. 2012 Mar 1;12(4):1–50.

Table A1: Characteristics of Included Randomized Control Trials*.

Author, Year	Patients	Comparison	Outcomes Definitions	Follow-up Period	Authors’ Conclusions	Notes
Pederson et al, 1991 (18)	Mean age: 53.4 years (SD 13.7) - Smokers admitted to hospital with exacerbation of COPD. COPD defined according to the American College of Chest Physicians and the American Thoracic Society (ACCP-ATS) Mean FEV₁FCV = 0.52 (SD = 0.17) Severity of COPD: Probably severe or very severe according to GOLD Motivation to quit: Advised to quit Total sample: N = 74	Self-help manual + counselling session by trained smoking cessation counselor (3 to eight 15–20 minute counselling sessions on alternate days while in hospital (min 45 minutes, max 160 minutes) [minimal counselling to intensive counselling]. vs. Usual care	Abstinence: Self-reported and verified by COHB analysis from blood drawn at 6 months. Mortality: All-cause, cardiovascular death, lung cancer death.	3 months, 6 months	No significant difference between the 2 groups.	Because of acute exacerbation, it was felt that inpatients were more likely to be amenable to quitting smoking. - Patients in the treatment group received smoking cessation on alternate days for the duration of their hospital stay. - Follow-up visits were used to offer support and encouragement and to answer patient’s questions. - Physicians were blinded to group membership.
Sundblad et al, 2008 (22)	Age range: 40–60 years. - Smokers with COPD according to Siafakas et al (32) and according to European Respiratory Society Guidelines. - Smoked at least 8 cigarettes per day) - Average pack-years: 34.9 (SD 12.8) Severity of COPD:- 71% had mild COPD, FEV₁ > 70% of predicted.	Comprehensive smoking cessation program Included 11-day hospitalizations, use of NRT and recommended physical exercise, 1 hour daily with trained cessation nurse (660 minutes), structured educational program (physician, physiotherapist, dietician, psychologist, occupational therapist, group discussion with spouse [intensive	Abstinence: At 3-year follow-up, confirmed by carbon monoxide testing using piCO Smokerlyzer. Abstinence from smoking for at least 6 months. Questionnaires were used to gather information about the smoking habits.	1 year, 3 years	This comprehensive smoking cessation program, including several components, resulted in a high rate of smoke-free patients after 1 year (52%) and long-lasting effect, with 38% of the smokers with COPD remaining free from smoking after 3 years.	Smokers had to be smoking more than 8 cigarettes/day. - Smoking cessation program lasted for 1 year, and included a 2-day stay at the pulmonary rehabilitation clinic. - Patients were hospitalized for 11 days to build up motivation to stop smoking through information and personal support. - Carbon monoxide testing
	- 23% had moderate COPD, FEV₁ = 69-50% of predicted. - 6% had severe COPD, FEV₁ ≤ 49% of predicted. Motivation to quit: Not stated Total sample: N = 247	counselling+ NRT]. vs. Usual care	Nicotine dependence was classified according to Fagerstrom test for nicotine independence.			performed in a random sample of patients. - NRT and distractive activities such as physical exercise were recommended. - Each participant met 1 hour daily with a trained smoking cessation nurse. - Structured educational program including a physician, physiotherapist, dietician, lab technician, psychologist, and occupational therapist, each with a specific role in the education program. - Spouses of smokers were invited to stay in the hospital if they accepted.
