1 00:00:07,140 --> 00:00:14,150 If basking young mate down the pub about FAPE in hands, one, they probably say. 2 00:00:14,150 --> 00:00:20,610 No one agrees if it's safer on nuts, so you might as well smoke anyway. 3 00:00:20,610 --> 00:00:27,310 Now, what Jemmy needs is a Cochrane review, all the facts have been checked at least twice. 4 00:00:27,310 --> 00:00:30,930 They find there's a lot that the experts agree on. 5 00:00:30,930 --> 00:00:42,740 I'd give you. Hi, everyone. 6 00:00:42,740 --> 00:00:47,000 My name's Nicola Linson. I'm Jamie Hertzman. 7 00:00:47,000 --> 00:00:49,460 And this is the second episode of our podcast series. 8 00:00:49,460 --> 00:00:56,620 Let's Talk E-cigarettes, which is a companion to our living systematic review of e-cigarettes for quitting smoking. 9 00:00:56,620 --> 00:01:01,520 This review. We search the e-cigarettes literature every month and find out what's new. 10 00:01:01,520 --> 00:01:09,290 And we'll be summarising what we find here in this podcast. So thank you to everyone who listened to our first episode of the podcast. 11 00:01:09,290 --> 00:01:17,620 We've had some really great feedback. Also, we are well aware that there is still plenty of room for improvement. 12 00:01:17,620 --> 00:01:25,310 And I think that's a good point for me to say. Thank you to everyone on Twitter for your kind of efforts to try and crowdfund me a microphone. 13 00:01:25,310 --> 00:01:30,980 Unfortunately, I have an unreliable authority that the issue is not actually with my microphone, but with my surroundings. 14 00:01:30,980 --> 00:01:35,150 So I had been recording for me there, my kitchen or my garage. 15 00:01:35,150 --> 00:01:40,610 Right now I am in my garage, which is a concrete block, essentially, 16 00:01:40,610 --> 00:01:45,710 because my three and five year old and are in the house, which would probably make sound quality even worse. 17 00:01:45,710 --> 00:01:51,020 But what I'm trying this time, and hopefully I sound a bit better, is I'm literally recording from under a blanket. 18 00:01:51,020 --> 00:02:00,860 So Nicola is looking at me covered by a huge pink fleecy blanket, which might improve the sound and certainly at least makes this feel a bit comedic. 19 00:02:00,860 --> 00:02:05,780 So our latest search was at the beginning of this month, at the beginning of January. 20 00:02:05,780 --> 00:02:09,050 And this time around, we found six new papers. 21 00:02:09,050 --> 00:02:14,660 One of those was linked to a study we'd already included, and another one is an ongoing study in the ongoing study. 22 00:02:14,660 --> 00:02:16,040 We don't have that much detail on it. 23 00:02:16,040 --> 00:02:23,150 So we don't know at this stage whether or not it will be included, but we'll look at any papers that eventually come out of it to cheque. 24 00:02:23,150 --> 00:02:27,740 So those remaining four papers were for completely new studies. 25 00:02:27,740 --> 00:02:32,390 And we're just about to take you on a whirlwind tour of those in our next section. 26 00:02:32,390 --> 00:02:41,360 In a nutshell, so the first new study we found was a paper where the lead author was Florian QAI, 27 00:02:41,360 --> 00:02:48,560 then from the Waterford Institute of Technology in Ireland and was published in the harm reduction journals in 2020. 28 00:02:48,560 --> 00:02:52,430 He was a very small study of twenty three people who were recruited and Irish 29 00:02:52,430 --> 00:02:57,400 supported temporary accommodation service for people experiencing homelessness. 30 00:02:57,400 --> 00:03:03,430 This was a non-random I study and all participants had to be currently smoking at the beginning of the study. 31 00:03:03,430 --> 00:03:10,840 All participants were given an e-cigarettes called the Injera T 22 E and to 10 millilitre nicotine liquids, 32 00:03:10,840 --> 00:03:14,440 which were available in a variety of strengths and flavours. 33 00:03:14,440 --> 00:03:21,530 The outcomes of interest to us in this study were carbon monoxide levels and side effects, which were measured at weeks one for eight and 12. 34 00:03:21,530 --> 00:03:30,310 Of the study, there was a high dropout rate of 20 percent, which meant that actually only nine participants completed the intervention. 35 00:03:30,310 --> 00:03:34,720 The participants had high levels of addiction and smoked a relatively high number of cigarettes per day. 36 00:03:34,720 --> 00:03:37,150 Approximately 25. 37 00:03:37,150 --> 00:03:46,750 Mean carbon monoxide measurements decreased from 21 parts per million to 16 parts per million, which was a 35 percent reduction in CO2 levels. 38 00:03:46,750 --> 00:03:49,090 This decrease was not statistically significant. 39 00:03:49,090 --> 00:03:55,900 However, that is not surprising as this study was underpowered due to the very low number of people that completed it. 40 00:03:55,900 --> 00:04:02,200 Six of the nine participants reported the following side effects coughing, runny nose, bleeding nose, 41 00:04:02,200 --> 00:04:08,050 slight sweating, dizziness, increased phlegm and a burning sensation at the back of the throat. 42 00:04:08,050 --> 00:04:12,820 However, all of these would be considered relatively minor in a randomised controlled trial. 43 00:04:12,820 --> 00:04:15,310 This study was funded by Knowledge Action Change, 44 00:04:15,310 --> 00:04:23,010 which is a private company funded by the Foundation for a Smoke Free World, which is linked to the tobacco industry. 45 00:04:23,010 --> 00:04:25,280 My second paper was published in the journal. 