Lesser Used Tests of Pulmonary Function: Compliance, Resistance and Dead Space

Abstract

The measurements of lung compliance, airway resistance and respiratory dead space as clinical tests have gradually fallen into disuse as the standard pulmonary function testing procedures; spirometry, lung volume and diffusing capacity measurement, followed, if necessary, by imaging have become the norm for diagnosis of COPD and other lung diseases. To have a real understanding of what spirometry and lung volume tests measure requires some knowledge of compliance and airway resistance. The respiratory dead space is an important global indicator of ventilation/perfusion relationships that remains of interest in the early detection of pulmonary emboli. There are other situations as well where it is clinically useful to perform the measurements described here, so these techniques, although generally set aside from the commonly used tests, should not be forgotten.

Key words: :

• Pulmonary function tests
• Respiratory physiology
• Lung compliance airway resistance
• Respiratory dead space

INTRODUCTION

Spirometry and measurements of static lung volumes measure lung function much in the same way that tests of weight lifting or foot racing evaluate the strength and function of the musculoskeletal system. These are the commonly used tests of respiratory mechanics. They tell us how the respiratory system behaves as a mechanical structure but not why it does. The measurement of the diffusing capacity (DL,co) determines the function of the alveolar-capillary membrane and is also a commonly employed test ([1]) of considerable importance in diagnosis and characterization of emphysema and interstitial lung diseases. Generally, these tests are all that is needed for clinical purposes as we use the test results to compare patients against data derived from populations of healthy people. If more is needed to define abnormalities noted in these tests, we usually employ modern imaging techniques and ultimately biopsy specimens if needed.

There are other lung function tests that delve deeper into the respiratory mechanism and tell us more about actual physiology. Those discussed here are the measurements of lung compliance, airway resistance and respiratory dead space. Compliance measurements can reveal the extent of lung destruction associated with emphysema. Airway resistance measurements assess airways obstruction in both chronic bronchitis and emphysema under conditions of quiet breathing. Before the advent of high-resolution CT scanning, these were frequently used methods of distinguishing these conditions. For the most part, these tests are now rarely performed or studied because, as West has written ([2]), pulmonary physiology has been displaced by molecular biology that attracts most interest and funding. I also suspect that the tests discussed in this paper are not perceived as adding useful clinical information.

Moreover, they are difficult to perform and are unfamiliar to the physician and pulmonary function technician and/or uncomfortable for the patient. The one exception to this is the measurement of airway resistance that is often performed incidentally along with thoracic gas volume (TGV) even if not requested and I suspect that the results, although printed out, are largely ignored. This paper is not intended to review the detailed performance of these tests and result calculations but rather to introduce and explain the theory behind them. The specific procedures for the tests are available from the references and other sources.

COMPLIANCE

Compliance, in general, is the property of matter to return to its resting shape after being distorted by an external pressure (e.g., spring, rubber band, elastic tissue). It is expressed as:

There are two forces that resist lung inflation: compliance and airway resistance. Compliance is a function of stretch while airway resistance is a function of airflow. Compliance is properly measured under zero flow to separate it from the effect of airway resistance. In clinical situations, compliance is sometimes measured during breathing and is then referred to as dynamic compliance. Dynamic compliance is the combination of compliance and airway resistance and can be of clinical use under certain situations as will be addressed later.

To measure static compliance, one needs to measure the volume changes that result from changes in driving pressure across the respiratory system. Total respiratory system compliance is composed of the compliance of the lung and the bellows (chest wall, diaphragm and the abdominal contents that stiffen the diaphragm) connected in series so that the total compliance is less than either of its parts (Figure 1).

Figure 1 Cartoon of lung and chest wall with elastic tension represented by arrows. The difference between the tension of the two structures is the pleural pressure.

It is calculated as its reciprocals:where C_tot = total compliance and C_lung and C_Thorax are self-explanatory. In normals, the compliance of the lung and chest wall are approximately equal at the degree of stretch achieved at functional residual capacity (FRC) so that the total respiratory compliance is about half that of the lung alone. This may seem counterintuitive at first since the lung is held in partial inflation at FRC but when we refer to lung compliance we mean the volume response to any change in transpulmonary pressure regardless of the starting point. To avoid the effects of airway resistance, the transpulmonary pressure is measured before and after a volume change. As I will discuss below, the procedure necessary to measure transpulmonary pressure (pleura to mouth) is one reason why this test is rarely used clinically.

