Gac Sanit. 2020;34(1):77–82 Special article Tackling second-hand exposure to tobacco smoke and aerosols of electronic cigarettes: the TackSHS project protocol Esteve Fernández a,b,c,∗ , María José López d,e,f , Silvano Gallus g , Sean Semple h , Luke Clancy i , Panagiotis Behrakis j , Ario Ruprecht k , Giuseppe Gorini l , Ángel López-Nicolás m , Cornel Radu-Loghin n , Joan B. Soriano o , TackSHS Project Investigators♦ a Institut Català d’Oncologia (ICO), L’Hospitalet de Llobregat (Barcelona), Spain b Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat (Barcelona), Spain c School of Medicine and Health Sciences, Bellvitge Campus, Universitat de Barcelona, L’Hospitalet de Llobregat (Barcelona), Spain d Agència de Salut Pública de Barcelona, Barcelona, Spain e CIBER de Epidemiología y Salud Pública (CIBERESP), Spain f Institut d’Investigació Biomèdica Sant Pau (IIB St. Pau), Barcelona, Spain g Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy h Institute for Social Marketing, University of Stirling, Stirling, Scotland, UK i TobaccoFree Research Institute Ireland, Dublin, Ireland j George D Behrakis Research Lab, Hellenic Cancer Society, Athens, Greece k Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy l Istituto per lo Studio, la Prevenzione e la Rete Oncologica, Florence, Italy m Universidad Politécnica de Cartagena, Cartagena, Spain n European Network for Smoking and Tobacco Prevention, Brussels, Belgium o Respiratory Department, Hospital Universitario La Princesa, Madrid, Spain a r t i c l e i n f o a b s t r a c t Article history: Objective: The TackSHS project aims to comprehensively elucidate the impact that exposure to second- Received 28 June 2019 hand smoke (SHS) from cigarettes and second-hand aerosols (SHA) from electronic cigarettes have on Accepted 8 July 2019 the respiratory health of the European population according to socioeconomic characteristics and other Available online 23 September 2019 determinants. Method: The TackSHS project involves a series of coordinated studies carried out by 11 academic and Keywords: public health organisations from six European countries. The project will investigate: a) the determinants Second-hand smoke of SHS and SHA exposure assessed at the individual level (surveys on representative general population Passive smoking Electronic cigarette samples) and in common environments (environmental sampling in specific settings); b) the overall Electronic nicotine delivery systems disease burden, mortality and morbidity attributable to such exposure; and c) its economic impact in Aerosols terms of direct health care costs. The project will also examine specific acute respiratory health changes Second-hand aerosols in healthy individuals and patients with respiratory diseases exposed to SHS and SHA. In addition, the Respiratory health project will examine the effectiveness of a novel intervention to reduce SHS exposure in households Burden of disease where smoking is permitted. All these studies are inter-related and involve collaborative coordination Economic impact among the participant organisations. Conclusion: The comprehensive, integrated approach of the TackSHS project will enable a significant step forward from the current status quo in the understanding of the impact of SHS and SHA exposure on health and provide the basis for health policy recommendations to help European countries to further reduce the harm caused by SHS and SHA exposure. © 2019 SESPAS. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Abordando la exposición a las emisiones del tabaco y de los cigarrillos electrónicos: protocolo del proyecto TackSHS r e s u m e n Palabras clave: Objetivo: El proyecto TackSHS pretende caracterizar el impacto global de la exposición al humo ambiental Humo ambiental del tabaco de tabaco (HAT) y al aerosol de los cigarrillos electrónicos (ACE) en la salud respiratoria de la población Tabaquismo pasivo europea según variables socioeconómicas y otros determinantes. Cigarrillos electrónicos Método: El proyecto TackSHS consiste en una serie de estudios coordinados y gestionados por 11 organiza- Sistemas electrónicos de administración ciones académicas y de salud pública de seis países europeos. El proyecto estudiará: a) los determinantes de nicotina de la exposición al HAT y al ACE a nivel individual (encuestas en muestras representativas de la población general) y en espacios comunes (muestras ambientales en lugares específicos); b) su carga general de ∗ Corresponding author. E-mail address: efernandez@iconcologia.net (E. Fernández). ♦ See Annex. https://doi.org/10.1016/j.gaceta.2019.07.002 0213-9111/© 2019 SESPAS. