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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Tobacco control strategies&#44; implemented in developed countries for several decades now&#44; have led to the emergence of new actors&#44; electronic cigarettes &#40;EC&#41;&#44; and novel tobacco products<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> in the shape of Heat not Burn &#40;HnB&#41; systems&#44; touted as risk-modifying devices&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The health authorities have repeatedly pointed out the negative impact that attaching &#8220;safety&#8221; or &#8220;low risk&#8221; messages on tobacco products have on control strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">ECs are included among the so-called &#8220;electronic nicotine delivery systems&#8221;&#46; They consist of a cartridge which contains a liquid&#44; with or without nicotine&#44; a battery that when activated heats the liquid&#44; and an atomizer that transforms the heated liquid into an aerosol&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">HnB devices heat the tobacco to high temperatures &#40;&#62;350&#176;<span class="elsevierStyleSmallCaps">C</span>&#41;&#44; without reaching the 900&#8211;1200&#176;C levels that are obtained with conventional cigarettes &#40;CC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A few years ago&#44; our scientific society&#44; SEPAR&#44; clearly set out its position with regard to ECs&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Similarly&#44; the Forum of International Respiratory Societies&#44; an association of the main international scientific societies in the field of lung health&#44; published a statement on these devices&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The aim of both documents was to disseminate updated written scientific knowledge and to express concern about the safety of ECs and the risks that &#8220;normalizing&#8221; their use could&#44; and indeed does&#44; have&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The initial concern has been seen to be well founded&#46; We have witnessed an exponential increase in sales of these devices&#44; with some tobacco companies entering the market&#44; and the initial deterrent messages have even given way to scientific societies recommending these products<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> as a strategy for quitting nicotine dependence&#46; Nevertheless&#44; uncertainty persists&#44; and recently the European Respiratory Society has clearly positioned itself against the use of ECs&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> For this reason&#44; the SEPAR believes it is time to release a new document&#44; with up-to-date evidence on safety and effectiveness&#46; The following methodology was followed in the preparation of this document&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#41;</span><p id="par0030" class="elsevierStylePara elsevierViewall">The principal author conducted a literature search for articles related to the safety and efficacy in smoking cessation of ECs and the safety of I-Quit-Ordinary-Smoking &#40;IQOS&#174;&#41; devices&#46;</p></li></ul></p><p id="par0035" class="elsevierStylePara elsevierViewall">The search was conducted in 2 multidisciplinary databases that provide citation data&#44; Science Citation Index Expanded of the Web of Science group&#44; owned by Clarivate Analytics&#44; and the Elsevier Scopus database &#40;which includes the entire Medline&#47;Pubmed database&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The search query was entered in the Topic field &#40;which includes title&#44; abstract and keywords&#41;&#46; Document types were limited to article and review&#44; no date limits were set&#44; and documents that had been included up to the year 2018 were retrieved &#40;date of the search 1 December 2018&#41;&#46; The article published by Hajek et al&#46; was subsequently detected &#40;NEJM&#41;&#44; and given its importance&#44; was also included for analysis&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The terms &#40;descriptors&#41; used in the search were&#58; smoking&#59; tobacco&#59; electronic cigarette&#42;&#59; electronic nicotine delivery system&#42;&#59; smoking device&#42;&#59; Heat not Burn tobacco product&#42;&#59; non-cigarette tobacco product&#42;&#59; e-cigarette&#42;&#46; Quotation marks were used so that the terms would appear in the search equation as described verbatim in the sequence&#44; and some of the terms were truncated &#40;with an asterisk&#41;&#44; in order to retrieve all possible variants of the same term &#40;for example&#58; cigarette&#42;&#44; retrieves both cigarette and cigarettes&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The strategy was the following&#58;</p><p id="par0055" class="elsevierStylePara elsevierViewall">TITLE-ABS-KEY &#40;smoking OR tobacco OR &#8220;electronic cigarette&#42;&#8221; OR &#8220;electronic nicotine delivery system&#42;&#8221; OR &#8220;smoking device&#42;&#8221; OR &#8220;Heat not burn tobacco product&#42;&#8221; OR &#8220;non-cigarette tobacco product&#42;&#8221; or &#8220;e-cigarette&#42;&#8221;&#41; AND LIMIT-TO &#40;DOCTYPE&#44; &#8220;ar&#8221;&#41; OR LIMIT-TO &#40;DOCTYPE&#44; &#8220;re&#8221;&#41;&#46;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">1&#41;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Articles obtained from both databases were reviewed independently by the 2 principal authors&#44; who subsequently came to an agreement&#44; excluding those that were not pertinent&#44; appropriate or relevant&#44; thus extracting the documents with the greatest evidence&#46;</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall">Positioning will be based on the following schema&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">1</span><p id="par0070" class="elsevierStylePara elsevierViewall">Epidemiology&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">2</span><p id="par0075" class="elsevierStylePara elsevierViewall">Effects on health&#47;safety&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">3</span><p id="par0080" class="elsevierStylePara elsevierViewall">Effectiveness as a method of smoking cessation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">4</span><p id="par0085" class="elsevierStylePara elsevierViewall">Conclusions&#46;</p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Epidemiology</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Electronic cigarettes</span><p id="par0090" class="elsevierStylePara elsevierViewall">The use of ECs has expanded throughout the world&#44; doubling between 2008 and 2012&#46; There are currently more than 460 brands&#44; including models such as pod mods&#44; for example the high-selling JUUL&#174; system&#44; that can release high doses of nicotine&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In a survey conducted in the United States&#44; between 9&#37;&#8211;13&#37; of respondents over the age of 18 had tried ECs and between 2&#37;&#8211;6&#37; reported use in the last 30 days&#44; and this form of nicotine consumption was more common among young adults&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The National Youth Tobacco Survey<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> found that more than 3&#46;5 million American students regularly use ECs&#44; a habit that has been listed as an epidemic by the FDA&#44; which is calling for greater controls on sales&#44; especially to children&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Data from the 2017 Eurobarometer<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> report that 9&#37; of respondents occasionally use ECs and 2&#37; are regular users&#46; Between 2014 and 2016&#44; the number of individuals who had tried them at least once rose from 12&#37; to 15&#37;&#46; There are large differences in consumption between countries &#40;in the United Kingdom&#44; 5&#37; are regular users&#41;&#46; With respect to the pattern of use&#44; more than 50&#37; report that they do not find these devices useful for cutting down smoking &#40;52&#37;&#41;&#44; 17&#37; have managed to cut down&#44; and only 14&#37; has stopped smoking with ECs&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Data from the latest survey on drug use in secondary schools in Spain<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> &#40;ESTUDES 2016&#41; indicate that 20&#46;1&#37; of students have used ECs on some occasion&#46; Use in men ranges from 15&#37; at 14 years of age and 32&#37; at 18 years&#44; and between 11&#37; and 21&#37; in women&#46; Use is greater in smokers&#44; in whom rates are higher than 40&#37;&#44; while 21&#37; of EC users had never smoked tobacco previously&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The use of ECs can lead to the use of CCs among young people who in other circumstances would not have smoked&#46; A study<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> in adolescents aged 14 years who had never tried combustible tobacco&#44; followed for 6 and 12 months&#44; showed that the use of ECs increases the possibility of initiating tobacco use &#40;adjusted OR&#58; 2&#46;73&#59; 2&#46;00&#8211;3&#46;73&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Heat not burn devices&#58; IQOS&#174;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Few epidemiological studies have been published on the use of IQOS&#174;&#46; A Japanese study on the knowledge of ECs and HnB products conducted in 2015 found that 48&#37; of respondents were aware of these products and 6&#46;6&#37; had used them at some time&#46; In total&#44; 8&#46;4&#37; of the respondents had tried IQOS&#174;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">With regard to use in Europe&#44; a survey carried out in Italy after the launch of IQOS&#174; is of particular interest&#46; Twenty percent of respondents were aware of the system and 1&#46;4&#37; had tried it&#46; About half of IQOS&#174; users &#40;45&#37;&#41; and people