Approach Considerations
The defining feature of COPD is irreversible airflow limitation during forced expiration. This may result from a loss of elastic recoil due to lung tissue destruction or from an increase in the resistance of the conducting airways. The formal diagnosis of COPD is made with spirometry; when the ratio of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) is less than 70% of that predicted for a matched control, it is diagnostic for a significant obstructive defect. Other studies, including laboratory studies and imaging, are particularly important during acute exacerbations of disease.
No blood-based biomarkers are accepted in COPD. However, a study by Sin et al investigated the use of serum pulmonary and activation-regulated chemokine (PARC/CCL-18) as a potential biomarker. [42] The study determined that PARC/CCL-18 levels are elevated in COPD and track clinical outcomes.
A large retrospective review from the United Kingdom found that in the 5 years preceding a diagnosis of COPD, primary care practitioners and specialists had missed opportunities to diagnose the disease in 85% of patients. Of the almost 39,000 patients in the study, 32,900 had presented with clinical or test findings consistent with early COPD. Missed opportunities included lower respiratory tract consultations resulting in a prescription for antibiotics or oral steroids and chest radiography not leading to a COPD diagnosis. Women were more likely to be underdiagnosed than men. [43]
Arterial Blood Gas Analysis
Arterial blood gas (ABG) analysis provides the best clues as to acuteness and severity of disease exacerbation.
Patients with mild COPD have mild to moderate hypoxemia without hypercapnia. As the disease progresses, hypoxemia worsens and hypercapnia may develop, with the latter commonly being observed as the FEV1 falls below 1 L/s or 30% of the predicted value. Lung mechanics and gas exchange worsen during acute exacerbations.
In general, renal compensation occurs even in chronic CO2 retainers (ie, bronchitics); thus, pH usually is near normal. Generally, consider any pH below 7.3 to be a sign of acute respiratory compromise.
Serum Chemistries
Patients with COPD tend to retain sodium. In addition, serum potassium should be monitored carefully, because diuretics, beta-adrenergic agonists, and theophylline act to lower potassium levels.
Beta-adrenergic agonists also increase renal excretion of serum calcium and magnesium, which may be important in the presence of hypokalemia.
Chronic respiratory acidosis leads to compensatory metabolic alkalosis. In the absence of blood gas measurements, bicarbonate levels are useful for following disease progression.
Alpha1-Antitrypsin
Measure alpha1-antitrypsin (AAT) in all patients younger than 40 years, in those with a family history of emphysema at an early age, or patients with emphysematous changes with no smoking history. The diagnosis of severe AAT deficiency is confirmed when the serum level falls below the protective threshold value of 11 mmol/L (ie, in the range of 3-7 mmol/L).
Specific phenotyping is reserved for patients in whom serum levels are 7-11 mmol/L or when genetic counseling or family analysis is needed.
Also see Alpha1-Antitrypsin Deficiency.
Sputum Evaluation
In persons with stable chronic bronchitis, the sputum is mucoid and macrophages are the predominant cells. With an exacerbation, sputum becomes purulent because of the presence of neutrophils. Although the quality of sputum can vary between patients in chronic stable disease, an increase in the quantity of sputum production is often a sign of an acute exacerbation.
A mixture of organisms often is visible with Gram stain (see Sputum Culture). The pathogens cultured most frequently during exacerbations are Streptococcus pneumoniae and Haemophilus influenzae.Moraxella catarrhalis is also a common organism, and Pseudomonas aeruginosa can be seen in patients with severe obstruction.
B-Type Natriuretic Peptide
Human B-type natriuretic peptide (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. BNP is secreted by the ventricles of the heart when there is increased stretch of the myocytes (ie, in CHF).
By measuring BNP, it was thought that the ability to differentiate between CHF and COPD exacerbations would become much easier. However, clinical observation and research have shown that in cases of mild CHF exacerbation, differentiation between CHF and COPD is still not straightforward. A mild elevation of BNP must be taken in context with the overall clinical picture.
