Chronic Obstructive Pulmonary Disease (COPD)

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Chronic obstructive pulmonary disease (COPD) is estimated to affect 32 million persons in the United States and is the third leading cause of death in this country. ^[1] Patients typically have symptoms of chronic bronchitis and emphysema, but the classic triad also includes asthma or a combination of the above (see the image below).

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 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.

Patients typically present with a combination of signs and symptoms of chronic bronchitis, emphysema, and reactive airway disease. Symptoms include the following:

Cough, usually worse in the mornings and productive of a small amount of colorless sputum

Breathlessness: The most significant symptom, but usually does not occur until the sixth decade of life

Wheezing: May occur in some patients, particularly during exertion and exacerbations

While the sensitivity of physical examination in detecting mild-to-moderate COPD is relatively poor, the physical signs are quite specific and sensitive for severe disease. Findings in severe disease include the following:

Tachypnea and respiratory distress with simple activities

Use of accessory respiratory muscles and paradoxical indrawing of lower intercostal spaces (Hoover sign)

Cyanosis

Elevated jugular venous pulse (JVP)

Peripheral edema

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

Coarse crackles beginning with inspiration in some cases

Certain characteristics allow differentiation between disease that is predominantly chronic bronchitis and that which is predominantly emphysema. 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

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

See Clinical Presentation for more detail.

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. Criteria for assessing the severity of airflow obstruction (based on the percent predicted postbronchodilator FEV₁) are as follows:

Stage I (mild): FEV₁ 80% or greater of predicted

Stage II (moderate): FEV₁ 50-79% of predicted

Stage III (severe): FEV₁ 30-49% of predicted

Stage IV (very severe): FEV₁ less than 30% of predicted or FEV₁ less than 50% and chronic respiratory failure

Arterial blood gas (ABG) findings are as follows:

ABGs provide 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

pH usually is near normal; a pH below 7.3 generally indicates acute respiratory compromise

Chronic respiratory acidosis leads to compensatory metabolic alkalosis

In patients with emphysema, frontal and lateral chest radiographs reveal the following:

Flattening of the diaphragm

Increased retrosternal air space

A long, narrow heart shadow

Rapidly tapering vascular shadows accompanied by hyperlucency of the lungs

Radiographs in patients with chronic bronchitis show increased bronchovascular markings and cardiomegaly

Advantages of high-resolution CT include the following:

Greater sensitivity than standard chest radiography

High specificity for diagnosing emphysema (outlined bullae are not always visible on a radiograph)

May provide an adjunctive means of diagnosing various forms of COPD (eg, lower lobe disease may suggest alpha1-antitrypsin (AAT) deficiency

May help the clinician determine whether surgical intervention would benefit the patient

Other tests are as follows:

Hematocrit – Patients with polycythemia (hematocrit greater than 52% in men or 47% in women) should be evaluated for hypoxemia at rest, with exertion, or during sleep

Serum potassium – Diuretics, beta-adrenergic agonists, and theophylline act to lower potassium levels

Measure AAT in all patients younger than 40 years, in those with a family history of emphysema at an early age, or with emphysematous changes in a nonsmoker (also see Alpha1-Antitrypsin Deficiency).

Sputum evaluation will show a transformation from mucoid in stable chronic bronchitis to purulent in acute exacerbations

Pulse oximetry, combined with clinical observation, provides instant feedback on a patient’s status

Electrocardiography can help establish that hypoxia is not resulting in cardiac ischemia and that the underlying cause of respiratory difficulty is not cardiac in nature

The distance walked in 6 minutes (6MWD) is a good predictor of all-cause and respiratory mortality in patients with moderate COPD ^{[2, 3]} ; patients with COPD who desaturate during the 6MWD have a higher mortality rate than do those who do not desaturate

Two-dimensional echocardiography can screen for pulmonary hypertension

Right-sided heart catheterization can confirm pulmonary artery hypertension and gauge the response to vasodilators

See Workup for more detail.

Smoking cessation continues to be the most important therapeutic intervention for COPD. Risk factor reduction (eg, influenza vaccine) is appropriate for all stages of COPD. Approaches to management by stage include the following:

Stage I (mild obstruction): Short-acting bronchodilator as needed

Stage II (moderate obstruction): Short-acting bronchodilator as needed; long-acting bronchodilator(s); cardiopulmonary rehabilitation

Stage III (severe obstruction): 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): 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 lung volume reduction surgery (LVRS) and lung transplantation

Agents used include the following:

Short-acting beta₂ -agonist bronchodilators (eg, albuterol, metaproterenol, levalbuterol, pirbuterol)

Long-acting beta₂ -agonist bronchodilators (eg, salmeterol, formoterol, arformoterol, indacaterol, vilanterol)

Respiratory anticholinergics (eg, ipratropium, tiotropium, aclidinium, revefenacin)

Xanthine derivatives (ie, theophylline)

Phosphodiesterase-4 Inhibitors (ie, roflumilast)

Inhaled corticosteroids (eg, fluticasone, budesonide): Peripheral blood eosinophil counts may help stratify the likelihood of efficacy.

