A Sleep Position Trainer for positional sleep apnea: a randomized, controlled trial.

We tested the effect of the Sleep Position Trainer, a vibrational device, for positional sleep apnea in an open, randomized controlled trial with 101 patients, where 52 patients were allocated to Sleep Position Trainer and 49 patients to a non-treatment control group for 2 months (Part 1). All patients were then followed as a cohort for a period of 6 months with use of the Sleep Position Trainer (Part 2). The participants were assessed with polygraphy at entry, and after 2 and 6 months. The mean apnea-hypopnea index supine was 35 per h (SD, 18) in the Sleep Position Trainer group and 38 per h (SD, 15) in the control group at entry. In a per protocol analysis, the mean total apnea-hypopnea index at entry and after 2 months in the Sleep Position Trainer group was 18 per h (SD, 10) and 10 per h (SD, 9; P < 0.001) versus 20 per h (SD, 9) and 18 per h (SD, 10; NS) in the control group. The mean supine sleep time decreased from 47% (SD, 22) to 17% (SD, 18; P < 0.001) in the Sleep Position Trainer group after 2 months. In the control group, the mean supine sleep time was 48% (SD, 20) at entry and 39% (SD, 21; NS) after 2 months. The positive effect of Sleep Position Trainer was maintained in all patients treated with Sleep Position Trainer after 6 months. Daytime sleepiness improved after 6 months. Compliance with the Sleep Position Trainer device during the first 2 months, defined as use of Sleep Position Trainer >4 h per night for all weekdays, was 75.5% (SD 21.2). The discontinuation rate was 28.8 and 49.4% after 2 and 6 months, respectively.

Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling.

RATIONALE: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS: A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). MEASUREMENTS AND MAIN RESULTS: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. CONCLUSIONS: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).

Home Non Invasive Ventilation (NIV) treatment for COPD patients with a history of NIV-treated exacerbation; a randomized, controlled, multi-center study.

BACKGROUND: In chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory failure, long-term noninvasive ventilation is controversial in unstable patients with frequent exacerbations, complicated by acute hypercapnic respiratory failure. In an uncontrolled group of patients with previous episodes of acute hypercapnic respiratory failure, treated with noninvasive ventilation, we have been able to reduce mortality and the number of repeat respiratory failure and readmissions by continuing the acute noninvasive ventilatory therapy as a long-term therapy. METHODS: Multi-center open label randomized controlled trial of 150 patients having survived an admission with noninvasive ventilatory treatment of acute hypercapnic respiratory failure due chronic obstructive pulmonary disease. The included patients are randomized to usual care or to continuing the acute noninvasive ventilation as a long-term therapy, both with a one-year follow-up period. The primary endpoint is time to death or repeat acute hypercapnic respiratory failure; secondary endpoints are one-year mortality, number of readmissions and repeat acute hypercapnic respiratory failure, exacerbations, dyspnea, quality of life, sleep quality, lung function, and arterial gases. DISCUSSION: Though previous studies of long-term noninvasive ventilation have shown conflicting results, we believe the treatment can reduce mortality and readmissions when applied in patients with previous need of acute ventilatory support, regardless of persistent hypercapnia. TRIAL REGISTRATION: clinicaltrials.org: NCT01513655 16-Jan-2012.

Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit.

Chronic obstructive pulmonary disease (COPD), lung cancer, asthma and pulmonary tuberculosis are common pulmonary diseases that are caused or worsened by tobacco smoking. Growing observational evidence suggests that symptoms and prognosis of these conditions improve upon smoking cessation. Despite increasing numbers of (small) randomised controlled trials suggesting intensive smoking cessation treatments work in people with pulmonary diseases many patients are not given specific advice on the benefits or referred for intensive cessation treatments and, therefore, continue smoking.This is a qualitative review regarding smoking cessation in patients with COPD and other pulmonary disorders, written by a group of European Respiratory Society experts. We describe the epidemiological links between smoking and pulmonary disorders, the evidence for benefits of stopping smoking, how best to assess tobacco dependence and what interventions currently work best to help pulmonary patients quit. Finally, we describe characteristics and management of any "hardcore" smoker who finds it difficult to quit with standard approaches.

