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Chronic bronchitis is defined clinically as the presence of a chronic productive cough for 3 months during each of 2 consecutive years

(other causes of cough being excluded). Emphysema, on the other hand, is defined pathologically as an abnormal, permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis.

Airflow limitation in emphysema is due to loss of elastic recoil, whereas chronic bronchitis leads to narrowing of airway caliber and increase in airway resistance. Although some patients predominantly display signs of one of these diseases or the other, most fall somewhere in the middle of the spectrum between the 2 conditions.

Pathophysiology
Pathologic changes in COPD occur in the large (central) airways, the small (peripheral) bronchioles, and the lung parenchyma. Most cases of COPD are the result of exposure to noxious stimuli, most often cigarette smoke. The normal inflammatory response is amplified in persons prone to COPD development. The pathogenic mechanisms are not clear but are most likely diverse. Increased numbers of activated polymorphonuclear leukocytes and macrophages release elastases in a manner that cannot be counteracted effectively by antiproteases, resulting in lung destruction.

Pathophysiology
Chronic bronchitis Mucous gland hyperplasia is the histologic hallmark of chronic bronchitis. Airway structural changes include atrophy, focal squamous metaplasia, ciliary abnormalities, variable amounts of airway smooth muscle hyperplasia, inflammation, and bronchial wall thickening

Damage to the endothelium impairs the mucociliary response that clears bacteria and mucus. Inflammation and secretions provide the obstructive component of chronic bronchitis. Neutrophilia develops in the airway lumen, and neutrophilic infiltrates accumulate in the submucosa. The respiratory bronchioles display a mononuclear inflammatory process, lumen occlusion by mucus plugging, goblet cell metaplasia, smooth muscle hyperplasia, and distortion due to fibrosis. These changes, combined with loss of supporting alveolar attachments, cause airflow limitation by allowing airway walls to deform and narrow the airway lumen.

In contrast to emphysema, chronic bronchitis is associated with a relatively undamaged pulmonary capillary bed. The body responds by decreasing ventilation and increasing cardiac output. This V/Q mismatch results in rapid circulation in a poorly ventilated lung, leading to hypoxemia and polycythemia. Eventually, hypercapnia and respiratory acidosis develop, leading to pulmonary artery vasoconstriction and cor pulmonale. With the ensuing hypoxemia, polycythemia, and increased CO2 retention, these patients have signs of right heart failure and are known as "blue bloaters.

Pathophysiology
Emphysema Emphysema is a pathologic diagnosis defined by permanent enlargement of airspaces distal to the terminal bronchioles. This leads to a dramatic decline in the alveolar surface area available for gas exchange. Furthermore, loss of alveoli leads to airflow limitation by 2 mechanisms. First, loss of the alveolar walls results in a decrease in elastic recoil, which leads to airflow limitation. Second, loss of the alveolar supporting structure leads to airway narrowing, which further limits airflow. Emphysema has 3 morphologic patterns: Centriacinar Panacinar Distal acinar, or paraseptal

Centriacinar emphysema is characterized by focal destruction limited to the respiratory bronchioles and the central portions of the acini. This form of emphysema is associated with cigarette smoking and is typically most severe in the upper lobes.

Panacinar emphysema involves the entire alveolus distal to the terminal bronchiole. The panacinar type is typically most severe in the lower lung zones and generally develops in patients with homozygous alpha1-antitrypsin (AAT) deficiency

Distal acinar emphysema, or paraseptal emphysema, is the least common form and involves distal airway structures, alveolar ducts, and sacs. This form of emphysema is localized to fibrous septa or to the pleura and leads to formation of bullae. The apical bullae may cause pneumothorax

Pathophysiology
The gradual destruction of alveolar septae and of the pulmonary capillary bed in emphysema leads to a decreased ability to oxygenate blood. The body compensates with lowered cardiac output and hyperventilation. This V/Q mismatch results in relatively limited blood flow through a fairly well oxygenated lung with normal blood gases and pressures in the lung, in contrast to the situation in chronic bronchitis. Because of low cardiac output, the rest of the body suffers from tissue hypoxia and pulmonary cachexia. Eventually, these patients develop muscle wasting and weight loss and are identified as "pink puffers."