interested in trying it had never been smokers&#46; If we extrapolate these data to the general population&#44; more than 730&#44;000 Italians had tried it&#44; 329&#44;000 of whom were not smokers of CCs&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">According to data from Philip Morris International &#40;PMI&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> IQOS&#174; is already used by more than 5 million people worldwide&#46; In Spain&#44; cumulative sales of 100&#44;000 units are estimated&#46; The fact that IQOS&#174; is considered a low-risk tobacco product means that the fiscal regime of CCs does not apply&#44; and health warnings appear on only 30&#37; of the packaging&#46; For all these reasons&#44; and in view of the experience in Italy&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> an increase in consumption over the next few years is likely as users progressively attempt to replace CCs&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Effects on health&#47;safety</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Electronic cigarette</span><p id="par0135" class="elsevierStylePara elsevierViewall">The design of the EC&#44; the composition of the liquid&#44; and the pattern of use all play a part in affecting health&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">In addition to nicotine&#44; carcinogenic substances and ultrafine particles have been identified in EC aerosols&#46; The most significant carcinogens include tobacco-specific nitrosamines&#44; aldehydes&#44; volatile organic compounds&#44; and polycyclic aromatic hydrocarbons&#46; The ultrafine particulate matter is significant for its heavy metal particles&#46; These particles&#44; with a diameter of less than 0&#46;5 microns&#44; penetrate the lungs easily and reach the bloodstream&#44; and are then distributed throughout the body&#44; causing damage to multiple organs and systems&#46; There is evidence that&#44; with the exception of nicotine and some metals&#44; in typical conditions of use&#44; exposure is lower than with tobacco smoke&#44; but by no means less toxic&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;20</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Biological effects of electronic cigarette aerosols</span><p id="par0145" class="elsevierStylePara elsevierViewall">Recent studies have shown that EC aerosols may induce acute endothelial cell dysfunction and can also promote the formation of reactive oxygen species &#40;oxidative stress&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Nicotine is present in varying amounts&#46; In experienced users who consume greater amounts of ECs&#44; nicotine consumption can be similar to that of CCs&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Surfactants such as propylene glycol and glycerol are safe in liquid form&#44; although it is not known with certainty if they have the same properties when used in the form of aerosols&#46; The same is true of the more than 150 EC flavoring chemicals&#44;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#8211;26</span></a> which contain toxic carbonyl compounds &#40;formaldehyde&#44; acetaldehyde&#44; acrolein and glyoxal&#41; derived from the thermal decomposition of propylene glycol&#44; glycerol&#44; and flavorings&#46; Formaldehyde is classified as a human carcinogen &#40;Group 1&#41;&#44; and acetaldehyde is a probable carcinogen &#40;Group 2B&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Radicals and reactive oxygen species are detected that cause oxidative stress and damage cellular proliferation and metabolism&#46; Volatile organic compounds and phenols also occur&#44; along with other substances such as furans&#44; phthalate diethyl malonate and diethylhexyl phthalate&#46; Various metals have been detected&#44; such as chromium&#44; nickel&#44; lead&#44; manganese&#44; aluminum&#44; tin&#44; and iron&#44; sometimes in quantities exceeding that of CCs<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;21&#44;22</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In vivo</span> studies in humans found data on oxidative stress and endothelial dysfunction&#44; with increased cardiovascular risk markers and increased levels of circulating endothelial progenitor cells &#40;EPC&#41; after exposure to ECs of the same magnitude as that produced by tobacco smoke&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22&#44;28</span></a> Other authors<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> found both <span class="elsevierStyleItalic">in vivo</span> and <span class="elsevierStyleItalic">in vitro</span> evidence that exposure to ECs causes levels of oxidative stress similar to tobacco smoke&#46; Most studies conclude that ECs induce less oxidative stress than tobacco smoke&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Effects of electronic cigarette aerosols on the cardiovascular system</span><p id="par0170" class="elsevierStylePara elsevierViewall">At present&#44; the results of the different studies indicate