Technique

VC is measured by having the patient inspire maximally and then exhale completely into a spirometer. (See Chapter 11 for a complete discussion of spirometers.) The patient is instructed to perform the maneuver slowly and completely. VC can also be measured from maximal expiration to maximal inspiration. The spirometer does not need to produce a graphic display if only VC is to be measured. However, if IC and ERV are to be determined (see Figure 2-1), some means of recording volume change is required. The graphic display may be a computer screen or a recording device (see Chapter 11). A graphic display allows the technologist to determine that the test is performed correctly (Criteria for Acceptability 2-1). A graphic display is also usually required for reimbursement purposes.

Obtaining a valid slow VC is important. The subdivisions of the VC (IC and ERV) are used in the calculation of residual volume (RV) and total lung capacity (TLC). An excessively large tidal volume or an irregular breathing pattern during the VC maneuver may alter ERV or IC. If either ERV or IC is erroneously recorded, other lung volumes may be incorrectly estimated (see Chapter 4).

IC is measured by having the patient breathe normally for three or four breaths and then inhale maximally. The volume inspired from the resting expiratory level is measured by the computer or from a spirogram. This is usually done as part of a slow VC maneuver. IC may also be calculated by subtracting the ERV from the VC. ERV is measured by having the patient breathe normally for three or four breaths and then exhale maximally. The change in volume from the end-expiratory level to the maximal expiratory level is the ERV. ERV may also be calculated by subtracting the IC from the VC. IC and ERV are usually measured from the same VC maneuver. IC and ERV should be reported as the average of at least three acceptable maneuvers, whereas VC is reported as the largest of at least three acceptable maneuvers.

The accuracy of the IC and ERV measurements depends on the stability of the end-expiratory level, which should vary by less than 100 mL. Three or more tidal breaths should be recorded before the VC maneuver is performed. If the end-expiratory volume is not consistent, IC and/or ERV may be measured incorrectly (i.e., too large or too small). Even if the end-expiratory level is constant, the V_T usually increases when the patient breathes through a mouthpiece with a noseclip in place. This increase in V_T may change the IC or ERV, depending on the patient’s breathing pattern. Erroneous estimates of ERV may affect the calculation of RV, as described in Chapter 4.

Significance and Pathophysiology

Spirometry is indicated in a variety of situations (see Chapter 1). According to the 2005 ATS-ERS recommendations, there is only one contraindication to spirometry but several conditions that could yield a suboptimal test (Box 2-1). However, testing personnel should be aware of other conditions, which should be evaluated before testing, such as recent stroke, eye surgery, thoracic/abdominal surgery or pneumothorax, uncontrolled hypertension or hypotension,and known thoracic, aortic, or cerebral aneurysm.

Normal VC may vary as much as 20% above or below the predicted value in healthy individuals, but it must be above the bottom 5th percentile (lower limit of normal; see Chapter 13) to be considered normal. The ATS-ERS guidelines recommend the use of the National Health and Nutrition Examination Survey III (NHANES III) reference equations (see Evolve website http://evolve.elsevier.com/Mottram/Ruppel/) for patients in the United States ages 8-80 years. For children under 8 years old, the guidelines recommend the equations of Wang and others. However, in 2007, Stanojevic and others extended the NHANES III dataset to age 4 years.

In adults, VC varies directly with height and inversely with age; tall patients have larger VCs than short patients. VC increases up to approximately age 20 and then decreases each year thereafter, with an average decrease of about 25-30 mL/yr. It is usually smaller in women than in men because of differences in body size. Recent evidence indicates that lung volumes may differ significantly according to ethnic origin. VC also varies in individuals, depending on body position or time of day. Interpretation of lung function should consider the key factors of age, sex, height, and race (see Chapter 13).

PF Tip 2-1

Normal values for lung function parameters are obtained by studying healthy subjects. The predicted or reference value for VC is computed using an equation like:

< ?xml:namespace prefix = "mml" />VC=xHeight−yAge−z

where:

x, y, and z are constants

Predicted values may be read from special diagrams called nomograms but are usually calculated by a computer. (See Chapter 13.) The lower limit of normal, representing the lower 5th percentile of the normal distribution curve, is recommended as the cutoff to judge normality.

As Hutchinson originally noted (see Chapter 1), a patient’s vital capacity is directly related to survival, and numerous studies have since supported his conclusion. In a study published in 2011 using data on spirometry and survival from the Atherosclerosis Risk in Communities (ARIC) dataset, 7489 participants with usable spirometry data were compared against measures of ventilatory function after controlling for many other factors likely to be associated with survival. The study concluded that survival was strongly associated with the forced vital capacity over all other spirometry parameters.

There are numerous causes of a decreased VC (Box 2-2). In general, these fall into the categories of loss of distensible lung tissue (i.e., fibrosis), obstructive lung disease, and reduced chest wall expansion (i.e., neuromuscular, kyphosis).

When the VC is reduced, additional pulmonary function measurements may be indicated. Forced expiratory maneuvers (see section, Forced Vital Capacity) can reveal whether the reduced VC is caused by obstruction. Reduced VC without slowing of expiratory flow is a nonspecific finding. Measurement of other lung volumes (see Chapter 4) may be indicated to determine whether a restrictive defect is present. Measurement of muscle pressures may help determine whether there is a problem with neuromuscular weakness (see Chapter 10).

In adults, VC less than the lower limit of normal (95% confidence limits, see Chapter 13) may be considered abnormal. Interpretation of the measured VC in relation to the reference value should consider the clinical question to be answered (Interpretive Strategies 2-1). The clinical question is often revealed in the history and physical findings of the patient (see Chapter 1). The terms mild, moderate, and severe may be used to qualify the extent of reduction of the VC in a manner similar to that described for FEV₁ (see following section, FEV₁).

Artificially low estimates of the VC may result from poor patient effort. Similarly, inadequate patient instruction may affect the performance of the test maneuver. These errors may be eliminated by applying appropriate criteria (Criteria for Acceptability 2-1). Values for at least two maneuvers should be reproducible within 150 mL (see Chapter 12).

