eMedicine Specialties > Emergency Medicine > Pulmonary

Chronic Obstructive Pulmonary Disease and Emphysema

Paul Kleinschmidt, MD, Consulting Staff, Department of Emergency Medicine, Womack Army Medical Center

Updated: Mar 13, 2008

Introduction

Background

Chronic obstructive pulmonary disease (COPD) is estimated to affect 32 million persons in the United States and is the fourth leading cause of death in this country. Patients typically have symptoms of both chronic bronchitis and emphysema, but the classic triad also includes asthma. Most of the time COPD is secondary to tobacco abuse, although cystic fibrosis, alpha-1 antitrypsin deficiency, bronchiectasis, and some rare forms of bullous lung diseases may be causes as well. 

Patients with COPD are susceptible to many insults that can lead rapidly to an acute deterioration superimposed on chronic disease. COPD exacerbation is an important but occasionally overlooked parameter. COPD exacerbations are very common, affecting about 20% of patients with moderate-to-severe COPD (1.3 events per year in patients with 40-45% predicted FEV₁). Quick and accurate recognition of these patients along with aggressive and prompt intervention may be the only action that prevents frank respiratory failure.

For more information, see Medscape's COPD Resource Center.

Pathophysiology

COPD is a mixture of 3 separate disease processes that together form the complete clinical and pathophysiological picture. These processes are chronic bronchitis, emphysema and, to a lesser extent, asthma. Progression of COPD is characterized by the accumulation of inflammatory mucous exudates in the lumens of small airways and the thickening of their walls. These walls become infiltrated by adaptive and innate inflammatory immune cells. Infiltration of the airways with substances such as polynuclear and mononuclear phagocytes and CD4 T cells increases with each stage of disease progression. This is also true for B cells and CD8 T cells, which organize into lymphoid follicles. This chronic inflammatory process is associated with tissue repair and remodeling that ultimately determines the pathologic type of COPD. 

It appears that smoking may overcome the body's natural mechanisms for limiting this immune response. This process can continue in susceptible individuals even after smoking cessation. Even if the original noxious insults are removed, COPD is still characterized by progressive accumulation of cells of the immune system, fibrosis, and mucus hypersecretion. The molecular basis for the lung inflammation seen in COPD is still an area of great research and debate, with the potential roles of cytokines, complex autoimmune processes, and immune modulation from chronic infection all under investigation.

The defining feature of COPD is irreversible airflow limitation during forced expiration. This may be a result of a loss of elastic recoil due to lung tissue destruction or an increase in the resistance of the conducting airways. The standard measure of COPD is the measure of forced expiratory volume in 1 second (FEV₁) and its ratio to forced vital capacity (FVC), FEV₁/FVC.

Each case of COPD is unique in the blend of processes; however, 2 main types of the disease are recognized.

Chronic bronchitis

In this type, chronic bronchitis plays the major role. Chronic bronchitis is defined by excessive mucus production with airway obstruction and notable hyperplasia of mucus-producing glands.

Damage to the endothelium impairs the mucociliary response that clears bacteria and mucus. Inflammation and secretions provide the obstructive component of chronic bronchitis. In contrast to emphysema, chronic bronchitis is associated with a relatively undamaged pulmonary capillary bed. Emphysema is present to a variable degree but usually is centrilobular rather than panlobular. 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

The second major type is that in which emphysema is the primary underlying process. Emphysema is defined by destruction of airways distal to the terminal bronchiole.

Physiology of emphysema involves gradual destruction of alveolar septae and of the pulmonary capillary bed, leading to 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 blue bloaters. Because of low cardiac output, however, the rest of the body suffers from tissue hypoxia and pulmonary cachexia. Eventually, these patients develop muscle wasting and weight loss and are identified as "pink puffers."

Frequency

United States

Two thirds of men and one fourth of women have emphysema at death. Approximately 8 million people have chronic bronchitis and 2 million have emphysema.

Mortality/Morbidity

COPD is the fourth leading cause of death in the United States, affecting 32 million adults. It is also the fifth leading cause of death worldwide.

Sex

Men are more likely to have COPD than women.

Age

COPD occurs predominantly in individuals older than 40 years.