that the use of ECs is associated with cardiovascular disease and subclinical atherosclerosis&#44; but we lack confirmatory evidence from long-term epidemiological studies&#46; With regard to the acute effects&#44; EC devices that use higher powered batteries show a steady increase in heart rate after use&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Another study found that switching from CCs to ECs slightly decreased systemic blood pressure at 52 weeks in a group of smokers&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Carcinogenic effects of electronic cigarette aerosols</span><p id="par0180" class="elsevierStylePara elsevierViewall">Hypothetically&#44; the risk of cancer with ECs would be less than that associated with CCs&#44; due to the reduced number and amount of potentially carcinogenic substances&#46; However&#44; there is uncertainty surrounding the carcinogenic capacity of other highly DNA reactive substances&#44; such as formaldehyde and acrolein&#44; which can cause tumors in laboratory animals&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">No long-term epidemiological studies have measured outcomes&#44; such as the presence of tumors or intermediate cancer endpoints after exposure to ECs&#44; although some studies show that rats exposed to EC aerosols develop DNA changes and mutations in urine&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Effects of electronic cigarette aerosols on the respiratory system</span><p id="par0190" class="elsevierStylePara elsevierViewall">Pulmonary exposure to ECs could damage the respiratory system or worsen pre-existing lung disease&#46; Studies have been published that examine smokers with previous lung disease who switch from CCs to ECs &#40;single or double use&#41;&#46; No changes were found in lung function&#44; although both quality of life and the number of exacerbations improved&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> A notable limitation of these studies is the sample size&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Some of the studies that examine the effects of ECs suggest that devices that contain nicotine can have short-term adverse effects on pulmonary defense mechanisms&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Cross-sectional studies that examine the impact of ECs on the respiratory health of adolescents found a significant association between the use of ECs and the presence of respiratory problems&#44; asthma exacerbations&#44; and school absenteeism&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Effects of electronic cigarette aerosols on infectious defense mechanisms</span><p id="par0205" class="elsevierStylePara elsevierViewall">With regard to the risk of infections&#44; EC vapors increase pneumococcal adherence to the epithelial cells of the airway&#44; both <span class="elsevierStyleItalic">in vitro</span> and in an experimental model with rats&#46; These findings suggest that ECs can increase susceptibility to pneumococcal infection&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Regarding oral disease&#44; a review of the risk of cancer concludes that recommendations on the use of ECs should be viewed with caution&#44; given the possible cumulative effect of mutations&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">A study found that similar levels of tobacco-specific nitrosamines are found the urine of non-smokers exposed to ECs and individuals exposed to CC&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Heat not burn devices&#58; IQOS&#174;</span><p id="par0220" class="elsevierStylePara elsevierViewall">These devices were first marketed in Japan in 2013 &#40;Ploom&#174;&#44; Japan Tobacco Company&#44; JTC&#41;&#46; The IQOS&#174; <span class="elsevierStyleItalic">&#40;I Quit Ordinary Smoking&#41;</span> model was developed by PMI&#46; It has been marketed in Spain since 2016 and is available in 43 countries&#46; It is presented as a less harmful product than CCs&#44; and in the United States&#44; PMI applied to the FDA for labeling as a low-risk tobacco product&#44; but this was refused&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">These devices use battery-powered heating systems to increase the temperature of the tobacco without achieving total combustion&#46; The temperature reached with IQOS&#174; produces smoke that contains fewer toxic substances than CCs&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However&#44; it has been shown that volatile compounds&#44; polycyclic aromatic hydrocarbons&#44; and carbon monoxide &#40;CO&#41;&#44; and even elements derived from pyrolysis are released in the mainstream emissions of the device&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Most publications that minimize the risk to health of using IQOS&#174; are studies sponsored by tobacco companies&#44; and their safety conclusions have been questioned&#46; A recent review<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> collected data available to date on emissions from these products&#59; of