Oral corticosteroids (eg, prednisone)

Beta₂ -agonist and anticholinergic combinations (eg, ipratropium and albuterol, umeclidinium bromide/vilanterol inhaled)

Beta₂ -agonist and corticosteroid combinations (eg, budesonide/formoterol, fluticasone and salmeterol, vilanterol/fluticasone inhaled)

Pulmonary rehabilitation programs are typically multidisciplinary approaches that emphasize the following:

Patient and family education

Smoking cessation

Medical management (including oxygen and immunization)

Respiratory and chest physiotherapy

Physical therapy with bronchopulmonary hygiene, exercise, and vocational rehabilitation

Psychosocial support

Indications for admission for acute exacerbations include the following:

Failure of outpatient treatment

Marked increase in dyspnea

Altered mental status

Increase in hypoxemia or hypercapnia

Inability to tolerate oral medications such as antibiotics or steroids

See Treatment and Medication for more detail.

Chronic obstructive pulmonary disease (COPD) is estimated to affect 32 million persons in the United States and is the third leading cause of death in the United States. ^[1] Patients typically have symptoms of chronic bronchitis and emphysema, but the classic triad also includes asthma (as seen in the image below). (See Clinical Presentation.)

In Western Europe, Badham (1808) and Laennec (1827) made the classic descriptions of chronic bronchitis and emphysema in the early 19th century. A British medical textbook of the 1860s described the familiar clinical picture of chronic bronchitis as an advanced disease with repeated bronchial infections that ended in right-sided heart failure. Overall, this malady caused more than 5% of all deaths in the Middle Ages and earlier. The condition was most common among the poor; therefore, it was attributed to “bad” living.

Developments in the 20th century included the widespread use of spirometry (see Workup), recognition of airflow obstruction as a key factor in determining disability, and the improvement of pathologic methods to assess emphysema. Participants in the Ciba symposium of 1958 proposed definitions of chronic bronchitis and emphysema, incorporating the concept of airflow obstruction.

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 and decrease in airway tethering, 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 between the spectrum of these two conditions.

Past guidelines of COPD have been pessimistic at best, indicating that the disease process is irreversible and that therapy has little to offer. However, a more optimistic view has come to be widely accepted. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines define COPD as a disease state characterized by airflow limitation that is not fully reversible, is usually progressive, and is associated with an abnormal inflammatory response of the lungs to inhaled noxious particles or gases, ^[4] (See Clinical Presentation.)

Oral and inhaled medications are used for patients with stable COPD to reduce dyspnea, improve exercise tolerance, and prevent complications. Most of the medications used in COPD treatment are directed at the potentially reversible mechanisms of airflow limitation. (See Medication.)

Pathologic changes in chronic obstructive pulmonary disease (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.

The primary offender has been found to be human leukocyte elastase, with synergistic roles suggested for proteinase-3 and macrophage-derived matrix metalloproteinases (MMPs), cysteine proteinases, and a plasminogen activator. Additionally, increased oxidative stress caused by free radicals in cigarette smoke, the oxidants released by phagocytes, and polymorphonuclear leukocytes all may lead to apoptosis or necrosis of exposed cells. Accelerated aging and autoimmune mechanisms have also been proposed as having roles in the pathogenesis of COPD. ^{[5, 6]}

Cigarette smoke causes neutrophil influx, which is required for the secretion of MMPs; this suggests, therefore, that neutrophils and macrophages are required for the development of emphysema.

Studies have also shown that in addition to macrophages, T lymphocytes, particularly CD8⁺, play an important role in the pathogenesis of smoking-induced airflow limitation.

To support the inflammation hypothesis further, a stepwise increase in alveolar inflammation has been found in surgical specimens from patients without COPD versus patients with mild or severe emphysema. Indeed, mounting evidence supports the concept that dysregulation of apoptosis and defective clearance of apoptotic cells by macrophages play a prominent role in airway inflammation, particularly in emphysema. ^[7] Azithromycin (Zithromax) has been shown to improve this macrophage clearance function, providing a possible future treatment modality. ^[8]

In patients with stable COPD without known cardiovascular disease, there is a high prevalence of microalbuminuria, which is associated with hypoxemia independent of other risk factors. ^[9]

Mucous gland hyperplasia (as seen in the images below) 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.”

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 (as seen in the images below). The apical bullae may cause pneumothorax. Paraseptal emphysema is not associated with airflow obstruction.

The gradual destruction of alveolar septae (shown in the image below) 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 also suffers from tissue hypoxia and pulmonary cachexia. Eventually, these patients develop muscle wasting and weight loss and are identified as “pink puffers.”

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.

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. ^{[10, 11, 12, 13, 14, 15, 16, 17]} 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). ^[7]

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. ^[18] These changes can be detected by body plethysmography and diffusing capacity measurement with routine spirometry.

