Br. J. clin. Pharmac. (1979), 8, 513-521

VENTILATION G.M. STERLING Southampton Western Hospital, Oakley Road, Southampton S09 4WQ

Ventilation (V') is the volume of gas moved into, or out of the lungs and airways over a given period of time and is usually expressed in litres per minute (1 min ') and called the minute volume. It is one of the easiest respiratory variables to measure and has occupied an important place in pulmonary physiology and pharmacology and in clinical medicine at least since the classical experiments of Haldane and others early in the present century (Haldane & Priestley, 1905; Boycott & Haldane, 1908). Essentially, the measurement of ventilation requires only a clock and a mechanical flow meter or some large volume collecting chamber such as a Tissot spirometer or Douglas bags, but these are bulky and are frequently replaced by a flowmeter and electrical integrator. It is widely recognized that the amount and pattern of ventilation may be altered by the method of measurement, which usually involves breathing through a mouth piece and valve box while wearing a nose clip and sitting in a pulmonary laboratory, all of which are unnatural practices (Gilbert, Auchincloss, Brodsky & Boden, 1972). As a result, several indirect ways of measuring ventilation have been developed.

Theoretical problems Before techniques of measurement are described, certain problems and pitfalls concerning the apparently simple notion of ventilation need to be considered.

(1) Inspired ventilation (VI) versus expired ventilation

(VE)

The expiratory exchange ratio for carbon dioxide and oxygen (R) is normally less than unity (average about 0.8, but dependent on diet and other factors) which means that less carbon dioxide is given out than oxygen taken up over a given time so that VE is less than VI. The volume involved is relatively small but must be taken into account for certain purposes such as the calculation of dead space. The respiratory exchange ratio effect is corrected for on the basis that there is no significant transfer of nitrogen across the lungs, so that the amount (i.e. number of molecules) of nitrogen inspired is the same as that expired. Therefore differences in the fractional concentration of nitrogen make it possible to calculate the

0306-5251/79/110513-09 $01.00

relationship of inspired and expired minute volumes (Cotes, 1975). V1XFIN2 = VE XFEN2 = >FEN2 X VI = VE FN F1N2

Generally, and unless specifically stated, ventilation is measured as expired volume, though it may be necessary to measure inspired volume if a dry gas meter is used. Differences in temperature and water vapour content also have to be corrected for, and this is done by adjusting measured volumes to BTPS for total ventilation, and to STPD for purposes of gas exchange calculations. (STPD = standard temperature, 0°C, and pressure, 760 mmHg, of dry gas.) (2) Subdivisions of ventilation

Minute volume is the product of tidal volume and frequency (VE = VT xf) and separate measurement of these components is important in the analysis of control of breathing (Hey, Lloyd, Cunningham, Jukes & Bolton, 1966; Clark & von Euler, 1972; Newsom-Davies & Stagg, 1975). Ventilatory responses to exercise and carbon dioxide have been investigated in this way (Cunningham & Gardner, 1972; Cunningham, Drysdale & Gardner, 1977; Gardner, 1977) as have those to vagus nerve blockade (Guz, Noble, Widdicombe, Trenchard, Mushin & Makey, 1966; Guz, Noble, Widdicombe, Trenchard & Mushin, 1966) and certain drugs (Gautier & Gaudy, 1978). Minute volume and tidal volume can also be divided into separate contributions from the alveoli and from the conducting airways or 'dead-space':

j- E = V~A + V~D j.VT = VA+ VD Normal dead space is about 150 ml and represents 20-30% of tidal volume at rest (Fowler, 1948; Riley, Permutt, Said, Godfrey, Cheng, Howell & Shephard, 1959). It increases only slightly during exercise, when it constitutes a smaller proportion of tidal volume (Jones, McHardy, Naimark & Campbell, 1966). Dead space can be thought of either as 'anatomical', representing simply the volume of the conducting airways, or as 'physiological', which includes the volume of alveoli that are overventilated in relation to

C) Macmillan Joumals Ltd.

