CARBON MONOXIDE, INDUSTRY AND PERFORMANCE
Third Joint Meeting of The British Occupational Hygiene Society, The Ergonomics Research Society, and The Society of Occupational Medicine, at Swansea, September 1974
Aim. occup. Hyj. VoL 18, pp. 1-14. Pergamon Preu 1975. Printed in Oreit Britain
SMOKING, CARBON MONOXIDE AND ARTERIAL DISEASE N.
W A L D and
S.
HOWARD
DHSS Cancer Epidemiology and Clinical Trials Unit, Department of the Regius Professor of Medicine, Radcliffe Infirmary, Oxford OX2 6HE
Abstract—This paper reviews the role of carbon monoxide (CO) as a measure of tobacco smoke absorption, and as a possible cause of arterial disease in man. Smoking is the most important single source of exposure to CO, and frequently leads to carboxyhaemoglobin (COHb) levels above 8%. Most filter-tipped cigarettes produce more CO than plain cigarettes. The main factors affecting the uptake and elimination of CO are considered and it is shown that a single COHb measurement combined with a recent smoking and exercise history can be used to estimate the COHb derived from each cigarette. In a cross-sectional study COHb levels were more closely associated with the prevalence of coronary heart disease (CHD) than was smoking history. CO exposure from smoking has been shown to be harmful in persons who already have CHD or intermittent claudication. The evidence that CO is also harmful in persons without arterial disease is inconclusive, but animal data suggest that this may be the case. Some implications relating to the use of 'Smoking Tables' and the modification of cigarettes are considered.
INTRODUCTION RECENTLY, considerable interest has been focused on carbon monoxide (CO) as a measure of tobacco smoke absorption and also as a toxic constituent in tobacco smoke which may be responsible for the development of arterial disease. In this paper we review these aspects of CO and consider some of the implications of modifying cigarettes in order to make them safer. The association between smoking and coronary heart disease (CHD) is now well established (DOYLE et al., 1964; MORRIS et al., 1966; KANNELef al., 1968; STAMLER et al., 1968) and many prospective studies have shown that middle-aged men who smoke 20 cigarettes a day have 2-3 times a non-smoker's risk of dying of CHD (DOLL and HILL, 1964; BEST, 1966; KAHN, 1966; HAMMOND, 1972), making CHD numerically one of the most important diseases associated with smoking.
CARBON MONOXIDE AS A MARKER OF TOBACCO SMOKE ABSORPTION
Man is exposed to CO from many sources, and these have been well reviewed (GOLDSMITH and LANDAW, 1968; WELFARE, 1972). CO is absorbed
U.S.
DEPARTMENT OF HEALTH, EDUCATION &
through the lungs to form carboxyhaemoglobin (COHb) and Table 1 summarises the approximate levels of COHb that various sources of exposure can produce. Data in this table relating to environmental and occupational exposure were obtained from non-smokers.
3.
N . WALD and S. HOWARD
TABLE 1. TYPICAL CARBON MONOXIDE AND CARBOXYHAEMOGLOBIN LEVELS ASSOCIATED WITH VARIOUS SOURCES OF EXPOSURE TO CARBON MONOXIDE
Approx. mean Approx. mean CO (ppm) COHb(%)
Source of CO
Metabolism Environment (non-smokers) Los Angeles commuters 30 London taxi drivers 22 Occupation (non-smokers) Motor car repair shops (Canada) 80 Parking attendants 80 Border inspectors (Mexico-U.S.) 114 Blast furnace workers — Smoking Pipes (lifelong U.S. & U.K.) 15,000 Cigarettes 40,000 Cigars (lifelong U.S. & U.K.) 70,000 Pipes+cigars (ex-cigarette smoker^) —
Source of COHb data
0-5
SJOSTRAND (1949)
2-5 1-6
DEANE and PERKINS (Unpub.)