Pathophysiology
Emphysematous destruction and small airway inflammation Emphysematous destruction and small airway inflammation often are found in combination in individual patients, leading to the spectrum that is known as COPD. When emphysema is moderate or severe, loss of elastic recoil, rather than bronchiolar disease, is the dominant mechanism of airflow limitation. By contrast, when emphysema is mild, bronchiolar abnormalities are most responsible for the majority of the deficit in lung function. Although airflow obstruction in emphysema is often irreversible, bronchoconstriction due to inflammation accounts for some reversibility. Airflow limitation is not the only pathophysiologic mechanism by which symptoms occur.

Pathophysiology
Dynamic hyperinflation Lung volumes, particularly dynamic hyperinflation, have also been shown to play a crucial role in the development of dyspnea perceived during exercise. In fact, the improvement in exercise capacity brought about by several treatment modalities, including bronchodilators, oxygen therapy, lung volume reduction surgery (LVRS), and maneuvers learned in pulmonary rehabilitation, is more likely due to delaying dynamic hyperinflation rather than improving the degree of airflow obstruction. Additionally, hyperinflation (defined as the ratio of inspiratory capacity to total lung capacity [IC/TLC]) has been shown to predict survival better than forced expiratory volume in 1 second (FEV1)

Etiology
Cigarette smoking The primary cause of COPD is exposure to tobacco smoke. Overall, tobacco smoking accounts for as much as 90% of COPD risk. Cigarette smoking induces macrophages to release neutrophil chemotactic factors and elastases, which lead to tissue destruction. Clinically significant COPD develops in 15% of cigarette smokers, although this number is believed to be an underestimate. Age of initiation of smoking, total pack-years, and current smoking status predict COPD mortality. People who smoke have an increased annual decline in FEV1: the physiologic normal decline in FEV1 is estimated to be 20-30 ml/y, but the rate of decline in COPD patients is generally 60 ml/y or greater. Secondhand smoke, or environmental tobacco smoke, increases the risk of respiratory infections, augments asthma symptoms, and causes a measurable reduction in pulmonary function. A study by Nagelmann et al concluded that lung function deviation and lung structural changes are present in people who smoke cigarettes before the clinical signs of airway obstruction reveal them.

Environmental factors COPD does occur in individuals who have never smoked. Although the role of air pollution in the etiology of COPD is unclear, the effect is small when compared with that of cigarette smoking. In developing countries, the use of biomass fuels with indoor cooking and heating is likely to be a major contributor to the worldwide prevalence of COPD. Long-term exposure to traffic-related air pollution may be a factor in COPD in patients with diabetes and asthma.

Airway hyperresponsiveness Airway hyperresponsiveness stipulates that patients who have nonspecific airway hyperreactivity and who smoke are at increased risk of developing COPD with an accelerated decline in lung function. Nonspecific airway hyperreactivity is inversely related to FEV1 and may predict a decline in lung function. The possible role of airway hyperresponsiveness as a risk factor for the development of COPD in people who smoke is unclear. Moreover, bronchial hyperreactivity may result from airway inflammation observed with the development of smoking-related chronic bronchitis. This may contribute to airway remodeling, leading to a more fixed obstruction, as is seen in persons with COPD.

Alpha1-antitrypsin deficiency Alpha1-antitrypsin (AAT) is a serine protease inhibitor family that is synthesized in the liver and is secreted into the bloodstream. The main purpose of this protein is to neutralize neutrophil elastase in the lung interstitium and to protect the lung parenchyma from elastolytic breakdown. Severe AAT deficiency predisposes to unopposed elastolysis with the clinical sequela of an early onset of panacinar emphysema AAT deficiency is the only known genetic risk factor for developing COPD and accounts for less than 1% of all cases in the United States. Severe AAT deficiency leads to premature emphysema at an average age of 53 years for nonsmokers and 40 years for smokers.

