Chapter 4: Lung Volumes, Airway Resistance, and Gas Distribution Tests

Functional residual capacity (FRC) is the volume of gas remaining in the lungs at the end of a quiet breath. On a simple spirogram, this point is termed the end-expiratory level (see Fig. 2.1). Residual volume (RV) is the volume of gas remaining in the lungs at the end of a maximal expiration, regardless of the lung volume at which exhalation was started (see Fig. 2.1). Total lung capacity (TLC) is the volume of gas contained in the lungs after maximal inspiration. FRC, TLC, and RV are reported in liters (L) or milliliters (mL) corrected to body temperature, pressure, and saturation (BTPS). The RV/TLC ratio defines the fraction of TLC that cannot be exhaled (RV), expressed as a percentage.

Thoracic gas volume (V_TG) is the absolute volume of gas in the thorax at any point in time and any level of alveolar pressure. V_TG is only measured when using a body plethysmograph to measure lung volumes. V_TG is usually measured at the end-expiratory level and is therefore usually close to the FRC. V_TG is not a physiologic measure like FRC; it is simply the lung volume where closed-shutter breathing is performed to calculate FRC. The V_TG is reported in liters or milliliters, BTPS.

Technique

There are a variety of methods for measuring absolute lung volumes (Table 4.1). FRC is measured directly with the open-circuit multiple-breath N₂-washout, closed-circuit multiple-breath He-dilution, and body plethysmographic techniques. Once FRC and VC have been measured, RV and TLC can be calculated. TLC can be estimated directly with the single-breath N₂ washout and single-breath He dilution as part of the diffusing capacity (Dlco) test and by chest imaging techniques. RV can only be measured indirectly once FRC or TLC has been determined.

Open-Circuit, Multiple-Breath Nitrogen Washout

Determination of FRC with the open-circuit multiple-breath nitrogen-washout technique (FRCN₂) 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% to 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 1.5%. 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:

FRC=FEN2final×Expiredvolume–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 to 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 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 section later in this chapter). The final FRC is then corrected to BTPS, and the volume of the equipment dead space (including filters) must be subtracted (see the Sample Calculations on the Evolve website, http://evolve.elsevier.com/Mottram/Ruppel/).

To obtain RV, the expiratory reserve volume (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–ERVexpiratoryreservevolume

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 (Fig. 4.1A). 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 nose clip, 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 (Fig. 4.2). The test is continued until the N₂ in alveolar gas has been reduced to approximately 1.5% (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 FRCN₂ 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.

Criteria for Acceptability 4.1

N₂-Washout FRC

1. 1. The washout tracing or display should indicate a continually falling concentration of alveolar N₂.
2. 2. The test should be continued until the N₂ concentration falls to 1.5% for three consecutive breaths.
3. 3. Washout times should be appropriate for the type of subject tested. Healthy subjects should wash out N₂ completely within 3 to 4 minutes.
4. 4. The washout time should be reported. Failure to wash out N₂ within 7 minutes should be noted.
5. 5. Multiple measurements should agree within 10%; the average FRC from acceptable trials should be used to calculate lung volumes. At least 15 minutes of room-air breathing should elapse between repeated trials.

4.1 How To …

Perform Nitrogen-Washout Maneuver

1. 1. Tasks common to all procedures:
   1. a. Calibrate and prepare equipment.
   2. b. Review order.
   3. c. Introduce yourself and identify patient according to institutional policies.
   4. d. Describe and demonstrate procedure.
2. 2. Arrange the chair so that the patient is at a comfortable height relative to the mouthpiece, sitting up straight.
3. 3. Nose clips on, mouthpiece in mouth, tight seal with lips.
4. 4. At the end of a normal exhalation, after about four steady breaths, open the valve to begin breathing 100% oxygen.
5. 5. Continue relaxed breathing until end-tidal N₂ concentration is less than 1.5%.
6. 6. Perform SVC maneuver from FRC; either ERV to RV followed by inhaled VC to TLC or IC to TLC followed by exhaled VC to RV, or both.
7. 7. At least one technically acceptable trial is required; if needed, you may repeat after a resting period on room air of at least 15 minutes; FRC should agree within 10%.
8. 8. Review data and note comments about test quality.