IC and ERV are approximately 75% and 25% of the VC, respectively. Changes in IC or ERV usually parallel increases or decreases in the VC. Increased V_T caused by exertion or acid-base disorders (e.g., metabolic acidosis, respiratory alkalosis) may reduce IRV or ERV. This occurs because end-inspiratory and end-expiratory levels (see Figure 2-1) are altered. A similar pattern is commonly seen when patients breathe into a spirometer through a mouthpiece with noseclips in place. Changes in IC or ERV are of minimal diagnostic significance when considered alone. Reduction of IC or ERV is consistent with restrictive defects. Obese patients typically show a decrease in ERV, usually resulting in a low VC. A reduced ERV is one of the earliest lung function changes in obese patients.

Technique

FVC is measured by having the patient, after inspiring maximally, expire as forcefully and rapidly as possible into a spirometer (see Chapter 1). The patient should inspire completely. The inhalation should be rapid but not forced. There should be little, if any, pause (less than 1-2 seconds) at maximal inspiration; a prolonged pause (4-6 seconds) may decrease flow during the subsequent expiration.

The volume expired may be read directly from a volume-time recording (Figure 2-2). This method is used by some small portable spirometers. More commonly, the maneuver is displayed on a computer monitor or liquid crystal display screen. The computer analyzes the signal from the spirometer, then calculates and displays the FVC. A spirometer that produces a graphical tracing (either volume-time or flow-volume) is essential for clinical

laboratory purposes to allow a visual inspection of the maneuver (Figure 2-3) and is also necessary for reimbursement purposes. Devices providing only numerical data may be helpful for simple screening. Whether used for diagnosis or monitoring, all spirometers should meet the criteria proposed by the ATS-ERS (see Chapter 12). The FVC maneuver depends on patient effort. Not all patients may be able to perform it acceptably (Criteria for Acceptability 2-2).

FEV₁ (and other FEV_T values) may be measured by timing the FVC maneuver over the described intervals. Historically, this was done by recording the FVC spirogram on graph paper moving at a fixed speed. The FEV for any interval could then be read from the graph, as shown in Figure 2-4. Most modern spirometers time the FVC maneuver using a computer. The computer then calculates and displays the FEV₁ or other FEV_T intervals. The spirometer should provide a volume-time display of each maneuver (Figure 2-5). A graphic representation allows the monitoring of patient effort at the beginning of the test. Accurate measurement of FEV₁ (and other FEV_T intervals) depends on the determination of the start-of-test (Figure 2-6). Computerized spirometers detect the start-of-test as a change in flow or volume above a certain threshold. The computer then stores volume and flow data points in memory and calculates the FEV₁.

Open circuit technique describes an FVC maneuver where the subject inhales maximally, places the mouthpiece or filter into their mouth, and then forcefully exhales until empty. Using this technique, the patient has to coordinate taking the deep breath, holding the breath at TLC, and placing the mouthpiece correctly, which can be a challenge for some subjects. Closed-circuit technique describes a maneuver where the subject breathes tidally on the spirometer, inhales maximally, forcefully exhales, and then may be instructed to inhale forcefully to measure the inspiratory flow and volume. Most computerized spirometers correct for a slow start-of-test by back-extrapolation (see Figure 2-5). Visualization of the volume-time spirogram is the best means of identifying poor initial effort. Some portable spirometers report FEV₁ without a spirogram. Such measurements should be used with caution because it may be difficult to determine whether the maneuver was performed acceptably.

The ratio of the FEV₁ to FVC is expressed as follows:

FEV1%=FEV1FVC  ×  100

FEV_1% is also commonly written as FEV₁/FVC. Both ratios are expressed as percentages, and this percentage is then related to normative values as a percentage of predicted. FEV₁ and FVC should be reported as the maximal values obtained from at least three acceptable FVC maneuvers. The FEV₁/FVC ratio based on these values may be different from the ratio obtained from any single maneuver. If both VC and FVC maneuvers have been performed, it is preferable to use the largest VC in the calculation. Some computerized spirometers calculate only the ratio obtained from FVC maneuvers.

The FEF_25%-75% is measured from an FVC maneuver. The FEF_25%-75% is the average flow during the middle half (from 25% to 75%) of the VC. A computerized measurement of the FEF_25%-75% requires storage of flow and volume data points for the entire maneuver. Calculation of the average flow over the middle portion of the exhalation is simply 50% of the volume expired divided by the time required to get from the 25% point to the 75% point. To manually calculate the FEF_25%-75%, a volume-time spirogram is used. The points at which 25% and 75% of the vital capacity have been expired are marked on the curve (see Figure 2-6). A straight line connecting these points can be extended to intersect two timelines 1 second apart. The flow (in liters per second) can then be read directly as the vertical distance between the points of intersection. Instantaneous flows, such as the FEF_50% or FEF_75%, cannot be read directly from a volume-time display but can be measured using a flow-volume curve (see later section, Flow-Volume Curve).

The FEF_25%-75% depends on the FVC. Large FEF_25%-75% values may be derived from maneuvers that produce small FVC measurements because the “middle half” of the volume is actually gas expired at the beginning of expiration. This effect may be particularly evident if the patient terminates the FVC maneuver before exhaling completely. When the FEF_25%-75% is used for assessing the response to bronchodilator or bronchial challenge, the effect of changes in the absolute lung volumes must be considered. Measuring the FEF_25%-75% at the same lung volumes in the comparison tests is called the isovolume technique. Isovolume corrections are usually applied when the FVC changes by more than 10% (indicating a change in TLC or RV). This technique requires that lung volumes (see Chapter 4) be measured in conjunction with flows. The isovolume technique may also be used with other flow measurements that are dependent on FVC.

The largest FEF_25%-75% is not necessarily the value reported. The FEF_25%-75% is recorded from the maneuver with the largest sum of FVC and FEV₁. Flows must be corrected to BTPS.

Acceptability and Repeatability for Spirometry Results

Criteria used to judge the acceptability of test results from the FVC maneuver include the following:

Data from all acceptable maneuvers should be examined. The largest FVC and the largest FEV₁ should be reported, even if the two values are from different test maneuvers. The reported FEV₁/FVC ratio is taken from these values. Flows that depend on the FVC (e.g., the FEF_25%-75%) should be taken from the single best test maneuver, which is the maneuver with the largest sum of FVC and FEV₁ (Table 2-1). The reported flow-volume curve is also taken from the single best test maneuver.

