Chronic Obstructive Pulmonary Disease

1 Chronic Obstructive Pulmonary Disease .. ( Chronic Obstructive Pulmonary Disease COPD) .. GOLD ( Global Initiative for Chronic Obstructive Lung Disease ) . 6 3 .. 2020 . ( . ) ( . ).. (not fully reversible) (progressive) . (extrapulmonary effects) .. COPD 90% .. 1 FEV1 (Force expiratory volume in one second) 1 . COPD . gene . alpha - 1 antitrypsin (severe hereditary deficiency of alpha - 1 antitrypsin ) inhibitor . 1 FEV1 .. Never smoked or 100 not susceptible to smoke FEV1 (% of value at age 25). 75. Smoked regularly 50 Stopped at 45. and susceptible to Disability its effects 25. Stopped at 65. Death 0. 25 50 75 Age (years). serine proteases .. COPD . chromosome2q, transforming growth factor beta 1. (TGF- 1), microsomal epoxide hydrolase 1 (mEPHX1), and tumor necrosis factor alpha (TNF ).. COPD .. / . 2. 2 . Genes Lung growth and development Exposure to particles Oxidative stress - Tobacco smoke Gender, Age - Occupational dusts : organic and inorganic Respiratory infections - Indoor air pollution from heating and Socioeconomic status cooking with biomass in poorly vented Nutrition dwellings Comorbidities - Outdoor air pollution.

2 3 . Inflammation Small airway Disease Parenchymal destruction Airway inflammation Loss of alveolar attachments Airway remodeling Decrease of elastic recoil Airflow limitation . 2 small airway (parenchymal destruction) (emphysema) 3 . inflammatory cells . COPD . 4 . 1. Inflammatory cells neutrophils, macrophages, CD8 T lymphocytes . inflammatory mediators chemotactic factors(LTB4, IL-8), proinflammatory cytokines (TNF- , IL-1 , IL-6), Growth factors(TGF- ) inflammatory cells . systemic effects . 2. Proteases inflammatory cells epithelial cells neutrophil elastase, cathepsins, metrix metalloproteinases (MMP) proteases and antiproteases imbalance elastin emphysema . 4 . Cigarette smoke Biomass particles Host factors Particulates Amplifying mechanisms LUNG INFLAMMATION. Anti-oxidants Anti-proteinases Oxidative stress Proteinases Repair mechanisms COPD PATHOLOGY. 3. oxidative stress hydrogen peroxide, superoxide anions histone deacetylase activity (HDAC).

3 Inflammatory genes glucocorticosteroids COPD .. 1. (airflow limitation) FEV1 . air trapping hyperinflation . dynamic hyperinflation .. 2. emphysema (gas exchange abnormailities) ventilation V/Q mismatch hypoxemia hypercapnia . 3. (mucous hypersecretion) .. epidermal growth factor receptor (EGFR) mediators proteases . 4. Pulmonary hypertension hypoxic vasoconstriction small Pulmonary arteries intimal hyperplasia, smooth muscle hypertrophy/hyperplasia right ventricular hypertrophy right-side cardiac failure (cor pulmonale) . 5. (systemic effects extrapulmonary effects). inflammatory mediators TNF- , IL-6, oxygen-derived free radicals COPD 5. 5 . Cachexia : loss of fat free mass Osteoporosis Skeletal muscle wasting : apoptosis, disuse atrophy Normochronic normocytic anemia Depression Increased risk of cardiovascular Disease : associated with CRP. Clinical manifestation and practical clinical approach.

