1. M.A.ZOHAL pulmonologist

2.  Third leading cause of death in the U.S.  Affects > 16 million persons in the U.S.  COPD will increase from the sixth to the third most common cause of death worldwide by 2020.  Sex  Higher prevalence in men, probably secondary to smoking  Prevalence of COLD among women is increasing as the gender gap in smoking rates has diminished.  Age  Higher prevalence with increasing age  Dose–response relationship between cigarette smoking intensity and decreased pulmonary function

3.  A disease state characterized by airflow limitation that is not fully reversible  Conditions include:  Emphysema: anatomically defined condition characterized by destruction and enlargement of the lung alveoli  Chronic bronchitis: clinically defined condition with chronic cough and phlegm  Small-airways disease: condition in which small bronchioles are narrowed

14.  Centrilobular In cigarette smoking and predominantly affects the upper lung zones  Centriacinar In the respiratory bronchiole,lower lung zones, higher degree of inflammation,with AAT deficiency  Paraseptal Mainly alveolar ducts, and sacs, parenchymal fibrous stranding,bullae formation

16.  Mucus gland hypertrophy  Hyperplasia of goblet cells  Neutrophilic inflammatory reaction  Intraluminal mucus plugging  Hypertrophy of airway smooth muscle  Fibrosis of small respiratory bronchioles

17.  Decreases in elastic recoil  Increases in dynamic airway compression  Fixed increase in airflow resistance  Destruction of alveolar septae

23. RISK FACTORS FOR COPD Host-RelatedEnvironmental Airway hyperresponsiveness Cigarette smoking Genetic factors (poorly characterized) Severe hereditary α 1 antitrypsin deficiency Indoor air pollution from biomass fuel use in setting of inadequate ventilation Occupational dusts and chemicals Low birth weight Maternal cigarette smoking during gestation History of severe childhood respiratory infection Pipe/cigar smoking HIV infection Outdoor air pollution Low socioeconomic status Intravenous drug use methylphenidate, methadone, talc granulomatosis

24.  Smoking  Cigarette smoking is a major risk factor.  Cigar and pipe smoking  Evidence less compelling; likely related to lower dose of inhaled tobacco by-products  Passive (secondhand) smoking  Associated with reductions in pulmonary function  Its status as a risk factor for COLD remains uncertain.  Airway hyperresponsiveness  Respiratory infections  Risk factor for exacerbations  The association of adult and childhood respiratory infections with development and progression of COLD remains unproven.

25.  Occupational exposures to dust and fumes (coal mining, gold mining,and cotton textile dust)  Likely risk factors  The magnitude of these effects appears substantially less important than the effect of cigarette smoking.  coal mine dust exposure was a significant risk factor for emphysema  Ambient air pollution  The relationship of air pollution to COLD remains unproven.  Prolonged exposure to smoke produced by biomass combustion  Genetic factors  α 1 antitrypsin (α 1 AT) deficiency

26.  Tobacco smoking accounts for 80% to 90% of the risk for COPD  There is poorer lung function and a more rapid decline in FEV 1 in smokers  Cough, sputum production, and dyspnea are much more common in smokers  Deaths ascribed to COPD are much more common in smokers

27. The likelihood of COPD increases with:  The number of cigarettes smoked per day  The cumulative pack-years of exposure  When smoking is started at an earlier age  Low-tar, filtered cigarettes are with less symptoms than unfiltered brands, but the effects on lung function do not differ

28.  FEV 1 declines  In the average nonsmoker =30 ml/yr  In the average smoker =60 ml/yr  In sensitive (15% to 20%) smoker =100ml/yr

29.  There is a direct relation between the number of cigarettes smoked and the development of COPD in susceptible individuals  Pulmonary function is lost at a faster rate in smokers than in nonsmokers. In most people with COPD, symptoms develop in the fifth or sixth decade of life when the FEV 1 falls below 1.0–1.5 L  At some point after smoking cessation, pulmonary function begins to fall at a rate approximating that of the nonsmoking population  At very low levels of pulmonary function, smoking cessation has very little beneficial effect on preserving remaining function

30.  Dutch hypothesis  British hypothesis

31.  α 1-Antitrypsin Deficiency AAT is a strong neutrophils elstase inhibitor The correlated gene on chromosome 14 The most common phenotype is MM (90%) The lowest levels of are in the ZZ phenotype There is strong correlation with smoking RISK FACTORS (continue)