Clinical

History

Patients with COPD present with a combination of signs and symptoms of chronic bronchitis, emphysema, and asthma. Symptoms include worsening dyspnea, progressive exercise intolerance, and alteration in mental status. In addition, some important clinical and historical differences can exist between the types of COPD.

• In the chronic bronchitis group, classic symptoms include the following:
  • Productive cough, with progression over time to intermittent dyspnea
  • Frequent and recurrent pulmonary infections
  • Progressive cardiac/respiratory failure over time, with edema and weight gain
• In the emphysema group, the history is somewhat different and may include the following set of classic symptoms:
  • A long history of progressive dyspnea with late onset of nonproductive cough
  • Occasional mucopurulent relapses
  • Eventual cachexia and respiratory failure

Physical

Depending on the type of COPD, physical examination may vary.

• Chronic bronchitis (blue bloaters)  
  • 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.
  • Because they share many of the same physical signs, COPD may be difficult to distinguish from congestive heart failure (CHF). One crude bedside test for distinguishing COPD from CHF is peak expiratory flow. If patients blow 150-200 mL or less, they are probably having a COPD exacerbation; higher flows indicate a probable CHF exacerbation.
• Emphysema (pink puffers)  
  • Patients may be very thin with a barrel chest.
  • They typically have little or no cough or expectoration.
  • Breathing may be assisted by pursed lips and use of accessory respiratory muscles; they may adopt the tripod sitting position.
  • The chest may be hyperresonant, and wheezing may be heard; heart sounds are very distant.
  • Overall appearance is more like classic COPD exacerbation.

Causes

In general, the vast majority of COPD cases are the direct result of tobacco abuse. While other causes are known, such as alpha-1 antitrypsin deficiency, cystic fibrosis, air pollution, occupational exposure (eg, firefighters), and bronchiectasis, this is a disease process that is somewhat unique in its direct correlation to a human activity.

Differential Diagnoses

Workup

Laboratory Studies

• Arterial blood gas  
  • Arterial blood gas (ABG) analysis provides the best clues as to acuteness and severity.
  • In general, renal compensation occurs even in chronic CO₂ retainers (ie, bronchitics); thus, pH usually is near normal.
  • Generally, consider any pH below 7.3 a sign of acute respiratory compromise.
• Serum chemistry  
  • These patients tend to retain sodium.
  • Diuretics, beta-adrenergic agonists, and theophylline act to lower potassium levels; thus, serum potassium should be monitored carefully.
  • Beta-adrenergic agonists also increase renal excretion of serum calcium and magnesium, which may be important in the presence of hypokalemia.
• CBC - Polycythemia
• BNP
  • Human BNP binds to particulate guanylate cyclase receptors of vascular smooth muscle and endothelial cells. Binding to the receptors causes an increase in cyclic guanosine monophosphate (GMP), which serves as a secondary messenger to dilate veins and arteries. 
  • By measuring the BNP level, it was thought that the ability to differentiate between CHF and COPD exacerbations in blue bloaters would have become much easier. However, clinical observation and research demonstrated that, in the cases of mild CHF exacerbations, the ability to differentiate between CHF and COPD is still not straightforward. A mild elevation of a BNP level still must be taken in context with the overall clinical picture.

Imaging Studies

• Chest radiography 
  • Chronic bronchitis is associated with increased bronchovascular markings and cardiomegaly.
  • Emphysema is associated with a small heart, hyperinflation, flat hemidiaphragms, and possible bullous changes.

Other Tests

• Pulse oximetry  
  • Pulse oximetry does not offer as much information as ABG analysis.
  • When combined with clinical observation, this test can be a powerful tool for instant feedback on the patient's status.
• Electrocardiography
  •  The presence of underlying cardiac disease is highly likely.
  • Establish that hypoxia is not resulting in ischemia.
  • Establish that the underlying cause of respiratory difficulty is not cardiac in nature.
• Pulmonary function tests  
  • Decreased forced expiratory volume in 1 second (FEV₁) with concomitant reduction in FEV₁/forced vital capacity (FVC) ratio
  • Poor/absent reversibility with bronchodilators
  • FVC normal or reduced
  • Normal or increased total lung capacity (TLC)
  • Increased residual volume (RV)
  • Normal or reduced diffusing capacity

Treatment

Prehospital Care

The mainstays of therapy for acute exacerbations of COPD are oxygen, bronchodilators, and definitive airway management.

