Transdermal clonidine reduced some withdrawal symptoms but did not increase smoking cessation.

BACKGROUND: Clonidine may be useful in controlling tobacco withdrawal and in facilitating smoking cessation. This study was developed to test the efficacy of transdermal clonidine in promoting smoking cessation. METHODS: We conducted a five-center, double-blind, placebo-controlled, randomized controlled trial of transdermal clonidine in conjunction with a minimal behavioral intervention for smoking cessation. The intervention was based on the American Lung Association's Freedom From Smoking program. Self report of not smoking was validated with exhaled air carbon monoxide of less than 8 ppm and salivary cotinine of less than 20 ng/mL. Transdermal clonidine therapy began 1 week before the target quit date: 0.1 mg/24 h for the first 4 days increasing to 0.2 mg/24 h for the next 3 days, if the lower dose was tolerated. The highest tolerated dose was then continued for 6 weeks after target quit day. Withdrawal symptoms were measured daily for the first 7 days after target quit day. RESULTS: A total of 213 patients were enrolled (106 active drug and 107 placebo). During the study, 15.5% of patients had drug therapy discontinued due to adverse effects, 24.5% (26/106) taking active drug vs 8.4% (9/107) receiving placebo. There was a significant reduction in anxiety score from 3.0 to 2.4 (placebo vs active) and irritability score from 2.2 to 1.7 (placebo vs active) during the first week after cessation. There was no reduction in other withdrawal symptoms. The overall 12-week abstinence rate was 33.0% (35/106) in the active drug group vs 34.5% (37/107) in the placebo group (not significant). CONCLUSION: This study demonstrated some reduction in early withdrawal symptoms with the use of a clonidine transdermal patch, but no increase in cessation rate, 6 weeks after medication had been discontinued.

Effect of transdermal nicotine delivery as an adjunct to low-intervention smoking cessation therapy. A randomized, placebo-controlled, double-blind study.

To assess the smoking cessation efficacy of transdermal nicotine patches as an adjunct to low-intervention therapy, we conducted a double-blind, placebo-controlled trial in 158 smokers. Participants were randomly assigned to one of the following three study regimens that required daily application of two 15-cm2 patches: (1) 24-hour nicotine delivery, (2) nicotine delivery during wakeful hours only, and (3) placebo. The impact of the three regimens on smoking cessation rates and tobacco withdrawal symptoms was examined. During the last 2 weeks of the trial, 39% of the 24-hour nicotine regimen delivery group, 35% of those on wakeful hour nicotine regimens, and 13.5% of the placebo treatment group achieved abstinence. Self-reported quit rates for the two nicotine patch-wearing regimens, as compared with that for the placebo group, continued to be significantly higher at 6 months. Moreover, compared with placebo, the transdermal nicotine patches significantly reduced tobacco withdrawal symptoms during the first few weeks of quitting. The differences in quit rates and tobacco withdrawal symptoms between the two active groups were not statistically significant. The patches were well tolerated both topically and systemically. We concluded that transdermal nicotine, when used as an adjunct to low-intervention therapy, significantly reduced tobacco withdrawal symptoms and enhanced smoking cessation rates.

Smoking cessation.

Cessation of cigarette smoking is the single most important therapeutic intervention that is effective in reducing the symptoms of COPD and in preventing its onset. Smoking cessation is, therefore, a major goal in efforts to mitigate the burden of this disease. This review will consider the pharmacologic and behavioral therapies that have been used to assist smokers in overcoming their addiction. These strategies assist a significant minority of smokers to stop smoking and, thus, they can have an important positive impact on COPD as well as on other health outcomes.

Smoking cessation is associated with an increase in exhaled nitric oxide.

STUDY OBJECTIVES: Nitric oxide (NO), a gas produced by cells lining the respiratory tract, has been reported to be decreased in the exhaled air of cigarette smokers. We hypothesized that smoking cessation would result in an increase in exhaled NO. DESIGN: Comparison of exhaled NO measured from nonsmokers, cigarette smokers, and smokers after smoking cessation. SETTING: University outpatient smoking cessation clinic. PATIENTS OR PARTICIPANTS: Twenty-five cigarette smokers and 23 normal, nonsmokers. INTERVENTIONS: Exhaled NO was measured by three techniques: (1) a peak oral method; (2) a mean oral method; and (3) a nasal method. The smokers were given nicotine patches and instructed to return after 1 and 8 weeks. The exhaled NO determinations were repeated on each visit. MEASUREMENTS AND RESULTS: Compared with nonsmokers, smokers had decreased NO levels measured by all three methods (p<0.05, each comparison). Nineteen smokers returned after 1 week. Fourteen were successfully abstinent from cigarettes and their exhaled NO increased compared with baseline (p<0.01 for each method) but not in the five subjects who had not successfully quit smoking (p>0.05 for each method). Ten subjects returned after 8 weeks. The exhaled NO levels increased further and were not significantly different from the normal nonsmokers for the peak oral and nasal NO methods (p>0.2), but were still lower than the normal nonsmoker mean oral NO (p=0.018). CONCLUSIONS: These data demonstrate that smoking cessation is associated with an increase in exhaled NO.