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their perfusion (West, 1974). Anatomical dead space can be measured by the Fowler method (Fowler, 1948), in which a single breath of oxygen is inhaled to total lung capacity and then exhaled through a nitrogen meter. The volume from TLC to a point mid-way up the steep initial rise of nitrogen concentration to the alveolar plateau (Figure 1) is the anatomical dead space (Birath, 1959). Physiological dead space is calculated from mixed expired and alveolar carbon dioxide concentrations, according to Bohr's formula:

VD = VT X (FACO2-FEC02) FAG02 and therefore requires some means of monitoring mixed expired gas composition. Estimation of FAC02 is difficult, particularly when breathing is increased as during exercise and it is preferable to substitute arterial carbon dioxide for alveolar, and to express the equation in terms of partial pressure instead of fractional concentration: VD = VT X

(PaCO2PECO2) PaCO2

(Bates, Macklem & Christie, 1971). In normal subjects anatomical and physiological dead spaces are equal but in patients with lung disease physiological dead space is enlarged, which means that more of each breath is useless for the purpose of gas exchange. The difference between physiological and anatomical dead space is called the alveolar dead space and is an index of ventilationperfusion imbalance in the lung (Severinghaus & Stupfel, 1957). Alveolar ventilation, which is what matters for the elimination of carbon dioxide is obtained by subtracting VD from VT and the adequacy of alveolar ventilation in respect of CO2 production is given by the arterial PC02.

Practical measurement of ventilation Methods of measuring ventilation fall into two broad groups: A. Direct: these involve direct measurement of expiratory or inspiratory minute volume and are invasive to the extent of requiring the subject to use a mouthpiece and nose clip. B. Indirect: these avoid the use of a mouthpiece in an attempt to render breathing more natural, but require calibration against a direct method.

A. Direct methods

(1) Expired gas collection This is the classical method for measuring ventilation and requires only a mouthpiece with a valve box to ensure one-way airflow, and a collecting chamber. Several quiet lightweight valve systems are now available, but all are liable to become sticky with prolonged use and require careful cleaning and maintenance. A convenient, though bulky and rather expensive way of collecting the expired gas is in a Tissot spirometer which is a large bell-in-water type of spirometer with a capacity of about 150 1. This makes it suitable for gas collections at rest and under moderate stimulation, but seriously limits the time over which gas can be collected at high levels of ventilation. The Tissot is usually provided with a kymograph which allows breath-by-breath ventilation to be followed and gives an automatic record of breathing frequency as well as expired volume. A fan mixes the expired gas under the bell prior to sampling for analysis and calculation of CO2 production, 02 uptake, respiratory exchange ratio and physiological dead space. The system is very reliable and accurate and provides a standard against which other methods of measuring ventilation can be calibrated (Finucane, Egan & Dawson, 1972; Cotes, 1975). An alternative collecting system is a series of Douglas bags which have the advantages of portability and larger total collecting volume than a Tissot spirometer, but the drawback that there is no built-in measurement of frequency, though this can be overcome by insertion of any simple flow sensing device or a fast reading CO2 analyser into the expiratory line. This system can then conveniently be used at the bedside or elsewhere whereas the Tissot spirometer is difficult to move from the laboratory. If expired gas is collected in a series of bags it is sampled for analysis from a narrow side-tube and the total volume of the bags is measured by emptying them through a flow meter. A variant of the gas collection methods is the use of a standard spirometer to monitor breath-by-breath expired volume. This method is suitable for rebreathing experiments and is expedited if the spitometer is fitted with a simple mechanical integrating device such as that used on the 'Expirograph' (by P.K. Morgan). (2) Mechanical.flow meters These generally work on the principle of rotation of a set of vanes by the gas stream and are similar to the meters used to monitor domestic gas supplies. Like gas collection methods flow meters require a mouthpiece, valve box, and clip assembly. The most suitable for respiratory work are dry gas meters (such as the Parkinson Cowan CD4) and if they are used 'on line' they should be placed in the inspiratory line to prevent corrosion by the

