The results retrieved for PICO questions were prioritized according to the highest level of evidence (randomized controlled trials [RCTs], meta-analyses and systematic reviews) and the most appropriate answer to the clinical question. If this was not possible, intermediate (observational) or low level (open-label, case series or consensus) studies in the hierarchy of evidence were selected. The recommended algorithmic selection method was used primarily for therapeutic questions.8 Studies published in Spanish, Portuguese and English were considered for inclusion. The end date of the search was May 2016 (Table 2).

Recommendations and templates developed by the CASPE network (www.redcaspe.org) were used for the critical appraisal of the selected references. The ACCP grading system was used to classify recommendations as strong1 or weak,2 according to the balance of risk, benefits, burdens, and, in some cases, cost. The quality of evidence was classified as high (A), moderate (B) or low (C), depending on the study design, consistency of results, and ability of the evidence to clearly answer the PICO question.9

The authors appointed two external reviewers with expertise in the field of COPD and smoking.

Significant efforts have been made to increase the rate of smoking cessation using motivational tools and measures, such as spirometry measurements, co-oximetry, and the calculation of lung age. It is of interest to determine the status of current clinical research aimed at answering this question.

Thirty-one references were retrieved (MeSH: 5; Trip database: 26), and 7 studies were selected to answer the question (2 systematic reviews, 4 randomized clinical trials [RCT], and 1 cohort study).

One systematic review found limited benefits from the use of spirometry as a motivating factor for increasing smoking cessation,10 and another11 evaluated the effectiveness of the use of biomedical instruments for increasing motivation in smoking cessation. Both included 15 RCTs, 2 of which used spirometry in primary care as a motivator. No statistically significant benefit was identified in the smoking cessation rate when spirometry was used. The analysis does not evaluate the motivating effect of the spirometry test when the result was abnormal. In this respect, a more recent RCT12 showed that bronchial obstruction was the most significant predictor of smoking cessation (OR: 4.215; 95% CI: 2.215–7.865). Similarly, in another study,13 4494 smokers selected from 100000 subjects with obstructive spirometry were informed in a phone call about COPD and given brief smoking cessation counseling. The results showed a cessation rate of 16.3% among patients with obstruction compared to 12% among those with normal spirometry (P=.0003). An RCT14 which compared COPD patients to smokers with normal spirometry, and included a 3-year follow-up and pharmacological interventions, found a higher rate of cessation among smokers with COPD at the 3-year follow-up (29% versus 14%; P=.003).

As for the motivating effect of explaining to the patient their lung age calculated according to spirometry, an RCT15 found a smoking cessation rate at 12 months of 13.6% compared to 6.4% in the control group (P=.05; NNT=14).

An RCT16 failed to show efficacy when smokers with no previous diagnosis of COPD were confronted with spirometry results, even though the cessation rate was twice that of the control group (OR: 2.02; 95% CI: 0.63–6.46).

Moderate evidence that spirometry results encourage smoking cessation in patients with COPD or in at-risk smokers.

Strong recommendation to perform spirometry in patients with a diagnosis or in symptomatic smokers as a motivational tool and for diagnostic purposes in active case-finding.

Grade of recommendation: 1B.

The conclusions from studies analyzing the treatment of smoking among smokers with COPD suggest that the combination of psychological counseling and pharmacological treatment is most effective.2,17–19

It seems clear that when the intensity of psychological counseling is mild, efficacy in this group of smokers is very limited or non-existent. In smokers with COPD, psychological counseling should be intense both in terms of number of sessions and time dedicated to each session. Counseling must be offered with empathy, respect and understanding for the patient. The intimate relationship between the consumption of tobacco and COPD should be clearly explained to the patient, and they must be shown that the only treatment that has been identified as capable of controlling the chronic evolution of the disease is to stop smoking. Similarly, it must emphasized that in COPD, giving up smoking contributes definitively to the control of the four major symptoms of COPD: cough, expectoration, dyspnea, and chest tightness.2,17–19