Exploratory survey study of long-term users of nicotine replacement therapy in Danish consumers.

BACKGROUND: Long-term use of nicotine replacement therapy (NRT) has been approved in several countries for smokers who are unable or unwilling to quit smoking. However, information on basic characteristics, degree of nicotine dependence, health status and contentment with long-term use of NRT is scarce. The aim of this study was to collect information on the characteristics of long-term NRT users, having used NRT for at least 12 months, reasons for, and contentment with, their continued use of NRT including reasons for wishing to quit or sustain use and an estimation of their degree of nicotine dependence. METHOD: Through advertisements in three national Danish newspapers, long-term NRT users were recruited to answer a short questionnaire about basic characteristics, health status and satisfaction with using NRT. A modified version of the Heaviness of Smoking Index (HSI) questionnaire was applied to estimate nicotine dependence. Linear regression was used to test association between time to first NRT and daily dosage of NRT. RESULTS: A total of 92 respondents were included in the data analysis. A majority of 88% wished to quit NRT for the following reasons: costs of NRT, being tired of feeling addicted and fear of adverse health effects. Scoring on the modified HSI scale was 22.0% low, 68.0% moderate and 9.3% high dependent. Of the respondents, 67.0% used NRT within the first 30 min after waking. A validation check found a significant linear association between the two items in the modified HSI. CONCLUSION: A significant majority of users wished to quit NRT because of the cost of products, being tired of feeling addicted and fear of adverse health consequences. The majority of these users were moderate to high nicotine dependent. The strong association found between time to first NRT and NRT dosages used per day gives reason to believe the validity of the modified HSI. Further studies are required for confirmation. Better counselling of long-term users on the benefits of using NRT compared to smoking should be provided, for those who are chronically dependent, as well as support to stop long-term use of NRT if wanted.

Smoking habits in the randomised Danish Lung Cancer Screening Trial with low-dose CT: final results after a 5-year screening programme.

BACKGROUND: We present the final results of the effect of lung cancer screening with low-dose CT on the smoking habits of participants in a 5-year screening trial. METHODS: The Danish Lung Cancer Screening Trial (DLCST) was a 5-year screening trial that enrolled 4104 subjects; 2052 were randomised to annual low-dose CT (CT group) and 2052 received no intervention (control group). Participants were current and ex-smokers (≥4 weeks abstinence from smoking) with a tobacco consumption of ≥20 pack years. Smoking habits were determined annually. Missing values for smoking status at the final screening round were handled using two different models. RESULTS: There were no statistically significant differences in annual smoking status between the CT group and control group. Overall the ex-smoker rates (CT + control group) significantly increased from 24% (baseline) to 37% at year 5 of screening (p<0.001). The annual point prevalence quit rate increased from 11% to 24% during the five screening rounds; the ex-smokers' relapse rate remained stable, around 11%, across the same period. CONCLUSIONS: Screening with low-dose CT had no extra effect on smoking status compared with the control group, but overall the screening programme probably promoted smoking cessation. CLINICAL TRIAL REGISTRATION: The DLCST is registered in Clinical Trials.gov Protocol Registration System (identification no. NCT00496977).

Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial.

