Scott P Marlow RRT and James K Stoller MD MSc FAARC Introduction
Epidemiology of Cigarette Smoking
Nicotine Addiction
Smoking Cessation Interventions: Overview
Behavioral Interventions
Pharmacologic Interventions

Nicotine Replacement Therapy
Second-Line Smoking Cessation Drugs

Alternative Smoking Cessation Interventions
Combined Smoking Cessation Interventions
The Respiratory Therapist’s Role in Smoking Cessation

Cigarette smoking is the primary cause of chronic obstructive pulmonary disease, and smoking
cessation is the most effective means of stopping the progression of chronic obstructive pulmonary
disease. Worldwide, approximately a billion people smoke cigarettes and 80% reside in low-income
and middle-income countries. Though in the United States there has been a substantial decline in
cigarette smoking since 1964, when the Surgeon General’s report first reviewed smoking, smoking
remains widespread in the United States today (about 23% of the population in 2001). Nicotine is
addictive, but there are now effective drugs and behavioral interventions to assist people to over-
come the addiction. Available evidence shows that smoking cessation can be helped with counseling,
nicotine replacement, and bupropion. Less-studied interventions, including hypnosis, acupuncture,
aversive therapy, exercise, lobeline, anxiolytics, mecamylamine, opioid agonists, and silver acetate,
have assisted some people in smoking cessation, but none of those interventions has strong research
evidence of efficacy. To promote smoking cessation, physicians should discuss with their smoking
patients “relevance, risk, rewards, roadblocks, and repetition,” and with patients who are willing to
attempt to quit, physicians should use the 5-step system of “ask, advise, assess, assist, and arrange.”
An ideal smoking cessation program is individualized, accounting for the reasons the person smokes,
the environment in which smoking occurs, available resources to quit, and individual preferences
about how to quit. The clinician should bear in mind that quitting smoking can be very difficult, so
it is important to be patient and persistent in developing, implementing, and adjusting each pa-
tient’s smoking-cessation program. One of the most effective behavioral interventions is advice
from a health care professional; it seems not to matter whether the advice is from a doctor,
respiratory therapist, nurse, or other clinician, so smoking cessation should be encouraged by
multiple clinicians. However, since respiratory therapists interact with smokers frequently, we
believe it is particularly important for respiratory therapists to show leadership in implementing
smoking cessation.
Key words: chronic obstructive pulmonary disease, COPD, smoking cessation.
[Respir Care 2003;48(12):1238 –1254. 2003 Daedalus Enterprises] RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Fig. 1. Percentage of adult current, former, and never smokers. (Adapted from Reference 4.) Introduction
that smoking prevalence has increased to approximately1.1 billion people (1 in 3 adults), with 80% of these re- In reviewing smoking cessation the present report first siding in low- and middle-income countries.2 Smoking summarizes the epidemiology of smoking cessation and remains widespread in the United States, though trends evidence that smoking causes harm. We next review the show a substantial decline since 1964. Cigarette smoking physiology of nicotine and smoking addiction and the ben- was rare in the early 20th century, when the annual per efits of smoking cessation. Finally, we present a system- capita United States consumption rate was 54 cigarettes. In atic review of smoking cessation methods, with evidence- 1964 the per capita consumption was 4,345 cigarettes/ person/y, and that rate had declined to 2,261 cigarettes/ Although primary smoking prevention (eg, education, person/y in 1998.3 As shown in Figure 1, the prevalence of regulation of advertising) is recognized as an integral part current smokers peaked in 1965 at 42.4% and had declined of combating smoking, the reader is referred to other re- to 23.4% in 2001.4,5 This decline has been referred to by cent publications for comprehensive reviews of this issue, the Centers for Disease Control and Prevention as one of such as the Report of the Surgeon General released in the “Ten Great Public Health Achievements in the 20th Though the decline in smoking certainly represents a Epidemiology of Cigarette Smoking
favorable trend, smoking is, disturbingly, most commonamong groups of lower socioeconomic status. Figure 2 Smoking is a modern day epidemic that poses substan- shows that the prevalence of smoking is higher among tial health burden and cost. Worldwide estimates suggest individuals in families with combined incomes Ͻ $9,000(35% prevalence) than in families with a combined in-come exceeding $75,000 (19% prevalence).7 Figure 3 Scott P Marlow RRT and James K Stoller MD MSc FAARC are affili- shows that these trends are also evident by education ated with the Department of Pulmonary and Critical Care Medicine, TheCleveland Clinic Foundation, Cleveland, Ohio.
level, with a higher frequency of smoking among thosewho have not completed high school (33%) than among Scott P Marlow RRT presented a version of this report at the 32nd those who have completed 4 years of college (14%).7 RESPIRATORY CARE Journal Conference, Chronic Obstructive PulmonaryDisease: Translating New Understanding Into Improved Patient Care, For example, in 1965, 51.9% of men and 33.9% of held July 11–13, 2003, in Los Cabos, Mexico.
