More than one-third of patients with chronic obstructive pulmonary disease (COPD) continue to smoke cigarettes despite knowing they have the disease. This behavior has a negative impact on prognosis and progression, as repeated injury enhances the pathobiological mechanisms responsible for the disease. A combination of counseling plus pharmacotherapy is the most effective cessation treatment of smokers with COPD, and varenicline seems to be the most effective pharmacologic intervention. Preventing exacerbations in patients with COPD is a major goal of treatment, and vaccination against influenza and pneumococcus is an effective preventive strategy to achieve this goal.
A significant proportion of patients continue to smoke despite knowing they have chronic obstructive pulmonary disease (COPD).
Smokers with COPD exhibit higher levels of nicotine dependence and have lower self-efficacy and self-esteem, which affects their ability to quit smoking.
The combination of counseling plus pharmacotherapy is the most effective cessation treatment of smokers with COPD.
Because of the high morbidity and mortality of influenza in patients with COPD, annual influenza vaccination has been recommended.
Although the clinical efficacy of pneumococcal vaccination is uncertain in COPD, evidence suggests that it provides protection against CAP and reduces the likelihood of exacerbation. Therefore, several international health authorities routinely recommend this vaccination in patients with COPD.
Smoking cessation in chronic obstructive pulmonary disease
Cigarette smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD) in developed countries and an important contributor to the burden in most societies around the world. Patients with COPD who continue to smoke have a higher prevalence of symptoms persistence, an accelerated decline in lung function, increased exacerbations, and higher mortality rate than nonsmokers. Therefore, smoking cessation has been identified as the single most cost-effective and effective strategy for slowing the progression of the disease.
Smoking prevalence in chronic obstructive pulmonary disease
A significant proportion of patients with COPD continue to smoke despite knowing they have the disease, and as a consequence this behavior has a negative impact on the prognosis and progression of the disease.
Several cross-sectional worldwide population-based studies have assessed the smoking status (never, former, and current smokers) in different COPD population. The IBERPOC study in Spain reported a prevalence of 15% and 12.8% for patients with COPD who are current and ex-smokers , respectively. The Behavioral Risk Factor Surveillance System, a survey conducted in the United States, showed a frequency of current smoking in patients with COPD of 45.1%, higher than that observed among adults with other chronic disease (23%), asthma (20.3%), and no chronic disease (18.9%). In Latin-America, the PLATINO study (Latin American Project for Investigation of Obstructive Lung Disease) reported that 31.5% of the patients with COPD were never smokers, 32.5% former smokers, and 36% current smokers. In a more recent review from Latin-America, current smokers in COPD ranged from 13% in Bucaramanga (Colombia) to 38.5% in Santiago de Chile ( Fig. 1 ). In a large survey from mainland China almost half of the patients with COPD were current smokers (47.7%), 15.8% former smokers, and 36.5% never smokers. Results from the Health Survey for England showed that current smoking was higher among people with COPD (34.9%) than those without COPD (22.4%), and the smoking prevalence increased with disease severity (current smokers 29.5% in mild, 38.3% in moderate, and 40.5% in severe/very severe COPD).
An analysis of individuals with COPD enrolled in the COPDGene cohort reported that 43.4% were current smokers, and similar results have been reported by some recent COPD pharmacologic clinical trials (current smoker frequency between 35% and 47%) ( Table 1 ).
|Study||Subjects (n)||Age (y)||FEV 1 (%)||Former Smoker (%)||Current Smoker (%)|
Characteristics of smokers with chronic obstructive pulmonary disease
There are differences in clinical characteristics between smoking patients with and without COPD. Smokers with COPD exhibit higher levels of nicotine dependence, smoke more cigarettes a day, have higher cotinine concentrations, and have less self-efficacy and self-esteem than those without the disease, all of which affect their ability to quit smoking. , , This does not seem to be due to lack of motivation to quit, which was not different between smokers with and without COPD. On the other hand, depression was more common among smokers with COPD, a fact that can influence the behavior of these patients.