46 00:04:25,280 --> 00:04:32,190 AIDS Cat in 2020 and was led by Jessica Yingst from the Penn State University College of Medicine in the US. 47 00:04:32,190 --> 00:04:39,210 It also recruited a population of people who smoked. So in this case, that was people living with HIV and AIDS. 48 00:04:39,210 --> 00:04:44,750 This study recruited 17 people, so it was also small and implemented across safer design. 49 00:04:44,750 --> 00:04:48,630 Over three weeks, there were two types of e-cigarettes used. 50 00:04:48,630 --> 00:04:55,040 One was the blue psychologic device with a 24 milligram per millilitre nicotine concentration, 51 00:04:55,040 --> 00:05:01,980 and the other was the ego button operated device with a 36 milligram per millilitre nicotine concentration. 52 00:05:01,980 --> 00:05:10,110 Both used tobacco flavoured liquids. Participants were randomly split into two groups, and each group use one of these cigarette types for a week. 53 00:05:10,110 --> 00:05:14,220 After that first week, they all had a week where they stopped using e-cigarettes. 54 00:05:14,220 --> 00:05:18,960 And then in the final week of the study, they used the cigarette that they hadn't used previously. 55 00:05:18,960 --> 00:05:25,860 Again, this study looked at carbon monoxide levels and compared these between the two different types of e-cigarettes that we used. 56 00:05:25,860 --> 00:05:31,200 They found that CO2 or carbon monoxide significantly reduced using based products, 57 00:05:31,200 --> 00:05:39,060 but there was no significant difference between the two product type stuff. Great to hear about those, McLoud, particularly, I think. 58 00:05:39,060 --> 00:05:43,350 Nice to see more and more work being done in some of these harder to reach populations. 59 00:05:43,350 --> 00:05:49,170 So people familiar with our existing review will know that there is a study in there as well. 60 00:05:49,170 --> 00:05:53,310 And people experiencing homelessness led by Lynn Dawkins and colleagues. That's, again, 61 00:05:53,310 --> 00:05:59,310 a relatively small pilot study in and I think I speak for Nicole and I when I say we really 62 00:05:59,310 --> 00:06:04,740 hope to be seeing more research and bigger studies in these populations moving forward. 63 00:06:04,740 --> 00:06:06,990 So the third paper we found was a bit different. 64 00:06:06,990 --> 00:06:13,410 It was published in the journal Addictive Behaviours and was led by Dr Jenny Oscar Haas at West Virginia University. 65 00:06:13,410 --> 00:06:17,860 It was supported through state funds, all federal and university funding. 66 00:06:17,860 --> 00:06:24,510 And it was a pilot study, which means it was conducted really to help inform the design of a potential larger study or studies. 67 00:06:24,510 --> 00:06:31,020 Because in this case, what the authors were particularly interested in this paper was whether the method they were using to collect data worked well. 68 00:06:31,020 --> 00:06:33,930 That's obviously not something that our review is interested in, 69 00:06:33,930 --> 00:06:39,990 but we are including the study because it did look at carbon monoxide as well, which is an outcome we're interested in. 70 00:06:39,990 --> 00:06:45,750 So in this study, 60 adults who smoked were assigned to either use only their brand of cigarettes or to a 71 00:06:45,750 --> 00:06:51,720 second generation a cigarette to use as they liked and were followed up over four weeks. 72 00:06:51,720 --> 00:06:58,710 The e-cigarettes in question was a Kanger mini protein, too, and they used a nicotine concentration of 18 milligrams per millilitre. 73 00:06:58,710 --> 00:07:04,560 They could choose between three flavour options. And as I said before, they did measure carbon monoxide levels. 74 00:07:04,560 --> 00:07:10,800 Now, it was in a relatively small group of participants, and the authors didn't formally test for a difference between the groups. 75 00:07:10,800 --> 00:07:16,980 But the levels of carbon monoxide appear to have been lower in the E cigarette group than in the cigarette group. 76 00:07:16,980 --> 00:07:25,230 And as I said earlier, there, a force that is the fourth one is from Kim Pulvers and her team published in JAMA Network. 77 00:07:25,230 --> 00:07:28,800 Open funding for this came from the National Institutes for Health. 78 00:07:28,800 --> 00:07:35,640 As I said, this trial was led by Dr. Kim Pulvers and she's based at the California State University, San Marcos. 79 00:07:35,640 --> 00:07:40,770 The senior author for this was Professor Giles Ahluwalia at Brown University in the US. 80 00:07:40,770 --> 00:07:44,700 And I was really excited to get the opportunity to speak to him about this. 81 00:07:44,700 --> 00:07:49,080 And so you'll hear more about this new study in our next section, which is our deep dive. 82 00:07:49,080 --> 00:07:51,660 And I think it's fair to say Nicole and I were also critically excited. 83 00:07:51,660 --> 00:07:57,630 As I've said before, we got pretty excited about e-cigarettes research generally. But here this was one we really wanted to cover and our deep dive, 84 00:07:57,630 --> 00:08:02,400 partly because it's one of the few to look at newer generation e-cigarettes devices and also 85 00:08:02,400 --> 00:08:08,670 because it looks at non-white populations in the US who are historically under researched. 86 00:08:08,670 --> 00:08:22,340 Now to my own mortification and just to set the scene. This interview also took place under a blanket. 87 00:08:22,340 --> 00:08:28,610 So first off, all that jazz tell you about his history and how he got into harm reduction research. 