5 7 4 4
BUCHWALD (1968) RAMSEY (1967) COHEN et al. (1971) BUTT et al. (1974)
2 6 2 5
JONES et al. (1972)
GOLDSMITH and LAND AW (1968)
WALD (unpublished) CASTELDEN and COLE (1973)
COWIE et al. (1973)
(i) CO in tobacco smoke Smoking as a source of exposure to CO dwarfs all others. For most types of cigarette the concentration of CO in the smoke averages about 4% by volume. Cigarettes deliver about 12 ml CO per cigarette when tested on a smoking machine under standard conditions as specified by the Tobacco Research Council (ROTHWELL and GRANT, 1972) (35ml puffs of 2 sec duration at a rate of 1 puff per minute smoked to a standard butt length). As a cigarette is smoked and becomes shorter, the quantity of air entering through the porous cigarette paper is reduced, and so the CO concentration increases with each puff. Since the paper surrounding the filter of filter-tipped cigarettes is relatively non-porous less air can enter to dilute the CO, producing a higher CO yield in a filtertipped cigarette than in a plain one. This surprising result has been confirmed on several brands of cigarette (EVANS, personal communication). Figure 1 which shows the CO concentration per puff of four brands of cigarette illustrates this. Two of these, Senior Service Filter and Players No. 6 Filter, have non-porous filter tips, and one is a typical plain cigarette, Senior Service Plain. The fourth, Silk Cut Extra — Players No;6 F i l t e r — S e n i o r Service Plain — S e n i o r Service Filter
- E x t r a Mill) Silk Cut Filter
nT 1
I 2
I 3
4
5
I 6
I 7
I I I I 8 91 0 1 1
FIG. 1. Carbon monoxide yields per puff of four brands of cigarette. Silk Cut Extra Mild has a ventilated filter.
Smoking, carbon monoxide and arterial disease
3
Mild, has a "ventilated" filter, which differs from conventional filters in having perforations in the paper surrounding the filter tip. With this last type of cigarette, air entering through the perforations dilutes the smoke, thereby reducing the quantity of CO per puff, and this can result in a CO yield even lower than that of plain cigarettes. When the perforations are artificially sealed the CO yield of the cigarette increases to levels which are more typical of conventional filter-tipped cigarettes (WALD and SMITH, 1973). (ii) Uptake and loss of CO by smokers The uptake of CO from tobacco smoke and the rate of elimination of COHb from the body depend on several factors which are listed in Table 2. Apart from the type and quantity of tobacco smoked, the main factor affecting CO uptake is the method TABLE 2. THE PRINCIPAL FACTORS INFLUENCING THE RATES OF UPTAKE AND ELIMINATION OF CARBON MONOXIDE BY SMOKERS
CO Uptake
CO Loss
Concentration of CO in tobacco smoke No. puffs, puff volume, puff flow rate Depth of inhalation Pulmonary transfer factor for CO Total haemoglobin+myoglobin mass
Initial COHb level and ambient CO levels Alveolar ventilation (physical exercise) Pulmonary transfer factor for CO Total haemoglobin+myoglobin mass Cardiac output
of smoking—that is, the size and frequency of the puffs as well as how deeply each puff is inhaled. The rate of loss of CO is determined chiefly by alveolar ventilation, which is itself dependent on physical exercise. Figure 2, derived from data published 240
\
SLEEPING
\
180
STUDYING
\
\
TYPING
20 WALKING SLOWLY
\
FOOTBALL
60 _
0
1 4
1 8
1 12
' 16
1 20
I
24
28
V E N T I L A T I O N RATE I l / m i n l
FIG. 2. Half-life of COHb in relation to alveolar ventilation rate. This figure was produced from data published by COBURN et al. (1965). Adjustment has been made for the increase in transfer factor for CO with activity, taking a value from 30 ml min- 1 mm Hg"1 at rest to 50 ml min"1 mm Hg" 1 with strenuous exercise such as football. The energy expenditure for each activity shown was taken from PASSMORE and DURNIN (1955), and converted into alveolar ventilation rates using 3-45 ml oxygen per calorie (BOOTHBY et al., 1936), a respiratory quotient of 0-82 and a mean alveolar CO 2 concentration of 5-6%. It has been assumed that the inspired air contains no CO.
