Open-Circuit, Multiple-Breath Nitrogen Washout

Determination of FRC with the open-circuit multiple-breath nitrogen washout technique (FRC_n2) is based on washing out the N₂ from the lungs while the patient breathes 100% O₂ for several minutes. At the start of the test, the N₂ concentration in the lungs is approximately 75%–80%. As the patient breathes 100% O₂, the N₂ in the lungs is gradually washed out, and the total expired volume is measured. At the end of the test, the N₂ concentration in the lungs is approximately 1%. The initial N₂ concentration, amount of N₂ washed out, and final N₂ concentration are measured and can then be used to calculate the volume of air in the lungs at the start of the test (FRC), using the following formula:

< ?xml:namespace prefix = "mml" />FRC=FEN2final×Expired Volume−N2tissueFAN2alveolar1−FAN2alveolar2

where:

F_EN_2final   = fraction of N₂ in volume expired

F_AN_2alveolar1 = fraction of N₂ in alveolar gas initially

F_AN_2alveolar2 = fraction of N₂ in alveolar gas at end (from an alveolar sample)

N_2tissue    = volume of N₂ washed out of blood/tissues

A correction must be made for N₂ washed out of the blood and tissue. For each minute of O₂ breathing, approximately 30–40 mL of N₂ is removed from blood and tissue. N_2tissue = 0.04 times T (where T is the time of the test). This value is subtracted from the total volume of N₂ washed out.

The original N₂ washout technique lasted 7 minutes. However, not all of the N₂ in the lungs may be washed out, even after 7 minutes of 100% O₂ breathing. The F_An_2alveolar2 is measured at the end of the test and subtracted from the initial N₂ concentration. Correction for the “switch-in” error should also be made (see Correcting for the Switch-in Error). The final FRC is then corrected to BTPS, and volume of the equipment dead space (including filters) must be subtracted (see the Sample Calculations on Evolve at http://evolve.elsevier.com/Mottram/Ruppel/).

To obtain RV, the ERV measured immediately after the acquisition of FRC as a “linked” maneuver (i.e., without the patient coming off the mouthpiece), is subtracted from the FRC:

RV=FRC−ERV(expiratory reserve volume)

To obtain TLC, the calculated value for RV is added to the “linked” inspiratory vital capacity (IVC): TLC = RV + IVC

Some available commercial systems use a rapid N₂ analyzer in combination with a spirometer to provide a “breath-by-breath” analysis of expired N₂ (Figure 4-1, A). An alternative approach is to use fast-response O₂ and carbon dioxide (CO₂) analyzers to calculate the concentration of N₂ in expired gas during the washout:

N2=1−FEO2−FECO2

where:

F_Eo₂ = fraction of O₂ in expired gas (dry)

F_Eco₂ = fraction of CO₂ in expired gas (dry)

In these fast methods, the patient, wearing a noseclip, breathes through a mouthpiece-valve system. Precisely at end-expiration, a valve is opened to allow 100% O₂ breathing to begin. Each breath of 100% O₂ washes out some of the residual N₂ in the lungs. Analog signals proportional to N₂ concentration and volume (or flow) are integrated to derive the volume of N₂ exhaled for each breath. Values for each breath are summed to provide a total volume of N₂ washed out (Figure 4-2). The test is continued until the N₂ in alveolar gas has been reduced to approximately 1% (Criteria for Acceptability 4-1). Some older systems terminate the test at 7 minutes. However, the O₂ breathing should be continued until alveolar N₂ falls to less than 1.5% for at least three consecutive breaths. A change in inspired N₂ concentration of greater than 1% or sudden large increases in expiratory N₂ concentrations indicate a leak, in which case the test should be stopped and repeated.

At least one technically satisfactory FRC_n2 determination should be made. If additional washouts are performed, a waiting period of at least 15 minutes is recommended to allow normal concentrations of N₂ to be reestablished in the lungs, blood, and tissues. If more than one FRC measurement is obtained, the mean of the technically acceptable results that agree within 10% should be reported.

Some pulmonary function systems use pneumotachometers that may be sensitive to the composition of expired gas. These devices correct for changes in the viscosity of the gas as O₂ replaces N₂ in the expirate. Such corrections are easily

accomplished by software or electronic correction of the analyzer output.