4 Pack-year . (1 20 ) COPD . > 20 pack-year . Chronic productive cough simple Chronic bronchitis smoker's cough .. (exertional dyspnea) .. (acute exacerbation of COPD, AECOPD) . advanced COPD . resting hypoxemia . COPD . myocardial infarction, angina, respiratory infection, bone fractures, diabetes, sleep-disorders, glaucoma and lung cancer .. nicotine stain . expiratory time (prolonged expiratory phase) expiratory wheezing hyperinflation anterior-posterior (AP). diameter (barrel-shaped chest) decreased breath sounds accessory muscles hypertrophy sternocleidomastoid scalene muscles (pursed lip breathing) expiratory time cyanosis . advanced COPD right sided heart failure decompensate Chronic Pulmonary hypertension (Cor Pulmonale) engorged jugular venous pressure, right ventricular heaving, 3rd heart sound, hepatic congestion, ascites, peripheral edema clubbing of fingers . COPD .. COPD.

5 Spirometry gold standard progression FEV1 FEV1/FVC ratio . short-acting inhaled bronchodilator salbutamal 400 g (post- bronchodilator FEV1, FEV1/FVC) . 4 6. 6 post-bronchodilator FEV1. Stage I : Mild FEV1/FVC < FEV1 80% predicted Stage II : Moderate FEV1/FVC < 50% FEV1 < 80% predicted Stage III : Severe FEV1/FVC < 30% FEV1 < 50% predicted Stage IV : Very Severe FEV1/FVC < FEV1 < 30% predicted or FEV1 < 50%. predicted plus Chronic respiratory failure (PaO2 < 60 mmHg with or without PaCO2 > 50 mmHg while breathing air at sea level). chest X-ray(CXR) . 7 .. hyperinflation bullous flattened diaphragm, retrosternal air space, hyperlucency of the lungs, rapid tapering of the vascular markings computed tomography (CT) . emphysema . high resolution CT (HRCT) scan 8 CXR CT chest 7 CXR . Intrathoracic Extrathoracic Chronic Obstructive Pulmonary Disease Postnasal drip Bronchial asthma Gastroesophageal reflux Central bronchial carcinoma Drug therapy ( , ACE inhibitors).

6 Endobronchial tuberculosis Bronchiectasis Left heart failure Interstitial lung Disease Cystic fibrosis 8 CXR (a) CT scan of chest (b) . arterial blood gas (ABG) FEV1< 50% predicted . respiratory failure right heart failure . room air (FiO2 at sea level) . 20-30 . alpha - 1 antitrypsin deficiency Caucasian . COPD 45 serum concentration of alpha - 1 antitrypsin 15-20% .. COPD Asthma ( ) .. COPD 9.. COPD . 10 . (assess and monitor Disease ) . (reduce risk factors) COPD (manage stable COPD) (manage exacerbations).. 9 . COPD Onset in mid-life, Symptoms slowly progressive, Most patients had long history of tobacco smoking, Dyspnea during exercise, Largely irreversible airflow limitation Asthma Onset early in life (often childhood), Symptoms vary from day to day, Symptoms at night/early morning, Allergy, rhinitis, and/or eczema also present, Family history of asthma, Largely reversible airflow limitation Congestive heart failure Fine basilar crackles on auscultation, Chest X-ray shows dilated heart, Pulmonary edema, Pulmonary function tests indicated volume restriction, not airflow limitation Bronchiectasis Large volumes of purulent sputum, Commonly associated with bacterial infection, Coarse crackles/ clubbing on auscultation Chest X-ray/CT shows bronchial dilation, bronchial wall thickening Tuberculosis Onset all ages, Chest X-ray shows lung infiltrate, Microbiological confirmation, High local prevalence of tuberculosis Obliterative bronchiolitis Onset in younger age, nonsmokers, May have history of rheumatoid arthritis or fume exposure.

