Pulmonary function tests provide key physiologic clues to disease processes, yet they remain underused in primary care settings.
Although pulmonary function testing (PFT) is simple and noninvasive, its individual components provide clinicians with a concise, in-depth picture of a patient’s respiratory physiology. PFT results reflect compliance, resistance, ventilation, perfusion, and gas exchange; most respiratory diseases adversely affect one or more of these factors. Many patients present with generalized symptoms, such as shortness of breath, but PFT results can allow clinicians to distinguish between restrictive and obstructive diseases and can help guide therapy and/or further diagnostic workup.
Lung Volumes And Airflow
Figure 1, page 34, illustrates static lung volumes. The total lung capacity (TLC) has four components: tidal volume (Vt), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), and residual volume (RV). Other physiologically useful measurements, such as inspiratory capacity and functional residual capacity (FRC), also incorporate some of these component volumes. The vital capacity (VC), or IRV Vt ERV, however, represents the most useful tool for identifying lung disease. In fact, VC is almost always reduced in restrictive lung disease, and is usually reduced in obstructive lung disease because air trapping limits the lungs’ ability to empty.
The forced expiratory VC also serves as a marker for detecting abnormalities in airflow rates. After a full inspiration, the patient forcefully exhales for at least 6 seconds until no more gas can be expelled. Figure 2, page 34, shows the time course of lung volume changes, which can be measured directly by a volume displacement spirometer or indirectly by an airflow transducer. In patients with high airway resistance, such as asthma patients during exacerbations, the time required to complete expiration is prolonged.
The forced expiratory volume in 1 second (FEV1) is another measure of airway resistance and can be a useful way to describe the time course of lung emptying. Figure 3, page 36, compares a healthy subject to patients with obstructive and restrictive lung disease. Clearly, FEV1 is reduced in both obstructive and restrictive disease. Its ratio to VC, however, is a useful marker for the presence of airflow obstruction. In healthy subjects, FEV1/VC is approximately 0.8; it tends to be much shorter in patients with obstructive lung disease; in fact, a reduced FEV1/VC is diagnostic of obstructive disease.
One can measure forced vital capacity (FVC) after the use of an inhaled bronchodilator to detect reversible obstruction. Albuterol and other b-agonists with a short onset of action are typically used to treat patients with reversible airway obstruction. An increase in FEV1 of 12 percent or more with an improvement in FEV1 of at least 200 mL is generally considered a significant bronchodilator response, although other criteria have been proposed. The lack of an improvement in FEV1 after bronchodilator use, however, does not mean that the patient will not respond clinically to bronchodilator therapy.
The Flow-Volume Loop
FVC maneuvers can be used to display airflow abnormalities graphically. When flow is plotted against volume, a continuous loop is formed. In healthy people, the expired flow rate quickly rises and peaks before approximately 25 percent of the VC has been exhaled. Flow then declines in an almost linear fashion with volume. In patients with appreciable airflow obstruction, exhalation begins with a rapid increase in flow but then slows radically as positive intrapleural pressure causes airways to collapse; this produces a concave flow-volume curve. In restrictive lung disease, the curve is usually normal in configuration but significantly smaller.
Spirometry cannot measure RV. As a result, spirometry alone cannot determine TLC. Fortunately, other methods, such as nitrogen washout, helium dilution, and body plethysmography allow the determination of RV by measuring FRC or the sum of RV and ERV.
Nitrogen washout measures the volume of nitrogen in the lung at the end of exhalation. Because air contains 79 percent nitrogen, the FRC can be easily calculated if the volume of nitrogen in the lung at the end of exhalation is known. The patient breathes through a valve; at the end of an exhalation, the gas supplied through the inspiratory port is changed from air to 100 percent oxygen. After the patient starts breathing 100 percent oxygen, the nitrogen contained in the exhaled gas reflects the amount originally residing in the lung. During the next few minutes, the nitrogen concentration in the lung declines as it is diluted by the inspired 100 percent oxygen. Within approximately 7 minutes, patients with normal lungs have exhaled virtually all of the nitrogen and replaced it with oxygen. The exhaled nitrogen is then measured, with FRC calculation being based on the total volume of nitrogen exhaled.
In FRC measurement through helium dilution, the patient, at the end of expiration, breathes exclusively from a gas bag with a known volume. The bag contains a known concentration of helium and air. At the end of several minutes of rebreathing, the helium is distributed evenly within the bag and the lungs. Assuming that no helium is present in the lungs before the test begins, the amount of helium in the bag before the test equals the amount of helium in the lungs and bag together after equilibration. Because the initial bag volume and initial helium fraction are known, the lung volume can be easily calculated.