Closed-Circuit, Multiple-Breath Helium Dilution

FRC can also be determined by equilibrating the gas in the lungs with a known volume of gas containing He (closed-circuit, multiple-breath helium dilution [FRC_he]). A spirometer is filled with a known volume of air, and then a volume of He is added so that a concentration of approximately 10% is achieved (see Figure 4-1, B). The exact concentration of He and spirometer volume is measured and recorded before the test is begun. The patient breathes through a valve that allows a connection to a rebreathing system. The valve is opened at the end of a quiet breath (i.e., the end-expiratory level). Then the patient rebreathes the gas in the spirometer, with a CO₂ absorber in place, until the concentration of He falls to a stable level (Figure 4-3). A fan or blower mixes the gas within the spirometer system. O₂ is added to the spirometer system to maintain the Fio₂ near or above 0.21 and to keep the system volume relatively constant.

An older method (i.e., the bolus method) added a large volume of O₂ to the spirometer at the beginning of the test. The patient then rebreathed and gradually consumed the O₂. Because of the possibility of equilibrium not being attained before the added O₂ was depleted, this method is no longer used.

Equilibration between normal lungs and the rebreathing system takes place in approximately 3 minutes when a 10% He mixture in a system volume of 6–8 L is used (Figure 4-4). The final concentration of He is then recorded. The system volume is computed first. System volume is the volume of the spirometer, breathing circuitry, and valves before the patient is connected. It can be calculated as follows:

System volume(L)=Headded(L)FHe initial

where:

He_added  = volume of He placed in the spirometer in liters (L)

F_{he initial} = % He converted to a fraction (%He/100)

When the system volume is known, FRC can be computed as follows:

FRC=%Heinitial−%Hefinal%Hefinal×System volume

Either percent or fractional concentration of He may be used because the FRC calculation is based on a ratio.

Some automated systems use a similar method to calculate the system volume; a small amount of He is added to the closed system, followed by a known volume of air. The change in He concentration after the addition of the air is used to determine the system volume. Rebreathing is continued until the He concentration changes by no more than 0.02% in 30 seconds (Criteria for Acceptability 4-2).

At least one technically satisfactory measurement should be obtained. If additional dilutions are performed, a waiting period of at least 5 minutes is recommended between repeated tests. If more than one measurement of FRC_he is obtained, it is recommended that the mean of the technically acceptable results that agree within 10% be reported.

Although a small volume of He dissolves in the blood during the test, it results in a negligible increase in FRC, and it is recommended that no correction be made. The volume of the equipment dead space (including filters) must also be subtracted from the measured FRC.

Correcting for the “Switch-In” Error

Most manufacturers provide “switch-in” error correction when the patient begins the test at a point either above or below the actual end-expiratory level (FRC). Depending on the patient’s breathing pattern, a volume difference of several hundred milliliters may result. The effect of the switch-in error may be insignificant, especially with the closed-circuit method. Equilibrium does not occur instantaneously at switch-in. The total volume of spirometer and lungs is constantly changing with tidal breathing, removal of CO₂, and the addition of O₂. If the switch-in error is large or the end-expiratory level appears to change during the maneuver, the test may need to be repeated.

Additional Comments on FRC by Gas Dilution Techniques

In the gas dilution techniques, RV is measured indirectly as a subdivision of the FRC. This method is preferred because the resting end-expiratory level depends less on patient effort than on maximal inspiration or expiration. The end-expiratory level (and the ERV) must be accurately measured. If tidal breathing is irregular, ERV may be overestimated or underestimated. Subtraction of an ERV value that is too large from the FRC will cause the RV to appear smaller than it actually is. Similarly, a small ERV will produce a larger than actual RV. The patient’s tidal breathing pattern must be carefully monitored during the VC measurement.

The accuracy of the gas dilution techniques depends on all parts of the lung being well ventilated. In patients who have an obstructive disease, some lung units are poorly ventilated. In these patients, it is often difficult to wash N₂ out or mix He to a stable level in poorly ventilated parts of the lungs. Thus, FRC, RV, and TLC may all be underestimated, usually in proportion to the degree of obstruction. Extending the time of these tests improves their accuracy. However, prolonging the test may not measure completely trapped gas, as found in bullous emphysema.