COPD does occur in individuals who have never smoked. ^[19] 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. ^[20]

Airway hyperresponsiveness (ie, Dutch hypothesis) 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 data regarding the possible role of airway hyperresponsiveness as a risk factor for the development of COPD in people who smoke are unclear. It is important to note, however, that 60% demonstrate bronchial hyperresponsiveness. ^[21] 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 (AAT) is a glycoprotein member of the serine protease inhibitor family that is synthesized in the liver and is secreted into the bloodstream. The main purpose of this 394-amino-acid, single-chain 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. To see complete information on Alpha1-Antitrypsin Deficiency, please go to the main article by clicking here.

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.

Nearly 24 variants of the AAT molecule have been identified, and all are inherited as codominant alleles. The most common M allele (PiM) may be found in 90% of people, and homozygous (PiMM) phenotypes produce serum levels within the reference range. The homozygous PiZZ state is the most common deficiency state and accounts for 95% of people in the severely deficient category.

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.

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. ^[22]

Apical and cortical bullous lung damage occurs in patients who have autoimmune deficiency syndrome and Pneumocystis carinii infection. Reversible pneumatoceles are observed in 10-20% of patients with this infection.

Hypocomplementemic vasculitis urticaria syndrome (HVUS) may be associated with obstructive lung disease. Other manifestations include angioedema, nondeforming arthritis, sinusitis, conjunctivitis, and pericarditis.

Cutis laxa is a disorder of elastin that is characterized most prominently by the appearance of premature aging. The disease usually is congenital, with various forms of inheritance (ie, dominant, recessive). Precocious emphysema has been described in association with cutis laxa as early as the neonatal period or infancy. The pathogenesis of this disorder includes a defect in the synthesis of elastin or tropoelastin.

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.

Salla disease is an autosomal recessive storage disorder described in Scandinavia; the disease is characterized by intralysosomal accumulation of sialic acid in various tissues. The most important clinical manifestations are severe mental retardation, ataxia, and nystagmus. Precocious emphysema has been described and likely is secondary to impaired inhibitory activity of serum trypsin.

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. ^[23] 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. ^[24] 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%. ^[25] 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.

Hannover, 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. As noted above, these reports are widely believed to be underestimates because COPD is known to be underdiagnosed and undertreated. Additionally, the prevalence in women is believed to be increasing.

Although current rates of COPD in men are higher than the rates in women, the rates in women have been increasing. COPD occurs predominantly in individuals older than age 40 years.

Severe, early onset disease likely represents a distinct genotype and is more commonly seen in females, African Americans, and those with a maternal family history of COPD. ^[26]

A study by Mintz et al estimated the prevalence of unidentified COPD. ^[27] Using the Lung Function Questionnaire (LFQ) and spirometry results, the study determined that approximately 1 in 5 patients (21%) aged 30 years or older with a history of smoking for 10 years or longer seen in a primary care center is likely to have COPD.

COPD is the third leading cause of death in the United States. ^[1] In terms of COPD as the underlying cause of death, absolute mortality rates for US patients aged 25 years or older (2005) were 77.3 deaths per 100,000 males and 56.0 deaths per 100,000 females, or 64.3 persons per 100,000 overall. Internationally, overall mortality rates from COPD vary markedly, from more than 400 deaths per 100,000 males aged 65-74 years in Romania to fewer than 100 deaths per 100,000 population in Japan.

The FEV₁ was used to predict outcome in COPD until other factors were identified to play a role in determining the outcome of COPD patients. These discoveries resulted in the creation of the multidimensional BODE index (body mass index, obstruction [FEV₁], dyspnea [modified Medical Research Council dyspnea scale], and exercise capacity [6MWD]). ^[28] This index was developed to assess an individual’s risk of death or hospitalization.

Prognosis is based on a point system, with all 4 factors used to determine the score, as follows:

Body mass index: greater than 21 = 0 points; less than 21 = 1 point

FEV₁ (postbronchodilator percent predicted): greater than 65% = 0 points; 50-64% = 1 point; 36-49% = 2 points; less than 35% = 3 points

Modified Medical Research Council (MMRC) dyspnea scale: MMRC 0 = dyspneic on strenuous exercise (0 points); MMRC 1 = dyspneic on walking a slight hill (0 points); MMRC 2 = dyspneic on walking level ground, must stop occasionally due to breathlessness (1 point); MMRC 3 = dyspneic after walking 100 yards or a few minutes (2 points); MMRC 4 = cannot leave house; dyspneic doing activities of daily living (3 points)

Six-minute walking distance: greater than 350 meters = 0 points; 250-349 meters = 1 point; 150-249 meters = 2 points; less than 149 meters = 3 points

The approximate 4-year survival based on the point system above is as follows:

0-2 points = 80%

3-4 points = 67%

5-6 points = 57%

7-10 points = 18%

The use of a clinical scoring system reinforces that determinants of prognosis in COPD remain multifactorial. Waschki et al argued that objective assessments of physical activity, including 6-minute walk test results, are best able to predict mortality. ^[29] However, additional socioeconomic factors also likely play a role in COPD prognosis; for example, a retrospective cohort study highlighted the increased risk of COPD-related mortality in patients who reside in isolated rural areas. ^[30]

A study by Sundh et al determined that the Clinical COPD Questionnaire (CCQ), which estimates quality of life in patients with COPD, is effective. ^[31] The CCQ identified that heart disease, depression, and underweight status are independently associated with lower health-related quality of life in patients with COPD.

