Chronic Obstructive Pulmonary Disease (COPD) Workup
- Author: Zab Mosenifar, MD, FACP, FCCP; Chief Editor: Ryland P Byrd, Jr, MD more...
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. 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.
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.
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.
Measure alpha1-antitrypsin (AAT) in all patients younger than 40 years or in those with a family history of emphysema at an early age. 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.
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.
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.
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.
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.)
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.
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.
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]), which was designed to help predict mortality in COPD patients.
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.
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.
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.
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