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CHRONIC OBSTRUCTIVE PULMONARY DISEASE CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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Chronic Obstructive Pulmonary Disease (COPD) Chronic Obstructive Airway disease (COAD) Chronic Obstructive Airway disease (COAD)

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DEFINITION COPD is a disease state characterized by increase in resistance to airflow due to partial or complete obstruction of airway at any level from the trachea to respiratory bronchiole. Changes are usually irreversible esp. in chronic bronchitis and emphysema. COPD is a disease state characterized by increase in resistance to airflow due to partial or complete obstruction of airway at any level from the trachea to respiratory bronchiole. Changes are usually irreversible esp. in chronic bronchitis and emphysema. - Predominant symptom; Dyspnoea - Predominant symptom; Dyspnoea - Predominant cause; Smoking - Predominant cause; Smoking

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Pulmonary function tests show : Pulmonary function tests show : 1-Increased pulmonary resistance 2- Limitation of maximal expiratory flow rates (reduced FEV1).

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1. EMPHYSEMA 2. CHRONIC BRONCHITIS 3. ASTHMA 4. BRONCHIECTASIS

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Emphysema. Emphysema. - Abnormal permanent enlargement of the distal air spaces due to destruction of the alveolar walls and loss of respiratory tissue. -Obstruction is caused by lack of elastic recoil.

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Etiology: Etiology: 1- Most common cause is smoking: produces combination of emphysema and chronic inflammation 1- Most common cause is smoking: produces combination of emphysema and chronic inflammation 2- Genetic deficiency of alpha1 antitrypsin (Pi locus on chromosome 14) ; alpha-1-antitrypsin deficiency produces almost pure emphysema

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Pathogenesis: Pathogenesis: 1- Protease-antiprotease imbalance : 1- Protease-antiprotease imbalance :. Alpha1 antitrypsin present in serum, tissue fluids, macrophages. Alpha1 antitrypsin present in serum, tissue fluids, macrophages. Inhibitor of proteases (esp. elastase secreted by neutrophils during inflammation). Inhibitor of proteases (esp. elastase secreted by neutrophils during inflammation).Stimulus--TNF,IL8--Increased neutrophils-- Release of proteases(elastase,proteinase- 3,cathepsin-G)--Elastic lung tissue destruction.Stimulus--TNF,IL8--Increased neutrophils-- Release of proteases(elastase,proteinase- 3,cathepsin-G)--Elastic lung tissue destruction

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Pathogenesis 2- Oxidant-antioxidant imbalance: Smoking--Free O2 radicals--Deplete Antioxidant in lung (superoxide dismutase, glutathione)Damage of lung tissue

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Types of Emphysema 1-Centroacinar (Centrilobar) Emphysema -- Affects central (proximal) parts of the acini (respiratory bronchioles) but spares the distal alveoli. -- Affects central (proximal) parts of the acini (respiratory bronchioles) but spares the distal alveoli. - More severe in upper lobes, especially apical segments.

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Causes: -Smoking -Coal dust

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2-Panacinar (Panlobar) Emphysema -- Uniform enlargement of the acini in a lobule. -- Uniform enlargement of the acini in a lobule. - May not necessarily involve entire lung - May not necessarily involve entire lung - Predominantly lower lobes. - Predominantly lower lobes. - Alpha -1- antitrypsin deficiency is prototype. - Alpha -1- antitrypsin deficiency is prototype.

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3-Paraseptal (Distal Acinar) Emphysema -- Proximal acinus normal, distal part involved -- Proximal acinus normal, distal part involved - Most prominent adjacent to pleura and along the lobular connective tissue septa. - Most prominent adjacent to pleura and along the lobular connective tissue septa. - Probably underlies spontaneous pneumothorax in young adults. - Probably underlies spontaneous pneumothorax in young adults.

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4-Bullous Emphysema -- Any form of emphysema which produces large subpleural blebs or bullae (> 1cm). -- Any form of emphysema which produces large subpleural blebs or bullae (> 1cm). - Localized accentuation of any one of the type. - Localized accentuation of any one of the type.

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5-Interstitial Emphysema Air penetration into the connective tissue stroma of the : Air penetration into the connective tissue stroma of the : - lung - lung - mediastinum or - mediastinum or - subcutaneous tissue. - subcutaneous tissue.

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6-Compensatory Emphysema - Dilatation of alveoli in response to loss of lung substance elsewhere. - Dilatation of alveoli in response to loss of lung substance elsewhere. - Actually hyperinflation since no destruction of septal walls.

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7-Senile Emphysema - Change in geometry of lung with larger alveolar ducts and smaller alveoli. - Change in geometry of lung with larger alveolar ducts and smaller alveoli. - No loss of lung tissue; hence not really an emphysema.