• Oxygen  
  • Adequate oxygen should be given to relieve hypoxia. A belief (ingrained from medical school) is held widely that too much oxygen causes significant respiratory depression. Multiple studies in the literature dispute this view. With administration of oxygen, PO₂ and PCO₂ rise but not in proportion to the very minor changes in respiratory drive.
  • The need for intubation can be established quickly at the bedside by asking the patient to hold the nebulizer in his or her hand. If the patient becomes so sleepy that the nebulizer starts to fall away, the patient should be intubated regardless of PCO₂ level. The cause of increased CO₂ production is not decreased respiratory drive but probably reversal of hypoxic arterial vasoconstriction in areas of less-ventilated lung tissue, which increases the extent of ventilation/perfusion defects and thus CO₂. "Stated another way, there is probably no single value for arterial PCO₂, pH, or PO₂ that by itself constitutes and indication for [intermittent positive pressure ventilation (IPPV)]."¹
  • Occasionally, large increases in CO₂ can lead to deterioration of mental status, causing stupor and obtundation. In such cases, decreasing O₂ delivery is the wrong action. The CO₂ narcosis inhibits respiratory drive to the point that decreasing O₂ delivery leads only to worsening of hypoxia. The correct action is immediate intubation and oxygenation.
  • Supply the patient with enough oxygen to maintain a near normal saturation (above 90%) and do not be concerned about oxygen supplementation leading to clinical deterioration. If the patient's condition is that tenuous, intubation most likely is needed anyway.
• Bronchodilator  
  • In the prehospital setting, administer short-acting beta-agonist nebulizer therapy, which should be given as needed. In addition, short-acting anticholinergics, such as ipratropium, can be given.
  • If necessary and available, continuous positive airway pressure (CPAP) may be used.
  • Of course, in times of respiratory failure, patients may need intubation in the field.

Emergency Department Care

In addition to oxygen, proper ED care may comprise bronchodilators, antibiotics, magnesium, CPAP or biphasic positive airway pressure (BiPAP), Heliox (ie, mixture of helium and oxygen), and definitive airway management via intubation. All of these should be considered in the context of the individual patient's condition.

For more information, please see either Medication or In/Out Patient Meds in the Follow-up section.

Consultations

• Consult a pulmonologist.

Medication

Medicines available for ED treatment of COPD include beta2-adrenoceptor agonists, anticholinergics, oxygen, methylxanthines, corticosteroids, some newer experimental classes of medication, and, possibly magnesium.