INTRODUCTION: This study evaluated the effect of varenicline in combination with counseling to assist long-term nicotine replacement therapy (NRT) users to quit NRT. METHODS: This was a double-blind, placebo-controlled, randomized trial of varenicline or placebo for 12 weeks, with 52-week follow-up, performed in 1 hospital-based smoking cessation specialist clinic. At the first visit, 139 ex-smokers and long-term NRT users were allocated to treatment according to a computer-generated list with random numbers. Visits were scheduled at Weeks 0, 2, 4, 6, 9, 12, and 52. At each visit, nurse-led counseling was delivered, carbon monoxide in expired air, plasma cotinine, and body weight were assessed, and subjects were asked about craving, nausea, and dreams. The primary outcome was 12-week point prevalence quit rate (PPR) of nicotine replacement therapy use. RESULTS: At all time points, the PPR was superior for varenicline versus placebo, although the difference was only statistically significant at 12 and 36 weeks. The PPR was 64.3% (varenicline) versus 40.6% (placebo) at 12 weeks (p = .006), and 42.9% (varenicline) versus 36.2% (placebo) at 52 weeks (NS). The continuous abstinence rate from Week 9 to Week 12 was 48.6 % (varenicline) versus 30.4 % (placebo) (p = .03). Withdrawal symptoms were statistically significantly lower in the varenicline group than the placebo group. CONCLUSION: Varenicline for 12 weeks combined with supportive visits was superior to placebo to get long-term NRT users to quit NRT. A larger study is needed to evaluate long-term efficacy.

Niccine®, a nicotine vaccine, for relapse prevention: a phase II, randomized, placebo-controlled, multicenter clinical trial.

INTRODUCTION: A nicotine vaccine could prevent relapse to smoking by hindering blood nicotine from reaching the brain. Niccine® is a nicotine hapten tetanus-toxoid conjugate vaccine. The present study evaluated the clinical efficacy of Niccine for tobacco smoking relapse prevention. METHODS: Cigarette smokers (n = 355) aged 25-50 years were enrolled in a randomized, double-blind, parallel group 1-year trial encompassing 16 visits and 16 telephone calls. Niccine 40 µg or placebo was administered on Days 0, 28, 56, 90, 150, and 210. Between Days 56-98, subjects were treated with varenicline to aid cessation, targeted for Day 70. Only individuals abstinent between Days 90-98 (n = 265) were allowed to continue to 1 year (n = 219). Relapse to smoking was defined as >5 cigarettes within 7 days or since the last contact, or smoking on >5 occasions within 7 days or since the last contact. RESULTS: At 1 year, nonrelapse was 43.3% in the Niccine versus 51.1% in the placebo groups (difference = -7.9%; 95% CI = -20.6% to 4.9%). There was no benefit of Niccine on smoking status at 6 or 9 months, exhaled carbon monoxide levels, time to relapse, abstinence, withdrawal symptoms, or smoking reinforcement. Nicotine antibody levels increased (mean = 1.34 µg/ml; SD = 2.84 µg/ml) in the Niccine group, but were not related to relapse. Adverse events except hypersensitivity and compensatory smoking did not differ between groups. CONCLUSIONS: This nicotine vaccine appeared well tolerated but did not influence trajectories of relapse possibly because of insufficient antibody levels or lack of efficacy of the vaccine concept for relapse prevention.

Long-term non-invasive ventilation for COPD patients following an exacerbation with acute hypercapnic respiratory failure: a randomized controlled trial.

Introduction: It remains unclear whether long-term non-invasive ventilation (LT-NIV) for patients with chronic obstructive pulmonary disease (COPD) improves survival and reduces admissions as results from randomized trials are inconsistent. We aim to determine whether LT-NIV initiated after an admission with acute hypercapnic respiratory failure (AHRF) can affect survival and admission rate in COPD patients. Methods: A randomized controlled open-label trial, allocating patients with COPD to LT-NIV or standard of care immediately after an admission with AHRF treated with acute NIV. LT-NIV was aimed to normalize PaCO2 using high-pressure NIV. Results: The study was discontinued before full sample size due to slow recruitment. 28 patients were randomized to LT-NIV and 27 patients to standard of care. 42% of patients had a history of ≥ 2 admissions with AHRF. Median IPAP was 24 cmH2O (IQR 20-28). The primary outcome, time to readmission with AHRF or death within 12 months, did not reach significance, hazard ratio 0.53 (95% CI 0.25-1.12) p = 0.097. In a competing risk analysis, adjusted for history of AHRF, the odds ratio for AHRF within 12 months was 0.30 (95% CI 0.11-0.87) p = 0.024. The LT-NIV group had less exacerbations (median 1 (0-1) vs 2 (1-4) p = 0.021) and readmissions with AHRF (median 0 (0-1) vs 1 (0-1) p = 0.016). Conclusion: The risk of the primary outcome, time to readmission with AHRF or death within 12 months was numerically smaller in the LT-NIV group, however, did not reach significance. Nevertheless, several secondary outcome analyses like risk of AHRF, number of episodes of AHRF and exacerbations were all significantly reduced in favour of high-pressure LT-NIV, especially in patients with frequent AHRF.

CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT.

BACKGROUND: The effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial. METHODS: 4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time<400 days) and nodules >15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice. RESULTS: Participation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p=0.535). More lung cancers were diagnosed in the screening group (69 vs. 24, p<0.001), and more were low stage (48 vs 21 stage I-IIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p=0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16 stage IIIA-IV NSCLC and extensive stage SCLC, p=0.509). At the end of screening, 61 patients died in the screening group and 42 in the control group (p=0.059). 15 and 11 died of lung cancer, respectively (p=0.428). CONCLUSION: CT screening for lung cancer brings forward early disease, and at this point no stage shift or reduction in mortality was observed. More lung cancers were diagnosed in the screening group, indicating some degree of overdiagnosis and need for longer follow-up.

Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial.

A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy, such as a faster uptake of nicotine and faster relief of craving. This multicentre, randomised (2:1), double-blind, placebo-controlled efficacy and safety study evaluated self-reported, carbon monoxide-verified continuous abstinence from smoking from week 2 until weeks 6, 24, and 52 in 479 smokers (≥ 1 cigarette per day) who were treated with either active (n=318) or placebo (n=161) spray for 12 weeks and low-intensity counselling at three smoking cessation clinics in Denmark and Germany. Active treatment yielded significantly higher continuous abstinence rates than placebo from week 2 until week 6 (26.1% versus 16.1%; relative success rate (RR) 1.62, 95% CI 1.09-2.41), week 24 (15.7% versus 6.8%; RR 2.30, 95% CI 1.23-4.30), and week 52 (13.8% versus 5.6%; RR 2.48, 95% CI 1.24-4.94). Most adverse events were mild to moderate, and 9.1% of subjects on active spray withdrew due to adverse events, compared to 7.5% on placebo. The overall rate of treatment-related adverse events was 87.4% with active spray versus 71.4% with placebo spray. Nicotine mouth spray delivered significantly higher 6-, 24- and 52-week continuous abstinence rates than placebo.

The European Respiratory Society spirometry tent: a unique form of screening for airway obstruction.

In order to raise public awareness of the importance of early detection of airway obstruction and to enable many people who had not been tested previously to have their lung function measured, the European Lung Foundation and the European Respiratory Society (ERS) organised a spirometry testing tent during the annual ERS Congresses in 2004-2009. Spirometry was performed during the ERS Congresses in volunteers; all participants answered a simple, brief questionnaire on their descriptive characteristics, smoking and asthma. Portable spirometers were freely provided by the manufacturer. Nurses and doctors from pulmonary departments of local hospitals/universities gave their service for free. Lower limit of normal (LLN) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for diagnosing and grading airway obstruction were used. Of 12,448 participants in six congress cities, 10,395 (83.5%) performed acceptable spirometry (mean age 51.0 ± 18.4 yrs; 25.5% smokers; 5.5% asthmatic). Airway obstruction was present in 12.4% of investigated subjects according to LLN criteria and 20.3% according to GOLD criteria. Through multinomial logistic regression analysis, age, smoking habits and asthma were significant risk factors for airway obstruction. Relative risk ratio and 95% confidence interval for LLN stage I, for example, was 2.9 (2.0-4.1) for the youngest age (≤ 19 yrs), 1.9 (1.2-3.0) for the oldest age (≥ 80 yrs), 2.4 (2.0-2.9) for current smokers and 2.8 (2.2-3.6) for reported asthma diagnosis. In addition to being a useful advocacy tool, the spirometry tent represents an unusual occasion for early detection of airway obstruction in large numbers of city residents with an important public health perspective.