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 Fig. 4.1B). The exact concentration of He and spirometer volume are 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 and desiccant (absorbs H₂O produced from CO₂ absorption) in place until the concentration of He falls to a stable level (Fig. 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 to 8 L is used (Fig. 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:

SystemvolumeL=HeaddedLFHeinitial

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×Systemvolume

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).

Criteria for Acceptability 4.2

He Dilution FRC

1. 1. A tracing or display of spirometer volume should indicate that no leaks are present (system baseline flat). He concentration should be stable before testing.
2. 2. The rebreathing pattern should be regular. If recorded, successive tidal breaths should show a gradually falling end-tidal level as O₂ is consumed. The addition of O₂ should return breathing to close to the system baseline.
3. 3. The test should be continued until the He readings change by less than 0.02% in 30 seconds.
4. 4. The addition of O₂ should be appropriate for quiet tidal breathing (i.e., 200–400 mL/min).
5. 5. The He equilibration curve, if plotted or displayed, should show a smooth and regular fall of He concentration until equilibrium is achieved.
6. 6. Multiple measurements of FRC (only practical for children) should agree within 10%; the average of acceptable multiple measurements should be reported.

4.2 How To …

Perform Helium Dilution Maneuver

1. 1. Tasks common to all procedures:
   1. a. Calibrate and prepare equipment.
   2. b. Review order.
   3. c. Introduce yourself and identify patient according to institutional policies.
   4. d. Describe and demonstrate procedure.
2. 2. Arrange the chair so that the patient is at a comfortable height relative to the mouthpiece, sitting up straight.
3. 3. Nose clips on, mouthpiece in mouth, tight seal with lips.
4. 4. At the end of a normal exhalation, after approximately four steady breaths, open the valve to begin closed-circuit rebreathing.
5. 5. Continue relaxed breathing until helium concentration stabilizes at a minimum level, no more than 0.02% in 30 seconds or a maximum of 10 minutes.
6. 6. Perform SVC maneuver from FRC—either ERV to RV followed by inhaled VC to TLC or IC to TLC followed by exhaled VC to RV, or both.
7. 7. At least one technically acceptable trial is required; if needed, you may repeat after a resting period on room air of at least 5 minutes; FRC should agree within 10%. (See Criteria for Acceptability Box 4.2.)
8. 8. Review data and note comments about test quality.

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.

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. For this reason, 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, such as is 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 to 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. The use of gas-dilution techniques to assess the distribution of ventilation is more commonly performed using radioisotope imaging and CT scanning.

PF Tip 4.1

The gas-dilution techniques of measuring lung volumes sometimes underestimate lung volumes in the presence of moderate or severe obstruction. Both methods (N₂ washout and He dilution) are also subject to leaks in their respective breathing circuits. Leaks usually cause the measured lung volume to be overestimated.

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 nose clips 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 (Fig. 4.5). Inaccuracy or malfunction of the gas analyzers in either method often causes errors. Leaks or analyzer problems should be considered whenever lung volume values are inconsistent with spirometry results, for example, an extremely high TLC and RV/TLC ratio with normal spirometry (Interpretive Strategies 4.1).

Interpretive Strategies 4.1

Dilutional Lung Volumes

1. 1. Was the FRC determination performed acceptably? Were multiple trials performed? If so, were they within 10%?
2. 2. Was the VC maneuver acceptable? Were the ERV and IC measurements within 5% or 60 mL?
3. 3. Were other lung volumes calculated appropriately (TLC, RV)?
4. 4. Are the reference values appropriate? Age, height, sex, race?
5. 5. Is the TLC less than the lower limit of normal (LLN)? If so, restriction is present. Are other lung volumes (FRC, RV) reduced in similar proportion?
6. 6. Is the TLC greater than the upper limit of normal (ULN)? If so, suspect hyperinflation.
7. 7. If the RV/TLC ratio is greater that the ULN, suspect air trapping
8. 8. Are lung volumes consistent with spirometric findings in regard to obstruction or restriction? Are they consistent with the history and physical findings?
9. 9. Are additional tests indicated (plethysmographic lung volumes)?