A common problem may occur when using these criteria to produce a spirometry report. If a single volume-time or flow-volume tracing is included in the final report, it may not contain the FVC or FEV₁ that appears in the tabular data. It is advisable to maintain recordings, or raw data, for all acceptable maneuvers. Other methods of selecting the best test have been suggested and are sometimes used. PEF may be used to assess patient effort for an FVC maneuver. Selecting the effort with the largest PEF may cause errors if FVC and FEV₁ are not also evaluated.

Spirometry may be performed in either the sitting or standing position for adults and children, although the sitting position is recommended for safety, especially in adults. There is some evidence that FEV₁ may be larger in the standing position in adults and in children younger than 12 years of age. The position used for testing should be indicated on the final report. The patient should keep their head slightly elevated and should keep false teeth in if they fit well. The use of noseclips is recommended for spirometric measurements that require rebreathing, even if just for a few breaths. Spirometers that record only expiratory flow may require the patient to place the mouthpiece into the mouth after maximal inspiration. If this is the case, noseclips are usually unnecessary. Care should be taken, however, that the patient places the mouthpiece into the mouth before beginning a forced expiration. Failure to do so may result in an undetectable loss of volume. It may be impossible to calculate the volume of back-extrapolation from a tracing that displays expiratory flow only. Spirometers that use mechanical recorders should have pen or paper moving at recording speed when the forced expiration begins. Recorders that trigger pen or paper movement with exhalation may be unable to accurately record the start-of-test. Such spirometers often underestimate the FEV₁. Most spirometers use computer-generated graphics, avoiding the problems associated with mechanical recorders.

See Interpretive Strategies 2-2. FVC usually equals VC in healthy individuals. In patients without obstruction, FVC and VC should be within 150 mL of each other. FVC and VC may differ if the patient’s effort is variable or if significant airway obstruction is present (i.e., FEV₁/FVC less than 0.70). FVC is often lower than VC in patients with obstructive diseases if forced expiration causes airway collapse. This pattern is often seen in emphysema because of a loss of tethering support of the airways. Large pressure gradients across the walls of the airways during forced expiration collapse the terminal portions of the airways. Gas is trapped in the alveoli and cannot be expired. This causes the FVC to appear smaller than the VC. The FVC can appear larger than the VC if the patient exerts greater effort on the forced maneuver.

FVC can be reduced by mucus plugging and bronchiolar narrowing, as is common in chronic

bronchitis, chronic or acute asthma, bronchiectasis, and cystic fibrosis. Reduced FVC is also present in patients whose trachea or mainstem bronchi are obstructed. Tumors or diseases affecting the patency of the large airways can produce this result.

Some obstructed patients have a relatively normal FVC in relation to their predicted values. However, the time required to expire their FVC (forced expiratory time or FET) is usually prolonged. Healthy adults can expire their FVC within 4 to 6 seconds. Normal children and adolescents may exhale their FVC in less than 4 seconds. Patients with severe obstruction (e.g., those with emphysema) may require 15 seconds or more to exhale completely (Figure 2-7). Accurate measurement of FVC in such individuals may be limited by how long the spirometer can collect exhaled volume. Some spirometers allow only 15 seconds of volume recording. This is usually long enough to diagnose airway obstruction. However, the FVC and FEV_1% may be inaccurate if the patient continues to exhale for a longer time. The ATS-ERS recommends that spirometers measure FVC for at least 15 seconds (see Chapter 12).

An alternative to measuring FVC in severely obstructed patients is to use FEV₆. Because normal patients can exhale their FVC in 6 seconds, substituting FEV₆ for FVC allows the FEV₁/FEV₆ to be used as an index of obstruction. Using FEV₆ in place of FVC eliminates the necessity of having the patient try to exhale for a long interval. Predicted values for FEV₆ and FEV₁/FEV₆ may be calculated using coefficients in Chapter 13. Because FEV₆ may underestimate FVC, use of FEV₁/FEV₆ instead of FEV₁/FVC may reduce the sensitivity of spirometry to detect airway obstruction, especially in older patients and in those with mild obstruction.

Decreased FVC is seen in the same circumstances as described for reduced VC, as discussed earlier. However, the reduction in FVC may be more evident than that of the slow VC in diseases that affect the bellows function of the chest, which is a key determinant of the force generation involved in the FVC compared to the VC maneuver. Such diseases include neuromuscular disorders as well as chest wall mechanical abnormalities, like kyphoscoliosis and obesity. A reduction in FVC when going from sitting to supine has been shown to be a good indicator of diaphragmatic weakness.

Reduced FVC (or VC) is a nonspecific finding. Values below the 5th percentile are considered abnormal (see Chapter 13). A low FVC may be caused by either obstruction or restriction (see Box 2-2). Interpretation of the FVC in obstructive diseases requires correlation with flows. An FVC that is significantly lower than VC suggests airway collapse and gas trapping. In restrictive patterns, low FVC may indicate the need to assess other lung volumes, particularly total lung capacity (TLC; see Chapter 4). Interpretation of FVC values close to the lower limit of normal depends on the clinical question to be answered. An FVC at the 5th percentile would be interpreted differently in a healthy patient with no symptoms than in a patient with a history of cough or wheezing. An FVC much lower than expected is often accompanied by the complaint of exertional dyspnea.

A low value for FVC may also occur if the patient’s effort is suboptimal. Patients who stop exhaling before achieving an obvious plateau (on a volume-time display) or who fail to take a maximal inhalation will typically have an underestimated FVC. These patients should be encouraged to inhale maximally at the start of the maneuver then exhale completely for 6 seconds (3 seconds for children less than age 10) or until a plateau occurs. Premature termination of the FVC effort may cause the FEV_1% to be overestimated, masking the presence of obstruction.

An important quality issue to recognize is that a large FVC (and its derived parameters) derived from a flow sensor may result from improper zeroing or contamination of the sensor by condensation or mucus. This problem can usually be recognized by poor repeatability of measurements, characterized by progressively increasing test results within a single testing session.

