Title 9. CHRONIC OBSTRUCTIVE AIRWAYS DISEASE.pdf ✅

PHARMD GURU Page 1 DEFINITION: The National Heart, Lung, and Blood Institute/World Health Organization (NHLBI/ WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of COPD is: “A disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.” The American Thoracic Society definition is similar: A disease state characterized by the presence of airflow limitation owing to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible. The two major forms of COPD: chronic bronchitis and emphysema.. 1. Chronic bronchitis is characterized by excessive mucus production by the tracheobronchial tree, which results in airway obstruction as a result of edema and bronchial inflammation. Bronchitis is considered chronic when the patient has a cough producing more than 30 mL of sputum in 24 hrs for at least 3 months of the year for 2 consecutive years and other causes of chronic cough have been excluded. 2. Emphysema is marked by permanent alveolar enlargement distal to the terminal bronchioles and destructive changes of the alveolar walls. There is a lack of uniformity in airspace enlargement, resulting in loss of alveolar surface area. The collapse of these small airways results in airflow limitation that is independent of exertion. EPIDEMIOLOGY: Approximately 17 million Americans have COPD. COPD is the third leading cause of death in the United States and the leading cause of hospitalization in the older population. It is most commonly diagnosed in older men; however, the incidence is increasing in women CHRONIC OBSTRUCTIVE AIRWAYS DISEASE
PHARMD GURU Page 2 owing to an increasing population of women smokers. Women may be more likely to have more rapidly progressive COPD than men. Asthma is a common comorbidity. STAGES OF COPD: ETIOLOGY: Various factors have been implicated in the development of COPD, including the following: 1. Cigarette smoking is the primary causal factor for the development of COPD, present in > 90% of patients. a) One mechanism suggests that pulmonary hyperreactivity secondary to smoking results in persistent airway obstruction. b) There is also an increased risk of COPD in people who have 1-antitrypsin (AAT) deficiency. One in three people with genetic AAT deficiency develop emphysema, usually as young adults.  AAT is a serine protease inhibitor, and it is also an acute-phase reactive protein. The major physiological function of AAT is inhibition of neutrophil elastase.  AAT deficiency should be suspected when emphysema develops early in the absence of a significant smoking history.
PHARMD GURU Page 3 2. Exposure to irritants such as sulfur dioxide (as in polluted air), noxious gases, and organic or inorganic dusts or combustible fuels in the home. 3. A history of respiratory infections or bronchial hyperreactivity. 4. Social, economic, and hereditary factors. PATHOPHYSIOLOGY: CHRONIC BRONCHITIS: a) Respiratory tissue inflammation results in vasodilation, congestion, mucosal edema, and goblet cell hypertrophy. These events trigger goblet cells to produce excessive amounts of mucus. b) Changes in tissue include increased smooth muscle, cartilage atrophy, infiltration of neutrophils and other cells, and impairment of cilia. c) Airways become blocked by thick, tenacious mucous secretions, which trigger a productive cough. d) Normally, sterile airways can become colonized with Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa species. Recurrent lung infections (viral and bacterial) reduce ciliary and phagocytic activity, increase mucus accumulation, weaken the body’s defenses, and further destroy small bronchioles. e) As the airways degenerate, overall gas exchange is impaired, causing exertional dyspnea. f) Hypoxemia results from a V/Q imbalance and is reflected in an increasing arterial carbon dioxide tension (i.e., increasing Paco2). g) Sustained hypercapnia (increased Paco2) desensitizes the brain’s respiratory control center and central chemoreceptors. As a result, compensatory action to correct hypoxemia and hypercapnia (i.e., a respiratory rate or depth increase) does not occur. Instead, hypoxemia serves as the stimulus for breathing. Use of narcotics or benzodiazepines, especially in combination, should be done cautiously in these patients to avoid respiratory failure.
PHARMD GURU Page 4 EMPHYSEMA: a) Anatomical changes are the result of loss of tissue elasticity.  Inflammation and excessive mucus secretion (as from long-standing chronic bronchitis) cause air trapping in the alveoli. This contributes to breakdown of the bronchioles, alveolar walls, and connective tissue.  As clusters of alveoli merge, the number of alveoli diminishes, leading to increased space available for air trapping.  Destruction of alveolar walls causes collapse of small airways on exhalation and disruption of the pulmonary capillary beds.  These changes result in V/Q abnormalities; blood is shunted away from destroyed areas to maintain a constant V/Q ratio, unlike the case in chronic bronchitis.  Hypercapnia and respiratory acidosis are uncommon in emphysema because V/Q imbalance is compensated for by an increased respiratory rate. b) There are specific regions of the lung in which characteristic anatomical changes of emphysema occur.  In centrilobular (centriacinar) emphysema associated with cigarette smoking, destruction is central, selectively involving respiratory bronchioles. Typically, bronchioles and alveolar ducts become dilated and merge.  In panlobular (panacinar) emphysema, all lung segments are involved. The alveoli enlarge and atrophy, and the pulmonary vascular bed is destroyed. This form of emphysema is associated with AAT deficiency.  In paraseptal emphysema, the lung periphery adjacent to fibrotic regions is the site of alveolar distention and alveolar wall destruction. This is associated with spontaneous pneumothorax. Detailed flow charts are given in additional information section at the end of the document. Please go through them.
PHARMD GURU Page 5 DIAGNOSIS:  COPD patients with characteristic symptoms of cough, dyspnea, sputum production, and/ or exposure to known risk factors (e.g., smoking) should be evaluated for a COPD diagnosis.  If the patient has FEV1/FVC <70% and a post bronchodilator FEV1< 80% predicted, he or she has airflow limitation that is not fully reversible.  Patients with a smoking history (e.g., > 20 pack/year history and >45 years old) should be considered for the diagnosis. Spirometry can be used to help make the diagnosis. EMPHYSEMA:  Sputum inspection reveals scanty sputum that is clear or mucoid. Infections are less frequent than in chronic bronchitis.  Arterial blood gas studies typically indicate a reduced or normal Pao2 level (65 to 75 mm Hg) and, in late disease stages, an increased Paco2 level (50 to 60 mm Hg).  Pulmonary function tests show a reduced FEV1/FVC ratio, normal or increased static lung compliance, reduced FEV1 and diffusing capacity, and increased TLC and RV.  Chest radiograph usually reveals bullae, blebs, a flattened diaphragm, lung hyperinflation, vertical heart, enlarged anteroposterior chest diameter, decreased vascular markings in the lung periphery, and a large retrosternal air space. CHRONIC BRONCHITIS:  Blood analysis may reveal polycythemia as a result of to erythropoiesis secondary to hypoxemia. With bacterial infection, the WBC count may be increased.  Sputum inspection reveals thick purulent or mucopurulent sputum tinged yellow, white, green, or gray; an acute change in color and/or quantity suggests infection.  Arterial blood gas studies may show a markedly decreased Pao2 level (45 to 60 mm Hg), reflecting hypoxemia, and a Paco2 level that is normal or elevated (50 to 60 mm Hg), reflecting hypercapnia.  Pulmonary function tests may be normal in the early disease stages. Later, they show a reduced FEV1/FVC ratio, increased residual lung volume, a decreased vital capacity,