Body Plethysmography

FRC measured with the body plethysmograph (FRC_pleth) (Fig. 4.6) refers to the volume of intrathoracic 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 lungs at the end of a normal expiration (i.e., at FRC). The airway is occluded momentarily at or near FRC; the patient is asked to gently breathe 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 gently compressed and decompressed. The breaths are shallow and should not create pressure changes >  10 cm H₂O. The closed-shutter breathing 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 a small piston that moves a small volume of gas into and out of the sealed box and relates the pressure change to the known volume (P_box). The calibration factor is then applied to measurements made on human patients. The term panting is often used to describe the gentle, shallow breathing pattern just discussed; however, in some patients, the use of the term panting may elicit fast breathing (e.g., >  1 breath per second). Breathing too quickly may result in an overestimation of lung volume.

The display of the shallow breathing 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 (Fig. 4.7). The resulting figure appears as a sloping line equal to ΔP/ΔV, where ΔP equals the change in alveolar pressure, and ΔV equals the change in alveolar volume (V_A). The change in V_A 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 the Evolve website at 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 breathes shallow with the mouth shutter open. The computer records the change in lung volume above or below the resting level (FRC). When asked to breathe shallowly, most patients do so slightly above FRC. The shutter then closes automatically, the patient continues to breathe shallowly, and V_TG is measured as described. The computer then adds or subtracts the change in volume from the end-expiratory level (before shallow breathing began) to calculate the true FRC. This computerized technique allows the patient to breathe 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 breathing (see following text). It should be noted that the correct breathing frequencies for measuring Raw and V_TG are slightly different. Raw measurements should be made with the patient breathing shallow at about 1.5 to 2.5 Hz (1.5–2.5 cycles per second, or 90–150 breaths/min), whereas V_TG should be measured with the patient breathing at a slower rate of 0.5 to 1 Hz. Many computerized systems display the breathing frequency so that 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 American Thoracic Society–European Respiratory Society (ATS-ERS) 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 shallow-breathing 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 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. The patient should be instructed on how to open the door from within the box. If the plethysmograph is equipped with a communication device, it should be adjusted so that the patient can hear instructions.

4.3 How To

Perform Body Plethysmography (“Body Box”) Maneuvers

1. 1. Task common to all procedures:
   1. a. Calibrate and prepare equipment.
   2. b. Review order.
   3. c. Introduce yourself and identify patient according to institutional policies.
   4. d. Describe and demonstrate procedure.
2. 2. Place the patient in a body box; adjust height of mouthpiece so the patient is sitting up straight; nose clips on; mouthpiece in mouth, tight seal with lips.
3. 3. Patient can practice breathing and shallow-breathing maneuvers.
4. 4. Close door; allow temperature stabilization.
5. 5. Have the patient place hands on cheeks and breathe normally.
6. 6. At end of a normal exhalation, after approximately four steady breaths, begin open shutter breathing; frequency = 1.5 to 2.5 breaths per second. Demonstrate and say “in-out-in-out” or “1-2-1-2-1-2.” This will allow the determination of Raw. Allow time for the subject to reestablish a stable FRC baseline.
7. 7. Warn the patient that the shutter is about to close. Then close the shutter and continue to coach shallow breathing at a slightly slower rate (0.5–1 breath per second). This will allow the determination of V_TG and sGaw.
8. 8. Alternatively, after recording open- then closed-shutter breathing, repeat closed-shutter breathing alone to obtain V_TG.
9. 9. Open shutter, perform SVC maneuver from end exhalation—either ERV to RV followed by inhaled VC to TLC (ATS-ERS preferred method) or IC to TLC followed by exhaled VC to RV (ATS-ERS alternative method).
10. 10. Repeat maneuver until you obtain at least three technically acceptable trials; FRC (V_TG) should agree within 5% (Criteria for Acceptability 4.3).
11. 11. Open door; test ends.
12. 12. Review data and make adjustments in slopes if needed.
13. 13. Note comments about test quality.