Intravenous drug use Emphysema occurs in approximately 2% of persons who use intravenous (IV) drugs. This is attributed to pulmonary vascular damage that results from the insoluble filler (eg, cornstarch, cotton fibers, cellulose, talc) contained in methadone or methylphenidate. The bullous cysts found in association with IV use of cocaine or heroin occur predominantly in the upper lobes. In contrast, methadone and methylphenidate injections are associated with basilar and panacinar emphysema.

Immunodeficiency syndromes Human immunodeficiency virus (HIV) infection has been found to be an independent risk factor for COPD, even after controlling for confounding variables such as smoking, IV drug use, race, and age.[19] Apical and cortical bullous lung damage occurs in patients who have autoimmune deficiency syndrome and Pneumocystis carinii infection.

Connective tissue disorders Marfan syndrome is an autosomal dominant inherited disease of type I collagen characterized by abnormal length of the extremities, subluxation of the lenses, and cardiovascular abnormality. Pulmonary abnormalities, including emphysema, have been described in approximately 10% of patients. Ehlers-Danlos syndrome refers to a group of inherited connective tissue disorders with manifestations that include hyperextensibility of the skin and joints, easy bruisability, and pseudotumors; it has also been associated with a higher prevalence of COPD.

Epidemiology
The National Health Interview Survey reports the prevalence of emphysema at 18 cases per 1000 persons and chronic bronchitis at 34 cases per 1000 persons. While the rate of emphysema has stayed largely unchanged since 2000, the rate of chronic bronchitis has decreased. Another study estimates a prevalence of 10.1% in the United States.However, the exact prevalence of COPD in the United States is believed to be underestimated. This is largely due to the fact that it is an underdiagnosed (and undertreated) disease, because most patients do not present for medical care until the disease is in a late stage.

The exact prevalence of COPD worldwide is largely unknown, but estimates have varied from 7-19%. The Burden of Obstructive Lung Disease (BOLD) study found a global prevalence of 10.1%. Men were found to have a pooled prevalence of 11.8% and women 8.5%. The numbers vary in different regions of the world. Cape Town, South Africa, has the highest prevalence, affecting 22.2% of men and 16.7% of women.

Germany, on the other hand, has the lowest prevalence, of 8.6% for men and 3.7% for women. The differences can be explained in part by site and sex differences in the prevalence of smoking. Additionally, the prevalence in women is believed to be increasing.

History
Most patients with COPD seek medical attention late in the course of their disease. Patients often ignore the symptoms because they start gradually and progress over the course of years. Patients often modify their lifestyle to minimize dyspnea and ignore cough and sputum production. With retroactive questioning, a multiyear history can be elicited.

Patients typically present with a combination of signs and symptoms of chronic bronchitis and emphysema. These include cough, worsening dyspnea, progressive exercise intolerance, sputum production, and alteration in mental status.

Symptoms include the following: Productive cough or acute chest illness is common. The cough usually is worse in the mornings and produces a small amount of colorless sputum Breathlessness:the most significant symptom, but it usually does not occur until the sixth decade of life (although it may occur much earlier). By the time the FEV1 has fallen to 50% of predicted, the patient is usually breathless upon minimal exertion. In fact, the FEV1 is the most common variable used to grade the severity of COPD, although it is not the best predictor of mortality.

Wheezing:Wheezing may occur in some patients, particularly during exertion and exacerbations. Systemic manifestations : COPD is now known to be a disease with systemic manifestations, and the quantification of these manifestations has proved to be a better predictor of mortality than lung function alone. Many patients with COPD may have decreased fat-free mass, impaired systemic muscle function, osteoporosis, anemia, depression, pulmonary hypertension, cor pulmonale, and even left-sided heart failure. Depression is not uncommon in subjects with COPD

Some important clinical and historical differences may help distinguish between the types of COPD. Classic findings for patients with chronic bronchitis include productive cough with gradual progression to intermittent dyspnea; frequent and recurrent pulmonary infections; and progressive cardiac/respiratory failure with edema and weight gain. Classic findings for patients with emphysema include a long history of progressive dyspnea with late onset of nonproductive cough; occasional mucopurulent relapses; and eventual cachexia and respiratory failure.