88 00:08:28,610 --> 00:08:34,190 So I've been working in this field of nicotine addiction and tobacco for about 30 years, 89 00:08:34,190 --> 00:08:40,100 and my focus for that time has been on marginalised and underserved populations. 90 00:08:40,100 --> 00:08:43,880 And I do a variety of different approaches to working on this. 91 00:08:43,880 --> 00:08:50,600 But basically clinical trials, but additional to that, qualitative research and some epidemiology work. 92 00:08:50,600 --> 00:08:56,930 And traditionally pharmacotherapy to help smokers quit smoking as well as behavioural approaches. 93 00:08:56,930 --> 00:09:02,870 In fact, when e-cigarettes began to come on the scene, I essentially ignored them. 94 00:09:02,870 --> 00:09:06,050 And I did not sort of move in that direction at all. 95 00:09:06,050 --> 00:09:15,440 And in fact, as well, I focussed and stayed on the course of quitting and thought of abstinence only, if you will. 96 00:09:15,440 --> 00:09:20,090 And I didn't have sort of believe in this concept, so to speak, of harm reduction. 97 00:09:20,090 --> 00:09:24,080 While I used seatbelts and didn't leap to big a slice of a cake. 98 00:09:24,080 --> 00:09:29,660 In terms of tobacco. I was not thinking about harm reduction in the way that I probably should. 99 00:09:29,660 --> 00:09:32,660 And in fact, was a little bit rigid about it. 100 00:09:32,660 --> 00:09:38,900 And then something maybe tipped off in me when I just began to realise that, you know, this may be something of interest. 101 00:09:38,900 --> 00:09:49,070 So we did some pilot work together. Dr. Kim Pulvers, Dr. Nikki Nolan and myself, collaborators across the country at different institutions. 102 00:09:49,070 --> 00:09:56,840 And we began to get excited about what we were finding. The pilot work suggested that people could switch and get off combustibles because, 103 00:09:56,840 --> 00:10:01,430 in fact, it's combustibles that were the worst and the most deadly. 104 00:10:01,430 --> 00:10:06,830 This led to us doing a randomised trial. And to some extent I've become a convert. 105 00:10:06,830 --> 00:10:10,040 I've become very interested in the concept of harm reduction. 106 00:10:10,040 --> 00:10:23,360 I accepted for some of the other aspects of medicine and healthcare in diabetes and obesity and nutrition and in substance use alcohol, 107 00:10:23,360 --> 00:10:27,770 opioids, seat belts, helmet laws. It's just sort of everywhere. 108 00:10:27,770 --> 00:10:30,590 We all practise harm reduction every day. 109 00:10:30,590 --> 00:10:40,640 And so I find it fascinating when people who generally accept all these things are not accepting it in the field of tobacco and nicotine research. 110 00:10:40,640 --> 00:10:50,090 So if you will, to some extent, I'm a convert. So in terms of harm reduction, there's actually no one agreed definition for what that means. 111 00:10:50,090 --> 00:10:56,090 But broadly speaking, what people tend to mean when they talk about harm reduction are a range of policies, 112 00:10:56,090 --> 00:11:01,100 usually in public health, that are designed to lessen the negative impact associated with various behaviours. 113 00:11:01,100 --> 00:11:08,330 So as John's mentioned, in the case of seat belts, the behaviour that we're lessening the negative impact of is driving. 114 00:11:08,330 --> 00:11:14,540 One of the most well-known harm reduction policies in addiction research is methadone treatment for people addicted to heroin. 115 00:11:14,540 --> 00:11:21,920 It's really interesting, Jamie, that a very well accepted harm reduction policies like you just mentioned, like seatbelts and wearing bicycle helmets. 116 00:11:21,920 --> 00:11:27,190 But in the field of tobacco research, people seem to be more split on how they feel about that. 117 00:11:27,190 --> 00:11:34,400 And do you think this could be dependent on how people and researchers view the addiction and that they're perceived in the main harm, 118 00:11:34,400 --> 00:11:40,250 maybe being from the addiction itself? And if that were the case, they might view switching one addiction for another, 119 00:11:40,250 --> 00:11:44,510 say, in the form of nicotine treatment, like an aisle, tea or e-cigarettes. 120 00:11:44,510 --> 00:11:55,550 They may see that as unacceptable, whereas maybe people who are research is in harm reduction see that as an acceptable 121 00:11:55,550 --> 00:12:02,870 alternative because we hope that it's basically reducing the harm from smoking. 122 00:12:02,870 --> 00:12:10,430 And certainly in the case of MLT, we have a lot of long term evidence to say that that is much safer smoking. 123 00:12:10,430 --> 00:12:17,240 And now we're accumulating more evidence that obviously suggests that e-cigarettes are less harmful than smoking as well. 124 00:12:17,240 --> 00:12:23,360 And so, yes, to some people, that's certainly a suitable alternative. 125 00:12:23,360 --> 00:12:24,560 I think is a really interesting point. 126 00:12:24,560 --> 00:12:33,300 I think there's probably a multitude of complex reasons why there might be slightly more hesitancy to embrace harm reduction in this area. 127 00:12:33,300 --> 00:12:35,450 And of course, you just mentioned nicotine replacement therapy. 128 00:12:35,450 --> 00:12:41,900 And in some ways, we might even think of nicotine replacement therapy as a harm reduction tool, but it's not often spoken about in that way. 129 00:12:41,900 --> 00:12:44,570 I think one of the challenges here, of course, 130 00:12:44,570 --> 00:12:51,680 is the troubled history of the tobacco industry and their potential role in e-cigarettes, research and and harm reduction methods. 