• Terbutaline can be considered for patients with such significant exacerbations that they are not moving enough air to take full advantage of nebulizer therapy.
• Beta2-adrenoceptor agonists  
  • These agents are first-line therapy for COPD, both for acute exacerbations and for acute treatment. Bronchodilators are given on an as-needed basis or on a regular basis to prevent or reduce symptoms. Short-acting agents are usually used for immediate relief of symptoms, whereas long-acting inhaled agents are better for day-to-day mitigation of the disease. Even longer-acting agents, which would allow once-daily dosing, are in development.
  • Combinations of bronchodilators may improve efficacy and reduce risk of adverse effects rather than increasing the dose of a single agent. Keep in mind that, based on several studies, the acute response to short-acting agents does not predict the future response to long-acting agents. 
  • Most of the beta-agonists used are racemic compounds that contain both the R and S enantiomers of the agonist. Much of the pharmacologic activity seems to reside in the R enantiomer, with the S thought to induce the negative side effects. Recently, the R enantiomer of both the short-acting agent albuterol (levalbuterol) and the long-acting agent formoterol (aformoterol) were approved for use in COPD. However, the cost effectiveness of these agents, in light of marginal observed clinical differences, remains controversial and needs further exploration.
  • Although the major action of beta2-agonists is relaxation of airway smooth muscles, they have also been shown to have several other potential effects. They seem to inhibit airway smooth muscle proliferation and inflammatory mediator release, as well as stimulation of mucociliary transport, cytoprotection of the mucosa, and attenuation of neutrophil recruitment and activation.
  • Multiple studies have demonstrated enhanced benefits of action when coadministered with inhaled anticholinergics and with corticosteroids.
  • The greatest single problem that persists in the acute phase is the under dosing of beta-agonists and the nonutilization of anticholinergics. Although only a small subset of patients respond to beta-agonists, a reasonable dose approaches continuous nebulization, as is seen in current asthma treatment.
  • Note that, in mild or moderate exacerbations, the use of MDIs with an aerosol chamber in higher doses (6-12 puffs) can achieve equivalent bronchodilation as the use of a nebulizer. This is particularly important in the office and prehospital setting.
• Anticholinergics 
  • Anticholinergics have an important role in the acute treatment of COPD exacerbations. The anticholinergics reduce airway tone and improve expiratory flow limitation, primarily by blocking parasympathetic activity in the large and medium-sized airways. They also block the release of acetylcholine, which has been linked to increased bronchial smooth muscle tone and mucus hypersecretion. 
  • Two anticholinergic agents are available at this time, a short-acting agent appropriate for management of acute exacerbations (ipratropium) and a long-acting agent (tiotropium).
• Methylxanthines: These agents increase collateral ventilation, respiratory muscle function, mucociliary clearance, and central respiratory drive. Despite this, many questions exist as to their true efficacy, and they have no real role in the acute exacerbation of COPD, except to increase the risk of adverse effects.
• Phosphodiesterase inhibitors: In theory, phosphodiesterase inhibitors would work to selectively inhibit of phosphodiesterase to cause smooth muscle relaxation and anti-inflammatory effects. These agents would have a better safety profile than the methylxanthines, but they are all still in various stages of development.
• Antibiotics
  • The use of antibiotics is still controversial. These patients are almost uniformly heavily colonized with Haemophilus influenzae, streptococcal pneumonia, and others; however, researchers have not proven these organisms to be the cause of the exacerbation. In fact, viruses are thought to be the instigating factor in as many as half of the cases.
  • The particular antibiotic chosen seems to have much less effect on outcome than the particular host factors of the patient in some studies, with other studies suggesting fluoroquinolones are the best strategy. This may really be a factor of the severity of the exacerbation and whether antibiotics are really indicated for minor exacerbations. 
  • If antibiotics are given, the choice should provide coverage against pneumococcus, H influenzae, Legionella species, and gram-negative enterics.
• Magnesium: Though controversial, administration of magnesium is thought to produce bronchodilation through the counteraction of calcium-mediated smooth muscle constriction. The addition of intravenous magnesium is now considered to have class B evidence supporting its use in difficult and life-threatening exacerbations.
• Heliox: Because of helium's low density, some class B evidence now exists for its use as the medium to drive nebulizer therapy. In theory, a mixture of helium and oxygen could improve gas exchange in patients who have an airway obstruction. In the realm of COPD exacerbations, however, the evidence is more slight, and more investigation is needed.
• Leukotriene receptor antagonists: Intravenous leukotriene receptor antagonists have been shown to have benefit in asthma in limited studies, but, at this time, they have no role in COPD exacerbations.

Bronchodilators

These agents act to decrease muscle tone in both small and large airways in the lungs, thus increasing ventilation. Category includes subcutaneous medications, beta-adrenergic agonists, methylxanthines, and anticholinergics. Note that only 10-15% of all patients with COPD have a true reversible (ie, bronchospastic) component; however, because predicting response is impossible on presentation, all patients should be treated with aggressive bronchodilator therapy.

Terbutaline (Brethaire, Bricanyl)

Acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.