Medication-assisted quit rates in participants with smoking-related diseases in EAGLES: Post hoc analyses of a double-blind, randomized, placebo-controlled clinical trial.

INTRODUCTION: Greater understanding is required of how smokers with smoking-related diseases respond to smoking cessation medications. This post hoc analysis of EAGLES data compared continuous abstinence rates (CARs) in smokers with/without smoking-related diseases and assessed participant demographic and baseline characteristics that may serve as predictors of continuous abstinence (CA). METHODS: EAGLES was a 24-week (12-week treatment, 12-week follow-up), double-blind, active- (nicotine replacement therapy; patch) and placebo-controlled study in motivated-to-quit smokers with/without psychiatric disorders. This analysis assessed CARs at weeks 9-12 (CAR9-12) and 9-24 (CAR9-24) in participants with smoking-related diseases [asthma, chronic obstructive pulmonary disease (COPD), diabetes, and/or cardiovascular disease (n=1372)] versus controls without these comorbidities (n=6039). Participants received varenicline 1 mg twice daily, bupropion 150 mg twice daily, nicotine patches 21 mg/day with taper, or placebo for 12 weeks. Stepwise logistic modeling was also performed to analyze odds ratio (OR) for predictors of CA at weeks 9-12 (CA9-12) and 9-24 (CA9-24). RESULTS: Smokers with smoking-related diseases were older, had a longer smoking history, more quit attempts, and were more likely to have a psychiatric disorder and reside in the US versus smokers without comorbidities. Fagerström Test for Cigarette Dependence scores and treatment adherence were comparable between cohorts. Smokers with smoking-related diseases had lower CARs versus controls (CAR9-12: 20.8% vs 24.0%; CAR9-24: 13.0% vs 16.9%). Use of smoking cessation medication was the strongest predictor of CA after control for demographics, smoking characteristics, and psychiatric disorder. By treatment, OR and CI were: varenicline CA9-12 (OR=3.82; 95% CI: 3.21-4.54) and CA9-24 (OR=2.92; 95% CI: 2.40-3.54); bupropion CA9-12 (OR=2.17; 95% CI: 1.81-2.60) and CA9-24 (OR=1.99; 95% CI: 1.63-2.44); nicotine patches CA9-12 (OR=2.23; 95% CI: 1.87-2.67) and CA9-24 (OR=1.86; 95% CI: 1.52-2.28). CONCLUSIONS: Smokers with smoking-related diseases had lower quit rates than controls. Of the active treatments compared, varenicline was most effective in smokers with asthma, COPD, diabetes, or cardiovascular disease. TRIAL REGISTRATION: NCT01456936 (https://clinicaltrials.gov/ct2/show/NCT01456936).

Short-term effect of changes in smoking behaviour on emphysema quantification by CT.

BACKGROUND: The effect of smoking cessation and smoking relapse on lung density was studied using low-dose CT. METHODS: Spiral, multidetector, low-dose CT was performed on 726 current and former smokers (>20 pack-years) recruited from a cancer screening trial. Lung density was quantified by calculating the 15th percentile density (PD15), which was adjusted to predicted total lung capacity. Data were analysed by linear regression models. RESULTS: At baseline mean PD15 was 45 g/l in former smokers (n=178) and 55 g/l in current smokers (n=548), representing a difference of 10 g/l (p<0.001). After smoking cessation (n=77) PD15 decreased by 6.2 g/l (p<0.001) in the first year, and by a further 3.6 g/l (p<0.001) in the second year, after which no further change could be detected. Moreover, the first year after relapse to smoking (n=18) PD15 increased by 3.7 g/l (p=0.02). CONCLUSIONS: Current smoking status has a major influence on lung density assessed by CT, and the difference in lung density between current and former smokers observed in cross-sectional studies corresponds closely to the change in lung density seen in the years after smoking cessation. Current smoking status, and time since cessation or relapse, should be taken into account when assessing the severity of diseases such as emphysema by CT lung density.

