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4. Lung Volume Measurement
4.1 Definition of Lung Volumes
Definition of lung volumes
Tidal volume (VT)
the volume of air inhaled and exhaled into the lungs in a normal resting breathing.
Inspiratory reserve volume (IRV)
The maximal volume of air that can be inhaled after a normal inspiration.
Expiratory reserve volume (ERV)
The maximal volume of air that can be exhaled after a normal expiration, also the volume of air exhaled from FRC to point of maximal exhalation (RV), so ERV equals FRC minus RV.
Residual volume (RV)
The volume of air still remaining in the lungs after the most forcible expiration.
Total lung capacity (TLC)
The volume of air contained in the lungs at the end of a maximal inspiration and equals IC plus FRC, also equals VC plus RV.
Vital capacity (VC)
The maximum amount of air exhaled from the lungs after a maximum inspiration. It is equal to the sum of IRV, VT, and ERV.
Functional residual capacity (FRC)
The volume of air present in the lungs at the end of a tidal volume breath, and is the sum of ERV and RV.
Inspiratory capacity (IC)
The maximum volume of air that can be inspired after reaching the end of a normal, quiet expiration. It is the sum of VT and the IRV.
Forced vital capacity (FVC)
The amount of air can be forcibly exhaled out of the lungs after taking a breath to fill the lungs as much as possible.
Forced expiratory volume in 1 s (FEV1)
The volume of air that can forcibly be blown out in the first 1 s, after full inspiration.
End-expiratory lung volume (EELV)
The volume of air present in the lungs at the end of a tidal volume expiration in mechanical ventilation patients. If PEEP (positive end-expiratory pressure) or CPAP (continuous positive airway pressure) is unused, EELV might be close to the FRC.
Plethysmography is a mature technique for the determination of lung function, especially FRC and TLC.
Sixty years ago, Dubois et al. used somatic plethysmography to measure lung volumes . Since then, the technology has been improved continuously. Besides the classical whole-body plethysmography, new kinds of plethysmography have been developed, such as optoelectronic plethysmography (OEP), respiratory inductance plethysmography (RIP), and dual band respiratory inductance plethysmography, most of which are mainly used in animal experiment. We will focus on the whole-body plethysmography and OEP in this section.
4.1.2 Body Plethysmography
184.108.40.206 Principle and Measuring Methods of Whole-Body Plethysmography
If absolute changes of volume are known and the initial and final pressure can be measured, the initial volume of the closed compartment can be calculated.
Prior to the measurement, the flow and volume should be calibrated using a syringe with calibrated volume . The cabin pressure and mouth pressure should also be calibrated according to the instruction of the manufacturer.
When measuring lung volumes by a body plethysmograph, the test subject should enter into a sealed chamber and hold a mouthpiece in the mouth . Commonly, the lung function test starts with resting normal breath. The pressure at the mouth and in the chamber are measured simultaneously. The mouthpiece will be closed at the end of a normal expiration. Then the patient is instructed to inhale. Inhalation starts from the end-expiration lung volume. As the inspiratory muscles contract, the thoracic and lungs expand, and volumes of thoracic and lungs increase at the same time. As the organs in the thorax are incompressible, the increase of volumes in thorax and lung would be equal. As the volume changes, the decrease of pressure would follow Boyle-Mariotte’s law because the instrument is sealed.
If the airway resistance is close to zero, an infinite airflow would quickly enter the lungs without any pressure gradient, and the pressure of the lungs and chamber will increase instantly. Conversely, if the airway is occluded during the inspiratory exercise, the alveolar pressure might decrease greatly, but no airflow enters the lungs.
Actually, there is resistance in the airway and the resistance is finite. Therefore, only when the pressure gradient between the lungs and the chamber overcomes the resistance of the airways, the flow will start to enter into lungs. In other words, the movement of airflow lags behind changes in lung volume. The airflow lag caused by the slight pressure difference in the breathing cycle is called “shift volume,” which is much smaller than tidal volume. Shift volume is dynamic and exists in both inhalation and exhalation processes. It is generated by the dynamic pressure change within the lungs and represents the amount of gas that needs to be compressed or decompressed in order to drive the airflow during inspiration or expiration.
