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16th October 2023
Tobacco dependency and e-cigarettes are never far from the headlines, and while progress is being made across the UK, there’s still a long way to go to ensure a consistent approach to smoking cessation support in secondary care. Here, Dr Zaheer Mangera, respiratory consultant at North Middlesex University Hospital, speaks to clinical writer Rod Tucker and shares his insights and advice around best practice.
Dr Zaheer Mangera is a respiratory consultant at North Middlesex University Hospital, where his main scope of practice is lung cancer, though he also sees patients with other respiratory diseases such as asthma and COPD.
He has a strong interest in tobacco dependency and is chair of the British Thoracic Society’s tobacco specialist advisory group. In addition to his clinical role, Dr Mangera is also involved in undergraduate medical education, teaching at University College London medical school.
As the lung cancer lead at North Middlesex University Hospital, part of Dr Mangera’s role is to maintain overall responsibility for the National Optimal Lung Cancer Pathway. Developed in 2017, it aims to improve and streamline the patient pathway to enable a more prompt diagnosis of those with lung cancer at the earliest possible stage when, of course, treatment is most effective.
‘You’re trying to get everyone diagnosed with cancer and treatment within 49 days of a referral being made of a suspected cancer,’ he says. And while he sees this target as quite challenging, it is evidence-based and therefore worth pursuing. An additional component of the pathway is the requirement to support those who continue to smoke when presenting with suspected lung cancer and encouraging cessation.
Another area of work that consumes a good deal of Dr Mangera’s time is spent on imaging interpretation. ‘The chest gets scanned for all sorts of different reasons and I spend a lot of time looking at incidental findings, which require someone to take a look and make a decision as to whether they need to be taken forward or whether they can be dismissed,’ he says.
Explaining these findings to patients can often pose a challenge, particularly when benign lung nodules are identified. ‘More than 90% of lung nodules under 1cm are not cancer, and most patients are able to understand and appreciate that the overall risk is low and recognise the need that some [nodules] will need follow-up,’ Dr Mangera explains. This could be further scanning over the next two years or an extended follow-up period of four years.
In September 2023, a Cochrane review updated its earlier findings on the most effective pharmacological interventions for smoking cessation in adults. They key messages centred on the fact that all available treatments are effective, albeit with varying degrees of success.
Interestingly, the Cochrane review found that e-cigarettes and varenicline have a success rate with an additional seven to eight more quitters per 100 when compared to control, which is slightly higher than combination nicotine replacement therapy (NRT). Dr Mangera believes that irrespective of the intervention, ‘the most important thing is that it’s being used to its maximum benefit’.
He proposes that part of the reason why established interventions such as NRT fail, is because ‘it’s not matching the needs of the patient who is trying to stop smoking, and it is very common for individuals to be underdosed and not getting a sufficiently strong background amount of nicotine’.
Over the years, Dr Mangera has come to appreciate the importance of having appropriately trained staff who are able to deliver additional advice for those wishing to stop smoking. Unfortunately, the provision of this specialist advice throughout the NHS is patchy.
‘My hospital is served by four different boroughs, but of the two main boroughs, one does have a stop smoking service whereas the other borough doesn’t have such a service. It’s a genuine postcode lottery as to how I can support patients. One group will be called up within a week and get access to specialist advice, whereas the other gets no support at all,’ he explains.
Specialist advice, often in the form of motivational interviewing, is a recognised strategy for increasing an individual’s success at smoking cessation. ‘That’s where you need the whole package. Just giving somebody the drugs and sending them on their way, the success rate is between 10 and 20%, but that is certainly better than willpower alone, which can be 2-3%,’ says Dr Mangera.
When patients receive a pharmacological intervention as well as specialist advice, ‘they are three times more likely to be successful in stopping smoking’, he adds.
Though NRT has slightly lower quit rates, Dr Mangera believes that the easy access to these products through pharmacies, supermarkets and online shops makes it a very worthwhile option to signpost to smokers.