The graphic method of displaying breath-by-breath N₂ washout provides a means of quantifying the evenness of ventilation. Some systems plot the logarithm of the N₂ concentration against time or volume exhaled. The slope of the washout curve is determined by the FRC, tidal volume, dead space volume, and frequency of breathing. If N₂ is washed out of the lungs evenly, the log N₂ plot appears as a straight line. Because the lung is not perfectly symmetric, the washout curve is slightly concave. The deviation from the expected curve indicates the extent to which ventilation is uneven. Washout should be complete within 3–4 minutes in healthy patients. The time to reach He equilibrium during the closed-circuit FRC determination can also be used as an index of distribution of ventilation. By simply recording the time to reach equilibrium and plotting the dilution curve, an estimate of the evenness of ventilation is obtained. Use of gas dilution techniques to assess the distribution of ventilation is more commonly performed using radioisotope imaging and CT scanning.

In either of the gas dilution techniques, a leak will cause erroneous estimates of FRC. Leaks may occur in breathing valves or circuitry, or at the patient connection. Some patients have difficulty maintaining an adequate seal at the mouthpiece throughout the test. Failure to properly apply noseclips can also result in a leak. Leaks usually result in an overestimate of lung volume. A leak in the open-circuit N₂ washout system allows room air to enter, increasing the volume of N₂ washed out. A leak in the closed-circuit He dilution system allows air to dilute the He concentration or He to escape. Each situation causes the test gas concentration to change more than it should. Leaks during the N₂ washout can usually be identified by an inspection of the graphic display or recording (Figure 4-5). Inaccuracy or malfunction of the gas analyzers in either method often causes errors. Leaks or analyzer problems should be considered whenever FRC values are inconsistent with spirometry results (See Interpretive Strategies Box 4-1).

Body Plethysmography

FRC measured with the body plethysmograph (FRC_pleth) (Figure 4-6) refers to the volume of intrathorax gas measured when airflow occlusion occurs at end-expiration (FRC) during shutter closure. The technique is based on Boyle’s law relating pressure to volume. A volume of gas varies in inverse proportion to the pressure to which it is subjected if the temperature remains constant (isothermal). The patient has an unknown volume of gas in the thorax at the end of a normal expiration (i.e., the FRC). The airway is occluded momentarily at or near FRC; the patient is asked to gently pant at a frequency between 0.5 and 1.0 Hz (0.5–1.0 cycles per second), allowing the air in the chest to be compressed and decompressed. This causes a change in volume and pressure. The changes in pressure are easily measured at the mouth (P_mouth) with a pressure transducer. Mouth pressure theoretically equals alveolar pressure when there is no airflow. Changes in pulmonary gas volume are estimated by measuring pressure changes in the plethysmograph. The pressure in the plethysmograph is measured by a sensitive transducer. This transducer is calibrated by introducing a small, known volume of gas into the sealed box and relating the pressure change to the known volume (P_box). The calibration factor is then applied to measurements made on human patients.

The display of the panting maneuver is a graph with P_mouth and P_box. P_mouth is plotted on the vertical axis, and P_box is plotted on the horizontal axis (Figure 4-7). The resulting figure appears as a sloping line equal to DP/DV, where DP equals change in alveolar pressure and DV equals change in alveolar volume. Change in alveolar volume is measured indirectly by noting the reciprocal change in plethysmograph volume.

The V_TG can then be obtained from the slope of the tracing by applying a derivation of Boyle’s law:

VTG=PBλVTG×PBOXcalPMOUTHcal×K

where:

V_TG  = thoracic gas volume

P_B    = barometric pressure minus water vapor pressure

^λV_TG    = slope of the displayed line equal to DP/DV

P_boxcal  = box pressure transducer calibration factor

P_mouthcal = mouth pressure transducer calibration factor

K    = correction factor for volume displaced by the patient

For the complete derivation of the equation and sample calculations, see Evolve (http://evolve.elsevier.com/Mottram/Ruppel/).