Lung Health Study Anthonisen et al, 1994; (17) Anthonisen et al, 2005 (14)	Age range: 35–60 years. - Presence of mild airway obstruction. - Smokers smoking 10 cigarettes/day during 30 days preceding the screening test. Severity of COPD: Mild to moderate, FEV₁/FCV < 70% and 55% < FEV₁ < 90% Motivation to quit: Not stated Total sample: N = 5887	Smoking intervention: ipratropium bromide [intensive counselling + bronchodilator]. vs. Smoking intervention: placebo [intensive counselling + NRT]. vs. Usual care Smoking intervention: physician message, individual session with interventionist for behavioral interview, group orientation meeting, 12 intensive group sessions, clinic visits every 4 months	Abstinence: Smoking cessation confirmed by salivary cotinine/carbon monoxide testing. Participants with cotinine levels > 20 ng/mL were considered to be smokers. Mortality: All-cause, cardiovascular mortality and lung cancer mortality. Lung function: FEV₁	1 year, 5 years, 14.5 years	An aggressive smoking intervention program significantly reduces age-related decline in middle-aged smokers with mild airway obstruction. - Use of anticholinergic bronchodilators results in a relatively small improvement in FEV₁ that appears to be reversed after the drug is discontinued. Use of bronchodilator did not influence the long-term decline of FEV_1. - All-cause mortality was significantly lower in the smoking intervention groups than in the usual	Spouses and significant others of both intervention groups were included in the cessation program if they wished and were treated the same way as participants. - Women tended to have greater improvement in lung function in response to smoking cessation than did men. - In addition to change in smoking status, determinants of the degree of improvement in, or stabilization of, FEV₁ included baseline function, baseline bronchodilator responsiveness, race, methacholine reactivity, intervention group, and age. - Smoking cessation reduced the frequency of lower respiratory illness physician visits.
		for 5 years, maintenance program for quitters, extended intervention program for patients still smoking or relapsing, and NRT gum.			care group. Smoking cessation intervention programs have a substantial effect on subsequent mortality even when successful in the minority of participants. - No linear relationship was found between smoking reduction and FEV_1.	- Quitting smoking for an interval followed by relapse to smoking appeared to provide a measurable and lasting benefit in comparison to continuous smoking. Attempts to quit smoking can prevent some loss of lung function. - Changes in AR were primarily related to changes in FEV₁ The greater the decline in FEV_1, the greater the increase in airway reactivity. Smoking cessation had a small additional benefit in AR beyond its favorable effects on FEV₁ changes.
Tashkin et al, 2001 (19)	Aged > 35 years. - Smoked 15 or more cigarettes/day for the previous year and had not stopped smoking for more than 3 months during that year. Severity of COPD: Mild-Moderate. Patients with Stage I and II COPD (FEV₁/FVC ≤ 0.70) according to ATS guidelines and presence of clinically defined COPD (emphysema, chronic bronchitis, and smoking-related small airways disease). Motivation to quit: Motivated to quit Total sample: N = 404	Counselling: All patients received brief, face-to-face counselling at each of the 9 visits to the clinic + 1 telephone session 3 days after the quit date. Bupropion SR 150mg—days 1–3: once per day; days 4–84: 150 mg twice per day + personalized counselling by trained counsellor. [intensive counselling + antidepressant]. vs. Placebo + personalized counselling for 12 weeks [intensive counselling].	Continuous abstinence: Zero cigarettes per day confirmed by exhaled carbon monoxide values of ≤ 10 ppm. Point-prevalence abstinence: Defined as abstinence during the previous 7 days.	6 months	Bupropion SR is a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.	12-week treatment phase with follow-up at 6 months. - Block randomization stratified by centre. - Target cessation date was selected. - Predictors of abstinence were tested using multivariable logistic regression, controlling for smoking history, age, sex, centre, and treatment group assignment. - Proportions of patients with either Stage I or Stage II COPD were evenly distributed between treatment groups, as were participants with sub-diagnoses of emphysema, bronchitis, or small airways disease.
