WORKUP

Lab Studies:

• Secondary polycythemia due to chronic hypoxemia may develop in severe COPD or in those patients who smoke excessively. A hematocrit of more than 52% in males and more than 47% in female indicates disease.

• Measure the AAT levels in all patients younger than 40 years or in those with a family history of emphysema at an early age. If the AAT level is low, then phenotyping should be obtained.

• Sputum

• In stable chronic bronchitis, sputum is mucoid, and macrophages are the predominant cell. With an exacerbation, sputum becomes purulent due to the presence of neutrophils. A mixture of organisms often is visible using a Gram stain.

• The pathogens most frequently cultured during exacerbation are Streptococcus pneumoniae and Haemophilus influenzae.

Imaging Studies:

• Chest radiograph

• Frontal and lateral chest radiographs reveal signs of hyperinflation, including a flattening of the diaphragm, 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 possible right ventricular enlargement and opacity in the lower retrosternal air space.

• Computed tomography scan

• High-resolution CT (HRCT) scan is more sensitive than the standard chest radiograph.

• HRCT scan is highly specific for diagnosing emphysema, and the outlined bullae are not always visible on a radiograph. This information does not alter therapy; therefore, a CT scan is not useful in the routine care of patients with COPD.

Other Tests:

• Pulmonary function tests

• These measurements are essential for the diagnosis and assessment of the severity of disease, and they are helpful in following its progress.

• FEV₁ is a reproducible test and is the most common index of airflow obstruction. Lung volume measurements may document an increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity decreases.

• Carbon monoxide diffusing capacity is decreased in proportion to the severity of emphysema.

• Arterial blood gases reveal mild-to-moderate hypoxemia without hypercapnia in the early stages. As the disease progresses, hypoxemia becomes more severe and hypercapnia supervenes. Hypercapnia commonly is observed as the FEV₁ falls below 1 L/s or 30% of the predicted value. The lung mechanics and gas exchange worsen during acute exacerbations.

• As many as 30% of patients have an increase in FEV₁ by 15% or more after inhalation of a bronchodilator. However, the absence of bronchodilator response does not justify withholding therapy.

TREATMENT

Medical Care: The goal of management is to improve daily living and the quality of life by preventing symptoms and the recurrence of exacerbations by preserving optimal lung function. Once the diagnosis of COPD is established, educate the patient about the disease. Encourage the patient to participate actively in therapy.

Smoking cessation continues to be the most important therapeutic intervention. Most patients with COPD have a history of smoking or are currently smoking tobacco products. A smoking cessation plan is an essential part of a comprehensive management plan. The success rates are low because of the addictive power of nicotine, the conditioned response to smoking-associated stimuli, and psychological problems, including depression, poor education, and forceful promotional campaigns by the tobacco industry. The process of smoking cessation must involve multiple interventions.

Oral and inhaled medications are used for patients with stable disease to reduce dyspnea and improve exercise tolerance. Most of the medications employed are directed at 4 potentially reversible causes of airflow limitation in a disease state that has largely fixed obstruction. The following factors may be present: (1) bronchial smooth muscle contraction, (2) bronchial mucosal congestion and edema, (3) airway inflammation, and (4) increased airway secretion.

Smoking cessation, physical intervention

The transition from smoking to not smoking occurs in 5 stages: precontemplation, contemplation, preparation, action, and maintenance. Smoking intervention programs include self-help, group, physician-delivered, workplace, and community programs.

Setting a quit date may be helpful. Physicians and other healthcare providers should participate in setting the target date and follow-up with respect to maintenance.

Successful cessation programs usually employ the following resources and tools: patient education, a quit date, follow-up support, relapse prevention, advice for healthy lifestyle changes, social support systems, and adjuncts to treatment (eg, pharmacological agents).

Smoking cessation, pharmacologic intervention

Supervised use of pharmacologic agents is an important adjunct to self-help and group smoking cessation programs.

Nicotine is the ingredient in cigarettes primarily responsible for the addiction. Withdrawal from nicotine may cause unpleasant adverse effects, including anxiety, irritability, difficulty concentrating, anger, fatigue, drowsiness, depression, and sleep disruption. These effects usually occur during the first several weeks.

Nicotine replacement therapies after smoking cessation reduce withdrawal symptoms. If a smoker requires his or her first cigarette within 30 minutes of waking up, they most likely are highly addicted and would benefit from nicotine replacement therapy.

Several nicotine replacement therapies are available. Nicotine polacrilex is a chewing gum and has better quit rates than counseling alone. Nicotine replacement therapy chewing pieces are marketed in 2 strengths (ie, 2 mg, 4 mg). An individual who smokes 1 pack per day should use 4-mg pieces. The 2-mg pieces are to be used by individuals who smoke less than 1 pack per day. Instruct the patient to chew hourly and also to chew when needed for their initial cravings for 2 weeks. Gradually reduce the amount chewed over the next 3 months.