Depending on the construction of the plethysmograph, venting to the atmosphere is usually required to establish thermal equilibrium. Equilibrium takes about 30 to 60 seconds and can be presumed when the flow-volume recording stabilizes (i.e., does not drift). Some systems compensate for thermal drift, so waiting for equilibrium is not necessary. The patient is then instructed to breathe shallowly. When the correct breathing 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 breathe shallowly against the closed shutter until a stable tracing is produced. Two to four breaths are usually sufficient. If the patient breathes too hard, the tracing may drift or appear as an “open” loop (see Fig. 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. A minimum of three technically satisfactory maneuvers should be recorded, each followed by ERV and IVC maneuvers (see 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 ΔP/ΔV 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 breathing maneuvers.

Criteria for Acceptability 4.3

FRC_pleth

1. 1. The shallow-breathing maneuver shows a closed loop without drift or another artifact.
2. 2. Pressure changes are within calibration ranges; the tracing does not go off-screen.
3. 3. Breathing frequency should be between 0.5 and 1.0 Hz.
4. 4. A minimum of three technically satisfactory shallow-breathing maneuvers should be recorded.
5. 5. At least three FRC_pleth values that agree within 5% should be obtained.
6. 6. Reported FRC_pleth is averaged from the three acceptable and repeatable panting maneuvers.

Significance and Pathophysiology

FRC varies with body size, change in body position, and time of day (i.e., diurnal variation). However, unlike TLC and RV, FRC is an effort-independent maneuver determined by the balance of lung and chest wall recoil at relaxed end expiration. As with other lung volumes, normal FRC may be affected by racial or ethnic background (see Interpretive Strategies 4.1 and 4.2). Equations for calculating predicted FRC can be found on the Evolve website, http://evolve.elsevier.com/Mottram/Ruppel/.

Increased FRC is considered pathologic. FRC values greater than the ULN represent hyperinflation. Hyperinflation may result from emphysematous changes or from obstruction caused by asthma or bronchitis. Compensation for surgical removal of lung tissue or thoracic deformity can also cause increased FRC. Elevated FRC usually results in muscular and mechanical inefficiency of the respiratory apparatus. As lung volume increases, the chest wall and lungs themselves become “stiffer.” This causes an increase in the work of breathing. FRC can increase dynamically; patients with airway obstruction may increase their end-expiratory lung volume (EELV) during exercise. This change in lung volume with increased ventilatory demand often results in a sensation of breathlessness and reduces exercise time. Reduction in the rate of air trapping is one of the primary benefits of bronchodilator therapy in chronic obstructive pulmonary disease (COPD).

The TLC is the maximal volume of inspired air. TLC is determined by the balance of lung recoil plus chest wall recoil, on the one hand, and muscle strength and effort, on the other hand. Thus diseases that reduce lung recoil will result in increased TLC; those that increase lung recoil may reduce TLC. Likewise, muscle weakness or suboptimal effort may reduce TLC.

The RV is the volume left in the lungs after the VC is exhaled. An increased RV indicates that despite maximal expiratory effort, the lungs contain a larger volume of gas than normal. Increased RV often results in an equivalent decrease in VC (Fig. 4.8). Elevated RV may occur during an acute asthmatic episode but is usually reversible. Increased RV is characteristic of emphysema and bronchial obstruction; both may cause chronic air trapping. RV and FRC usually increase together. As RV becomes larger, increased ventilation is needed to adequately exchange O₂ and CO₂ in the lung. This requires an increase in the tidal volume, respiratory rate, or both. Because of altered pressure–volume characteristics of the lung, the work of breathing is also increased. Patients with increased RV often display gas exchange abnormalities such as hypoxemia or CO₂ retention. Because RV is effort dependent, elevated RV may also be caused by muscle weakness or suboptimal effort.