131 00:12:51,680 --> 00:12:56,630 But I think you're absolutely right that another element of it is just when we think about tobacco addiction, 132 00:12:56,630 --> 00:13:01,910 what do we think the fundamental problem is? How do we frame it is the fundamental problem of addiction, 133 00:13:01,910 --> 00:13:06,290 in which case switchin one addiction with another doesn't necessarily seem the most 134 00:13:06,290 --> 00:13:11,630 intuitive solution or is the fundamental problem the harms caused by that addiction? 135 00:13:11,630 --> 00:13:16,550 Right. And I think you and I probably both fall fall more into that latter paradigm of thinking. 136 00:13:16,550 --> 00:13:23,340 The fundamental problem is. The harms. And I think that actually brings us nicely onto to the next thing James talked about, 137 00:13:23,340 --> 00:13:30,180 which is why he was talking about some of the harm he's seen and why he is is really motivated to address that. 138 00:13:30,180 --> 00:13:37,560 But it's profound, if I think about it. I'm I'm a physician. I'm trained in medicine policy and epidemiology and public health. 139 00:13:37,560 --> 00:13:43,620 And so I think about things at the population level. But I also think about things at the individual level. 140 00:13:43,620 --> 00:13:52,950 I'll never forget a patient I had when I was a resident at North Carolina Chapel Hill in the late 80s who had late stage COPD, 141 00:13:52,950 --> 00:14:01,110 very late stage, so much so that when they had to sleep at night, they couldn't sleep in a bed because when you lie flat, you're suffocated. 142 00:14:01,110 --> 00:14:11,040 So they would sleep in a reclining chair, but not reclining it and not sit facing forward to get ready for this sit, facing backwards, 143 00:14:11,040 --> 00:14:17,820 leaning over the head of the chair, because that's the only way they could sort of breathe without feeling suffocated. 144 00:14:17,820 --> 00:14:23,020 So I think for those that work in this area who don't practise health care. 145 00:14:23,020 --> 00:14:30,600 Thank you for working in this area. But sometimes what they don't appreciate fully is the individual level situation. 146 00:14:30,600 --> 00:14:34,260 Wow. I find that really. I do know. 147 00:14:34,260 --> 00:14:46,620 Not really affecting example. And it is a good reminder, I think, of why we work in this field, certainly why I work in this field. 148 00:14:46,620 --> 00:14:55,380 It resonates with me because a big reason why I'm interested in this area is through 149 00:14:55,380 --> 00:15:00,180 observing a very close family member of mine quit smoking when I was a child. 150 00:15:00,180 --> 00:15:10,450 And I remember it quite vividly, mainly because of how difficult I could see that they were finding it and. 151 00:15:10,450 --> 00:15:22,540 Therefore, it just became something that I wanted to do, that I wanted to help people to to give up smoking because I'd seen how difficult it was. 152 00:15:22,540 --> 00:15:26,770 And so often, I think in this field, if you're working on a trial or something like that, 153 00:15:26,770 --> 00:15:31,210 the participants ask you whether you've been a smoker yourself. 154 00:15:31,210 --> 00:15:42,850 And I completely understand why they might do that. But I think it's important for people to know that just because we may not have smoked ourselves, 155 00:15:42,850 --> 00:15:48,760 it doesn't mean that we don't have a huge amount of empathy for people who do. 156 00:15:48,760 --> 00:15:54,730 And for me, that's solely, you know, why I have an interest in this field. 157 00:15:54,730 --> 00:16:03,820 And obviously examples that like that justice just give only reinforce the reasons why and why I wanted to do this. 158 00:16:03,820 --> 00:16:08,710 So I think that's a really powerful example. I agree. I think it's it's incredibly powerful and. 159 00:16:08,710 --> 00:16:15,880 And just like you, I sometimes get asked if I have ever smoked as well, and I never have. 160 00:16:15,880 --> 00:16:18,120 And also completely understand the question. 161 00:16:18,120 --> 00:16:25,440 And for me, the reason, I suppose, that I first got involved in tobacco research was actually back as an undergraduate in university when I, 162 00:16:25,440 --> 00:16:28,720 I was getting really interested in public health and not interest for me came 163 00:16:28,720 --> 00:16:34,840 from a place where I have lived with a long term condition since a young age. 164 00:16:34,840 --> 00:16:42,430 I have type one diabetes. I got as a child and realised pretty quickly that there, having been a long term illness, is absolutely rubbish. 165 00:16:42,430 --> 00:16:47,320 I wouldn't wish it on anyone. And got really interested in it. 166 00:16:47,320 --> 00:16:55,360 Kind of, I suppose, acknowledging that no one wants to have an illness and trying to do what we can do to help people try and prevent those. 167 00:16:55,360 --> 00:17:01,210 And for me, I suppose one of my really illuminating moments further on down the line and what got me hooked, I suppose, 168 00:17:01,210 --> 00:17:05,890 on on a cigarette research is that when e-cigarettes were first coming out and we had, I suppose, 169 00:17:05,890 --> 00:17:10,960 a growing body of evidence, really, that they were they looked significantly less harmful than cigarettes. 