women reported smoking, whereas in 2000 25.7% ofmen and 21.0% of women reported smoking.4,8 Smok- Correspondence: Scott P Marlow RRT, Department of Pulmonary and ing rates among high school students continue to exceed Critical Care Medicine, A90, The Cleveland Clinic Foundation, 9500Euclid Avenue, Cleveland OH 44195. E-mail:
the national rate for adults, having increased during the RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Fig. 2. Percentage of people Ն 18 years old who reported smoking in the past month, by combinedtotal family income, 1999 –2000. (Adapted from Reference 7.) Fig. 3. Percentage of people Ն 18 years old who reported smoking in the past month, by educationlevel, 1999 –2000. (Adapted from Reference 7.) 1990s to a peak of 36.4% in 1997 and since decreased smoking.10 Smoking also increases the risk of death in to 28.5% in 2001 (29.2% among boys versus 27.7% many illnesses. Table 1 shows the relative risk of smok- ing-attributable morbidity and mortality from various con- Because smoking is common, the economic impact is ditions, largely including respiratory, cardiovascular, and profound. In 1998 the direct medical cost of smoking neoplastic diseases.11 Table 2 shows estimates of the num- was estimated to be $75.5 billion, with productivity ber of deaths attributed to smoking. Notably, the 35,053 losses estimated at $82 billion and smoking-related neo- second-hand-smoke-related deaths are not included in those natal costs estimated at $366 million.10 When all ex- penses are combined, they represent a total of $3,391 Smoking confers a risk of serious illness, and smoking per smoker per year, which amounts to approximately cessation offers health benefits, which is evident in Table 8% of all annual health care expenditures in the United 1: former smokers have lower relative risk of death in all disease categories.11 For example, compared to never- The morbidity and mortality attributed to smoking are smokers, men who are current or former smokers have a also substantial. For example, between 1995 and 1999 higher relative risk of death from cancer of the trachea, approximately 440,000 deaths annually were attributed to lung, or bronchus (23.26 times higher in current smokers RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Relative Risk of Death: Current Smokers Versus Former decline (30.2 mL/y among men and 21.5 mL/y amongwomen) than active smokers (66 mL/y among men and and 8.7 times higher in former smokers).11 The 1990 re- port of the United States Surgeon General on the healthbenefits of smoking cessation concluded that people who Nicotine Addiction
quit smoking before the age of 50 have half the risk ofdying in the next 15 years, compared to continuing smok- Concepts of nicotine addiction have evolved over the 40 ers.12 Smokers have twice the risk of dying of coronary years since the Surgeon General’s report first reviewed heart disease or stroke, and the risk of coronary heart smoking. For example, in 1964 the Report of the Advisory disease diminishes by half in the first year after cessa- Committee to the Surgeon General classified tobacco as tion.12 After 5–15 years of abstinence from smoking, the “an habituation rather than an addiction” and that prevent- risk of both stroke and heart disease drops to the level of ing the psychogenic drive of the habit was more important Another benefit of quitting smoking is a slowing of the Concepts about the physiology of nicotine addiction have accelerated rate of lung function decline that occurs in since evolved. For example, in 1979 the Report of the Sur- susceptible smokers. For example, the Lung Health Study geon General cited nicotine as “a powerful addictive drug.”16 randomized and followed 5,887 smokers with early chronic And in 1988 the Report of the Surgeon General on The obstructive pulmonary disease in one of 3 arms: usual Consequences of Smoking: Nicotine Addiction17 concluded: care; aggressive smoking intervention with ipratropium • Cigarettes and other forms of tobacco are addicting.
bromide via metered-dose inhaler; and smoking inter-vention with placebo inhaler.13 Long-term follow-up of • Nicotine is the drug in tobacco that causes addiction.
the Lung Health Study cohort found that 11-year sus-tained ex-smokers experienced a lower rate of FEV • Pharmacologic and behavioral processes that determine RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 tobacco addiction are similar to those that determine addiction to drugs such as heroine and cocaine.
Though debated, the physiology of nicotine addiction Individual counseling by nurse or other nonphysician has recently been characterized as biphasic, in that it stim- ulates the pleasure response to the brain, and when taken for longer periods, also creates a relaxed state. As with cocaine, amphetamines, and morphine, addiction to nico- tine is believed to result from increased release of dopa- First-Line: Nicotine replacement therapy (transdermal patch, gum, mine in the region of nucleus acumbens.18–20 Nicotinic acetylcholine receptors are located throughout the central nervous system, but the neurons located in the ventral tegmental area increase activity with nicotine administra- tion and concurrently activate the increased release of do- pamine into the nucleus acumbens.18,21,22 Corrigall et al23,24 found that self-administered nicotine in vivo is reduced by lesions to these pathways or by a nicotinic antagonist in- fused into the ventral tegmental area.
As with all addictions, nicotine withdrawal elicits a num- ber of clinical consequences, avoidance of which promotessmoking. Nicotine withdrawal symptoms are time-limited,can last for several weeks, and include physical symptoms mends discussing the 5 “R”s: relevance, risk, rewards, of irritability, anxiety, depression, difficulty concentrating, roadblocks, and repetition (Table 5).28 weight gain, restlessness, and impatience.25 The intensity In summarizing the literature and offering recommen- of these withdrawal symptoms can be related to the level dations, we first present evidence from the Cochrane Col- of nicotine dependence. A common measuring tool is the laboration reviews of smoking cessation interventions, Fagerstrom Test for Nicotine Dependence, which rates which considered studies up to 2002. We also review data addiction on a 0 –10 scale. The test places the most em- presented in the USDHHS Clinical Practice Guideline for phasis on the length of time after waking before the first Treating Tobacco Use and Dependence, originally pub- cigarette and the number of cigarettes smoked per day.26 lished in 1996 and updated in 2000.28 To identify the most As evidence of the power of nicotine addiction, estimates recent available data, we searched MEDLINE for research suggest that 70% of smokers would like to quit, that ap- conducted in 1999 through June 2003, using the search proximately 41% try to quit each year, but that only 4.7% terms “smoking cessation” and “tobacco.” Our ratings of the strength of the available evidence are based on thesystem adopted by Fiore et al (Table 6).28 To assess the Smoking Cessation Interventions: Overview
efficacy of the available interventions, we largely restrictedthe analysis to studies that compared interventions to no- The spectrum of available smoking cessation interven- tions can be classified into behavioral, pharmacologic, and Overall, the available literature supports the efficacy of alternative methods (Table 3). Behavioral interventions behavioral counseling, nicotine replacement, and bupro- include physician advice, individual counseling, group pion in smoking cessation (Table 7). Clinicians should counseling, and telephone counseling. Pharmacologic in- know that an ideal smoking cessation program is individ- terventions include nicotine replacement therapy, sus- ualized, accounting for the person’s reasons to smoke, the tained-release bupropion, clonidine, and nortriptyline. Fi- environment in which smoking occurs, available resources nally, alternative (and less-studied) interventions include to quit, and individual preferences about how to quit.