Forced Expiratory Volume (FEV₁)

FEV₁ measures the volume expired over the first second of an FVC maneuver. FEV₁ is reported as a volume, although it measures flow over a specific interval. FEV₁, like FVC, may be reduced in either obstructive or restrictive patterns (Figures 2-7 and 2-8). FEV₁ values may also be reduced because of poor effort or cooperation by the patient.

An obstructive ventilatory defect is characterized by the reduction of maximal airflow at all lung volumes (e.g., the classic concave shape to the flow-volume curve). Flow is limited by airway narrowing during forced expiration. Airway obstruction may be caused by mucus secretion, bronchospasm, and inflammation such as in asthma or bronchitis. Airflow limitation may also result from a loss of elastic support for the airways themselves, as in emphysema. The earliest changes in obstructive patterns may occur in the small airways (i.e., those less than 2 mm), which may or may not be detected by changes in FEV₁.

FEV₁ may also be decreased in large airway obstruction (trachea and bronchi). Tumors or foreign bodies that limit airflow cause the FEV₁ to be reduced. These defects can be identified by flow reductions across the entire forced expiration (see later section, Flow-Volume Curve).

FEV₁ and FEV₁/VC are the most standardized indices of obstructive disease. An obstructive defect is defined best by a reduced FEV₁/VC ratio. The severity of obstructive disease may be gauged by the extent to which FEV₁ is reduced. The ability to work and function in daily life is related to FEV₁and VC. Mortality (likelihood of dying) caused by respiratory disease is similarly related to the degree of obstruction as measured by FEV₁. Patients with markedly reduced FEV₁ values are much more likely to die from chronic obstructive pulmonary disease (COPD), lung cancer, and even cardiovascular disease, including myocardial infarction and stroke. Although FEV₁ correlates with prognosis and severity of symptoms in obstructive lung disease, outcomes for individual patients cannot be accurately predicted.

While the ratio of FEV₁/VC defines obstruction, the severity of obstruction is defined by the degree to which the FEV₁ is reduced. The ATS-ERS Task Force suggests the following classifications of severity:

MildFEV₁ > 70% predicted

ModerateFEV₁ = 60%-69% predicted

Moderately severeFEV₁ = 50%-59% predicted

SevereFEV₁ = 35%-49% predicted

Very severeFEV₁ < 35% predicted

The concept of grading severity based on FEV₁ applies best when the VC is in the normal range. Once the VC is below normal, a concomitant restrictive defect may also be present, and this can be determined only by further measurement of lung volumes, in particular TLC. Because the FEV₁ in restriction is reduced, in part, by the restrictive process itself, the decrement in FEV₁ resulting from the obstructive component of disease can no longer be assumed to reflect the severity of obstruction only. Thus, the severity of obstruction in a combined restrictive and obstructive defect is typically overestimated when basing severity solely on the reduction in FEV₁.

Restrictive processes, such as fibrosis, edema, space-occupying lesions, neuromuscular disorders, obesity, and chest wall deformities, may all cause FEV₁ to be decreased. Reduction in FEV₁ occurs in much the same way as reduction in VC. Unlike the pattern seen in obstructive disease, in which VC is preserved and FEV₁ is reduced, in restriction VC and FEV₁, values are proportionately decreased. Some patients with moderate or severe restriction have an FEV₁ nearly equal to the VC. The entire VC, because it is reduced, is exhaled almost completely in the first second. To distinguish between obstructive and restrictive causes of reduced FEV₁ values, the FEV₁/VC ratio (FEV_1%) and other flow measurements are useful. Further definition of obstruction versus restriction may require the measurement of lung volumes (e.g., functional residual capacity or FRC, and TLC). However, studies have shown that when the FVC and FEV₁/VC ratio are both normal, restriction, as defined by a low TLC, is very unlikely.

FEV₁ is the most widely used spirometric parameter, particularly for the assessment of airway obstruction. FEV₁ is used in conjunction with VC for simple screening, assessment of response to bronchodilators, inhalation challenge studies, and detection of exercise-induced bronchospasm (see Chapters 7 and 9). FEV₁ is the most robust pulmonary function test, making it the measurement of choice in evaluating lung function in general. In fact, the motto of the National Lung Health Education Program (NLHEP) is “Test your lungs. Know your numbers,” and these numbers are the FEV₁ and FVC (or FEV₆). The NLHEP advocates for the widespread use of simple office spirometry in order to increase the awareness and detection of COPD as well as other respiratory disorders. In particular, the NLHEP recommends that all smokers age 45 years and older have spirometry done to detect airflow obstruction, even before the onset of clinical symptoms.

Technique

The patient performs an FVC maneuver, inspiring fully and then exhaling as rapidly as possible. To complete the loop, the patient inspires as rapidly as possible from the maximal expiratory level back to maximal inspiration. Volume is plotted on the horizontal X-axis, and flow is plotted on the vertical Y-axis. The F-V loop is usually displayed on a computer screen. It can also be printed or plotted. Expiratory flow is plotted upward. Expired volume is usually plotted from left to right. Sometimes, when concomitant lung volumes have also been measured, an absolute lung volume scale is used, usually with TLC on the left and RV on the right. Airflow should be recorded at 2 L/sec/unit distance on the Y-axis. Volume should be recorded at 1 L/unit distance on the volume axis. Scale factors should be at least 5 mm/L/sec for flow and 10 mm/L for volume. These factors are required so that manual measurements can be made from a printed copy of the maneuver. This one-to-two flow-volume relationship also ensures the visual prospective of the graphic data is consistent regardless of the size of the display.

FVC, as well as peak expiratory flow (PEF) and peak inspiratory flow (PIF), can be read directly from the F-V loop. Instantaneous flow at any lung volume can be measured directly from the F-V loop. Maximal flow at 75%, 50%, and 25% of the FVC is commonly reported as the max₇₅, max₅₀, and max₂₅. The subscript in these terms refers to the portion of the FVC remaining. The same flows are also reported as the FEF_25%, FEF_50%, and FEF_75% with the subscripts referring to the percentage of FVC exhaled. This latter terminology is now preferred by the ATS-ERS guidelines. Most computerized spirometers superimpose timing marks (ticks) on the MEFV curve (Figure 2-10). These marks allow FEV₁ (or other FEV_T) values to be read from the F-V loop.