VENTILATION

saturated expired gas, or isolated from warm saturated expired air by a cooling chamber. They can also be used to measure the volume of expired gas collected in Douglas bags and allowed to cool to ambient temperature since there is less risk of condensation on the vanes under these conditions. Standard gas meters are rather large but are accurate potentially to 1% over a complete revolution, though many fail to reach this standard and all are less accurate over fractions of a revolution. They tend to deteriorate with time and should be calibrated at intervals against a large volume spirometer such as the Tissot. A refinement is to fit a rotary potentiometer to the vane spindle so that a continuous electrical signal proportional to ventilation can be obtained and respiratory frequency recorded. A much smaller and cheaper mechanical flow meter is the familiar Wright Anemometer which is accurate at steady moderate flow rates but is too delicate for measurement of maximum flow rates and under-reads at very low flow rates. Because of these deficiencies it has only limited application in experimental work although commonly used to monitor ventilation in clinical practice, particularly during anaesthesia or artificial ventilation. (3) Pneumotachograph/integrator systems These are now widely used and have the advantage over gas

collection methods of being less bulky and cumbersome and of providing a continuous electrical signal of volume and frequency. The pneumotachograph can be placed in either the inspired or expired gas stream and a mouthpiece and valve box assembly is required as described above. With modern electronics the earlier problems of integrator 'drift' have largely been overcome and although a little less accurate than gas collection on account of the limitations of pneumotachograph responses to oscillating flow (Finucane et al., 1972) the system has the advantage that it can be used for long periods of time at high ventilatory rates since there is no limitation on the total volume of gas that can be measured. There is automatic recording of both tidal volume and frequency and greater detail of the ventilatory wave form is available and can be conveniently displayed together with cumulative volume on any conventional chart recorder. Thus the system is particularly useful in analysis of patterns of breathing where subdivisions of the cycle are thought to give information about different aspects of regulation of ventilation (Clark & von Euler, 1972). The electrical analogue signals for frequency and volume can be stored on magnetic tape and large amounts of data therefore become available for computer analysis. A major drawback of this system and of the mechanical flow meter described above is the lack of a mixed expired gas sample for the analysis needed for calculation of gas exchange and dead-space but this

515

can be overcome by putting a mixing chamber in the expiratory line to enable gas to be sampled. For steady state experiments of relatively long duration, the mixing chamber can be large so long as it is thoroughly flushed with expired gas before sampling is started, and the Tissot spirometer has been used in this way (Godfrey, Davies, Wozniak & Barnes, 1971), vented to air to prevent over-filling of the spirometer. For rapidly changing conditions, as in graded exercise, breath-by-breath analysis of mixed expired gas may be needed (Spiro, Hahn, Edwards & Pride, 1974) in which case a much smaller mixing chamber containing baffles or a fan is used, commonly with a volume of 3-61 (Rebuck, Jones & Campbell, 1972; Spiro, Juniper, Bowman & Edwards, 1974) depending on the level of ventilation.

B. Indirect methods

(1) Plethysmograph In an early attempt to avoid the interference associated with a mouthpiece the subject was seated in a whole-body plethysmograph with the head outside. The interior of the plethysmograph was connected by wide-bore tubing to a spirometer so that a continuous record of respiratory displacement could be made (Haldane & Priestley, 1905). This method, though accurate, had the disadvantage of needing the subject to sit in a restricted space and limited the sort of experiments that could be performed. It is rarely used today but was a forerunner of modern indirect methods of measuring ventilation.

(2) Thermistor The thermistor consists of a fine wire with an expanded tip, the electrical resistance of which is sensitive to temperature change such as that caused by a flow of air. If the tip is placed in the airstream either at the mouth or nostril it is possible to follow frequency and timing of ventilation accurately though volume is less reliable. The thermistor can be calibrated against a known steady air-flow to give an estimate of flow which can then be integrated to give volume, but small changes of the position of the thermistor tip in relation to the centre of the air stream will affect its output. It is therefore only semi-quantitative in terms of volume but has the advantages of lightness and cheapness and does permit measurement at least of respiratory frequency over long periods of time while allowing the subject some freedom of movement and avoiding the artificial consciousness of breathing inevitable with methods involving a mouthpiece. (3) Transthoracic electrical methods (a) Impedance This is another indirect way of measuring ventilation which goes a stage further than the thermistor in removing extraneous influences on ventilation in that there is no interference at all with