Chronic inflammation is associated with an increased proportion of goblet cells recovered by bronchial lavage.

To evaluate the possibility that bronchoalveolar lavage could provide sufficient respiratory epithelial cells to quantify changes in epithelial cell types associated with chronic inflammation, we examined the epithelial cells obtained in the first infused (20 ml) aliquots that were processed separately from later aliquots, a process known to enrich for bronchial contents. Epithelial cells, including ciliated cells, goblet cells, and fragments of desquamated epithelium, were easily identified after preparation by cytocentrifugation and staining with a modified Giemsa stain. Quantification of the columnar cell types revealed that those with chronic bronchitis and asymptomatic smokers have increased goblet cells as a percentage of the total columnar epithelial cells (chronic bronchitics 36 +/- 2 percent, asymptomatic smokers 22 +/- 2 percent) compared with normal subjects (9 +/- 1 percent, p less than 0.001, ANOVA). Significantly, the goblet cell percentage was strongly correlated with other measures of bronchitis and measures of airflow obstruction such as the bronchitis index, a visually derived score at bronchoscopy of airway inflammation (r = 0.72, p less than 0.001), the percent neutrophils in the first infused aliquots (r = 0.44, p less than 0.05), and the FEV1 percent (r = -0.74, p less than 0.001). Thus, bronchoalveolar lavage is capable of providing sufficient bronchial epithelial cells for analysis, and the changes seen in the spectrum of columnar epithelial cells may reflect important underlying pathologic changes.

General vs local anesthesia. Effect on bronchoalveolar lavage findings.

Bronchoalveolar lavage (BAL) can be performed with the patient undergoing either local or general anesthesia (GA). This study investigates whether the type of anesthesia affects BAL fluid and cell recovery. Eighty patients, were selected for study. Fluid recoveries were significantly less in the GA group for both the bronchial and alveolar lavages. The differences were confirmed for BAL fluid recovery in a subsequent group of 120 unselected patients. Bronchoscope size did not appear to affect recovery, nor did anesthesia time; BAL fluid recovery from patients with respiratory failure who were intubated and mechanically ventilated was similar to that in the GA group, suggesting that lower recovery rates may be due to mechanical ventilation. The BAL fluid cell counts were related to fluid recovery, but airway neutrophils represented a higher percentage of BAL lavage fluid cells in the GA lavages, independent of differences in the volume of lavage fluid recovered.

Bronchoalveolar lavage fluid obtained from smokers exhibits increased monocyte chemokinetic activity.

Alveolar macrophages, which are cells derived from blood monocytes, accumulate within the lower respiratory tract of cigarette smokers. One mechanism to account for this accumulation of alveolar macrophages may be an increase in the migration of blood monocytes into the lungs of smokers. To evaluate this hypothesis, bronchoalveolar lavage fluid (BALF) was obtained from 15 smokers and 16 nonsmokers. The smokers' BALF possessed a significantly increased capacity to attract normal blood monocytes when evaluated using a blind-well chamber technique (26.2 +/- 7.6 vs 14.8 +/- 6.9 cells/high-power field, P less than 0.01). Checkerboard analysis of the activity revealed that it was predominantly chemokinetic. Partial characterization of the activity in smokers' BALF revealed that it was lipid soluble but only partially sensitive to trypsin and heat. The chemokinetic activity correlated with alveolar macrophage numbers in the BALF (r = 0.4391, P = 0.009). Furthermore, both the chemokinetic activity and alveolar macrophage number correlated with alterations of respiratory function (forced expiratory volume in 1 s, diffusing capacity for carbon monoxide, and forced expiratory flow at 75% of the vital capacity). These results suggest that the increase in alveolar macrophage number present in the BALF of cigarette smokers may be due, at least in part, to an increased amount of chemokinetic factor(s) in the smokers' BALF, and these factor(s) may participate in the decline of respiratory function associated with cigarette smoking, probably by recruiting monocytes into lung.