Measuring lung volumes is critical to understanding changes in FVC. A normal FVC almost always excludes significant restriction. But because decrements in FVC can be from restriction, neuromuscular weakness, suboptimal effort, or severe obstruction, knowledge of TLC, FRC, and RV is invaluable in sorting out these possibilities.

FRC, RV, and TLC are typically decreased in restrictive diseases. Decreased lung volumes are seen in interstitial diseases associated with extensive fibrosis (e.g., sarcoidosis, asbestosis, and idiopathic pulmonary fibrosis). Restrictive disorders affecting the chest wall include kyphoscoliosis, neuromuscular disorders, and obesity. Diseases that impair the diaphragm often result in reduced lung volumes, particularly TLC. Lung volumes may also be decreased in diseases that occlude many alveoli, such as pneumonia. Congestive heart failure causes pulmonary congestion and pleural effusions, which can also reduce lung volume. Any disease process that occupies volume in the thorax (e.g., tumors) can reduce lung volume.

Table 4.2 lists comparative lung volumes for a healthy adult male and for patients with air trapping (as in emphysema), hyperinflation, restriction (as in sarcoidosis), and neuromuscular weakness (as in amyotrophic lateral sclerosis [ALS]).

In obstruction, two different patterns may be observed. RV is usually increased. This increase may be at the expense of a reduction in VC (see Fig. 4.6) with TLC remaining close to normal, in which case the elevated RV/TLC ratio reflects air trapping. Elevated TLC is referred to as hyperinflation, which is usually accompanied by air trapping. TLC may be either normal or increased in obstructive processes such as asthma, chronic bronchitis, bronchiectasis, cystic fibrosis, and emphysema. TLC does not appear to change dynamically, even though FRC may increase acutely during exercise (dynamic hyperinflation).

The RV/TLC ratio describes the percentage of total lung volume that cannot be emptied during expiration. In healthy adults, the RV/TLC ratio may vary from 20% in young adults to 35% in older patients. Values greater than 35% may result from absolute increases of RV (as in emphysema) or from a decrease in TLC because of a loss of VC. As mentioned previously, an elevated RV/TLC in the presence of increased TLC is often indicative of both hyperinflation and air trapping. An increased RV/TLC with a normal TLC indicates that air trapping is present. As an indicator of air trapping, the RV/TLC ratio is a weak but statistically significant indicator of outcome after lung volume reduction surgery (LVRS).

In neuromuscular weakness, FRC is typically normal because lung and chest wall recoil are not specifically affected. However, TLC is low, and RV is high, relative to FRC, because of the reduced muscle strength required to reach these upper and lower limits of lung volume, respectively.

Processes that occupy space in the lungs, such as edema, atelectasis, neoplasms, or fibrotic lesions, may decrease TLC. Other diseases that commonly result in decreased TLC include pulmonary congestion, pleural effusions, pneumothorax, and thoracic deformities. Pure restrictive defects show proportional decreases in most lung compartments, as described for FRC and RV. When the TLC value is less than the LLN, a restrictive process is present. Reduced VC, along with a normal or increased FEV₁/FVC ratio, is suggestive of restriction, but a measurement of TLC is needed to confirm the diagnosis of a restrictive defect.