New biomarkers such as pro-BNP peptide assays are in development and may prove helpful in differentiating COPD from CHF exacerbations in the future.
Chest Radiography
As demonstrated in the images below, frontal and lateral chest radiographs of patients with emphysema reveal signs of hyperinflation, including flattening of the diaphragm, increased retrosternal air space, and a long, narrow heart shadow. Rapidly tapering vascular shadows accompanied by hyperlucency of the lungs are other signs of emphysema.
Chronic bronchitis is associated with increased bronchovascular markings and cardiomegaly.
With complicating pulmonary hypertension, the hilar vascular shadows are prominent, with possible right ventricular enlargement and opacity in the lower retrosternal air space.
Posteroanterior (PA) and lateral chest radiograph in a patient with severe chronic obstructive pulmonary disease (COPD). Hyperinflation, depressed diaphragm, increased retrosternal space, and hypovascularity of lung parenchyma are demonstrated.
A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragm on lateral chest radiograph.
A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragm on posteroanterior chest radiograph.
Computed Tomography
High-resolution CT (HRCT) scanning is more sensitive than standard chest radiography and is highly specific for diagnosing emphysema (outlined bullae are not always visible on a radiograph).
HRCT scanning may provide an adjunct means of diagnosing various forms of COPD (ie, lower lobe disease may suggest AAT deficiency) and may help the clinician to determine whether surgical intervention would benefit the patient. (See the CT image below.)
Severe bullous disease as seen on a computed tomography (CT) scan in a patient with chronic obstructive pulmonary disease (COPD).
Two-Dimensional Echocardiography
Many patients with long-standing COPD develop secondary pulmonary hypertension from chronic hypoxemia and vascular remodeling. This may result in eventual right-sided heart failure (cor pulmonale). However, even with severe COPD, the degree of pulmonary hypertension is usually only mild to moderate. Findings of severe pulmonary hypertension on echocardiogram or cardiac catheterization warrant further workup.
Two-dimensional echocardiography may be helpful as a screening tool to estimate pulmonary arterial systolic pressure and right ventricular systolic function, although formal cardiac catheterization is necessary to accurately confirm the diagnosis.
Pulmonary Function Tests
Pulmonary function tests are essential for the diagnosis and assessment of the severity of disease, and they are helpful in following its progress. (See the images below.) FEV1 is a reproducible test and is the most commonly used index of airflow obstruction.
In addition to the spirometry findings that define the disease, lung volume measurements often show an increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity often decreases. Dynamic hyperinflation during exercise is now thought be a greater contributor to the sensation of dyspnea than airflow obstruction alone (as measured by FEV1).
As many as 30% of patients have an increase in FEV1 of 15% or more after inhalation of a bronchodilator. However, the absence of bronchodilator response does not justify withholding therapy.
Carbon monoxide diffusing capacity is decreased in proportion to the severity of emphysema.
Pressure volume curve comparing lungs with emphysema, lungs with restrictive disease, and normal lungs.
Flow volume curve of a patient with emphysema shows marked decrease in expiratory flow, hyperinflation, and air trapping (patient B) compared with a patient with restrictive lung disease, who has reduced lung volumes and preserved flow (patient A).
Forced expiratory volume in 1 second (FEV1) can be used to evaluate the prognosis in patients with emphysema. The benefit of smoking cessation is shown here because the deterioration in lung function parallels that of a nonsmoker, even in late stages of the disease. Redrawn from Fletcher C, Peato R. The natural history of chronic airflow obstruction. Br Med J 1977; 1: 1645-1648.
Using lung function thresholds of 80% predicted and fixed cut points to determine whether a test result is abnormal could result in the misdiagnosis of more than 20% of patients referred for pulmonary function testing. This misclassification can be avoided by using the lower limit of normal-based 95% confidence interval. [44]
Six-Minute Walking Distance
The distance walked in 6 minutes (6MWD) is a good predictor of all-cause and respiratory mortality in patients with moderate COPD. [2, 3] Patients with COPD who desaturate during the 6MWD have a higher mortality rate than do those who do not desaturate.