The likelihood that a patient will stop smoking can dramatically change if there is a significant life event such as hospitalisation. Such an event often makes current smokers acutely aware of the adverse health sequalae linked to their smoking.
This transtheoretical model includes six different stages moving from starting to consider quitting to complete cessation: precontemplation, contemplation, preparation, action, maintenance or termination.
But one factor that is likely to serve as a motivator for change is a significant life event such as hospitalisation. Such an event often makes current smokers acutely aware of the adverse health sequalae linked to their smoking.
Dr Mangera clarifies: ‘When you are an inpatient, you are twice as likely to want to stop smoking than at other times in your life.’ This provides a huge opportunity for buy-in from patients and a greater willingness to want to quit.
The NHS long-term plan seeks to capitalise on this fact and already includes funding for tobacco dependency treatment for all inpatients who smoke. Dr Mangera says that while the complete rollout of this service is yet to be realised throughout the NHS, there has been considerable engagement to date in many hospitals.
The NHS approach is based on the findings of the Ottawa Model for Smoking Cessation (OMSC) in which quit rates for hospitalised patients supported by this systematic approach to provider-level support ranged from 18-48% after 180 days.
But whereas the NHS plan has been met with some success, Dr Mangera describes how it seems that the NHS has gone full circle. In the past, he says, a number of specialist tobacco advisors were recruited but then ‘the service was de-funded’ and rebuilding the expertise of the past is challenging and time consuming.
‘You can’t just find tobacco advisors off the shelf. The period of training that’s required can take weeks, if not months,’ he says. Consequently, the whole process of recruitment and development of a business case can take many months before a service is up and running.
A further problem he outlines is that aspects of the NHS long-term plan were introduced during the Covid-19 pandemic, and with the current strikes by medical staff and increased waiting times, the full implementation has been hampered.
That being said, Dr Mangera cites the success of The CURE Project – a secondary care treatment programme for tobacco addiction in Greater Manchester.
The project systematically identifies all active smokers admitted to secondary care and offers NRT and other medications, as well as specialist support, for the duration of the admission and after discharge.
Preliminary results reveal that of nearly 2,400 individuals identified in the project, 22% self-reported that they had stopped smoking 12 weeks later. Dr Mangera believes that with the necessary political willpower and funding there is little reason to suggest that the success of the CURE project could not be replicated across England and perhaps beyond.
That’s not to say, however, that there wouldn’t be challenges to overcome with the wider rollout of an in-patient tobacco dependency service. Dr Mangera identifies one such logistical challenge as access to an appropriate IT system to help identify current smokers. This problem is further compounded by the fact that hospitals often use different systems with dissimilar methods of reporting the data, he says.
A much more challenging issue is recruitment and training of the necessary workforce. Even the training of doctors he feels will be difficult to embed within the current undergraduate medical curriculum.
‘Every single speciality wants to put their bit into the curriculum, so trying to create that consistency across medical schools is not easy,’ he says.
Though all doctors will receive some degree of training in smoking cessation as undergraduates, in reality, this knowledge does not appear to be utilised in practice. Dr Mangera cites British Thoracic Society National Secondary Care audits that demonstrate that a patient’s smoking status is often not being recorded in secondary care and smokers are often not offered any form pharmacotherapy or even referred to a specialist service.
In short, he believes that the limited training in the delivery of smoking cessation advice is compounded by the fact that ‘newly qualified doctors are not entering a hospital where systems are in place to make these things as easy as possible’. Furthermore he emphasises the importance of framing this as ’everybody’s business’, as all healthcare providers should be trained in offering patients advice and direction on how they can access stop smoking support.
But it’s not all doom and gloom. Where tobacco dependency services have been established in some hospitals, several important aspects attributed with successful implementation are evident.
For example, Dr Mangera believes that strong leadership from a senior clinician or a member of the executive team, with direct responsibility for the service, is a must. Repositories of information, such as detailed guidelines and protocols, are also vital to allow clinical staff to quickly get up to speed with the service and ensure consistent delivery.