In a multicenter, prospective, observational study of 201 consecutive patients with moderate-to-severe COPD, Martinez-Garcia et al reported that in addition to smoking, pulmonary hypertension, and declining lung function (known risk factors for mortality in patients with COPD), ^[32] bronchiectasis (which is common in patients with moderate-to-severe COPD) is independently associated with increased risk of all-cause mortality. ^{[32, 33]}

In this study, those who had bronchiectasis were found to be 2.5 times more likely to die than those who did not. ^[33] Bronchiectasis remained an independent factor after adjustment for dyspnea, partial pressure of oxygen, body mass index, presence of potentially pathogenic microorganisms in sputum, presence of daily sputum production, number of severe exacerbations and peripheral albumin, and ultrasensitive C-reactive protein concentrations.

It is important to educate the patient with COPD about the disease and to encourage his or her active participation in therapy. The 2 most essential points for the patient to understand are as follows:

The dangers of smoking and the improvement in quality of life attainable with smoking cessation

The need to seek medical care early during an exacerbation and to not wait until they are in distress

For more information, see Emphysema.

Brooks M. FDA Clears Olodaterol (Striverdi Respimat) for COPD. Medscape Medical News. Available at http://www.medscape.com/viewarticle/829248. Accessed: August 4, 2014.

Maclay JD, Rabinovich RA, MacNee W. Update in chronic obstructive pulmonary disease 2008. Am J Respir Crit Care Med. 2009 Apr 1. 179(7):533-41. [Medline].

Casanova C, Cote C, Marin JM, Pinto-Plata V, de Torres JP, Aguirre-Jaime A, et al. Distance and oxygen desaturation during the 6-min walk test as predictors of long-term mortality in patients with COPD. Chest. 2008 Oct. 134(4):746-52. [Medline].

[Guideline] Global strategy for diagnosis, management, and prevention of COPD: 2016. Global Initiative for Chronic Obstructive Lung Disease. Available at http://goldcopd.org/gold-reports/ . Accessed: May 7, 2016.

Feghali-Bostwick CA, Gadgil AS, Otterbein LE, Pilewski JM, Stoner MW, Csizmadia E. Autoantibodies in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. Jan 15 2008. 177(2):156-63.

Houben JM, Mercken EM, Ketelslegers HB, Bast A, Wouters EF, Hageman GJ. Telomere shortening in chronic obstructive pulmonary disease. Respir Med. 2009 Feb. 103(2):230-6. [Medline].

Morissette MC, Vachon-Beaudoin G, Parent J, Chakir J, Milot J. Increased p53 level, Bax/Bcl-x(L) ratio, and TRAIL receptor expression in human emphysema. Am J Respir Crit Care Med. 2008 Aug 1. 178(3):240-7. [Medline].

Hodge S, Hodge G, Jersmann H, Matthews G, Ahern J, Holmes M, et al. Azithromycin improves macrophage phagocytic function and expression of mannose receptor in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008 Jul 15. 178(2):139-48. [Medline].

Casanova C, de Torres JP, Navarro J, Aguirre-Jaime A, Toledo P, Cordoba E, et al. Microalbuminuria and hypoxemia in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010 Oct 15. 182(8):1004-10. [Medline].

Ofir D, Laveneziana P, Webb KA, Lam YM, O’Donnell DE. Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage I chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008 Mar 15. 177(6):622-9. [Medline].

Belman MJ, Botnick WC, Shin JW. Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996 Mar. 153(3):967-75. [Medline].

O’Donnell DE, Lam M, Webb KA. Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Aug. 160(2):542-9. [Medline].

Marin JM, Carrizo SJ, Gascon M, Sanchez A, Gallego B, Celli BR. Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 May. 163(6):1395-9. [Medline].

O’Donnell DE, Fluge T, Gerken F, Hamilton A, Webb K, Aguilaniu B. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004 Jun. 23(6):832-40. [Medline].

Martinez FJ, de Oca MM, Whyte RI, Stetz J, Gay SE, Celli BR. Lung-volume reduction improves dyspnea, dynamic hyperinflation, and respiratory muscle function. Am J Respir Crit Care Med. 1997 Jun. 155(6):1984-90. [Medline].

Celli BR. Update on the management of COPD. Chest. 2008 Jun. 133(6):1451-62. [Medline].

Casanova C, Cote C, de Torres JP, Aguirre-Jaime A, Marin JM, Pinto-Plata V. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 Mar 15. 171(6):591-7. [Medline].

Nagelmann A, Tonnov A, Laks T, Sepper R, Prikk K. Lung Dysfunction of Chronic Smokers with No Signs of COPD. COPD. 2011 Apr 22. [Medline].