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Chronic Bronchitis - Clinical definition: persistent cough with sputum production for at least three months in at least two consecutive years. - Clinical definition: persistent cough with sputum production for at least three months in at least two consecutive years. - Can occur with or without evidence of airway obstruction - Smoking is the most important cause. - Smoking is the most important cause.

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: Basic Mechanism: Basic Mechanism: Hypersecretion of mucus Hypersecretion of mucus Histology Histology -Increased numbers of goblet cells in small airways as well as large airways. -Increased numbers of goblet cells in small airways as well as large airways. -Increased size of submucosal glands in large airways (Reid index: ratio of thickness of mucosal glands to thickness of wall between epithelium and cartilage) -Peribronchiolar chronic inflammation. -Peribronchiolar chronic inflammation.

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Bronchiectasis - Permanent abnormal dilation of bronchi and bronchioles, - Permanent abnormal dilation of bronchi and bronchioles, - Usually associated with chronic necrotizing inflammation - Usually associated with chronic necrotizing inflammation - Patients have fever, cough, foulsmelling sputum. - Patients have fever, cough, foulsmelling sputum. - More common in left lung, lower lobes. - More common in left lung, lower lobes.

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Causes: Obstruction (tumor, mucus) Obstruction (tumor, mucus) Congenital Congenital Intralobar sequestration Intralobar sequestration Cystic fibrosis Cystic fibrosis Immotile cilia syndrome Immotile cilia syndrome Necrotizing pneumonia Necrotizing pneumonia Kartaganers Syndrome Kartaganers Syndrome

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Asthma - Increased responsiveness of tracheobronchial tree to various stimuli, leading to paroxysmal airway constriction - Increased responsiveness of tracheobronchial tree to various stimuli, leading to paroxysmal airway constriction - Unremitting attacks (status asthmaticus) can be fatal. - Unremitting attacks (status asthmaticus) can be fatal.

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Etiology : Etiology : 1- Extrinsic Factors (atopic, allergic); most common 1- Extrinsic Factors (atopic, allergic); most common 2- Intrinsic Factors (idiosyncratic); now recognize mixed. 2- Intrinsic Factors (idiosyncratic); now recognize mixed.

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Basic Mechanism Basic Mechanism - Bronchial plugging by thick mucous plugs containing eosinophils, whorls of shed epithelium (Curschmanns spirals), and Charcot Leyden crystals (Eosinophil membrane protein); - Bronchial plugging by thick mucous plugs containing eosinophils, whorls of shed epithelium (Curschmanns spirals), and Charcot Leyden crystals (Eosinophil membrane protein); - Distal air- spaces become over distended. - Distal air- spaces become over distended.

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Histology: Histology: -Thick basement membrane -Thick basement membrane -Edema and infiltration of the bronchial walls by inflammatory cells with prominence of eosinophils, -Edema and infiltration of the bronchial walls by inflammatory cells with prominence of eosinophils, - Hypertrophy of bronchial wall muscle. - Hypertrophy of bronchial wall muscle.

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Therapeutic agents are aimed at increasing cAMP levels either by : Therapeutic agents are aimed at increasing cAMP levels either by : - increasing production (-agonists, e.g epinephrine) or - increasing production (-agonists, e.g epinephrine) or - decreasing degradation (Methyl xanthines, e.g theophylline). - decreasing degradation (Methyl xanthines, e.g theophylline). - Cromolyn sodium prevents mast cell degranulation. - Cromolyn sodium prevents mast cell degranulation.

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Allergic Bronchopulmonary Aspergillosis Occur in chronic asthmatics; hypersensitivity to non invasive Aspergillus. Occur in chronic asthmatics; hypersensitivity to non invasive Aspergillus. Bronchocentric granulomatous inflammation, mucus impaction of bronchi, eosinophilic pneumonia. Distinctive promixal bronchiectasis (?Pathgnomonic)

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Burden of Asthma Prevalence increasing in developed countries more than developing or underdeveloped countries affecting 10 - 15% of population. Prevalence increasing in developed countries more than developing or underdeveloped countries affecting 10 - 15% of population. The number of children with asthma has increased six- fold in the last 25 years The number of children with asthma has increased six- fold in the last 25 years Between 100 and 150 million people around the globe Between 100 and 150 million people around the globe 5.1 million people in the UK have asthma 5.1 million people in the UK have asthma In South Asia (including Pakistan) rough estimates indicate a prevalence of between 10% and 15% In South Asia (including Pakistan) rough estimates indicate a prevalence of between 10% and 15%

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Burden of Asthma World-wide, the economic costs associated with asthma are estimated to exceed those of TB and HIV/AIDS combined. World-wide, the economic costs associated with asthma are estimated to exceed those of TB and HIV/AIDS combined. In the United States, for example, annual asthma care costs (direct and indirect) exceed US$6 billion. In the United States, for example, annual asthma care costs (direct and indirect) exceed US$6 billion. At present Britain spends about US$1.8 billion on health care for asthma and because of days lost through illness At present Britain spends about US$1.8 billion on health care for asthma and because of days lost through illness