hypnosis, acupuncture, aversive therapy, exercise, lobe-line, anxiolytics, mecamylamine, opioid agonists, and sil-ver acetate.
Behavioral Interventions
Smoking cessation should begin with assessing the smok- er’s desire to quit. Table 4 describes the 5 “A”s: ask, Behavioral interventions differ according to who is per- advise, assess, assist, and arrange. For smokers unwilling forming the intervention: the physician, nurse, nonphysi- to attempt quitting, the United States Department of Health cian clinician, telephone counselor, or patient self-help.
and Human Services (USDHHS) Clinical Practice Guide- The present analysis compares cessation rates for each line for Treating Tobacco Use and Dependence recom- behavioral intervention to a control group with no (or RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Smoking Cessation Intervention: The 5 “A”s If patient is willing to quit, assess potential intensity of support If patient is not willing to quit, see Table 5 Enlist support and understanding of family and friends Anticipate challenges, especially first few weeks Provide practical counseling (eg, problem-solving and skills training) Review relationship of alcohol to tobacco use Point out that having other smokers in the home will increase the difficulty Provide a supportive clinical environment Help obtain extra treatment social support Help obtain patient-environment support from family, friends, and coworkers Sources: organizations that promote smoking cessation, including federal, state, and nonprofit organizations Type: Are the materials appropriate for the patient, in relation to culture, race, education, and age? Location: Are the materials readily available? Timing: Follow up within the first week of the quit date, and follow up again within the first month Remind that lapse is a learning experience Consider increased intervention when necessary minimal) intervention. Limitations of available studies 1.23–1.68 and OR 2.66, 95% CI 2.06 –3.45).29 In agree- are that behavioral interventions are supplied in a vari- ment with the Cochrane Collaboration reviews, findings ety of environments or with other (confounding) inter- from the USDHHS Clinical Practice Guideline review of ventions. For example, a study may provide physician available studies showed that brief (ie, 2–5 min) physician and group advice for smoking cessation along with nic- advice was associated with a 2–3% higher rate of smoking otine gum, as in the Lung Health Study,13 thereby con- cessation (OR 1.3, 95% CI 1.1–1.6).28 Denny et al30 re- founding direct comparisons of the nicotine and the ported that 70% of smokers who had seen their doctor within the last 12 months received advice to quit smoking.
Among the simplest of behavioral interventions, even However impressive that 70% figure appears, the 30% of brief, direct physician advice to quit smoking is effective.
smokers who did not receive quit-smoking advice is ap- For example, in the Cochrane Library review of 16 stud- proximately 1,915,000 smokers in the 10-state survey ar- ies, Silagy et al29 found that brief physician advice in- ea—a tremendous number of missed opportunities to en- creased the absolute rate of abstinence by 2.5% over usual courage smoking cessation.29 If only 2.3–2.5% of those care (odds ratio [OR] 1.69, 95% confidence interval [CI] individuals had quit after brief advice, an additional 1.45–1.98). Furthermore, the rate of smoking abstinence 44,000 – 48,000 smokers may have quit.
increased when the intensity of advice was increased and With regard to counseling by nurses, Rice and Stead31 when follow-up visits were included (OR 1.44, 95% CI reported small increases in smoking cessation rate follow- RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Enhancing Motivation to Quit Tobacco: The 5 “R”s Why would quitting be personally relevant? Consider family, children, health concerns, previous experience, work Clinician should ask patient to identify negative consequences of smoking: Emphasize that low-tar, low-nicotine, and other forms of tobacco do not eliminate risk Cancer: lung, larynx, oral cavity, pharynx, esophagus, pancreas, bladder, cervix Increased risk of lung cancer and heart disease in spouse Higher rate of smoking among children of tobacco users Increased risk of low birth weight, sudden infant death syndrome, asthma, middle ear disease, and respiratory infections Ask patient to identify potential rewards and highlight those most relevant to the patient Home, clothing, and breath will smell better Ask patient to identify barriers to quitting and address elements of treatment that can assist Repeat every time an unmotivated patient visits the clinic setting. Tobacco users who have failed in previous quit attempts should be told that most people make repeated quit attempts before they are successful.
ing nurse advice (OR 1.5, CI 1.29 –1.73). Pooled results of and should be encouraged (OR 1.7, CI 1.3–2.1), and no 16 trials in a Cochrane Collaboration review showed that specific clinician type demonstrated superiority, so smok- receipt of nursing advice was associated with a cessation ing cessation should be encouraged by multiple health care rate of 13.3%, compared with the control group rate of providers. The strength of evidence supporting these rec- 12.1%.31 A review of 29 studies by Fiore et al28 offered 2 ommendations is rated A (see Table 7).