Lamprecht B, McBurnie MA, Vollmer WM, Gudmundsson G, Welte T, Nizankowska-Mogilnicka E, et al. COPD in Never Smokers: Results From the Population-Based Burden of Obstructive Lung Disease Study. Chest. 2011 Apr. 139(4):752-763. [Medline].

Andersen ZJ, Hvidberg M, Jensen SS, Ketzel M, Loft S, Sorensen M, et al. Chronic obstructive pulmonary disease and long-term exposure to traffic-related air pollution: a cohort study. Am J Respir Crit Care Med. 2011 Feb 15. 183(4):455-61. [Medline].

Tashkin DP, Altose MD, Bleecker ER, Connett JE, Kanner RE, Lee WW, et al. The lung health study: airway responsiveness to inhaled methacholine in smokers with mild to moderate airflow limitation. The Lung Health Study Research Group. Am Rev Respir Dis. 1992 Feb. 145 (2 Pt 1):301-10. [Medline].

Crothers K, Butt AA, Gibert CL, Rodriguez-Barradas MC, Crystal S, Justice AC. Increased COPD among HIV-positive compared to HIV-negative veterans. Chest. 2006 Nov. 130(5):1326-33. [Medline].

Adams PF, Barnes PM, Vickerie JL. Summary health statistics for the U.S. population: National Health Interview Survey, 2007. Vital Health Stat 10. 2008 Nov. 1-104. [Medline].

Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet. 2007 Sep 1. 370(9589):741-50. [Medline].

Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM. Global burden of COPD: systematic review and meta-analysis. Eur Respir J. 2006 Sep. 28(3):523-32. [Medline].

Foreman MG, Zhang L, Murphy J, et al. Early-Onset COPD is Associated with Female Gender, Maternal Factors, and African American Race in the COPDGene Study. Am J Respir Crit Care Med. 2011 May 11. [Medline].

Mintz ML, Yawn BP, Mannino DM, et al. Prevalence of airway obstruction assessed by lung function questionnaire. Mayo Clin Proc. 2011 May. 86(5):375-81. [Medline]. [Full Text].

Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004 Mar 4. 350(10):1005-12. [Medline].

Waschki B, Kirsten A, Holz O, et al. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest. 2011 Aug. 140(2):331-42. [Medline].

Abrams TE, Vaughan-Sarrazin M, Fan VS, Kaboli PJ. Geographic isolation and the risk for chronic obstructive pulmonary disease-related mortality: a cohort study. Ann Intern Med. 2011 Jul 19. 155(2):80-6. [Medline].

Sundh J, Stallberg B, Lisspers K, Montgomery SM, Janson C. Co-Morbidity, Body Mass Index and Quality of Life in COPD Using the Clinical COPD Questionnaire. COPD. 2011 Apr 22. [Medline].

McNamara D. Bronchiectasis Linked to Higher Mortality in COPD Patients. Medscape Medical News. February 8, 2013. [Full Text].

Martinez-Garcia MA, de la Rosa D, Soler-Cataluna JJ, Donat-Sanz Y, Catalan Serra P, Agramunt Lerma M, et al. Prognostic Value of Bronchiectasis in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2013 Feb 7. [Medline].

[Guideline] Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease: A Clinical Practice Guideline Update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2. 155(3):179-191. [Medline].

Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010 Sep 16. 363(12):1128-38. [Medline].

Casanova C, Cote C, Marin JM, Pinto-Plata V, de Torres JP, Aguirre-Jaime A, et al. Distance and oxygen desaturation during the 6-min walk test as predictors of long-term mortality in patients with COPD. Chest. 2008 Oct. 134(4):746-52. [Medline].

Spitzer C, Koch B, Grabe HJ, et al. Association of airflow limitation with trauma exposure and post-traumatic stress disorder. Eur Respir J. 2011 May. 37(5):1068-75. [Medline].

Singh B, Parsaik AK, Mielke MM, et al. Chronic obstructive pulmonary disease and association with mild cognitive impairment: the Mayo Clinic study of aging. Mayo Clin Proc. 2013 Nov. 88(11):1222-30. [Medline]. [Full Text].

Barclay L. COPD linked to cognitive impairment and memory loss. Medscape Medical News. December 12, 2013. [Full Text].

Bronchial hyperresponsiveness in cardiac failure. N Engl J Med. 1989 Dec 21. 321 (25):1756-8. [Medline].

Prosen G, Klemen P, Strnad M, Grmec S. Combination of lung ultrasound (a comet-tail sign) and N-terminal pro-brain natriuretic peptide in differentiating acute heart failure from chronic obstructive pulmonary disease and asthma as cause of acute dyspnea in prehospital emergency setting. Crit Care. 2011. 15(2):R114. [Medline].

Sin DD, Miller BE, Duvoix A, et al. Serum PARC/CCL-18 Concentrations and Health Outcomes in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2011 May 1. 183(9):1187-1192. [Medline].

