eMedicine Specialties > Pulmonology > Obstructive Airways Diseases

Emphysema

Berj George Demirjian, MD, Fellow, Division of Pulmonary/Critical Care Medicine, Cedars-Sinai Medical Center
Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center

Updated: Oct 26, 2009

Introduction

Background

Emphysema is chronic obstructive pulmonary disease (COPD). Emphysema is defined pathologically as an abnormal permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by the destruction of alveolar walls and without obvious fibrosis. Emphysema frequently occurs in association with chronic bronchitis. These 2 entities have been traditionally grouped under the umbrella term COPD. Patients have been classified as having COPD with either emphysema or chronic bronchitis predominance. The current definition of COPD put forth by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) does not distinguish between emphysema and chronic bronchitis.¹

The 3 described morphological types of emphysema are centriacinar, panacinar, and paraseptal.

Centriacinar emphysema begins in the respiratory bronchioles and spreads peripherally. Also termed centrilobular emphysema, this form is associated with long-standing cigarette smoking and predominantly involves the upper half of the lungs.

Panacinar emphysema destroys the entire alveolus uniformly and is predominant in the lower half of the lungs. Panacinar emphysema generally is observed in patients with homozygous alpha1-antitrypsin (AAT) deficiency. In people who smoke, focal panacinar emphysema at the lung bases may accompany centriacinar emphysema.

Paraseptal emphysema, also known as distal acinar emphysema, preferentially involves the distal airway structures, alveolar ducts, and alveolar sacs. The process is localized around the septae of the lungs or pleura. Although airflow frequently is preserved, the apical bullae may lead to spontaneous pneumothorax. Giant bullae occasionally cause severe compression of adjacent lung tissue.

Gross pathology of bullous emphysema shows bullae on the surface of the lungs.

Gross pathology of emphysema shows bullae on the lung surface.

Pathophysiology

Emphysema is a pathological 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 commonly presents with chronic bronchitis. Chronic bronchitis leads to obstruction by causing narrowing of both the large and small (<2 mm) airways. In the large airways, an increase in Goblet cells, squamous metaplasia of ciliary epithelial cells, and loss of serous acini can be seen. In the small airways, Goblet cell metaplasia, smooth muscle hyperplasia, and subepithelial fibrosis can be seen. In healthy individuals, small airways contribute little to airway resistance; however, in COPD patients, these become the main site of airflow limitation.

Pathogenesis

Most of 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.¹ Genetics are believed to play a role in this response because not all smokers develop the disease. The cellular composition of airway inflammation is predominantly mediated by neutrophils, macrophages, and lymphocytes. These cells release chemotactic factors to recruit more cells (proinflammatory cytokines that amplify the inflammation) and growth factors that promote structural change. The inflammation is further amplified by oxidative stress and protease production. Oxidants are produced from cigarette smoke and released from inflammatory cells. Proteases are produced by inflammatory and epithelial cells. This leads to a protease-antiprotease imbalance that leads to destruction of elastin and other structural elements. This is believed to be central in the development of emphysema.

Alpha1-antitrypsin deficiency

AAT is a glycoprotein member of the serine protease inhibitor family that is synthesized in the liver and is secreted into the blood stream. 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.

Deficiency of AAT is inherited as an autosomal codominant condition. The gene is located on the long arm of chromosome 14 and has been sequenced and cloned. The most common type of severe AAT deficiency occurs in individuals who are homozygous for the Z-type protein. Homozygous individuals (PIZZ) have serum levels well below the reference range levels (reference range, 20-53 mmol/L). The risk of emphysema occurs below a threshold of 11 mmol/L.

Frequency

United States

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.² While the rate of emphysema has stayed largely unchanged since 2000, the rate of chronic bronchitis has decreased. This prevalence is based on the number of adults who have ever been told by any health care provider that they have emphysema or chronic bronchitis. This is felt to be an underestimate because most patients do not present for medical care until the disease is in a late stage.

International

The Burden of Obstructive Lung Disease (BOLD) study showed that the worldwide prevalence of COPD (stage II or higher) was 10.1%.³ This figure varied by geographic location and by sex. Pooled prevalence among men was 11.8% (8.6-22.2%) and among women was 8.5% (5.1-16.7%). The differences can, in part, be explained by site and sex differences in the prevalence of smoking. These rates are similar to rates observed in the Proyecto Latino Americano de Investigacion en Obstruccion Pulmonar (PLATINO study), which studied 5 countries in Latin America.⁴

Mortality/Morbidity

A US Centers for Disease Control and Prevention (CDC) Morbidity Mortality Weekly Report study of the National Vital Statistics System reported an age-standardized death rate from COPD in the United States for adults older than 25 years of 64.3 deaths per 100,000 population.⁵ This rate varied by location, with the lowest rate in Hawaii (27.1 deaths per 100,000 population) and the highest rate in Oklahoma (93.6 deaths per 100,000 population).

Sex

In the past, COPD was more prevalent among men. This was attributed to the difference in smoking rates in men versus women. With the increase in smoking among women, the difference has declined. Some studies have suggested women may be more susceptible to COPD.⁶

Clinical

History

Most patients 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 phlegm production. With retroactive questioning, a multiyear history can be elicited.