Body plethysmography is also used to determine FRC. The patient, in a sealed enclosure, breathes through a mouthpiece connected to the outside of the enclosure. The RCP then briefly occludes the mouthpiece and watches as the patient pants against the closed shutter. The pressure fluctuation in the lung gas is measured at the mouth during the panting maneuver. The volume change in the thorax produced by this pressure fluctuation in the lung gas is measured indirectly using the pressure fluctuation within the body plethysmograph. The larger the volume of gas within the lung, the larger the volume change of the thorax (for a given change in pressure).
When FRC is added to inspiratory capacity, TLC can be calculated. In obstructive lung disease, TLC can be greater than predicted or can be normal. In restrictive lung disease, TLC will be lower than predicted.
Maldistribution Of Ventilation
Because airway resistance and compliance vary in different regions of the lung, ventilation does not occur uniformly. There is also a gravity-based tendency for inspired gas to go to basilar alveoli. In obstructive lung disease, the distribution of ventilation worsens because regional differences in airway resistance and airspace compliance affect the rate at which airspaces empty and fill. In fact, this maldistribution may be an earlier manifestation of obstructive lung disease than are detectable spirometric changes.
The most commonly used measure of maldistribution of ventilation is the single-breath oxygen test. The patient exhales fully and takes one breath of 100 percent oxygen. The patient is then asked to exhale slowly while an instrument continually measures the concentration of nitrogen in the exhalate. The gases exhaled first are from the anatomic dead space and contain no nitrogen. Subsequently, there is a rapid rise in nitrogen concentration as the alveolar gas is exhaled. At first, the alveolar gases come from airways with lower resistance, while alveoli with higher resistance tend to empty later. When the concentration of nitrogen is plotted against volume (Figure 3), the initial slope of the curve serves as an index of maldistribution of ventilation. In normal subjects, the change in nitrogen concentration between 0.75 L and 1.251 L of exhalation will increase at a rate of less than 2 percent. If nitrogen concentration increases at a greater rate, substantial maldistribution of ventilation may be occurring.
Diffusing capacity reflects a functioning and cohesive capillary bed is in contact with alveoli. Because the pulmonary capillary partial pressure of carbon monoxide is essentially zero, and because carbon monoxide binds strongly to hemoglobin, carbon monoxide is an ideal marker for measuring gas transfer. After maximal exhalation, the patient takes in a maximal inhalation of the test gas (containing carbon monoxide), holds his or her breath for 10 seconds, then exhales fully. During this 10-second period, the alveolar concentration of carbon monoxide declines exponentially as it diffuses into the blood. After 10 seconds, the concentration of carbon monoxide in the exhaled gas is measured. Alveolar volume can be determined because an inert gas, such as helium, neon, or methane, is added to the test gas. The calculated single-breath diffusing capacity of the lung for carbon monoxide (Dlco) is proportional to the difference between the initial and final carbon monoxide concentrations. The Dlco may be reduced in situations where alveolar surface area has been lost–such as lobectomy, pulmonary fibrosis, or pneumonia–or when the pulmonary capillary bed has been reduced, as in patients with pulmonary embolism. In emphysema, both the alveolar surface and the pulmonary capillary bed have been reduced. Causes for elevated Dlco include polycythemia, intra-alveolar hemorrhage, obesity, and a supine position.
What may appear to be abnormal PFT results are not necessarily an indication of lung disease. Unfortunately, there is no gold standard for normal values. Abnormal results may merely denote significant statistical differences from similar normal subjects. Patient results are compared to a set of normal values generated using healthy subjects (with equations that use age, height, gender, and race, but not weight, as predictive variables). Because there is no universally accepted set of normal values used in all PFT laboratories, there may be modest differences in normal values between laboratories for a given set of subject characteristics. Statistical analysis of predicted values does give a range for normal values called the standard error of the estimate (SEE). SEE is similar to the standard deviation of a predicted value for a given set of subject characteristics. Assuming that the test subjects accurately represent the entire population of individuals with healthy lungs, results from approximately 68 percent of all normal subjects with a given set of characteristics will lie within 1 SEE of the predicted values, and 95 percent will be within 2 SEEs.
PFT results provide key physiologic clues to disease processes that would otherwise be difficult to detect, yet PFT procedures are underused in the primary care setting. Obtaining reliable measurements requires diverse skills on the part of the technician; he or she must be adept at patient communication to obtain adequate cooperation, be familiar with the instrumentation, and also have an understanding of respiratory physiology in order for PFT results to be accurate.
Mark Talavera, MD, is a fellow in the Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center, Torrance, Calif. Dinesh Kumar, MD, is a fellow in the same division. Richard Casaburi, PhD, MD, is division chief.
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