In vivo and in vitro methods for evaluating airways inflammation: implications for respiratory toxicology.

The lung is frequently the target of injury for toxic exposures. Often these exposures lead to significant disease. Assessment of toxic exposures to the lung, however, may be made using both in vitro and in vivo methods. Recent advances in respiratory cell biology have made possible in vitro analyses of the interactions between airway cells and potential toxins. In addition, the lung can be sampled in vivo using bronchoscopy and bronchoalveolar lavage. This opens up the possibility of assessing potential toxins prior to the development of clinically significant disease. Together, these advancing methodologies promise new potential for the assessment and evaluation of toxic exposures to the lung.

Three-year survival rates of pulmonary rehabilitation patients with chronic obstructive pulmonary disease.

A retrospective study analyzed medical and psychosocial factors associated with the three-year survival rates of clinically stable chronic obstructive pulmonary disease patients enrolled in a pulmonary rehabilitation program. The 69 percent three-year survival rate was similar to rates reported in previous studies. Neither continued cigarette smoking nor psychological variables were significantly associated with patient longevity. Discriminant analysis revealed that the combination of arterial O(2) and CO(2) tensions or its simple approximation (PaO(2) - PaCO(2)) was the best predictor of patient survival at three years.

Smoking reduction: an alternative approach for smokers who cannot quit.

Cigarette smoking is the foremost cause of death in the United States and is a major health problem worldwide. Clearly, the best way to eliminate the risk of smoking-related diseases, is to quit smoking. Smoking cessation has immediate and long-term benefits and substantially reduces the risk of many smoking-related diseases. Unfortunately, quitting smoking is rarely easy. For those smokers who cannot or do not wish to quit, reduction in their total smoking may represent a potential health benefit. Reduction in total smoking can, theoretically, be achieved by: 1) reducing the number of cigarettes smoked daily; and/or 2) switching to a low tar/low nicotine cigarette. Smokers, however, tend to self-adjust nicotine to maintain relatively constant levels. Reduction in tar/nicotine content or number of cigarettes, therefore, may not produce health benefits. Smoking reduction with alternative nicotine delivery, however, may represent an alternative option for smokers who cannot, or do not, wish to quit.

Cigarette smoking, urinary acidity, and nicotine excretion under natural conditions.

For 40 males who smoked 20 cigarettes a day titratable acidity of the urine was significantly correlated with nicotine/cotinine excretion at several sample intervals, as was urinary pH, but not urinary acidity and daily cigarette consumption or serum COHB.

Self-recognition of alcohol and cigarette dependency among high school seniors.

A brief, anonymous survey of 284 high school seniors at one midwestern metropolitan public high school assessed current smoking, history of alcohol use, and students' beliefs in future risk of dependency. A major purpose was to assess students' self-recognition of alcohol and cigarette dependency. Of the seniors surveyed, 92 (32%) were current smokers, and 237 (84%) reported a previous history of alcohol use. 52% of current smokers indicated they were already "hooked" on cigarettes or anticipated a good chance of cigarette addiction five years later. In contrast, 94% of regular alcohol users indicated there was either no chance (71%) or only a mild chance (23%) of ever becoming an alcoholic. Six of every ten high school smokers surveyed reported that quitting cigarettes for three days would be difficult.

Relationship between a pulmonary function test (FEV1) and the ADAPT quality-of-life scale.

In a previous study the Additive Daily Activities Profile Test (ADAPT) correlated .83 with maximum oxygen consumption among pulmonary rehabilitation patients. The present study expanded the pulmonary population base and compared the ADAPT scores of 41 patients at two independent centers with a more readily available parameter, the forced expiratory volume in the first second of forced exhalation (FEV1). The relationships between the two major ADAPT subscales and FEV1 were significant but lower in magnitude than that found with maximum oxygen consumption. The ADAPT continues to be sensitive to physical impairment and in translating the effect of impairment upon daily physical activity.

Immediate carbon monoxide estimates and self-reported smoking.

Because carbon monoxide (CO) is an easily understood danger of cigarette smoking, new breath CO analyzers may be useful in cessation programs. Self-reported cigarette consumption and breath CO correlated .70 using a 90-sec. CO-determination method. Smokers averaging 17 daily cigarettes had average breath CO of 24 parts per million (ppm), falling to 7.71 ppm for smokers claiming at least 24-hr. abstinence. Corresponding carboxyhemoglobin (COHb) estimates were 4.34% (slightly above World Health Organization 4% safety limit) and 1.39%. Smoking clinics can use CO-monitoring devices for feedback or surveillance, although feedback would provide the most benefits for participants.