• Commonly, patients present in their fifth decade of life with productive cough or acute chest illness. The cough usually is worse in the morning and produces small amounts of colorless sputum from concomitant chronic bronchitis.
• Breathlessness, the most significant symptom, does not occur until the sixth decade of life. By the time the forced expiratory volume in 1 second (FEV₁) has fallen to 50% of predicted, the patient is breathless upon minimal exertion.
• Wheezing may occur in some patients, particularly during exertion and exacerbations.

Physical

The sensitivity of the physical evaluation in mild-to-moderate disease is relatively poor. However, the physical signs are quite sensitive and specific for severe disease. Patients with severe disease experience tachypnea and respiratory distress with simple activities.

• The respiratory rate increases in proportion to disease severity. The use of accessory respiratory muscles and paradoxical indrawing of lower intercostal spaces are evident.
• In advanced disease, cyanosis, elevated jugular venous pressure, and peripheral edema can be observed.
• Measurement of the forced expiratory time maneuver is a simple bedside test; a forced expiratory time greater than 6 seconds indicates severe expiratory airflow obstruction.
• Thoracic examination reveals hyperinflation (ie, barrel chest), wheezing, diffusely decreased breath sounds, hyperresonance upon percussion, and prolonged expiration.

Causes

• Cigarette smoking: Smoking is by far the single most clearly established environmental risk factor for emphysema and chronic bronchitis. One in 5 persons who smoke develops COPD, and 80-90% of COPD patients have a smoking history.
• AAT deficiency syndrome: This syndrome leads to protease-antiprotease imbalance and unopposed action of neutrophil elastases.
• Persons who use intravenous drugs
  • Emphysema occurs in approximately 2% of persons who use intravenous drugs and 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 intravenous use of cocaine or heroin occur predominantly in the upper lobes. In contrast, methadone and methylphenidate injections are associated with basilar and panacinar emphysema.
• Immune deficiency syndromes
  • Human immunodeficiency virus (HIV) infection was found to be an independent risk factor for COPD, even after controlling for confounding variables such as smoking, intravenous drug use, race, and age.⁷
  • 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.
• Vasculitis syndrome
  • Hypocomplementemic vasculitis urticaria syndrome (HVUS) may be associated with obstructive lung disease.
  • Other symptoms include angioedema, nondeforming arthritis, sinusitis, conjunctivitis, and pericarditis.
• Connective-tissue disorders
  • 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.
• Salla disease
  • 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.

Differential Diagnoses

Bronchiectasis
Bronchitis
Chronic Bronchitis
Lymphangioleiomyomatosis

Other Problems to Be Considered

Common alternative diagnoses and suggestive diagnostic features

Congestive heart failure: This condition may produce wheezing and often may be difficult to differentiate from emphysema. However, a history of orthopnea and paroxysmal nocturnal dyspnea, the presence of fine basal crackles, and typical findings on chest radiographs can lead to the diagnosis of congestive heart failure.

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: Obliterative bronchiolitis 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 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.

Workup

Laboratory Studies

• Arterial blood gas analysis: Patients with mild chronic obstructive pulmonary disease (COPD) have mild-to-moderate hypoxemia without hypercapnia. As the disease progresses, hypoxemia worsens and hypercapnia develops.
• Hematocrit value: Chronic hypoxemia may lead polycythemia. A hematocrit value greater than 52% in men and greater than 47% in women is indicative of the condition. Patients should be evaluated for hypoxemia at rest, with exertion, or during sleep. Correction of hypoxemia should reduce secondary polycythemia in patients who have quit smoking.
• Bicarbonate value: 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 level: Of the approximately 75 different alleles for alpha1-antitrypsin (AAT) deficiency variants, 10-15 are associated with serum levels below the protective threshold of 11 mmol/L. The most common severe variant is the Z allele, which accounts for 95% of the clinically recognized cases of severe AAT deficiency. The diagnosis of severe AAT deficiency is confirmed when the serum level falls below the protective threshold value (ie, 3-7 mmol/L). Specific phenotyping is reserved for patients in whom serum levels are 7-11 mmol/L or when genetic counseling or family analysis is needed.
• Sputum evaluation: In patients with stable chronic bronchitis, the sputum is mucoid and the predominant cells are macrophages. With an exacerbation, the sputum becomes purulent, with excessive neutrophils and a mixture of organisms visualized through Gram staining. Streptococcus pneumoniae and Haemophilus influenzae are pathogens frequently cultured during exacerbations.

Imaging Studies

• Chest radiography
  • Frontal and lateral chest radiographs reveal signs of hyperinflation, which involves flattening of diaphragms, increased retrosternal air space, and a long narrow heart shadow.
  • Rapid tapering vascular shadows accompanied by hyperlucency of the lungs are signs of emphysema.
  • With complicating pulmonary hypertension, the hilar vascular shadows are prominent; with right ventricular enlargement, opacity in the lower retrosternal air space may occur.

Chest radiograph shows hyperinflation, flattened diaphragms, increased retrosternal space, and hyperlucency of the lung parenchyma in emphysema.

An emphysematous lung shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on posteroanterior (PA) film.

An emphysematous lung shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on lateral chest radiograph.

The differential diagnosis of unilateral hyperlucent lung includes pulmonary arterial hypoplasia and Swyer-James syndrome. The expiratory chest radiograph exhibits evidence of air trapping and is helpful in making the diagnosis. Swyer-James syndrome is unilateral bronchiolitis obliterans, which develops during early childhood.

Lateral chest radiograph of Swyer-James syndrome may demonstrate some of the features of emphysema.