F-V loop data, stored in computer memory, can be easily manipulated. Multiple loops can be compared by superimposing them with contrasting colors. Bronchodilator or inhalation challenge F-V loops can be presented in a similar manner. A predicted MEFV curve can be plotted using points for PEF and maximal flows at 75%, 50%, and 25% of the FVC. A patient’s flow-volume curve can then be superimposed directly over the expected values (see Figure 2-10). Superimposing multiple FVC maneuvers as F-V loops can be used to assess reproducibility of the patient’s effort. Positioning loops side by side or superimposing can also help detect decreasing flows with repeated efforts. This pattern may be seen because FVC maneuvers can induce bronchospasm (i.e., FVC-induced bronchospasm or FVC worsening). Storing tests in the order performed is recommended. This allows a review of the test session and detection of bronchospasm or fatigue.

Reproducible MEFV curves, particularly the PEF, are good indicators of adequate patient effort (Criteria for Acceptability 2-3). Assessing the start-of-test and determining whether exhalation lasted at least 6 seconds may be difficult if only the F-V loop is displayed. Simultaneous display of flow-volume and volume-time curves is useful (Figure 2-11). Although computerized systems calculate back-extrapolated volume, a volume-time tracing may be necessary to perform back-extrapolation manually (see Figure 2-5). Common technical problems with volume-time tracings and F-V loops are shown in Figure 2-12.

Significance and Pathophysiology

See Interpretive Strategies 2-3. Maximal flow at any lung volume during forced expiration or forced inspiration can be easily measured from the F-V loop (see Figure 2-9). Significant decreases in flow or volume are easily detected from a single graphic display. Many clinicians prefer to include the F-V loop or MEFV curve as part of the patient’s medical record.

The shape of an MEFV curve from approximately 75% of FVC to maximal expiration is largely independent of patient effort. Flow over this segment is determined by two properties of the lung: elastic recoil and flow resistance. The lung is stretched by maximal inspiration. Elastic recoil determines the pressure applied to gas in the lung during a forced expiration. This pressure is determined by the recoil of the lung and chest wall. Resistance to flow in the airways is the second factor affecting the shape of the flow-volume curve. Flow limitation occurs in the large and medium airways during the early part of a forced expiration. The site of flow limitation migrates “upstream” rapidly during forced expiration. Resistance to flow in small (less than 2 mm) airways is determined primarily by the cross-sectional area. This cross-sectional area can be affected by a number of factors. Destruction of alveolar walls, as in emphysema, reduces support of the small airways. Bronchoconstriction and inflammation directly reduce the lumen of the small airways.

In healthy patients flow () over the effort-independent segment decreases linearly as lung volume decreases. Pressures around airways are balanced by gas pressures in the airways so that flow is limited at an “equal pressure point.” As the lung empties, the equal pressure point moves upstream into increasingly smaller airways and continues until small airways begin to close, trapping some gas in the alveoli (the RV). This pattern of airflow limitation in healthy lungs causes the MEFV curve to have a linear or slightly concave appearance (see Figure 2-9). This degree of concavity increases with age, presumably because of reduced flows secondary to loss of elastic recoil with aging.

Flow-Volume Loops in Large Airway Obstruction

Obstruction of the upper airway, trachea, or mainstem bronchi also shows characteristic patterns. Both expiratory and inspiratory flow may be limited. The F-V loop is extremely useful in diagnosing these large airway abnormalities (see Figure 2-13). Comparison of expiratory and inspiratory flows at 50% of the FVC (FEF_50% and FIF_50%, respectively) may help determine the site of obstruction. In healthy patients, the ratio of FEF_50% to FIF_50% is approximately 1.0 or slightly less. Fixed large airway obstruction causes equally reduced flows at 50% of the VC during inspiration and expiration (Figure 2-13). Obstructive lesions that vary with the phase of breathing also produce characteristic patterns. Variable extrathoracic obstruction usually shows normal expiratory flow but diminished inspiratory flow. The FEF_50%/FIF_50% is often greater than 1.0 because the obstructive

PF Tip 2-6

The classic analogy for an emphysematous lung is a balloon that has been blown up for several days and the air has escaped. The balloon (B), much like the emphysematous lung, is distended and floppy. It has lost its elastic recoil and is very compliant. The neck of the balloon is also affected and is collapsed. This gives the maximal expiratory flow volume curve its characteristic obstructive concave or “scooped” appearance (A, C).

process is outside of the thorax, the MEFV portion of the curve appears as it would in a healthy individual, but the inspiratory portion of the loop is flattened. Inspiratory flow depends on how much obstruction is present. A common cause of variable extrathoracic obstruction, resulting in truncated inspiratory flow, is paradoxical vocal cord closure during inspiration, also known as vocal cord dysfunction. In variable intrathoracic obstruction, PEF is reduced. Expiratory flow remains constant until the site of flow limitation reaches the smaller airways. This gives the expiratory limb a “squared-off” appearance (see Figure 2-13). The inspiratory portion of the loop may be completely normal. The FEF_50%/FIF_50% will be typically much less than 1.0, depending on the severity of obstruction. In patients with truncation of both the inspiratory and expiratory loops, a fixed obstruction may be present.

PF Tip 2-7

A simple mnemonic for determining variable obstruction: “What’s in is out, what’s out is in.” In other words, a variable inspiratory obstruction affects the expiratory portion of the F-V curve, and a variable expiratory obstruction affects the inspiratory portion of the F-V curve.

Airway obstruction associated with abnormality of the muscular control of the posterior pharynx and larynx sometimes produces a “sawtooth” pattern visible on the inspiratory and expiratory limbs of the MEFV curve (Figure 2-14). This pattern, although neither sensitive or specific for, is sometimes observed in patients suspected of having sleep apnea. If this pattern is observed on the F-V curve and the subject complains of daytime hypersomnolence, a referral to a sleep center may be warranted. The interpretation of this noise is sometimes termed redundant tissue of the upper airway.

Peak inspiratory flow and the pattern of flow during inspiration are largely effort-dependent. Poor patient effort may result in inspiratory flow patterns similar to variable extrathoracic obstruction. Instruction by the technologist should emphasize maximal effort during inspiration as well as expiration. If repeated efforts produce reduced inspiratory flows, an obstructive process should be suspected.