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airflow and nothing attached to the face. It is based on the principle that the electrical impedance of the thorax depends on its volume and the relative amounts of air and tissue contained. Electrodes are attached to the chest wall in such a way that a rapidly oscillating electrical signal can be passed across the thorax from side-to-side and/or from front to back. The size of the signal decreases as impedance increases with inspiration and increased intrathoracic gas volume (Hamilton, Beard & Kory, 1965). Other factors such as pulmonary blood volume and lung water also affect thoracic impedance but these do not show regular oscillations in time with breathing and the ventilatory signal can be recognized easily. Although changes in impedance can be calibrated against tidal volume measured spirometrically at the mouth the method is difficult to use quantitatively since changes in posture and chest wall configuration may cause large changes in impedance (Ashutosh, Gilbert, Auchincloss, Erlebacher & Peppi, 1974). Thus although the method has the advantage of being 'non-invasive', it has proved disappointing in terms of quantitative long term monitoring of ventilation, though like the thermistor it can give a good guide to ventilatory frequency and timing. (b) Mercury-in-rubber strain gauge This is another indirect guide to ventilation, which is derived from the measurement of changes in thoracic size by mercury-in-rubber strain gauges encircling the chest and abdomen (Dornhorst & Leathart, 1952). Changes in electrical resistance can be calibrated against tidal volume to give a semi-quantitative measure of ventilation, but the system is very posture dependent and it is difficult to fix the strain gauges to the chest wall in such a way that they do not move. It is therefore an unreliable method for long-term monitoring as in sleep studies, and though theoretically simple has been superceded by impedance and magnetometer methods. (c) Magnetometers If the shape of the chest and abdomen is assumed to be a simple geometrical form, such as a segment of a cone or an elliptical cylinder, it is possible to derive volume change from the linear motion of the surfaces. This principle was initially employed using a series of threads attached to the chest wall and running over pulleys to linear transducers (Konno & Mead, 1967) but was much improved by the introduction of magnetometers (Mead, Peterson, Grimby and Mead, 1967). Each magnetometer consists of a pair of electromagnetic coils; one of these is placed on the back of the chest and is excited with a high frequency alternating current. The resulting magnetic flux is sensed by an identical coil placed opposite the first one on the front of the chest, and the voltage induced in the second coil is measured. As magnetic flux decreases with distance, any increase in antero-posterior length of the chest causes a fall in this voltage. A similar pair of

coils is placed across the abdomen, and from the combined motion of chest and abdomen it is possible to derive volume change, preferably with the aid of a computer. The system can be calibrated against a spirometer at the mouth and gives an accurate measure of tidal volume in normal subjects breathing quietly over a short period of time (Grimby, Bunn & Mead, 1968) but discrepancies arise with larger breaths (Stagg, Goldman & Newsom-Davies, 1978) and more complicated arrangements with both antero-posterior and lateral pairs of magnetometers may be required. Positioning of the coils has to be accurate, to prevent any angular displacement which will alter the magnetic flux unpredictably in relation to linear displacement. A further problem is that movement and change of posture may markedly alter the output of the magnetometers (Gilbert, Auchincloss, Baule, Peppi & Long, 1971) which makes the method unsatisfactory for long-term monitoring such as during sleep. Thus the magnetometer method is complex and requires expensive equipment and calculating facilities, but is probably the best of the non-invasive ways of measuring ventilation. When properly set up it provides an accurate measurement not only of tidal volume and frequency, but also of the relative contributions of the rib-cage and diaphragm to ventilation (Grimby et al., 1968; Sharp, Goldberg, Druz & Danon, 1975). Summary The methods described above are all designed to measure total ventilation; if information on gas exchange is required, one of the direct methods must be used, and the most popular is the pneumotachograph and integrator system, since this also gives information about timing and tidal volume. If accurate information on the pattern of breathing is required an indirect method is preferable and despite its expense and limitations the magnetometer one is probably best for experimental purposes, though the impedance method is more applicable to clinical monitoring.