170 00:17:10,960 --> 00:17:17,620 I was at a family dinner and and a family member who was very much addicted to smoking said to me, 171 00:17:17,620 --> 00:17:23,350 oh, I considered switching to e-cigarettes, but I heard on the radio various scientists disagreed. 172 00:17:23,350 --> 00:17:28,120 And some someone said that e-cigarettes have been worse for you than smoking. So I'm just gonna keep on smoking. 173 00:17:28,120 --> 00:17:32,020 And and I really felt at that moment that we were doing something wrong. 174 00:17:32,020 --> 00:17:41,260 As scientists in this area. So I think it's it's a privilege to work on this and we need to keep working on it, basically. 175 00:17:41,260 --> 00:17:47,890 So on that note, I am going to let Jazz talk to us a bit about the reason why we contacted him in the first place, 176 00:17:47,890 --> 00:17:54,370 which is that we wanted to hear about his really exciting new study with regards to our clinical trial. 177 00:17:54,370 --> 00:17:58,060 So with the pilot data, we said we need to do a randomised trial. 178 00:17:58,060 --> 00:18:07,720 We got some NIH funding, albeit a small grant, and we randomised in a two to one ratio so that we could get more experience with the e-cigarettes. 179 00:18:07,720 --> 00:18:17,330 So we enrolled about 180 participants in total with a two to one randomisation scheme joule five percent compared to smoke your own, as usual. 180 00:18:17,330 --> 00:18:21,850 And we enrolled people who were interested in switching to e-cigarettes in the United States. 181 00:18:21,850 --> 00:18:31,600 We can't study as an outcome variable cessation. In essence, when you're switching the switch, a goal is to come off the combustible. 182 00:18:31,600 --> 00:18:36,680 But stay on the e-cigarettes if you want to. I mean, to some extent, we're encouraging that. 183 00:18:36,680 --> 00:18:44,440 That's sort of the approach. Well, the short term study, six weeks and the primary outcome was the study and A-L. 184 00:18:44,440 --> 00:18:49,090 This is a potent pulmonary carcinogen. And that was the outcome of interest. 185 00:18:49,090 --> 00:18:55,810 Obviously, we measured other things, including carbon monoxide or respiratory symptoms, score that's been validated, 186 00:18:55,810 --> 00:19:02,440 curtaining pulmonary function tests, some basic ones, as well as systolic and diastolic pressure. 187 00:19:02,440 --> 00:19:07,330 Great. Well, it's really interesting to hear about some of the the methods of the study. 188 00:19:07,330 --> 00:19:17,980 And what kind of struck me with that is that the e-cigarettes that they use, Joule, is something that we don't really hear a lot about in the UK. 189 00:19:17,980 --> 00:19:24,800 And. Obviously just mentioned that they used it at quite a high dosage. 190 00:19:24,800 --> 00:19:30,230 And again, I don't think that dosage is used commonly in the case. 191 00:19:30,230 --> 00:19:34,160 Do you know anything more about that, Jane? So that's absolutely right, Nick. 192 00:19:34,160 --> 00:19:38,960 I mean, I think in the U.S., jewel is really, really commonly used. 193 00:19:38,960 --> 00:19:43,550 And I suppose those of us working on a cigarette research in the U.K. kind of 194 00:19:43,550 --> 00:19:47,120 watched and waited to some extent to see if that was going to happen here. 195 00:19:47,120 --> 00:19:51,760 And it hasn't Jewel hasn't taken off here in the same way as it has in the U.S. 196 00:19:51,760 --> 00:20:01,780 There probably are a whole host of reasons for that, not least of which are are advertising regulations, but also, as just touched upon in the states, 197 00:20:01,780 --> 00:20:05,540 jaw's available and e-cigarettes generally are available at a higher nicotine 198 00:20:05,540 --> 00:20:09,620 concentration than they are here in the U.K. and indeed throughout Europe. 199 00:20:09,620 --> 00:20:17,750 Because the reason we have a cap on the amount of nicotine that's an e-cigarettes comes from the European Union's Tobacco Products Directive, 200 00:20:17,750 --> 00:20:22,910 which basically limits the amount of nicotine, any cigarettes does something that's less than, I suppose, 201 00:20:22,910 --> 00:20:29,390 the most common dose you'd have via duel in the U.S. and less than the dose that's tested in the study at face value. 202 00:20:29,390 --> 00:20:35,330 I think that seems, you know, a really sensible thing to do to limit the amount of nicotine in e-cigarettes, 203 00:20:35,330 --> 00:20:38,360 et cetera, especially if you're concerned about youth uptake. 204 00:20:38,360 --> 00:20:43,090 But there is, of course, a flip side to that which which there's more and more research into. 205 00:20:43,090 --> 00:20:48,830 And I suppose it touches back again to the fact that nicotine itself is not what the harmful thing is in cigarettes, 206 00:20:48,830 --> 00:20:51,920 nor is it the harmful thing in e-cigarettes. 207 00:20:51,920 --> 00:21:01,030 So jazz did actually go on and chat a little bit more about this nicotine dose issues, all that you listened to him explain it and a bit more detail. 208 00:21:01,030 --> 00:21:09,440 Yes. So with our pilot data, we found through an open label trial single arm that looked like people could switch. 209 00:21:09,440 --> 00:21:16,850 We used your five percent. So in the United States, five percent nicotine is the dose that's available. 210 00:21:16,850 --> 00:21:22,520 And. Let me just say right now that that's the right percentage. 211 00:21:22,520 --> 00:21:29,540 In fact, that should be the floor, not the ceiling. And I know in the UK that that dose is not available, if you will. 212 00:21:29,540 --> 00:21:31,130 It's three percent. 