Physical Examination
The sensitivity of a physical examination in detecting mild to moderate COPD is relatively poor; however, physical signs are quite specific and sensitive for severe disease. Patients with severe disease experience tachypnea and respiratory distress with simple activities.

The respiratory rate increases in proportion to disease severity. Use of accessory respiratory muscles and paradoxical indrawing of lower intercostal spaces is evident (known as the Hoover sign). In advanced disease, cyanosis, elevated jugular venous pulse (JVP), and peripheral edema can be observed.

Thoracic examination reveals the following: Hyperinflation (barrel chest) Wheezing Frequently heard on forced and unforced expiration Diffusely decreased breath sounds Hyperresonance on percussion Prolonged expiration In addition, coarse crackles beginning with inspiration may be heard.

Certain characteristics allow differentiation between disease that is predominantly chronic bronchitis and that which is predominantly emphysema.
Emphysema characteristics include the following: Patients may be very thin with a barrel chest Patients typically have little or no cough or expectoration Breathing may be assisted by pursed lips and use of accessory respiratory muscles; patients may adopt the tripod sitting position The chest may be hyperresonant, and wheezing may be heard Heart sounds are very distant Overall appearance is more like classic COPD exacerbation Chronic bronchitis characteristics include the following: Patients may be obese Frequent cough and expectoration are typical Use of accessory muscles of respiration is common Coarse rhonchi and wheezing may be heard on auscultation Patients may have signs of right heart failure (ie, cor pulmonale), such as edema and cyanosis

Differential Diagnoses
Congestive heart failure (CHF) may produce wheezing and often may be difficult to differentiate from emphysema. A history of orthopnea and paroxysmal nocturnal dyspnea, fine basal crackles on chest auscultation, and typical findings on chest radiographs can lead to the diagnosis of CHF.

Bronchiectasis: Patients with bronchiectasis have chronic production of copious purulent sputum, coarse crackles and clubbing upon physical examination, and abnormal findings on chest radiographs and CT scans. Bronchiolitis obliterans: is observed in younger persons who do not smoke and in persons with collagen-vascular diseases. A CT scan characteristically shows areas of mosaic attenuation without evidence of generalized emphysema. Chronic asthma: The delayed onset of severe asthma may be difficult to distinguish from COPD in older patients, but the important distinction is a significant bronchodilator response and normal diffusion (ie, diffusing capacity of lung for carbon monoxide [DLCO]) on pulmonary function tests.

Investigations
The defining feature of COPD is irreversible airflow limitation during forced expiration. This may result from a loss of elastic recoil due to lung tissue destruction or from an increase in the resistance of the conducting airways. The formal diagnosis of COPD is made with spirometry; when the ratio of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) is less than 70% of that predicted for a matched control, it is diagnostic for a significant obstructive defect. Other studies, including laboratory studies and imaging, are particularly important during acute exacerbations of disease.

Arterial Blood Gas Analysis


provides the best clues as to acuteness and severity of disease exacerbation. Patients with mild COPD have mild to moderate hypoxemia without hypercapnia. As the disease progresses, hypoxemia worsens and hypercapnia may develop, with the latter commonly being observed as the FEV1 falls below 1 L/s or 30% of the predicted value. Lung mechanics and gas exchange worsen during acute exacerbations. In general, renal compensation occurs even in chronic CO2 retainers (ie, bronchitics); thus, pH usually is near normal. Generally, consider any pH below 7.3 to be a sign of acute respiratory compromise.

Serum Chemistries
Patients with COPD tend to retain sodium. In addition, serum potassium should be monitored carefully, because diuretics, beta-adrenergic agonists, and theophylline act to lower potassium levels. Beta-adrenergic agonists also increase renal excretion of serum calcium and magnesium, which may be important in the presence of hypokalemia. Chronic respiratory acidosis leads to compensatory metabolic alkalosis. In the absence of blood gas measurements, bicarbonate levels are useful for following disease progression.