conclusions: smoking cessation intervention by nonphysi- In a Cochrane Library review of 15 studies Lancaster cians increases abstinence, compared to control groups, and Stead32 compared individual smoking intervention by RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Strength of Evidence Categories for Recommendations junct to face-to-face intervention and can be provided pro-actively or reactively (eg, telephone help lines). Meta- analyses by Stead et al34 and Fiore et al28 found a similar magnitude of effect. Telephone counseling, compared tominimal or no intervention, conferred an approximately Multiple well designed randomized clinical 2% absolute rise in the cessation rate (OR 1.56, CI 1.38 – trials, directly relevant to therecommendation, that yield a consistent 1.77 and OR 1.2, CI 1.1–1.4, respectively).
Telephone help lines have been harder to assess. How- Some evidence from randomized clinical trials ever, in a comparison of smokers who received mailed self-help material to those who received self-help material and notification of a help line, Ossip-Klein et al35 reported instance, few randomized trials exist, the a 2.6% absolute increase in abstinence among those who trials that exist are somewhat inconsistent, orthe trials are not directly relevant to the knew about the help line. Evidence that telephone contact is effective in supporting smoking cessation is rated A (see Reserved for important clinical situations where the panel achieved consensus on the Self-help information is marginally beneficial for in- recommendation in the absence of relevant creasing smoking cessation. Examples of self-help mate- rials include booklets, leaflets, brochures, videotapes, com- pact discs, help lines, and various computer and Internetinterventions. For example, Lancaster and Stead36 con-firmed benefit in a review of 12 studies that compared a counselor trained in smoking cessation to no intervention self-help cessation materials to no intervention; self-help and found that counseling by an individual improved the materials slightly improved cessation rates (OR 1.24, CI abstinence rate by 4% (OR 1.62, CI 1.35–1.94). The 1.07–1.45). Enhanced or tailored self-help material was USDHHS Clinical Practice Guideline used a different ap- associated with better cessation rate than standard self- proach; Fiore et al28 assessed the effectiveness of individ- help material (OR 1.36, 1.13–1.64), but the addition of ual counseling by pooling 58 studies involving physicians, self-help material to counseling did not increase cessation nurses, and nonphysicians. They reported an overall 6% rate, nor did the use of multiple self-help interventions, absolute increase in the abstinence rate (OR 1.7, CI 1.4 – such as multiple mailings.36 Fiore et al28 reported only a 2.0). In summary, available meta-analyses and key indi- minimally better cessation rate with self-help materials vidual studies establish the efficacy of individual counsel- than with no intervention (OR 1.2 1.02–1.3). Overall, ing from a physician, nurse, or nonphysician in increasing though the effectiveness was nominal, self-help also achieved evidence level A (see Table 7).28,36 Other reasons Available studies also suggest that group counseling is that self-help, despite its small impact, should be included effective in promoting smoking cessation.28,33 Examples in smoking programs are increased population awareness, of group formats include the American Lung Associa- low expense, and the opportunity to customize the mes- tion’s “Freedom from Smoking” program and the Amer- ican Cancer Society’s “Fresh Start” program. In a Co- Another lesson from available meta-analyses of behav- chrane Library review of 54 trials of various group ioral interventions is that adding formats confers incre- intervention formats, Stead and Lancaster33 found a 10% mental effectiveness.28 As shown in Figure 4, combining higher abstinence rate in the 6 trials that compared group up to 3– 4 formats (eg, self-help with individual counsel- intervention to no intervention (OR 2.19, CI 1.42–3.37). In ing, or individual counseling and telephone counseling) a concordant analysis of pooled studies, the USDHHS may increase the absolute cessation rate by 12%.28 study reported an overall 3% absolute rise in the absti- Also, increasing the intensity of interventions enhances nence rate after group counseling (OR 1.3, CI 1.1–1.6).28 smoking cessation rates (Figures 5–7). Fiore et al28 found The difference in cessation rates (10% vs 3%) between the a strongly dose-related increase in cessation rate as the 2 reviews may reflect the fact that the USDHHS review number of separate interventions increased. Factors in- did not directly compare group intervention to no inter- creasing effectiveness include the duration of each indi- vention, but rather pooled 58 studies and used a variety of vidual session, the total time spent in all sessions, and the comparators.28 Overall, the evidence supporting the effi- number of sessions. With minimal (Ͻ 3 min) counseling, cacy of group counseling satisfies level A (see Table 7).
the cessation rate was 13.4%; with low-intensity counsel- Telephone counseling is simple and permits reaching a ing (3–10 min), the rate was 16.0%; with high-intensity large number of people at critical cessation moments. Tele- counseling (Ͼ 10 min), the rate was 22.1%.28 Total con- phone counseling can be provided in lieu of or as an ad- tact time ranged from zero to Ͼ 300 min, with no en- RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Summary of Behavioral and Pharmacologic Smoking Cessation Interventions Physician advice is effective and should be routinely .
Marginal but measurable benefit from intervention.
Improvement increased with pooled USDHHS data.
Better margin of improvement with the Cochrane Collaboration data because of looking only at group versus no intervention. If group versus self-help were included, effect size would diminish.