213 00:21:31,130 --> 00:21:38,840 And that's, you know, that's concerning to me because, you know, we don't if we think about therapeutics, we don't say to someone, oh, 214 00:21:38,840 --> 00:21:46,070 use a seven milligram nicotine patch or a 40 milligram because over twenty one is too much or it's dangerous or anything like that. 215 00:21:46,070 --> 00:21:51,850 In fact, the pharmacokinetics show that all those doses are too low for the average smoker. 216 00:21:51,850 --> 00:21:56,390 So sometimes we use double nicotine patches. Likewise, here's a product. 217 00:21:56,390 --> 00:22:01,190 And let me keep saying during this podcast that this is a product that is not safe. 218 00:22:01,190 --> 00:22:06,590 That's not we're not trying to it this is not we're not trying to get a therapeutic indication, at least in my state, or at least right now. 219 00:22:06,590 --> 00:22:09,650 It's not a safe product. It's a harm reduction product. 220 00:22:09,650 --> 00:22:16,900 So the goal is to have the nicotine level in the product high and then to minimise the use of the product, if you will. 221 00:22:16,900 --> 00:22:22,070 Right. Because if it's a lower nicotine strength, then you're going to use it to extract more nicotine. 222 00:22:22,070 --> 00:22:23,360 You're going to use more of it. 223 00:22:23,360 --> 00:22:30,980 And then you get, if you will, to so-called bad things, whatever they might be, heavy metals, Crowley and and things like that. 224 00:22:30,980 --> 00:22:40,410 So another thing I know is, Jamie, when Jess was talking about the outcomes that they measured in their study was that they didn't actually 225 00:22:40,410 --> 00:22:46,640 mention or seem to measure smoking cessation or the number of people who managed to quit smoking. 226 00:22:46,640 --> 00:22:50,330 And that seems to be a little bit strange in a study of this type, 227 00:22:50,330 --> 00:22:56,270 that they wouldn't look at the number of people who actually ended up stopping using combustible cigarettes. 228 00:22:56,270 --> 00:23:00,690 Did you speak to him anymore about that, Jamie? Yeah. So, Niccola, absolutely. 229 00:23:00,690 --> 00:23:02,600 For us and the UK, that does seem strange. 230 00:23:02,600 --> 00:23:09,320 We think of the big trials here, which, of course, have measured smoking cessation, which is the ultimate aim. 231 00:23:09,320 --> 00:23:13,830 I was also really puzzled about the situation in the US and trying to wrap my head around it. 232 00:23:13,830 --> 00:23:19,820 So I did ask us to elaborate. And again, I'll let him explain the situation to you. 233 00:23:19,820 --> 00:23:23,990 And the reason we can't study cessation is outcome the United States. 234 00:23:23,990 --> 00:23:30,260 The best I understand that is, is that the FDA has different arms to it, if you will. 235 00:23:30,260 --> 00:23:36,830 One is a device unit. Another is a medicinal therapeutics unit. 236 00:23:36,830 --> 00:23:47,320 And in order to have. In order to study this for cessation, then you have to have a therapeutic indications, so you have to go through Ceder. 237 00:23:47,320 --> 00:23:52,240 The Centre for Drug Evaluation and get it approved as a medicinal product, 238 00:23:52,240 --> 00:23:59,580 as a therapeutic indication, the way nicotine patch, nicotine gum, veranda, clean perper undoes. 239 00:23:59,580 --> 00:24:04,570 And you could also take it through the device category. But that probably wouldn't make much sense. 240 00:24:04,570 --> 00:24:09,640 Sort of like a implantable defibrillator or something along those lines. 241 00:24:09,640 --> 00:24:16,360 As such, it goes to the Centre for Tobacco Products. As a tobacco products, so is Sig's. 242 00:24:16,360 --> 00:24:21,580 Interesting enough in the United States or categories categorised as a tobacco product? 243 00:24:21,580 --> 00:24:25,150 I actually don't think they should be. But that's how they're categorised. 244 00:24:25,150 --> 00:24:31,960 So because they didn't measure cessation in this study, Necla, their primary outcome was changes in measure of exposure. 245 00:24:31,960 --> 00:24:41,650 And what they found is that at week six, the cigarette group had significantly greater reductions in an NHL carbon monoxide respiratory systems. 246 00:24:41,650 --> 00:24:46,570 And the number of cigarettes smoked in the past seven days amongst those people who are still smoking. 247 00:24:46,570 --> 00:24:52,810 And that is compared to the control group. There didn't seem to be any big change in Kotin in levels, 248 00:24:52,810 --> 00:25:02,260 which is a measure of how much nicotine you're taking in and lung function and blood pressure remained unchanged and didn't differ between the group. 249 00:25:02,260 --> 00:25:07,510 So essentially, those were the main findings in terms of their primary outcomes of what they set out to measure. 250 00:25:07,510 --> 00:25:11,980 But actually, when I was talking to Johns about this, he was also really excited about some of their other results. 251 00:25:11,980 --> 00:25:17,380 So we're now going to play a clip where he's explaining some of the other things they found in terms of their secondary outcomes. 252 00:25:17,380 --> 00:25:25,120 So the primary study, of course, in a randomised trial is to compare the two different arms, the cigarette group, to the smoke your own. 253 00:25:25,120 --> 00:25:33,160 And in our paper, which was published in JAMA Network Open, that's, of course, the primary finding that we report. 