As the Volumefree is computed, the shift volume can be derived from the pressure change according to Boyle-Mariotte’s law. Thereby, airway resistance can be evaluated.
Due to the effect of the inspiratory muscles, the volume of the chest cavity increases with the increase of air in lungs. The muscles will maintain their tension for a short period of time. At the end of inspiration, pressure equilibration is reached and the shift volume is reduced to zero. The inspired volume measured at the mouth equals the increase in lung volume, and both represent inspiratory tidal volume (VTin). Exhalation is reversed but similar to inhalation. With the relaxation of the respiratory muscles, the lung volumes decrease due to the chest and lung elastic recoil. The expiratory movement continues until the recoil forces of lung and chest wall become equal, and the pressures of alveolar and the box reach equilibrium. At the end of expiration, airflow and shift volume return to zero. Both the expired volume and the volume reduction of lungs can be measured and represent expiratory tidal volume (VTex).
Other lung volume parameters can be measured by the shutter maneuver. After opening of the shutter, the subject can be instructed to inhale maximally after a normal inspiration, and the IVC can be measured. A similar way can be used to measure the ERV. Then RV and TLC can be computed. Combined with spirometry, a prolonged forced expiration can be performed to measure the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC). Airway resistance can also be measured by spirometry. In this way, information about lung mechanics can be obtained (Fig. 4.1).
220.127.116.11 Clinical Application
Differential diagnosis of obstructive airway diseases and restrictive diseases by lung function test
Obstructive airway diseases
Normal or elevated
Normal or elevated
Reduced or normal
Body plethysmography is the gold standard of TLC and FRC. However, it is irremovable and needs the cooperation of patients, and it is unsafe and impracticable to place a patient undergo mechanical ventilation into a sealed chamber. Therefore, it is not suitable for most of the critically ill patients.
4.1.3 Optoelectronic Plethysmography (OEP)
18.104.22.168 Principle of OEP
For the standing position, an 89-marker protocol is usually used [9, 10]. According to Aliverti et al.  and Romei et al. , for subjects in supine position or prone position, such as patients in intensive care unit (ICU), a 52-marker protocol can be used. Four to eight infrared (IR) cameras are used to capture and track the movement of markers that can reflect infrared light. A dedicated workstation is used to synchronize the input and output information to and from cameras. The specialized software in the workstation will compute the three-dimensional trajectories of makers by integrating the information collected from each camera. Then, a geometrical model is applied to measure lung volumes. In this model, every three markers form a triangle and one triangle is defined as a closed surface. The software will calculate the volume contained in each surface. Therefore, we can obtain volume variations of the entire chest wall and its different compartments by using OEP.
The equipment of OEP should be calibrated before using. First, the 3D position (x, y, and z axes) of a calibration tool need to be calibrated. Each camera should recognize all three axes, otherwise the camera’s position needs to be readjusted until it can cover three axes. Then the y-axis to the plane where the subject is located should be measured by moving the wand. At the same time, it is necessary to ensure that cameras can detect the wand as it moves in the range of motion. If the wand cannot be detected, the technician should adjust the speed and movement of cameras .
22.214.171.124 Volume Measurements
As shown in Fig. 4.2, the thoracoabdominal lung volume can be divided into three different parts: pulmonary rib cage (RCp), abdominal rib cage (RCa), and the abdomen (AB). RCp begins at the clavicles and jugular notch and ends at the xiphoid; the range of RCa is from the xiphisternum to the lower costal margin; AB ranges from the lower costal margin to the bilateral anterior superior iliac crests. Abdominal volume change refers to the volume change caused by abdominal wall movement, and is the result of the combined action of the diaphragm and expiratory abdominal muscles. This model is the most suitable for studying chest wall kinematics in most conditions, including rest and exercise. It takes into consideration the differences of pressures acting on the RCp and RCa during inspiration. The diaphragm acts directly only on RCa, while other inspiratory muscles mainly act on RCp other than RCa . Lung volumes can be divided into right and left lung volumes.