Alpha1-Antitrypsin
Measure alpha1-antitrypsin (AAT) in all patients younger than 40 years or in those with a family history of emphysema at an early age. The diagnosis of severe AAT deficiency is confirmed when the serum level falls below the protective threshold value of 11 mmol/L (ie, in the range of 3-7 mmol/L).

Sputum Evaluation
In persons with stable chronic bronchitis, the sputum is mucoid and macrophages are the predominant cells. With an exacerbation, sputum becomes purulent because of the presence of neutrophils. Although the quality of sputum can vary between patients in chronic stable disease, an increase in the quantity of sputum production is often a sign of an acute exacerbation. A mixture of organisms often is visible with Gram stain. The pathogens cultured most frequently during exacerbations are Streptococcus pneumoniae andHaemophilus influenzae.Moraxella catarrhalis is also a common organism, and Pseudomonas aeruginosa can be seen in patients with severe obstruction.

Chest Radiography
of patients with emphysema reveal signs of hyperinflation, including flattening of the diaphragm and a long, narrow heart shadow. Rapidly tapering vascular shadows accompanied by hyperlucency of the lungs are other signs of emphysema. Chronic bronchitis is associated with increased bronchovascular markings and cardiomegaly. With complicating pulmonary hypertension, the hilar vascular shadows are prominent, with possible right ventricular enlargement.

Computed Tomography
CT scanning is more sensitive than standard chest radiography and is highly specific for diagnosing emphysema (outlined bullae are not always visible on a radiograph). CT scanning may provide an adjunct means of diagnosing various forms of COPD (ie, lower lobe disease may suggest AAT deficiency) and may help the clinician to determine whether surgical intervention would benefit the patient

Echocardiography
Many patients with long-standing COPD develop secondary pulmonary hypertension from chronic hypoxemia and vascular remodeling. This may result in eventual rightsided heart failure (cor pulmonale). However, even with severe COPD, the degree of pulmonary hypertension is usually only mild to moderate. Findings of severe pulmonary hypertension on echocardiogram or cardiac catheterization warrant further workup.

Pulmonary Function Tests


Pulmonary function tests are essential for the diagnosis and assessment of the severity of disease, and they are helpful in following its progress. FEV1 is the most commonly used index of airflow obstruction. In addition to the spirometry findings that define the disease, lung volume measurements often show an increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity often decreases. Dynamic hyperinflation during exercise is now thought be a greater contributor to the sensation of dyspnea than airflow obstruction alone (as measured by FEV1). As many as 30% of patients have an increase in FEV1 of 15% or more after inhalation of a bronchodilator. However, the absence of bronchodilator response does not justify withholding therapy.

GOLD CLASSIFICATION

The GOLD staging system classifies people with COPD based on their degree of airflow limitation (obstruction). The airflow limitation is measured during pulmonary function tests (PFTs). When blowing out forcefully, people with normal lungs can exhale most of the air in their lungs in one second. Pulmonary function tests measure this and other values, and are used to diagnose COPD and its severity: The volume in a one-second forced exhalation is called the forced expiratory volume in one second (FEV1), measured in liters. The total exhaled breath is called the forced vital capacity (FVC), also measured in liters. In people with normal lung function, FEV1 is at least 70% of FVC. Because of lung damage, people with COPD take longer to blow air out. This impairment is called obstruction or airflow limitation. An FEV1 less than 70% of FVC can make the diagnosis of COPD in someone with compatible symptoms and history. In GOLD COPD, classifications are then used to describe the severity of the obstruction or airflow limitation. The worse a person's airflow limitation is, the lower their FEV1. As COPD progresses, FEV1 tends to decline. GOLD COPD staging uses four categories of severity for COPD, based on the value of FEV1:

Stage I-Mild COPD FEV1/FVC<0.70FEV1 80% normal Stage II-Moderate COPD FEV1/FVC<0.70FEV1 50-79% normal Stage III-Severe COPD FEV1/FVC<0.70FEV1 30-49% normal Stage IV-Very Severe COPD FEV1/FVC<0.70FEV1 <30% normal, or <50% normal with chronic respiratory failure presen

Treatment
The goal of COPD management is to improve a patients functional status and quality of life by preserving optimal lung function, improving symptoms, and preventing the recurrence of exacerbations. Currently, no treatments aside from lung transplantation have been shown to significantly improve lung function or decrease mortality. Once the diagnosis of COPD is established, it is important to educate the patient about the disease and to encourage his or her active participation in therapy.

Approaches to management include recommendations such as those provided by GOLD: Stage I (mild obstruction): reduction of risk factors (influenza vaccine); short-acting bronchodilator as needed Stage II (moderate obstruction): reduction of risk factors (influenza vaccine); short-acting bronchodilator as needed; long-acting bronchodilator(s); cardiopulmonary rehabilitation Stage III (severe obstruction): reduction of risk factors (influenza vaccine); short-acting bronchodilator as needed; long-acting bronchodilator(s); cardiopulmonary rehabilitation; inhaled glucocorticoids if repeated exacerbations Stage IV (very severe obstruction or moderate obstruction with evidence of chronic respiratory failure): reduction of risk factors (influenza vaccine); short-acting bronchodilator as needed; long-acting bronchodilator(s); cardiopulmonary rehabilitation; inhaled glucocorticoids if repeated exacerbation; long-term oxygen therapy (if criteria met); consider surgical options such as LVRS and lung transplantation

Oral and inhaled medications are used for patients with stable disease to reduce dyspnea and improve exercise tolerance. Most of the medications used are directed at the following 4 potentially reversible causes of airflow limitation in a disease state that has largely fixed obstruction: Bronchial smooth muscle contraction Bronchial mucosal congestion and edema Airway inflammation Increased airway secretions

Bronchodilation Bronchodilators are the backbone of any COPD treatment regimen. They work by dilating airways, thereby decreasing airflow resistance. This increases airflow and decreases dynamic hyperinflation. Lack of response in pulmonary function testing should not preclude their use. These drugs provide symptomatic relief but do not alter disease progression or decrease mortality.

Beta2 agonists and anticholinergics The initial choice of agent remains in debate. Historically, beta2 agonists were considered first line and anticholinergics were added as adjuncts. Not surprisingly, studies have shown combination therapy results in greater bronchodilator response and provides greater relief. Monotherapy with either agent and combination therapy with both are acceptable options. The adverse effect profile may help guide therapy. Generally, long-acting bronchodilators are more beneficial than short-acting ones.

Beta2-agonist bronchodilators Even patients who have no measurable increase in post-bronchodilator expiratory airflow may benefit from treatment with beta2 agonists. The inhaled route is preferred because it minimizes adverse systemic effects. The adverse effects are predictable and include tachycardia and tremors. Although rare, beta2 agonists may also precipitate a cardiac arrhythmia.

Anticholinergic drugs compete with acetylcholine for postganglionic muscarinic receptors, thereby inhibiting cholinergically mediated bronchomotor tone, resulting in bronchodilation. They block vagally mediated reflex arcs that cause bronchoconstriction. Clinical benefit is gained through a decrease in exercise-induced dynamic hyperinflation. These agents are poorly absorbed systemically and are relatively safe. Reported adverse effects include dry mouth, dry eyes, metallic taste, and prostatic symptoms

Inhaled delivery of medications is preferred over the oral route to help minimize potential adverse effects. Some patients may have difficulty achieving effective delivery of the medication using a metered-dose inhaler; use of a spacer or nebulizer may be beneficial in these patients.