Hilberink et al, 2010 (25)	Aged > 35 years - Current smokers. - Diagnosis of COPD confirmed by GP. - Recorded medication with ICPC code R95/96. - At least 3 prescriptions for bronchodilators in the past year. - At least 3 prescriptions for inhaled anti-inflammatory medication in the past year. Severity of COPD: Not defined, but probably mild to moderate according to GOLD. Motivation to quit: Not stated Total sample: N = 667	Counselling + NRT [minimal counselling + NRT]. vs. Counselling + NRT + bupropion [minimal counselling + NRT + antidepressant]. vs. Usual Care SMOCC intervention: A multi-faceted strategy containing: 4-hour central training for GPs and practice nurses 4 support visits at the practice location detection of patients using an algorithm for electronic medical records a patient counselling protocol (invitation for control visits, assessment of motivational stage, education materials, 1-3 follow-up visits depending on stage of change, NRT, telephone follow-up by practice nurse)	Point-prevalence abstinence: Self-reported abstinence, biochemically verified by urinary cotinine levels of < 50 ng/mL.	6 months, 12 months	The program doubled the cessation rates (statistically nonsignificant). Too few participants used additional bupropion SR to prove its effectiveness.	- Professionally directed intervention consisted of 4-hour group training on COPD, smoking, and smoking cessation. More individual support was provided by an outreach visitor by means of counselling and feedback about performance at the practice location. Support materials included information on smoking and smoking cessation, educational tools for patients, and questionnaires assessing smoking habits. - Data collection included motivation to quit smoking and Fagerstrom test. Severity of COPD was determined according to Medical Research Council Questionnaire and self-efficacy. - Patients were divided into 3 categories: preparers, contemplators, and pre-contemplators.
Wilson et al, 2008 (27)	Mean age: 61 years (SD84) - Smokers with diagnosis of COPD attending the regional respiratory centre.	Individual support by nurse (5 weekly hour-long sessions) + 12-week course of NRT for those wishing to stop (300 minutes) [intensive counselling + NRT].	Abstinence: Self-report of complete cessation confirmed by biochemical validation (carbon monoxide ≤ 10 ppm and salivary cotinine ≤ 10 ng/mL).	12 months	Patients with COPD were unable to stop smoking, regardless of the type of support they received.	Study objective was to gain an insight into the nurse’s role in changing the smoking behavior of adults with COPD requiring secondary care. - Hypothesis was that intensive
	Mean (SD) pack-years: 41.4 (20). Severity of COPD: Not defined Motivation to quit: Not stated Total sample: N = 91	vs. Group support (5 weekly, hour-long sessions) by nurse + 12-week course of NRT for those wishing to stop [intensive counselling + NRT]. vs. Control (minimal counselling 5-10 min by GP + leaflet about smoking cessation).	Stages of change— Nicotine dependence: Measured by heaviness of smoking index. Dyspnea: Assessed by Medical Research Council dyspnea scale.			nursing sessions (individual or group) would increase cessation rates. - Respiratory nurses and a physician providing individual and group support received standardized training. - Stage of Change criteria were used to categorize motivation and assist nurses to stage-match interventions.
Tonnesen et al, 2006 (16)	Aged >18 years - Patients with COPD. Severity of COPD: Mild: 9% had FEV₁ > 80% Moderate: 53% had < 50% < FEV₁ < 80% Severe: 30% had < 30% <FEV₁ < 50% Very Severe: 8% had FEV₁ < 50% Motivation to quit: Not stated Total sample: N = 370	2 mg nicotine sublingual tablet + low behavioral support [intensive counselling + NRT]. vs. 2 mg nicotine sublingual tablet + high behavioral support [intensive counselling + NRT]. vs. Placebo + low behavioral support [intensive counselling]. vs. Placebo + low behavioral support [intensive counselling]. Low behavioral support: (individual + telephone sessions (total of 150 minutes by a respiratory nurse) + take-home	Point-prevalence abstinence at 6 and 12 months: Self-reported smoking during previous week; cessation verified by exhaled carbon monoxide level < 10 ppm. Point-prevalence smoking reduction: Degree of smoking reduction after 12 months. Those still smoking but who reduced their smoking to less than 7 cigarettes daily or who reduced their daily smoking to less than 50%. Sustained abstinence: Self-reported smoking cessation at all visits from week 2 to 12 months verified by exhaled carbon monoxide level < 10 ppm.	6 months, 12 months	The results demonstrate that the use of sublingual nicotine tablets in addition to a nurse-run smoking program results in higher rates of smoking cessation compared to placebo.	Low support: (4 individual visits + 6 telephone calls: total hours = 2.5). High support: (7 individual visits + 5 telephone calls; total hours =4.5). NRT or placebo tablets were taken for 12 weeks with possibility of continued use for up to 12 months. Recommended study dose of medication was dependent on baseline cigarette consumption (≥16 cigarettes = 1-2 tablets per hour [min 10 and max 40]; 10–15 cigarettes = 1–2 tablets per hour [min 6 and max 30]; 6–9 cigarettes = 1 tablet per hour [min 3 and max 10]). - The term “smoker’s lung” was used to explain COPD to patients. - Nurses received standardized training on counselling and counselling guidelines.
