Effects of smoking abstinence and chain-smoking on puffing topography and diurnal nicotine exposure.

Effects of chain-smoking, a 15-h smoking abstinence, and the nicotine yield of cigarettes on puff indices were studied in eight healthy smokers by using a controlled crossover study design. Puff parameters were measured puff by puff with a portable measuring device when 10 or 20 cigarettes, with nicotine yields of 0.3 and 1.0 mg, were smoked per day. The interval between sessions was 1 h, and the 20 cigarettes per day were chain-smoked 2 at a time. Serum cotinine indicated that smokers compensate completely for the lower nicotine delivery from the 0.3-mg cigarette. Smokers almost doubled total puff volume per cigarette and per day mainly by taking more puffs from the low-nicotine cigarettes and slightly prolonging puff duration. However, nicotine deprivation and chain-smoking had a relatively minor effect on puffing indices with both brands, a fact that agrees poorly with the nicotine titration hypothesis. However, in the course of every single cigarette of the day smokers significantly reduced puff duration and puff volume toward the end of the cigarette, which probably involves satiation of the nicotine crave but may also be due to changes in taste of the smoke.

Puffing behavior during the smoking of a single cigarette in a naturalistic environment.

The 36 participants in this study were habitual low-yield cigarette smokers, medium-yield cigarette smokers, and switchers from medium- to low-yield cigarettes. All participants smoked both low- (0.4 mg) and medium-nicotine (0.9 mg) cigarettes during the study. Puffing indices were recorded during the first two cigarettes, after an overnight abstinence of smoking, by a portable flowmeter processor unit in a naturalistic environment. The puff volumes per cigarette and per day were significantly lower while switching to higher-yield cigarettes, mainly due to a decrease in the number of puffs and longer interpuff intervals, but also due to a decline in puff duration and flow rate. However, the downregulation by puff volume was incomplete, at most two thirds, as calculated by machine smoking yields. Within the course of smoking a single cigarette, the flow rate was quite stable, puff duration and puff volume decreased toward the end of the cigarette, and interpuff interval was longest during the middle of the cigarette. Total puff volumes per cigarette were similar in the first two cigarettes of the day after an overnight abstinence of smoking, with no significant differences in other puff parameters. Diurnal cotinine excretion revealed that nicotine titration in switching situations was very accurate among switchers and medium-yield cigarette smokers, but not among the low-yield cigarette smokers, and so called oversmoking was found with the higher-nicotine brand. Preferred cigarette type had little effect on the puffing patterns of smokers in single cigarettes.

Smoking behavior in low-yield cigarette smokers and switchers in the natural environment.

Urinary cotinine and puffing parameters were studied in 36 smoking students. Three smoking groups, formed according to the tar content of their preferred cigarette, were compared. Eighteen students had always smoked low-yield, 10 medium-yield and 8 were switchers from medium- to low-yield cigarettes. The subjects smoked their preferred brand (the first week), low-yield cigarettes (the second week) and medium-yield cigarettes (the third week). Day urine samples were collected for cotinine analysis during the two last days of the test weeks. Puffing indices were reported on the last day of every test week with a portable microcomputer assisted analyzer with flowhead cigarette holder. Urinary cotinine concentrations were rather constant within the groups, but lower among the low-yield cigarette smokers as compared to the switchers (p less than 0.05). Also the female smokers had lower cotinine concentrations than the male smokers (p less than 0.05). The compensatory behavior seen in every smoking group while they were smoking low-yield cigarettes was based on up-regulation in single puff volume, puff duration and total smoking time when compared to values with medium-yield cigarettes. The correlation between cotinine concentration and diurnal puff volume (1/day) was poor. It is concluded that the benefit possibly gained with low-yield cigarettes is not long lasting.

Assessment of the automated colorimetric and the high-performance liquid chromatographic methods for nicotine intake by urine samples of smokers' smoking low- and medium-yield cigarettes.

We have compared the high-performance liquid chromatographic method with the direct barbituric acid test in an assessment of nicotine exposure. The effect of the endogenous colour in urine on the direct barbituric acid method was also studied. The applicability of methods was evaluated with urine samples from 15 smokers who smoked 5, 10 and 20 low- and medium-nicotine cigarettes per day. Assessments of nicotine intake with the methods were well correlated, although the high-performance liquid chromatographic method detects only cotinine and the direct barbituric method most of the nicotine metabolites. Before endogenous colour subtraction in the DBA method the correlation coefficient was 0.558 and after that 0.784. Both methods indicated similar changes in nicotine exposure with the change of brand and also a dose dependent relationship to the number of cigarettes smoked. The coefficients of variation for both of the methods were 3.4%. The endogenous colour determination lessened the capacity of direct barbituric acid method to one half being about 150 samples per day. With the high-performance liquid chromatographic method the capacity was about 50 samples per working day.

Microcomputer-aided measurement of puff parameters during smoking of low- and medium-tar cigarettes.

