Chronic Obstructive Pulmonary Disease ( Copd)

Chronic Obstructive Pulmonary Disease ( COPD) • COPD is a disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema • The airflow obstruction is generally progressive, may be accompanied by airway hyper-reactivity, and may be partially reversible • Most patients with COPD have features of both emphysema and chronic bronchitis

COPD

Chronic bronchitis • It is a clinical diagnosis • Defined by excessive secretion of bronchial mucus • Manifested by daily productive cough occuring on most days for at least 3 consecutive months or more in at least 2 consecutive years

Emphysema • It is a pathologic diagnosis • Denotes abnormal permanent enlargement of air spaces distal to the terminal bronchiole, with destruction of their walls and without obvious fibrosis

Etiology Cigarette smoking • The most important cause of COPD • Nearly all smokers suffer an accelerated decline in lung function that is dose- and duration-dependent • Fifteen percent develop progressively disabling symptoms in their 40s and 50s • It is estimated that 80% of patients seen for COPD have significant exposure to tobacco smoke

Other Exposures • Combination of exposures to environmental tobacco smoke • Occupational dusts and chemicals • Indoor air pollution from biomass fuel used for cooking and heating in poorly ventilated buildings • Outdoor air pollution • Airway infection • Familial factors • Allergy

Hereditary factors • Deficiency of α 1-antiprotease

Other Factors • Low socioeconomic status • Maternal smoking • Low birth weight

Pathogenesis • Enlargement of mucous secreting gland and increased number of goblet cells contribute to enhanced secretion of airway mucous that manifests as chronic bronchitis • Loss of elastic tissue, inflammation and fibrosis in airway wall result in premature airway closure, gas trapping and dynamic hyperinflation leading to changes in pulmonary and chest wall compliance • Excessive lysis of elastin and other structural proteins in the lung matrix by elastase and other proteases derived from lung neutrophils, macrophages, and mononuclear cells causes destruction of alveoli and appearance of emphysema

Emphysematous dysfunction in COPD

Clinical Findings Symptoms and Signs • Patients with COPD characteristically present in the fifth or sixth decade of life • Complaining of excessive cough, sputum production, and shortness of breath • Symptoms have often been present for 10 years or more • Dyspnea is noted initially only on heavy exertion, but as the condition progresses it occurs with mild activity. In severe disease, dyspnea occurs at rest

• A hallmark of COPD is frequent exacerbations of illness that result in absence from work and eventual disability • Pneumonia, pulmonary hypertension, cor pulmonale, and chronic respiratory failure characterize the late stage of COPD • Death usually occurs during an exacerbation of illness in association with acute respiratory failure

• Clinical findings may be completely absent early in the course of COPD • As the disease progresses, two symptom patterns tend to emerge, historically referred to as "pink puffers" and "blue bloaters" • They represent pure forms of emphysema and bronchitis • Most COPD patients have pathologic evidence of both disorders

Patterns of disease in advanced COPD. Type A: Pink Type B: Blue Puffer

Bloater

(EmphysemaPredomi (BronchitisPredominant nant) )

History and physical examinati on

•Major complaint is dyspnea, •Major complaint is chronic often severe cough, productive of mucopurulent sputum, with •Usually presenting after age frequent exacerbations due to 50 chest infections •Cough is rare, with scant •Often presents in late 30s and clear, mucoid sputum 40s •Patients are thin, with recent •Dyspnea usually mild, though weight loss common patients may note limitations to •They appear uncomfortable, exercise with evident use of accessory •Patients frequently overweight muscles of respiration and cyanotic but seem •Chest is very quiet without comfortable at rest adventitious sounds •Peripheral edema is common •No peripheral edema •Chest is noisy, with rhonchi invariably present; wheezes are

Type A: Pink Puffer Type B: Blue (EmphysemaPredominan Bloater (Bronchitis t)

Laborato •Hemoglobin usually ry normal (12–15 g/dL) studies •PaO2 normal to slightly reduced (65– 75 mm Hg) but SaO2 normal at rest •PaCO2 normal to slightly reduced (35– 40 mm Hg) •Chest radiograph shows hyperinflation with flattened diaphragms

Predominant)

•Hemoglobin usually elevated (15–18 g/dL) •PaO2 reduced (45–60 mm Hg) and PaCO2 slightly to markedly elevated (50–60 mm Hg) •Chest radiograph shows increased interstitial markings ("dirty lungs"), especially

Chest film. Chronic Bronchitis Irregular bronco-vascular markings as sign of chronic inflammation of the walls of the bronchi.

