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A technique for monitoring the inhalation of cigarette smoke in man, using krypton-81m
A Technique for Monitoring the Inhalation of Cigarette Smoke in Man, Using Kryptodlm N6IRfN F. SHEAHAN, DEMETRI PAVIA, JOHN R. M. BATEMAN, JOHN E. AGNEW” and STEWART W. CLARKE Departments of Thoracic Medicine and “Medical Physics, The Royal Free Hospital, Pond Street, Hampstead, London NW3, 2QG, England
FIG. I. Cigarette chamber.
(Received 1 October 1979; in revised form 9 January 1980) A novel technique has been devised for monitoring quantitatively the inhalation of cigarette smoke into a smoker’s lungs, using the isotope krypton-8lm as a tracer for the smoke.
Introduction THEextent of inhalation of cigarette smoke is usually onitored by ascertaining carboxyhaemoglobin levels”~2’ )!I urinary nicotine. (3*4’However, the uptake and retention of both substances depends on many physiological factors and results may therefore be misleading. The intake of smoke from cigarette to mouth may be directly and very precisely measured t5-” but, as remarked by GUILLERM,‘*’ this may also be misleading since smoke may be incompletely inhaled from the mouth. A direct technique for determining the quantity of smoke entering the lungs is therefore needed, and this report describes such a technique wherein the isotope s’“‘Kr (E.. = 190 keV, Tt = 13 s) is used to trace the entry of cigarette smoke into the human lung.
Method The ‘i’“Kr generator*r9’ is eluted by air at a flow rate of 200 f 10 ml min-‘. A Geiger counter is collimated so that it views 3 cm of a 1 cm bore tubing carrying the output gas from the generator. The total length of tubing and the position of the Geiger counter along the tube is kept constant from day to day so that the signal from the ratemeter (PANAX@, RM 202) coupled to the Geiger counter may be .tised-to-correct for the output activity of the generator bbid;g h&d. The krypton/air mixture is fed into a cigarette chamber (Fig. 1) which consists of a rubber sleeve having an outlet valve at one end. A coarse metal grid prevents the rubber from touching the burning cigarette but does not inhibit gas exchange within the chamber. As the subject draws smoke into his mouth from the cigarette, a sub-atmospheric pressure is created in the chamber. This causes the closure of the outlet valve and the gradual collapse of the rubber sleeve so that gases within the chamber are delivered via the cigarette to the subject. Air passing through the burning tip reacts to form smoke products, while s’“‘Kr passes through chemically unchanged. Since ““‘Kr is evenly distributed in air within the cigarette chamber (Fig. 2) it follows that smoke is also homogeneously mixed with *imKr.
The puff volume may vary up to a maximum of 80 ml, i.e. the capacity of the rubber sleeve. The puff flow rate is unaffected by the chamber because the resistance to flow provided by the rubber sleeve is negligible in comparison to that of the cigarette. Thus the system gives a means of producing smoke evenly mixed with s”“Kr without interference with the subject’s normal smoking technique. The subject smokes from the chamber while seated in front of a single probe scintillation counter (I.D.L.@ type 663C) collimated (I.D.L.@ shield assembly 2220, with wide angle collimator) to view the whole lung field. As the subject inhales the krypton/smoke mixture into his lungs, the signal from the scaler/ratemeter (Nuclear Enterprises* SR5) coupled to the scintillation counter rises; the maximal count rate recorded during inhalation is corrected for *imKr decay and S*mKr generator output activity. Results The relationship between the detector count rate and the puff volume drawn into the mouth was tested in a control subject trained to inhale completely. The puff volume was measured by integrating the pressure signal across a pneumotachygraph placed between the cigarette and cigarette holder. Since the pneumotachygraph was not suitable for use with cigarette smoke, these measurements were made using an unlit cigarette. No limitations were imposed on the volume of inspiration or the inspiratory flow rate. The “whole lung count” derived from the corrected maximal count rate recorded during the inspiration showed a linear relationship (r = 0.99) to the puff volume (Fig. 3). r
. . .
/
MC-J Puff vckrne (ml)
* Supplied by the M.R.C. Cyclotron Unit, Hammersmith Hospital, London, England. 438
FIG. 3. Variation of whole lung count with puff volume for subject trained to inhale completely.
OUTlIT VALVE FIG. 2. Gamma-camera
CIGARETTE HOLDER
picture of cigarette chamber showing even distribution of acti vity.