With a lack of specialist advisors, it becomes all the more necessary to ensure secondary care professionals are able to deliver smoking cessation advice to in-patients. Dr Mangera says that a short, online smoking cessation course, such as those developed by the National Centre for Smoking Cessation and Training, can be used train health professionals on the delivery very brief smoking cessation advice.
He adds that all doctors – and ideally all patient facing healthcare professionals – should be able to ask patients about their smoking status and offer advice and, where appropriate, have NRT prescribed within the first 24 hours. These patients may be able to experience a temporary smoking abstinence, which will improve their inpatient experience and reduce the effects of withdrawal, as well as signpost the impact of smoking on their overall health.
In addition, because many NRT products are freely available over the counter, some centres have adopted a home remedy approach. In other words, hospitalised patients are not denied access to products that are available to the wider public and accessible during their hospital stay and on discharge.
Although once outside of hospital, access a specialist tobacco advisor can be variable, Dr Mangera suggests that patients can turn to either the national or regional smoking cessation services. Whilst not able to provide a full package, patients are always able to access ‘some form of support’, he says.
Although e-cigarettes have been available for many years, Dr Mangera feels that these products represent an important component of smoking cessation outside of a traditional programme.
‘Vaping is interesting in that it’s a way of reliably delivering nicotine replacement, but there are so many confounding concerns about it that the messaging around vaping is very confusing for patients,’ he says.
There is no doubt that it is safer than cigarettes, and vaping is recognised as having a role by multiple organisations including NICE and the Royal College of Physicians. However, there remain concerns about its uptake in young adults and children and the longer-term impacts on health.
For this reason, vaping has polarised medical opinion. For instance, some doctors consider it to be a much safer option than smoking whereas others are much more apprehensive about its role, particularly as NRT is already widely available. And Dr Mangera is aware of a number of case reports from around the world showing how vaping can lead to lung injury in specific circumstances, although the overall numbers are small.
Despite these concerns, a living Cochrane review suggests e-cigarettes help people to quit smoking better than traditional NRT, and Dr Mangera believes there is a general consensus that vaping is far less harmful than smoking. His personal view is that younger smokers and vapers should be supported with their nicotine addiction with the goal of complete abstinence, but that there is a role for vaping to be used as a harm reduction strategy alone in older smokers, with or without a smoking-related disease, who have considered all other options.
Finally, Dr Mangera says that while there are still teething problems with the national roll-out of the NHS long-term plan and its associated tobacco dependency services, he remains hopeful that this innovation is likely to have a major impact on the quit rates of smokers admitted to hospital in England.
He says that as whole, the UK is performing better than other countries in reducing smoking rates, and legal changes such as the ban of public smoking and strict controls on advertising have the largest impact. Right now, the UK Government is working through a plan to ban smoking completely for future smokers and, for Dr Mangera, this marks a moment in history.
Continued success does require the necessary political commitment to sustained funding, but at the present time, the current direction of travel remains positive.
7th August 2023
With varenicline currently unavailable, it is possible that cytisine might serve as an alternative pharmacotherapy to help patients to stop smoking. Here, clinical writer Rod Tucker investigates.
Tobacco smoking is a major cause of premature death and it is estimated that current smokers will die an average of 10 years earlier than non-smokers. But, despite the widespread acknowledgement of the dangers associated with smoking, millions of people across the world continue to smoke. In its most recent assessment, the World Health Organization suggests that tobacco kills more than eight million people each year – a figure that includes 1.3 million non-smokers who are exposed to secondhand smoke.
Although smoking is linked to a range of adverse health effects, much attention has been directed at the links with lung cancer. In fact, estimates suggest that 90% of lung cancer deaths are due to smoking. Fortunately, there is a large body of robust evidence supporting the effectiveness of pharmacotherapies for smoking cessation. In fact, even if smoking cessation is started at the time of a lung cancer diagnosis, there is still an improvement in overall survival.