Transdermal nicotine patches are available readily for replacement therapy. Long-term success rates are 22-42%, compared to 2-25% with a placebo. These agents are well tolerated, and the adverse effects are limited to localized skin reaction. Nicotine replacement therapy patches are sold under the following trade names: Nicoderm, Nicotrol, and Habitrol. Each of these products is dosed with a scheduled graduated decrease in nicotine over 6-10 weeks.

The use of the antidepressant bupropion (Zyban) also is effective for smoking cessation. This nonnicotine aid to smoking cessation enhances central nervous nonadrenergic function. A recent study demonstrated that 23% of patients sustained cessation at 1 year, compared to 12% who sustained cessation with the placebo. Bupropion also may be effective in patients who not been able to quit smoking with nicotine replacement therapy.

Anti-inflammatory agents, inhaled steroids

A minority of COPD patients who respond to oral corticosteroids can be maintained on long-term inhaled steroids.

Despite a lack of conclusive evidence to support the role of inhaled corticosteroids in the management of COPD, the use of these agents is widespread. Researchers completed 3 large placebo-controlled trials investigating the use of these agents in severe, mild, and very mild disease. Based on the rate of decline in FEV₁, results from these 3 trials suggest that inhaled corticosteroids did not slow the decline in lung function but decreased the frequency of exacerbations and improved disease-specific and health-related quality of life.

Inhaled corticosteroids have fewer adverse effects than oral agents. Although effective, these agents improve expiratory flows less effectively than oral preparations, even at high doses. These agents may be beneficial in slowing the rate of progression in a subset of patients with COPD who have rapid decline.

Bronchodilators

Inhaled beta2-agonist bronchodilators activate specific B2-adrenergic receptors on the surface of smooth muscle cells, which increases intracellular cyclic adenosine monophosphate (AMP) and smooth muscle relaxation. Patients, even those who have no measurable increase in expiratory flow, benefit from treatment using beta2 agonists.

The popularity of methylxanthines has decreased over last decade because of the narrow therapeutic range and frequent toxicity. The mechanism of actions may involve increased intracellular calcium transport, adenosine antagonism, and prostaglandin E2 inhibition. Additionally, methylxanthines may improve diaphragm muscle contractility.

In COPD, beta2 agonists produce less bronchodilatation compared to asthma. Furthermore, spirometric changes may be insignificant despite symptomatic benefit. Patients primarily use beta2 agonists for relief of symptoms of COPD. Inhaled beta2 agonists are the initial treatment of choice for acute exacerbations of COPD.

In stable patients, beta2 agonists have an additive effect when used with an anticholinergic agent (eg, ipratropium bromide). Although oral preparations of beta2 agonists are available, the preferred route of administration is inhalation. Use a spacer if indicated to improve aerosol delivery and reduce adverse effects.

Two long-acting beta2 agonists (ie, formoterol, salmeterol) are available. They may be useful in patients who use short-acting bronchodilators frequently or for prevention of nocturnal symptoms. More studies should establish the best role for these agents.

Anticholinergic agents

Treatment with aerosolized anticholinergic agents (eg, ipratropium bromide) may be more effective than a beta2 agonist in patients with COPD. Ipratropium bromide has bronchodilatory activity with minimum adverse effects and is administered by a metered-dose inhaler.

Studies in patients with stable COPD have shown that ipratropium bromide has equivalent or superior activity when compared with a beta2 agonist. In combination with a beta2 agonist, an additional 20-40% bronchodilation occurs. This medication has slower onset and a longer duration than a beta2 agonist and is less suitable for use as on an as needed basis.

Inhaled anticholinergic bronchodilators do not influence the long-term decline of FEV₁. Initiate regular therapy with ipratropium at 2-4 puffs 4 times a day and add a beta2 agonist as needed.

Anticholinergic drugs compete with acetylcholine for postganglionic muscarinic receptors, thereby inhibiting cholinergically mediated bronchomotor tone, resulting in bronchodilatation. They block vagally mediated reflex arcs that cause bronchoconstriction. The onset of action is slower (eg, 30-60 min) than inhaled beta2 agonists.

Long-acting bronchodilators

In addition to its anti-inflammatory effects, theophylline improves respiratory muscle function, stimulates the respiratory center, and promotes bronchodilation. Adding theophylline to the combination of bronchodilators can result in further benefit in stable COPD. The response to theophylline therapy also may vary among patients with severe COPD. Patients metabolize theophylline primarily by the hepatic enzyme system, a process affected by age, the heart, and liver abnormalities. Monitor serum levels of theophylline during therapy because of the drug's potential for toxicity. Adverse effects include anxiety, tremors, insomnia, nausea, cardiac arrhythmia, and seizures.

Oral steroids

The use of corticosteroids requires a careful evaluation for individual patients on adequate bronchodilator therapy who do not improve sufficiently or who develop an exacerbation. Most studies suggest that 20-30% of patients with COPD improve if administered long-term oral steroid therapy. Carefully document the effectiveness of such therapy (ie, >20% improvement in FEV₁) before administering prolonged daily or alternate day treatment.

