Color profile: Disabled Composite Default screen ORIGINAL ARTICLE Implementing the three-equation method of measuring single breath carbon monoxide diffusing capacity BRIAN LGRAHAM PhD,JOSEPH TMINK BSc,DAVID JCOTTON MD FRCPC Division of Respiratory Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan BL GRAHAM,JTMINK,DJCOTTON. Implementing the Utilisation de la méthode à trois équations three-equation method of measuring single breath carb- pourmesurerlacapacitédediffusiondu on monoxide diffusing capacity. Can Respir J 1996; 3(4):247-257. monoxyde de carbone en apnée RÉSUMÉ : Les méthodes traditionnelles pour mesurer la Conventional methods of measuring the single breath dif- capacité de diffusion du monoxyde de carbone (DLco) en fusing capacity of the lung for carbon monoxide (DLcoSB) apnée sont basées sur la formule de Krogh, qui est valide are based on the Krogh equation, which is valid only during uniquement pendant l’apnée. On procède alors à une nor- breath holding. Rigid standardization is used to approxi- malisation arbitraire pour se rapprocher de la manoeuvre en mate a pure breath hold manoeuvre, but variations in per- apnée pure, mais les variations qui se produisent en prati- forming the manoeuvre cause errors in the measurement of quant la manoeuvre sont une source d’erreur dans la mesure DLcoSB. The authors previously described a method of de la DLco en apnée. Les auteurs ont précédemment décrit measuring DLcoSB using separate equations describing une méthode de mesure de la DLco en apnée où l’on utilisait carbon monoxide uptake during each phase of the manoeu- des équations séparées décrivant la capture du monoxyde de vre: inhalation, breath holding and exhalation. The method carbone pendant chaque phase de la manoeuvre : inspira- is manoeuvre-independent, uses all of the exhaled alveolar tion, apnée et expiration. La méthode est indépendante de la gas to improve estimates of mean DLcoSB and lung volume, manoeuvre, utilise la totalité du gaz alvéolaire expiré pour and is more accurate and precise than conventional meth- améliorer les estimations de la DLco moyenne en apnée et ods. A slow, submaximal, more physiological single breath du volume pulmonaire, et est plus fiable et précise que les manoeuvre can be used to measure DLcoSB in patients who méthodes traditionnelles. Une manoeuvre en apnée lente, cannot achieve the flow rates and breath hold times neces- sous-maximale et plus physiologique peut être utilisée pour sary for the standardized manoeuvre. The method was in- mesurer la DLco en apnée chez les patients qui ne peuvent itially implemented using prototype equipment but atteindre les débits et rester en apnée pendant le temps commercial systems are now available that are capable of nécessaire à la manoeuvre normalisée. La méthode a été implementing this method. The authors describe how to initialement développée en utilisant un matériel prototype, implement the method and discuss considerations to be cependant des appareils commerciaux sont maintenant dis- made in its use. ponibles pour permettre la mise en application de cette Key Words: Diffusion, Diffusing capacity, Gas exchange, Lung méthode. Les auteurs décrivent comment procéder et dis- volume, Transfer factor cutent des considérations relatives à son utilisation. Correspondence and reprints: Dr BL Graham, Division of Respiratory Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W8. Telephone 306-966-8274, fax 306-966-8694, e-mail [email protected] Can Respir J Vol 3 No 4 July/August 1996 247 graham.chp Sun Jul 21 13:07:47 1996 Color profile: Disabled Composite Default screen Graham et al he single breath diffusing capacity of the lung for carbon the flow rates and breath hold times do not cause errors in the SB SB Tmonoxide (DLco ) was first measured by Krogh (1), measurement of DLco . who developed an equation to describe the uptake of carbon With the three-equation method, gas concentrations and monoxide during breath holding. Conventional methods of lung volume are monitored continuously throughout the sin- SB measuring DLco still use the Krogh equation (1) and are gle breath manoeuvre. These data are used to calculate the therefore constrained by the requirement of a rigidly stand- carbon monoxide concentrations in the alveolar space and to ardized single breath manoeuvre, which approximates a pure predict the uptake of carbon monoxide. By comparing the breath hold but obviously includes inhalation and exhalation. observed with the predicted carbon monoxide uptake, Although the uptake of carbon monoxide by the lungs meas- DLcoSB can be calculated. Because the inspiratory flow and ured in this manner is more appropriately called the transfer gas concentrations are monitored and the carbon