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Burden of Asthma 0 20 40 60 80 Deaths per Million 1999 2011 2010 Target Age-adjusted death rate per million Under 5 years 5-14 years 15-34 years 35-64 years 65 years and over

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CLASSIFICATION OF ASTHMA EXTRINSIC EXTRINSIC Implying a definite external cause Atopic individuals Positive skin prick test More common Early onset in childhood INTRINSIC OR CRYPTOGENIC INTRINSIC OR CRYPTOGENIC Late onset (middle age)

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Etiology and Pathogenesis Allergy Allergy Airway hyperresponsiveness Airway hyperresponsiveness Genetic factors Genetic factors Asthma triggers Asthma triggers

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The Underlying Mechanism INFLAMMATION Risk Factors (for development of asthma) Airway Hyperresponsiveness Airflow Limitation Symptoms- (shortness of breath, cough, wheeze) Risk Factors (for exacerbations)

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Pathological changes

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Genetic Factors Candidate genes on chromosome 5q31-33 (IL4 GENE CLUSTER) Responsible for production of cytokines,IL3,IL4,IL9,IL13, GM-CSF Gene A Gene B Gene D Gene E Gene C Atopy susceptible Asthma susceptible

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Asthma triggers Indoor allergens Outdoor allergens Occupational sensitizers Tobacco smoke Air Pollution Respiratory Infections Parasitic infections Socioeconomic factors Family size Diet and drugs Obesity Exercise Acid reflux

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Burden of COPD The global burden of COPD will increase enormously over the foreseeable future as the toll from tobacco use in developing countries becomes apparent. In UK and USA COPD occurs in 18% male smokers 14% female smokers 6-7% those who have never smoked

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Direct and Indirect Costs of COPD, (US $ Billions) Direct Medical Cost:$18.0 Total Indirect Cost:$ 14.1 Mortality related IDC 7.3 Morbidity related IDC 6.8 Total Cost $32.1

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Risk Factors for COPD Host Factors Genes (e.g. alpha1-antitrypsin deficiency) Hyperresponsiveness Lung growth Exposure Tobacco smoke Occupational dusts and chemicals Infections Socioeconomic status

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Pathogenesis of COPD NOXIOUS AGENT (tobacco smoke, pollutants, occupational agent) Genetic factors Respiratory infection Other COPD

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Symptoms and Signs Acute attack of asthma Acute attack of asthma Intermittent dyspnoea Cough, sputum,wheeze Tachypnoea Hyperinflated chest Hyperresonant percussion note Diminished air entry Widespread polyphonic wheeze Acute exacerbation of COPD Dyspnoea, cough,sputum, wheeze Tachyponea Use of accessory muscles reduced cricosternal distance

Signs of severe attack of asthma Inability to complete sentence Inability to complete sentence Pulse>110 Pulse>110 Respiratory rate >25 Respiratory rate >25 PEFR PEFR

Effects of Corticosteroids in Acute Asthma Systemic Corticosteroids Anti-inflammatory Anti-inflammatory Late improvement in outcomes (> 6 hrs) Late improvement in outcomes (> 6 hrs) Corticosteroids induce transcriptional effects synthesis of new proteins Corticosteroids induce transcriptional effects synthesis of new proteins Inhaled Corticosteroids Topical Early improvement in outcomes (< 3 h) Corticosteroids up- regulating postsynaptic adrenergic receptors airway mucosa, vasoconstriction decrease airway mucosal blood flow, mucosal decongestion

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Complications Respiratory failure Respiratory failure Type I continuous O2 Type II controlled O2 Intubation and ventilation Intubation and ventilation Cor pulmonale Cor pulmonale Pneumothorax (ruptured bulla bullous lung disease, Indication of surgery) Pneumothorax (ruptured bulla bullous lung disease, Indication of surgery) Chest infection (pneumonia) Chest infection (pneumonia) Polycythemia Polycythemia

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Complications Respiratory failure Respiratory failure Treatment options; Treatment options; Noninvasive Positive Pressure Ventilation Intubation Sedatives and Neuromuscular Blockers

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PREVENTION Elimination of risk factors Elimination of risk factors Patient education and information Patient education and information Advice on not missing the dose Advice on not missing the dose Proper management plan Proper management plan Addition of mast cell stabilizers like sodium cromoglycate and nedocromil and leukotriene antagonists e.g; montelukast and zafirlukast to traditional therapy Addition of mast cell stabilizers like sodium cromoglycate and nedocromil and leukotriene antagonists e.g; montelukast and zafirlukast to traditional therapy

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