the 31 studies retrieved&#44; 20 were associated with tobacco companies&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Data have been obtained on the levels of harmful and potentially harmful constituents &#40;HPHC&#41; in the mainstream emissions of IQOS&#174;&#44; although only 2 of the studies were published by independent authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41&#44;43</span></a> When the data are compared with the results of the studies sponsored by the tobacco industry&#44; no differences were found in levels of CO&#44; water&#44; and the total number of particles&#59; however&#44; lower levels of tar &#40;nicotine-free dry particulate matter&#41; and higher levels of tobacco-specific nitrosamines delivered by the IQOS&#174; device were detected&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#44;45</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">The results regarding particles in secondhand smoke from IQOS&#174; are contradictory&#46; HPHC is detected in air at lower levels than from CCs&#44; but the content of the emissions varies considerably between the different studies&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> In an independent study&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> acrolein&#44; an irritative substance&#44; was detected&#44; but not in the studies sponsored by PMI&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Glantz<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> has reviewed PMI data on the levels of potentially harmful biomarkers in IQOS&#174; compared to CCs&#46; No significant differences were found in 23 of 24 studies analyzed&#44; leading the author to conclude that the statistical analyses were manipulated&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Nabavizadeh<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> analyzed the effect of IQOS&#174; on the vascular endothelium using arterial flow-mediated dilatation&#44; a validated measure of cardiovascular effect&#46; The effects in rats which inhaled IQOS&#174; are comparable to the effects of CCs&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">To end this safety section&#44; we wish to point out the interest that some studies show in demonstrating that the toxicity of ECs and HnB devices is less than that of CCs&#44; when what we really need to take into account is that the respiratory apparatus must not be gratuitously exposed to any harmful substance &#40;even if&#44; as they insist&#44; CC smoke is worse&#41;&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Effectiveness as a method of smoking cessation</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Electronic cigarettes</span><p id="par0260" class="elsevierStylePara elsevierViewall">Since their launch&#44; ECs have been continuously promoted as a tool for smoking cessation&#46; The clinical trials published to date have not been able to fully clarify this issue&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Bullen<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> reports the results of 657 smokers willing to quit&#44; randomized to nicotine patches&#44; ECs&#44; or placebo&#46; ECs were recognized as moderately effective&#44; and significant methodological deficiencies were observed&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> the most important being the lack of a double-blind design&#44; differences in therapeutic adherence &#40;around 80&#37; in the EC group and 46&#37; in the group that received patches&#41;&#44; and the fact that ECs were shipped directly free of charge to homes&#44; while patches had to be purchased in pharmacies&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Another non-blinded clinical trial<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> was conducted in smokers who had no intention to quit smoking&#46; Finally&#44; a study<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> also conducted in smokers with no intention to quit used an unconventional methodology and a short follow-up of scarcely 5 months&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Therefore&#44; the first Cochrane meta-analysis<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> performed in 2014 concluded that confidence in ECs assisting in smoking cessation was low&#46; A new revision was published in 2016&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> in which the usefulness of the EC in helping smokers to quit was re-examined on the basis of 15 articles that met the selection criteria&#46; Two randomized controlled trials with a total of 662 participants were analyzed&#44; revealing that ECs containing nicotine may help smokers to quit for a period of 6&#8211;12 months compared with placebo&#46; However&#44; the authors added that due to the small number of trials&#44; the imprecise nature of the studies&#44; and the wide confidence intervals&#44; confidence in the results was low&#44; so the quality of evidence&#44; according to GRADE standards&#44; was classified as