Researchers found a positive correlation between bronchial eosinophilia and bronchodilator response in patients who had mild-to-moderate airflow obstruction. Outpatients have used oral steroids with success to treat acute exacerbations. However, after stabilization, gradually wean patients off oral corticosteroids because of their potential adverse effects.

In a recent meta-analysis of 16 controlled trials in stable COPD, researchers found that approximately 10% of individuals respond to these drugs. Carefully identify recipients. An increase in FEV₁, by more than 20% has been used as a surrogate marker for steroid response. In acute exacerbation of COPD, use steroids routinely to improve symptoms and lung function.

Antibiotics

In patients with COPD, chronic infection or colonization of the lower airways is common from Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. The goal of antibiotic therapy in COPD is not to eliminate organisms but to treat acute exacerbations. Exacerbations are indicated by increased sputum purulence and volume and the development of dyspnea along with other features, including fever, leukocytosis, or infiltrate on a chest radiograph.

The first-line treatment choices include amoxicillin, cefaclor, or trimethoprim/sulfamethoxazole. Second-line antibiotic regimens are the more expensive antibiotics, including azithromycin, clarithromycin, and fluoroquinolones.

The use of antibiotics in patients with COPD is supported by the results of a meta-analysis showing that patients who received oral antibiotic therapy had a small, but clinically significant, improvement in peak expiratory flow rate and a more rapid resolution of symptoms. Patients who benefitted most were those whose exacerbations were characterized by at least 2 of the following: increases in dyspnea, sputum production, and sputum purulence (ie, Winnipeg criteria).

Mucolytic agents

These agents reduce sputum viscosity and improve secretion clearance. Viscous lung secretions in patients with COPD consist of mucous-derived glycoproteins and leukocyte-derived DNA.

The oral agent N-acetylcysteine has antioxidant and mucokinetic properties and is used to treat patients with COPD. However, the efficacy of mucolytic agents in the treatment of COPD is debatable.

Oxygen therapy

COPD commonly is associated with progressive hypoxemia. Oxygen administration reduces mortality rates in patients with advanced COPD because of the favorable effects on pulmonary hemodynamics.

Two landmark trials, The British Medical Research Counsel (MRC study) and the National Heart, Lung, Blood Institutes Nocturnal Oxygen Therapy Trial (NOTT), showed that long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD. Hypoxemia is defined as PaO₂ of less than 55 mm Hg or oxygen saturation of less than 90%. Oxygen was used from 15-19 hours per day.

Specialists recommend long-term oxygen therapy, therefore, for patients with a PaO₂ of less than 55 mm Hg, a PaO₂ of less than 59 mm Hg with evidence of polycythemia, or cor pulmonale. Reevaluate these patients 1-3 months after initiating therapy because some patients may not require long-term oxygen.

Many patients with COPD who are not hypoxemic at rest worsen during exertion. Even though the studies designed to determine the long-term benefit of oxygen solely for exercise have not yet been conducted, home supplemental oxygen commonly is prescribed for these patients. Oxygen supplementation during exercise can prevent increases in pulmonary artery pressure, reduce dyspnea, and improve exercise tolerance.

Oxygen therapy generally is safe. Oxygen toxicity from high-inspired concentrations (ie, >60%) is well recognized. Little is known about the long-term effects of low-flow oxygen. The increased survival and quality of life benefits of long-term oxygen therapy outweigh the possible risks. PaCO₂ retention from depression of hypoxic drive has been overemphasized. PaCO₂ retention is more likely a consequence of ventilation/perfusion mismatching rather than respiratory center depression. While this complication is not common, it is best avoided by titration of oxygen delivery to maintain PaO₂ at 60-65 mm Hg.

The major physical hazards of oxygen therapy are fires or explosions. Patients, family, and other caregivers must be warned not to smoke. Overall, major accidents are rare and can be avoided by good patient and family training.

• Oxygen delivery systems

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

• Oxygen conserving devices function by delivering all of the supplemental oxygen during early inhalation. These devices improve the portability of oxygen therapy and may reduce overall costs. Three distinct oxygen-conserving devices exist—reservoir cannulas, demand pulse delivery devices, and transtracheal oxygen delivery.

• Transtracheal oxygen delivery involves the insertion of a catheter percutaneously between the second and third tracheal interspace. Transtracheal oxygen delivery is invasive and requires special training by the physician, the patient, and the caregiver. The procedure has risks as well as medical benefits but has limited application.

Surgical Care: Over the past 50-75 years, researchers have described a variety of surgical approaches to improve symptoms and restore function in patients who have emphysema. Only giant bullectomy and, possibly, the lung volume reduction surgery (LVRS) are useful.

• Bullectomy

• Removal of giant bullae has been a standard approach in selected patients for many years.