• CT scanning: High-resolution CT (HRCT) scanning is more sensitive than standard chest radiography. HRCT scanning is highly specific for diagnosing emphysema and outlines bullae that are not always observed on radiographs. A CT scan is indicated when the patient is being considered for a surgical intervention such as bullectomy or lung-volume reduction surgery. A CT scan is not indicated in the routine care of patients with COPD.

A CT scan shows emphysematous bullae in upper lobes.

Diffuse emphysema secondary to cigarette smoking.

A CT scan showing severe emphysema and bullous disease.

Other Tests

• Pulmonary function tests
  • These measurements are necessary for the diagnosis of obstructive airway disease and for assessments of its severity. In addition, spirometry is helpful for assessing responses to treatment and disease progression.
  • Forced expiratory volume in 1 second (FEV₁) is a reproducible test and is the most common index of airflow obstruction. Lung volume measurements show an increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity is decreased.
  • DLCO is decreased in proportion to the severity of emphysema.
  • Lung mechanics and gas exchange worsen during acute exacerbations.
  • As many as 30% of patients have an increase in FEV₁ of 15% or more after inhalation of a bronchodilator. The absence of bronchodilator response does not justify withholding bronchodilator therapy.

Pressure-volume curve is drawn for a patient with restrictive lung disease and obstructive disease and is compared to healthy lungs.

Flow-volume curve of lungs with emphysema shows marked decrease in expiratory flows, hyperinflation, and air trapping (patient B) compared to a patient with restrictive lung disease, who has reduced lung volumes and preserved flows (patient A).

Forced expiratory volume in 1 second (FEV₁) can be used to evaluate the prognosis in patients with emphysema. The benefit of smoking cessation is shown here because the deterioration in lung function parallels that of a nonsmoker, even in late stages of the disease.

Staging

The FEV₁ is used to stage the severity of COPD. It is normalized as a percentage of predicted for healthy controls. The following Global Initiative for Chronic Obstructive Lung Disease staging system is widely used:

• Stage I (mild) - FEV₁ greater than or equal to 80% of predicted.
• Stage II (moderate) - FEV₁ less than 80% and greater than or equal to 50% of predicted
• Stage III (severe) - FEV₁ less than 50% and greater than or equal to 30% of predicted
• Stage IV (very severe) - FEV₁ less than 30% of predicted or FEV₁ less than 50% and chronic respiratory failure

Respiratory failure is defined as a PaO₂ less than 60 mm Hg (kPa 8.0) or a PaCO₂ greater than 50 mm Hg (kPa 6.7).

Treatment

Medical Care

Once the diagnosis of chronic obstructive pulmonary disease (COPD) is established, the patient should be educated about the disease and should be encouraged to participate actively in therapy. The goal of therapy is to relieve symptoms, prevent disease progression, improve exercise tolerance and health status, prevent and treat complications and exacerbations, and reduce mortality¹ Treatments should be added in a stepwise fashion to reach these goals.

Smoking cessation

Smoking cessation is the single most effective therapy for the majority of COPD patients.¹ A smoking cessation plan is an essential part of a comprehensive treatment plan. The success rates for smoking cessation are low because of the addictive potential of nicotine, the conditioned response to smoking-associated stimuli, psychosocial problems, and forceful promotional campaigns by the tobacco industry. The process of smoking cessation must involve multiple interventions.

Physician intervention

The transition from smoking to nonsmoking status involves 5 stages. These stages are (1) precontemplation, (2) contemplation, (3) preparation, (4) action, and (5) maintenance. Smoking intervention programs include self-help, group, physician-delivered, workplace, and community programs. Setting a target date to quit may be helpful. Physicians and other health care providers should participate in setting the target date and should follow up with respect to maintenance. Successful cessation programs usually use the following resources and tools:

• Patient education
• A target date to quit
• Follow-up support
• Relapse prevention
• Advice for healthy lifestyle changes
• Social support systems
• Adjuncts to treatment (ie, pharmacological agents)

• Ask about tobacco use.
• Advise to quit through personalized messages.
• Assess willingness to quit.
• Assist with quitting.
• Arrange follow-up care and support.

Surgical Care

Various surgical approaches to improve symptoms and restore function in patients with emphysema have been described. These should be offered to carefully selected patients as they may provide great benefit.

Bullectomy

Removal of giant bullae has been a standard approach in selected patients for many years. Bullae can range from a few centimeters to occupying a third of the hemithorax. Giant bullae may compress adjacent lung tissue, reducing the blood flow and ventilation to the relatively healthy lung. Removal of these bullae may result in expansion of compressed lungs and improvement of lung function. Giant bullectomy can produce subjective and objective improvement in selected patients, ie, those who have bullae that occupy at least 30%—and preferably 50%—of the hemithorax that compress adjacent lung, with an FEV₁ of less than 50% of predicted and relatively preserved lung function otherwise.

Lung volume reduction surgery

Lung volume reduction surgery (LVRS) attempts to decrease hyperinflation by surgically resecting the most diseased parts of the lung. This improves airflow by increasing the elastic recoil of the remaining lung and the mechanical efficiency of the respiratory muscles to generate expiratory pressures. The National Emphysema Treatment Trial (NETT) compared LVRS with medical management over a 4-year period.²³ Subgroup analysis revealed the greatest benefit was achieved for patients with upper lobe–predominant emphysema and low exercise tolerance. These patients had improvement in mortality, work capacity, and quality of life. LVRS was shown to improve mortality in subjects considered to be high-risk patients (eg, FEV₁ <20% predicted and either DLCO <20% predicted or homogeneous changes on chest CT scan).