Emphysema p.a. and lateral: - Hypertransparency

of lung fields, - straightened vascular markings - The peripheral zone in the p.a. chest film where one can see no vessels - Small, dropletshaped heart, barrel chest, - widened intercostal spaces, - sudden transition of wide central pulmonary arteries to small vessels.

Unilateral emphysema

Chronic Bronchitis

Pulmonary function tests

Type A: Pink Puffer (Emphysema Predominant)

Type B: Blue Bloater (Bronchitis Predominant)

•Airflow obstruction ubiquitous •Total lung capacity increased, sometimes markedly so •DLCO reduced •Static lung compliance increased

•Airflow obstruction ubiquitous •Total lung capacity generally normal but may be slightly increased •DLCO normal •Static lung compliance normal

Special Type A: Pink evaluations Puffer (Emphysema Predominant)

V/Q matching

elevated and increase with exercise

Exercise ventilation

Predominant

Increased ventilation to Increased perfusion to high V/Q areas, ie, high low V/Q areas dead space ventilation.

Hemodynami Cardiac output normal to slightly low. Pulmonary cs artery pressures mildly

Nocturnal ventilation

Type B: Blue Bloater (Bronchitis

Mild to moderate degree of oxygen desaturation not usually associated with obstructive sleep apnea.

Cardiac output normal. Pulmonary artery pressures elevated, sometimes markedly so, and worsen with exercise Severe oxygen desaturation, frequently associated with obstructive sleep apnea.

Increased minute Decreased minute ventilation for level of ventilation for level of oxygen consumption. oxygen consumption. PaO2 tends to fall, PaCO2 PaO2 may rise; PaCO2

Investigations Laboratory Findings

Spirometry: • Pulmonary function tests early in the course of COPD reveal only evidence of abnormal closing volume and reduced midexpiratory flow rate • Reductions in FEV1 and in the ratio of forced expiratory volume to vital capacity (FEV1% or FEV1/FVC ratio) occur later • In severe disease, the FVC is markedly reduced • Lung volume measurements reveal a marked increase in residual volume (RV) • Increase in total lung capacity (TLC), Elevation of the RV/TLC ratio, indicative of air trapping, particularly in emphysema

Arterial blood gas measurements gas measurements characteristically • Arterial blood

show no abnormalities early in COPD other than an increased A–a–DO2

• • • •

They are necessary if (1) hypoxemia or hypercapnia is suspected (2) the FEV1 is < 40% of predicted (3) there are clinical signs of right heart failure

• Hypoxemia occurs in advanced disease, particularly when chronic bronchitis predominates • Compensated respiratory acidosis occurs in patients with chronic respiratory failure, particularly in chronic bronchitis, with worsening of acidemia during acute exacerbations.

Examination of the sputum • Examination of the sputum may reveal Streptococcus pneumoniae, H influenzae, or Moraxella catarrhalis • Positive sputum cultures are poorly correlated with acute exacerbations, and research techniques demonstrate evidence of preceding viral infection in a majority of patients with exacerbations.