Three types of drugs have been used in clinical studies: nicotine replacement therapy (NRT), varenicline and bupropion. All these studies have shown that the association between active drug and psychological counseling is more effective than the association between counseling and placebo. NRT and varenicline have been shown to be effective at 6 and 12 months of follow-up, whereas bupropion was effective at 6 months only.2,17–19

A study has found that the efficacy rates in these patients are higher when pharmacological treatment is offered in addition to counseling (for more than 3 months, or in a combination of several drugs, or at high doses).3,4

It is important to determine which components are indispensable in the counseling of smokers, in order to make it more effective. It is also important to determine how to provide the most effective pharmacological treatment.

Thirty-one references were retrieved (MeSH: 5; Trip database: 22), and 8 studies were selected to answer the question (3 systematic reviews, 2 meta-analyses, 2 RCTs, and 1 cross-sectional study).

One of the first reviews on smoking cessation in smokers with COPD showed that the combination of behavioral counseling and pharmacological treatment was superior to no treatment (RR: 4.0; 95% CI: 3.25–4.93) or the use of behavioral counseling only (RR: 4.19; 95% CI: 3.41–5.15).17

Another meta-analysis evaluated 7332 patients with COPD who received different treatments for smoking cessation, and found that the combination of behavioral counseling plus NRT was the most effective type of intervention (OR: 5.08; P<.0001) compared to behavioral counseling only (OR: 2.8; P=.001) and compared to behavioral counseling in combination with an antidepressant (OR: 3.32; P=.002). Behavioral counseling only came close to achieving efficacy when compared with standard care (OR: 1.81; P=.07).20

Another study evaluated the effectiveness of high-intensity smoking treatment in smokers with COPD compared with standard care. The high-intensity program consisted of a combination of pharmacological treatment plus hospitalization for 2 weeks and the administration of intensive behavioral counseling; telephone contacts and continuous monitoring were also programmed for a period of 1–3 years. Abstinence figures in the group that received the intensive treatment were 52% and 38% at 1 and 3 years of follow-up, respectively, vs 7% and 10%, respectively, in the group that received standard care.21

One of studies that has shed most light on the issue is probably that of Hoogendoon et al.,18 who conducted a systematic review of various clinical trials in patients with COPD. The different interventions were grouped into 4 categories: standard care, minimal intervention, intensive behavioral counseling, and intensive behavioral counseling plus pharmacological treatment. The abstinence rates after 1 year of follow-up for each of the categories were: 1.4%, 2.6%, 6% and 12.3%, respectively. Compared to standard treatment, the cost per quality-adjusted life year (QALY) gained for the minimum intervention was 16900 euros, 8200 euros for intensive behavioral counseling, and 2400 euros for intensive behavioral counseling plus pharmacological treatment. The authors conclude that the combination of intensive behavioral counseling plus pharmacological treatment is the most successful and cost-effective treatment of smoking in COPD patients.

Bartlett et al.22 evaluated 17 randomized trials to determine what type of behavioral counseling for smoking cessation is most effective in smokers with COPD. This study identified 5 counseling techniques that are significantly associated with the best results: (1) action planning; (2) recording course of symptoms, achievements, and failures; (3) weight control; (4) social support; and (5) explaining clearly explain the relationship between COPD and smoking.

Two clinical trials have examined the efficacy and safety of bupropion. One found that bupropion was more effective than placebo in achieving continuous abstinence at 6 months of follow-up (16% vs 9%; P<.05).23 The other also showed similar results at 6 months of follow-up (difference of 18.9% [95% CI: 3.6–34.2]; P=.02.24

The efficacy and safety of varenicline was analyzed in an RCT which found that varenicline was more effective than placebo for helping smokers to quit at 3, 6 and 12 months of follow-up. At the end of the year, the figures were 18.6% vs 5.6% (OR: 4.04 [95% CI: 2.13–7.67]; P<.0001).25

A recent review analyzing 16 studies that included more than 13000 patients has reached similar conclusions to those discussed here.26

The available evidence indicates that the most effective intervention to help subjects with COPD to quit smoking is a combination of intensive behavioral counseling plus pharmacological treatment. This intervention is highly cost-effective.