N. WALD and S. HOWARD
by COBURN et al. (1965), shows the considerable effect that level of physical activity has on the half-life of COHb, ranging from 4 hr during sleep to 1 hr during vigorous exercise. COHb levels in smokers normally show a diurnal rhythm with levels rising during the day and declining during sleep. The large diurnal variation in COHb level makes a "random" level difficult to interpret. Figure 3 shows how the pattern of COHt%
»r
BACKGROUND 08.00
16.00
24.00
08.00
FIG. 3. Examples o" COIIb pa.aerui. Lu. 1 iLucLcn. ii-;1— ^LIIULC 2U ci^cacs. ditl> bus. u. ditUieat times. They both eliminate COHb at the same rate (half-life of 4 hr while asleep from 00-00 to 08-00 hr and a half-life of 2 hr while awake from 0800 to 2400 hr). Vertical lines represent the increase in COHb level produced by each cigarette; this COHb "boost" has been taken as 1% COHb per cigarette for both smokers. For simplicity, each cigarette has been shown to have been smoked instantaneously. The "background" COHb level due to endogenous CO production and atmospheric CO exposure has been taken as 1 %.
recent smoking can affect the daily COHb levels of two hypothetical cigarette smokers, 'A' who smokes mainly in the evening and 'B' who smokes steadily throughout the day. Both 'A' and 'B' smoke 20 cigarettes a day, inhale to the same extent (that is, produce the same rise in COHb level per cigarette), eliminate CO at the same rate but smoke their cigarettes at different times of the day. Thus 'A' and 'B' have the same exposure to tobacco smoke but their COHb levels are the same only at 09.00 and 19.00, and at any other time their COHb levels would be misleading in suggesting that one smoker was being exposed to more CO than the other. However, if instead of simply comparing COHb levels, the CO uptake were measured from each cigarette smoked by each of the two persons, it would be demonstrated that the two were, in fact, being exposed to the same total quantity of CO. One problem of this approach is that the CO uptake, and hence the amount of COHb derived from a single cigarette (the COHb 'boost' per cigarette), is likely to vary considerably from cigarette to cigarette according to the circumstances of smoking, even for a given individual. However, it is reasonable to suppose that a smoker's average COHb boost per cigarette is likely to be a characteristic of that particular person. In fact, this measure can be estimated from a single COHb measurement and a smoking and exercise history covering the previous 24 hr (WALD et al, in press). Such estimates have been shown to vary much less within an individual smoker from one day to another than between different smokers. A smoker's COHb pattern can be plotted as in Fig. 3, and the mean daily COHb can be calculated. Figure 4 shows the estimated mean COHb levels on several different days for each of 8 subjects who smoke 15-25 cigarettes daily, and one (PH) who smokes 40 a day. Although there is a day-to-day variability, some subjects are consistently and substantially different from others.
Smoking, carbon monoxide and arterial disease
PH D«
FIG. 4. Estimated mean daily COHb levels (above the "background" level due to endogenous CO production and atmospheric CO exposure) for nine smokers. For each subject, the points represent estimated values for several different days, based on a single COHb measurement. ASSOCIATION BETWEEN CARBOXYHAEMOGLOBIN AND THE PREVALENCE O F A R T E R I A L DISEASE
The association between COHb levels in smokers and the prevalence of arterial disease has been studied in a factory population in Copenhagen (WALD et ah, 1973). Satisfactory data were obtained from 950 subjects of whom 58 had either CHD or intermittent claudication. All the subjects were classified into four categories according to the estimated weight of tobacco smoked. Blood was taken for COHb measurement after lunch, the subjects having smoked as usual that day. The COHb level was not corrected for times of smoking or level of physical activity. Table 3 shows that the proportion of subjects affected by at least one of these disorders increases not only with tobacco consumption (11 % among heavy smokers) but also with COHb level (18% among smokers with a COHb level of 8% or more). A multiple regression analysis using a logistic model showed that the only factors found to be significantly associated with CHD or intermittent claudication TABLE 3. PROPORTIONS OF SUBJECTS WITH CORONARY HEART DISEASE AND/OR INTERMITTENT CLAUDICATION, GROUPED BY C O H B LEVEL AND SMOKING CATEGORY. PERCENTAGES IN PARENTHESES (TAKEN FROM WALD et at., 1973)
Smoking category Nil Light Moderate Heavy Total
COHb% 02/180 0/90 4/206 5/60 11/536
4(1) (0) (2) (8) (2)
1/27 15/178 10/95 26/300
8+ (4) (8) (ID (9)
0/4 (0) 13/51 (25) 8/59 (14) 21/114 (18)
Total 2/180 1/121 32/435 23/214 58/950
(1) (1) (7) (11) (6)
Definition of smoking categories: Light: l-14g tobacco per day; Moderate: 15-24g tobacco per day; Heavy: 25g or more tobacco per day (assuming that each cigarette provided lg of tobacco, and each cigar 3g).
