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.

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.

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.

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.

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.

Physician reporting of and referral for patient complaints about sleep disorders.

The first goal of this Nebraska-based study was to determine physician reporting of patient complaints about sleep. The second goal was to determine the patterns of referral to sleep disorders laboratories by geographic location and specialty practice. A total of 299 Nebraska physicians (177 in urban areas and 122 in rural areas) completed a questionnaire concerning sleep complaints among patients. We found no statistically significant differences between urban and rural physicians in the percentage of patients reporting insomnia, excessive daytime sleepiness, snoring, or other sleep complaints. Psychiatrists reported on significantly more patients with insomnia and excessive daytime sleepiness than did other physicians; however, they tended to refer fewer patients to sleep disorders laboratories than did physicians practicing internal medicine. Urban physicians referred significantly more patients to sleep disorders laboratories than did rural physicians. We concluded that physician reporting of patient complaints about sleep is similar in urban and rural areas of Nebraska. However, physicians in rural areas tend to refer fewer patients to sleep disorders laboratories than do physicians in urban communities.

Smoking cessation in the workplace: evaluation of relapse factors.

Relapse factors associated with a well-supported worksite smoking cessation program were examined in a prospective study. Of 104 employee-participants, 81 (78%) were confirmed as abstinent at 8 days after quit day. Forty-six employees (44%) continued to report total abstinence at 1 year. Stepwise regression analysis of baseline variables found two significant, but weak, predictors of 1-year smoking status: Fagerstrom score and number of other smokers residing in the home. Analysis of tobacco withdrawal symptom data of confirmed abstainers found only self-reported anxiety scores to be predictive of smoking status at 1 year. Early abstainers with elevated anxiety scores appear to be at high risk for smoking relapse.

Smoking intervention: combination therapy using nicotine chewing gum and the American Lung Association's "Freedom from Smoking" manuals.

The smoking cessation efficacy of a two-session group program using the American Lung Association's "Freedom from Smoking" self-help manuals, nicotine gum, and brief, repeated professional supervision was estimated in an uncontrolled clinical trial. Of the 39 participants, 12 (31%) remained cigarette free for 1 year, and 4 others (10%) had not smoked during the 3 months prior to the 1-year follow-up. Claims of cessation were verified by expired-air carbon monoxide measurement. Nearly all successful abstainers were able to achieve 48-hr cessation during their first week using the gum. This finding suggests that nicotine gum is best used to help the smoker quit abruptly, rather than as an aid in a tapering-off strategy. This study's smoking intervention program appears to provide a relatively low-cost method of improving the success rates among smokers who wish to quit.

Altered epithelial lining fluid parameters in old normal individuals.

Pneumonia is a leading cause of morbidity and death in older patients, and immunosenescence is believed to contribute to their susceptibility. In order to investigate whether age-related changes occur on the epithelial surfaces of the lung, bronchoscopy and bronchoalveolar lavage (BAL) were performed without complication in 19 young (27.7 +/- 4.2 yrs), 6 middle-aged (49.8 +/- 3.5 yrs), and 8 old (74.1 +/- 4.3 yrs) normal, nonsmoking subjects. BAL was performed by instilling and retrieving five 20 ml aliquots of normal saline into three sites. The returns from the first aliquots (the bronchial sample) were analyzed separately from the returns from the subsequent aliquots (the distal sample). Lavage fluid cellularity was characterized and IgA, IgG, and albumin were measured by ELISA. Lavage fluid returns were lower in the elderly group and correlated with spirometric parameters. Significantly elevated numbers of neutrophils were recovered by the bronchial sample fluid from the old group. In contrast, no consistent difference in macrophage recovery by either the bronchial or distal sample was noted. In both the bronchial and distal samples, IgG, but not IgA or albumin, was elevated in the group of old subjects. Alterations occurring in BAL fluid with aging may reflect changes in local host defenses.

Total indoor smoking ban and smoker behavior.

METHODS: To assess smoking policy support and effects, 1,083 hospital employees (203 smokers) were surveyed by anonymous questionnaire 1 year after the announcement (5 months after implementation) of a new total indoor smoking ban. A second follow-up, limited to smoker respondents only, was conducted 2 years postannouncement. RESULTS: A total indoor smoking ban was supported by the vast majority of nonsmokers (89%) and ex-smokers (86%) and by nearly half of the then-smoking population (45%). Consistent with previous reports, the smoking ban was associated with a significant decrease in cigarette use during work hours, particularly among moderate to heavy smokers. However, the ban did not result in increased institutional quit rates. Light smokers (< 10 cig/day), compared with heavy smokers (> or = 30 cig/day), were more likely to support the no-smoking policy and had fewer problems observing the ban. They were also less apt to report a decrease in work productivity. CONCLUSION: A total indoor smoking ban had little effect on overall institutional quit rates. Heavy smokers will, predictably, experience the greatest difficulty complying with a total indoor nonsmoking policy.

Modulation of elastase binding to elastin by human alveolar macrophage-derived lipids.

Human neutrophil elastase (HNE), an enzyme secreted by activated neutrophils, can bind to and degrade extracellular matrix including human lung elastin. This protease is believed to play an important role in several destructive processes including pulmonary emphysema. In this study, we hypothesized that an alveolar macrophage (AM) product or products may interact with neutrophil elastase (NE) and modulate its binding to elastin. Elastase binding to elastase was evaluated by a modified elastase functional assay using a synthetic substrate. Supernatants from cultured AM inhibited elastase binding to elastin at a dose-dependent manner without inhibiting functional elastase activity. The AM products had a heterogeneous molecular weight ranging from 440,000 to 54,000. The activity was heat-stable, but was lost after ultracentrifugation. After lipid fractionation, neither the aqueous nor the lipid fractions contained activity, suggesting that the factor may be a lipid complex. Culture supernatants from smokers' AM released significantly higher amounts of the factor than nonsmokers. In addition, high-molecular-weight elastase was present in bronchoalveolar lavage fluid (BALF) obtained from patients with pneumonia. Most of the in vivo high-molecular-weight elastase was lost after lipid extraction. In conclusion, macrophages release a factor or factors, probably lipid, which can interact with NE and inhibit its binding to human lung elastin without inhibiting elastase activity. This macrophage-derived factor may play a role in protecting the lung from NE by partitioning elastase into the airspace and thus protecting the interstitial connective tissue matrix from elastase degradation.

Evaluation of elastase and antielastase balance in patients with chronic bronchitis and pulmonary emphysema.

On the basis of the "protease-antiprotease imbalance" theory for the pathogenesis of pulmonary emphysema, we hypothesized that measurement of elastase burden and antielastase capacity in the alveolar space might correlate with emphysema. To evaluate this, the severity of emphysema, the elastase burden, and the elastase inhibitory capacity were estimated in 28 patients with chronic bronchitis and variable degrees of emphysema, none of whom had congenital deficiency of alpha-1-protease inhibitor, and all of whom underwent bronchoalveolar lavage. Emphysema was assessed by both computed tomography and diffusing capacity. To examine "elastase burden," elastase:alpha-1-protease inhibitor complex and free elastase activity in alveolar lavage fluids were measured. To evaluate "antielastase" capacity, elastase inhibiting capacity in alveolar lavage fluid was measured. Elastase burden correlated directly and antielastase capacity correlated inversely with emphysema. These data provide direct support for the "protease-antiprotease imbalance" theory of emphysema in a group of smokers without congenital deficiency of alpha-1-protease inhibitor.