   

• The bullae in patients with emphysema generally range in size from 1-4 cm in diameter; however, on occasion, bullae can occupy more than 33% of the hemithorax (eg, giant bullae).

   

• Giant bullae may compress adjacent lung tissue, thereby reducing the blood flow and ventilation to the healthy tissue. Removal of these bullae may result in the expansion of compressed lungs and improved function.

   

• Patients who are symptomatic and have an FEV₁ of less than 50% of the predicted value have a better outcome after bullectomy. This surgery is performed through midline sternotomy, a lateral incision, or by video-assisted thoracoscopy. Postoperative bronchopleural air leak is the major potential complication.

   

• Giant bullectomy can produce subjective and objective improvement in selected patients—in those who have bullae that occupy at least 30%, and preferably 50%, of the hemithorax and compress adjacent lung, who have FEV₁ of less than 50% of the predicted value, and who otherwise have relatively preserved lung function.

• Lung volume reduction surgery

• Nearly 40 years ago, Brantigan et al first reported resectional surgery for diffuse emphysema in 33 patients. They resected 20-30% of each lung that appeared most diseased. Brantigan hypothesized that removal of a portion of the emphysematous lung increased the radial traction on the airways in the remaining lung, improving expiratory airflow and mechanical function of the respiratory system, thereby reducing symptoms.

• Recently, the LVRS gained considerable momentum after researchers documented a marked improvement in the FEV₁ (ie, +82%), the FVC (ie, +27%), and the 6-minute walk distance and quality of life indices. Currently, large prospective studies are underway in the United States and Canada to evaluate the effectiveness and the long-term outcome and benefits of LVRS.

• The indications and patient selection criteria for LVRS are not rigorously defined. Generally, the candidates for LVRS have symptoms secondary to severe emphysema, marked hyperinflation (ie, elevated residual volume [RV]/total lung capacity [TLC] ratio), and CT scan evidence of heterogeneous emphysema. The study excluded patients who are hypercapnic or have pulmonary hypertension or other cardiac risk factors.

• The surgical approach uses a midline sternotomy with stapling of the lung margins. Surgeons generally resect 20-30% of each lung from the upper zones. The LVRS procedure has a mortality rate of 0-18%. Several complications, including pneumonia and prolonged air leaks, have been observed.

• Lung transplantation

• Lung transplantation is a relatively new therapy for advanced lung disease. Patients with COPD are the largest single category of patients who undergo the process. The timing of transplant is difficult, but patients selected to receive a transplant should have a life expectancy of 2 years or less due to COPD.

• With lung transplantation, the profound dyspnea and limited lifestyle is exchanged for an improved quality of life but at the risk of worsening survival.

MEDICATION

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Bronchodilators -- These agents act to decrease muscle tone in both small and large airways in the lungs, thereby increasing ventilation. Category includes subcutaneous medications, beta-andrenergics, methylxanthines, and anticholinergics.

Drug Name	Albuterol (Proventil, Ventolin) -- Beta agonist for bronchospasm refractory to epinephrine. 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 are prescribed initially as needed. May increase frequency. Institute regular schedule in patients on anticholinergic drugs who remain symptomatic. Available as liquid for nebulizer, metered-dose inhalers, and dry powder inhalers.
Adult Dose	MDI: 2 puffs q3-4h Nebulizer: 0.2-0.3 mL of 5% albuterol solution diluted to 2.5 mL with NS tid/qid; unit dose vials are available
Pediatric Dose	MDI: <12 years: Not recommended >12 years: Administer as in adults Nebulizer: Infants and children: 0.01-0.02 mL of 5% solution diluted in 2-3 mL NS q4-6h Adolescents: Administer as in adults
Contraindications	Documented hypersensitivity; preexisting cardiac arrhythmia associated with tachycardia
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
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	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; adverse effects include muscle tremors, nervousness, insomnia, transient hypoxemia, and tachycardia; caution in hyperthyroidism, diabetes mellitus, hypertension, ischemic heart disease, seizures, and pheochromocytoma

Drug Name	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 are still symptomatic. Available as liquid for nebulizer, metered-dose inhalers, and dry powder inhalers.
Adult Dose	MDI: 2 puffs q3-4h Nebulizer: 0.2-0.3 mL of 5% solution diluted to 2.5 mL with NS tid/qid
Pediatric Dose	MDI: <12 years: Not recommended >12 years: Administer as in adults Nebulizer: Infants and children: 0.01-0.02 mL of 5% solution diluted in 2-3 mL NS q4-6h Adolescents: Administer as in adults
Contraindications	Documented hypersensitivity; cardiac arrhythmias
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
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism, diabetes mellitus, pheochromocytoma, and cardiovascular disorders; adverse effects include muscle tremors, nervousness, insomnia, transient hypoxemia, and tachycardia

Drug Name	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 beta agonist.
Adult Dose	MDI: 2-4 puffs q4-6h Nebulizer: 250 mcg diluted with 2.5 mL NS q4-6h
Pediatric Dose	MDI: 1-2 puffs tid; not to exceed 6 puffs per d Nebulizer: 250 mcg tid
Contraindications	Documented hypersensitivity
Interactions	Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol may increase effects
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Not indicated for acute episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction

Drug Name	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 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.
Adult Dose	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 Dose	Children: 10 mg/kg/d PO divided doses q8-12h initial; 10 mg/kg/d PO qd or bid maintenance; adjust dose in 25% increments to maintain serum theophylline level of 5-15 mcg/mL; not to exceed 16 mg/kg/d
Contraindications	Documented hypersensitivity; uncontrolled arrhythmias; peptic ulcers; hyperthyroidism; uncontrolled seizure disorders
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
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Name	Salmeterol (Serevent) -- 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 >12h. Used on a fixed schedule in addition to regular use of anticholinergic agents.
Adult Dose	2 puffs bid
Pediatric Dose	<4 years: Not established 4-12 years: 1 inhalation (50 mcg) bid at least 12h apart >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; angina; cardiac arrhythmias associated with tachycardia
Interactions	Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta agonists; 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
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Not indicated to treat acute asthmatic symptoms; adverse effects are tremors, nervousness, and tachycardia

Drug Name	Formoterol (Oxis, Foradil) -- By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, formoterol 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 >12h. Used on a fixed schedule in addition to regular use of anticholinergic agents.
Adult Dose	12-25 mcg bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; angina; cardiac arrhythmias associated with tachycardia
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
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Not indicated to treat acute asthmatic symptoms; adverse effects are tremors, nervousness, and tachycardia

Drug Category: Corticosteroids -- A recent meta-analysis of 16 controlled trials in stable COPD found that approximately 10% of patients respond to these drugs. The responders should be identified carefully. An increase in FEV₁ >20% is used as surrogate marker for steroid response. In acute exacerbation, steroids improve symptoms and lung functions. Inhaled steroids have fewer adverse effects compared to oral agents. Although effective, these agents improve expiratory flows less effectively than oral preparations, even at high doses. These agents may be beneficial in slowing rate of progression in a subset of patients with COPD who have rapid decline.

Drug Name	Fluticasone (Flovent) -- Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary-adrenocortical axis inhibitory potency when applied topically. Effectiveness is not established.
Adult Dose	Initial: 250-500 mcg bid Previous therapy: Bronchodilator alone: 88 mcg bid; may titrate to 440 mcg bid prn Inhaled corticosteroids: 88-220 mcg bid; may titrate to 440 mcg bid prn Oral steroids: 880 mcg bid; not to exceed 880 mcg bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral, fungal, and bacterial infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Prolonged use, application 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

Drug Name	Budesonide (Pulmicort Turbuhaler) -- Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary-adrenocortical axis inhibitory potency when applied topically. Effectiveness is not established.
Adult Dose	Previous therapy: Bronchodilator alone: 200-400 mcg bid; may titrate to 400 mcg bid prn Inhaled corticosteroids: 200-400 mcg bid; may titrate to 800 mcg bid prn Oral steroids: 400-800 mcg bid; may titrate to 800 mcg bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral, fungal, and bacterial infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Prolonged use, application 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

Drug Name	Prednisone (Deltasone, Meticorten, Orasone) -- Conduct steroid trial to identify responders. Start corticosteroid therapy at 0.5-1 mg/kg of prednisone daily for 2-3 wk. If the FEV1 increases by 20% or more, taper dose to the minimum to maintain improvement.
Adult Dose	0.5-1 mg/kg/d PO qd, gradually taper to minimum 10-20 mg/d, the dose that maintains improvement is continued long-term
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Interactions	Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Category: Nicotine replacement therapies -- Works best when used in conjunction with a support program, such as counseling, group therapy, or behavioral therapy.

Drug Name	Nicotine patches (Habitrol, Nicoderm CQ) or nicotine polacrilex (Nicorette) -- Nicotine patches: Individuals who smoke >1 pack per d initially need a 21-mg patch, followed by 14-mg and 7-mg patches. Nicotine polacrilex: Nicotine is absorbed through the oral mucosa. Is absorbed quickly and closely approximates time course of plasma nicotine levels observed after cigarette smoking. Available as 2-mg or 4-mg gum in a box containing 96 pieces. Careful adherence to chewing instructions is important for effective use. The manufacturer recommends that the gum not be used longer than 6 mo. An individual who smokes one pack per d should use 4-mg pieces. The 2-mg pieces are to be used by individuals who smoke <1 pack per d. Instruct the patient to chew hourly and for initial cravings for 2 wk, then gradually reduce amount chewed over 3 mo.
Adult Dose	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 Nicotine polacrilex: 1 piece of gum (2 mg) per h as needed to abstain from smoking; not to exceed 30 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; nonsmokers; children; pregnancy; life-threatening arrhythmias; severe or worsening angina pectoris
Interactions	May decrease diuretic effects of furosemide and decrease cardiac output; may decrease absorption of glutethimide; may increase circulating cortisol and catecholamines; not for use in patients who continue to smoke, use snuff, chew tobacco, or use other nicotine products because it may increase toxicity of nicotine
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in peptic ulcer, coronary artery disease, angina, hypertension, peripheral arterial disease, diabetes, severe renal dysfunction, and hepatic dysfunction; may cause skin irritation

Drug Category: Beta-adrenergic agonist and anticholinergic agent combinations -- Combine the benefits of the rapid onset of a beta-adrenergic agonist with the prolonged action of an anticholinergic agent.