254 00:25:33,160 --> 00:25:42,940 But in addition, we do report in the paper the secondary analysis, which, of course, break randomisation, but are more intriguing, if you will. 255 00:25:42,940 --> 00:25:51,670 And very interesting, which is that if you take all the people who are in the arm of getting the e-cigarettes at the end of six weeks, 256 00:25:51,670 --> 00:25:57,430 they can be in one of four buckets, one bucket, which many people might view as the ideal bucket. 257 00:25:57,430 --> 00:26:05,560 And in fact, I would too, as well, is that they quit cigarettes and they quit e-cigarettes, that they just sort of no longer want anything. 258 00:26:05,560 --> 00:26:09,880 In our study. We had zero people in that bucket, and that's fine. 259 00:26:09,880 --> 00:26:16,750 That's expected. The other bucket, if you will, maybe the ideal outcome in a harm reduction study is, 260 00:26:16,750 --> 00:26:22,870 is that you are only using e-cigarettes and you're completely off combustibles. 261 00:26:22,870 --> 00:26:28,360 And for us, that was about 25 percent plus or minus the second bucket, 262 00:26:28,360 --> 00:26:36,190 which most people view as a failure or as a no different than going back to cigarettes is a very common bucket. 263 00:26:36,190 --> 00:26:43,660 It's the dual users. And for us, that was about fifty five percent plus or minus who are doing using. 264 00:26:43,660 --> 00:26:51,890 Come back to that. And second, the third bucket. Is a bucket where you're going back fully to combustible cigarettes. 265 00:26:51,890 --> 00:26:56,090 And that was about 25 percent as well. 266 00:26:56,090 --> 00:26:57,800 Plus or minus. 267 00:26:57,800 --> 00:27:06,890 So that's a very interesting analysis because it suggests that if you get the cigarette and you're followed over time and you can switch, 268 00:27:06,890 --> 00:27:11,360 which about a quarter of them could. That's quite good news. 269 00:27:11,360 --> 00:27:16,370 Interesting enough. We also followed people we have the funding for up to six months. 270 00:27:16,370 --> 00:27:19,740 We didn't see them in person. And we did phone follow follow up. 271 00:27:19,740 --> 00:27:25,520 So there's no biochemical verification. But we have self report and the data gets more interesting. 272 00:27:25,520 --> 00:27:29,900 The number who successfully quit to e-cigarettes goes up. 273 00:27:29,900 --> 00:27:35,270 The people who actually quit both products. We actually had about seven, eight percent quit both products. 274 00:27:35,270 --> 00:27:41,060 And if you combine that those two numbers. That's a number that, if you will, are off combustibles. 275 00:27:41,060 --> 00:27:44,120 You're going above one third of the group. 276 00:27:44,120 --> 00:27:50,540 So another notable part of this study that we haven't touched on yet is that it's conducted in African-American and Latin text populations. 277 00:27:50,540 --> 00:27:57,110 And I asked Johns to talk a bit more about that as well. You know, things have histories to them. 278 00:27:57,110 --> 00:28:06,080 Not to get too dramatic, but slavery, civil rights, immigrants, immigrants who don't enter in so called legally and so on, so forth. 279 00:28:06,080 --> 00:28:15,440 And as such, folks are marginalised. And then unfortunately, there's a correlation between socioeconomic status and being an underrepresented, 280 00:28:15,440 --> 00:28:19,340 historically under marginalised minority and such. 281 00:28:19,340 --> 00:28:27,560 You get further marginalised. So what happens is traditionally and you look at sort of pharmaceutical trials that lead to medications, 282 00:28:27,560 --> 00:28:33,080 they're basically white participants, White Middle-Class Participants in this country. 283 00:28:33,080 --> 00:28:37,010 And so when I got started in 1992, thinking about how I could contribute, 284 00:28:37,010 --> 00:28:43,290 I've always been interested both personally, professionally and even from my religious perspective. 285 00:28:43,290 --> 00:28:49,430 I'm a practising Sikh. Is that social justice, caring for the underserved? 286 00:28:49,430 --> 00:28:56,150 Worrying about marginalised populations is just core to what I do professionally and as a physician. 287 00:28:56,150 --> 00:29:03,380 So I began to study African-Americans and I think, you know, when I was doing that work, you're not going to believe this. 288 00:29:03,380 --> 00:29:11,330 There is really maybe one or two other people in the United States who are doing work in African-Americans or landmarks. 289 00:29:11,330 --> 00:29:15,050 Now, think God through efforts that we started and many others, 290 00:29:15,050 --> 00:29:20,660 that there are now hundreds and there are many people interested in setting these groups. 291 00:29:20,660 --> 00:29:27,440 And, you know, we've learnt things like metabolism being different in African-Americans, nicotine intake being different, 292 00:29:27,440 --> 00:29:33,100 levels of carcinogens being higher per unit, cigarette that Neal Benowitz has done some elegant work on. 293 00:29:33,100 --> 00:29:36,610 It's led to some very concerning and profound findings. 294 00:29:36,610 --> 00:29:43,200 The average number of cigarette smoke being lower in African-Americans, African-Americans and Latin X trying to quit more often, 295 00:29:43,200 --> 00:29:49,130 but especially African-Americans having a harder time quitting and not interested enough. 296 00:29:49,130 --> 00:29:57,290 The prevalence of smoking and then over cigarette smoke per day for Latin X and African-Americans is lower than whites. 