Osterweil N. COPD: Clinicians Miss Myriad Chances to Spot It Early. Medscape Medical News. Available at http://www.medscape.com/viewarticle/820597. Accessed: February 18, 2014.

Miller MR, Quanjer PH, Swanney MP, Ruppel G, Enright PL. Interpreting lung function data using 80% predicted and fixed thresholds misclassifies more than 20% of patients. Chest. 2011 Jan. 139(1):52-9. [Medline].

Rice KL, Dewan N, Bloomfield HE, Grill J, Schult TM, Nelson DB, et al. Disease management program for chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med. 2010 Oct 1. 182(7):890-6. [Medline].

Dewan NA, Rice KL, Caldwell M, Hilleman DE. Economic Evaluation of a Disease Management Program for Chronic Obstructive Pulmonary Disease. COPD. 2011 Apr 22. [Medline].

Stephenson A, Seitz D, Bell CM, et al. Inhaled anticholinergic drug therapy and the risk of acute urinary retention in chronic obstructive pulmonary disease: a population-based study. Arch Intern Med. 2011 May 23. 171(10):914-20. [Medline].

Gershon A, Croxford R, Calzavara A, To T, Stanbrook MB, Upshur R, et al. Cardiovascular Safety of Inhaled Long-Acting Bronchodilators in Individuals With Chronic Obstructive Pulmonary Disease. JAMA Intern Med. 2013 May 20. 1-9. [Medline].

Wood S. Inhaled Long-Acting Bronchodilators in COPD Flagged Again for CV Hazard. Medscape Medical News. Available at http://www.medscape.com/viewarticle/804441. Accessed: June 4, 2013.

Canavan N. Dual-Action Bronchodilator Eases COPD Exacerbations. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/810739. Accessed: September 16, 2013.

Decramer ML, Chapman KR, Dahl R, et al. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study. The Lancet Respiratory Medicine. Available at http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70158-9/abstract. Accessed: October 7, 2013.

Macfarlane L. Indacaterol and Tiotropium Similar in Effect and Safety. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/811871. Accessed: October 7, 2013.

Mahler DA, Kerwin E, Ayers T, FowlerTaylor A, Maitra S, Thach C, et al. FLIGHT1 and FLIGHT2: Efficacy and Safety of QVA149 (Indacaterol/Glycopyrrolate) versus Its Monocomponents and Placebo in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2015 Nov 1. 192 (9):1068-79. [Medline].

Rabe K, Martinez F, Rodriguez-Roisin R, Fabbri LM, Ferguson GT, Jones P, et al. PT003, a novel co-suspension MDI glycopyrronium/formoterol fixed-dose combination is superior to monocomponents in patients with COPD. Eur Respir J. 2015 Sep 01. 46(suppl 59):[Full Text].

US Food and Drug Administration. FDA approves Anoro Ellipta to treat chronic obstructive pulmonary disease [press release]. December 18, 2013. Available at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm379057.htm. Accessed: December 30, 2013.

Brown T. FDA approves umeclidinium and vilanterol combo for COPD. Medscape Medical News. December 18, 2013. [Full Text].

Donohue JF, Maleki-Yazdi MR, Kilbride S, Mehta R, Kalberg C, Church A. Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Respir Med. 2013 Oct. 107(10):1538-46. [Medline].

Koch A, Pizzichini E, Hamilton A, Hart L, Korducki L, De Salvo MC. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014. 9:697-714. [Medline].

Ferguson GT, Feldman GJ, Hofbauer P, Hamilton A, Allen L, Korducki L, et al. Efficacy and safety of olodaterol once daily delivered via Respimat in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014. 9:629-45. [Medline]. [Full Text].

Casaburi R, Mahler DA, Jones PW, Wanner A, San PG, ZuWallack RL, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002 Feb. 19(2):217-24. [Medline].

Donohue JF, van Noord JA, Bateman ED, Langley SJ, Lee A, Witek TJ Jr, et al. A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest. 2002 Jul. 122(1):47-55. [Medline].

Vincken W, van Noord JA, Greefhorst AP, Bantje TA, Kesten S, Korducki L, et al. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J. 2002 Feb. 19(2):209-16. [Medline].

Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008 Oct 9. 359(15):1543-54. [Medline].

Brusasco V, Hodder R, Miravitlles M, Korducki L, Towse L, Kesten S. Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax. 2003 May. 58(5):399-404. [Medline]. [Full Text].

Vogelmeier C, Hederer B, Glaab T, Schmidt H, Rutten-van Molken MP, Beeh KM, et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med. 2011 Mar 24. 364(12):1093-103. [Medline].

Singh S, Loke YK, Enright PL, Furberg CD. Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials. BMJ. 2011 Jun 14. 342:d3215. [Medline]. [Full Text].

Jones PW, Rennard SI, Agusti A, Chanez P, Magnussen H, Fabbri L, et al. Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease. Respir Res. 2011 Apr 26. 12:55. [Medline]. [Full Text].

Hand L. FDA OKs Umeclidinium (Incruse Ellipta) for COPD. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/824419. Accessed: May 4, 2014.