Lung transplantation

COPD makes up the largest single category of patients who undergo lung transplantation. Lung transplantation provides improved quality of life and functional capacity but does not result in survival benefit. The lack of survival benefit makes the timing of transplant difficult. The patients selected to receive transplants should have a life expectancy of 2 years or less. Current guidelines by the International Society of Heart and Lung Transplantation recommends referring for transplantation when the BODE (body mass index, obstruction [FEV₁], dyspnea [ie, Medical Research Council Dyspnea Scale], and exercise capacity [ie, 6-min walking distance) index is greater than 5.²⁴

Consultations

Consultation with a pulmonary specialist is recommended.

Diet

Inadequate nutritional status associated with low body weight in patients with COPD is associated with impaired pulmonary status, reduced diaphragmatic mass, lower exercise capacity, and higher mortality rates. Nutritional support is an important part of their comprehensive care.

Medication

Oral and inhaled medications are used for patients with stable emphysema to reduce dyspnea and improve exercise tolerance. Most of the medications used in emphysema treatment are directed at the 4 potentially reversible mechanisms of airflow limitation: (1) bronchial smooth muscle contraction, (2) bronchial mucosal congestion and edema, (3) airway inflammation, and (4) increased airway secretions.

Bronchodilators

These agents decrease muscle tone in both the small and large airways of the lungs, thereby increasing ventilation. This category beta-adrenergic agents, methylxanthines, and anticholinergics.

Albuterol (Proventil, Ventolin)

Beta2 agonist that relaxes bronchial smooth muscle by action on beta2 receptors, with little effect on cardiac muscle contractility. Most patients (even those who have no measurable increase in expiratory flow) benefit from treatment. Inhaled beta-agonists initially are prescribed as needed. Frequency may be increased. Institute regular schedule in patients on anticholinergic drugs who remain symptomatic. Available as liquid for nebulizer, metered-dose inhalers (MDIs), and dry-powder inhalers.

Dosing

Adult

MDI: 1-4 puffs q3-4h; use of a spacer/chamber device may improve delivery and reduce adverse effects
Nebulizer: 0.2-0.3 mL of 5% solution diluted to 2.5 mL with NS tid/qid

Pediatric

Not established

Interactions

Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, diabetes mellitus, pheochromocytoma, and cardiovascular disorders; adverse effects include muscle tremors, nervousness, insomnia, transient hypoxemia, and tachycardia

Metaproterenol (Alupent)

Relaxes bronchial smooth muscle by action on beta2 receptors, with little effect on cardiac muscle contractility. Most patients (even those who have no measurable increase in expiratory flow) benefit from treatment. Inhaled beta-agonists initially are prescribed as needed. Frequency may be increased. Institute regular schedule in patients on anticholinergic drugs who remain symptomatic. Available as liquid for nebulizer, MDIs, and dry-powder inhalers.

Dosing

Adult

MDI: 2 puffs q3-4h; use of a spacer/chamber device may improve delivery and reduce adverse effects
Nebulizer: 0.2-0.3 mL of 5% solution diluted to 2.5 mL with NS tid/qid

Pediatric

Not established

Interactions

Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by metaproterenol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents

Contraindications

Documented hypersensitivity; cardiac arrhythmia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, diabetes mellitus, pheochromocytoma, and cardiovascular disorders; adverse effects include muscle tremors, nervousness, insomnia, transient hypoxemia, and tachycardia

Levalbuterol (Xopenex)

Used for treatment or prevention of bronchospasm. A selective beta2-agonist agent. Albuterol is a racemic mixture, while levalbuterol contains only the active R- enantiomer of albuterol. The S-enantiomer does not bind to beta2-receptors, but may be responsible for some adverse effects of racemic albuterol, including bronchial hyperreactivity and reduced pulmonary function during prolonged use.

Dosing

Adult

0.63 mg via nebulizer tid, separate each dose by 6-8 h

Pediatric

<6 years: Not established
6-12 years: 0.31 mg via nebulizer tid, separate each dose by 6-8 h; not to exceed 0.63 mg tid
>12 years: Administer as in adults

Interactions

Decreased efficacy with beta-blockers; digoxin levels may be decreased; may potentiate the kaliuretic effects of drugs, such as, loop or thiazide diuretics; decreases serum digoxin levels by 16-22%; MAOIs may potentiate vascular constriction, extreme caution advised with coadministration

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Doses >0.63 mg tid may cause tachycardia; immediate hypersensitivity reactions reported; caution in patients with hypokalemia; may cause paradoxical bronchospasm and increased pulse rate or blood pressure

Ipratropium (Atrovent)

Chemically related to atropine. Has antisecretory properties, and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Used on a fixed schedule with a beta-agonist.

Dosing

Adult

MDI: 2-4 puffs q4-6h; use of a spacer/chamber device may improve delivery and reduce adverse effects
Nebulizer: 250 mcg diluted with 2.5 mL NS q4-6h

Pediatric

Not established

Interactions

Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol increases effects of ipratropium

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Because of slower onset of action than albuterol, ipratropium is less suitable for acute bronchoconstriction; on the other hand, it should be included in the regimen for exacerbations of COPD; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction; medication delivery may cause pupillary dilatation; may cause constipation

Salmeterol (Serevent)

By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasm. Effect also may facilitate expectoration. May be useful when bronchodilators are used frequently. More studies are needed to establish the role for these agents. When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. The bronchodilating effect lasts >12 h. Used on a fixed schedule in addition to regular use of anticholinergic agents.

