Chronic Obstructive Pulmonary Disease (COPD) 2003 PDF

db 2003 Chronic Obstructive Pulmonary Disease (COPD) Prof. Dr. Miron BOGDAN Dr. Tudor CONSTANTINESCU  db 2003 What is COPD? COPD is a heterogeneous lung condition characterized by chronic respiratory sympt...

db 2003 Chronic Obstructive Pulmonary Disease (COPD) Prof. Dr. Miron BOGDAN Dr. Tudor CONSTANTINESCU  db 2003 What is COPD? COPD is a heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, sputum and/or exacerbations) due to abnormalities of the airways (bronchitis) and / or alveoli (emphysema) that cause persistent, progressive, airflow obstruction  db 2003 COPD = Genes + environment, over the lifetime  db 2003 Teaching Slide Set © 2023, 2024 Global Initiative for Chronic Obstructive Lung Disease  db 2003 Epidemiology Leading cause of morbidity / mortality that is substantial and increasing 3rd cause of death in 2019 ( > 3 millions) Global prevalence is 10.3% (> 40 years), men > women  db 2003 Teaching Slide Set © 2023, 2024 Global Initiative for Chronic Obstructive Lung Disease  db 2003 Chronic Bronchitis = cough + expectoration (productive cough):  Most days  > 3 months/year, > 2 consecutive years  Without any other cause = CLINICALLY useful term  db 2003 Pulmonary Emphysema = permanent dilatation of airway spaces distal to the terminal bronchiole, with destruction of airway walls Centriacinar (respiratory bronchioles) Panacinar (entire alveolus) = term used in PATHOLOGY with less clinical utility  db 2003  db 2003  db 2003 Pathological types of PE Centriacinar Panacinar  db 2003 Risk factors - Smoking Cigarette smoke: – major risk factor (80-90%) – dose – effect relationship (PY) – other factors also needed (15-20% of smokers develop BPOC) Leaf cigarettes, pipe smokers: smaller risk Passive smoking ?  db 2003 Risk Factors  db 2003 COPD Pathogenicity Microparticles and gases Host factors Pulmonary inflammation Antioxidants Antiproteases Proteases Oxidative stress Repair mechanisms Morphopathological Changes of COPD  db 2003 Inflammatory cells in COPD H&E Celule T CD8+ Elastaza neutrofilică CD68+  db 2003 Inflammatory cells in induced sputum Barnes PJ. Chest. 2000;117:10S-14S  db 2003 Oxidative stress in COPD Smoking Antioxidants Inflammatory cells (glutathione, vitamin C,E) + -- Activation NF-kB  antiproteases α1-AT and SLPI O2- H2O2 TNF-α IL-8 OH-  secreţiei de mucus ONOO- Neutrophil Recruitment Isoprostans Extravasation of plasma Bronchoconstriction  db 2003 The protease-antiprotease balance Neutrophilic elastase 1-antitripsine Catepsine Inhibitor of Secreted Proteinase 3 LeucoProteinase (SLPI) Matrix MetalloProteinase Tissue Inhibitor of MMP (TIMP) (MMP) NORMAL  db 2003 The protease-antiprotease balance Neutrophilic elastase 1-antitripsină Inhibitor al leucoproteazei Catepsine secretorii (SLPI) Proteinase 3 Inhibitor tisular al MMP (TIMP) Matrix MetalloProteinase (MMP) COPD  db 2003 COPD Pathology Goblet cell hyperplasia and that of mucous secreting glands Bronchiolitis with  subepithelial macrophages and neutrophils as well as intraepithelial T CD8+ +/-eosinophils in exacerbations Fibrosis and remodeling (narrowing) of respiratory airways Emphysema: destruction of alveolar walls and enlargement of the airspace walls  db 2003 Physiopathology Mucus hypersecretion and cilliary disfunction Airflow obstruction and hyperinflation Gas exchange anomalies Pulmonary hypertension and chronic pulmonary heart disease (+ secondary polycythemia) Systemic effects (systemic inflammation and skeletal muscle dysfunction)  db 2003 Airflow obstruction Irreversible causes: – Fibrosis and narrowing of airways – Decrease of elastic recoil (alveolar destruction) – Loss of small bronchial wall support for alveoli (alveolar destruction) Reversible causes – Accumulation of inflammatory