Anoro Ellipta (umeclidinium and vilanterol inhalation powder) [package insert]. Research Triangle Park, NC: GlaxoSmithKline. 2013. Available at [Full Text].

Kerwin EM, Donohue JF, Sethi S, Haumann B, Pendyala S, Dean L, et al. Revefenacin, a once-daily, long-acting muscarinic antagonist for nebulized therapy of chronic obstructive pulmonary disease (COPD): Results of a 52-week safety and tolerability phase 3 trial in participants with moderate to very severe COPD (poster A4239). Presented at the American Thoracic Society 2018 International Conference. San Diego, CA. May 21, 2018. [Full Text].

Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009 Aug 29. 374(9691):685-94. [Medline].

Gifford AH, Mahler DA, Waterman LA, et al. Neuromodulatory Effect of Endogenous Opioids on the Intensity and Unpleasantness of Breathlessness during Resistive Load Breathing in COPD. COPD. 2011 Apr 22. [Medline].

Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ. 2011 May 10. 342:d2549. [Medline]. [Full Text].

Mottillo S, Filion KB, Belisle P, Joseph L, Gervais A, O’Loughlin J. Behavioural interventions for smoking cessation: a meta-analysis of randomized controlled trials. Eur Heart J. 2009 Mar. 30(6):718-30. [Medline].

Wood-Baker RR, Gibson PG, Hannay M, Walters EH, Walters JA. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2005. (1):CD001288. [Medline].

Walters JA, Walters EH, Wood-Baker R. Oral corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2005 Jul 20. CD005374. [Medline].

Spencer S, Calverley PM, Burge PS, Jones PW. Impact of preventing exacerbations on deterioration of health status in COPD. Eur Respir J. 2004 May. 23(5):698-702. [Medline].

Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007 Feb 22. 356(8):775-89. [Medline].

Sin DD, Tashkin D, Zhang X, Radner F, Sjobring U, Thoren A. Budesonide and the risk of pneumonia: a meta-analysis of individual patient data. Lancet. 2009 Aug 29. 374(9691):712-9. [Medline].

Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med. 2015 Jun. 3 (6):435-42. [Medline].

Siddiqui SH, Guasconi A, Vestbo J, Jones P, Agusti A, Paggiaro P, et al. Blood Eosinophils: A Biomarker of Response to Extrafine Beclomethasone/Formoterol in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2015 Aug 15. 192 (4):523-5. [Medline].

Bafadhel M, Peterson S, De Blas MA, Calverley PM, Rennard SI, Richter K, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. 2018 Feb. 6 (2):117-126. [Medline].

Chen D, Restrepo MI, Fine MJ, et al. Observational study of inhaled corticosteroids on outcomes for COPD patients with pneumonia. Am J Respir Crit Care Med. 2011 Aug 1. 184(3):312-6. [Medline].

Seemungal TA, Wilkinson TM, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008 Dec 1. 178(11):1139-47. [Medline].

Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011 Aug 25. 365(8):689-98. [Medline].

Daniels JM, Snijders D, de Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010 Jan 15. 181(2):150-7. [Medline].

Sasaki T, Nakayama K, Yasuda H, Yoshida M, Asamura T, Ohrui T, et al. A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc. 2009 Aug. 57(8):1453-7. [Medline].

Duiverman ML, Wempe JB, Bladder G, Jansen DF, Kerstjens HA, Zijlstra JG. Nocturnal non-invasive ventilation in addition to rehabilitation in hypercapnic patients with COPD. Thorax. 2008 Dec. 63(12):1052-7. [Medline].

Crockett AJ, Moss JR, Cranston JM, Alpers JH. Domicilary oxygen for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2000. (2):CD001744. [Medline].

Ringbaek TJ. Continuous oxygen therapy for hypoxic pulmonary disease: guidelines, compliance and effects. Treat Respir Med. 2005. 4(6):397-408. [Medline].

Sandland CJ, Morgan MD, Singh SJ. Patterns of domestic activity and ambulatory oxygen usage in COPD. Chest. 2008 Oct. 134(4):753-60. [Medline].

Lightowler JV, Wedzicha JA, Elliott MW, Ram FS. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ. 2003 Jan 25. 326(7382):185. [Medline]. [Full Text].

Carrera M, Marin JM, Anton A, Chiner E, Alonso ML, Masa JF, et al. A controlled trial of noninvasive ventilation for chronic obstructive pulmonary disease exacerbations. J Crit Care. 2009 Sep. 24(3):473.e7-14. [Medline].

Keenan SP, Kernerman PD, Cook DJ, Martin CM, McCormack D, Sibbald WJ. Effect of noninvasive positive pressure ventilation on mortality in patients admitted with acute respiratory failure: a meta-analysis. Crit Care Med. 1997 Oct. 25(10):1685-92. [Medline].

Confalonieri M, Garuti G, Cattaruzza MS, Osborn JF, Antonelli M, Conti G. A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J. 2005 Feb. 25(2):348-55. [Medline].

