OBJECTIVES. Sources of measurement error in assessing smoking status are examined. METHODS. The Lung Health Study, a randomized trial in 10 clinical centers, includes 3923 participants in a smoking cessation program and 1964 usual care participants. Smoking at first annual follow-up was assessed by salivary cotinine, expired air carbon monoxide, and self-report. Each of these measures is known to contain some error. Sensitivity and specificity were calculated by comparing a biochemical measure with self-report to produce an undifferentiated estimate of error. Classification error rates due to imprecision of the biochemical measures and to the error in self-report were estimated separately. RESULTS. For cotinine compared with self-report, the sensitivity was 99.0% and the specificity 91.5%. For carbon monoxide compared with self-report, the sensitivity was 93.7% and the specificity 87.2%. The classification error attributed to self-report, estimated by comparing the results from intervention and control groups, was associated with the responses of 3% and 5% of participants, indicating a small but significant bias toward a socially desirable response. CONCLUSIONS. In absolute terms in these data, both types of error were small.

We related serum nicotine and cotinine levels while subjects were smoking their usual numbers of cigarettes to levels while wearing a nicotine patch under carefully controlled, smoke-free conditions in a clinical research center. Twenty-four volunteers who needed intensive treatment for severe nicotine dependence were admitted to the clinical research center and were treated with a 22 mg transdermal nicotine patch each day and an intensive smoking-cessation program. Serum nicotine and cotinine levels, withdrawal symptoms, and hours and quality of sleep were noted. The steady-state serum nicotine and cotinine levels produced with the nicotine patch were lower than those observed when the subjects were smoking. Mean nicotine and cotinine levels were inversely related to mean withdrawal scores for the first 6 days. A fixed dose of transdermal nicotine will not be effective for all smokers. Individualization of therapy should be based on objective biologic measures such as serum cotinine and subjective assessment of withdrawal relief.

Objective.\p=m-\To determine the efficacy of a 22-mg nicotine patch combined with the National Cancer Institute program for physician advice and nurse follow-up in providing withdrawal symptom relief, 1-year smoking cessation outcome, and percentage of nicotine replacement.Design.\p=m-\Randomized,double-blind, placebo-controlled trial. Subjects.\p=m-\Two-hundredforty healthy volunteers who were smoking at least 20 cigarettes per day.Interventions.\p=m-\Basedon the National Cancer Institute program, subjects received smoking cessation advice from a physician. Follow-up and relapse prevention were provided by a study nurse during individual counseling sessions. Subjects were randomly assigned to 8 weeks of a 22-mg nicotine or placebo patch.Main Outcome Measures.\p=m-\Abstinencefrom smoking was verified by expired air carbon monoxide levels. Withdrawal symptoms were recorded during patch therapy, and the percentage of nicotine replacement was calculated by dividing serum nicotine and cotinine levels at week 8 of patch therapy by levels obtained while smoking.Results.\p=m-\Highersmoking cessation rates were observed in the active nicotine patch group at 8 weeks (46.7% vs 20%) (P<.001) and at 1 year (27.5% vs 14.2%) (P=.011). Higher smoking cessation rates were also observed in subjects assigned to the active patch who had lower serum levels of nicotine and cotinine at baseline, and withdrawal symptom relief was better in the active patch group compared with placebo.Conclusions.\p=m-\Clinicallysignificant smoking cessation can be achieved using nicotine patch therapy combined with physician intervention, nurse counseling, follow-up, and relapse prevention. Smokers with lower baseline nicotine and cotinine levels had better cessation rates, which provides indirect evidence that they had more adequate nicotine replacement with this fixed dose of transdermal nicotine than those smokers with higher baseline levels.

Transdermal nicotine has been shown to relieve nicotine withdrawal and to double smoking cessation rates compared to placebo in clinical trials. A 21 or 22 mg/day dose provides a steady state serum nicotine that is less than obtained from smoking. Limited information is available about higher nicotine patch doses. To define better the optimal dosing of nicotine patch therapy, we undertook an open-label study to determine the safety and tolerability of 44 mg/day dose for smoking cessation in subjects smoking > or = 20 cigarettes per day. Forty smokers received 44 mg/day of transdermal nicotine for 4 weeks followed by 4 weeks of 22 mg/day. Of the 40 subjects enrolled, 38 (95%) completed the 4 weeks of 44 mg patch therapy and 36 (90%) completed the entire 8 weeks of patch therapy. Non-smokers at week 4 had a mean serum nicotine level of 23.4 +/- 11.7 ng/ml and cotinine of 152.2 +/- 87.3 ng/ml. Percent replacement was calculated by dividing the steady state level at week 4 by the baseline level while the subjects were smoking their usual number of cigarettes. Percent nicotine replacement for non-smokers at week 4 (while on 44 mg nicotine patch) averaged 158% +/- 108.4, and for cotinine was 112.0 +/- 73.8. For nicotine, 33% of non-smokers at week 4 had < or = 100% nicotine replacement and for cotinine 63% < or = 100% replacement. Biochemically confirmed point prevalence smoking cessation rates were 65% and 55% at weeks 4 and 8 of patch therapy, respectively, and self-reported smoking cessation at 3 months was 50%. The most common effect was skin irritation at the patch site. A single subject was admitted for myocardial infarction following step-down from 44 to 22 mg of replacement nicotine. The subject was not smoking and the adverse event was deemed to be not related to the patch therapy. Sleep complaints were reported in 33% of subjects during the 44 mg phase. Other complaints were infrequent. We conclude that 44 mg per 24-h nicotine patch therapy in heavy smokers is safe, tolerable, and without significant adverse events.

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