ECG • The ECG may show sinus tachycardia, and in advanced disease, chronic pulmonary hypertension may produce electrocardiographic abnormalities typical of cor pulmonale • Supraventricular arrhythmias (multifocal atrial tachycardia, atrial flutter, and atrial fibrillation) and ventricular irritability also occur

Imaging • Radiographs of patients with chronic bronchitis typically show only nonspecific peribronchial and perivascular markings • Plain radiographs are insensitive for the diagnosis of emphysema; they show hyperinflation with flattening of the diaphragm or peripheral arterial deficiency in about half of cases • Parenchymal bullae in the setting of either of these findings are diagnostic of emphysema • Doppler echocardiography is an effective way to estimate pulmonary artery pressure if pulmonary hypertension is suspected

Emphysema

Centrilobular emphysema. CT scan

Paraseptal emphysema. CT scan, magnified view

Differential Diagnosis • • • • •

Bronchial asthma Bronchiectasis Cystic fibrosis Bronchopulmonary mycosis Central airflow obstruction

Complications • Acute bronchitis, pneumonia, pulmonary thromboembolism, and concomitant left ventricular failure may worsen otherwise stable COPD • Pulmonary hypertension, cor pulmonale, and chronic respiratory failure are common in advanced COPD • Spontaneous pneumothorax occurs in a small fraction of patients with emphysema. Hemoptysis may result from chronic bronchitis or may signal bronchogenic carcinoma.

Prevention • COPD is largely preventable through elimination of long-term exposure to tobacco smoke • Smokers with early evidence of airflow limitation can alter their disease by smoking cessation. Smoking cessation slows the decline in FEV1 in middle-aged smokers with mild airways obstruction • Vaccination against influenza and pneumococcal infection may also be of benefit

Treatment Ambulatory Patients Smoking cessation • The single most important intervention in smokers with COPD is to encourage smoking cessation • Nicotine transdermal patch, nicotine gum, and bupropion increase cessation rates in motivated smokers

Oxygen therapy • The only drug therapy that is documented to improve the natural history of COPD is supplemental oxygen in those patients with resting hypoxemia • Survival in hypoxemic patients with COPD treated with supplemental oxygen therapy is directly proportionate to the number of hours per day oxygen is administered • Oxygen by nasal prongs must be given at least 15 hours a day unless therapy is intended only for exercise or sleep

• Arterial blood gas analysis is used to guide initial oxygen therapy • Hypoxemic patients with pulmonary hypertension, chronic cor pulmonale, erythrocytosis, impaired cognitive function, exercise intolerance, nocturnal restlessness, or morning headache are particularly likely to benefit from home oxygen therapy • For most patients, a flow rate of 1–3 L/min achieves a PaO2 greater than 55 mm Hg

Bronchodilators • Bronchodilators are the most important agents in the pharmacologic management of patients with COPD • Bronchodilators offer some patients improvement in symptoms, exercise tolerance, and overall health status • Aggressiveness of bronchodilator therapy should be matched to the severity of the patient's disease • In patients who experience no symptomatic improvement, bronchodilators should be discontinued.

• The two most commonly prescribed bronchodilators:

• Anticholinergic ipratropium bromide • Short-acting β 2-agonists eg, albuterol, metaproterenol

• Ipratropium bromide is generally preferred to the shortacting β2-agonists as a first-line agent because of its longer duration of action and absence of sympathomimetic side effects • Typical doses are two to four puffs (36–72 mcg) every 6 hours • Short-acting β2-agonists are less expensive and have a more rapid onset of action, commonly leading to greater patient satisfaction • At maximal doses, β2-agonists may cause tachycardia, tremor, or hypokalemia

• Oral theophylline: • It is a third-line agent in COPD patients who fail to achieve adequate symptom control with anticholinergics and β2-agonists • Sustained-release theophylline improves arterial oxygen hemoglobin saturation during sleep in COPD patients and is a first-line agent for those with sleep-related breathing disorders

Corticosteroids • Apart from acute exacerbations, COPD is not generally a corticosteroid-responsive disease • Empiric trials of oral prednisone for 14–21 days and inhaled corticosteroids for 6–12 weeks of therapy are common • The drug should be discontinued unless there is a 20% or greater increase in FEV1 after the trial of therapy.