Total compliance (lungs and bellows treated as a single system) is easy to directly measure in a highly relaxed, sedated or anesthetized person. Using a mouthpiece, cuffed endotracheal tube or full face mask, a known level of airway pressure is applied and the volume of air that enters the lungs is measured. The volume change divided by the pressure change gives the total compliance (assuming complete relaxation). To determine the compliance of the lungs separately, we must know the driving pressure across the lung. This requires estimating the pressure within the pleural space as this is the point at which the lungs and chest wall are connected.

The direct measurement of pleural pressure is impractical but it was found in the 1950s that the pressure in the esophagus very closely mirrors the pleural pressure and can be accessed by placing a slightly inflated thin wall balloon in the esophagus connected to a pressure transducer by a thin plastic catheter ([3], [4], [5], [6]). Such balloons can be purchased or can be easily made. The procedure of measuring compliance is straightforward but delicate and technically demanding. The esophageal balloon is lubricated with lidocaine jelly and inserted through the nose, swallowed and placed in the distal esophagus but not crossing the diaphragm. When in proper position, the measured pressure fluctuations during quiet breathing will be appropriate for a pleural pressure tracing, that is, the pressure falls on inspiration and returns to near baseline during expiration. It does not reach zero or go positive during quiet breathing. The subject is then instructed to breathe through a pneumotachograph. The airflow signal is integrated to yield volume, which is displayed on an x/y plot against esophageal pressure changes. Alternately, a rolling seal spirometer can be used instead of a pneumotachograph to directly measure volume changes. If this tracing is viewed during breathing, the resultant curve will show hysteresis (the inspiratory limb will be different from the expiratory limb) mostly due to the effects of airway resistance. Having the subject pause at several points during the maneuver will diminish the hysteresis and allow a cleaner estimate of compliance (Figure 2).

Figure 2 Graph of single breath interrupted technique for determining lung compliance. The subject slowly inspired from residual volume (RV) to total lung capacity and then expired back to RV. At several levels of the vital capacity maneuver, a shutter momentarily interrupts flow to eliminate the effect of airway resistance and diminish the hysteresis. After Forster et al. ([15]), Figure 25.

Clinical value of compliance measurements

The laboratory measurement of lung compliance is rarely done today for clinical purposes. However, compliance measurements in intensive care are important and useful. These measurements are the so-called dynamic and static total respiratory system compliance routinely assessed on patients with stiff lung diseases, such as acute respiratory distress syndrome (ARDS), who are connected to mechanical ventilators. The changes in lung stiffness can occur rapidly in such patient, indicating improvement or deterioration. As the bellows stiffness can be assumed to remain stable day-to-day, changes in total compliance can reasonably be attributed to the lungs.

We do not need to know the absolute value of the lung compliance but rather just the changes over time. With the patient on a volume ventilation mode, either assisted or controlled, but relaxed (respiratory muscle activity during the breath will invalidate the measurement), the dynamic compliance is simply the delivered volume divided by the peak pressure (in ml/cmH₂O). This is the combination of the effects of compliance and airway resistance and so will vary with airflow velocity. To eliminate the airway resistance, the flow is stopped after delivery of the set volume but the exhalation valve is kept closed (either using a manual switch or software control, depending on the ventilator). The pressure then settles at a lower level determined by the compliance of the lung and bellows. The delivered volume divided by that pressure gives the total respiratory compliance. This is a useful and simple way to follow a patient's progress and is easily and quickly performed. Some ventilators are designed to perform this task automatically and display the compliance calculations on their readout.

Frequency dependence of compliance

The many different lung units in the respiratory system; the two lungs, five lobes, 18 segments, etc. are connected in parallel, they fill and empty together. The effect of this parallel arrangement on total lung compliance is additive.

It is clear that the removal of any of the component units will decrease total compliance. As the healthy lung is remarkably homogeneous, all lung units fill and empty in unison and, within limits, lung compliance is normally independent of breathing rate. In diseases such as COPD, where there is increased airway resistance in some regions more than others (due to secretions, swelling or airway collapse), compliance may decrease at higher breathing rates as some of these lung units do not have enough time to fill. This is the basis for the “frequency-dependence of compliance” test where compliance is determined at a variety of breathing rates. As a test, it is an interesting phenomenon and tells us something about the pathology of COPD but it is not of much clinical significance as there are easier and more accepted methods of diagnosing and characterizing COPD such as the commonly used pulmonary function tests.