6
N. WALD and S. HOWARD
were COHb level, age and serum cholesterol (P
Third Joint Meeting of The British Occupational Hygiene Society, The Ergonomics Research Society, and The Society of Occupational Medicine, at Swansea, September 1974
Aim. occup. Hyj. VoL 18, pp. 1-14. Pergamon Preu 1975. Printed in Oreit Britain
SMOKING, CARBON MONOXIDE AND ARTERIAL DISEASE N.
W A L D and
S.
HOWARD
DHSS Cancer Epidemiology and Clinical Trials Unit, Department of the Regius Professor of Medicine, Radcliffe Infirmary, Oxford OX2 6HE
Abstract—This paper reviews the role of carbon monoxide (CO) as a measure of tobacco smoke absorption, and as a possible cause of arterial disease in man. Smoking is the most important single source of exposure to CO, and frequently leads to carboxyhaemoglobin (COHb) levels above 8%. Most filter-tipped cigarettes produce more CO than plain cigarettes. The main factors affecting the uptake and elimination of CO are considered and it is shown that a single COHb measurement combined with a recent smoking and exercise history can be used to estimate the COHb derived from each cigarette. In a cross-sectional study COHb levels were more closely associated with the prevalence of coronary heart disease (CHD) than was smoking history. CO exposure from smoking has been shown to be harmful in persons who already have CHD or intermittent claudication. The evidence that CO is also harmful in persons without arterial disease is inconclusive, but animal data suggest that this may be the case. Some implications relating to the use of 'Smoking Tables' and the modification of cigarettes are considered.
INTRODUCTION RECENTLY, considerable interest has been focused on carbon monoxide (CO) as a measure of tobacco smoke absorption and also as a toxic constituent in tobacco smoke which may be responsible for the development of arterial disease. In this paper we review these aspects of CO and consider some of the implications of modifying cigarettes in order to make them safer. The association between smoking and coronary heart disease (CHD) is now well established (DOYLE et al., 1964; MORRIS et al., 1966; KANNELef al., 1968; STAMLER et al., 1968) and many prospective studies have shown that middle-aged men who smoke 20 cigarettes a day have 2-3 times a non-smoker's risk of dying of CHD (DOLL and HILL, 1964; BEST, 1966; KAHN, 1966; HAMMOND, 1972), making CHD numerically one of the most important diseases associated with smoking.
CARBON MONOXIDE AS A MARKER OF TOBACCO SMOKE ABSORPTION
Man is exposed to CO from many sources, and these have been well reviewed (GOLDSMITH and LANDAW, 1968; WELFARE, 1972). CO is absorbed
U.S.
DEPARTMENT OF HEALTH, EDUCATION &
through the lungs to form carboxyhaemoglobin (COHb) and Table 1 summarises the approximate levels of COHb that various sources of exposure can produce. Data in this table relating to environmental and occupational exposure were obtained from non-smokers.
3.
N . WALD and S. HOWARD
TABLE 1. TYPICAL CARBON MONOXIDE AND CARBOXYHAEMOGLOBIN LEVELS ASSOCIATED WITH VARIOUS SOURCES OF EXPOSURE TO CARBON MONOXIDE
Approx. mean Approx. mean CO (ppm) COHb(%)
Source of CO
Metabolism Environment (non-smokers) Los Angeles commuters 30 London taxi drivers 22 Occupation (non-smokers) Motor car repair shops (Canada) 80 Parking attendants 80 Border inspectors (Mexico-U.S.) 114 Blast furnace workers — Smoking Pipes (lifelong U.S. & U.K.) 15,000 Cigarettes 40,000 Cigars (lifelong U.S. & U.K.) 70,000 Pipes+cigars (ex-cigarette smoker^) —
Source of COHb data
0-5
SJOSTRAND (1949)
2-5 1-6
DEANE and PERKINS (Unpub.)