monoxide factor (2), we have used the American Thoracic Society uptake is computed during inhalation, the assumptions for (ATS) convention of calling it diffusing capacity (3). start of breath holding time and carbon monoxide concentra- Most current clinical measurements of DLcoSB use some tion at ‘time zero’ used by conventional methods are not variation of the technique described by Ogilvie et al (4). The required. Jones and Meade method (5) applies corrections to the timing The three-equation method permits the measurement of of the breath hold period and recommends the collection of a DLcoSB at different lung volumes (10), different breath hold very small alveolar gas sample immediately following dead times (11) and different flow rates (9). The method also space washout. The method recommended by Ferris (6), permits all of the exhaled alveolar gas to be used in the referred to as Epidemiology Standardization Project method, calculation of DLcoSB. This yields a measurement of DLcoSB appears to have been developed for ease of computation and that more accurately reflects the mean carbon monoxide standardization without a theoretical or clinical rationale. We uptake of the entire lung. In contrast, conventional methods have previously shown that all of these methods overestimate use smaller alveolar gas samples collected immediately after DLcoSB measured from a lung model (7) and normal subjects dead space washout to reduce timing errors, but, unfortu- (8), particularly when the exhaled flow rates are reduced. nately, the measurements of both the DLcoSB and the absolute DLcoSB is overestimated by conventional methods be- lung volume are more influenced by ventilation inhomo- cause they are based on a single equation that is valid only geneities in the lung when measured using small gas samples. during breath holding. The methods rely on the use of a We have focused the implementation of this method on standardized manoeuvre consisting of rapid inhalation, 10 s the use of a manoeuvre with relaxed flow rates with submaxi- of breath holding and rapid exhalation to approximate a pure mal lung volumes that can be done equally well by subjects breath hold manoeuvre (2,3). However, the measurement of or patients and that more closely approximates normal DLcoSB depends on how well the subject can perform the breathing. The manoeuvre can be done with or without breath manoeuvre. If the inspiratory or expiratory flow rates are holding. The method is by no means restricted to this or any reduced, if the breath hold time is changed, if the alveolar other particular manoeuvre. sample is collected later in exhalation, or if the volume of the The three-equation DLcoSB method was initially devel- alveolar sample is changed, then the measured DLcoSB will oped using a mass spectrometer, a modified infrared absorp- be spuriously affected (7-9). tion type carbon monoxide analyzer and other prototype For normal subjects who can inhale and exhale with high equipment (8,9). With the continuing refinement of comput- flow rates and hold their breath for 10 s, measurement of erized pulmonary function equipment and the improvement DLcoSB is not a problem because the differences between the of gas analyzers, it is now feasible to use commercial pulmo- various methods are small (9). For patients with airflow nary function systems to implement this method. We present obstruction, or any other subject who cannot adequately considerations for the implementation of the method and an perform the standardized single breath manoeuvre, DLcoSB is efficient computer algorithm for rapid calculation of DLcoSB. usually overestimated (8). We developed a method of measuring DLcoSB based on EQUIPMENT three equations – one each for inhalation, breath holding and Gas analyzers: While, in theory, the three-equation method exhalation (7). These equations analytically account for the could be implemented by using the mean carbon monoxide differences in the rate of carbon monoxide uptake during concentration measured from any size of gas sample col- inhalation, breath holding and exhalation. Diffusion of carb- lected during exhalation (7), in practice, problems of dead on monoxide during all three phases of the manoeuvre – space washout, sample timing and sample volume prevent inhalation, breath holding and exhalation – can be deter- the advantages of the three-equation method from being fully mined, eliminating the need to assume that all carbon mon- realized when applied to data collected by conventional oxide transfer occurs during breath hold. This makes the DLcoSB equipment (12). The availability of continuously measurement of DLcoSB independent of the manoeuvre, and measured concentrations of carbon monoxide and a tracer