Drug Name	Ipratropium and albuterol (DuoNeb) -- Ipratropium is chemically related to atropine. Has antisecretory 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.
Adult Dose	3-mL vial administered qid via nebulization with up to 2 additional 3-mL doses allowed per d, if needed
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
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
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction

Drug Category: Antidepressants -- Used as a nonnicotine aid to smoking cessation. A recent study demonstrated 23% sustained cessation with bupropion tablets at 1 y, compared to a 12% sustained cessation with placebo. Bupropion also may be effective in patients for whom nicotine replacement therapy is ineffective.

Drug Name	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.
Adult Dose	150-mg tab qd for 3 d, then increase to 150 mg bid with at least 8 h between each dose for 7-12 wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; seizure disorder; anorexia nervosa; concurrent use with MAOIs
Interactions	Carbamazepine, cimetidine, phenytoin, and phenobarbital may decrease effects; toxicity increases with concurrent administration of levodopa and MAOIs
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal or hepatic insufficiency; doses >450/d significantly decrease seizure threshold; adverse effects include pruritus, angioedema, dyspnea, and insomnia; delusions and/or hallucinations may occur in patients who are depressed

Drug Category: Antibiotics -- Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Name	Cefuroxime (Zinacef) -- Second-generation cephalosporin. Maintains gram-positive activity that first-generation cephalosporins have. Adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Condition of patient, severity of infection, and susceptibility of microorganism determines proper dose and route of administration.
Adult Dose	2 g IV q6-8h
Pediatric Dose	80-160 mg/kg/d IV divided q4-6h
Contraindications	Documented hypersensitivity
Interactions	Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patient receiving potent diuretics such as loop diuretics; coadministration with aminoglycosides increase nephrotoxic potential
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Administer half dose if creatinine clearance is 10-30 mL/min and one-quarter dose if <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy

Drug Name	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 as well as potential for improved compliance through reduced dosing frequency. They also afford improved action against H influenzae.
Adult Dose	Day 1: 500 mg PO Days 2-5: 250 mg PO qd Alternatively, administer 500 mg IV qd
Pediatric Dose	<6 months: Not established >6 months: Day 1: 10 mg/kg PO once; not to exceed 500 mg/d Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide, sudden death may occur
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
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

Drug Name	Clarithromycin (Biaxin) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Initial therapy in otherwise uncomplicated pneumonia.
Adult Dose	500 mg PO bid for 10 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; coadministration of pimozide
Interactions	Toxicity increases with coadministration of fluconazole, astemizole, and pimozide; clarithromycin effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

FOLLOW-UP

Further Inpatient Care:

• Acute exacerbation of COPD

• Acute exacerbation of COPD is one of the major reasons for hospital admission in the United States.

   

• Because of the lack of clinical studies, the general consensus supports the need for hospitalization of patients who develop severe respiratory dysfunction, disease progression, and other comorbid conditions (eg, pneumonia, poor response to outpatient management).

   

• The purpose of hospitalization is to manage the patient's acute decompensation and to prevent further deterioration.

• Pharmacotherapy of COPD exacerbations

• Physicians recommend a stepwise approach to drug therapy that takes into consideration the causes and complications related to the exacerbation, the degree of reversible bronchospasm, recent drug use, and contraindications to treatment. Sedation and pain management must be provided, despite a potential for respiratory depression, to ensure patient comfort and safety.

   

• Patients with exacerbations respond to inhaled beta2 agonists and anticholinergic aerosols. Treatment is initiated with an inhaled beta2 agonist delivered via a spacer or nebulizer; inhaled ipratropium bromide usually is added. The combination therapy may act synergistically and may allow using lower dosages of beta agonists. The efficacy of theophylline or intravenous aminophylline is not definitely established, and theophylline and intravenous aminophylline may cause toxicity.

   

• Corticosteroids generally are recommended and may be used intravenously for a short period. When response occurs, lower the dosage. Careful observation and spirometric evaluation are needed to prove the continuing benefit of steroids after a course of 1-2 weeks.

• Antibiotic therapy

• When the patient has 2 or more Winnipeg criteria, prescribe an antibiotic.

   

• The risk stratification scheme for antibiotic selection is recommended as follows: treat low-risk patients with amoxicillin, trimethoprim/sulfamethoxazole, or doxycycline. Treat high-risk patients, those who had multiple exacerbations in the past, and/or those with underlying cardiopulmonary dysfunction with a new generation macrolide, a second-generation cephalosporin, or a fluoroquinolone.