Dosing

Adult

0.25 mg (0.25 mL of 1 mg/mL concentration) SC; not to exceed 0.5 mg SC q4h

Pediatric

Not established

Interactions

Beta-blockers may inhibit bronchodilating, cardiac, and vasodilating effects; concomitant MAOIs may result in a hypertensive crisis; concomitant oxytocic drugs such as ergonovine may result in severe hypotension

Contraindications

Documented hypersensitivity; tachycardia resulting from cardiac arrhythmias

Precautions

Pregnancy

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

Precautions

Caution in coronary disease; through intracellular shunting, may decrease serum potassium levels, which can produce adverse cardiovascular effects (decrease usually transient and may not require supplementation)

Albuterol (Proventil)

Beta-agonist useful in treatment of bronchospasm. Drug selectively stimulates beta2-adrenergic receptors of lungs. Bronchodilation results from relaxation of bronchial smooth muscle, which relieves bronchospasm and reduces airway resistance. Note that prior use of long-acting agents, such as salmeterol, does not seem to compromise response to albuterol during acute attacks.
Use 5 mg/mL solution for nebulization; usually underdosed in acute settings. Many studies have demonstrated that high-dose therapy is most efficacious. Goal is continuous therapy in initial treatment phase. Note that properly used MDI with spacer is equal in effectiveness to nebulized therapy.

Dosing

Adult

5 mg/mL solution: 1 mL (5 mg) in 2-3 mL of saline solution minimum; give multiple nebs in succession; goal is continuous therapy in initial treatment phase
Properly used MDI with spacer equal in effectiveness to nebulized therapy

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, and cardiovascular disorders

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

Acts to increase collateral ventilation, respiratory muscle function, mucociliary clearance, and central respiratory drive. Acts partly by inhibiting phosphodiesterase, elevating cellular cyclic AMP levels, or antagonizing adenosine receptors in bronchi, resulting in relaxation of smooth muscle.
However, clinical efficacy is controversial, especially in acute setting. Author advocates this medicine only if patient was taking medicine already and had subtherapeutic level. Do not give IV form (aminophylline) because it can precipitate arrhythmias, especially in patients such as these who are already in an excess catecholamine state. Measure serum level to adjust dose.
Note that most recent meta-analyses and other literature have failed to show a benefit from the use of methylxanthines in acute exacerbations.

Dosing

Adult

Target concentration: 10 mcg/mL
Dosing = (Target Concentration - Current Level) X 0.5 (Ideal Body Weight)
Alternatively, 1 mg/kg results in approximately 2 mcg/mL increase in serum levels

Pediatric

Not established

Interactions

Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects; 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; hyperthyroidism

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, or compromised cardiac function; do not inject IV solution faster than 25 mg/min; patients with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance
Again, author recommends not giving the IV form at all

Ipratropium bromide (Atrovent)

Anticholinergic medication that appears to inhibit vagally mediated reflexes by antagonizing action of acetylcholine specifically with muscarinic receptor on bronchial smooth muscle. Vagal tone can be increased by as much as 50% in patients with COPD, so this can have a profound effect.
Dose can (and should) be mixed with first beta-agonist nebulizer because it can take up to 20 min to begin having effect. Admitted controversy exists regarding efficacy of ipratropium, but it still should be part of total treatment picture.

Dosing

Adult

0.5 mg/nebulizer treatment; can be mixed with albuterol and used as part of first nebulized treatment on presentation to hospital; can be given up to 3 times over the first hour of therapy

Pediatric

Not established

Interactions

Drugs with anticholinergic properties, such as dronabinol, may increase toxicity; albuterol increases effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

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

Precautions

Not indicated for acute episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction

Ipratropium and albuterol (Combivent)

Ipratropium is chemically related to atropine. Has anti-secretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa.
Albuterol is a beta-agonist for bronchospasm refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility.
Recommended to "test spray" 3 times before using the first time and in cases where the aerosol has not be used for >24 h.

Dosing

Adult

2 inhalations qid; may take additional inhalations prn; not to exceed 12 inhalations/24 h

Pediatric

Administer as in adults

Interactions

Drugs with anticholinergic properties, such as dronabinol, may increase toxicity; albuterol increases effects of ipratropium
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, 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, and cardiovascular disorders; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction

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 a capsule dosage form containing a dry powder for oral inhalation via the HandiHaler inhalation device. Helps patients with COPD 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 also cause constipation, increased heart rate, blurred vision, glaucoma, and urinary difficulty or retention; monitor patients with moderate-to-severe renal impairment

Salmeterol (Serevent Diskus)

By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasms. Effect also may facilitate expectoration.
Shown to improve symptoms and morning peak flows. 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