Dianicline, a novel α4ß2 nicotinic acetylcholine receptor partial agonist, for smoking cessation: a randomized placebo-controlled clinical trial.

INTRODUCTION: Dianicline is a α4ß2 nicotinic acetylcholine receptor partial agonist, a class of drugs that includes varenicline and cytisine. Varenicline is efficacious for smoking cessation, while cytisine has not been studied systematically. The efficacy of dianicline has not been previously tested in an adequately powered study. METHODS: In a randomized, double-blind, parallel group placebo-controlled trial, 602 generally healthy cigarette smokers were assigned to dianicline (n = 300) or placebo (n = 302) for 7 weeks followed by a 19-week off drug follow-up period. RESULTS: Exhaled carbon monoxide and cotinine-confirmed continuous abstinence rates for Weeks 4-7 were 24.0% for dianicline versus 20.5% for placebo (odds ratio 1.22; 95% CI, 0.83-1.80; p = .307). For Weeks 4-26, the abstinence rates were 16.7% for dianicline versus 13.9% for placebo (odds ratio 1.24; 95% CI, 0.79-1.93; p = .366). Craving for a cigarettes was reduced by dianicline compared with placebo after 7 weeks (p = .0175). Nicotine withdrawal symptoms measured by the Hughes and Hatsukami Minnesota Withdrawal Scale were lower for dianicline compared with placebo in the first 3 weeks of treatment during which time quit rates were also higher in the dianicline-treated group. CONCLUSIONS: Dianicline did not increase cigarette smoking abstinence rates beyond the initial phase of treatment. However, self-reported craving and nicotine withdrawal symptoms were reduced.

TOB-STOP-COP (TOBacco STOP in COPd trial): study protocol-a randomized open-label, superiority, multicenter, two-arm intervention study of the effect of "high-intensity" vs. "low-intensity" smoking cessation intervention in active smokers with chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15-20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. METHODS: This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 1:1 to either a standard treatment (guideline-based municipal smoking cessation program, "low intensity" group) or an intervention ("high-intensity" group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and "buddy-matching" (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. DISCUSSION: The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019.

Smoking cessation: How compelling is the evidence? A review.

OBJECTIVES: To provide a short review of the evidence base supporting smoking cessation interventions, including behavioral therapy and pharmacological treatment options. METHODS: Published meta-analysis was mainly used supplemented with a limited literature search. RESULTS: Effective smoking cessation consists of pharmacotherapy and behavioral support. Counseling increases abstinence rates parallel to the intensity of support. First-line pharmacological drugs for smoking cessation are nicotine replacement products (patch, gum, inhaler, nasal spray, lozenge/tablets), varenicline and bupropion SR with scientific well-documented efficacy when used for 2-3 months and mostly mild side effects. Alternative therapies such as hypnosis and acupuncture have no scientifically proven effects. CONCLUSIONS: With the most optimal drugs and counseling today a 1-year abstinence rate of approximately 25% can be expected in smoking cessation. On-going research is examining the potential effects of nicotine vaccination as relapse prevention.

The effect of inhaled corticosteroids on the development of emphysema in smokers assessed by annual computed tomography.

The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 microg bid, or placebo. COPD was defined as FEV(1) < or = 70% pred, FEV(1)/FVC < or = 60% and no reversibility to beta(2)-agonists and oral corticosteroids. The patients were followed for 2-4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15th percentile density (PD15) and the relative area of emphysema at a threshold of -910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV(1) was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was -1.12 g/L in the budesonide group and -1.81 g/L in the placebo group (p = 0.09); the annual increase in RA-910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV(1) between ICS (-54 mL) and placebo (-56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.

Secular trends in smoking in relation to prevalent and incident smoking-related disease: A prospective population-based study.