Distribution of ventilation Another aspect of ventilation that is of great physiological and clinical importance is the distribution of inspired gas through the lung. This can be examined either on a geographical basis by isotope imaging (Milic-Emili, Henderson, Dolovich, Trop & Kaneko, 1966) or on a functional one by singlebreath gas dilution methods.

VENTILATION

A. Radioactive methods: Regional ventilation.

Radio-isotope imaging of the distribution of ventilation is now commonly used in clinical practice, mainly in the diagnosis and assessment of pulmonary embolism but it has also had some applications in functional studies. These have been reviewed more fully elsewhere (Ackery & Sterling, 1976) and will be described only briefly. Radioactive isotopes can be inhaled either as a gas or as labelled particles, of which the former gives the most accurate information about gas distribution. The most widely used radio-active gas is probably still 133-xenon which has a half-life of 5.3 days making it convenient for delivery and storage, and the distribution of ventilation can be visualized either after inhalation of a single breath or by following the respiratory wash-out of radioactivity after rebreathing to equilibrium (Maclntyre & Inkley, 1973). A recent advance has been the introduction of 81-m Krypton which is generated on site by blowing air over a block of 81-rubidium and has a half-life of only 13 s making it possible to take lateral as well as antero-posterior views and to make dynamic studies of normal ventilation. The radioactive gas methods can show regional ventilation defects in patients with airways obstruction at a time when standard pulmonary function tests are normal or only mildly impaired (Alderson, Secker-Walker & Forrest, 1974; Chopra, Taplin, Tashkin, Trevor & Elam, 1979) but their experimental use in this field is limited by the radiation involved, which renders them unsuitable for repeated studies such as those needed in assessing response to treatment. B. Physiological methods: Gas mixing and closing volume.

Although radioactive gas methods give a very sensitive record of regional abnormalities of gas distribution they have limited resolution and cannot demonstrate diffuse abnormalities at an alveolar level. These may be very important physiologically and to detect them the single breath oxygen test for efficiency of gas mixing, described briefly in an earlier article in this series in relation to lung volumes (Freedman, 1979), was introduced about 30 years ago (Fowler, 1949). Apart from diffuse lung pathology an important factor in the distribution of inspired gas in upright man is gravity, which has the effect of reducing static trans-pulmonary pressure in the dependent regions of the lungs. This is thought to cause closure of peripheral airways in the lower lobes at low lung volumes which is the basis of measurements of closing volume (Milic-Emili et al., 1966; Engel, Grassino & Anthonisen, 1975). This has become widely used as a proposed test of small airway function (McCarthy, Spencer, Greene &

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Milic-Emili, 1972; Collins, 1973) and can be measured either (a) as an extension of the single breath oxygen test or (b) by a bolus technique. The value of having such a test of the small airways lies in the difficulty of locating the main site of abnormality in patients with airways obstruction which was emphasized earlier in this series (Pride, 1979). There is some evidence that at least in chronic airways obstruction associated with bronchitis and emphysema the main pathological obstruction is situated peripherally (Hogg, Macklem & Thurlbeck, 1968; Niewoehner & Kleinerman, 1974). By the time the patient presents with breathlessness standard tests for airways obstruction will be abnormal but it is essential to detect the condition at an earlier stage in order to study its natural history and epidemiology (Ingram & McFadden, 1977). Conventional techniques such as forced expiratory manoeuvres and body plethysmography are relatively insensitive for this purpose since they tend to measure overall airways resistance, to which the peripheral airways normally contribute only about 20% (Macklem & Mead, 1967; Mead, 1970). Measurement of closing volume (a) Single breath 02 or 'resident gas' method This is the most commonly used method and involves simply the inhalation of a slow breath of 100% oxygen from RV to TLC, followed by slow exhalation through a nitrogen meter into a spirometer. Expired nitrogen concentration can then be plotted directly against exhaled volume as shown in Figure 1, from which it can be seen that the N2 concentration is divided into four phases: I Dead space-in which oxygen occupying the large conducting airways not involved in gas exchange is exhaled and nitrogen concentration is zero. II Dead space/alveolar gas interface-the steepness of which gives a rough guide to uniformity of

