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)

Research questions Among patients with COPD: (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? (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? Background 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. Aims and objectives 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. 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). Methods 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. 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. Anticipated impact and dissemination 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.