from exposure to inhaled irritants such as tobacco smoke and other pollutants.
Inflammation of the airways is present from the onset of COPD1 and increases with disease severity.1,2
Inflammatory cells accumulate in the lung tissue and trigger an inflammatory cascade that results in airflow limitation and systemic inflammation outside the lung.
In COPD, these cells include neutrophils, CD8+ T-lymphocytes, and macrophages.1,3 They release inflammatory mediators such as tumour necrosis factor-α (TNFα), matrix-metalloproteinases (MMP-9), and interleukins (IL-1, IL-6, IL-8).3,4
An acute COPD exacerbation represents a further amplification of the inflammation that is present in the stable state. 5,6
References
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645–2653.
Saetta M. Airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:S17–S20.
Barnes PJ, Hansel TT. Prospects for new drugs for Chronic Obstructive Pulmonary Disease. Lancet 2004;364:985–996.
Barnes PJ. Chemokines in COPD. In: Stockley RA, Rennard SI, Rabe K, Celli B, editors. Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
Papi A, Bellettato CM, Braccioni F, et al. Infections and Airway Inflammation in Chronic Obstructive Pulmonary Disease Severe Exacerbations. Am J Respir Crit Care Med 2006;173:1114–1121.
Perera W, Hurst JR, Wilkinson TM, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J 2007;29:527–534. 3

4. L’infiammazione nella BPCO 2
Increased in neutrophils and eosinophils during exacerbations
Mucociliary dysfunction
Alveolar destruction
CD45
CD8
Speaker notes
Chronic inflammation of the airways, lung tissue and pulmonary blood vessels results from exposure to inhaled irritants such as tobacco smoke and other pollutants.
Inflammation of the airways is present from the onset of COPD1 and increases with disease severity.1,2
Inflammatory cells accumulate in the lung tissue and trigger an inflammatory cascade that results in airflow limitation and systemic inflammation outside the lung.
In COPD, these cells include neutrophils, CD8+ T-lymphocytes, and macrophages.1,3 They release inflammatory mediators such as tumour necrosis factor-α (TNFα), matrix-metalloproteinases (MMP-9), and interleukins (IL-1, IL-6, IL-8).3,4
An acute COPD exacerbation represents a further amplification of the inflammation that is present in the stable state. 5,6
References
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645–2653.
Saetta M. Airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:S17–S20.
Barnes PJ, Hansel TT. Prospects for new drugs for Chronic Obstructive Pulmonary Disease. Lancet 2004;364:985–996.
Barnes PJ. Chemokines in COPD. In: Stockley RA, Rennard SI, Rabe K, Celli B, editors. Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
Papi A, Bellettato CM, Braccioni F, et al. Infections and Airway Inflammation in Chronic Obstructive Pulmonary Disease Severe Exacerbations. Am J Respir Crit Care Med 2006;173:1114–1121.
Perera W, Hurst JR, Wilkinson TM, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J 2007;29:527–534. 4

5. Cellule e mediatori infiammatori: target terapeutici nella BPCO
Alveolar macrophage
TNFa
CD8+
T-cell
Mast cell
PROTEASES
IFNg
Speaker notes
Chronic inflammation of the airways, lung tissue and pulmonary blood vessels results from exposure to inhaled irritants such as tobacco smoke and other pollutants.
Inflammation of the airways is present from the onset of COPD1 and increases with disease severity.1,2
Inflammatory cells accumulate in the lung tissue and trigger an inflammatory cascade that results in airflow limitation and systemic inflammation outside the lung.
In COPD, these cells include neutrophils, CD8+ T-lymphocytes, and macrophages.1,3 They release inflammatory mediators such as tumour necrosis factor-α (TNFα), matrix-metalloproteinases (MMP-9), and interleukins (IL-1, IL-6, IL-8).3,4
An acute COPD exacerbation represents a further amplification of the inflammation that is present in the stable state. 5,6
References
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645–2653.
Saetta M. Airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:S17–S20.
Barnes PJ, Hansel TT. Prospects for new drugs for Chronic Obstructive Pulmonary Disease. Lancet 2004;364:985–996.
Barnes PJ. Chemokines in COPD. In: Stockley RA, Rennard SI, Rabe K, Celli B, editors. Chronic Obstructive Pulmonary Disease. Oxford, England: Blackwell Publishing; 2007:860.
Papi A, Bellettato CM, Braccioni F, et al. Infections and Airway Inflammation in Chronic Obstructive Pulmonary Disease Severe Exacerbations. Am J Respir Crit Care Med 2006;173:1114–1121.
Perera W, Hurst JR, Wilkinson TM, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation. Eur Respir J 2007;29:527–534.
Perforin/granzymes
Mucus-hypersecretion
Emphysema
Neutrophil 5

6. Differenze dell’infiammazione nella BPCO e nell’asma
Asthma
COPD
Noxious agent
Triggers
Sensitising agent
Neutrophils
CD8+ T-lymphocytes
Macrophages
Eosinophils
CD4+ T-lymphocytes
Mast cells
Inflammatory cells
Speaker notes
Although COPD and asthma are both respiratory diseases characterised by underlying inflammation, the nature of the inflammatory cascade is different in each disease.
COPD-specific inflammation is characterised by increased activity of neutrophils, CD8+ T-lymphocytes and macrophages. The airflow limitation is not fully reversible.
In asthma, airflow limitation is often reversible, either spontaneously or with treatment, and is characterised by a different profile of inflammatory cells that includes eosinophils and CD4+ T-lymphocytes.
Structurally, both the airways and lung parenchyma are affected by COPD and airflow limitation is progressive. In asthma, only the airways are affected.
Patients with COPD are typically 40 years or older and have a history of smoking. Asthma typically begins during childhood and is not associated with smoking.
Establishing the correct diagnosis of COPD ensures that patients can be given appropriate anti-smoking and lifestyle advice, treatments and prognosis.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of COPD
Not fully reversible
Reversible
Airflow limitation
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease,
Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from 6

7. BPCO
ASMA
Fabbri L, et al. AJRCCM 2003;167:

8. Infiammazione delle vie aeree in relazione alla gravità della BPCO
GOLD Stage I
GOLD Stage II and III
GOLD Stage IV
100 80 60
Airways with measurable cells (%) 40
Speaker notes
Chronic inflammation is present from the onset of COPD1 and increases with disease severity.1,2
Inflammation may persist long after the patient stops smoking.1,3
References
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:
Saetta M. Airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160:S17-S20.
Gamble E, Grootendorst DC, Hattotuwa K, et al. Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis. Eur Respir J 2007;30: 20
Neutrophils
Macrophages
CD8+ cells
Adapted from Hogg JC, Chu F, Utokaparch S, et al. Thorax 2006;61:96-97. 8

9. Concetti chiave
Chronic inflammation in the airways and systemic circulation contributes to the pathology of COPD
COPD-specific inflammation is characterised by increased neutrophils, CD8+ T-lymphocytes and macrophages, as well as cytokines and other inflammatory mediators
Inflammatory processes activated in asthma are different from COPD- specific inflammation
Chronic inflammation is present from the onset of COPD and increases with disease progression. Airway inflammation increases during exacerbations
Effective COPD management should include agents that target the chronic inflammation underlying the disease 9