The lung is a major target organ for smoking-related disease. Because of the risk of lung disease, smokers have been recommended to give up the habit, or failing that, to change to cigarettes with lower yields of tar, nicotine and carbon monoxide. While there is evidence that cessation of smoking results in a slow improvement in abnormal pulmonary function, we are unaware of any evidence of improvement in pulmonary function test results when smokers change to lower yield cigarettes. However, a difficulty with this type of study arises from the long time course required for improvement in conventional tests of lung function even after complete cessation of smoking.
A sensitive measure of a smoking-related abnormality in lung function is the increased rate of clearance of the hydrophilic tracer molecule 90mTc diethylenetri-amine penta acetate (90mTc DTPA) across the alveolar capillary barrier. Cigarette smokers have a significantly increased clearance of this solute from the lungs. This clearance falls toward normal within 24 hrs of stopping smoking. This rapid alteration in clearance of 90mTc DTPA when changing smoking habits suggested that the test may be a useful guide to the pulmonary effects of changing to a lower yield cigarette.
The aim of the present study was to test the hypothesis that the abnormality in clearance of 90mTc DTPA from the lungs of smokers would be reduced when subjects switched to cigarettes with lower yields of tobacco smoke constituents. In this context, “yields” are defined as the delivery of carbon monoxide (CO), nicotine and tar of cigarettes “smoked” by a machine set to take a 35 ml puff over 2 seconds every minute until the cigarette is smoked to within 1 cm of the filter. These are the values used to define whether a cigarette is mid-, low- or ultra-low tar and used in government publications to promote safer cigarettes. However, these “yields” may not necessarily be synonymous with the deliveries of the smoke constituents when smoked by different individuals. The investigation was carried out in two parts, because a change in the nicotine yield from a cigarette may cause the subjects to compensate by smoking more. The medical aspects of different diseases and their ways of treatment may be found on Canadian Neighbor Pharmacy website.
Material and Methods
Both parts of this study were approved by the Northwick Park Hospital Ethical Committee. In the first part, we measured the effect on 96mTc DTPA clearance of switching from a commercially available cigarette defined as middle tar by the Government Chemist to a commercially available low-tar cigarette. The low-tar cigarette had a reduced yield of tar, nicotine, and CO. We called this the mid-tar to low-tar study.
In the second part, we studied the effects of switching smokers between two specially manufactured cigarettes which had been formulated so that the nicotine and tar yields were similar, but in one cigarette, the CO production was reduced. This was called the mid-CO to low-CO study.
Mid-tar to Low-tar Study
The subjects were 20 male cigarette smokers aged 18 to 59 years (mean 30 years) with a cigarette consumption of 4-89 pack/yrs (mean 25 pack/yrs). All subjects normally smoked a brand of cigarette classified as middle tar by the Government Chemist. The subjects were randomly allocated to two groups. Both groups of subjects were supplied with a commonly smoked brand of middle tar (MT) cigarettes. The cigarettes were supplied at weekly intervals for the Yields (ml/cigarette) were determined by the laboratory of the Government Chemist for each cigarette studied. Cigarettes were smoked under the following standard conditions: a 35 ml puff over 2 s was taken every min until the cigarette was smoked to within 1 cm of the filter. The subjects were asked to smoke normally and to use only the cigarettes provided. The cigarettes were packaged in identical unmarked boxes and the subjects were not informed when the change to low-tar cigarettes was made. After two weeks, one group was supplied with a commercially available brand of low tar cigarettes for the following two weeks, while the other group continued with MT cigarettes. Tkble 1 shows the yields of tar, nicotine and carbon monoxide for both cigarettes determined by the laboratory of the Government Chemist under the standard conditions defined in the introduction. The half time clearance rate of 96mTc DTPA from the lung into the blood was assessed at the end of each week for the four weeks of the study. Subjects breathed an aerosol of the tracer for three minutes while in the supine position. The tracer was generated from an Acorn nebulizer. Tb ensure minimal deposition of the tracer in the airways, the output was passed through a bead separator to produce an aerosol with only 6 percent of particles >2|tm.° Two scintillation detectors, one positioned over the right upper part of the chest and the other over the thigh, measured the clearance of the 96mTc DTPA from the lung to the blood and tissues. The background activity in vascular tissues within the counting field of the lung detector was subtracted as previously described. Clearance across the alveolar-capillary barrier was expressed as the time taken for the corrected activity in the lung field to fall to half its peak activity (tVkLB min). Each subject had a venous blood sample analyzed for carboxyhemo-globin concentration (COHb %) using an IL 282 CO-oximeter. The blood samples were taken at weeks 2 and 4 at 21:00 hrs to obtain an estimate of peak daily levels.
Mid-CO to Low-CO Study
In this study, subjects smoked the two types of specially manufactured cigarettes. Table 1 shows the yields of tar, nicotine and carbon monoxide for both types of cigarette as determined by the laboratory of the Government Chemist. Fifteen smokers, aged 23-60 years (mean 38 years) took part with a middle-tar cigarette consumption of 6-85 pack/yrs (mean 25 pk/yrs). The study was carried out as a double blind cross-over trial. The subjects were randomly allocated to two groups. The first group of seven subjects smoked the mid-carbon monoxide cigarette (MCO) for three weeks and were then changed to the low-carbon monoxide cigarette (LCO) for a further three weeks. The protocol for the second group of eight subjects was identical except that the order in which they smoked the cigarettes was reversed. Subjects were not informed when the changeover occurred.
Clearance of 96mTc DTPA and peak carboxyhemoglobin level were measured at the end of each week for the six-week study period. In addition, subjects were requested to collect butts of all the cigarettes smoked on the measurement day. These were counted to obtain an estimate of cigarette consumption. On the same day, subjects performed a 24-hr urine collection, an aliquot of which was analyzed for nicotine and cotinine concentration (using a modification of the method of Feyerabend and Russell) to estimate an index of total nicotine absorption.
Mid-tar to Low-tar Study
A two-way analysis of variance was used to analyze the data for significant differences within each group. An unpaired t test was used for comparison between groups 1 and 2. The data were analyzed for any significant correlation between MLB and COHb using linear least squares regression.
Mid-CO to Low-CO Study
A two-way analysis of variance was used to compare the measured variables for the six-week study period. In addition, the mean values for weeks 2 and 3 (mid CO) were compared with the mean values for weeks 5 and 6 (low CO) using a series of t tests, as recommended for crossover trials by Hill and Armitage. Linear least squares regression was used to identify any significant correlation between the variables measured. For both studies a significant level of p <0.05 was chosen.
Table 1—Standard Machine Smoking Yields of Cigarettes Used
|Study 1||Study 2|
|Mid Tkr Low Tar||Mid CO||Low CO|