1 inhalation (50 mcg) bid at least 12 h apart

Pediatric

<4 years: Not established
>4 years: Administer as in adults

Interactions

Concomitant use of beta-blockers may decrease bronchodilating, and vasodilating effects of beta-agonists such as 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, tachycardia, 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; black box FDA warning describes that chronic use may result in increased asthma morbidity and mortality, use only as additional therapy for patients not adequately controlled on other asthma-controller medications (eg, low- to medium-dose inhaled corticosteroids) or for patients whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies, including salmeterol

Corticosteroids

These agents have been shown to be effective in accelerating recovery from acute COPD exacerbations. Although they may not make a clinical difference in the ED, they have some effect by 6-8 h into therapy; therefore, early dosing is critical.

Some newer studies are suggesting that inhaled corticosteroids (eg, nebulized budesonide) may be equally effective as IV or PO steroids in the mild-to-moderate exacerbation. In addition, level B evidence suggests that the addition of inhaled corticosteroids to oral agents at discharge may be very beneficial.

Methylprednisolone (Solu-Medrol, Medrol)

Usually given in IV form in ED for initiation of corticosteroid therapy, although PO form theoretically equally efficacious. Two forms equal in potency, time of onset, and adverse effects. Inhaled corticosteroids probably equally efficacious and have fewer adverse effects for patients discharged from ED.

Dosing

Adult

125 mg IV q6h recommended dose, but true optimal dose not known
Alternative: 1-2 mg/kg IV q6h; not to exceed 125 mg; this dose often used in children

Pediatric

Not established

Interactions

Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking concurrent diuretics

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular 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

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications

Electrolyte supplements

Magnesium is used to replenish stores that become depleted in periods of adrenergic excess such as asthma attacks, COPD exacerbations, and diuretic use.

Magnesium sulfate

Thought to produce bronchodilation through counteraction of calcium-mediated smooth muscle constriction. Again, for every study showing positive finding, probably another shows no benefit, but given properly, magnesium is safe and may have some benefit.

Dosing

Adult

1.2-2 g IV over 15 min; not to exceed 150 mg/min

Pediatric

Not established

Interactions

Concurrent nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade seen with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, or succinylcholine; may increase CNS effects and toxicity of CNS depressants and betamethasone; may increase cardiotoxicity of ritodrine

Contraindications

Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

May alter cardiac conduction, leading to heart block in digitalized patients; respiratory rate, deep tendon reflexes, and renal function should be monitored when administered parenterally; caution when administering magnesium dose because may produce significant hypertension or asystole; in overdose, calcium gluconate, 10-20 mL IV of 10% solution, can be given as antidote for clinically significant hypermagnesemia

Follow-up

Further Inpatient Care

• In patients in extremis, CPAP or BiPAP may be attempted prior to intubation. This can be started in the ED and continued for several hours in the hospital. Usual recommended settings are an inspiratory positive airway pressure (IPAP) of 10 cm H₂ O and an expiratory positive airway pressure (EPAP) of 2 cm H₂ O, with further adjustments based on the individual. This is contingent on the patient's ability to withstand the mask. This treatment is not a substitute for intubation; rather, it is a means of trying to avoid intubation.
• Heliox is an additional strategy that can be attempted prior to intubation. Whether Heliox or CPAP is used will depend on the individual patient and local hospital availability. Again, like several other therapies mentioned in this article, study results both for and against Heliox have been published. The current summation of that literature indicates that Heliox may actually decrease the work of breathing while the patient is breathing the mixture, but its effects are not long lasting once it is removed. The proper mixture of the gases and the ability to deliver enough oxygen to the patient are also issues.
• Inhaled nitric oxide has been suggested, but at this point does not seem to have a role in acute treatment.
• Lung volume reduction surgery has also been touted as effective, but most recent studies demonstrate varying levels of success.