As described in detail in previous studies [6, 15, 16], lung volumes are calculated by summing the changes of the triangulated surface areas. The following volume variables can be measured by OEP: end-expiratory volume of chest wall (Veecw), pulmonary rib cage (Veercp), abdominal rib cage (Veerca), and abdomen (Veeab); end-inspiratory volume of chest wall (Veicw), pulmonary rib cage (Veircp), abdominal rib cage (Veirca), and abdomen (Veiab). Tidal volumes of chest wall (Vcw), pulmonary rib cage (VRCp), abdominal rib cage (VRCa), and abdomen (VAB) can be assessed by calculating differences of end-inspiratory volumes and end-expiratory volumes. The percentages of volumes of each part to the entire chest volume can also be calculated.
126.96.36.199 Clinical Application
OEP can be used to measure changes in lung volumes in a different status, such as exercising and resting. OEP has also been validated for measuring lung volumes of infants and patients with chronic obstructive pulmonary disease [11, 17, 18]. It is particularly suitable for critically ill patients as the measuring process is noninvasive and does not need the cooperation of patients, and it has also been validated on patients in the prone and supine positions. For mechanically ventilated patients, OPE can assess volume changes of each compartment of the chest wall precisely and can assess action and control of different respiratory muscle groups. Combined with pressure variables, chest wall dynamics can also be assessed.
A spirometer is an instrument that can measure the volume of air inhaled and exhaled by the lungs. Spirometry is the most commonly used pulmonary function test and is useful in the diagnosis and differential diagnosis of respiratory diseases. Spirometry uses a pneumotachograph to measure volumes, flow rate of air, and frequency of the ventilatory cycle simply and noninvasively .
The earliest spirometer appeared in nineteenth century [20, 21]. In 1813, Kentish invented his “Pulmometer,” which had a graduated bell jar in water, with an outlet at the top controlled by a tap. He was the first to try to study ventilatory volumes in disease, and he used his Pulmometer to measure the ventilatory volumes of his three “bronchitis chronica.” He found that the ventilatory volumes of the patients were much lower than those expected, and thought that ventilatory volumes were affected by “mechanical obstruction” and “inflamed state of the bronchiae (sic), causing spasmodic action” . An English physician named John Hutchinson invented a spirometer, and he recorded the vital capacities of over 4000 subjects. He found that the vital capacity had a linear relationship with height. Since then, a number of papers described different machines to measure ventilation. Gad (1879) and Regnard (1879) were regarded as the first ones to use spirometers with graphic records . In the twentieth century, more elaborate closed-circuit machines were invented and used to measure lung volumes . In 1959, Wright B.M. and McKerrow C.B. introduced the peak flow meter, which was much cheaper, lighter, and easier for use and could give rapid information in the ward or in the home of patient .
4.2.1 Measuring Method
With the improvement of technologies, many spirometers designed for use in primary care do not require daily calibration. However, equipment maintenance, accuracy, and precision checks are still essential for quality spirometry. The international standards state that the volume accuracy and airtightness of the spirometer should be checked at least once a day with a 3 L calibrated syringe, and the measurement errors of volumes should be within acceptable ranges . At the same time, the accuracy of the syringe volume must be guaranteed. The environment of storage and use of the syringe should be with the same temperature and humidity of the test site. The linearity of flow should be checked weekly and that of volume should be checked quarterly. The accuracy of the time scale of the mechanical recorder should be checked with a stopwatch at least quarterly. If a large number of subjects are tested within a day, or the ambient temperature of the test site is changing, the accuracy of the spirometer should be checked more frequently than daily. Volume-type spirometers must be checked for airtightness every day .