mixing. III Alveolar plateau during which mixed gas from the alveoli is exhaled and the slope of which gives an index of gas mixing. IV Closing volume-the volume measured along the

horizontal axis between the second inflexion point of the nitrogen trace and RV. Phase III Alveolar plateau The single breath oxygen test was introduced to give an indication of the efficiency of gas mixing, it being argued that if all alveoli filled simultaneously during inspiration there would be uniform dilution of the 'resident' alveolar nitrogen and that during the subsequent exhalation there would be little change in the nitrogen concentration of the expirate, resulting in a relatively flat plateau (Fowler, 1949; Comroe & Fowler, 1951;

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Phase --

I A

-

2

3

4

Volume expired (I) Figure 1 Stylized record of nitrogen concentration against lung volume during slow expiration after a vital capacity breath of 100% 02- See text for discussion of the different phases.

Fowler, 1952). If mixing were uneven, for example due to patchy airways obstruction, some alveoli would start to fill only late in inspiration and hence would receive less oxygen: they would also empty late, contributing a higher nitrogen concentration to the later part of the expirate and increasing the slope of the alveolar plateau. The slight upward slope of the normal Phase III may be due to minor inequalities in alveolar filling times or to the different initial volumes of alveoli in different parts of the lung. Thus at residual volume alveoli in the dependent regions are smaller than those at the apex, but at TLC there is greater uniformity of alveolar volume, which means that the initially smaller basal alveoli will have been diluted to a greater extent with 02. If, as is likely from the effect of gravity on transpulmonary pressure up and down the lung, these alveoli empty first during expiration a rising slope of N2 concentration will occur.

The slope of the alveolar plateau was originally measured over 0.5 1, between 0.75 1 and 1.25 1 below TLC and this was called the nitrogen index (Fowler, 1952). It increases with age and is higher in smokers than non-smokers, as well as being abnormal in a wide variety of lung disorders (Buist & Ross, 1973b). Because it is affected by factors other than small airway calibre, such as initial alveolar volume, it is a difficult test to interpret and although often measured in clinical practice is rarely used for experimental purposes.

Phase I V-Closing volume Recent interest has concentrated on the observation that in the course of a single breath oxygen test there is often a sharp change in the slope of the nitrogen concentration, which rises steeply from the alveolar plateau at a

volume slightly above RV, and the cause for this inflexion is thought to be closure of small airways in the dependent regions of the lungs (Engel et al., 1975). These airways will thus be closed at RV, so that at the start of inhalation of 100% 02 for a single breath test, the gas will go to the upper zones, where the alveoli are already partly expanded due to the gravitational gradient of transpulmonary pressure and can therefore only accept a small amount Of 02 before reaching their regional TLC. Dependent alveoli will commence filling a little later in inspiration as their airways open up, but will accommodate more oxygen since they start close to their own RV. During expiration all alveoli will contribute so long as their respective airways are open and this mixed gas constitutes the alveolar plateau described above. At closing volume, the dependent airways close and from this point on only upper zone alveoli rich in N2 will contribute to the expired gas, causing an upward deviation of the N2 concentration from the alveolar