Individual counseling Health care specialist Health care specialist counseling improves cessation and Proactive telephone calls are successful for improving Marginal effectiveness but an important adjunct to Evidence clear that nicotine gum improves success of smoking cessation. Increase dose to 4 mg for highlydependent smokers (odds ratio 2.18, 95% confidenceinterval 1.48–3.7) Evidence supports nicotine patch for improved smoking abstinence. No difference found between 16-h and Improvement in smoking cessation rate. Limited number of studies compared to other NRT interventions.
Evidence supports inhaler use. Limited number of studies compared to other NRT interventions.
Bupropion (300 mg/d 150 mg/d for 3 d, then Evidence is strong that bupropion increases cessation rate. May also prove effective with NRT.
*When possible, studies compare intervention to no or minimal intervention.
†Absolute increase in smoking cessation rate (ie, intervention vs control)‡Italicized data is from the Cochrane Collaboration reviews.
USDHHS ϭ United States Department of Health and Human ServicesNRT ϭ nicotine replacement therapy(Adapted from References 28, 29, 31–34, 36, 38, 39.) hanced effectiveness beyond 90 min of counseling.28 A a quit rate of 12.4%, whereas those with Ն 8 sessions had review of the impact of the number of counseling sessions a quit rate of 24.7% (see Fig. 7).28 In the Cochrane Col- found that the greater the number of sessions, the greater laboration review, the intensity of interventions was de- the chance for cessation. Programs with 0 –1 sessions had fined differently. For example, nursing interventions were RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Fig. 4. Meta-analysis of estimated cigarette-smoking abstinence rates relative to number of smokingcessation formats used. The formats included self-help, proactive counseling, group counseling, andindividual counseling (n ϭ 54). (Adapted from Reference 28.) Fig. 5. Estimated cigarette-smoking abstinence rates relative to the duration of the individual coun-seling session (n ϭ 43 studies). (Adapted from Reference 28.) Fig. 6. Meta-analysis of estimated cigarette-smoking abstinence rates relative to the total amount ofcontact time (n ϭ 35 studies). (Adapted from Reference 28.) considered low intensity if Յ 10 min and high intensity with one follow-up.28 Based on these definitions, increased if Ͼ 10 min with a follow-up appointment,30 whereas phy- intensity of nursing intervention did not significantly in- sician interventions were defined as minimal intensity if Յ crease cessation rates (low intensity OR 1.67, CI 1.14 – 20 min with one follow-up visit and intensive if Ͼ 20 min 2.45, high intensity OR 1.47, CI 1.26 –1.72),30 whereas RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Fig. 7. Estimated cigarette-smoking abstinence rates relative to the number of counseling sessions(n ϭ 43 studies). (Adapted from Reference 28.) increasing intensity of physician intervention did modestly cations assist in smoking cessation, and some are available increase the smoking cessation rate (OR 1.67, CI 1.45– over-the-counter, caution is advised not to overestimate 1.98).28 In contrast, in an analysis of 3 trials involving their efficacy and undermine the power of will in quitting.
individual counseling with various intensities, Lancaster Prochazka42 cautioned against considering cessation med- and Stead32 did not find evidence to suggest that increased icines a “magic bullet,” but instead counsels against un- intensity of individual counseling increased cessation rate realistic expectations and advises a detailed understanding A more recent study by Simon et al37 randomized 228 patients to either low- or high-intensity intervention, with Nicotine Replacement Therapy
all receiving nicotine replacement therapy (NRT) via patch.
The 1-year abstinence rate was significantly higher in thehigher-intensity counseling group (29% vs 20%, OR 1.6, Nicotine replacement therapy is supplied in several forms: patch, gum (polacrilex), nasal spray, inhaler, and Overall, evidence suggesting that increased intensity of lozenges. Favorable features of NRT are that it is readily counseling enhances abstinence achieves evidence level A available, easy to use, relatively inexpensive, and effec- (see Table 7). Limitations of counseling include the cost of counseling sessions, limited availability to large popula- Nicotine patch is applied transdermally and nicotine is tions, and the time-intensiveness of the interventions for absorbed through the skin. Nicotine patches are available over-the-counter and come in doses of 7 mg, 14 mg, or 21mg (generic or Nicoderm CQ patch) or 5 mg, 10 mg, or 15 Pharmacologic Interventions
A Cochrane Library review by Silagy et al38 of 96 trials The first-line pharmacologic interventions are NRT and comparing all forms of NRT to controls found that absti- bupropion (an antidepressant). The 2 second-line drugs are nence rates were 7% better with NRT (OR 1.74, CI 1.64 – clonidine (an antihypertensive) and nortriptyline (a tricy- 1.86). Nicotine patch was associated with a 6% better clic antidepressant). Available guidelines suggest that NRT, abstinence rate than controls (OR 1.74, CI 1.57–1.93).
antidepressants, and certain antihypertensives effectively Similar findings were reported by the USDHHS Clinical increase smoking cessation rates.28,38–40 Table 8 summa- Practice Guideline,28 which showed an increased quit rate rizes the 5 first-line Food and Drug Administration (FDA) of 7.7%, based on review of 26 studies (OR 1.9, CI 1.7– approved smoking cessation medications.
The mechanisms of drugs to aid smoking cessation dif- Regarding the duration of patch use, the 16-hour and fer. NRT offsets the craving for nicotine. Although the 24-hour patches appear to confer similar benefit.38 Still, precise mechanism is unknown, bupropion is thought to the long-term effectiveness of NRT has decreased since blunt the impact of nicotine withdrawal in smoking ces- NRT became available over-the-counter in 1996, possibly sation by diminishing the uptake of dopamine and norepi- because advice from health care providers diminished as nephrine, thus decreasing cravings.41 Though these medi- the need for a prescription to receive the patch vanished.43 RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 First-Line Medications for Smoking Cessation nicotine achievedwithin 20–30 min.