The benefits of smoking cessation treatment were highlighted in a 2021 systematic review, which suggested that there was strong evidence for a range of pharmacologic and behavioural interventions at increasing smoking cessation. One such treatment is varenicline, which, according to the systematic review, was associated with a more than two-fold increase in the smoking cessation success rate.
However, varenicline is currently unavailable in the UK and Europe. It was withdrawn by the manufacturer, Pfizer in 2021 due to the presence of high levels of N-nitroso-varenicline – a probable human carcinogen.
Attention then turns to the most suitable alternatives to varenicline. One potential treatment cytisine but, despite being available for over 50 years, the drug is still not licensed in many countries beyond Eastern Europe. So, how effective is cytisine as an aid to smoking cessation, and why is it not widely available?
Cytisine, or, more correctly, cytisinicline, is an alkaloid that is a partial nicotinic acetylcholine receptor agonist. Derived from the plant Cytisus laburnum, it was discovered in 1865, but it was not until 1912, that its pharmacological actions were described as almost indistinguishable from that of nicotine.
The drug was brought to market in 1964 under the brand name Tabex by the Bulgarian company Sopharma, which described it as a plant-based drug used for smoking secession. Today, cytisine is marketed in 18 countries, but is not authorised in the UK, European or US markets, nor any country where the regulatory approval processes of these countries are followed, such as New Zealand.
Much of the early research on cytisine was undertaken during the 1960s in Eastern Europe. However, due to a combination of language and Iron-Curtain barriers, many clinicians in westernised countries were largely unfamiliar with the drug.
Nevertheless, the early research had not gone completely unnoticed. The development of varenicline for instance, which has an identical mode of action to cytisine, was influenced by the recognition that partial nicotinic acetylcholine receptor agonists were implicated in regulating the mesolimbic dopaminergic pathway, which mediates many aspects of tobacco dependence.
The first systematic review of the clinical data on cytisine was undertaken in 2006. The review included data from 10 studies published between 1967 and 2005 in Bulgaria, Germany, Poland and Russia, three of which, were placebo-controlled trials. Although the authors of the review concluded that cytisine appeared to be effective, they also noted how most trials were of poor quality.
Since that first review, several more rigorous randomised trials have been conducted. One such trial in 2011, observed a significantly higher rate of sustained 12-month abstinence of 8.4% for cytisine compared to 2.4% with placebo (p = 0.001). The following year, a double-blind, randomised, placebo-controlled trial, also showed that cytisine was associated with a significantly greater abstinence rate compared to placebo (p = 0.01).
But, the true value of a drug‘s efficacy is really only established in trials using an active comparator. To date, several such trials have been undertaken with either varenicline or nicotine replacement therapy (NRT).
One such trial from 2014 compared cytisine for 25 days to eight weeks of NRT. In terms of continuous abstinence, cytisine was superior to NRT after one week, two months and six months.
When it comes to comparing varenicline, a trial in 2021 concluded that cytisine treatment for 25 days, compared with varenicline for 84 days, failed to demonstrate non-inferiority regarding smoking cessation. A second 2021 trial also concluded that cytisine and varenicline were not significantly different.
In contrast, however, a comparative study published in 2023, found that the standard 12-week varenicline treatment was more effective than the standard 4-week cytisine treatment. The study, which was undertaken in primary care practices in Croatia and Slovenia, showed that the smoking cessation rate after 24 weeks was 32.5% for varenicline but only 23.1% for cytisine. Despite this lower efficacy, the authors did conclude that adherence was higher, and the rate of adverse events lower, among participants assigned to cytisine.
The most recent trial, published in July 2023, compared a 3 mg dose of cytisine taken three times daily for 12 weeks, to the same dose for only six weeks followed by six weeks of placebo, or a placebo for 12 weeks. In both active regimens, cytisine significantly improved smoking cessation rates more than placebo.