The most important lung volumes that can be measured by spirometry are FVC and FEV1. When measuring those lung volumes, patients are usually in a sitting position with nares occluded by nose clips or hands to prevent leakage of air through the nasal passages. The technician needs to instruct and encourage the patient to perform the breathing maneuvers. First, ask the patient to inhale deeply. Then, a mouthpiece should be put into the mouth of the patient immediately and be held tightly with lips. Exhalation should be performed with as much force as possible, and make sure there is no air leakage during maximal forced exhalation. For subjects older than 10 years, exhalation should last at least 6 s and until no more air can be expelled from the lungs while maintaining an upright posture. For patients with airways obstruction or older age, exhalation times often require>6 s. However, exhalation times does not need to exceed 15 s. The patient is allowed to rest for a few seconds and the breathing maneuvers need to be repeated until three acceptable maneuvers are obtained . Usually, at least three maneuvers are performed, but if one or more of the maneuvers do not meet the requirement, more attempts should be performed. However, the number of attempts should be not more than eight, which is generally a practical upper limit for most subjects [25, 26]. Multiple prolonged exhalations within a short time may lead to different uncomfortable symptoms, such as light-headedness, syncope, fatigue, and so on. If a patient feels dizzy, the test should be stopped, otherwise syncope might occur due to decreased venous return caused by increased intrathoracic pressure. In order to guarantee the accuracy of lung volumes measured by spirometers, the most important task is to instruct the subject to inhale and exhale rapidly and completely. The waveforms and data should be assessed for reliability and accuracy before analysis. Even if the instrument is accurate, the results obtained by spirometers might be misleading for clinical diagnosis and treatment if the patient did not breath with maximum strength. During measurement, a cough, hesitation, or hold of breath may affect the measured values of FEV1 and FVC . Leakage at the mouth or near or obstruction of the mouthpiece may also influence the accuracy of measured values. Patients with neuromuscular disease may need assistance from technicians or family members to keep the airtightness of the mouth.
A spirometer can also be used to measure VC and IC. However, the spirometer must meet the requirements for measuring FVC and can be capable of accumulating volume for at least 30 s. When measuring VC, the subject should be instructed and demonstrated how to breathe appropriately in the VC maneuver. The subject should wear a nose clip and be in a seated position. The subject needs to inhale completely from the full expiration position (RV) to assess the IVC or exhale completely from the full inspiration position (TLC) to assess the EVC. If significant differences between IVC and EVC are detected, there might be airways obstruction . Subjects should be relaxed except at the end of the inspiration and expiration. During the test process, the subject exhales completely to RV, then inhales to TLC, and finally exhales to RV again. When measuring IC, subjects should also be relaxed and breathe regularly for several times until the end-expiratory lung volume is stable. Then the subjects should inhale deeply to TLC without hesitation. At least three acceptable maneuvers should be performed and selected for the measurement of VC and IC.
4.2.2 Clinical Application
Spirometers can be used to diagnose certain types of respiratory diseases, such as asthma, bronchitis, emphysema, and so on. Spirometry can measure FEV1 and FVC, which is widely accepted and used as a clinical tool for diagnosing and differential diagnosing of obstructive, restrictive, or mixed ventilatory dysfunction [28–30]. FEV1 can also be used to evaluate the efficacy of treatments and to monitor the severity of respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD).
For patients with mechanical ventilation, side-stream spirometers can be used to measure flow continuously and lung volumes can also be evaluated by the area under velocity-time curve . Spirometers can also be used to measure PEEP-induced recruitment volumes (PEEP-volumes) at the bedside. When measuring the PEEP-volume, a long expiration hold maneuver should be performed and zero end-expiratory pressure (ZEEP) is required, where FRC is assumed to be reached. If FRC is the same at different levels of PEEP, the difference in end-expiratory lung volumes (EELV) (ΔEELV = EELVhigh PEEP − EELVlow PEEP) should theoretically be close to the difference in ΔPEEP-volume (PEEP volumehigh PEEP − PEEP volumelow PEEP).
There are some limitations to spirometry. First, using a fixed FEV1/FVC ratio to define airflow limitation has been criticized as it might result in underdiagnosis in younger subjects and overdiagnosis in elderly subjects. Furthermore, the measurement of lung volumes by spirometers is highly dependent on effort and cooperation of the subject .
4.3 Washout/Washin Technique
Washin/washout technique has been applied to measure static lung volumes, and the technique analyzes the concentration changes of a gas with low solubility, such as nitrogen during washin/washout maneuvers.
4.3.1 Washout/Washin technique
Washout/washin technique can be used to measure static lung volumes by inhaling a gas with low blood solubility and continuously measuring and analyzing the concentration of the gas.