Further Outpatient Care

• Disposition from the ED depends on the clinical picture for each patient more than any single laboratory value or test. In general, the longer the exacerbation, the more airway edema and debris are present, making resolution in the ED increasingly more difficult. Patients who state that they "feel back to normal" and have no overt reason for admission can reasonably be discharged home with follow-up arrangements. The corollary to this is that patients who state they "do not feel comfortable," regardless of the numbers, are the best predictors of outcome and probably should be admitted. Data on risk factors for relapse and need for admission are limited at present.
• For patients who are sent home, nearly all should receive a short steroid burst and an increase in the frequency of inhaler therapy. Close follow-up should be arranged with the patient's regular care provider. Other therapies should be considered on a case-by-case basis.
• Patients with severe or unstable disease should be seen monthly.
• When their condition is stable, patients may be seen biannually.
• Check theophylline level with each dose adjustment, then every 6-12 months.
• For patients on home oxygen, check ABGs yearly or with any change in condition. Monitor oxygen saturation more frequently than ABGs.
  

Inpatient & Outpatient Medications

• Bronchodilators 
  • Beta2-adrenoceptor agonists
    • See the Medication. Again, these agents are first-line therapy for COPD, both for acute exacerbations and for acute treatment. Bronchodilators are given on an as-needed basis or on a regular basis to prevent or reduce symptoms. Short-acting agents are usually used for immediate relief of symptoms, whereas long-acting inhaled agents are better for day-to-day mitigation of the disease.
    • Epinephrine or terbutaline can be administered subcutaneously when intravenous access is not possible or the patient is moving so little air that nebulizer therapy is ineffective. Terbutaline is thought to be safer in older patients, and it has shown to be more efficacious than epinephrine.
  • Methylxanthines: Theophylline increases collateral ventilation, respiratory muscle function, mucociliary clearance, and central respiratory drive. Despite this, many questions exist as to its true efficacy. In general, if the patient is already on theophylline and has a subtherapeutic level, a mini-loading dose is appropriate. If the patient is not on theophylline, the delay before benefit of the oral form makes it not worth using. Intravenous aminophylline has a propensity to cause arrhythmias, especially in a population that already has cholinergic excess coupled with coronary disease.
  • Anticholinergics: These are as effective as beta-agonists in acute attacks, and they have synergistic properties with the beta-agonists. They act by antagonizing the vagal innervation of the tracheobronchial tree. Vagal tone can be increased by as much as 50% in patients with COPD.
• Corticosteroids: These also have bronchodilatory properties, although they primarily act by decreasing inflammation in the tracheobronchial tree. Although 8-12 hours are required for full effect, corticosteroids should be administered in the ED, as some mild improvements may be noted much earlier.
• Antibiotics
  • Antibiotics effectively reduce treatment failure and mortality rates in patients with severe COPD exacerbations. However, with mild or moderate exacerbations, antibiotics may or may not be indicated.
  • In cases of severe acute exacerbations of chronic bronchitis (AECB), recent guidelines suggest using fluoroquinolone antibiotics as first-line therapy. This suggestion is based on level I evidence from several trials that show clinical and microbial superiority of these agents.
  • Use of fluoroquinolones has also been shown to shorten hospital stay, reduce recurrences, and lower costs.
  • Fortunately, resistance to these agents is still very low, and reserving them for use in populations at risk should preserve their effectiveness for some time.
• Magnesium  
  • Although controversial, administration of magnesium is thought to produce bronchodilation through the counteraction of calcium-mediated smooth muscle constriction.
  • Magnesium depletion is known to occur in periods of adrenergic excess (eg, asthma exacerbations, diuretic use).
• CPAP and BiPAP
  • These devices help to decrease the work of breathing and maintain positive end-expiratory pressure (PEEP).
  • Patients must be alert with no excess secretions.
• Heliox
  • Heliox usually is a 60:40 mixture of helium and oxygen.
  • Helium is a smaller particle than oxygen and in small airways promotes laminar flow and facilitates both oxygen transport and carbon dioxide diffusion.
  • Many patients who seem to breathe better on Heliox return to a worsened respiratory state when removed from Heliox.

Deterrence/Prevention

• For the vast majority of patients, cessation of smoking is the only true means of prevention.