Dosing

Adult

2 puffs bid; use of a spacer/chamber device may improve delivery and reduce adverse effects
Diskus device: 1 inhalation bid; no spacer needed with Diskus

Pediatric

Not established

Interactions

Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists (eg, salmeterol); concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen when coadministered with salmeterol

Contraindications

Documented hypersensitivity; angina and cardiac arrhythmias associated with tachycardia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not indicated to treat acute asthmatic symptoms; adverse effects are tremors, nervousness, and tachycardia

Formoterol (Oxis, Foradil)

Currently not available in the United States (investigational beta-agonist with rapid onset and long duration of action). By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, it can relieve bronchospasms. Effect also may facilitate expectoration.
Shown to improve symptoms and morning peak flows in asthma. May be useful when bronchodilators are used frequently. More studies are needed to establish the role for these agents.
When administered at high or more frequent doses than recommended, incidence of adverse effects is higher. The bronchodilating effect lasts >12 h. Used on a fixed schedule in addition to regular use of anticholinergic agents.

Dosing

Adult

12-25 mcg via inhalation bid

Pediatric

Not established

Interactions

Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists (eg, formoterol); concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen when coadministered with formoterol

Contraindications

Documented hypersensitivity; angina and cardiac arrhythmias associated with tachycardia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not indicated to treat acute asthmatic symptoms; adverse effects are tremors, nervousness, and tachycardia

Tiotropium (Spiriva)

A quaternary ammonium compound. Elicits anticholinergic/antimuscarinic effects with inhibitory effects on M₃ receptors on airway smooth muscles, leading to bronchodilation. Available as cap dosage form containing a dry powder for oral inhalation via HandiHaler inhalation device. Helps COPD patients by dilating narrowed airways and keeping them open for 24 h.

Dosing

Adult

Inhale contents of 1 cap (18 mcg) via HandiHaler device qd

Pediatric

Not established

Interactions

Coadministration with other anticholinergic containing drugs (eg, ipratropium) may increase toxicity risk

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

For maintenance treatment only; not effective for acute (rescue) therapy of bronchospasm; discontinue use and consider other treatments if immediate hypersensitivity reactions (including angioedema) or paradoxical bronchospasm occur; caution with narrow-angle glaucoma, prostatic hyperplasia, or bladder neck obstruction; commonly causes dry mouth; may cause constipation, increased heart rate, blurred vision, glaucoma, and urinary difficulty or retention; monitor patients with moderate-to-severe renal impairment

Theophylline (Aminophylline, Theo-24, Theo-Dur, Slo-bid)

Potentiates exogenous catecholamines. Stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which stimulates bronchodilation.
Popularity has decreased because of narrow therapeutic range and frequent toxicity. Bronchodilation may require near-toxic (>20 mg/dL) levels. However, clinical efficacy is controversial, especially in the acute setting.
Shown to increase exercise capacity, decrease dyspnea, and improve gas exchange. A longer-acting agent is used qd or bid.
Target concentration is 5-10 mcg/mL. Dosing = (target concentration - current level) X 0.5 (ideal body weight). Alternatively, 1 mg/kg results in approximately a 2-mcg/mL increase in serum levels.

Dosing

Adult

Initial: 10 mg/kg/d PO divided q8-12h
Maintenance: 10 mg/kg/d PO divided qd or bid; adjust dose in 25% increments to maintain serum theophylline level of 5-15 mcg/mL; not to exceed 800 mg/d

Pediatric

Not established

Interactions

Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects of theophylline; theophylline effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon

Contraindications

Documented hypersensitivity; uncontrolled arrhythmias; peptic ulcers; hyperthyroidism; uncontrolled seizure disorders

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in peptic ulcer, hypertension, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; do not inject IV solution faster than 25 mg/min; patients diagnosed with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance; adverse effects include nausea, vomiting, tremor, seizures, coma, esophageal reflux, and atrial and ventricular arrhythmias

Corticosteroids

These agents attempt to moderate the inflammatory component of COPD. They should only be added to a regimen that includes a long-acting bronchodilator.

Fluticasone (Flovent, Cutivate, Flonase)

Has extremely potent vasoconstrictive and anti-inflammatory activity. Has weak inhibitory effects on HPA axis when used at high doses for prolonged periods of time. Effectiveness is not established in COPD.

Dosing

Adult

250-500 mcg inhaled PO bid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use, applying over large surface areas, application of potent steroids, and occlusive dressings may increase systemic absorption of corticosteroids and may cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria; adverse effects include oral thrush, hoarseness, adrenal suppression, glaucoma, skin bruising, and alteration in bone metabolism

Budesonide (Pulmicort Turbuhaler)

Has extremely potent vasoconstrictive and anti-inflammatory activity. Has weak inhibitory effects on HPA axis when used at high doses for prolonged periods of time. Effectiveness is not established in COPD.

Dosing

Adult

400-800 mcg inhaled PO bid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use, applying over large surface areas, application of potent steroids, and occlusive dressings may increase systemic absorption of corticosteroids and may cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria; adverse effects include oral thrush, hoarseness, adrenal suppression, glaucoma, skin bruising, and alteration in bone metabolism

Smoking cessation therapies

Most effective when used in conjunction with a support program (ie, counseling, group therapy, and behavioral therapy).