Hubbard RC, Crystal RG. Augmentation therapy of alpha 1-antitrypsin deficiency. Eur Respir J Suppl. 1990 Mar. 9:44s-52s. [Medline].

Hurst JR, Donaldson GC, Quint JK, Goldring JJ, Baghai-Ravary R, Wedzicha JA. Temporal clustering of exacerbations in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009 Mar 1. 179(5):369-74. [Medline].

Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003 May 22. 348(21):2059-73. [Medline].

Titman A, Rogers CA, Bonser RS, Banner NR, Sharples LD. Disease-specific survival benefit of lung transplantation in adults: a national cohort study. Am J Transplant. 2009 Jul. 9(7):1640-9. [Medline].

Burton CM, Milman N, Carlsen J, Arendrup H, Eliasen K, Andersen CB, et al. The Copenhagen National Lung Transplant Group: survival after single lung, double lung, and heart-lung transplantation. J Heart Lung Transplant. 2005 Nov. 24(11):1834-43. [Medline].

Cote CG, Celli BR. Pulmonary rehabilitation and the BODE index in COPD. Eur Respir J. 2005 Oct. 26(4):630-6. [Medline].

Dodd JW, Hogg L, Nolan J, et al. The COPD assessment test (CAT): response to pulmonary rehabilitation. A multicentre, prospective study. Thorax. 2011 May. 66(5):425-9. [Medline].

[Guideline] Guirguis-Blake JM, Senger CA, Webber EM, Mularski RA, Whitlock EP. Screening for Chronic Obstructive Pulmonary Disease: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2016 Apr 5. 315 (13):1378-93. [Medline].

[Guideline] US Preventive Services Task Force. Counseling and interventions to prevent tobacco use and tobacco-caused disease in adults and pregnant women: US Preventive Services Task Force Reaffirmation Recommendation Statement. Ann Int Med. Apr 21 2009. 150(8):551-555. [Full Text].

[Guideline] Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease 2018 Report. Goldcopd.org. Available at https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf. 2018; Accessed: October 23, 2018.

[Guideline] Management of Chronic Obstructive Pulmonary Disease Working Group. VA/DoD clinical practice guideline for the management of chronic obstructive pulmonary disease. Washington (DC): Department of Veterans Affairs, Department of Defense. Available at http://www.healthquality.va.gov/guidelines/cd/copd/. December 2014; Accessed: May 7, 2016.

[Guideline] Keenan SP, Sinuff T, Burns KE, Muscedere J, Kutsogiannis J, Mehta S, et al. Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. CMAJ. 2011 Feb 22. 183(3):E195-214. [Medline]. [Full Text].

[Guideline] Criner GJ, Bourbeau J, Diekemper RL, et al. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 2015 Apr. 147 (4):894-942. [Medline].

Mirza S, Clay RD, Koslow MA, Scanlon PD. COPD Guidelines: A Review of the 2018 GOLD Report. Mayo Clin Proc. 2018 Oct. 93 (10):1488-1502. [Medline].

[Guideline] Institute for Clinical Systems Improvement. Diagnosis and Management of Chronic Obstructive Pulmonary Disease (COPD). 10th Edition. January 2016. Available at https://www.icsi.org/guidelines__more/catalog_guidelines_and_more/catalog_guidelines/catalog_respiratory_guidelines/copd/ . Accessed: May 6, 2016.

Currow DC, McDonald C, Oaten S, Kenny B, Allcroft P, Frith P, et al. Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study. J Pain Symptom Manage. 2011 Sep. 42(3):388-99. [Medline].

Pavord ID, Chanez P, Criner GJ, Kerstjens HAM, Korn S, Lugogo N, et al. Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017 Oct 26. 377 (17):1613-1629. [Medline].

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women’s Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Annie Harrington, MD Fellow in Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center

Annie Harrington, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians

Disclosure: Nothing to disclose.

Nidhi S Nikhanj, MD Fellow, Department of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles

Nidhi S Nikhanj, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

John J Oppenheimer, MD Clinical Professor, Department of Medicine, Rutgers New Jersey Medical School; Director of Clinical Research, Pulmonary and Allergy Associates, PA

John J Oppenheimer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, New Jersey Allergy, Asthma and Immunology society

Disclosure: Received research grant from: quintiles, PRA, ICON, Novartis: Adjudication<br/>Received consulting fee from AZ for consulting; Received consulting fee from Glaxo, Myelin, Meda for consulting; Received grant/research funds from Glaxo for independent contractor; Received consulting fee from Merck for consulting; Received honoraria from Annals of Allergy Asthma Immunology for none; Partner received honoraria from ABAI for none. for: Atlantic Health System.

Ryland P Byrd Jr, MD Professor, Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, Program Director of Pulmonary Diseases and Critical Care Medicine Fellowship, East Tennessee State University, James H Quillen College of Medicine; Medical Director of Respiratory Therapy, James H Quillen Veterans Affairs Medical Center

Ryland P Byrd Jr, MD is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society

Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Chronic Obstructive Pulmonary Disease (COPD)

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