Behavioral counseling should be intensive and prolonged; the greater the intensity and the longer the duration, the greater the efficacy.

A choice of NRT, bupropion or varenicline can be used as pharmacological treatment. Bupropion showed efficacy only at 6 months of follow-up. NRT and varenicline have been shown to be effective at 6 and 12 months of follow-up.

High evidence and strong recommendation for intensive behavioral counseling plus pharmacological treatment (NRT and varenicline are superior to bupropion) to help smokers with COPD to quit.

Grade of recommendation: 1A.

Around 25%–35% of COPD patients admitted to hospital are smokers. Hospitalization is an ideal situation to help smokers quit. Taking into account these premises, hospitalization of an individual with COPD represents an important opportunity to determine their smoking status and to intervene decisively.27,28

Seven references were retrieved (MeSH: 3; Trip database: 1; and by snow-balling: 3), and 6 studies were selected to answer the question (3 RCTs, 1 systematic review, 1 economic evaluation, and 1 cohort study).

A systematic review found that intensive behavioral interventions that begin in the hospital and continue for at least 1 month after discharge increase abstinence rates (RR: 1.37; 95% CI: 1.27–1.48).29 One study found that the combination of intensive intervention plus NRT increased abstinence rates compared with intensive intervention alone (RR: 1.54; 95% CI: 1.34–1.79). However, 2 other studies failed to show that adding varenicline or bupropion increases abstinence rates. Similar results were found in a subgroup of smokers who were admitted for cardiovascular diseases; in this subgroup, intensive intervention followed by subsequent support increased abstinence rates (RR: 1.42; 95% CI: 1.29–1.56) when compared with non-intensive intervention.

Abstinence rates were compared in 2 groups of smokers enrolled in a clinical trial.30 One group received intensive intervention (free pharmacological treatment for 90 days, regular phone calls and behavioral reinforcement), while the control group only received recommendations on the use of the medication at the time of discharge. Point prevalence abstinence at 6 months was significantly higher in the intervention group (26% vs 15%; RR: 1.71; 95% CI: 1.14–2.56; P=.009; NNT: 9.4; 95% CI: 6.4–35.5). The same was observed for continuous abstinence rates at 6 months (27% vs 16%; RR: 1.70; 95% CI: 1.15–2.51).

A pharmacoeconomic study analyzed the cost-effectiveness of the Ottawa model for smoking cessation (OMSC) in patients hospitalized for various diseases, including COPD.31 The OMSC includes psychological counseling and pharmacological treatment. The authors found that the OMSC program was very cost-effective with a 1-year cost per QALY gained of C$1386, and lifetime cost per QALY gained of C$68. The study showed that using the Ottawa model in 15326 hospitalized smokers in 1 year would achieve a total of 4689 quitters, and would prevent 116 re-hospitalizations, 923 hospital days, and 119 deaths in all of these chronic diseases.

A clinical trial carried out by Borglykke et al.32 compared the rates of abstinence in 2 groups of smokers with COPD attending the emergency department of a hospital. One group was randomized to receive intensive intervention and the other was the control group. Patients were followed up at 1 year and 3 years after the intervention. The results showed that at the 1-year follow-up, the abstinence rate in the intervention group was significantly higher than in the control group (30% vs 13%; OR: 2.83; 95% CI: 1.40–5.74). Moreover, no significant differences were found in terms of the amount of phlegm or survival (50.4% vs 43.1%; HR: 0.80; 95% CI: 0.55–1.16). However, at the 3-year follow-up, the intervention group had been hospitalized significantly fewer days for COPD or other causes.

