Il ruolo dell’infiammazione nella BPCO 1

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

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

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

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

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. 2010. www.goldcopd.org 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) 2010. Available from www.goldcopd.org 6

BPCO ASMA Fabbri L, et al. AJRCCM 2003;167:418-24.

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;350:2645-2653. 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;30:467-471. 20 Neutrophils Macrophages CD8+ cells Adapted from Hogg JC, Chu F, Utokaparch S, et al. Thorax 2006;61:96-97. 8

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