Smokers with COPD seem to have similar susceptibility to smoking cessation intervention than those without COPD. A study showed that 1-year quit rates in smokers with COPD was higher compared with those without the disease. However, results of real-life studies and clinical trials found that the combination of brief or intensive counseling in smokers with COPD had comparable abstinence rates over 1 year to smokers in general.
Data from the COPDGene study showed that current smokers were on average younger, had longer duration of cigarette smoking, and were more likely to be African American than former smokers. The cigarette consumption in pack-years was similar between former and current smokers, as well as other functional parameters (forced expiratory volume in the first second of expiration [FEV 1 ]/forced vital capacity 0.54 vs 0.56 and FEV 1 % 63.1% vs 63.3%, respectively). In the visual analysis of CT, former smokers had an emphysema index 5.5% higher than current smokers, and the difference was evident in each GOLD categories.
Smoking diagnosis in chronic obstructive pulmonary disease
The approach to the smoking patient in general should consider the mental situation in which the subject is at the time of consultation, paying attention to 2 aspects intimately linked with tobacco use: motivation and dependence.
Assessment of Motivation and Self-Efficacy in Smokers with Chronic Obstructive Pulmonary Disease
Self-efficacy in smokers with COPD is usually low and associated with low quit rates. Therefore, increasing motivation and building self-efficacy are particularly important in these patients.
In general, the first approach to assess motivation is to classify the patient according to the phase model of Prochaska and Di Clemente. A correct phase motivational stage identification allows an adequate therapeutic intervention, timely treatment, appropriate use of resources, and increases the chances of success. It is not recommended to initiate pharmacotherapy for smoking cessation until the patient is in the preparation stage. Fig. 2 shows a motivational phase diagnostic diagram.
Assessment of Tobacco Dependence in Smokers with Chronic Obstructive Pulmonary Disease
The assessment of the nicotine dependence in smokers involves the evaluation of the number of package-years, the degree of physical dependence to nicotine with the Fagerström test, the analysis of the previous attempts to quit, and determination of carbon monoxide (CO) levels in the exhaled air.
Number of package-years
The number of package-years can be obtained multiplying the amount of cigarette that the patient smokes per day by the number of years that the person has smoked, then divided by 20 (average number of cigarettes in a package). Patients with more than 5 package-years will have more difficulty quitting smoking than those with lower values.
Assessment of the degree of physical dependence to nicotine
The Fagerström test is the most used tool to measure nicotine dependence ( Table 2 ). This test predicts the difficulty of quitting, severity of withdrawal symptoms, and need for pharmacologic treatment. The most distinctive indicators of nicotine dependence are as follows: How soon after you wake up do you smoke your first cigarette? and How many cigarettes do you smoke per day? Smokers who start within 30 min after waking and those who consume more than or equal to 20 cigarettes a day have a high degree of dependence. Another indicator of high dependence is nocturnal smoking. A short version of the Fagerström test (Heaviness Smoking Index) that only include 2 questions has been developed. Assessment of the Fagerström test and the Heaviness Smoking Index are shown in Tables 2 and 3 , respectively.
|1. How soon after you wake up do you smoke your first cigarette?||After 60 min||0|
|Within 5 min||3|
|2. Do you find it difficult to refrain from smoking in places where it is forbidden?||No||0|
|3. Which cigarette would you hate most to give up?||The first in the morning||0|
|4. How many cigarettes do you smoke per day?||10 or less||0|
|31 or more||3|
|5. Do you smoke more frequently during the first hours after waking than during the rest of the day?||No||0|
|6. Do you smoke even if you are so ill that you are in bed most of the day?||No||0|
|1. How soon after you wake up do you smoke your first cigarette?||After 60 min||0|
|Within 5 min||3|
|2. How many cigarettes do you smoke per day?||10 or less||0|
|31 or more||3|
Assessment of previous attempts to quit smoking
This assessment helps identify certain characteristics of the subject’s smoking habit. Most smokers take 4 to 7 attempts to successfully quit and many have tried to quit before. , The characteristics of the attempts that led the subject to remain without smoking for at least 24 hours should be considered, because they may help improve the chance of the next attempt. The following variables must be known: number of attempts made, duration of each abstinence, severity and timing of nicotine withdrawal symptoms, treatments used and its effects, and reasons for relapse.