32.  Air Pollution: Ozone, NO,NO 2, SO 2, a mixture of solid and liquid particles suspended in the air. Exposure to these pollutants is associated with bronchospasm and exacerbations of asthma or COPD, increased rates of hospitalization and mortality

35.  3 most common  Cough  Sputum production  Exertional dyspnea, frequently of long duration  Additional signs and symptoms  Dyspnea at rest  Prolonged expiratory phase and/or expiratory wheezing on lung examination  Decreased breath sounds  Barrel chest  Large lung volumes and poor diaphragmatic excursion, as assessed by percussion  Use of accessory muscles of respiration  Pursed lip breathing (predominantly emphysema)  Characteristic "tripod" sitting position to facilitate the actions of the sternocleidomastoid, scalene, and intercostal muscles  Cyanosis, visible in lips and nail beds  Systemic wasting  Significant weight loss  Bitemporal wasting  Diffuse loss of subcutaneous adipose tissue

36.  Paradoxical respiration  Inward movement of the rib cage with inspiration (Hoover's sign) in some patients  "Pink puffers" are patients with predominant emphysema—no cyanosis or edema, with decreased breath sounds.  "Blue bloaters" are patients with predominant bronchitis— cyanosis and edema.  Most patients have elements of each.  Advanced disease: signs of cor pulmonale  Elevated jugular venous distention  Right ventricular heave  Third heart sound  Hepatic congestion  Ascites  Peripheral edema

37.  Initial assessment  History and physical examination (see Signs & Symptoms)  Pulmonary function testing to assess airflow obstruction  Radiographic studies

38.  Chest radiography  Emphysema: obvious bullae, paucity of parenchymal markings, or hyperlucency  Hyperinflation: increased lung volumes, flattening of diaphragm  Does not indicate chronicity of changes  Chest CT  Definitive test for establishing the diagnosis of emphysema, but not necessary to make the diagnosis

39.  Chronically reduced ratio of FEV 1 to forced vital capacity (FVC)  In contrast to asthma, the reduced FEV 1 in COLD seldom shows large responses (>30%) to inhaled bronchodilators, although improvements up to 15% are common.  Reduction in forced expiratory flow rates  Increases in residual volume  Increases in ratio of residual volume to total lung capacity  Increased total lung capacity (late in the disease)  Diffusion capacity may be decreased in patients with emphysema.

40.  General  Institute therapy after assessment of symptoms, potential risks, costs, and benefits.  Only 3 interventions have been demonstrated to influence the natural history.  Smoking cessation  Oxygen therapy in chronically hypoxemic patients  lung volume reduction surgery  All other current therapies are directed at improving symptoms and decreasing frequency and severity of exacerbations.  Therapeutic response should determine continuation of treatment.

41.  Exacerbation  Assess the severity of both the acute and chronic components of the patient's illness.  Attempt to identify and treat the precipitant of the exacerbation.

42.  Smoking cessation  General medical care  Annual influenza vaccine  Polyvalent pneumococcal vaccine is recommended.  Pulmonary rehabilitation  Improves health-related quality of life, dyspnea, and exercise capacity  Rates of hospitalization are reduced over 6 to 12 months.

43.  Produces symptomatic and functional benefit in selected patients  Emphysema  Predominant upper lobe involvement  Contraindications  Significant pleural disease  pulmonary artery systolic pressure > 45 mm Hg  Extreme deconditioning  Congestive heart failure  Other severe comorbid conditions  FEV 1 < 20% of predicted and diffusely distributed emphysema on CT or diffusing capacity for CO < 20% of predicted (due to increased mortality)

44.  COPD is the leading indication.  Candidates  ≤65 years  Severe disability despite maximal medical therapy  No comorbid conditions, such as liver, renal, or cardiac disease  Anatomic distribution of emphysema and presence of pulmonary hypertension are not contraindications.

45.  Smoking prevention or cessation  Prevention of exacerbations  Long-term suppressive antibiotics are not beneficial.  Inhalation glucocorticoids should be considered in patients with frequent exacerbations or in patients with an asthmatic component.  Vaccination against influenza and pneumococcal infection

46.  The principal determinant of morbidity in COPD is the degree of airway obstruction.  Patients who continue to smoke cigarettes experience a yearly decrease in FEV 1 of 80–100 mL.  Even for patients who quit smoking, the FEV 1 decreases by 30 mL per year.  Median survival for severe disease (FEV 1 < 1 L) is 4 years.