• Intensive care admission: Indications for intensive care admission are confusion, lethargy, respiratory muscle fatigue, worsening hypoxemia, respiratory acidosis (ie, pH <7.30), or when a patient requires invasive or noninvasive mechanical ventilation.

• Assisted ventilation

• Progressive airflow obstruction may impair oxygenation and/or ventilation to the degree that the patient requires assisted ventilation.

   

• The general guidelines for determining the ideal time to initiate ventilatory support are (1) patients who have experienced progressive worsening of respiratory acidosis and/or altered mental status and (2) clinically significant hypoxemia despite supplemental oxygen.

• Patients may be treated with noninvasive mask ventilation or translaryngeal intubation and mechanical ventilation. Following noninvasive ventilation, provide adequate patient supervision and ensure patient's mental alertness and tolerance of appliances. Hemodynamic instability, difficulty with clearing of secretions, and copious secretions are contraindications to noninvasive assisted ventilation.

   

• The main goal of assisted positive pressure ventilation in acute respiratory failure complicating COPD is to rest the ventilatory muscles and restore gas exchange. Major risks are ventilator associated pneumonia, barotrauma, and laryngotracheal complications associated with intubation.

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 the patient's quality of life by decreasing airflow limitation, preventing secondary medical complications, and alleviating respiratory symptoms.

     

  • The 3 major goals of the comprehensive management of COPD are the following:

     

    1. Lessen airflow limitation

        

    2. Prevent and treat secondary medical complications (eg, hypoxemia, infection)

        

    3. Decrease respiratory symptoms and improve quality of life

• Pulmonary rehabilitation, a multidisciplinary team approach

• Successful implementation of a pulmonary rehabilitation program usually requires a team approach, with individual components provided by health care professionals who have experience in managing COPD (eg, physician, dietitian, nurse, respiratory therapist, exercise physiologist, physical therapist, occupational therapist, recreational therapist, cardiorespiratory technician, pharmacist, psychosocial professionals).

• This multidisciplinary approach emphasizes patient and family education, smoking cessation, medical management (eg, oxygen, immunization), respiratory and chest physiotherapy, physical therapy with bronchopulmonary hygiene, exercise, vocational rehabilitation, and psychosocial support.

• Benefits of pulmonary rehabilitation: As a result of rehabilitation, improvements occur in the objective measures of quality of life, well being, and health status, including a reduction in respiratory symptoms and an increase in exercise tolerance and functional activities (eg, walking, less anxiety and depression, increased feelings of control, self-esteem). Pulmonary rehabilitation also results in substantial savings in healthcare costs by reducing use of hospital and medical resources.

• Components of pulmonary rehabilitation

• Pulmonary rehabilitation programs usually are conducted in an outpatient setting. A rehabilitation program may include a number of components and should be tailored to the needs of the individual patient. Provide all patients who complete the program with guidelines for continuing at home.

• Education is key to comprehensive pulmonary rehabilitation. The educational component prepares the patient and families to be actively involved in providing care. This reliance on patients to assume charge of their care is known as collaborative self-management.

• Exercise training is a mandatory component of pulmonary rehabilitation. Patients with COPD should perform aerobic lower extremity endurance exercises regularly to enhance performance of daily activities and reduce dyspnea. Upper extremity exercise training improves dyspnea and allows increased activities of daily living requiring the use of upper extremities.

• Breathing retraining techniques (eg, diaphragmatic, pursed lip breathing) may improve the ventilatory pattern and prevent dynamic airway compression.

Prognosis:

• The predictors of mortality are aging, continued smoking, accelerated decline in FEV₁, moderate-to-severe airflow obstruction, poor bronchodilator response, severe hypoxemia, the presence of hypercapnia, development of cor pulmonale, and overall poor functional capacity.

• The mortality rate is 24% in patients admitted to the ICU with an acute exacerbation; this doubles for patients aged 65 years or older. FEV₁ is a reliable predictor of mortality from COPD. The mortality rate for patients who have an FEV₁ of less than 0.75 L/s is 30% at 1 year and 95% at 10 years.

• The American Thoracic Society (ATS) has recommended the clinical staging of COPD severity according to lung function. Stage I is FEV₁ of equal or more than 50% of the predicted value. Stage II is FEV₁ 35-49% of the predicted value, and stage III is FEV₁ less than 35% of the predicted value.

MISCELLANEOUS

Medical/Legal Pitfalls:

• Differentiating COPD from asthma is difficult because of overlap in the pathophysiology, clinical presentation, pulmonary function test results, and treatment. The approach to treatment and prognosis differ because of relative importance of anticholinergic versus beta2-agonist therapy and the use of corticosteroids or other inflammatory agents.

• Although exacerbations are an important event in the natural history of patients who have COPD, limited information is available on the frequency of exacerbations and their effect on the course of COPD. Many patients have subclinical exacerbations that should be treated aggressively to prevent complications.