The levels of carbon monoxide in the exhaled air
This test can be used to validate the withdrawal of the patient, to objectively measure the tobacco consumption, and as a motivating instrument to quit smoking. Levels of greater than or equal to 10 parts per million (ppm) of CO correspond to smoking subjects, between 5 and 10 ppm to sporadic smoking individuals or daily consumers of very small number of cigarettes, and less than 5 ppm for nonsmokers.
Smoking cessation treatments
Several studies have shown that a combination of counseling plus pharmacotherapy is the most effective cessation intervention for smokers with COPD.
Counseling and Behavioral Interventions
Smoking cessation counseling (SCC) can be offered individually, by group or by telephone.
In the general population of smokers, the effectiveness of simple advice from physicians has a small effect on cessation rates. Assuming an unassisted quit rate of 2% to 3%, a brief advice intervention can increase quitting by a further 1% to 3%. Two meta-analysis in general smoker population reported that combining SCC and pharmacotherapy increase smoking cessation success compared with a minimal intervention or usual care. ,
In patients with COPD a meta-analysis showed that SCC in combination with nicotine replacement therapy (NRT) had the greatest effect on prolonged abstinence rate: 5 times higher compared with no intervention or usual care (odds ratio [OR] 5.08, 95% confidence interval [CI] 4.32–5.97), 3 times higher compared with SCC alone (OR 2.80, 95% CI 1.49–5.26), and a nonsignificant statistical increase compared with SCC in combination with an antidepressant (OR 1.53, 95% CI 0.71–3.30). A trend of SCC alone to be superior versus usual care (1.81, P = .07) was also observed. In addition, another systematic review on smoking cessation in patients with COPD found an average 12-month continuous abstinence rates of 1.4% for usual care, 2.6% for minimal counseling, 6.0% for intensive counseling, and 12.3% for pharmacotherapy.
Limited information exists regarding the use of pharmacotherapy for smoking cessation in patients with COPD. The main objectives of this pharmacotherapy are to control the long-term abstinence (nicotine patch, bupropion, and varenicline) and to provide rapid relief of acute cravings and withdrawal symptoms (rapidly acting nicotine replacement products).
A meta-analysis evaluated the effectiveness of SCC or pharmacologic smoking cessation interventions, or both, in smokers with COPD. NRT (risk ratio [RR] 2.60; 95% CI 1.29–5.24) and varenicline (RR 3.34; 95% CI 1.88–5.92) increased the quit rate over placebo. Pooled results also showed a positive effect of bupropion compared with placebo (RR 2.03; 95% CI 1.26–3.28).
Table 4 shows the main results of some smoking cessation pharmacotherapy studies conducted in COPD.
|Study||Subjects (n)||FEV 1||Medication||Time Period||Sustained Quit Rates||OR (95% CI) or P Value|
|Anthonisen et al, 1994||5887||78.3% pred||Nicotine gum||12 mo||Nicotine 35% |
|Tønnesen et al, 2006||370||56% pred||Nicotine sublingual tablets||2–12 mo||Nicotine 14% |
|OR 2.88 (1.34–6.15)|
|Tashkin et al, 2001||404||71.3% pred||Bupropion SR||7–26 wk||Bupropion 15.7% |
|P = .040|
|Wagena et al, 2005||144||Not available||Bupropion SR |
|4–26 wk||Bupropion SR 27.3% |
|% Difference |
SR vs placebo 18.9 (3.6–34.2; P = .02)
Nortriptyline vs placebo 12.9 (−0.8 to 26.4; P = .07)
|Tashkin et al, 2011||505||70% pred||Varenicline||9–52 wk||Varenicline 18.6% |
|OR 4.04 (2.13–7.67)|
|Jiménez Ruiz et al, 2012||472||Gold 3 (79%) |
Gold 4 (21%)
|Nicotine patches |
|9–24 wk||Nicotine patches 44% |
Bupropion alone 60%
Varenicline alone 61%
|Varenicline vs nicotine patches (OR: 1.98; 95% CI: 1.25–3.12; P = .003). |
Varenicline vs bupropion (OR: 1.43; 95% CI: 0.49–2.2)
|Hernández Zenteno et al, 2018||31 COPD |
|1.5 L |
|Varenicline||12 mo||COPD 61.2% |
|P = .072|
Nicotine Replacement Therapy
Results from the Lung Health Study showed that after 12 months nicotine gum combined with an intensive behavioral program was more effective in helping smokers at risk for COPD to abstain from smoking than usual care. Tønnesen and colleagues found in smokers with COPD that the continuous abstinence rates from 2 to 12 months were superior in the NRT (14%) than the placebo group (5.4%) (OR 2.88; 95% CI, 1.34–6.15).