5 7 4 4
BUCHWALD (1968) RAMSEY (1967) COHEN et al. (1971) BUTT et al. (1974)
2 6 2 5
JONES et al. (1972)
GOLDSMITH and LAND AW (1968)
WALD (unpublished) CASTELDEN and COLE (1973)
COWIE et al. (1973)
(i) CO in tobacco smoke Smoking as a source of exposure to CO dwarfs all others. For most types of cigarette the concentration of CO in the smoke averages about 4% by volume. Cigarettes deliver about 12 ml CO per cigarette when tested on a smoking machine under standard conditions as specified by the Tobacco Research Council (ROTHWELL and GRANT, 1972) (35ml puffs of 2 sec duration at a rate of 1 puff per minute smoked to a standard butt length). As a cigarette is smoked and becomes shorter, the quantity of air entering through the porous cigarette paper is reduced, and so the CO concentration increases with each puff. Since the paper surrounding the filter of filter-tipped cigarettes is relatively non-porous less air can enter to dilute the CO, producing a higher CO yield in a filtertipped cigarette than in a plain one. This surprising result has been confirmed on several brands of cigarette (EVANS, personal communication). Figure 1 which shows the CO concentration per puff of four brands of cigarette illustrates this. Two of these, Senior Service Filter and Players No. 6 Filter, have non-porous filter tips, and one is a typical plain cigarette, Senior Service Plain. The fourth, Silk Cut Extra — Players No;6 F i l t e r — S e n i o r Service Plain — S e n i o r Service Filter
- E x t r a Mill) Silk Cut Filter
nT 1
I 2
I 3
4
5
I 6
I 7
I I I I 8 91 0 1 1
FIG. 1. Carbon monoxide yields per puff of four brands of cigarette. Silk Cut Extra Mild has a ventilated filter.
Smoking, carbon monoxide and arterial disease
3
Mild, has a "ventilated" filter, which differs from conventional filters in having perforations in the paper surrounding the filter tip. With this last type of cigarette, air entering through the perforations dilutes the smoke, thereby reducing the quantity of CO per puff, and this can result in a CO yield even lower than that of plain cigarettes. When the perforations are artificially sealed the CO yield of the cigarette increases to levels which are more typical of conventional filter-tipped cigarettes (WALD and SMITH, 1973). (ii) Uptake and loss of CO by smokers The uptake of CO from tobacco smoke and the rate of elimination of COHb from the body depend on several factors which are listed in Table 2. Apart from the type and quantity of tobacco smoked, the main factor affecting CO uptake is the method TABLE 2. THE PRINCIPAL FACTORS INFLUENCING THE RATES OF UPTAKE AND ELIMINATION OF CARBON MONOXIDE BY SMOKERS
CO Uptake
CO Loss
Concentration of CO in tobacco smoke No. puffs, puff volume, puff flow rate Depth of inhalation Pulmonary transfer factor for CO Total haemoglobin+myoglobin mass
Initial COHb level and ambient CO levels Alveolar ventilation (physical exercise) Pulmonary transfer factor for CO Total haemoglobin+myoglobin mass Cardiac output
of smoking—that is, the size and frequency of the puffs as well as how deeply each puff is inhaled. The rate of loss of CO is determined chiefly by alveolar ventilation, which is itself dependent on physical exercise. Figure 2, derived from data published 240
\
SLEEPING
\
180
STUDYING
\
\
TYPING
20 WALKING SLOWLY
\
FOOTBALL
60 _
0
1 4
1 8
1 12
' 16
1 20
I
24
28
V E N T I L A T I O N RATE I l / m i n l
FIG. 2. Half-life of COHb in relation to alveolar ventilation rate. This figure was produced from data published by COBURN et al. (1965). Adjustment has been made for the increase in transfer factor for CO with activity, taking a value from 30 ml min- 1 mm Hg"1 at rest to 50 ml min"1 mm Hg" 1 with strenuous exercise such as football. The energy expenditure for each activity shown was taken from PASSMORE and DURNIN (1955), and converted into alveolar ventilation rates using 3-45 ml oxygen per calorie (BOOTHBY et al., 1936), a respiratory quotient of 0-82 and a mean alveolar CO 2 concentration of 5-6%. It has been assumed that the inspired air contains no CO.
N. WALD and S. HOWARD
by COBURN et al. (1965), shows the considerable effect that level of physical activity has on the half-life of COHb, ranging from 4 hr during sleep to 1 hr during vigorous exercise. COHb levels in smokers normally show a diurnal rhythm with levels rising during the day and declining during sleep. The large diurnal variation in COHb level makes a "random" level difficult to interpret. Figure 3 shows how the pattern of COHt%
»r
BACKGROUND 08.00
16.00
24.00
08.00
FIG. 3. Examples o" COIIb pa.aerui. Lu. 1 iLucLcn. ii-;1— ^LIIULC 2U ci^cacs. ditl> bus. u. ditUieat times. They both eliminate COHb at the same rate (half-life of 4 hr while asleep from 00-00 to 08-00 hr and a half-life of 2 hr while awake from 0800 to 2400 hr). Vertical lines represent the increase in COHb level produced by each cigarette; this COHb "boost" has been taken as 1% COHb per cigarette for both smokers. For simplicity, each cigarette has been shown to have been smoked instantaneously. The "background" COHb level due to endogenous CO production and atmospheric CO exposure has been taken as 1 %.