A less common pattern is mixed obstructive-restrictive lung disease, characterized by a low FEV₁/FVC ratio and a low TLC. This is suggested by simple spirometry when both FEV₁/FVC and FVC are reduced but can only be confirmed by measuring TLC. Measuring the reduction in TLC may allow for more accurate characterization of the concomitant degree of airway obstruction. Another interesting pulmonary function test (PFT) pattern is the so-called “nonspecific” pattern characterized by a reduced FEV₁ and FVC, normal FEV₁/FVC ratio, and normal TLC. This pattern may represent lung volume decruitment occurring in the presence of airway disease or thoracic restriction such as obesity. Obesity is typically characterized by larger decrements in FRC and ERV than in TLC.

Technique

Raw can be measured as the ratio of alveolar pressure (P_A) to airflow (V.). Gas flow at the mouth is measured with a pneumotachometer (see Chapter 11). P_A is measured in the body plethysmograph (Fig. 4.9A). For gas to flow into the lungs during inspiration, P_A must fall below atmospheric pressure (mouth pressure). During expiration, P_A rises above atmospheric pressure. Changes inV̇are plotted against plethysmograph pressure changes. Changes in plethysmograph pressure are proportional to V_A changes. The patient breathes with a small V_T at a rate of about 1.5 to 2.5 breaths/sec (1.5–2.5 Hz). Shallow rapid breathing may produce an S-shaped pressure–flow curve (see Fig. 4.9B). A tangent (the slope) is measured from this curve. Traditionally, the tangent is drawn to pass through zero flow and connects the +  0.5 L/sec and −  0.5 L/sec flow points. The slope of this line is the ratio of V./PBOX. V. is flow at the mouth, and P_box is plethysmograph pressure.

Problems with the open-shutter breathing technique are illustrated by the loops seen in Fig. 4.10. The most common problems are thermal drift and breathing at too high or low of a frequency or volume.

To measure V_TG in association with Raw, the shutter at the mouthpiece is closed immediately after the open-shutter breathing, and the patient continues to breathe shallowly. The optimal rate for closed-shutter breathing is about 0.5 to 1.0 Hz, slightly slower than open-shutter panting. Changes in P_box are then plotted against P_mouth. Because there is no flow into or out of the lungs, P_mouth equals P_A. A second tangent is measured from this curve. The slope of this line is P_A/P_box, where P_A equals alveolar pressure. Computerized plethysmographs usually calculate a “best-fit” line to measure the open-shutter and closed-shutter tangents. The technologist should visually inspect all computer-fitted lines. PFT systems allow the technologist to adjust computer-generated tangents manually. Problems with the closed-shutter breathing technique are similar to those that plague the open-shutter breathing measurement and also include leak around the mouth or nose.

Raw is then calculated by taking the ratio of these two slopes, as follows:

Raw=PA/PBOXV./PBOX×MouthcalFlowcal

This formula shows how Raw is calculated from the ratio of P_A and V., as P_box cancels out. Calibration factors for the flow and mouth pressure transducers are included in the previous equation (see the Sample Calculations on the Evolve website, http://evolve.elsevier.com/Mottram/Ruppel/).

Shallow breathing eliminates several artifacts from the tracing. Small rapid breaths (1.5–2.5 per second) reduce thermal drift, both in the box and in the pneumotachometer. Shallow breathing helps keep the glottis open, allowing measurement of alveolar pressure. Shallow breathing also allows measurements to be made near FRC. The resistances of the mouthpiece and pneumotachometer are subtracted from the patient’s Raw.

Gaw can be calculated as the reciprocal of Raw. Specific conductance is calculated by dividing Gaw by the lung volume at which it was measured, which is V_TG calculated from the closed-shutter maneuver. sGaw should be calculated separately for each Raw maneuver because the lung volume at which measurements are made influences Raw and Gaw. After three to five acceptable trials are obtained, calculated Raw and sGaw are averaged. Individual values should be within approximately 10% of the mean (Criteria for Acceptability 4.4).

sRaw is calculated from the ratio of change in box volume (measured through changes in box pressure) to flow during tidal breathing, which is done in practice by taking the slope of the flow-pressure (or specific resistance) loop. The slope may be drawn through the +  0.5 L/s and −  0.5 L/s fixed flow rates or may be drawn between the points of maximal change in box pressure. Measurements should be made at breathing frequencies of 30 to 45 breaths per minute, which is usually near spontaneous breathing frequency for very young children. The final value is taken as the median of five technically valid specific resistance loops.

