Habib GHEDIRA, MD, Prof. Medical Faculty of Tunis COPD Consensus GOLD Global Initiative for chronic Obstructive Lung Disease Habib GHEDIRA, MD, Prof. Medical Faculty of Tunis

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 Proportion of 1965 Rate 3.0 Coronary Heart Disease Stroke Other CVD COPD All Other Causes 2.5 2.0 1.5 1.0 0.5 –59% –64% –35% +163% –7% 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 Source: NHLBI/NIH/DHHS

Definition of COPD COPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.

Risk Factors for COPD Lung growth and development Oxidative stress Genes Exposure to particles Tobacco smoke Occupational dusts, organic and inorganic Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings Outdoor air pollution Lung growth and development Oxidative stress Gender Age Respiratory infections Socioeconomic status Nutrition Comorbidities

COPD ASTHMA COPD : Pathology Airflow Limitation Small airway narrowing Alv macrophage Ep cells CD8+ cell (Tc1) Neutrophil Cigarette smoke Small airway narrowing Alveolar destruction COPD ASTHMA Allergens Y Ep cells Mast cell CD4+ cell (Th2) Eosinophil Bronchoconstriction AHR Airflow Limitation Reversible Irreversible Source: Peter J. Barnes, MD

Squamous metaplasia of epithelium No basement membrane thickening Changes in Large Airways of COPD Patients Mucus hypersecretion Neutrophils in sputum Squamous metaplasia of epithelium No basement membrane thickening Goblet cell hyperplasia ↑ Macrophages ↑ CD8+ lymphocytes Changes in large airways of COPD patients. The epithelium often shows squamous metaplasia and there is goblet cell and submucosal gland hyperplasia, resulting in mucus hypersecretion. The airway wall is infiltrated with macrophages and CD8+ lymphocytes, whereas neutrophils predominate in the airway lumen and around submucosal glands. Airway smooth muscle and basement membrane are minimally increased compared to the findings in asthma. Mucus gland hyperplasia Little increase in airway smooth muscle Source: Peter J. Barnes, MD 6

Changes in Small Airways in COPD Patients Inflammatory exudate in lumen Disrupted alveolar attachments Changes in small airways in COPD patients. The airway wall is thickened and infiltrated with inflammatory cells, predominately macrophages and CD8+ lymphocytes, with increased numbers of fibroblasts. In severe COPD there are also lymphoid follicles. The lumen is often filled with an inflammatory exudate and mucus. There is peribronchial fibrosis and airway smooth muscle may be increased, resulting in narrowing of the airway. Thickened wall with inflammatory cells - macrophages, CD8+ cells, fibroblasts Peribronchial fibrosis Lymphoid follicle Source: Peter J. Barnes, MD 7

Alveolar wall destruction Changes in the Lung Parenchyma in COPD Patients Alveolar wall destruction Loss of elasticity Changes in the lung parenchyma in COPD patients. There is loss of elasticity and alveolar wall destruction, and accumulation of inflammatory cells, predominantly macrophages and CD8+ lymphocytes. The destructive changes reduce the pulmonary capillary bed. The left panel shows a scanning electron micrograph of a patient with emphysema demonstrating the enlargement of alveoli and destruction of the alveolar walls. Destruction of pulmonary capillary bed ↑ Inflammatory cells macrophages, CD8+ lymphocytes Source: Peter J. Barnes, MD 8

indoor/outdoor pollution Diagnosis of COPD EXPOSURE TO RISK FACTORS SYMPTOMS cough tobacco sputum occupation shortness of breath indoor/outdoor pollution è è è SPIROMETRY

Spirometry: Normal and Patients with COPD

Classification of COPD Severity by Spirometry Stage I: Mild FEV1/FVC < 0.70 FEV1 > 80% predicted Stage II: Moderate FEV1/FVC < 0.70 50% < FEV1 < 80% predicted Stage III: Severe FEV1/FVC < 0.70 30% < FEV1 < 50% predicted Stage IV: Very Severe FEV1/FVC < 0.70 FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure

Therapy at Each Stage of COPD I: Mild II: Moderate III: Severe IV: Very Severe FEV1 80% 50% 30% Add long term oxygen if chronic respiratory failure. Consider surgery Add inhaled glucocorticosteroids if repeated exacerbations Add regular treatment with one or more long-acting bronchodilators* (when needed); Add rehabilitation * ß2- agonists, anticholinergics and methylxanthines Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed)

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