Antibiotics

• Antibiotics are commonly prescribed to outpatients with COPD for the following indications: • (1) to treat an acute exacerbation • (2) to treat acute bronchitis • (3) to prevent acute exacerbations of chronic bronchitis (prophylactic antibiotics) • Common agents include trimethoprimsulfamethoxazole (160/800 mg every 12 hours), amoxicillin or amoxicillin-clavulanate (500 mg every 8 hours), or doxycycline (100 mg every 12 hours) given for 7–10 days • Broader spectrum therapy may be indicated in patients with more severe baseline airflow obstruction.

Other measures • In patients with chronic bronchitis, increased mobilization of secretions may be accomplished through the use of adequate systemic hydration, effective cough training methods, or use of a hand-held flutter device and postural drainage, sometimes with chest percussion or vibration • Expectorant-mucolytic therapy has generally been regarded as unhelpful in patients with chronic bronchitis • Cough suppressants and sedatives should be avoided as routine measures.

• Human α 1-antitrypsin: • It is available for replacement therapy in emphysema due to congenital deficiency of α1-antitrypsin • Patients over 18 years of age with airflow obstruction by spirometry and levels less than 11 mcmol/L are potential candidates for replacement therapy • α1-Antitrypsin is administered intravenously in a dose of 60 mg/kg body weight

• Graded aerobic physical exercise programs (eg, walking 20 minutes three times weekly, or bicycling) are helpful to prevent deterioration of physical condition and to improve the patient's ability to carry out daily activities • Training of inspiratory muscles • Pursed-lip breathing to slow the rate of breathing and abdominal breathing exercises to relieve fatigue of accessory muscles of respiration may reduce dyspnea in some patient

Hospitalized Patients Hospitalization is indicated for acute worsening of COPD that fails to respond to measures for ambulatory patients Patients with acute respiratory failure or complications such as cor pulmonale and pneumothorax should also be hospitalized

Management of the hospitalized patient with an acute exacerbation of COPD includes: • Supplemental oxygen • Inhaled ipratropium bromide • Inhaled 2-agonists • Broad-spectrum antibiotics • Corticosteroids • Chest physiotherapy

• Theophylline should not be initiated in the acute setting, but patients taking theophylline prior to acute hospitalization should have their theophylline serum levels measured and maintained in the therapeutic range • Oxygen therapy should not be withheld for fear of worsening respiratory acidemia; hypoxemia is more detrimental than hypercapnia • Cor pulmonale usually responds to measures that reduce pulmonary artery pressure, such as supplemental oxygen and correction of acidemia • Cardiac arrhythmias, particularly multifocal atrial tachycardia, usually respond to aggressive treatment of COPD itself. Atrial flutter may require DC cardioversion after initiation of the above therapy • If progressive respiratory failure ensues, tracheal intubation and mechanical ventilation are necessary

Surgery for COPD Lung transplantation • Requirements for lung transplantation are severe lung disease, limited activities of daily living, exhaustion of medical therapy, ambulatory status, potential for pulmonary rehabilitation, limited life expectancy without transplantation, adequate function of other organ systems, and a good social support system • Substantial improvements in pulmonary function and exercise performance have been noted after transplantation

Lung volume reduction surgery • Lung volume reduction surgery (LVRS), or reduction pneumoplasty, is a surgical approach to relieve dyspnea and improve exercise tolerance in patients with advanced diffuse emphysema and lung hyperinflation • Bilateral resection of 20–30% of lung volume in selected patients results in modest improvements in pulmonary function, exercise performance, and dyspnea

Bullectomy • Bullectomy is an older surgical procedure for palliation of severe dyspnea in patients with severe bullous emphysema • In this procedure, the surgeon removes a very large emphysematous bulla that demonstrates no ventilation or perfusion on lung scanning and compresses adjacent lung that has preserved function • Bullectomy can now be performed with a CO2 laser via thoracoscopy

Prognosis • The outlook for patients with clinically significant COPD is poor • The median survival of patients with severe COPD (FEV1 1 L) is about 4 years • The degree of pulmonary dysfunction (as measured by FEV1) at the time the patient is first seen is probably the most important predictor of survival