low or very low&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Another study<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> evaluated the association between ECs and smoking cessation in adult smokers&#44; regardless of their motivation&#44; and found that the likelihood of quitting smoking was 28&#37; lower in the group that used ECs &#40;OR 0&#46;72&#44; 95&#37; CI&#58; 0&#46;57&#8211;0&#46;91&#41;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Another study&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> aimed at generating new real-life evidence on the effectiveness of ECs in helping young adults to quit smoking&#44; found that the odds ratio adjusted for smoking cessation was lower when using ECs compared with individuals who did not use them&#59; the authors concluded that no evidence was available to claim that ECs were useful to help quit smoking&#46; Similarly&#44; Rigotti et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> in a study that sought to determine whether the use of ECs after discharge from hospital was associated with cessation in smokers who were planning to quit&#44; found that individuals who used ECs after discharge were less likely to remain abstinent 6 months later than those who did not use them&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">A recent clinical trial<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> compared the effectiveness of ECs with nicotine-replacement therapy &#40;NRT&#41;&#46; The cessation rate at 1<span class="elsevierStyleHsp" style=""></span>year was 18&#37; with ECs compared to 9&#46;9&#37; with NRT &#40;adjusted RR 1&#46;75 &#91;1&#46;24&#8211;2&#46;46&#93;&#41;&#46; This study has important methodological limitations&#58; for example&#44; it is not double-blind or placebo-controlled&#59; at the 4-week follow-up&#44; only 10&#46;3&#37; of the individuals who received patches were using them&#44; while 53&#37; of those who received ECs continued&#46; Another potentially alarming aspect is the fact that 80&#37; of EC users continued using them 12 months later&#44; compared to 9&#37; of the NRT group&#46; This suggests that EC can create addiction&#44; and smokers would appear to be switching from 1 addiction to another&#44; with the public health problems that this might imply&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">For this reason&#44; we currently do not have sufficient scientific evidence to conclude that ECs help to reduce the consumption of cigarettes or quit smoking&#46; We need more independent research&#44; randomized&#44; double-blind&#44; placebo-controlled clinical trials with no methodological deficiencies&#44; and more rigorous observational studies conducted in real life to answer our questions and determine whether EC might be useful in helping to reduce tobacco use and quit smoking&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Heat not burn devices&#58; IQOS&#174;</span><p id="par0300" class="elsevierStylePara elsevierViewall">There is no evidence to suggest that HnB devices could be useful for smoking cessation&#46; Furthermore&#44; the experience<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> observed in some countries shows that users of IQOS&#174; become smokers of both ECs and CCs&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0305" class="elsevierStylePara elsevierViewall">Our analysis&#44; conducted using the available evidence&#44; prompts the SEPAR to conclude with a few warnings about ECs and HnB devices&#44; in particular IQOS&#174;&#44; the only system available in Spain&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">The growth experienced by ECs&#44; in particular the so-called pods&#44; has alarmed the health authorities&#44; since teenage users of Juul&#174; &#40;a type of pod that contains high amounts of nicotine&#41; have levels of urinary cotinine that are almost double those found in smokers of CCs&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> This confirms initial fears that these devices are becoming a gateway to nicotine addiction&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Even though tobacco companies insist that their devices replace CCs&#44; the reality is that smokers become dual users&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Studies carried out in ECs and IQOS&#174; confirm that the emission of toxic substances is quite probably lower than with CCs&#59; however&#44; it is clear that safety in the short&#44; medium and long term is not guaranteed&#46; Moreover&#44; there is a demonstrated risk to people&#44; especially children&#44; who passively inhale the fumes and vapors of these devices&#46; It should be noted that toxicity should not be compared between CCs and these devices&#44; but between the use of these devices and abstinence from any type of tobacco use&#46; It is not natural to smoke&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">With regard to effectiveness in smoking cessation&#44; we currently we do not have sufficient scientific