Title: Effectiveness of Electronic Cigarettes compared with combination nicotine replacement therapy for smoking cessation in patients with chronic obstructive pulmonary disease And effect on Lung health (ECAL study)
Funder: Department of Health and Social Care

Abstract: Introduction_x000D_ Many patients with chronic obstructive pulmonary disease (COPD) smoke. It is important for COPD patients to stop as continued smoking worsens their condition. E-cigarettes (ECs) are a device that vapourise a liquid that can contain nicotine which is then inhaled by the user. They can be bought from shops or online, and many people have used them successfully to stop smoking. We know that people with COPD are also using ECs to help them stop. However there are some unanswered questions about how well they work for people with COPD compared to other effective treatments (e.g. nicotine replacement therapy (NRT)) and what effects they might have on the lung. EC vapour is likely to be much less harmful than cigarette smoke, but there is a possibility that it might irritate the lung. Some laboratory studies have shown vapour has an effect on lung cells but it is unknown if this would also be true when ECs are used by people, or if it would affect their health. _x000D_ _x000D_ Methods_x000D_ In order to compare how well ECs work compared with combination NRT (use of a nicotine patch and also an oral nicotine product such as gum, lozenge or tablet), we will carry out a trial in 1250 COPD patients who smoke to test if more people are able to stop smoking using ECs. In patients who are able to stop smoking and vape instead we will look at important measures of lung health, and compare this with people who stop smoking but don’t vape and with people who aren’t able to stop smoking but continue smoking instead._x000D_ _x000D_ COPD smokers who are under the care of a participating hospital or are registered with a GP local to a participating hospital will be asked if they want to take part. To take part, a patient must be smoking daily and want to try and stop smoking. At an initial hospital visit, patients will complete questionnaires, give blood samples and undertake some lung function tests. All patients will be assigned an EC or combination NRT and given instructions on how to use their assigned product and will receive stop smoking support through telephone calls. The first call will be within a few days of their hospital appointment to give support and set a date when they will stop smoking altogether. Participants will be called back on the day they plan to stop and after 1, 2, 3 and 4 weeks to give support and answer any questions. After 26 and 52 weeks, all participants will return to the hospital to give another blood sample, complete questionnaires and repeat the tests they did at the first visit. _x000D_ _x000D_ Patient involvement and communicating the results_x000D_ We have presented this plan at patient groups, and many felt that it was important to know if ECs help COPD patients stop smoking, and to understand what effect they have on the lungs. Two patients with COPD are also members of our study team and one patient is part of a wider group that we will consult with on a regular basis during the running of the research. We will present our findings at research conferences, and let patients and clinicians know the results through publication in scientific journals, releasing to the press and contacting key organisations (e.g. related charities, Public Health England).

Lay abstract: Research questions_x000D_ Among patients with COPD:_x000D_ (1) What is the effectiveness, cost-effectiveness and safety of e-cigarettes (ECs) compared with combination nicotine replacement therapy (NRT) as an aid to smoking cessation? _x000D_ _x000D_ (2) What is the effect of switching from smoking to exclusive EC use on lung health measures compared with quitting smoking without vaping, and continuing to smoke? _x000D_ _x000D_ Background _x000D_ Around 35% of patients with COPD smoke. Smoking cessation is the only known strategy that slows the accelerated decline in lung function in these patients, and although there are effective smoking cessation treatments over 80% return to smoking. ECs are commercially available devices that many people have used successfully to stop smoking. However there remain some unanswered questions about their effectiveness and effects on the lungs. _x000D_ _x000D_ Aims and objectives_x000D_ Conduct a two-arm, multicentre randomised controlled trial (RCT) in 1250 patients with COPD to evaluate the effectiveness, cost-effectiveness and safety of e-cigarettes for quitting smoking compared with combination NRT. _x000D_ _x000D_ In nested cohort analyses of trial participants, we will investigate change in clinical, physiological and cellular measures of lung health in participants who switch from smoking to exclusive vaping (vapers) and compare this with those who quit smoking without vaping (quitters) and those who continue to smoke (smokers)._x000D_ _x000D_ Methods_x000D_ The study will take place in a hospital setting and the primary outcome will be biochemically confirmed prolonged abstinence from smoking at 52 weeks. Eligible patients will be recruited from COPD clinics in participating hospitals or will be invited from local GP practices to take part at the hospital. At the initial hospital visit, participants will be randomly assigned to EC or combination NRT and asked to complete questionnaires, give a blood sample and undertake lung function tests. All will receive standard stop smoking behavioural support through telephone calls from a trained smoking cessation advisor within a few days of their hospital appointment, on their planned quit day and after 1, 2, 3 and 4 weeks post quit. After 26 weeks, participants will be followed up by phone, post or electronically to complete questionnaires. After 52 weeks, participants will return to hospital to complete questionnaires, lung function tests and give blood samples. Trial outcomes will be analysed using regression analyses. Nested cohort analyses conducted in trial participants will re-group patients by smoking/vaping status, and compare changes in clinical, physiological and cellular lung health measures between the three exposure groups. _x000D_ _x000D_ This study will be powered to confirm if ECs are better than combination NRT for smoking cessation, and will enable investigation of the effect of EC on the lungs in a group of patients who are likely to be susceptible to any harmful effects. _x000D_ _x000D_ Anticipated impact and dissemination_x000D_ Findings of this research will be relevant to policy and practice recommendations for essential stakeholder groups including academia, healthcare professionals, industry, public health agencies and also importantly the lay public understanding of the effectiveness and safety of ECs. We will ensure wide dissemination through academic, health organisation and media channels.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: RESPIRATORY