Consequently, this test is used as a part of the BODE index (body mass index, obstruction [FEV1], dyspnea [modified Medical Research Council dyspnea scale], and exercise capacity [6MWD]), [28] which was designed to help predict mortality in COPD patients.
Other Studies
Pulse oximetry does not offer as much information as arterial blood gas (ABG) analysis. However, when combined with clinical observation, this test can be a powerful tool for instant feedback on a patient's status.
Electrocardiography
Coexisting cardiac disease is highly likely in patients with COPD. Electrocardiography can be used in establishing that hypoxia is not resulting in cardiac ischemia and that the underlying cause of respiratory difficulty is not cardiac in nature.
Right-Sided Heart catheterization
If pulmonary hypertension is suspected based on clinical findings or on estimates from 2-dimensional echocardiography, then right-sided heart catheterization may be performed to measure pulmonary artery pressures directly and to gauge the response to vasodilators.
Hematocrit
Chronic hypoxemia may lead polycythemia. A hematocrit greater than 52% in men or 47% in women is indicative of polycythemia. Patients should be evaluated for hypoxemia at rest, with exertion, or during sleep. Correction of hypoxemia should reduce secondary polycythemia in patients who have quit smoking.
CBC count
Also consider a CBC count with differential to aid in determining those more likely to respond to inhaled corticosteroids based on eosinophils. [45]
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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 airflow obstruction that is not fully reversible.
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Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells.
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Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells (high-powered view).
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Gross pathology of advanced emphysema. Large bullae are present on the surface of the lung.
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Gross pathology of a patient with emphysema showing bullae on the surface.
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At high magnification, loss of alveolar walls and dilatation of airspaces in emphysema can be seen.
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Posteroanterior (PA) and lateral chest radiograph in a patient with severe chronic obstructive pulmonary disease (COPD). Hyperinflation, depressed diaphragm, increased retrosternal space, and hypovascularity of lung parenchyma are demonstrated.
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A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragm on lateral chest radiograph.
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A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragm on posteroanterior chest radiograph.
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Severe bullous disease as seen on a computed tomography (CT) scan in a patient with chronic obstructive pulmonary disease (COPD).
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Pressure volume curve comparing lungs with emphysema, lungs with restrictive disease, and normal lungs.
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Flow volume curve of a patient with emphysema shows marked decrease in expiratory flow, hyperinflation, and air trapping (patient B) compared with a patient with restrictive lung disease, who has reduced lung volumes and preserved flow (patient A).
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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. Redrawn from Fletcher C, Peato R. The natural history of chronic airflow obstruction. Br Med J 1977; 1: 1645-1648.
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Oxygen therapy via nasal cannula.
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Home supplemental oxygen.
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Bilevel positive airway pressure (BiPAP).
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Pulmonary rehabilitation.
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Chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation.
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Chest radiograph of an emphysematous patient shows hyperinflated lungs with reduced vascular markings. Pulmonary hila are prominent, suggesting some degree of pulmonary hypertension (Correa da Silva, 2001).
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Schematic representation of another sign of emphysema on the lateral chest radiograph. When the retrosternal space (defined as the space between the posterior border of the sternum and the anterior wall of the mediastinum) is larger than 2.5 cm, it is highly suggestive of overinflated lungs. This radiograph is from a patient with pectus carinatum, an important differential diagnosis to consider when this space is measured (Correa da Silva, 2001).
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Close-up image shows emphysematous bullae in the left upper lobe. Note the subpleural, thin-walled, cystlike appearance (Correa da Silva, 2001).
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A, Frontal posteroanterior (PA) chest radiograph shows no abnormality of the pulmonary vasculature, with normal intercostal spaces and a diaphragmatic dome between the 6th and 7th anterior ribs on both sides. B, Image in a patient with emphysema demonstrating reduced pulmonary vasculature resulting in hyperlucent lungs. The intercostal spaces are mildly enlarged, and the diaphragmatic domes are straightened and below the extremity of the seventh rib (Correa da Silva, 2001).