Bupropion Sustained Release
Bupropion sustained release (SR) is an antidepressant drug with an added effect on smoking cessation, particularly in patients with COPD. , Taskhin and colleagues found a continuous abstinence rate at 6 months higher in the bupropion group (15.7%) versus placebo (9%) in patients with mild to moderate COPD. Another placebo-controlled randomized trial in smokers at risk for or with COPD showed that continuous abstinence rate at 6 months were 27.9%, 25%, and 14.6% for bupropion, nortriptyline, and placebo, respectively. No significant difference was found between nortriptyline and placebo.
Varenicline is a drug developed for smoking cessation that in “healthy” smokers has proven to over twice as effective as placebo and around 50% more effective than bupropion to promote long-term abstinence.
A study conducted in smokers with mild and moderate COPD showed a higher continuous abstinence rate at 1-year follow-up for varenicline (18.6%) versus placebo (5.6%) without differences in side effects. Another study on smokers with severe-very severe COPD that received SCC plus pharmacotherapy showed an overall abstinence rate at 24-week of 48.5%. The rates of continuous abstinence were 38.2% for NRT, 55.6% for bupropion and 58.3% for varenicline. Patients treated with varenicline for 24-week had higher abstinence rates than those treated for 12-week. The onset of psychiatric symptoms due to medication was rare and evenly distributed across groups. A recent study found no differences in the abstinence rate at 12-month between smokers with and without COPD (61.2% vs 42.8%, P = .072) receiving treatment with varenicline.
Pharmacotherapies Approaches for Smoking Cessation in Chronic Obstructive Pulmonary Disorder
The doses and time of use of the different pharmacotherapies for smoking cessation are shown in Table 5 . The treatment approach is based on the nicotine physical dependence severity. Smokers with mild to moderate degree of nicotine dependence can be treated with a controller drug (nicotine patch, bupropion, or varenicline) with or without a reliever medication (nicotine gum, lozenge, nasal spray, and oral inhaler). In those subjects with high degree of nicotine dependence, it is possible to combine controller drugs (bupropion and/or varenicline, or nicotine patch and/or bupropion, or combine the 3 controllers) with multiple relievers.
|Medication||Varenicline||Bupropion||Nicotine Replacement Therapy|
|Mechanism of action||Partial agonist for the α 4 β 2 nicotinic acetylcholine receptor (dopamine release in the nucleus accumbens)||Inhibit neuronal reuptake of dopamine and norepinephrine in the nucleus accumbens and locus ceruleus||Acts at the level of nicotinic central nervous system receptors|
|Dose||12 wk |
Days 1–3: 0.5 mg QD
Days 4–7: 0.5 mg BD
Days 8+: 1 mg BD
|12 wk. |
150 mg/12 h
First week progressive dose
|Side effects||Nausea (most common), insomnia, vivid dreams, dyspepsia, constipation, flatulence, emesis||Insomnia (most common), dry mouth, anxiety, irritability, restlessness, headache, tinnitus, skin rash, seizures (rate)||Redness or itching of skin where patch applied |