439
Technical Note
A puff taken into the mouth but extruded prior to inspiration is not detected by this system and if the puff is partially extruded prior to inspiration the whole lung count is proportionately lower than if the puff is completely inhaled. Thus the system responds only to radioactivity within the lung field and not that which remains in the buccal cavity or is extruded prior to inspiration. Each inhalation may be assessed independently and without interference from prior inhalations because the combination of washout and radioactive decay reduce the lung count to a negligible level within a few breaths. The whole lung count observed per kBq of *lmKr inhaled is not constant for ali subjects, but varies somewhat with chest size. Twenty subjects (10 male and 10 female, whose chest circumferences varied from 82 to 108cm) puffed from a cigarette as described above. The whole lung count per kBq of inhaled *‘“‘Kr showed a significant, negative correlation with chest circumference (r = -0.57, P < 0.01). Seventeen of the subjects showed deviations from the regression line of < 150/, but three subjects showed deviations of 20-35%. so that for work requiring a greater degree of accuracy than this, a pneumotachygraph calibration should be performed on each subject. Diacuaaion This is a simple, safe (the total lung dose per 35 ml puff is less than 2 x lo-‘Gy), and rapid investigation requiring little subject co-operation. Furthermore few constraints are imposed upon the individual’s natural smoking technique. It provides a direct and quantitative measurement of the
441
amount of smoke inhaled for each puff of the cigarette. With minor modifications, cigar or pipe smoking or indeed the efficacy of ventilatory filters may also be studied. Acknowledgements-We would like to thank Miles Laboratories for providing financial assistance for this project, and are also indebted to Mr A. Lister for his help in constructing the cigarette chamber.
References
6. 7. 8.
WALD N.. IDLE M. and BAILEYA. Thorax 33, 201 (1978). RAWII~NER. G., COPPINC. A. and Guz A. Clin. Sci. molec. Med. 51,495 (1976). ARMITAGE A. K., D~LLERYC. T., GEORGEC. F., HOUSEMANT. H., LEWISP. J. and TURNERD. M. Br. med. J. 4, 313 (1975). RUX~ELLM. A. H. and FEYERABEND C. Lancer 1, 179 (1975). RAWBONER. G., MURPHYK., TATE M. E. and KANE S. J. In Smoking Behaviour. Physiological and Psvchological Ing?uenc& (Edited by THORN&N R. E.), p: 171. Churchill Livingstone. Edinburah (1978). CREIGH~~ND. E. and LEWISP.H.‘ibid.,‘p. 289. SCHULZW. and SEEHOFER F. ibid., p. 259. GUILLERMR. and RADZISZEWSKI E. Annls Tabac 13,
9.
YANO
4. 5.
101 (1975).
Y., MCRAEJ. and ANGERH. 0. J. nucl. Med. 11, 674 (1970).
FIG. I. Cigarette chamber.
(Received 1 October 1979; in revised form 9 January 1980) A novel technique has been devised for monitoring quantitatively the inhalation of cigarette smoke into a smoker’s lungs, using the isotope krypton-8lm as a tracer for the smoke.
Introduction THEextent of inhalation of cigarette smoke is usually onitored by ascertaining carboxyhaemoglobin levels”~2’ )!I urinary nicotine. (3*4’However, the uptake and retention of both substances depends on many physiological factors and results may therefore be misleading. The intake of smoke from cigarette to mouth may be directly and very precisely measured t5-” but, as remarked by GUILLERM,‘*’ this may also be misleading since smoke may be incompletely inhaled from the mouth. A direct technique for determining the quantity of smoke entering the lungs is therefore needed, and this report describes such a technique wherein the isotope s’“‘Kr (E.. = 190 keV, Tt = 13 s) is used to trace the entry of cigarette smoke into the human lung.
Method The ‘i’“Kr generator*r9’ is eluted by air at a flow rate of 200 f 10 ml min-‘. A Geiger counter is collimated so that it views 3 cm of a 1 cm bore tubing carrying the output gas from the generator. The total length of tubing and the position of the Geiger counter along the tube is kept constant from day to day so that the signal from the ratemeter (PANAX@, RM 202) coupled to the Geiger counter may be .tised-to-correct for the output activity of the generator bbid;g h&d. The krypton/air mixture is fed into a cigarette chamber (Fig. 1) which consists of a rubber sleeve having an outlet valve at one end. A coarse metal grid prevents the rubber from touching the burning cigarette but does not inhibit gas exchange within the chamber. As the subject draws smoke into his mouth from the cigarette, a sub-atmospheric pressure is created in the chamber. This causes the closure of the outlet valve and the gradual collapse of the rubber sleeve so that gases within the chamber are delivered via the cigarette to the subject. Air passing through the burning tip reacts to form smoke products, while s’“‘Kr passes through chemically unchanged. Since ““‘Kr is evenly distributed in air within the cigarette chamber (Fig. 2) it follows that smoke is also homogeneously mixed with *imKr.