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A, Lateral radiograph of the chest shows normal pulmonary vasculature, a retrosternal space within normal limits (< 2.5 cm), and a normal angle between the diaphragm and the anterior thoracic wall. B, Lateral view of the chest shows increased pulmonary transparency, increased retrosternal space (>2.5 cm), and an angle between the thoracic wall and the diaphragm >90 degrees. Straightening of the diaphragm can be more evident in this projection than on others (Correa da Silva, 2001).
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High-resolution CT (HRCT) in a patient after viral bronchiolitis obliterans demonstrates areas of airtrapping, which is predominant in the inferior lobes and associated with bronchiectasis in the left lower lobe. Note that the decreased attenuation caused by the airtrapping can simulate emphysema (Correa da Silva, 2001).
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Pediatric high-resolution CT (HRCT) shows a hyperinflated right lung with large pulmonary bullae due to congenital lobar emphysema (Correa da Silva, 2001).
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High-resolution CT (HRCT) demonstrates areas of centriacinar emphysema. Note the low attenuation areas without walls due to destruction of the alveoli septae centrally in the acini. Red element shows the size of a normal acinus (Correa da Silva, 2001).
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High-resolution CT (HRCT) shows large bullae in both inferior lobes due to uniform enlargement and destruction of the alveoli walls causing distortion of the pulmonary architecture (Correa da Silva, 2001).
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Panacinar emphysema of the left lung in a patient with a right lung transplant. Note the red element showing the size of a normal acinus and its discrepancy with the destroyed and enlarged airspaces of the left lower lobe (Correa da Silva, 2001).
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High-resolution CT (HRCT) shows subpleural bullae consistent with paraseptal emphysema. Red mark shows the size of a normal acinus (Correa da Silva, 2001).
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High-resolution CT (HRCT) shows enlarged air-spaces or bullae adjoining pulmonary scars, consistent with paracicatricial emphysema. Red mark shows the size of a normal acinus (Correa da Silva, 2001).
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CT densitovolumetry of a nonsmoker, healthy young patient shows normal lungs. Less than 0.35% of lungs have attenuations below -950 HU (Correa da Silva, 2001).
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Expiratory CT densitovolumetry shows no areas of airtrapping (Correa da Silva, 2001).
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CT densitovolumetry in a patient with lung cancer. Three-dimensional (3D) image shows that the cancer is in the portion of the right lung that was less affected by emphysema in a patient with poor pulmonary function (Correa da Silva, 2001).
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CT densitovolumetry shows the attenuation mask. Green areas are those with attenuation below the selected threshold (here, -950 HU to evaluate emphysema), and pink areas are those with attenuations above the threshold. Area outside the patient is highlighted in green because of air (Correa da Silva, 2001).
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CT densitovolumetry demonstrates irregular distribution of the emphysema, with substantial predominance in the left lung (Correa da Silva, 2001).
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Smoking Cessation
- Management of Inflammation
- Management of Infection
- Management of Sputum Viscosity and Secretion Clearance
- PPIs for Exacerbations and the Common Cold
- Oxygen Therapy and Hypoxemia
- Vaccination to Reduce Infections
- Alpha1-Antitrypsin Deficiency Treatment
- Inpatient Care
- Bullectomy
- Lung Volume Reduction Surgery
- Lung Transplantation
- Long-term Monitoring
- End-of-Life Care
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- Guidelines
- Medication
- Medication Summary
- Beta2-Adrenergic Agonists, Short-Acting
- Beta2-Adrenergic Agonists, Long-Acting
- Anticholinergics, Respiratory
- Xanthine Derivative
- Phosphodiesterase-4 Inhibitors
- Corticosteroids, Inhalant
- Corticosteroids, Oral
- Beta-Adrenergic Agonist and Anticholinergic Agent Combinations
- Beta2-Adrenergic Agonist and Corticosteroid Combinations
- Antibiotics
- Smoking Cessation Therapies
- Other Combinations
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