Phosphodiesterase inhibitors Phosphodiesterase inhibitors result in bronchodilation. Additionally, they may improve diaphragm muscle contractility and stimulate the respiratory center. Theophylline is a nonspecific phosphodiesterase inhibitor and is now limited to use as an adjunctive agent. Theophylline has a narrow therapeutic window with significant adverse effects, including anxiety, tremors, insomnia, nausea, cardiac arrhythmia (particularly multifocal atrial tachycardia), and seizures. It is reserved for patients with hard-tocontrol COPD or for individuals who are not able to use inhaled agents effectively. Theophylline is metabolized primarily via the hepatic cytochrome P450 system, a process affected by age, cardiac status, and liver abnormalities. Serum levels of theophylline need to be monitored because of the potential for toxicity. The previously recommended target range of 15-20 mg/dL has now been reduced to 8-13 mg/dL.

Cilomilast (Ariflo) and roflumilast are secondgeneration, selective phosphodiesterase-4 inhibitors. They cause a reduction of the inflammatory process (macrophages and CD8+ lymphocytes) in patients with COPD. Cilomilast is completely absorbed following oral administration and has a half-life of approximately 6.5 hours. A dose of 15 mg twice daily has been found to be clinically effective. Nausea, presumably of central origin, is the principal adverse reaction. Preliminary clinical studies suggest a favorable clinical effect in COPD; these results need to be confirmed in larger trials.

Smoking Cessation
Smoking cessation continues to be the most important therapeutic intervention for COPD. Most patients with COPD have a history of smoking or are currently smoking tobacco products. A smoking cessation plan is an essential part of a comprehensive management plan. However, the success rates for cessation programs are low because of the addictive power of nicotine. These rates can also be negatively impacted by such factors as conditioned responses to smoking-associated stimuli, poor education, forceful promotional campaigns by the tobacco industry, and psychological problems, including depression. The process of smoking cessation typically requires multiple interventional approaches, including both pharmacologic and non-pharmacologic modalities, and will likely require multiple attempts to maintain success.

Management of Inflammation
Inflammation plays a significant role in the pathogenesis of COPD. Systemic and inhaled corticosteroids attempt to temper this inflammation and positively alter the course of disease. The use of systemic steroids in the treatment of acute exacerbations is widely accepted and recommended, given their high efficacy. A meta-analysis concluded that oral and parenteral corticosteroids significantly reduced treatment failure and the need for additional medical treatment and that they increased the rate of improvement in lung function and dyspnea over the first 72 hours.Note that systemic steroids are not as effective in treating COPD exacerbations as they are in treating bronchial asthma exacerbations.

On the other hand, the use of oral steroids in persons with chronic stable COPD is widely discouraged, given their adverse effects, which include hypertension, glucose intolerance, osteoporosis, fractures, and cataracts.

Inhaled corticosteroids provide a more direct route of administration to the airways and, similar to other inhaled agents, are only minimally absorbed. Consequently, aside from the development of thrush, the systemic adverse effects of these medications at standard doses are negligible. Despite the theoretical benefit, the current consensus is that inhaled corticosteroids do not decrease the decline in FEV1, although they have been shown to decrease the frequency of exacerbations and improve quality of life for symptomatic patients with an FEV1 of less than 50%.[56] The 2011 ICSI guidelines conclude that inhaled steroids are appropriate in patients with recurrent exacerbations of COPD

Inhaled corticosteroids are not recommended as monotherapy and should be added to a regimen that already includes a long-acting bronchodilator. The Towards a Revolution in COPD Health (TORCH) trial showed that a combination of an inhaled corticosteroid and a long-acting beta agonist was more beneficial than inhaled corticosteroids alone.[57] These data suggest that in patients with COPD, inhaled corticosteroids should be used only in conjunction with a long-acting beta agonist.

Intravenous steroids are often used in high doses for acute exacerbations in the inpatient setting; recent research suggests that there is likely no benefit of IV over oral steroid formulations in acute exacerbations, and thus IV steroids should be reserved only for those patients unable to tolerate oral intake.