Flow-Volume Loops in Restrictive Disease

Restrictive disease processes may show normal or greater than normal peak flows with linear decreases in flow versus volume. The lung volume displayed on the X-axis is decreased. Moderate or severe restriction demonstrates equally reduced flows at all lung volumes. Reduced flows are primarily caused by the decreased cross-sectional area of the small airways at low lung volumes. Simple restriction causes the F-V loop to appear as a miniature of the normal curve (see Figure 2-12), often with supranormal flow as seen by elevated FEV₁/VC.

PF Tip 2-8

The restrictive flow volume loop pattern (A) is often compared to a very small balloon where it takes high pressure to flow up the balloon, the balloon does not get big (B), yet the air comes out very fast. Another analogy is the “ant hill” or “witches hat” (C) with very steep flows secondary to high elastic recoil but decreased volumes.

Before- and after-bronchodilator F-V loops can be superimposed to measure changes in flow at specific lung volumes. The curves are usually positioned by superimposing at maximal inspiration. This method assumes that any increase in FVC occurs while TLC remains constant. If postbronchodilator lung volume tests are performed, the curves may be superimposed on an absolute volume scale (i.e., isovolume correction). This method shows bronchodilator-induced changes in lung volumes as well as flows. Sometimes, lung volumes will change after bronchodilator without any change in FEV₁. Inhalation challenge studies (see Chapter 10) can be displayed similarly to assess the reduction in flows at specific lung volumes.

Tidal breathing curves or maximal voluntary ventilation (MVV) curves can also be superimposed on the F-V loop. The patient’s ventilatory reserve can be assessed by comparing the areas enclosed under each of the curves. Patients who have obstructive lung disease may generate F-V loops only slightly larger than their tidal breathing curves. In severe obstruction, flow during tidal breathing may actually exceed flow during a forced expiration. Dynamic compression of small airways during forced expiration causes airway collapse, whereas tidal breathing may not. These patients have limited ventilatory reserve and shortness of breath with exertion.

F-V loops may also be measured during exercise (see Chapter 7). By superimposing a flow-volume curve during exercise over the maximal F-V loop, specific patterns of ventilatory response can be assessed. Patients who have airflow limitation are typically unable to increase ventilation during exercise when expiratory flow equals maximal flow. Exercise F-V curves can be used to demonstrate this phenomenon.

Technique

PEF can be easily measured from a flow-volume curve (MEFV). PEF may also be measured by using devices that sense flow directly (see Chapter 11), or by using volume displacement spirometers and deriving the rate of volume change. Many portable devices (i.e., peak flow meters) are available to measure maximal flow during forced expiration. Most sense flow as movement of air against a turbine or through an orifice. PEF done in conjunction with spirometry is performed as described for F-V loops.

Measuring PEF with a peak flow meter may be done at the bedside, in the emergency department, in the clinic setting, or at home. In each setting, the individual performing the measurement must know how to operate the specific peak flow meter. The maneuver should be demonstrated to the patient. A return demonstration is essential when the patient is being trained to use the peak flow meter at home.

The peak flow meter should be set or zeroed, as required. When performed at home with a portable device as part of ambulatory monitoring, the standing position is usually recommended (if performed as part of a spirometry maneuver in the office or hospital setting, the patient should be sitting). The patient should inhale maximally; the inhalation should be rapid but not forced. The patient then exhales with maximal effort as soon as the teeth and lips are placed around the mouthpiece. The neck should be in a neutral position in order to avoid tracheal compression with neck flexion or extension because these will reduce PEF. As in the FVC maneuver, a long pause (4 to 6 seconds) at maximal inspiration may decrease the PEF; there should be no more than 1 second of hesitation. The expiratory effort needs to be only 1 to 2 seconds to record PEF.

At least three maneuvers should be performed and recorded, along with the order in which the values were obtained. All readings are recorded in order to detect effort-induced bronchospasm. The largest PEF obtained should be reported. The PEF is effort-dependent and variable. It may be particularly variable in patients with hyperreactive airways (Criteria for Acceptability 2-4). Up to five attempts should be made to achieve adequate repeatability, defined as no more than 0.67 L/sec (40 L/min) difference between the largest of two out of three acceptable efforts.

When PEF is used to monitor asthmatic patients, it is important to establish each person’s best PEF (i.e., the largest PEF achieved). Best values can be obtained over 2 to 3 weeks. PEF should be measured twice daily (morning and evening). The personal best is usually observed in the evening after a period of maximum therapy. Daily measurements are then compared with the personal best. The personal best PEF should be reevaluated annually. This allows PEF to be adjusted for growth in children or for progression of disease. PEF should be periodically compared with regular spirometry results (FEV₁).

Portable peak flow meters need to be precise (low variability in the same instrument). Precision is more important than accuracy for detecting changes from serial measurements. Peak flow meters should have ranges of 60 to 400 L/min for children and 100 to 850 L/min for adults. Standards for peak flow monitoring devices have been published by the ATS-ERS (see Chapters 11 and 12).

Significance and Pathophysiology

See Interpretive Strategies 2-4. The PEF attainable by healthy young adults may exceed 10 L/sec or 600 L/min, BTPS. Even when an accurate pneumotachometer is used, the value of PEF measurements may be limited. Peak flow is effort-dependent. It primarily measures large airway function and muscular effort. Decreased PEF values should be evaluated for consistent patient effort. PEF values for patients without hyperreactive airways are usually similar with repeated efforts. Asthmatic patients often have a pattern of decreasing PEF with repeated trials. Widely varying peak flows without a pattern of induced bronchospasm suggest poor effort or cooperation. However, PEF measurements alone are not sufficient to make a diagnosis of asthma. Spirometry, lung volumes, diffusing capacity, and airway resistance measurements may be required to evaluate fully the associated physiologic impairment.

Effort dependence of PEF makes it a good indicator of patient effort during spirometry. Maximal transpulmonary pressures (Ptp) correlate well with maximal PEF. Patients who exert variable effort during FVC maneuvers are seldom able to reproduce their PEF. Some clinicians use PEF in addition to the FVC and FEV₁ to gauge maximal effort during spirometry. PEF measurements, when performed with a good effort, correlate well with the FEV₁ as measured by spirometry.