297 00:29:57,290 --> 00:30:01,430 But unfortunately, especially for African-Americans, somehow they have greater harm. 298 00:30:01,430 --> 00:30:06,980 But the net population effect is that these two groups are affected more adversely. 299 00:30:06,980 --> 00:30:09,530 And that's sort of a whole nother our dialogue. 300 00:30:09,530 --> 00:30:16,580 So what's really notable that is when just talks about these differences that we're seeing emerge between the different 301 00:30:16,580 --> 00:30:23,890 ethnic groups and say things like he was saying the levels of carcinogens and the differences in metabolism. 302 00:30:23,890 --> 00:30:27,020 And that is something that really seems to be emerging. 303 00:30:27,020 --> 00:30:34,970 And I hope we see a lot more of in future studies, because obviously it's something that's really important to understand. 304 00:30:34,970 --> 00:30:39,560 Yeah, I think it's a great research, you know, is somewhat in its infancy. 305 00:30:39,560 --> 00:30:45,940 But this is an area that that now we really need to do better on and actually probably in health care research overall. 306 00:30:45,940 --> 00:30:52,880 But certainly cigarette research is not an exception. So for me, I think this interview just touched on so many interesting things. 307 00:30:52,880 --> 00:30:55,660 I kind of talked to jazz for hours. 308 00:30:55,660 --> 00:31:01,940 And at the core of all these these things we touched on and arguably at the core value, cigarette research is the issue of harms. 309 00:31:01,940 --> 00:31:04,940 So we're gonna leave you today with some closing remarks from jazz, 310 00:31:04,940 --> 00:31:12,230 talking about how he conceptualises the relative safety of e-cigarettes and how we might operate in this context. 311 00:31:12,230 --> 00:31:20,150 Let's just briefly talk about youth. Let me be let me go on record by saying if you don't use nicotine, don't start. 312 00:31:20,150 --> 00:31:29,090 If you use nicotine or combustible tobacco products or even non-combustible tobacco products, quit if you can't quit. 313 00:31:29,090 --> 00:31:35,060 Try to use harm reduction products, get off combustibles. There's a whole spectrum of risk. 314 00:31:35,060 --> 00:31:42,200 There's no question about it. It would be almost unbelievable, not impossible that e-cigarettes are as or more dangerous than cigarettes. 315 00:31:42,200 --> 00:31:49,120 It's almost unfathomable, especially because we know the ingredients in cigarettes when they're 60 tumour accelerators, 316 00:31:49,120 --> 00:31:51,350 co carcinogens and carcinogens. 317 00:31:51,350 --> 00:31:59,530 And it's a combusted product versus a heated product that lacks essentially all those things that this is going to be more dangerous. 318 00:31:59,530 --> 00:32:07,290 I think what we're going to learn is that e-cigarettes, you know, it's probably not good for your lungs. 319 00:32:07,290 --> 00:32:12,580 That's the bottom line. E-cigarettes that's doing. Subject to the cilia, doing something to the epithelium. 320 00:32:12,580 --> 00:32:20,240 And we need to understand that the concern that people have the lay public or even the scientific world is that, 321 00:32:20,240 --> 00:32:26,060 oh, well, we don't know the long term outcome of e-cigarettes that's going to I can't argue against. 322 00:32:26,060 --> 00:32:30,380 So I'm going to agree. We don't know the long term outcomes. We never will. 323 00:32:30,380 --> 00:32:33,920 Until we have the long term. But if you can use I mean, if you when no. 324 00:32:33,920 --> 00:32:41,960 Does it decrease the onset of COPD or heart attacks? You're going to need cohort or randomised trials, 50 feet, 15 to 20 years. 325 00:32:41,960 --> 00:32:49,130 I can't wait 15 to 20 years. I can't wait for that patient that I saw in 1988 and watch him smother and die. 326 00:32:49,130 --> 00:32:53,530 I need to get him off combustibles. That's it from us. Thank you so much for listening. 327 00:32:53,530 --> 00:33:00,500 And a massive thanks to Jazz for the interview. If you haven't already, please do subscribe to us via iTunes or Spotify. 328 00:33:00,500 --> 00:33:07,240 We very much hope to be bringing you another episode next month. 329 00:33:07,240 --> 00:33:20,630 This is me. But some mention the findings we have can tell us what happened long. 330 00:33:20,630 --> 00:33:48,400 Safer than smoking. Still buying cars. That's why. 331 00:33:48,400 --> 00:33:51,880 Thank you so much for listening to our second episode of Let's Talk E-cigarettes. 332 00:33:51,880 --> 00:33:58,060 You've been listening to Nicola Linson and Jamie Harben Boyce with thanks to our guests this month, Professor Jazz Ahluwalia. 333 00:33:58,060 --> 00:33:59,920 Music is performed by Johnny Berliner. 334 00:33:59,920 --> 00:34:05,410 Thanks also to Jonathan Livingston Banks for running our monthly searches to Elsa Butler for editing this podcast. 335 00:34:05,410 --> 00:34:09,850 And to all our brilliant Cochran co-authors for helping us sift through and interpret the literature. 336 00:34:09,850 --> 00:34:14,170 This podcast was made possible through funding from Cancer Research UK and through core infrastructure 337 00:34:14,170 --> 00:34:18,310 funding to the Cochrane Tobacco Addiction Group from the National Institute for Health Research. 338 00:34:18,310 --> 00:34:21,970 The views expressed are those of the authors and not necessarily those of the 339 00:34:21,970 --> 00:34:26,048 National Institute for Health Research or the Department of Health and Social Care.