recent smoking can affect the daily COHb levels of two hypothetical cigarette smokers, 'A' who smokes mainly in the evening and 'B' who smokes steadily throughout the day. Both 'A' and 'B' smoke 20 cigarettes a day, inhale to the same extent (that is, produce the same rise in COHb level per cigarette), eliminate CO at the same rate but smoke their cigarettes at different times of the day. Thus 'A' and 'B' have the same exposure to tobacco smoke but their COHb levels are the same only at 09.00 and 19.00, and at any other time their COHb levels would be misleading in suggesting that one smoker was being exposed to more CO than the other. However, if instead of simply comparing COHb levels, the CO uptake were measured from each cigarette smoked by each of the two persons, it would be demonstrated that the two were, in fact, being exposed to the same total quantity of CO. One problem of this approach is that the CO uptake, and hence the amount of COHb derived from a single cigarette (the COHb 'boost' per cigarette), is likely to vary considerably from cigarette to cigarette according to the circumstances of smoking, even for a given individual. However, it is reasonable to suppose that a smoker's average COHb boost per cigarette is likely to be a characteristic of that particular person. In fact, this measure can be estimated from a single COHb measurement and a smoking and exercise history covering the previous 24 hr (WALD et al, in press). Such estimates have been shown to vary much less within an individual smoker from one day to another than between different smokers. A smoker's COHb pattern can be plotted as in Fig. 3, and the mean daily COHb can be calculated. Figure 4 shows the estimated mean COHb levels on several different days for each of 8 subjects who smoke 15-25 cigarettes daily, and one (PH) who smokes 40 a day. Although there is a day-to-day variability, some subjects are consistently and substantially different from others.
Smoking, carbon monoxide and arterial disease
PH D«
FIG. 4. Estimated mean daily COHb levels (above the "background" level due to endogenous CO production and atmospheric CO exposure) for nine smokers. For each subject, the points represent estimated values for several different days, based on a single COHb measurement. ASSOCIATION BETWEEN CARBOXYHAEMOGLOBIN AND THE PREVALENCE O F A R T E R I A L DISEASE
The association between COHb levels in smokers and the prevalence of arterial disease has been studied in a factory population in Copenhagen (WALD et ah, 1973). Satisfactory data were obtained from 950 subjects of whom 58 had either CHD or intermittent claudication. All the subjects were classified into four categories according to the estimated weight of tobacco smoked. Blood was taken for COHb measurement after lunch, the subjects having smoked as usual that day. The COHb level was not corrected for times of smoking or level of physical activity. Table 3 shows that the proportion of subjects affected by at least one of these disorders increases not only with tobacco consumption (11 % among heavy smokers) but also with COHb level (18% among smokers with a COHb level of 8% or more). A multiple regression analysis using a logistic model showed that the only factors found to be significantly associated with CHD or intermittent claudication TABLE 3. PROPORTIONS OF SUBJECTS WITH CORONARY HEART DISEASE AND/OR INTERMITTENT CLAUDICATION, GROUPED BY C O H B LEVEL AND SMOKING CATEGORY. PERCENTAGES IN PARENTHESES (TAKEN FROM WALD et at., 1973)
Smoking category Nil Light Moderate Heavy Total
COHb% 02/180 0/90 4/206 5/60 11/536
4(1) (0) (2) (8) (2)
1/27 15/178 10/95 26/300
8+ (4) (8) (ID (9)
0/4 (0) 13/51 (25) 8/59 (14) 21/114 (18)
Total 2/180 1/121 32/435 23/214 58/950
(1) (1) (7) (11) (6)
Definition of smoking categories: Light: l-14g tobacco per day; Moderate: 15-24g tobacco per day; Heavy: 25g or more tobacco per day (assuming that each cigarette provided lg of tobacco, and each cigar 3g).
6
N. WALD and S. HOWARD
were COHb level, age and serum cholesterol (P