A clinical trial33 randomized 172 patients to 2 groups. The intervention group received medical counseling for quitting smoking and screening for gastroesophageal reflux, depression and/or anxiety, in addition to education on the use of inhalers. Compared with the control group, the results showed no significant differences in readmissions or consultations within 30 days after discharge, or in the rate of readmissions at 90 days.

Another study in a cohort of COPD patients hospitalized for exacerbations34 reviewed the effectiveness of a brief anti-smoking counseling session during admission and the use of medication to assist smoking cessation after discharge. A total of 1334 patients were included: 19.8% reported having stopped smoking at 6 and 12 months of follow-up, 17.5% had no reported status, and 63.7% continued smoking. It is interesting to note that only 33.7% of the patients used smoking cessation medication. The results did not show higher rates of abstinence among those who received medication to quit smoking. Nor was any association found between anti-smoking counseling at the time of discharge and abstinence, or between those who received medication in the 48-h period after discharge or in those who had received treatment in the year prior to admission. Patients who received varenicline presented significantly higher rates of abstinence (OR: 2.44; 95% CI: 1.48–4.05), while those who received NRT in monotherapy showed the worst results (OR: 0.66; 95% CI: 0.51–0.85). Patients treated with bupropion or combination therapy were no more likely to report cessation.

The available evidence indicates that intensive intervention to help quit smoking initiated while the patient is hospitalized plus at least 1 month of follow-up after hospital discharge achieves higher abstinence rates when compared with smokers who received standard treatment. Effectiveness increases significantly when psychological counseling is added to treatment with NRT or varenicline. This intervention is highly cost-effective.

High evidence and strong recommendation for initiating interventions to help COPD patients stop smoking during hospitalization.

Grade of recommendation: 1A.

COPD places a considerable economic burden on public health systems. In Spain, costs amount to €3bn. a year. It is also known that the cost of care incurred by a smoker with COPD is approximately €3700/year, while individuals with COPD who have stopped smoking incur costs of €2000/year. Accordingly, then, when a smoker with COPD quits, savings to the National Health System amount to around €1300/year.35

Twenty-two references were retrieved (MeSH: 17; Trip database: 5), and 4 studies were selected to answer the question (3 cohort studies and 1 case–control).

A case–control study conducted in Spain, in which costs generated by smokers with COPD were compared with those of former smokers with COPD over a 12-month period, found that the smokers with COPD consumed more health care resources compared to former smokers, regardless of their COPD severity stage.35

Three simulated cohort studies in the United Kingdom, Spain and France have analyzed the scenario of funding smoking cessation in patients with COPD using a Markov model: (1) in COPD patients in the United Kingdom,36 the ICER (incremental cost-effectiveness ratio) was £2686 per QALY and continued to yield savings after 10 years in all patients, regardless of COPD severity and percentage of success of the intervention applied; (2) in Spain,37 the model was developed with a time horizon of 5 years and considered the 3 approved first-line drugs (varenicline, bupropion and NRT). Estimates were that 17756 COPD patients would give up smoking if the treatment were funded, compared to 1303 patients if it was not.38 In the reimbursement scenario, accumulated savings would be €4.3 million; (3) in France, a cost-effectiveness study in patients with COPD, cancer, and cardiovascular disease allowed the authors to conclude that for a 5-year horizon, cost savings would be made in the range of €15–215 million with an ICER of €11187 per QALY.

Studies analyzing the impact of funding of smoking cessation in patients with COPD make the following conclusions: (a) COPD patients who continue to smoke use more health care resources and generate greater social and economic costs; and (b) the funding of smoking cessation in smokers with COPD is highly effective and cost-effective.

Moderate evidence and strong recommendation for the funding of the treatment of smoking in smokers with COPD, due to the impact on health and health economics.

Grade of recommendation: 1B.