Computerized plethysmographs permit thoracic gas volume (V_TG), Raw, and sGaw to be measured from a combined maneuver. The patient breathes through the pneumotachometer with the plethysmograph sealed. Tidal breathing is recorded with the patient breathing near FRC. The computer stores this end-expiratory volume as a reference point. Then the patient pants, and the open-shutter slope of V./PBOX is recorded. The mouth shutter is then closed, and P_mouth /P_box is recorded as described previously. The V_TG in this maneuver does not equal the FRC because the shutter is closed at a volume different from the FRC. However, the change in volume from the tidal breathing level was stored at the beginning of the maneuver. This volume is the “switch-in” volume described earlier and can be added to or subtracted from the V_TG to determine FRC. Most patients pant above their FRC, so the V_TG in this combined method is usually slightly greater (Fig. 4.11). Because of this issue, a separate test to measure FRC for use in calculating absolute lung volumes may need to be done and is often recommended.

Significance and Pathophysiology

Lesions obstructing the larger airways (e.g., tumors, traumatic injuries, or foreign bodies) may also cause a significant increase in Raw. Large airway obstruction is often accompanied by increased work of breathing and dyspnea on exertion. Airflow in the trachea and mainstem bronchi is predominantly turbulent. Any large airway obstruction can exaggerate this turbulent flow. For this reason, Raw and sGaw may be more sensitive to elevations in central airway resistance than FEV₁. Breathing low-density gas mixtures (e.g., helium + oxygen) reduces Raw and therefore the work of breathing. The shapes of the open-shutter breathing loops may give clues as to the underlying pathophysiology, as seen in Fig. 4.10.

Because some patients have changes in sGaw without changes in FEV₁ or FVC after a bronchodilator, and such changes are thought to be clinically significant, measuring bronchodilator response by sGaw may be more sensitive than relying on spirometric indices only. Part of the reason for this may be caused by the anatomic location of airway obstruction, and part may relate to the bronchodilating ability of the deep breath necessarily associated with measuring spirometry, which occurs in healthy subjects and those with mild airway obstruction. Because of this increased sensitivity, sGaw may be less specific for patients with asthma compared with healthy subjects.

Raw is decreased at increased lung volume. The airways (particularly large and medium airways) are distended slightly, and their cross-sectional area increases. For this reason, the V_TG is obtained with Raw to derive sGaw. This allows a comparison of values in different patients or in the same patient after treatment. sGaw is particularly useful for assessing changes in airway caliber after bronchodilator therapy or inhalation challenge. sGaw may change significantly after a bronchodilator or inhalation challenge even though other measures of flow (i.e., FEV₁) vary only slightly. The primary site of airway obstruction (i.e., large versus small airways) may determine which parameters reflect changes in airway caliber.

sRaw is similar to sGaw because it considers lung volume. However, sGaw reflects only Raw, whereas sRaw reflects both Raw and lung volume. This may be illustrated by considering an obstructed patient with hyperinflation versus an obstructed patient without hyperinflation. In the former, Raw is elevated and sRaw is increased (increased work to move air through a higher lung volume), but the increased V_TG associated with hyperinflation corrects conductance back to normal (normal sGaw). In the latter, Raw is increased and sRaw is increased (increased work to move air through an increased resistance), but sGaw is reduced (elevated Raw is not reduced by altered lung volume).