Complications

• Some complications that must be anticipated in COPD treatment include the following:
  • Incidence of pneumothorax due to bleb formation is relatively high; consider pneumothorax in all patients with COPD who have increased shortness of breath.
  • In patients who require long-term steroid use, the possibility of adrenal crisis is very real; at a minimum, patients with steroid-dependent COPD should receive stress dosing in the event of an exacerbation or any other stressor.
  • Infection (common)
  • Cor pulmonale
  • Secondary polycythemia
  • Bullous lung disease
  • Acute or chronic respiratory failure
  • Pulmonary hypertension
  • Malnutrition

Prognosis

• Patient's age and postbronchodilator FEV₁ are the most important predictors of prognosis. Young age and FEV₁ greater than 50% of predicted are associated with a good prognosis. Older patients and those with more severe lung disease do worse.
• Supplemental oxygen (when indicated) has been shown to increase survival rates.
• Smoking cessation improves the prognosis.
• Cor pulmonale, hypercapnia, tachycardia, and malnutrition indicate a poor prognosis.

Patient Education

• The best education comes in 2 forms.
• Educate patients to the dangers of smoking and the improvement in quality of life attainable with smoking cessation.
• Instruct patients with COPD to present early during an exacerbation and to not wait until they are in distress.
• This author's observation is that many people with respiratory disease do not know the basic ways to monitor their own disease fluctuations. In addition, they are frequently not taking/using their inhalers as prescribed. Spending the 5 minutes it takes to make sure they have an aero chamber, are using the right dosages, the right medicines, and know when to seek help can go a long way in preventing a respiratory disaster.
• Printed material is available from the National Jewish Hospital in Denver, Colorado, as well as the American Lung Association.
• Instruct patients about appropriate pulmonary toilet.
• For excellent patient education resources, visit eMedicine's Lung and Airway Center. Also, see eMedicine's patient education articles Chronic Obstructive Pulmonary Disease (COPD), Cigarette Smoking, Asthma, and Emphysema.

Miscellaneous

Medicolegal Pitfalls

• Be wary of discharging patients with exacerbations when they do not feel comfortable with their breathing, regardless of their oxygen saturation, ABG, or other test results.
• Always look for underlying cardiac ischemia with acute exacerbations. With hypoxia and distress, many of these patients can have unrecognized underlying ischemia.
• Administer as much oxygen as necessary to avoid hypoxia. If the patient retains excessive carbon dioxide, intubate.
• A common mistake is utilizing a high respiratory rate after intubation. The patient most likely is acidotic and has marginally normal or low potassium level due to diuretic and bronchodilator therapy. With a too-rapid respiratory rate, the patient will become alkalotic, causing an intracellular shift in potassium with potentially dangerous hypokalemia as a result.

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Keywords

COPD, chronic bronchitis, cough, dyspnea, pulmonary infections, cardiac failure, respiratory failure, edema, weight gain, obesity, mucopurulent relapses, cachexia, blue bloater, pink puffer, asthma, wheeze, wheezing, emphysema, tobacco abuse, cystic fibrosis, alpha-1 antitrypsin deficiency, bronchiectasis, bullous lung disease, excessive mucus production, hyperplasia of mucus-producing glands, hypoxemia, polycythemia, hypercapnia, respiratory acidosis, cor pulmonale, hypoxemia, right heart failure, progressive exercise intolerance, recurrent pulmonary infections, progressive cardiac failure, progressive respiratory failure, progressive dyspnea, coarse rhonchi, wheezing, cyanosis, barrel chest, air pollution

Contributor Information and Disclosures

Author

Paul Kleinschmidt, MD, Consulting Staff, Department of Emergency Medicine, Womack Army Medical Center
Paul Kleinschmidt, MD is a member of the following medical societies: American Academy of Emergency Medicine and Special Operations Medical Association
Disclosure: Nothing to disclose.

Medical Editor

David FM Brown, MD, Assistant Professor, Department of Medicine, Division of Emergency Medicine, Harvard Medical School; Associate-Chief, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital
David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Paul Blackburn, DO, FACOEP, FACEP, Program Director, Department of Emergency Medicine, Maricopa Medical Center; Assistant Professor, Department of Surgery, University of Arizona
Paul Blackburn, DO, FACOEP, FACEP is a member of the following medical societies: American College of Emergency Physicians, American College of Osteopathic Emergency Physicians, American Medical Association, and Arizona Medical Association
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Program Director, Department of Emergency Medicine, University Hospitals, Case Medical Center
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

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