• Controversy exists about which patients should receive a trial of systemic or inhaled corticosteroids. Although a small fraction improves markedly, no screening test identifies the responders and the characteristics that constitute improvement are unclear.

• AAT replacement therapy for those who are deficient is controversial. Long-term studies are underway to determine the efficacy of this treatment. Researchers have yet to determined the optimal dose and dosing regimen.

• Noninvasive ventilation to provide intermittent respiratory muscle rest is beneficial in a select group of patients but is considered controversial and requires further clinical studies.

• More information is required to determine whether pulmonary rehabilitation, lung volume reduction surgery, and/or lung transplantation represent cost effective interventions.

• Although preliminary studies show that inhaled corticosteroids may reduce progression of airflow obstruction, this should be confirmed with large prospective studies.

Special Concerns:

• Air travel

• Many commercial planes fly at altitudes of 30,000-40,000 feet. However, the cabin is pressurized to an altitude of 5000-8000 feet. At these altitudes, atmospheric partial pressure of oxygen (PO₂) is 132-109 mm Hg, compared to 159 mm Hg at sea level.

• Acute reduction in PO₂ stimulates peripheral chemoreceptors, which results in hyperventilation. A prediction equation used to estimate PaO₂ at 8000 feet (2440 m) is as follows:

   

  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 8000 feet is an indication for supplemental oxygen. Arrange supplemental oxygen prior to the flight directly through the airline or through the airline agent (at an extra expense).

• Sleep and COPD

• Patients with COPD may develop substantial decreases in nocturnal PaO₂ during all phases of sleep, but particularly during the rapid eye movement phase. These episodes initially are associated with a rise in pulmonary arterial pressures and disturbance in sleep architecture, but they may develop into pulmonary arterial hypertension and cor pulmonale if hypoxemia remains untreated.

• Prescribe oxygen for patients who have daytime PaO₂ greater than 60 mm Hg but demonstrate substantial nocturnal hypoxemia.

PICTURES

Caption: Picture 1. Venn diagram of chronic obstructive pulmonary disease (COPD). Chronic obstructive lung disease is a disorder in which subsets of patients may have dominant features of chronic bronchitis, emphysema, or asthma. The result is irreversible airflow obstruction.
Picture Type: Graph

Caption: Picture 2. Chronic obstructive pulmonary disease (COPD). Gross pathology of advanced emphysema. Large bullae are present on the surface of the lung.
Picture Type: Photo

Caption: Picture 3. Chronic obstructive pulmonary disease (COPD). Gross pathology of a patient with emphysema showing bullae on the surface.
Picture Type: Photo

Caption: Picture 4. Chronic obstructive pulmonary disease (COPD). Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells.
Picture Type: Photo

Caption: Picture 5. Chronic obstructive pulmonary disease (COPD). Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells (high powered view).
Picture Type: Photo

Caption: Picture 6. Chronic obstructive pulmonary disease (COPD). At high magnification, in emphysema, loss of alveolar walls and dilatation of airspaces occurs.
Picture Type: Photo

Caption: Picture 7. Chronic obstructive pulmonary disease (COPD). Pressure volume curve comparing lungs with emphysema lungs and restrictive lungs to normal lungs.
Picture Type: Graph

Caption: Picture 8. Chronic obstructive pulmonary disease (COPD). Flow volume curve of lungs in 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).
Picture Type: Graph

Caption: Picture 9. Chronic obstructive pulmonary disease (COPD). 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.
Picture Type: Graph

Caption: Picture 10. Posteroanterior (PA) and lateral chest radiograph in a patient with severe Chronic obstructive pulmonary disease (COPD). Hyperinflation, depressed diaphragms, increased retrosternal space, and hypovascularity of lung parenchyma is demonstrated.
Picture Type: X-RAY

Caption: Picture 11. Chronic obstructive pulmonary disease (COPD). A CT scan shows hyperlucency due to hypovascularity and bullae formation diffusely, predominantly in upper lobes.
Picture Type: CT

Caption: Picture 12. Chronic obstructive pulmonary disease (COPD). A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on lateral chest radiograph.
Picture Type: X-RAY

Caption: Picture 13. Chronic obstructive pulmonary disease (COPD). A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on posteroanterior chest radiograph.
Picture Type: X-RAY

Caption: Picture 14. Severe bullous disease observed on CT scan in a patient with chronic obstructive pulmonary disease (COPD).
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Picture Type: CT

Caption: Picture 15. Chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation.
Picture Type: Photo

Caption: Picture 16. Chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation.
Picture Type: Photo

Caption: Picture 17. Chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation.
Picture Type: Photo

Caption: Picture 18. Chronic obstructive pulmonary disease (COPD).
Picture Type: Photo

Caption: Picture 19. Chronic obstructive pulmonary disease (COPD). Bilevel positive airway pressure (BiPAP).
Picture Type: Photo