		material). High behavioral support: (individual + telephone sessions (total of 270 minutes by a respiratory nurse) + take-home material).	HRQOL: Changes in QOL measures according to the SGRQ. A reduction in a total SGRQ score of ≥ 4 is considered to represent a clinically significant improvement.			- Nicotine dependence assessed by Fagerstrom test. - Motivation to quit smoking assessed on 10-cm visual analog scale.
Kotz et al, 2009 (23)	Mean age: 53.8 years, SD 7.0. - Patients with smoking history of ≥ 10 pack-years and had airflow limitation defined as FEV₁/FCV < 70%, FEV₁ ≥ 50% according to GOLD guidelines. Severity of COPD: Mild-Moderate GOLD I (n): 160 GOLD II (n): 136 Motivation to quit: Motivated to quit Total sample: N = 296	Confrontation with spirometry results during face-to-face session + 1 telephone session by respiratory nurse (165 minutes) + nortriptyline for 7 weeks [intensive counselling + antidepressant]. vs. Face-to-face session + 1 telephone session by a respiratory nurse (165 min) + nortriptyline for 7 weeks without confrontation [intensive counselling + antidepressant]. vs. Usual care (care as usual for smoking cessation provided by patient’s own GP [minimal counselling].	Prolonged abstinence: defined as urine cotinine–validated (< 50 ng/mL) abstinence from smoking at all 3 follow-up visits.	5 weeks, 26 weeks, 52 weeks	Study did not provide evidence that confrontational approach to smoking cessation increases the rate of long-term abstinence from smoking compared with equally intensive treatment without confrontation with spirometry or usual care.	Nortriptyline dose: Days 1–3: 25 mg OD Days 4–7: 50 mg OD Days 8–49: 75 mg OD
Wagena et al, 2005 (21)	Age range: 30–70 years. - Patients with COPD or at risk of COPD according to GOLD. - Had a smoking history of at least 5 years, with an average of 10 cigarettes per day in the last year. Severity of COPD: Stages 0— III Motivation to quit: Had motivation to stop smoking Total sample: N = 255	All patients received individual face-to-face (60–minute) and telephone counselling (30–minute) sessions by a respiratory nurse. Bupropion hydrochloride SR [intensive counselling + antidepressant]. vs. Nortriptyline hydrochloride [intensive counselling + antidepressant]. vs. Placebo [intensive counselling].	Prolonged abstinence: Zero cigarettes per day from weeks 4 to week 26— confirmed by urinary cotinine values of 60 ng/mL or less. Point-prevalence abstinence: No smoking for previous 7 days assessed at weeks 4, 12, and 26— confirmed by urinary cotinine values of < 60 ng/mL.	4 weeks, 12 weeks, 26 weeks	A small but nonsignificant difference in prolonged abstinence rates was observed between the 2 groups. Smaller differences in prolonged abstinence were observed in patients at risk of COPD (Stage 0). - Authors concluded that bupropion SR treatment is an efficacious aid to smoking cessation in patients with COPD. Nortriptyline treatment seems to be a useful alternative to bupropion.	Includes patients at risk for COPD (Stage 0 according to GOLD). - Patients were stratified based on disease severity according to European Respiratory Society and GOLD.

Abbreviations: AR, airway reactivity; ATS, American Thoracic Society; COHB, carboxyhemoglobin; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GP, general practitioner; ICPC, International Classification for Primary Care; max, maximum; min, minimum; NRT, nicotine replacement therapy; OD, once daily; ppm, parts per million; SD, standard deviation; SGRQ, St. George’s Respiratory Questionnaire; SMOCC, Smoking Cessation in Patients With COPD; SR, sustained release.