Management of Infection
In patients with COPD, chronic infection or colonization of the lower airways is common from S pneumoniae, H influenzae, and M catarrhalis. In patients with chronic severe airway obstruction, P aeruginosa infection may also be prevalent. The use of antibiotics for the treatment of acute exacerbations is well supported.[20] Patients who benefited most from antibiotic therapy were those with exacerbations that were characterized by at least 2 of the following: increases in dyspnea, sputum production, and sputum purulence (The Winnipeg criteria). No evidence supports the continuous or prophylactic use of antibiotics to prevent exacerbations.

Empiric antimicrobial therapy is recommended in patients with an acute exacerbation (as evidenced by an increase in baseline dyspnea and/or a change in the quantity or quality of cough) and evidence of an infectious process, such as fever, leukocytosis, or an infiltrate on chest radiograph. The antibiotic choice must be comprehensive and should cover all likely pathogens in the context of the clinical setting and local resistance patterns.

Management of Sputum Viscosity and Secretion Clearance


Mucolytic agents reduce sputum viscosity and improve secretion clearance. The oral agent N -acetylcysteine has antioxidant and mucokinetic properties and is used to treat patients with COPD. However, the efficacy of mucolytic agents in the treatment of COPD remains controversial. Although they have been shown to decrease cough and chest discomfort, they have not been shown to improve dyspnea or lung function, and they have also been shown to elicit bronchospasm. When used as an inhalational therapy, N acetylcysteine should be administered along with a bronchodilator such as albuterol in order to counteract potential induction of bronchospasm.

Oxygen Therapy and Hypoxemia


COPD is commonly associated with progressive hypoxemia. Oxygen administration reduces mortality rates in patients with advanced COPD because of the favorable effects on pulmonary hemodynamics. Long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD, according to 2 landmark trials, the British Medical Research Council (MRC) study and the US National Heart, Lung and Blood Institutes Nocturnal Oxygen Therapy Trial (NOTT). Hypoxemia is defined as PaO2 (partial pressure of oxygen in arterial blood) of less than 55 mm Hg or oxygen saturation of less than 90%. Oxygen was used for 15-19 hours per day

Therefore, specialists recommend long-term oxygen therapy for patients with a PaO2 of less than 55 mm Hg, a PaO2 of less than 59 mm Hg with evidence of polycythemia, or cor pulmonale. Reevaluate these patients 1-3 months after initiating therapy, because some patients may not require long-term oxygen. Many patients with COPD who are not hypoxemic at rest worsen during exertion. Home supplemental oxygen commonly is prescribed for these patients. Oxygen supplementation during exercise can prevent increases in pulmonary artery pressure, reduce dyspnea, and improve exercise tolerance.

The continuous-flow nasal cannula is the standard means of oxygen delivery for the stable hypoxemic patient. It is simple, reliable, and generally well tolerated. Each liter of oxygen flow adds 3-4% to the fraction of inspired oxygen (FiO2). Nasal oxygen delivery also is beneficial for most mouth-breathing patients. Humidification generally is not necessary when the patient receives oxygen by nasal cannula at flows of less than 5 L/min

Treatment for acute exacerbation of COPD


Acute exacerbation (AE) COPDs are a major reason for hospital admission in the United States, although mild episodes may be treated in an outpatient setting. Indications for admission include failure of outpatient treatment, marked increase in dyspnea, altered mental status, increase in hypoxemia or hypercapnia, and inability to tolerate oral medications such as antibiotics or steroids. Care must be taken to evaluate for other conditions that may mimic AECOPD.

Patients with COPD are susceptible to many insults that can lead rapidly to an acute deterioration superimposed on chronic disease. AECOPDan important, but occasionally overlooked, parameteris defined as worsening of cough, increase in sputum production, change in sputum quality, and increase in dyspnea. AECOPDs are very common, affecting about 20% of patients with moderate to severe COPD. Quick and accurate recognition of these patients, along with aggressive and prompt intervention, may be the only action that prevents frank respiratory failure. Care must also be taken to evaluate for other conditions that may mimic acute exacerbations of COPD. evaluate for other conditions that may mimic acute exacerbations of COPD.