Computerized plethysmograph systems permit the monitoring of tidal breathing in conjunction with the V_TG maneuver. Instantaneous changes in

lung volume can be monitored by continuously integrating the flow through the plethysmograph’s pneumotachometer. The end-expiratory level can be determined from tidal breathing. The patient then pants with the mouth shutter open. The computer records the change in lung volume above or below the resting level (FRC). When asked to pant, most patients do so slightly above FRC. The shutter then closes automatically, the patient continues panting, and V_TG is measured as described. The computer then adds or subtracts the change in volume from the end-expiratory level (before panting began) to calculate the true FRC. This computerized technique allows the patient to pant at the correct frequency and depth before the shutter is closed. It also eliminates the necessity of closing the shutter precisely at end-expiration. Raw and sGaw can also be measured simultaneously during the open-shutter panting (see following text). It should be noted that the correct panting frequencies for measuring Raw and V_TG are slightly different. Raw measurements should be made with the patient panting at about 1.5–2.5 Hz (1.5–2.5 cycles per second, or 90–150 breaths/min), whereas V_TG should be measured with the patient panting at a slower rate of 0.5–1 Hz. Many computerized systems display the panting frequency so the technologist can coach the patient to achieve the correct rate.

A VC maneuver along with its subdivisions (ERV and IC) should be performed immediately after the acquisition of FRC_pleth. The ATS-ERS (American Thoracic Society-European Respiratory Society)Task Force recommends that a linked ERV maneuver to RV followed by an IC maneuver to TLC be performed. An alternative method is to perform linked maneuvers with an IC first to TLC followed by a VC breath to RV. Most plethysmograph systems allow these measurements using the built-in pneumotachometer. The same standards for accuracy should be applied to a slow VC measured in the plethysmograph as for any other spirometer. When FRC_pleth has been determined, the remaining lung volumes can be calculated as described for the gas dilution techniques.

Measurement of FRC_pleth is a complex procedure. Each patient must be carefully instructed in the required maneuvers. Allowing the patient to sit in the box with the door open is helpful. A few patients may experience claustrophobia in the plethysmograph. The panting maneuver should be demonstrated by the technologist and then practiced by the patient. The patient should be instructed to place both hands against the cheeks. This prevents unwanted pressure changes in the mouth when the patient pants against the closed shutter. If practical, the shutter may be closed so that the patient knows what to expect during the test. The door of the plethysmograph can then be closed. The patient should understand that the plethysmograph can be opened if he or she becomes uncomfortable. Most systems allow the patient to open the door from within the box. If the plethysmograph is equipped with a communication device, it should be adjusted so the patient can hear instructions.

Depending on the construction of the plethysmograph, venting to the atmosphere is usually required to establish thermal equilibrium. Equilibrium takes about 30-60 sec and can be presumed when the flow-volume recording stabilizes (i.e., does not drift). The patient is then instructed to pant. When the correct panting frequency and depth have been established, the shutter may be closed. Some plethysmograph systems require tidal breathing before shutter closure to establish the patient’s end-expiratory level. In either type of system, the patient should pant against the closed shutter until a stable tracing is produced. Two to four pants are usually sufficient. If the patient pants too hard, the tracing may drift or appear as an “open” loop (see Figure 4-7). The recorded pressure changes should be within the range over which the transducers were calibrated. The entire tracing should be visible on the display. If the tracing goes off-screen, the pressure changes probably exceed the calibration ranges. Three or more technically satisfactory maneuvers should be recorded, each followed by ERV and IVC maneuvers (Criteria for Acceptability 4-3). At least three FRC_pleth values that agree within 5% should be obtained and the mean value reported. The technologist’s comments should note the acceptability of the maneuvers. Most computerized plethysmographs automatically measure the slope of the DP/DV tracings. This is done by using the least-squares method to calculate a “best-fit” line through the recorded data points. The technologist may need to correct computer-generated tangents, depending on data quality from the panting maneuvers.

Additional Comments on FRC by Plethysmography

The plethysmographic method is a quick and accurate means of measuring lung volumes. It can be used in combination with simple spirometry to derive all lung volume compartments. The plethysmograph’s primary advantage is that it measures all gas in the thorax, whether in ventilatory communication with the atmosphere or not. The plethysmographic measurement of FRC is often larger than that measured by He dilution or N₂ washout. This is the case in emphysema and other diseases characterized by air trapping, as well as in the presence of an uneven distribution of ventilation. When gas dilution tests are continued for more than 7 minutes, the results for FRC determinations approach the V_TG value. See Interpretive Strategies 4-2.