evidence &#40;randomized&#44; double-blind&#44; placebo-controlled clinical trials with no methodological deficiencies and more rigorous observational studies&#41; to conclude that ECs help to reduce the consumption of cigarettes and quit smoking&#46; This&#44; coupled with the safety problems associated their use&#44; means that these devices cannot yet be recommended as a treatment for smoking cessation&#44; especially when we currently have sufficient scientific evidence that demonstrates that the only safe and effective treatment for help quitting smoking is the use of drugs &#40;varenicline&#44; NRT&#44; and bupropion&#41;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">61&#8211;63</span></a> in combination with psychological counselling&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interests</span><p id="par0330" class="elsevierStylePara elsevierViewall">JS-C has received honoraria for presentations&#44; participation in clinical studies&#44; and publications from&#58; AstraZeneca&#44; Boehringer&#44; Ferrer&#44; GSK&#44; Menarini&#44; Pfizer&#44; and Rovi&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">JIG-O has received honaria for presentations&#44; participation in clinical studies&#44; and publications from&#58; AstraZeneca&#44; Esteve&#44; Gebro&#44; Menarini&#44; Pfizer&#44; and Rovi&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">ARP has received honoraria for presentations&#44; participation in clinical studies&#44; and publications from&#58; AstraZeneca&#44; Esteve&#44; Ferrer&#44; MundiPharma&#44; Novartis&#44; and Pfizer&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">ACE states no conflict of interests&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">EHM has received honoraria for presentations&#44; participation in clinical studies&#44; and publications from&#58; AstraZeneca&#44; Chiesi&#44; Esteve&#44; Ferrer&#44; GSK&#44; MundiPharma&#44; Novartis&#44; and Pfizer&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">CRC has received honoraria for presentations&#44; participation in clinical studies&#44; and publications from&#58; Esteve&#44; GSK&#44; MundiPharma&#44; Novartis&#44; and Pfizer&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">ECC states no conflict of interests&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">CAJ-R has participated in studies and given presentations for pharmaceutical companies that produce and market drugs for smoking cessation</p></span></span>"
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          "titulo" => "Effects on health&#47;safety"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The use of novel tobacco products&#44; particularly the electronic cigarette &#40;EC&#41; and partial tobacco combustion devices &#40;HnB systems&#58; Heat not Burn&#41;&#44; has increased exponentially&#44; particularly among adolescents and young people&#46; The health authorities and scientific societies have shown concern about issues surrounding safety and effectiveness &#40;as a method of smoking cessation&#41;&#46; A study of the available scientific evidence has concluded that the safety of the vapor or fumes inhaled by the users of these devices cannot be guaranteed&#46; Contradictory results from various clinical trials and meta-analyses also mean that these devices cannot be recommended for their effectiveness in cessation&#44; especially when safe and effective treatments are available to help quit smoking &#40;varenicline&#44; nicotine replacement therapy&#44; and bupropion&#44; combined with psychological counseling&#41;&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El uso de productos del tabaco novedosos&#44; en especial el cigarrillo electr&#243;nico &#40;CE&#41; y los dispositivos de combusti&#243;n parcial de tabaco &#40;sistemas HnB&#58; Heat not Burn&#41;&#44; ha aumentado de forma exponencial&#44; sobre todo en j&#243;venes y adolescentes&#46; Las autoridades sanitarias y las sociedades cient&#237;ficas han mostrado preocupaci&#243;n ante las dudas que existen sobre su seguridad y eficacia &#40;como m&#233;todo de abandono del tabaco&#41;&#46; Tras el estudio de la evidencia cient&#237;fica disponible&#44; no es posible asegurar la inocuidad de los vapores o humos que inhalan los usuarios de estos dispositivos&#46; Respecto a la eficacia&#44; no pueden recomendarse&#44; tras los resultados contradictorios&#44; de diferentes ensayos cl&#237;nicos y metan&#225;lisis&#59; m&#225;xime cuando existen tratamientos seguros y eficaces para ayudar a dejar de fumar &#40;vareniclina&#44; terapia sustitutiva con nicotina y bupropion&#44; unido a asesoramiento psicol&#243;gico&#41;&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Signes-Costa J&#44; et al&#46; Declaraci&#243;n Oficial de la Sociedad Espa&#241;ola de Neumolog&#237;a y Cirug&#237;a Tor&#225;cica &#40;SEPAR&#41; sobre cigarrillos electr&#243;nicos e IQOS&#174;&#46; Arch Bronconeumol&#46; 2019&#59;55&#58;581&#8211;586&#46;</p>"
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