plateau. (b) Bolus method In this method a small volume (approximately 50 ml) of a marker gas which can be measured either as a result of its physico-chemical properties or by means of radioactive emission, is inhaled at RV and is followed by a vital capacity breath of air to TLC. Since the small airways in the dependent lung regions are closed when the bolus is inhaled, it goes mainly to the upper zones. During the subsequent expiration a concentration pattern is seen which is exactly similar to the nitrogen one described above, with a sharp rise in marker gas concentration at closing volume, since from this point only the marker gas-rich upper lobes contribute to the expirate. Much of the early work on this technique was done with radio-active gases, mainly 133-xenon, which confirmed the preferential distribution of the bolus to the upper zones (Dollfuss, Milic-Emili & Bates, 1967). Because of limitations on repeated tests with radioactive gases these have largely been superseded by inert gases, of which helium is the most commonly used, though argon is a satisfactory alternative (Jones & Clarke, 1969). The basic technique sounds simple and the method has been developed for large-scale use as an epidemiological tool, but there remain several practical difficulties in the measurement of closing volume. First, good subject co-operation and motivation are essential since failure to exhale fully to RV will cause a large proportional change in closing volume and in CV/VC%/O, which is a common way of expressing the result. This difficulty can be overcome by doing the test with the subject seated in a plethysmograph for simultaneous measurement of absolute lung volumes which makes it possible to estimate closing capacity, or the volume above zero lung volume at which airway closure occurs. This technique is preferred by some workers, but adds

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considerable complexity and expense and makes the test much less suitable for epidemiological work. Second, the shape of the expired gas concentration curve and the point of airway closure are very dependent on expiratory flow rate which has to be slow and even and is generally controlled at less than 0.5 1 s- 1 by a resistance in the expiratory line (Jones & Clarke, 1969). Inspiratory flow rate has a similar but less marked effect and should also be controlled (Martin, Anthonisen & Zutter, 1972). Even when these factors are taken into account and a standardized technique is used (U.S. Department of Health, Education and Welfare, 1973) measurements of closing volume show considerable variability, due to a combination of true biological variability, difficulty in reading an inflexion point which is often curved rather than angled, and observer inconsistency. As a result of these problems, CV and CV/VC % have been found to have a coefficient of variation of up to 20% for repeated tests in the same subject, compared with 5% or less for spirometric values (McFadden, Holmes & Kiker, 1975). Another difficulty is comparison between values obtained by the nitrogen and bolus methods respectively: some authors have found close agreement (Travis, Green & Don, 1973) but most have found that the bolus method gives slightly but consistently higher values in normal subjects (Farebrother, Paredes-Martinez, Soejima & McHardy, 1973; Knudson, Lebowitz, Burton & Knudson, 1977), though this is unimportant provided the same method is used throughout any particular study. Similar discrepancies have been reported in some experimental and pathological situations (Benson, Newberg & Jones, 1975; Stanescu, Veriter & Brasseur, 1977). Despite all these difficulties, closing volume has achieved a wide degree of acceptance as a test of small airway function though this interpretation may be a little over-specific (Scand. J. resp. Dis., 1974). The nitrogen method in particular is easy to perform according to a standard procedure though the

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inflexion point at closing volume tends to be sharper with the bolus method (Farebrother et al., 1973). There is rather a wide range of normal values (Buist, 1975) but satisfactory agreement between different laboratories (Buist & Ross, 1973a; Collins, Clark, McHardy-Young, Cochrane & Crawley, 1973; Buist, 1975), all of which find a linear rise in CV/VC % with age (Anthonisen, Danson, Robertson & Ross, 1969) and higher values in smokers than non-smokers. Some studies have suggested that closing volume is a sensitive method of detecting early airways obstruction (Buist, Van Fleet & Ross, 1973) and there is some epidemiological evidence that it is a useful guide to the effects of cigarette smoke on lung function (Becklake, Leclerc, Strobach & Swift, 1975; Bode, Dosman, Martin & Macklem, 1975; Buist, Sexton, Nagy & Ross, 1976). In summary, closing volume is easy to measure, particularly using the resident gas method, but the bolus one may give a sharper end-point. Interpretation is more complex than sometimes suggested, since regional alveolar volume is a contributory factor, but the test probably does give some indication of small airway function which is otherwise difficult to obtain.

Glossary of terms Ventilation (flow) Inspiratory ventilation Expiratory ventilation Fractional gas concentration Respiratory exchange ratio Vital capacity Total lung capacity Residual volume Tidal volume Dead space volume Respiratory frequency Closing volume Closing volume/Vital capacity

V V,

VE F R VC TLC RV VT VD f CV

(1 min-1) (1 minm ) (1 minm ) (1) (1) (1) (1) (1) (1)

CV/VC%/O

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