A portable microcomputer-assisted flow transducer was developed for analysing puff parameters during smoking of low- and medium-tar cigarettes. Smoke flow was determined by measuring pressure difference between two sites within an orifice flowmeter. According to the Bernoulli equation, the pressure difference is proportional to the square of flow. For calibration of the method, various sizes of air volumes were puffed through the flowmeter by a piston syringe. The calibration curve, which consisted of the flow as a function of the square root of pressure difference, was linear (r = 0.98). The automatic microcomputer analysis consists of the following variables: mean flow and mean volume of inhaled smoke gas, puff duration, time interval between two puffs, number of puffs and total volume inhaled. Eight volunteers smoked 10 low- and 10 medium-tar cigarettes during the cross-over experiments. The investigation indicated that the total inhalation volume of smokers in the case of low-tar cigarettes is twice as large as in the case of medium-tar cigarettes.

Antitussive effect of dextromethorphan and dextromethorphan-salbutamol combination in healthy volunteers with artificially induced cough.

The antitussive effects of dextromethorphan (30 mg) + salbutamol (2 mg), dextromethorphan (30 mg) alone and placebo on artificial cough induced by citric acid were compared in 19 healthy non-smoking volunteers in a double-blind crossover study. The method using inhaled citric acid with increasing concentrations to establish the cough threshold level showed an acceptable reproducibility and proved to be suitable for comparison of antitussive drugs. The cough threshold level was assessed before as well as 90 and 180 min after each medication. After placebo the cough threshold level showed no statistically significant rise. However, significant rises were shown following dextromethorphan (p less than 0.001) and the dextromethorphan-salbutamol combination (p less than 0.001). Between the treatments significant differences were shown in favour of the dextromethorphan-salbutamol combination. The results indicate that salbutamol has antitussive action enhancing the effect of plain dextromethorphan.

No difference between urinary mutagenicity in smokers of low-tar and medium-tar cigarettes: a double-blind cross-over study.

Urinary mutagenicity, blood carboxyhemoglobin and serum thiocyanate levels were measured in young, healthy volunteers smoking a fixed number of either low-tar (5 mg/cig.) or medium-tar (15 mg/cig.) cigarettes. The experiment was performed in a double-blind cross-over fashion. The volunteers were under daily control, and their diet and environment were standardized. The urinary mutagenic activity responded dose-dependently to the number of cigarettes smoked (0, 5, 10 or 20 per day), but there was no difference between the smokers of low-tar and medium-tar cigarettes. Neither were any significant differences found in blood carboxyhemoglobin nor serum thiocyanate. These results suggest that there is no substantial difference between the low-tar and medium-tar cigarette as to the inhalation of hazardous compounds in the real smoking situation.

The mycotic flora of adenoids and antibodies to Candida albicans in children.

We cultured the adenoid tissues of 72 children with recurrent respiratory infections for fungal organisms. We also took fungal cultures of nasopharyngeal secretions from 20 healthy children and 13 healthy adults as controls. Culture for fungi were positive in 15% of the patients, in 15% of the healthy adults and in 25% of the healthy children. Candida albicans, C. parapsilosis, C. tropicalis and Aspergillus sp. were the most common organisms found. In studying the children with recurrent respiratory infections, we were unable to find any significant correlation between the positive cultures and the age, type of day-care and previous antibiotic therapy given. We then studied the hemagglutination titers against C. albicans in 44 patients. This titer was 1:160 or lower in all but three patients, and was 1:320 in these latter three patients. However, fungal cultures were negative in all patients having hemagglutination titers of 1:80 or more.

Microcomputer assisted measurement of inhalation parameters during smoking.

A microcomputer aided, battery operated method for analysing puff parameters during smoking was developed. The equipment included a sensitive, differential pressure transducer, a portable microcomputer and a modified cigarette flowmeter. The method is based on measuring pressure differences between two points within the flowmeter. The pressure difference is linearly proportional to smoke flow according to the Poiseuille-Hagen principle. The calibration curve, the mean flow as a function of (the area of puff curve)/puff duration, showed to be linear (r = 0.99) for calculating flow and volume of smoke. In experiments with 11 male volunteers the total inhalation volume reached the range 296-678 ml, the mean puff volume 19-65 ml, the mean puffing rate 15-26 ml/s, the mean puff duration 1.3-3.5 s, the number of puffs 9-16 and the mean interval between puffs 17-25 s.

The effect of clonidine and yohimbine on audiogenic seizures (AGS) in rats.

Clonidine in high doses (0.5,1.0 mg/kg) significantly increased the latency for audiogenic seizures (AGS) in rats and reduced seizure severity. At a dose (0.05 mg/kg) which acts more specifically on presynaptic alpha 2-receptors, clonidine did not affect seizure latency, but showed a slight proconvulsant action. Yohimbine tended to decrease seizure-latency at all doses, but statistical significance (p less than 0.05) was only reached at 10 mg/kg. Smaller doses of yohimbine (0.5 and 1.0 mg/kg) showed a proconvulsant effect, while a high dose (10 mg/kg) markedly reduced the severity of AGS. The effect of clonidine on seizure-latency was only antagonized by high-dose yohimbine (10 mg/kg), the combination of these drugs being of marked anticonvulsant efficacy. From these results it can be concluded that the anticonvulsant effect of clonidine does not seem to be mediated through presynaptic alpha 2-receptors. Action on other central noradrenergic receptors, and influences on other transmitters must be taken into account when interpreting the effect of clonidine and yohimbine on AGS in rats.