While cost is always an important consideration for any treatment, cytisine has been shown in many analyses to be a cost-effective treatment option. For instance, one 2014 cost-effectiveness analysis concluded that cytisine is estimated to be both more clinically effective and cost-effective than varenicline. This was reaffirmed in a 2018 analysis, which concluded that the current provision of smoking cessation services in the Netherlands and England could benefit economically from the inclusion of cytisine.
With little doubt over its efficacy, other factors serve as a barrier to wider approval. Perhaps most pertinent is the concern that regulatory authorities in the UK, Europe and the US may require further placebo-controlled trials of cytisine in western European and/or North American populations. The current manufacturers, Sopharma in Bulgaria and Aflofarm in Poland, have little incentive to conduct such trials, especially as cytisine is now a generic product.
But, the current situation is more than likely to change in the near future. One US company, Achieve Life Sciences, has made great strides in evaluating cytisine through a series of randomised controlled trials. In fact, the company describes itself as ‘committed to advancing cytisinicline (cytisine) as a widely available treatment option to help people battling nicotine addiction.‘
Achieve Life Sciences established the Ongoing Research of Cytisinicline for Addiction (ORCA) program of clinical trials to advance the development and commercial availability of cytisine. Recently, the company reported findings from the ORCA-V1 Phase 2 trial in which a 3 mg dose of cytisine three times a day demonstrated a significantly significant better quit rate than placebo among adult users of nicotine e-cigarettes or vapes.
In the absence of a marketing authorisation, it is unlikely that cytisine will serve as an alternative to varenicline, at least in the short term. But, armed with a dossier of positive data, it is possible that cytisine will gain FDA approval in the next year or so. This is likely to lead to regulators in the UK and Europe also approving the drug, finally allowing many more millions of patients access to an effective smoking cessation aid.
20th January 2022
Smoking cessation at the time of a lung cancer diagnosis is linked to an improved survival from both non-small and small cell lung cancer, according to the findings of a systematic review by a team from the Institute for Cancer Research, Prevention and Clinical Network, Florence, Italy
Data from the World Health Organization shows that in 2020, globally, there were 2.21 million cases of lung cancer and which led to 1.8 million deaths. In addition, lung cancer has a poor prognosis and Cancer Research UK suggests that only around 15% of those with lung cancer will survive for 5 years or more after diagnosis.
Cigarette smoking is a major factor in the development of lung cancer, with one analysis of the burden of respiratory tract cancers indicating that smoking contributed to an estimated 64·2% of all deaths from tracheal, bronchus, and lung cancer and 63·4% of all deaths from larynx cancer in 2019.
Although one study with 517 smokers, found that smoking cessation at the time of a lung cancer diagnosis can reduce the risk of future lung cancer, for the present study, the Italian team sought to provide a more robust estimate of the overall prognostic value of smoking cessation at or around the time of a lung cancer diagnosis.
They searched for articles which included those who continued to smoke and those who quit in relation to their cancer diagnosis and the associated changes in survival. The team calculated relative risks for the association between smoking cessation and the survival from lung cancer.
A total of 21 studies were included in the systematic review with patients diagnosed with non-small cell lung cancer (10 studies, 5315 patients) and small cell lung cancer (5 studies, 1133 patients), together with a further six studies of both cancer subtypes or where the subtype was not specified.
The mean age of lung cancer diagnosis across the studies ranged from 60 to 70 years and the proportion of men ranged from 40.2% to 91.8%. The duration of follow-up also ranged from 12 months to 27.7 years.
Smoking cessation at or around the time of diagnosis was associated with a better overall survival regardless of lung cancer type. For smoking cessation at any time, compared to those who continued smoking (used as the reference group), the relative risk for non-small cell lung cancer was 0.77 (relative risk, RR = 0.77, 95% CI 0.66 – 0.90) and this reduction was broadly similar compared to those stopping strictly at or after their diagnosis or up to 12 months before the diagnosis.