Bupropion is used as a nonnicotine aid to smoking cessation. One study demonstrated 23% sustained cessation with bupropion tablets at 1 year, compared with a 12% sustained cessation with placebo. Bupropion also may be effective in patients who do not quit with nicotine replacement therapy.

Varenicline (Chantix) is a partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. It is used in conjunction with support groups and/or behavioral counseling. Gradually increase dose upward within 1 wk before quit date to 1 mg PO bid pc. Decrease dose with severe renal impairment or end-stage renal disease

Nicotine transdermal system (Nicotrol, Habitrol, NicoDerm CQ)

Individuals who smoke >1 pack/d initially need a 21-mg patch followed by 14- and 7-mg patches.

Dosing

Adult

Habitrol/NicoDerm CQ: one 21-mg patch qd for 3-4 wk, then one 14-mg patch qd for 3-4 wk, followed by one 7-mg patch qd for 3-4 wk
Nicotrol: one 15-mg patch qd for 6 wk, then one 10-mg patch qd for 2 wk, followed by one 5-mg patch qd for 2 wk

Pediatric

Not established

Interactions

May decrease diuretic effects of furosemide and decrease cardiac output; may decrease absorption of glutethimide; may increase circulating cortisol and catecholamines; do not use if patient continues to smoke, use snuff, chew tobacco, or use other nicotine products because these may increase toxicity of nicotine

Contraindications

Documented hypersensitivity; people who do not smoke; children; pregnancy; life-threatening arrhythmias; severe or worsening angina pectoris

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in peptic ulcer, coronary artery disease, angina, hypertension, peripheral arterial disease, diabetes, severe renal dysfunction, and hepatic dysfunction; may cause skin irritation

Nicotine polacrilex (Nicorette)

Nicotine is absorbed through oral mucosa. Quickly absorbed and closely approximates time course of plasma nicotine levels observed after cigarette smoking.
Available as 2- or 4-mg gum in box containing 96 pieces. Careful adherence to chewing instructions is important for effective use. Manufacturer recommends that gum not be used longer than 6 mo.
Individual who smokes 1 pack/d should use 4-mg pieces. The 2-mg pieces are to be used by individuals who smoke <1 pack/d. Instruct patient to chew hourly and for initial cravings for 2 wk, then gradually reduce amount chewed over 3 mo.

Dosing

Adult

1 piece of gum (2 mg) per h as needed to abstain from smoking; not to exceed 30 mg/d

Pediatric

Not established

Interactions

May decrease diuretic effects of furosemide and decrease cardiac output; may decrease absorption of glutethimide; may increase circulating cortisol and catecholamines; do not use if patient continues to smoke, use snuff, chew tobacco, or use other nicotine products because these may increase toxicity of nicotine

Contraindications

Documented hypersensitivity; people who do not smoke; children; pregnancy; life-threatening arrhythmias; severe or worsening angina pectoris; recent MI

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in peptic ulcer, coronary artery disease, angina, hypertension, peripheral arterial disease, diabetes, severe renal dysfunction, and hepatic dysfunction

Bupropion (Zyban)

Used in conjunction with a support group and/or behavioral counseling. Inhibits neuronal dopamine reuptake in addition to being a weak blocker of serotonin and norepinephrine reuptake.

Dosing

Adult

150 mg PO qd for 3 d, then increased to 150 mg bid with at least 8 h between each dose for 7-12 wk

Pediatric

Not established

Interactions

Carbamazepine, cimetidine, phenytoin, and phenobarbital may decrease effects; toxicity increases with concurrent administration of levodopa and MAOIs

Contraindications

Documented hypersensitivity; seizure disorder; anorexia nervosa; concurrent use with MAOIs

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal or hepatic insufficiency; doses >450 mg/d significantly decrease seizure threshold; adverse effects include pruritus, angioedema, dyspnea, and insomnia; delusions and/or hallucinations may occur in patients who are depressed

Varenicline (Chantix)

Partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. Action is thought to be the result of activity at a nicotinic receptor subtype where its binding produces agonist activity, while simultaneously preventing nicotine binding. The agonistic activity is significantly lower than nicotine. Also elicits moderate affinity for 5-HT3 receptors. Maximum plasma concentrations occur within 3-4 h after oral administration. Following regular dosing, steady state is reached within 4 d.

Dosing

Adult

Initiate 1 wk before date chosen to stop smoking
Days 1-3: 0.5 mg PO qd pc
Days 4-7: 0.5 mg PO bid pc
Day 8 to end of treatment: 1 mg PO bid pc
Continue treatment for 12 wk; if successfully stopped smoking at end of 12 wk, an additional course of 12 wk treatment is recommended; take pc with full glass of water
Severe renal impairment (ie, CrCl <30 mL/min): Do not exceed 0.5 mg PO bid
End-stage renal disease with hemodialysis: Do not exceed 0.5 mg PO qd

Pediatric

<18 years: Not established

Interactions

Data limited; coadministration with nicotine replacement therapy may increase incidence of nausea, headache, vomiting, dizziness, and dyspepsia compared with nicotine replacement therapy alone