Patients with early small airways obstruction may initially develop high flows during an FVC maneuver. Despite obstruction, these individuals show relatively normal PEF values. When small airway obstruction becomes severe, PEF also decreases. Reduction in PEF is often less than the decrease in FEF_50% or FEF_75% in patients with severe obstruction.

PEF measurements are particularly useful for monitoring asthma patients at home. Daily monitoring of PEF can provide early detection of asthmatic episodes. It can be used to detect day-night patterns (circadian rhythms) related to airway reactivity. PEF monitoring provides objective criteria for treatment. It can help determine specific triggers (e.g., allergens) or workplace exposures that cause symptoms. Daily morning and evening readings are recommended. For patients taking inhaled bronchodilators, PEF may be measured before and after treatment. Significant variation from their personal best or from one reading to the next should be emphasized.

The National Asthma Education and Prevention Program suggests a “zone” system, based on the individual’s personal best or predicted PEF (Interpretive Strategy 2-4). The zone system uses green, yellow, and red as indicators for maintaining or altering therapy. Green (80% to 100% of the personal best PEF) indicates a continuation of routine therapy. Yellow (50% to 80% of the personal best PEF) indicates that an acute episode may be starting. Patients should be instructed to take their medication immediately according to their physicians’ orders. Red (less than 50% of the personal best PEF) indicates that an acute change has occurred. Immediate treatment is required, and the clinician should be notified or after taking their medication, the patient should go to the ER. This approach dramatically improves the patient’s ability to communicate symptomatic changes to the clinician (Figure 2-15).

Uniformly decreased PEF is often associated with upper airway obstruction but is non-specific. PEF assessed from F-V loops (along with PIF) helps define both the severity and site of large airway obstruction.

Technique

MVV is measured by having the patient breathe deeply and rapidly for a 12-second interval. Patients should set the rate but breathe rapidly and deeply. The volume breathed should be greater than their V_T but less than their VC. Instruct the patient to move as much air as possible into and out of the spirometer. The technologist should encourage the patient throughout the maneuver. An ideal rate is 90-110 breaths per minute, and an ideal tidal volume is approximately 50% of the VC.

MVV is continued for at least 12 seconds but no more than 15 seconds. The patient is hyperventilating, so efforts longer than 15 seconds may exaggerate the sensation of lightheadedness. Even the 12-second interval may produce dizziness or syncope. The test may be performed with the patient in either a sitting or standing position. If done while standing, a chair should be available in case of dizziness. Some automated spirometers allow MVV to be terminated before 12 seconds. This accommodates patients who cannot continue because of coughing or lightheadedness. If MVV does not last 12 seconds, it should be noted in the technologist’s comments (see Chapter 12). At least two MVV maneuvers should be performed. The two largest should be within 20% of each other. The largest value is reported (Criteria for Acceptability 2-5).

The volume expired is measured by a spirometer. The spirometer must have adequate frequency response over a wide range of flows (see Chapters 11 and 12). Historically, the volume of each breath was read from a volume-time spirogram or from a recording of accumulated volume (Figure 2-16). Now volume data from each breath are summed by a computer for the interval measured. The MVV (for a 12-second test) is calculated as flow in liters per minute, as follows:

MVV=Vol12×6012

where:

Vol₁₂ = volume in liters expired in 12 seconds

60 = factor for extrapolation from seconds to minutes

For other intervals, the MVV is calculated similarly. The MVV must be corrected to BTPS.

Significance and Pathophysiology

See Interpretive Strategies 2-5. MVV tests the overall function of the respiratory system. It is influenced by airway resistance, respiratory muscles, compliance of the lung and/or chest wall, and ventilatory control mechanisms. Values in healthy young men average between 150 and 200 L/min. Values are slightly lower in healthy women. MVV decreases with age in both men and women and varies considerably in healthy patients. Only large reductions in MVV (25% or more) are considered significant.

MVV is decreased in patients with moderate or severe obstructive disease. This may be the result of the increased airway resistance caused by bronchospasm or mucus secretion. Reduction of MVV may also occur because of airway collapse and hyperinflation, as in emphysema. The MVV maneuver exaggerates air trapping and airflow limitation. Volume-time MVV tracings may show a shift if gas trapping occurs during the test. A slight shift is usually noted during the first few breaths even in healthy patients. The patient adjusts to a lung volume that allows maximal airflow. These first few breaths are usually excluded from the MVV calculation.

The MVV maneuver also places a load on the respiratory muscles. Both inspiratory and expiratory muscles are used in the MVV maneuver. Weakness or decreased endurance of either system may result in low MVV values. Poor coordination of the respiratory muscles caused by a neurologic deficit may also cause a low MVV. Disorders such as paralysis or nerve damage reduce MVV as well.

A markedly reduced MVV correlates with postoperative risk for patients having abdominal or thoracic surgery. Patients who have low preoperative MVV values show an increased incidence of complications. Reduced strength or endurance of the respiratory muscles may be the factor that allows MVV to predict postoperative problems.

The MVV value may be helpful in estimating ventilation during exercise. Note, however, that the MVV maneuver does not mimic the true respiratory pattern during maximal exercise, and thus is only an estimate of maximal breathing capacity during exercise (see Chapter 7). Airway-obstructed patients who have an MVV less than 50 L/min often have a ventilatory limitation to exercise. Maximal exercise ventilation in healthy patients is usually less than 70% of their MVV. In airway-obstructed patients, maximal ventilation during exercise approaches or even exceeds their MVV. This pattern occurs partly because the MVV itself is reduced in obstruction. Highly conditioned healthy patients may also reach their MVV during maximal exercise (see Chapter 7).

MVV may be normal in patients who have restrictive pulmonary disease. Diseases that limit lung or chest wall expansion may not interfere significantly with airflow. Patients who have restrictive disease can compensate by performing the MVV maneuver with low V_T and high breathing rates.

The MVV maneuver depends on patient effort and cooperation. Low MVV values may indicate obstruction, muscular weakness, defective ventilatory control, or poor patient performance.