*Cost data are from average price from 3–4 national pharmacies(Adapted from Reference 28 and manufacturers’ information.) Overall, the evidence supporting nicotine patches warrants Murray et al44 found no adverse cardiovascular effects from nicotine gum, even among those who smoked and Nicotine gum (polacrilex) has also been available over- continued to chew gum. Still, approximately 25% of nic- the-counter since 1996 and is also effective in promoting otine gum users experienced one or more adverse effects, smoking cessation.28,38 Nicotine gum is available in 2-mg including mouth irritation, headache, and indigestion.44 The and 4-mg doses (Nicorette, Nicorette Mint, or generic).
evidence supporting the efficacy of nicotine gum to in- Nicotine gum allows absorption of nicotine through the crease smoking abstinence is substantial and is rated A Regarding efficacy, a Cochrane review of 51 studies by Nicotine nasal spray (Nicotrol NS) provides the most Silagy et al38 found that nicotine gum increased the effec- rapid nicotine administration of all the NRTs, with peak tiveness of cessation attempts by 8%, compared to controls effects within 5–10 min.28,38 Nicotine nasal spray must be (OR 1.66, CI 1.52–1.81). Similarly, in a meta-analysis of administered correctly for maximum effectiveness. One squirt 13 studies Fiore et al28 estimated a 6.6% better cessation (0.5 mg) into each nostril delivers a total dose of 1 mg.
rate with nicotine gum (OR 1.5, CI 1.3–1.8). Patients who The dose should not be inhaled or sniffed and should be are highly nicotine dependent (who smoke Ͼ 25 ciga- delivered with the head slightly tilted.28 Adverse effects rettes/d) or those who have failed the 2-mg dose should are common, with 94% of users reporting some nasal ir- use the 4-mg dose, but should use no more than 24 pieces ritation, which persists in 81% of users for up to 3 weeks per day.28,38 In a study of 3,094 patients receiving nicotine after initiation.28 Attractive features of nicotine spray are gum in both treatment arms of the Lung Health Study, that it is rapidly absorbed and can reduce nicotine craving, RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 offers a substitute for the cues of smoking, and can be Regarding combined NRT use, the Cochrane Collabo- administered as needed, up to 40 doses per day. Disad- ration analysis38 pooled 5 studies of combined nicotine vantages are the adverse effects, which include the social replacement therapies and observed a small benefit with stigma of squirting a spray into one’s nostrils, and that the combination NRT (OR 1.55, CI 1.17–2.05). A recent study drug is contraindicated in patients with reactive airway by Hand et al48 found no benefit from combining coun- disease.28 The Cochrane Library analysis by Silagy et al38 seling, nicotine patch, and nicotine inhaler, compared to of 4 studies reported a 12% absolute increase in the rate of counseling alone (15% and 14% 1-year cessation rates, smoking cessation (OR 2.28, 1.61–3.20). The USDHSS respectively). Conversely, Blondal et al49 found a signifi- review of 3 studies found a higher quit rate: 16.6%.28 The cantly higher 1-year cessation rate with nicotine patch and difference in those cessation rate estimates may be due to nasal spray (28% cessation rate) compared to nicotine patch exclusion in one meta-analysis of the trial by Hjalmarson alone (11% cessation rate). Overall, the evidence is too et al,45 which found a 12-month cessation rate of 12%.
sparse at present to allow specific recommendations on Evidence supporting the efficacy of nicotine nasal spray is Regarding the dose responsiveness of NRT, the Co- Nicotine inhaler (Nicotrol inhaler) is the fifth FDA- chrane Collaboration analysis pooled 6 studies that used approved NRT. The inhaler cartridge contains 10 mg of higher doses of nicotine patch, but found only marginal nicotine that can supply 4 mg of nicotine (2 mg are sys- evidence of additive benefit (OR 1.2, CI 1.03–1.42).38 temically available) over 80 inhalations (suggested to take In summary, all forms of NRT recommended by the place over 20 min; see Table 8). Advantages of the nico- FDA as first-line drugs are effective for smoking cessa-tion. At this time there is insufficient evidence to recom- tine inhaler include that it mimics smoking (albeit with mend one form of NRT over another. Patients with lesser rapid puffing), it delivers nicotine rapidly, and it has min- dependence on nicotine (ie, Յ 10 cigarettes/d) may con- imal side effects. Disadvantages are that the inhaler is the sider lower-dose or alternative interventions.28 Given the most expensive form of NRT (average wholesale price lack of clear-cut evidence supporting one NRT form over $1.08 per cartridge) and requires more intense puffing than another, patient and physician preference should play a smoking. The Cochrane Library meta-analysis of 4 studies large role in choosing a specific NRT drug.
demonstrated an absolute 8% increase in the cessation rateover placebo inhalers (OR 2.09, CI 1.49 –3.04).38 The meta- Bupropion
analysis by Fiore et al28 reported a 12.3% increase in ces-sation rates with nicotine inhaler (OR 2.5, CI 1.7–3.6).