Raw and sGaw measurements are not influenced by the degree of patient effort, so Raw and sGaw measurements may be useful for determining airway status in patients who are unable or unwilling to exert maximum effort. However, acceptable shallow-breathing maneuvers in the plethysmograph require a certain degree of patient coordination. Not all patients may be able to perform these maneuvers. Patients with severe obstruction may produce pressure–flow curves during shallow breathing that are difficult to measure. Such curves may be flat (see Fig. 4.10) or show widening (hysteresis). Inspiratory and expiratory flows may produce different resistances, causing the curve to appear as a loop (see Fig. 4.10). In these cases, inspiratory flow resistance is usually reported.

In addition to resistance caused by flow through conducting airways, some frictional resistance is caused by the displacement of the lungs, rib cage, and diaphragm. In healthy patients, this tissue resistance is only approximately one-fifth of the total resistance, and therefore total pulmonary resistance is approximately 20% greater than the measured Raw.

In addition to measuring Raw by use of the body plethysmograph, measurement of Raw by means of the forced oscillation technique is becoming increasingly common. For further discussion, see Chapter 10. Another method, more popular outside the United States, especially in children, is the use of the interrupter technique to measure Raw. Both methods do not require special breathing maneuvers and are conducted during quiet tidal breathing, thus making them appealing from the standpoint of ease of performance on the part of the patient.

The single-breath nitrogen-washout test (SBN₂) measures the distribution of ventilation. Distribution is analyzed by measuring the change in N₂ concentration during expiration of the VC after a single breath of 100% O₂. The evenness of distribution is assessed by two parameters: the change in percentage of N₂ between the 750- and 1250-mL portion of the SBN₂ test (Δ%N_{2 750–1250}) and the slope of phase III of the expiratory tracing. Each of these indices is recorded as a percentage. Closing volume (CV) is the portion of the VC that can be exhaled from the lungs after the onset of airway closure. CV is also measured from the SBN₂ maneuver and is usually expressed as a percentage of the VC. A related measurement, closing capacity (CC), is the sum of the CV and RV. CC is expressed as a percentage of the TLC.

Technique

The test is performed with equipment like that used for the open-circuit FRCN₂ determination (see Fig. 4.1A). The patient exhales to RV and then inspires a VC breath of 100% O₂ from a reservoir or demand valve. The 100% O₂ dilutes the N₂ present in the lungs. Without holding the breath, the patient exhales slowly and evenly at a flow of 0.3 to 0.5 L/sec. The N₂ concentration is measured by an N₂ analyzer, and the exhaled volume is measured by the spirometer. The volume expired is plotted against the N₂ concentration on a graph (Fig. 4.12). This washout curve can be divided into four phases:

• Phase I: Upper airway gas from the anatomic dead space (V_Danat), consisting of 100% O₂.
• Phase II: Mixed dead space gas in which the relative concentrations of O₂ and N₂ change abruptly as the V_Danat volume is expired.
• Phase III: A plateau caused by the exhalation of alveolar gas in which relative O₂ and N₂ concentrations change slowly and evenly.
• Phase IV: An abrupt increase in the concentration of N₂ that continues until RV is reached.

The initial 750 mL of expired gas contains dead-space gas from phases I and II and is not used to assess the distribution of ventilation. The difference in the N₂ concentration between the 750-mL and 1250-mL points is called the ΔN₂ (%N_{2 750–1250}).

The slope of phase III is the change in N₂ concentration from the point at which 30% of the VC remains up to the onset of phase IV. It is recorded as Δ%N₂ per liter of lung volume.

The volume expired after the onset of phase IV is the CV. CV may be added to the RV, if the RV has been determined, and expressed as the CC. CV is reported as a percentage of VC:

CVVC×100

This method is accurate only in patients who do not have significant obstruction or dead-space–producing disease. CV and CC measurements may be in error if the patient does not perform an acceptable VC maneuver (Criteria for Acceptability 4.5). The inspired and expired VC should be within 5%. The VC during the SBN₂ should match the FVC or VC within 5% or 200 mL. Expiratory flow should be maintained between 0.3 and 0.5 L/sec.

Significance and Pathophysiology

See Interpretive Strategies 4.3.

Technique

Significance and Pathophysiology