INTRODUCTION: We examined changes in smoking habits in the general population according to prevalence and incidence of chronic diseases affected by smoking. METHODS: We included 12283 individuals enrolled from 2003 in the Copenhagen General Population Study and re-examined from 2014. Participants were classified as either healthy or suffering from chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus, heart disease or stroke. RESULTS: At entry, smoking prevalence was 15.4% in healthy participants, 29.8% with COPD, 15.8% with asthma, 21.7 % with diabetes mellitus, 17.2 % with ischemic heart disease/heart failure and 18.6% in participants with previous stroke. Smoking prevalence declined during the 10 years of observation. Among healthy subjects who developed one of the above mentioned diseases during follow-up, those who developed COPD had the highest initial smoking prevalence (51.5%). Quit rates were highest in those who developed asthma resulting in smoking prevalence of 8.2% versus 27.7% in COPD. After adjustment for age, smoking severity and genotype previously associated with heavy smoking (CHRNA3 rs1051730 AA), significant predictors of quitting were new diagnosis of ischemic heart disease/heart failure (OR=2.33, 95 % CI: 1.61-3.42), new diagnosis of asthma (OR=1.84, 95% CI: 1.18-2.90) and low number of pack-years. CONCLUSIONS: Individuals with prevalent smoking related diseases continued to smoke more than healthy individuals. Incident heart disease and asthma, but not incident COPD, stroke or diabetes were associated with a higher chance of quitting. Special focus on smokers with COPD, asthma, diabetes, stroke and ischemic heart disease/heart failure is warranted to decrease smoking prevalence in these groups. Smokers with a new diagnosis of diabetes, stroke and COPD need special smoking cessation support.

Mortality and use of psychotropic medication in sleep apnoea patients: a population-wide register-based study.

BACKGROUND: This study aimed to evaluate all-cause mortality in relation to the use of benzodiazepines, antidepressants and antipsychotics in obstructive sleep apnoea (OSA) patients and matched controls. METHODS: Patients with a diagnosis of OSA and no pre-index use of psychotropic medication (n = 38,735) were compared with control subjects (n = 75,941) matched by age, gender, marital status and community location. National register data were used to obtain information on diagnoses (the Danish National Patient Registry), mortality (the Central Person Register) and psychotropic medication use (the Danish Register on Medicinal Product Statistics). RESULTS: All-cause mortality was higher in patients with OSA than in control subjects. Mortality hazard ratios were higher for OSA patients and controls who were prescribed serotonergic antidepressant drugs (HR = 1.808, SD = 0.015, p = 0.001 in OSA patients; HR = 2.607, SD = 0.158, p < 0.001 in controls), tricyclic antidepressants (HR = 1.846, SD = 0.166, p < 0.001; HR = 2.087, SD = 0.172, p < 0.001), benzodiazepines (HR = 2.590, SD = 0.040, p < 0.001); (HR = 3.705, SD = 0.085, p < 0.001), benzodiazepine-like drugs (HR = 1.980, SD = 0.087, p < 0.001; HR = 2.227, SD = 0.083, p < 0.001), first-generation antipsychotics (HR = 2.894, SD = 0.268, p < 0.001; HR = 1.210, SD = 0.509, NS), and second-generation antipsychotics (HR = 2.069, SD = 0.182, p < 0.001; HR = 1.355, SD = 0.171, NS), compared with those who did not receive the drugs. Interaction analysis suggested that similar or slightly lower mortality was associated with selective serotonin re-uptake inhibitors, benzodiazepines and second-generation antipsychotics in OSA compared with controls when comorbidities were taken into consideration. CONCLUSION: All-cause mortality was higher in OSA patients and especially controls treated with benzodiazepines, antidepressants or antipsychotics than in untreated controls. The findings were not controlled for psychiatric comorbidity and the results may have partly been attributable to confounding by indication. The results raised the possibility that the use of psychotropic medication may have deleterious health consequences, but the risk did not seem to be higher in OSA than in controls.