The antidepressant bupropion is the first non-NRT in- Adverse effects reported by Hjalmarson et al46 were in- tervention recommended by the FDA as a first-line drug creased cough (28%) and irritation of the mouth or throat for smoking cessation.28,39,50 The Cochrane Collaboration (15%). With caution, because of the small number of stud- analysis39 of 7 trials found 10% better cessation among ies available, the evidence regarding nicotine inhalers also those who received bupropion than among control subjects (OR 2.54, CI 1.9 –3.41). The USDHHS Clinical Practice Nicotine lozenge/tablet (Commit) is not an FDA-ap- Guideline also found better cessation rate with bupropion: proved first-line medication but does show promise. Nic- 13.2% higher than controls (OR 2.1, CI 1.5–3.0).28 With otine lozenges (polacrilex) come in 2-mg and 4-mg doses.
regard to combined bupropion and NRT Jorenby et al51 They are easy to use, have minimal adverse effects (heart- found significantly better cessation rates with the combi- burn, hiccups, and nausea), and provide 25% more nico- nation of NRT and bupropion than with nicotine patch tine than similar doses of nicotine gum.47 In a large, ran- alone (OR 2.07, CI 1.22–3.53 and 2.65 CI 1.58 – 4.45, domized trial (n ϭ 1,818 smokers) concurrently conducted in the United States and England, Shiffman et al47 found Another observed benefit of bupropion is its ability to an increased abstinence rate in high-dependence smokers blunt the weight gain that may accompany smoking ces- (receiving the 4-mg dose) of 8.7% over placebo and in sation.50 For example, Jorenby et al51 reported that com- low-dependence smokers (receiving the 2-mg dose) of 8.2% bined bupropion and nicotine patch recipients experienced over placebo. Though there are few studies reviewing nic- a lower mean weight gain than did nonrecipients (ie, 2.1kg vs 1.1 kg at 7 wk).
otine lozenges or tablets, these medications are promising.
Overall, the evidence regarding bupropion for smoking Despite the substantial body of supportive evidence, there is continuing uncertainty about some aspects of NRT.
For example, does the use of multiple forms of NRT en- Second-Line Smoking Cessation Drugs
hance effectiveness? Is there a dose-response beyond theusual recommended doses? Do nicotine lozenges or tablets Clonidine is an antihypertensive medication that is pro- vided orally or transdermally (Catapres). In a meta-anal- RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 ysis of 6 studies, Gourlay et al40 found that clonidine in- be done in the presence of a health care professional. Our creased smoking cessation rate by 11% (OR 1.89, CI 1.30 – view is that currently the evidence is insufficient to sup- 2.74). Similarly, Fiore et al28 analyzed 5 studies and reported a similar enhanced abstinence rate: 11.7% (OR 1.4 –3.2).
The 4 available meta-analyses of alternative interven- Unfortunately, clonidine can produce important adverse tions fail to support efficacy in aiding smoking cessation.
events, such as dry mouth, dizziness, sedation, and pos- For example, 2 available meta-analyses of acupuncture tural hypotension, which may discourage its use.28,40 failed to show efficacy (OR 1.08, CI 0.77–1.52 and OR Overall, although the evidence supporting clonidine for 1.1, CI 0.7–1.6).28,54 A meta-analysis and a recent study of smoking cessation achieves an A rating, the adverse effect exercise intervention with 299 smokers showed no in- profile relegates it to second-line status. Clonidine has not creased rate of smoking cessation.55,56 Similarly, neither a been approved by the FDA for smoking cessation, but has review of available studies nor an unpublished pharma- found use as a salvage regimen with individuals who have ceutical study of lobeline, a partial nicotine agonist, showed Finally, nortriptyline is a tricyclic antidepressant that The Cochrane Collaboration review58 of trials of anx- has been used to assist smoking cessation.28,39 Results of 3 iolytics (3 trials of buspirone, 1 trial of diazepam, 1 trial of available studies demonstrate a 12% absolute improve- meprobamate, and 1 trial of ␤ blockers) concluded that ment in cessation rates over controls (OR 1.73, 1.73– none of the trials supported efficacy for improving smok- 4.44).52 Also, the USDHHS Clinical Practice Guideline28 ing cessation. Adverse effects and the availability of other review of 2 studies noted 18.4% improvement over control interventions discourage the use of any of these drugs.
cessation rates (OR 3.2, 1.8 –2.7).
In a review of 2 studies of the nicotine antagonist Overall, the limited number of trials and the adverse mecamylamine, Lancaster et al59 found that mecamylamine effects of nortriptyline make it a second-line intervention.
combined with nicotine patch produced better cessation Evidence supporting the use of nortriptyline in smoking rates than nicotine patch alone. However, lack of any long- term studies precludes current endorsement ofmecamylamine. Similarly, the USDHHS Clinical Practice Alternative Smoking Cessation Interventions
Guideline report did not advocate mecamylamine.28 Silver acetate is a pharmaceutical aversive therapy that Alternative behavioral interventions for smoking cessa- leaves an unpleasant taste in the mouth when combined tion include hypnotherapy, aversive therapies, acupunc- with cigarettes.60 The Cochrane Collaboration reported 2 ture, and exercise. Other medications that have been tried studies comparing silver acetate to placebo and found no for smoking cessation include lobeline, anxiolytics, measurable improvement in cessation rates (OR 1.05, CI mecamylamine, opioid agonists, and silver acetate. There 0.63–1.73). The USDHSS Clinical Practice Guidelines re- is less supportive research for these interventions than for view also found no benefit from silver acetate.28 In light of current available information, we do not recommend silver Regarding hypnotherapy, a review of 9 trials by Abbot et al52 did not find efficacy for smoking cessation. Chal-lenges to validating hypnotherapy include the small size of Combined Smoking Cessation Interventions
most of the trials and the confounding issue of separatingthe impact of time spent with the therapist from the hyp- Many studies establish the superiority of combined in- nosis itself.52 The USDHHS Clinical Practice Guideline terventions over individual smoking cessation strategies.