Patient effort during the MVV maneuver may be estimated by multiplying their FEV₁ by 40. For example, a patient with an FEV₁ of 2.0 L might be expected to ventilate approximately 80 L/min (40 × 2.0 L) during the MVV test. If the measured MVV is less than 80% of (FEV₁ × 40), poor patient effort or neuromuscular weakness may be suspected. If the MVV exceeds (FEV₁ × 40) by a large volume, the FEV₁ may be erroneous.

Technique

The patient may perform an array of tests, including spirometry, lung volumes, and diffusing capacity (Dlco). Lung volumes should be recorded before bronchodilator administration. This provides a baseline for comparing lung volume changes after bronchodilator therapy. Even though indices of flow (FEV₁, FEF_25%-75%, and sGaw) usually show the greatest change, lung volumes and Dlco may also respond to bronchodilator therapy.

Patients referred for spirometry testing should withhold routine bronchodilator therapy before the procedure (Table 2-2). Some patients may be unable to manage their symptoms if bronchodilators are withheld. These patients should be instructed to take their bronchodilator medication as needed. In these instances, the time when the medication was last taken should be noted. Some patients who use bronchodilators shortly before testing (within 4 hours) still show significant improvement after a repeated dose.

Inhaled bronchodilators can be administered by a metered-dose inhaler (MDI) or a small-volume nebulizer. An MDI provides a reproducible means of administering the bronchodilator. Some patients are unable to coordinate activation of the MDI with slow, deep inspiration. For these patients, use of an aerosol reservoir, or spacer, may provide a more consistent delivery of medication. If the patient is unfamiliar with the MDI, the technologist may need to activate the device (How-to 2-2). Small-volume, jet-powered nebulizers may be used to administer more bronchodilator over a longer interval. Nebulizers, if reused, must be carefully disinfected between patients.

β₂ agonist aerosols, such as albuterol, are most commonly used. Each of these drugs has a rapid onset of action, usually within 5 minutes. Maximum bronchodilatation usually takes longer. An interval of 10-15 minutes between administration and repeat testing is recommended for short-acting β₂ agonist, and 30 minutes later for ipratropium bromide.

The ATS-ERS guidelines recommend a relatively high dose of bronchodilator be used in order to ensure that if a bronchodilator response exists, it will be seen. Thus, the recommended dose of albuterol is 400 mcg delivered as four inhalations of 100 mcg each by MDI, separated by 30-second intervals. For ipratropium bromide, the recommended dose is 160 mcg delivered as four inhalations of 40 mcg each by MDI.

Bronchodilator administration often causes side effects. The most common side effect of β₂ agonist use is tachycardia. Increased blood pressure, flushing, dizziness, or lightheadedness is not unusual. Monitoring pulse rate and blood pressure is recommended for susceptible patients. This includes patients with known cardiac arrhythmias or elevated blood pressure. Marked changes in heart rate, rhythm, or blood pressure, or symptoms like chest pain indicate a need to stabilize the patient. The test should be stopped and the referring physician or laboratory medical director should be notified immediately. Management of the patient’s symptoms and continuation of testing are the decision of the physician.

Measurements of FEV₁, FVC, FEF_25%-75%, PEF, and sGaw (Chapter 4) are commonly made before and after bronchodilator administration. In each case, the percentage of change is calculated as follows:

%Change  =  Post– drug−Pre– drugPre– drug  × 100

where:

Post-drug = test parameter after administration

Pre-drug = test parameter before administration

If the test value improves, the percentage of change will be positive. If the parameter worsens, a negative percentage results. Small prebronchodilator values (e.g., an FEV₁ of 0.5 L) may show large changes even though the improvement is minimal.

FEV₁ is the most commonly used test for quantifying bronchodilator response. If FEF_25%-75% or flows such as are used, they should be isovolume-corrected for changes in the FVC. If FVC increases more than FEV₁ after bronchodilator therapy, FEV_1% may actually decrease. FEV_1% should not be used to judge bronchodilator response. sGaw may show a marked increase after bronchodilator therapy. Improved conductance may occur despite minimal change in FEV₁ or conventional measures of flow. Spirometry or plethysmography after bronchodilator therapy should meet the usual criteria for acceptability and reproducibility.

Significance and Pathophysiology

See Interpretive Strategies 2-6. Reversibility of airway obstruction is considered significant for increases of greater than 12% and 200 mL for either the FEV₁ or FVC (Table 2-3). If the sGaw is assessed, an increase of 30% to 40% is usually considered significant. Some patients may show little or no improvement in FEV₁ but have a significant improvement in sGaw (Chapter 4). Changes in FEF_25%-75% of 20% to 30% are sometimes considered significant. However, flows that depend on the FVC should be volume-corrected (Case Study 2-2). If not corrected, FEF_25%-75% may appear to decrease although FEV₁ and FVC improve. Likewise, the FEF_25%-75% may appear to increase even though there is no change in FEV₁. This tends to occur when the postbronchodilator FVC falls from the baseline value, often as a result of suboptimal technique or effort.

Diseases involving the bronchial (and bronchiolar) smooth muscle usually improve most from “before” to “after.” Increases greater than 50% in the FEV₁ may occur in patients with a clinical history of asthma. Patients with chronic obstructive diseases may show little improvement in flows. Poor bronchodilator response may be related to inadequate deposition of the inhaled drug because of poor inspiratory effort. Failure to show a significant improvement after inhaled bronchodilator therapy does not exclude a response. This is especially true if only the FEV₁ is being monitored. Changes in lung volumes, in particular, may occur without substantial change in FEV₁, but this may not be evident during spirometry. Such changes may still result in significant symptomatic improvement. Some patients have a significant response to one drug but little or no response to another. Efficacy of a specific drug may require repeat testing after a trial on the medication. Long-acting bronchodilators or inhaled corticosteroids may significantly improve a patient’s lung function, even if there is no acute response to an inhaled β₂ agonist.

Some patients show a paradoxical response to bronchodilator therapy. In these individuals, flows may actually decrease after the bronchodilator therapy. Decreased flows after bronchodilator therapy may also be related to fatigue from multiple FVC efforts. Changes of less than 8% or 150 mL are within the variability of measurement of FEV₁. Such small changes may occur just with testing and are unlikely to be significant.