Airway resistance

The direct measurement of airway resistance is a conceptually simple technique that many talented physiologists failed to develop into an accurate test until several technical problems were resolved ([2], [7]). The test is a variation of the measurement of lung volume using body plethysmography. As mentioned in the introduction, both measurements are usually performed together. The theory is based on Boyle's Law that describes the reciprocal relationship between pressure and volume of a gas in an enclosed space (other variables such as temperature held constant). To explain how resistance is measured, it is helpful to start with the measurement of thoracic gas volume.

Simply stated, a person sits in an air-tight rigid box and attempts to pant for a few seconds, against a closed shutter. A pressure transducer on the mouth side of the shutter measures the airway pressure fluctuations (and therefore the intrathoracic pressure fluctuations since there is no airflow) as the patient attempts to pant. Another transducer measures the pressure changes in the box. As the intrathoracic pressure falls during attempted inspiration, the air in the lungs expands and the chest slightly enlarges occupying a bit more of the space in the box. This in turn slightly compresses the air in the box causing the box pressure to rise, although by a smaller amount than the corresponding drop in the intrathoracic pressure since the box volume is about 200 times greater than the thoracic volume at functional residual capacity (FRC). The opposite happens during attempted expiration.

After adjusting for the relative differences in pressure amplitudes, the signals are displayed against one another on an x-y oscilloscope screen. This creates a diagonally flattened loop, the long axis of which forms an angle against the horizontal baseline. That angle represents the ratio between the (unknown) thoracic lung volume and the (known) box volume and allows us to calculate the FRC using Boyle's law (Figure 3, upper panel).

Figure 3 Simplified schematic diagrams of a body plethysmograph set up to measure lung volume (upper panel) and airway resistance (lower panel). See text for explanation.

Airway resistance is measured by a small modification of this method (Figure 3, lower panel). Instead of panting against a closed shutter, the shutter is open and the subject pants through a pneumotachograph to measure airflow. At first glance, this would seem to measure nothing as air is just moving from the box to the patient and back out to the box. However, when the subject inspires, the chest volume starts to increase and air begins to flow from the box to the subject. Since there is resistance in the airways, the flow slightly lags the pressure change as it overcomes the resistance. As a result, there is a momentary pressure rise in the box until flow stops. This lag in flow is proportional to the airway resistance. The opposite happens on expiration. This is displayed as a change in flow against change in box pressure and the angle of that relationship reflects the flow lag and therefore airway resistance.

In practice, the two measurements are performed in sequence. After instructing the patient on what to do and letting him or her practice panting while holding the cheeks to avoid artifacts from variations in mouth volume, the test begins with panting through the open shutter during which the airway resistance measurements are made. Once the subject is panting correctly, the shutter is closed at the end of expiration and panting efforts continue for a few seconds to measure FRC which together with the inspiratory reserve volume makes up the TGV. The whole sequence takes about ten seconds and can easily be repeated several times if necessary. Clearly, the patient must be well coached as panting at a volume other than FRC will result in an erroneous measurement. The measurement of airway resistance can be repeated after administration of a bronchodilator to assess reversibility of airway obstruction although this is not standardized as is the change in FEV₁ after bronchodilator administration. It is true that the measurement of airway resistance is much less dependent on physical effort than is spirometry but it still requires considerable cooperation so there is little advantage over spirometry except perhaps to determine reversibility of airway obstruction in a patient with severe weakness who cannot perform a forced vital capacity but is otherwise cooperative. The need for the subject to pant was the key discovery that made plethysmography a feasible test as tidal breaths introduced artifacts (noise) related to heating and cooling of the air and gas exchange.

Respiratory dead space

During inspiration, the respiratory system fills with air. Most of this air reaches the terminal alveoli or alveolated respiratory bronchioles and participates in gas transfer with the pulmonary capillaries. Some of it doesn't make it that far and remains in the conducting airways where no air exchange takes place. The volume within these conducting airways is referred to as anatomic dead space. An additional amount of air fills lung units that, for one reason or another, contain little or no capillary blood and so fail to participate in adequate gas exchange. This component is called alveolar dead space and is generally considered to be small in healthy individuals. Both dead space components together are termed physiological dead space.

Normally, physiologic dead space makes up about 22 to 25% of the normal tidal volume, rising slightly in older individuals ([8]). Whereas anatomic dead space is a stable quantity, the alveolar component can increase markedly in several common conditions that effect the distribution of blood flow and ventilation in the lungs. This includes left to right shunts, COPD, asthma and pulmonary emboli or any other condition that caused a mismatch in the ventilation-perfusion relationship.