For example, in the largest available trial with chronic Aversive therapies were mainly used before current in- obstructive pulmonary disease patients, the Lung Health terventions became available; they include rapid smoking, Study (n ϭ 5,887 subjects) found that the group that re- smoke holding, rapid puffing, excessive smoking, and elec- ceived nicotine gum and counseling (physician counseling tric shock. The theory underlying aversive therapy is that and group counseling) had a better smoking cessation rate linking a negative sensation to smoking will encourage (22% at 11 years) than the usual-care group (6%).14 cessation. Hajek and Stead53 reviewed aversive smoking Regarding the additive effect of bupropion, Tashkin et therapies and found rapid smoking to be the most effec- al61 compared individual counseling plus proactive tele- tive. However, they concluded that there was insufficient phone calls plus bupropion to individual counseling plus evidence to support the effectiveness of aversive therapy.
proactive telephone calls plus placebo, and found that the In contrast, the USDHHS Clinical Practice Guideline re- bupropion group had a higher cessation rate than the con- ported that rapid smoking improved abstinence rates by trol group (16% versus 9% at 26 wk, OR 1.74, CI 1.01– 8% over controls (OR 2.0, CI 1.1–3.5).28 One important 3.0). Overall, given the effectiveness of individual strate- limitation is that, if attempted, rapid smoking should only gies and the weight of evidence supporting combined RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 approaches, current practice often offers both counseling interventions. Also, the paucity of available literature in- and drug interventions to assist smoking cessation.
vites further study of RTs’ effectiveness in smoking ces-sation.
As with all medications, cost is an important issue for smoking cessation therapy. At the same time, the cost of Because smoking remains common and is associated therapy must be offset against the cost associated with with substantial morbidity, mortality, and costs, aggressive buying cigarettes and the personal and societal costs of efforts to eradicate smoking are justified. Of the available sequelae of smoking. Currently, the average cost of a pack methods to effect smoking cessation, level A evidence of cigarettes is $3.15.62 Thus, the yearly cost of a 1 pack/ supports the efficacy of various behavioral and pharma- day habit is $1,149.75. An estimate of the cost of medical cologic interventions: counseling by various health care care associated with each pack of cigarettes sold is $3.45.10 providers, nicotine replacement therapy, and bupropion. In Additionally, the estimated cost of lost productivity due to addition, combination therapy (eg, counseling plus nico- morbidity and mortality from smoking add $3.73 as the tine replacement therapy, nicotine plus bupropion) seems societal cost per pack.10 Thus, the aggregate cost per pack to confer additional benefit. Still, disappointing longer- of cigarettes is $7.18. In this context the daily cost of term abstinence rates for the strongest available studies (ie, nicotine patches ($3.57) looks quite favorable. Table 8 Ͻ 25%) establish the need for continued investigation of shows price estimates for the available medications.
smoking cessation strategies. Finally, we believe that RTscan and should play key roles in smoking cessation pro- The Respiratory Therapist’s Role
grams and that this subject warrants further study.
in Smoking Cessation
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bacco use. I think it’s called price elas- 2. Lewitt EM, Coate D. The potential for using excise taxes to reduce smoking. J Health Econ MacIntyre:
dicate that as you raise cigarette taxes, MacIntyre:
their cigarettes by the carton, they’re ing the tax increase is the smugglers.
there. We chose to limit this report just have a very low tax and they haulcigarettes off to New York and sell Mannino:
1. Ross H, Chaloupka FJ. The effect of ciga- rette prices on youth smoking. Health Econ RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 Heffner:
because that’s all we had back then.
solute reduction rates; they’re not per- that might justify the intervention.
1. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Heffner:
vices’ smoking cessation indicators.
1. Pierson DJ. The future of respiratory care.
Davis A, Boehlecke B. Attitudes of respira- tory care practitioners and students regard-ing pulmonary prevention. Chest 1998; Mannino:
ple don’t smoke in the first place.
is added to the baseline cessation rate.
ers receive an “attaboy”-type compli- RESPIRATORY CARE • DECEMBER 2003 VOL 48 NO 12 tioned prices; typically, increased taxes sation, but in hospitals they don’t do a sibly, some of those external factors are Mannino:
there are 3 things that have worked, both available in our health care system.
from starting. One is to increase the price everyone to get involved in their com-munities and support ordinances to limit Enright:
tucky, in the heart of tobacco country, is public places. Yet in Europe it’s still is hard-hitting anti-smoking advertising: have been pretty good models for that.
What we know doesn’t work are those not to sell cigarettes to kids. That just Wedzicha:
after the other, and it’s usually a mat- ing to obtain. They don’t really work.
certainly by far the major interven- Operating Officer, American Association forRespiratory Care, Dallas, Texas.


Bulgarian Chemistry and Industry, 74, No 4 ( 2003 ) 118–119 CONTENTS FOR VOLUME 74 G. VISSOKOV: Nanoscience and nanotechnology research directions in chemical industries . 1H.-J. BART, D. KAMENSKI: Modelling the kinetics of the reactive solvent extraction of zinc withZH. BALGARANOVA, L. PHILLIPOV: Stabilisation of aniline by addition of hydrazine .19G. N. VASSILEV: Synthesis, chemical

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