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include nausea, headache, vomiting, flatulence, insomnia, abnormal dreams, and dysgeusia; decrease dose with severe renal impairment (ie, CrCl <30 mL/min) or end-stage renal disease undergoing hemodialysis
Serious neuropsychiatric symptoms have been reported during postmarketing surveillance and may include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide; these adverse events have been exhibited in patients without preexisting psychiatric illness, and patients with preexisting psychiatric illness have reported worsening symptoms during varenicline treatment; for more information, see the FDA MedWatch Safety Information

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Amoxicillin (Amoxil, Trimox, Moxatag)

Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria

Dosing

Adult

250-500 mg PO q8h; not to exceed 3 g/d

Pediatric

Not established

Interactions

Reduces efficacy of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; may enhance chance of candidiasis

Doxycycline (Doryx, Monodox, Doxy, Adoxa)

Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Dosing

Adult

100 mg PO bid on day 1, then 100 mg PO qd for 7-10 d

Pediatric

Not established

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Sulfamethoxazole and Trimethoprim (Co-Trimoxazole, TMP-SMZ)

Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, resulting in inhibition of bacterial growth. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa. Like tetracycline, it has in vitro activity against Bartonella pertussis. Not useful in mycoplasmal infections.

Dosing

Adult

160 mg TMP/800 mg SMZ PO q12h

Pediatric

Not established

Interactions

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency; age <2 mo

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use during last trimester of pregnancy due to potential toxicity to newborn (eg, jaundice, hemolytic anemia, kernicterus)
Dosage adjustments (adult adjustments)
CrCl (mL/min) 80-50: Recommended IV dose q18h
CrCl 50-10: Recommended IV dose q24h
CrCl <10: Not recommended
Hemodialysis: 4-5 mg/kg after HD
During peritoneal dialysis: 0.16-0.8 g q48h
Discontinue at first appearance of rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholism, elderly persons, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in patients with G-6-PD deficiency; AIDS patients may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Azithromycin (Zithromax)

These agents are replacing erythromycin as therapy for community-acquired pneumonia. They cover most potential etiologic agents, including Mycoplasma. The newer macrolides offer decreased GI upset and potential for improved compliance through reduced dosing frequency. They also afford improved action against Haemophilus influenzae.

Dosing

Adult

Day 1: 500 mg PO
Days 2-5: 250 mg PO qd
Alternatively, 500 mg IV qd

Pediatric

Not established

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine

Contraindications

Documented hypersensitivity; hepatic impairment; do not administer with pimozide

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Follow-up

Further Inpatient Care

Acute exacerbation of COPD

Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) is defined as worsening of cough, increase in phlegm production, change in phlegm quality, and increase in dyspnea. AECOPDs are common in the course of the disease. Previously thought to occur at random, careful analysis by Hurst et al has shown AECOPDs occur in clusters.²⁵ The study showed patients with an AECOPD were at an increased risk of another attack in the 8 weeks following their initial episode. Close follow up during this “brittle” period may lead to earlier treatment and better clinical outcomes.

AECOPDs 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, and increase in hypoxemia or hypercapnia. Care must be taken to evaluate for other conditions that may mimic AECOPD.

AECOPD can result in hypoxemia and hypercapnia. Mild episodes may be managed with supplemental oxygen to keep PaO₂ of 60 mm Hg. If the episode is severe, the patient may require ventilatory support in the form of either noninvasive positive-pressure ventilation (NIPPV) or invasive positive-pressure ventilation. The use of NIPPV is now well studied and supported in patients who have no contraindication to its use. A Cochrane review showed NIPPV reduces mortality, avoids endotracheal intubation, and decreased treatment failure.²⁶

Pharmacological treatment of COPD includes bronchodilators, antibiotics, and steroids. Short-acting bronchodilators are the mainstay of therapy. Combinations of a beta2-agonist and anticholinergic agent are commonly used together, although the benefit of both over either is marginal. Oral or parenteral steroids are indicated in the treatment of AECOPD and have been shown to shorten recovery time and improve outcome. Importantly, taper the steroid course over 7-14 days because prolonged courses offer no additional benefit and increase adverse effects. Antibiotics have been shown to provide benefit in patients who present with dyspnea, increased purulence, and increased volume of sputum. The choice of antibiotics should be based on suspected etiology, patient history, and prevalent resistance patterns.

Further Outpatient Care

Pulmonary rehabilitation

Many patients with COPD are unable to enjoy life to the fullest because of shortness of breath, physical limitations, and inactivity. Pulmonary rehabilitation encompasses an array of therapeutic modalities designed to improve patients' quality of life by decreasing airflow limitation, preventing secondary medical complications, and alleviating respiratory symptoms.

Successful implementation of a pulmonary rehabilitation program usually requires a team approach, with individual components provided by healthcare professionals who have experience in managing COPD. These individuals include physicians, nurses, dietitians, respiratory therapists, exercise physiologists, physical therapists, occupational therapists, recreational therapists, cardiorespiratory technicians, pharmacists, and psychosocial professionals. This multidisciplinary approach emphasizes 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

Prognosis

The forced expiratory volume in 1 second (FEV₁) has been historically used to predict outcome in COPD. Recent appreciation for other factors that determine outcome has resulted in creation of the BODE index (ie, body mass index, obstruction [FEV₁], dyspnea [ie, Medical Research Council Dyspnea Scale, MMRC], and exercise capacity [ie, 6MWD]).²⁸ This index was developed to assess an individual’s risk of death or hospitalization. All 4 factors are used to determine the score.