Nitrogen washout/washin maneuvers (or Fowler’s method) are the most commonly used methods in clinical practice. Nitrogen has low solubility in blood and tissues, low exchange rate in the alveoli, and cannot be absorbed and metabolized by the human body. Thus, it is suitable as a tracer to measure lung volumes, such as dead space volume, functional residual capacity (FRC), or end-expiratory lung volume (EELV), and some other parameters related to airways occlusion, and this method is not directly affected by changes in body metabolism during the measurement process.
The nitrogen washout/washin technique is based on the law of conservation of mass. There are two types of nitrogen washout/washin techniques, which are single-breath nitrogen test and multiple-breath nitrogen test. Both tests require similar equipment and can estimate FRC/EELV. However, the multiple-breath test might be more accurate in measuring absolute lung volumes.
4.3.3 Single-breath Nitrogen Test
When measuring lung volumes using single-breath nitrogen test, the first step is to increase the fraction of inhaled oxygen (FiO2) to 1.0, and the patient is directly connected to a spirometer. Ask the subject to take a normal breath of 100% oxygen after a normal exhalation (at this time the lung volume is FRC or EELV). Then, the subject exhales from Vt. The concentration of N2, oxygen, and carbon dioxide in exhaled gas are continuously monitored, as well as the gas flow rate.
4.3.4 Multiple-Breath Nitrogen Washout/Washin (MBNW) Test
MBNW method is commonly used for lung function tests in patients with spontaneous breath or mechanical ventilation. Similar to single-breath nitrogen test, at the beginning of MBNW test, FiO2 is adjusted from the baseline to 1.0. After a normal exhalation (at this time, the amount of gas in the lung is FRC or EELV), the patient is directly connected to a spirometer, and the gas flow rate during breathing is continuously monitored. The concentration of nitrogen is measured from the beginning (C1) to the end of the test. Because there may be nitrogen flushing out of human tissue or signal noise affecting the measurement results, the test can be completed when the nitrogen concentration in the exhaled gas reaches 3% of the baseline . The total amount of exhaled nitrogen (MN) can be calculated according to the total amount of exhaled gas and the real-time concentration of nitrogen. At the beginning and end of the experiment, the amount of N2 is the same, which is just the amount of N2 in the FRC. Since there is no material leakage in the system, during the test, the amount of nitrogen remains unchanged (concentration × volume = amount), and the FRC is calculated by the same way of single-breath nitrogen test.
If the patient is initially connected to the spirometer at other lung volumes (such as TLC or RV), the corresponding lung volumes might be measured by the same method. PEEP-induced lung volume changes (referred to as PEEP-volume) can also be assessed simply at the bedside by using passive spirometry. EELV at different PEEP levels can be measured, and the difference in EELV (that is, ΔEELV = EELVhigh PEEP − EELVlow PEEP) can be calculated. The patient exhales to zero end-expiratory pressure (ZEEP) for a long time until FRC is assumed to be reached, and the PEEP-volume at different PEEP can be obtained, as well as the difference in PEEP volume (ΔPEEP volume = PEEP-volume high PEEP − PEEP-volume low PEEP). If the ΔEELV is similar to ΔPEEP volume, we can assume that the FRC has not been modified by the PEEP changes and vice versa.
4.3.5 Modified Nitrogen Washout/Washin Method
Under certain conditions, such as high FiO2 or high PEEP, the nitrogen washout/washin method might be restricted. Modified nitrogen washout/washin technology can be used to measure FRC or EELV in this situation  as this method can be used with a step of small change in FiO2, and there is no need to interrupt mechanical ventilation. Traditional MBNW methods measure the total amount of nitrogen washed out from the lungs. However, the modified technique estimates the changes of alveolar nitrogen concentration and the variation of tidal volume during washout .
The measurement is based on two assumptions: (1) The heterogeneity of the alveolar gas distribution is constant during the measurement process, and the total FRC/EELV does not change until the alveolar gas composition reaches a new equilibrium after changing the FiO2 ; (2) During the measurement, the body’s cell metabolism and gas exchange between the pulmonary capillaries and the alveoli are stable.