The puff volume may vary up to a maximum of 80 ml, i.e. the capacity of the rubber sleeve. The puff flow rate is unaffected by the chamber because the resistance to flow provided by the rubber sleeve is negligible in comparison to that of the cigarette. Thus the system gives a means of producing smoke evenly mixed with s”“Kr without interference with the subject’s normal smoking technique. The subject smokes from the chamber while seated in front of a single probe scintillation counter (I.D.L.@ type 663C) collimated (I.D.L.@ shield assembly 2220, with wide angle collimator) to view the whole lung field. As the subject inhales the krypton/smoke mixture into his lungs, the signal from the scaler/ratemeter (Nuclear Enterprises* SR5) coupled to the scintillation counter rises; the maximal count rate recorded during inhalation is corrected for *imKr decay and S*mKr generator output activity. Results The relationship between the detector count rate and the puff volume drawn into the mouth was tested in a control subject trained to inhale completely. The puff volume was measured by integrating the pressure signal across a pneumotachygraph placed between the cigarette and cigarette holder. Since the pneumotachygraph was not suitable for use with cigarette smoke, these measurements were made using an unlit cigarette. No limitations were imposed on the volume of inspiration or the inspiratory flow rate. The “whole lung count” derived from the corrected maximal count rate recorded during the inspiration showed a linear relationship (r = 0.99) to the puff volume (Fig. 3). r
. . .
/
MC-J Puff vckrne (ml)
* Supplied by the M.R.C. Cyclotron Unit, Hammersmith Hospital, London, England. 438
FIG. 3. Variation of whole lung count with puff volume for subject trained to inhale completely.
OUTlIT VALVE FIG. 2. Gamma-camera
CIGARETTE HOLDER
picture of cigarette chamber showing even distribution of acti vity.
439
Technical Note
A puff taken into the mouth but extruded prior to inspiration is not detected by this system and if the puff is partially extruded prior to inspiration the whole lung count is proportionately lower than if the puff is completely inhaled. Thus the system responds only to radioactivity within the lung field and not that which remains in the buccal cavity or is extruded prior to inspiration. Each inhalation may be assessed independently and without interference from prior inhalations because the combination of washout and radioactive decay reduce the lung count to a negligible level within a few breaths. The whole lung count observed per kBq of *lmKr inhaled is not constant for ali subjects, but varies somewhat with chest size. Twenty subjects (10 male and 10 female, whose chest circumferences varied from 82 to 108cm) puffed from a cigarette as described above. The whole lung count per kBq of inhaled *‘“‘Kr showed a significant, negative correlation with chest circumference (r = -0.57, P < 0.01). Seventeen of the subjects showed deviations from the regression line of < 150/, but three subjects showed deviations of 20-35%. so that for work requiring a greater degree of accuracy than this, a pneumotachygraph calibration should be performed on each subject. Diacuaaion This is a simple, safe (the total lung dose per 35 ml puff is less than 2 x lo-‘Gy), and rapid investigation requiring little subject co-operation. Furthermore few constraints are imposed upon the individual’s natural smoking technique. It provides a direct and quantitative measurement of the
441
amount of smoke inhaled for each puff of the cigarette. With minor modifications, cigar or pipe smoking or indeed the efficacy of ventilatory filters may also be studied. Acknowledgements-We would like to thank Miles Laboratories for providing financial assistance for this project, and are also indebted to Mr A. Lister for his help in constructing the cigarette chamber.
References
6. 7. 8.
WALD N.. IDLE M. and BAILEYA. Thorax 33, 201 (1978). RAWII~NER. G., COPPINC. A. and Guz A. Clin. Sci. molec. Med. 51,495 (1976). ARMITAGE A. K., D~LLERYC. T., GEORGEC. F., HOUSEMANT. H., LEWISP. J. and TURNERD. M. Br. med. J. 4, 313 (1975). RUX~ELLM. A. H. and FEYERABEND C. Lancer 1, 179 (1975). RAWBONER. G., MURPHYK., TATE M. E. and KANE S. J. In Smoking Behaviour. Physiological and Psvchological Ing?uenc& (Edited by THORN&N R. E.), p: 171. Churchill Livingstone. Edinburah (1978). CREIGH~~ND. E. and LEWISP.H.‘ibid.,‘p. 289. SCHULZW. and SEEHOFER F. ibid., p. 259. GUILLERMR. and RADZISZEWSKI E. Annls Tabac 13,
9.
YANO
4. 5.
101 (1975).
Y., MCRAEJ. and ANGERH. 0. J. nucl. Med. 11, 674 (1970).