cells, mucus and exudate in bronchia – Bronchoconstriction – Effort-related dynamic hyperinflation  db 2003  db 2003 Pulmonary hyperinflation Causes: – Diminished elastic recoil (alveolar destruction) – Early expiratory bronchial obstruction – Dynamic factor (precocious inspiratory effort) Initially exertional eventually even at rest  db 2003 Blood gas anomalies Hypoxemia - V/Q mismatch: – Emphysematous spaces (V/Q ) – Obstructed bronchi (V/Q ) – Vascular anomalies – altered response to hypoxic vasoconstriction Hypercapnia: – Net alveolar hypoventilation (through respiratory muscle dysfunction)  db 2003 Pulmonary Hypertension Mechanisms: – Vasoconstriction through: Alveolar hypoxia Anomalies of local factors (NO, endothelin) – Pulmonary arterial wall remodeling – Chronic inflammation – Pulmonary capillary bed destruction (emphysema)  db 2003 Symptoms Productive cough (history of chronic bronchitis) – sometimes absent Dyspnea – expiratory – Interindividual variability – Progresses through the years (from intense effort rest) Hemoptoic sputum OSA symptoms  db 2003 Teaching Slide Set © 2023, 2024 Global Initiative for Chronic Obstructive Lung Disease  db 2003 Physical signs Obesity  cachexia Variable respiratory frequency Increased thoracic diameters Increased pulmonary percussion sounds Diminished vesicular murmur Prolonged expiratory flow Sibilants and rhonchi on auscultation  db 2003 Physical signs of severity Use of accesory inspiratory muscles RR > 25/min HR > 110/min Respiratory muscle fatigue (paradoxical breathing) Flapping tremor Altered consciousness  db 2003 Thoracic radiography Hyperinflation: – Low, flat diaphragm – Increased retrosternal space – Diminished peripheral vascularization – Diffused hypertransparency Sometimes: “dirty” pulmonary radiograph +/- emphysema bleb CT: preoperatively in giant bleb surgery  db 2003  db 2003  db 2003  db 2003  db 2003  db 2003  db 2003 Functional exploration Obstruction: – FEV1/FVC< 70% – Then  FEV1 – FVC normal then  Irreversible (FEV1< 12% post 2) Hyperinflation:  VR, CRF, CPT Decrease in TLco and Kco (~emphysema)  db 2003 Teaching Slide Set © 2023, 2024 Global Initiative for Chronic Obstructive Lung Disease  db 2003  db 2003  db 2003 COPD severity (post-2) Stage FEV1/FVC FEV1 Symptoms I Mild  80% II Moderate 50-80% +/- III Severe < 70% 30-50% Very < 30% Yes IV severe 30-50% CRI  db 2003 Arterial Blood Gases Normal Hypoxemia with normocapnia Hypercapnia later on normal pH Respiratory acidosis - compensated / decompensated (pH< 7,3)  db 2003 ECG – signs of CPC Low voltage rSr’ in V1 / R6 < S6 / S1S2S3 / S1Q3 Â-QRS > 110º Pulmonary P wave dominant R in V cu negative ST-T 1  db 2003 Diagnostic strategy Routine: Moderate / Severe: – Spirometry – Arterial blood gases – Bronchodilator test – ECG – Thoracic radiograph – ecocardiography – Blood count – Hb – HRCT – DLCO Other investigations: – pletismograpy Emphysema of youth: A1AT deficiency (genetic – SERPINA 1 gene > serology) – ZZ aprox 0,1-0,2 % COPD patients  db 2003 Initial assessment Severity of airflow obstrudtion Nature / magnitude of symptoms History of moderate/ severe exacerbations Blood eosinophil count Presence and type of other diseases  db 2003 Natural history of COPD FEV1 % 100 Non-smokers, non-susceptible smokers 75 Stop at 45 years Susceptible 50 smokers (15 - 20%) invalidity 25 Stop at 65 Death 25 50 75 years ACCELERATED EVOLUTION:  FEV1 with > 50 ml / year  PaO2 with > 2mmHg / year (increased risk of PHT)  db 2003 © 2023, 2024 Global Initiative for Chronic Obstructive Lung Disease  db 2003 Teaching Slide Set © 2023, 2024 Global Initiative for Chronic Obstructive Lung Disease  db 2003 Comorbidities (systemic disease) Systemic atherosclerosis Metabolic disturbances (type II diabetes) Systemic myopathy Osteoporosis SAS Depression