BODE index 

• 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
• 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
• Approximate 4-year survival
  • 0-2 points = 80%
  • 3-4 points = 67%
  • 5-6 points = 57%
  • 7-10 points = 18%

Patient Education

• For excellent patient education resources, visit eMedicine's Public Health Center and Lung and Airway Center. Also, see eMedicine's patient education articles Cigarette Smoking and Emphysema.

Miscellaneous

Medicolegal Pitfalls

• The natural history of alpha1-antitrypsin (AAT) deficiency is unknown. The effect of replacement therapy has not been determined in randomized controlled trials. Although some investigators have argued that the duration and associated costs of controlled studies make such clinical trials impractical, the cost of AAT replacement is enormous, and the lack of consistent data regarding the course of untreated disease results in considerable skepticism about its efficacy. Whether widespread population screening should be undertaken also is unclear.
• Differentiating COPD from asthma has been difficult because of overlap in pathophysiology, clinical presentation, pulmonary function testing, and treatment; approaches to treatment and prognosis differ.
• The cost effectiveness of various interventions (eg, pulmonary rehabilitation, lung reduction surgery, lung transplantation) needs to be established.
• The role of noninvasive ventilation to provide intermittent respiratory muscle rest needs be further defined.

Special Concerns

Air travel  

Many commercial airplanes fly at altitudes os 30,000-40,000 feet, but the cabin is pressurized to an altitude of 5,000-8,000 feet. At these altitudes, atmospheric partial pressure of oxygen (PO₂) is 132-109 mm Hg, compared with 159 mm Hg at sea level. Acute reduction in PO₂ stimulates peripheral chemoreceptors, which results in hyperventilation. The following is a prediction equation used to estimate PaO₂ at 8000 feet (2440 m): 

PaO₂ = 22.8 - 2.74x + 0.68y
x = Altitude
y = Arterial PO2 at sea level

A predicted PaO₂ of 50 mm Hg or less at an altitude of 8,000 feet is an indication for supplemental oxygen. This can be arranged prior to the flight through the airline directly or through the airline agent but requires extra expense.

Sleep and COPD

Patients with COPD may develop substantial decreases in nocturnal PaO₂ during all phases of sleep but particularly during rapid eye movement sleep. These episodes are associated with rises in pulmonary arterial pressures and disturbance in sleep architecture initially, but patients may develop pulmonary arterial hypertension and cor pulmonale if the hypoxemia remains untreated. Therefore, patients who have a daytime PaO₂ greater than 60 mm Hg but demonstrate substantial nocturnal hypoxemia should be prescribed oxygen supplementation for use during sleep.

Multimedia

Media file 1: Gross pathology of bullous emphysema shows bullae on the surface of the lungs.

Media file 2: Gross pathology of emphysema shows bullae on the lung surface.

Media file 3: At high magnification, loss of airway walls and dilated airspaces are observed in emphysema.

Media file 4: Chest radiograph shows hyperinflation, flattened diaphragms, increased retrosternal space, and hyperlucency of the lung parenchyma in emphysema.

Media file 5: A CT scan shows emphysematous bullae in upper lobes.

Media file 6: Diffuse emphysema secondary to cigarette smoking.

Media file 7: Pressure-volume curve is drawn for a patient with restrictive lung disease and obstructive disease and is compared to healthy lungs.

Media file 8: Flow-volume curve of lungs with emphysema shows marked decrease in expiratory flows, hyperinflation, and air trapping (patient B) compared to a patient with restrictive lung disease, who has reduced lung volumes and preserved flows (patient A).

Media file 9: Forced expiratory volume in 1 second (FEV₁) can be used to evaluate the prognosis in patients with emphysema. The benefit of smoking cessation is shown here because the deterioration in lung function parallels that of a nonsmoker, even in late stages of the disease.

Media file 10: A CT scan showing severe emphysema and bullous disease.

Media file 11: An emphysematous lung shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on posteroanterior (PA) film.

Media file 12: An emphysematous lung shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on lateral chest radiograph.

Media file 13: The differential diagnosis of unilateral hyperlucent lung includes pulmonary arterial hypoplasia and Swyer-James syndrome. The expiratory chest radiograph exhibits evidence of air trapping and is helpful in making the diagnosis. Swyer-James syndrome is unilateral bronchiolitis obliterans, which develops during early childhood.

Media file 14: Lateral chest radiograph of Swyer-James syndrome may demonstrate some of the features of emphysema.

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Keywords

emphysema, chronic obstructive pulmonary disease, COPD, chronic obstructive lung disease, chronic lung, chronic bronchitis, airflow obstruction, centriacinar emphysema, centrilobular emphysema, panacinar emphysema, paraseptal emphysema, distal acinar emphysema, alpha1-antitrypsin deficiency, AAT

Contributor Information and Disclosures

Author

Berj George Demirjian, MD, Fellow, Division of Pulmonary/Critical Care Medicine, Cedars-Sinai Medical Center
Berj George Demirjian, MD is a member of the following medical societies: American College of Chest Physicians, American Medical Association, California Medical Association, California Thoracic Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center
Nader Kamangar, MD, FACP, FCCP, FAASM is a member of the following medical societies: American Academy of Sleep Medicine, American Association of Bronchology, American College of Chest Physicians, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, California Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

Helen M Hollingsworth, MD, Director, Adult Asthma and Allergy Services, Associate Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, Boston Medical Center
Helen M Hollingsworth, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American Thoracic Society, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Sat Sharma, MD, FRCPC, to the development and writing of this article.

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