For small cell lung cancer, overall survival was also broadly similar (RR = 0.75, 95% CI 0.57 – 0.99). Even in studies where the cancer subtype was not specified, there were survival benefits among quitters (RR = 0.81, 95% CI 0.68 – 0.96).
The authors calculated an overall benefit for those who undertook smoking cessation at or around the time of their lung cancer diagnosis, finding that such individuals had a 29% improvement in their overall survival compared to those who continued to smoke (RR = 0.71, 95% CI 0.64 – 80).
The authors concluded that advice to quit smoking at or around the time of a lung cancer diagnosis, should arguably become a non-optional part of the management of these patients.
Caini S et al. Quitting smoking at or around diagnosis improves the overall survival of lung cancer patients: a systematic review and meta-analysis J Thorac Oncol 2022.
6th September 2021
Smoking is a risk factor for cardiovascular disease (CVD) and responsible for 1 of every 4 CVD deaths although smoking is a very preventable CVD risk factor. In one observational study of over 8,000 former heavy (i.e., more than 20 cigarettes/day) it was found that within 5 years of cessation, there was a 39% reduced risk of CVD among those who quit, compared to current smokers. Other evidence indicates a potential dose-response relationship between smoking and ischaemic stroke, such that any reduction is beneficial. However, while a meta-analysis has found that reduced use of cigarettes decreases the risk of lung cancer, the impact on CVD was less clear. This led a team from the Department of Family Medicine/Supportive Care Centre, Seoul, Korea, to compare the effect of either smoking cessation or reduction on the risk of cardiovascular disease outcomes. The team used a Korean national health database and collected information of individuals over 40 years of age who had undergone two health examinations in 2009 and again in 2011 to determine any changes in smoking behaviour. A smaller subgroup who had undergone a third examination in 2013 were also included. The team focused on a group of current smokers and excluded those with prior CVD or cancer and used information on smoking status obtained from a biennial national health examination self-administered questionnaire. Individuals were classed as heavy smokers (> 20 cigarettes/day), moderate smokers (10 – 19/day) and light smokers (< 10/day). Compared with the first examination in 2009, participants were then categorised as quitters, reducers I (> 50% reduction), reducers II (20 – 50% reduction), sustainers (reduced by < 20%) and increasers (>20% in smoking). The primary endpoints for the study were newly diagnosed stroke and myocardial infarction (MI) and secondary endpoints included overall mortality, fatal strokes and fatal Mis. Many other health parameters were collected included age, sex, body mass index, duration of smoking, alcohol consumption, levels of exercise, co-morbidities, all of which were adjusted for in the analyses.
A total of 897,975 current smokers with a mean age of 53 years (94.5% male) were followed over 6.2 years. There were a total of 17,748 strokes and 11,271 MI events during the follow-up period. Among smokers, 52.8% were classed as heavy, 37.3% as moderate and the remainder as light during their first examination. Among smoking quitters, there was a significantly reduced risk of stroke (adjusted Hazard ratio, aHR = 0.77, 95% CI 0.74 – 0.81) and MI (aHR = 0.74) compared to sustainers. In addition, smoking cessation was also associated with a significant reduction in all-cause mortality (aHR = 0.92, 95% CI 0.89 – 0.94). However, among reducers I and II, the risk of both stroke and MI were not significantly lower. For example, for reducers I, stroke aHR = 1.02 (95% CI 0.97 – 1.08) and MI aHR = 0.99 (95% CI 0.92 – 1.06).
At the third examination in 2013, quitters who had relapsed to either the level of reducer I, II, sustainer or increaser, had a 42 to 66% increased risk of stroke and a 54 – 69% increased risk of MI compared to quitters, depending where they were in terms of their relapsed level of smoking.
The authors concluded that only smoking cessation and not reduction was associated with a reduced risk of adverse cardiovascular outcomes.
Jeong SM et al. Smoking cessation, but not reduction, reduces cardiovascular disease incidence. Eur Heart J 2021