Dead space is usually written as the ratio of dead space (V_D) to tidal volume (V_T) expressed as a decimal or percentage rather than the absolute volume and the symbol for dead space reflects this. Anatomic dead space can be estimated from a single-breath nitrogen washout curve using the method first described by Fowler ([9]). Determining the physiologic dead space is a bit more complicated and involves comparing the amount of CO₂ in the end tidal alveolar air or arterial blood, presumed to come only from gas exchanging lung units, to the CO₂ in mixed expired air that contains contributions from both the air exchanging units and the dead space. There are two similar ways of doing this. The oldest is by using the Bohr equation:where F_ETCO₂ = the end tidal fraction of CO₂ and F_ECO₂ = mixed expired fraction of CO₂. This formula works equally well using partial pressures so long as all the measurement are in the same units. After all, we are only calculating a ratio.

An example makes this clear.So 0.4 × 600 ml = 240 ml physiologic dead space.

Enghoff described a modification of the Bohr equation that uses a mixed sample of air and the partial pressure of CO₂ in the arterial blood as a surrogate for end tidal CO₂.Partial pressure of arterial CO₂ (PaCO₂) = 37 mmHg Partial pressure of mixed expired CO₂ (P_ECO₂) = 22.2 mmHg Expired volume = 600 mlSo if done properly, it works by either method and in fact can be used with other gases using the expired concentrations. One indication that the alveolar dead space component in healthy subjects is small in comparison to the anatomic dead space is the finding that the dead space is similar whether CO₂ or inert gases are used ([10]).

Is dead space a useful test? Since as far back as the late 1950s, there has been interest in dead space measurements to detect the presence of pulmonary emboli (PE). This is an attractive idea and was more so when the only definitive means of making such a diagnosis was pulmonary angiography. Unfortunately, in practice, dead space determinations were usually equivocal and no one was able to state with confidence that dead space determination was accurate enough to supplant angiography. In a famous article published in 1977 ([11]), Robin stated that dead space for diagnosis of PE did not work and should be given up.

In 1986, Burki et al. ([12]) evaluated dead space in a series of hospitalized patients suspected of having PE. They found that if a dead space of 40% was used as a cutoff, and spirometry was normal (excluding patients with obstructive airway disease), the test had a sensitivity and specificity comparable to ventilation/perfusion lung scanning. However, many patients suspected of having PE cannot adequately perform spirometry and many others have COPD so the number of patients on whom the test can be used appropriately is limited and the test has not gained acceptance. Furthermore, the test is difficult to perform correctly and requires trained technical staff to be present around the clock.

The drive to develop a non-invasive test for PE has also diminished as contrast-enhanced CT scanning has supplanted pulmonary angiography. Although much less invasive than conventional pulmonary angiography, CT scanning is expensive, involves risk to the kidneys and is not universally available so some interest remains in dead space measurements for PE diagnosis. Most recently, measurements of D-dimer, an indicator of blood clotting, have been combined with dead space to improve sensitivity and specificity for PE diagnosis ([13]). Although this combination was found to be very sensitive, it was relatively nonspecific leading to the conclusion that when both tests were normal, PE was unlikely.

However, positive tests were not helpful and had to be confirmed. Acute thromboembolic disease is common and presents with a broad spectrum of symptoms ([14]). As the consequences of failing to diagnose this condition are so serious, emergency room physicians do not hesitate to order PE Protocol CT scans on most patients in whom PE is a possibility. A screening test that can reliably detect this condition or exclude it in unaffected patients would be welcome and dead space measurement remains an attractive part of that solution. It has not yet paid off but may do so in the future.

CONCLUSION

The measurements of lung compliance, airway resistance and dead space can legitimately be considered “orphan” tests, at least for clinical purposes. Nevertheless, an understanding of these tests helps illuminate the fundamental nature of respiratory physiology and pathology that underlies the more “adopted” tests of spirometry and static lung volume. An understanding of the relationship of lung compliance to total respiratory compliance can assist in the management of patients on mechanical ventilation. Airway resistance can be used to probe the airways of patients who cannot perform adequate spirometry and dead space measurements still offer hope for the development of a useful screening test for acute PE.

Dr. Kraman is supported by the Margaret Logan Colvin Chair in Lung Disease Research.