7 CT on expiration shows hypodense areas Diffuse panbronchiolitis Most patients are male and nonsmokers, Almost all have Chronic sinusitis, Chest X-ray and HRCT show diffuse small centrilobular nodular opacities and hyperinflation 10 . Relieve symptoms Prevent Disease progression Improve exercise tolerance Improve health status Prevent and treat complications Prevent and treat exacerbations Reduce mortality Prevent or minimize side effects from treatment . 2 .. (end-of-life care). (Stable COPD). (pharmacologic treatment) . (non-pharmacologic treatment) 11. COPD . COPD inspiratory capacity (IC) . static dynamic hyperinflation .. COPD . glucocorticosteroids Bronchodilators airway smooth muscle tone .. (as-needed basis) . (regular basis) 3 . 11 . I : Mild II : Moderate III : Severe IV : Very Severe FEV1/FVC < FEV1/FVC < FEV1/FVC < FEV1/FVC < 50% FEV1 < 80% 30% FEV1 < 50% FEV1 < 30% predicted or FEV1 80% predicted predicted predicted FEV1 < 50% predicted plus Chronic respiratory failure Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed Add regular treatment with one or more long-acting bronchodilators (when needed).)

8 Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Add long term oxygen if Chronic respiratory failure Consider surgical treatments 1. 2-agonists airway smooth muscle 2- adrenergic receptors cyclic AMP . aerosol (metered-dose inhaler, MDI) (dry powdered inhaler, DPI) . (nebulizer) short-acting 2-agonists (salbutalmol, terbutaline) 4- 6 long-acting 2-agonists (formoterol, salmeterol) 12. onset 3-5 20-30 (salbutalmaol, terbutaline, formeterol) 30-45 (salmeterol) .. 2. Anticholinergics acetylcholine muscarinic receptor central airway smooth muscle (M3 receptors) short-acting anticholinergics (ipratropium bromide) M2 receptors 3-5 short-acting 2-agonists 1-2 8 long-acting anticholinergics(tiotropium) M3 M1 receptors 2 . 24 . nebulizer acute glaucoma 3. Methylxanthines (xanthine derivatives aminophylline, theophylline) . sustained-release . phosphodiesterase non-selective potent.

9 Bronchodilators . ventricular arrhythmias, grand mal convulsions, heartburn therapeutic range metabolized cytochrome P450 . inhaled bronchodilators cilomilast roflumilast . phosphodiesterase 4 .. spacer small volume nebulizer . AECOPD . (combination bronchodilator therapy) . short-acting 2-agonists anticholinergic FEV1 . Glucocorticosteroids systemic local . MDI, DPI, nebulizer systemic glucocorticosteroids short-term . long-term . inhaled glucocorticosteroids . FEV1 COPD FEV1 < 50% (stage III IV) . (3 3 ) . health status budesonide 800-1,600 g/day fluticasone proprionate 1,000 g/day . skin bruising bone density inhaled glucocorticosteroid long- acting 2-agonists . Vaccines influenzae vaccine 1 influenza COPD 50 % . pneumococal vaccine COPD 65 Antibiotics .. Psychoactive agents hypnotics . antihistamine choral hydrate benzodiazepine . Mucolytic agents Antioxidant agents N-acetylcysteine (NAC).

10 Inhaled corticosteroids . Antitussis Nitric oxide (vasodilators). hypoxic regulation . (exacerbations). COPD .. mild moderate .. accessory muscles, paradoxical chest wall movement vital signs stable SpO2 ABG respiratory failure (PaO2 < 60 mmHg, PaCO2 >. 50 mmHg pH < ).. (small volume nebulizer, SVN) . short-acting inhaled 2-agonists . anticholinergic methylxanthines second-line intravenous therapy . (controlled oxygen therapy) . hypoxemia PaO2 > 60 mmHg SaO2 > 90%. hypercapnia SVN . hypercapnia (CO2 narcosis). ABG 30-60 hypoxemia, hypercapnia glucocorticosteroid methylprednisolone mg/kg/day 30-40 mg oral prednisolone 7-10 .. 12 Noninvasive ventilator Selection criteria Moderate to severe dyspnea with use of accessory muscles and paradoxical abdominal motion Moderate to severe acidosis (pH ) and/or hypercapnia (PaCO2 > 45 mmHg). Respiratory frequency > 25 breaths per minute Exclusion criteria (any may be present).