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/). 78 E. Fernández et al. / Gac Sanit. 2020;34(1):77–82 Exposición al aerosol enfermedad y la morbimortalidad atribuible a tal exposición; y c) su impacto económico en términos de Salud respiratoria costes sanitarios directos e indirectos. Además, el proyecto investigará cambios específicos a corto plazo Carga de enfermedad en la salud respiratoria en personas sanas y en pacientes con enfermedades respiratorias expuestos al Impacto económico HAT y al ACE. También examinará la efectividad de una intervención novedosa para reducir la exposición al HAT en hogares donde se permite fumar. Todos estos estudios están interrelacionados y conllevan una coordinación colaborativa entre las instituciones participantes. Conclusión: El enfoque integral del proyecto TackSHS permitirá un avance significativo en la evidencia sobre la comprensión del impacto de la exposición al HAT y al ACE en la salud, y proporcionará una base para desarrollar recomendaciones políticas sanitarias para ayudar a los países europeos a reducir los daños causados por la exposición al HAT y al ACE. © 2019 SESPAS. Publicado por Elsevier España, S.L.U. Este es un artı́culo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). Introduction France, Germany, Greece, Ireland, Italy, Poland, Portugal, Roma- nia, Spain and the United Kingdom) representing geographical, Research produced during the past three decades has provided legislative (country-specific smoke-free policies) and cultural vari- substantial evidence of the harm that short- and long-term expo- ations across the European Union (EU). Private settings studied will sure to second-hand smoke (SHS) represents to respiratory and include homes and cars, while outdoor settings will include ter- cardiovascular health of adults and children.1,2 While interest in races of hospitality venues, children playgrounds and entrances SHS exposure prevalence and its effects is increasing,3 important to primary school buildings. Around 1000 environmental mea- gaps remain when designing national and international health poli- surements will be collected: 180 measurements from homes in cies aiming to protect populations. One of them is a scarcity of 9 countries and 660 measurements from outdoor settings in the studies objectively measuring markers of SHS in settings where 11 countries involved in the study; and 120 environmental mea- smoking is not regulated, such as private and outdoor public places. surements will be collected in cars in two countries (Spain and the In addition, electronic cigarettes (e-cigarettes) have irrupted United Kingdom). These countries were selected considering dif- into the market of tobacco products in the past decade, creat- ferences in smoking legislation in cars. A convenience sample will ing an on-going debate among the research community on their be obtained considering neighbourhoods from different socioeco- health effects and potential impact on public health.4 While active nomic status, which will be assessed using local ecological synthetic e-cigarette use and its health effects have received substantial indexes. SHS will be assessed through the measurement of airborne attention in research, evidence on the health impact of bystanders’ nicotine. Nicotine samplers, which consist of a 37-mm diameter exposure to second-hand aerosols (SHA) generated by its use is still plastic cassette containing a filter treated with sodium bisulphate, scarce.5 will be used. A passive sampling will be performed in homes (7- The project “Tackling secondhand tobacco smoke and e- day sampling) and cars (24-hour sampling). In outdoor settings, cigarette emissions: exposure assessment, novel interventions, active sampling will be used attaching a nicotine sampler to an air impact on lung diseases and economic burden in diverse European pump with a flow rate of 3 L/min, and 30-min measurements will populations” (the TackSHS project: www.tackshs.eu) was devel- be taken. Sampling will be done avoiding the warmest and the cold- oped to address these and other challenges in the research of SHS est months of the year. All the nicotine samples will be analysed by and SHA. The TackSHS project intends to comprehensively eluci- gas chromatography/mass spectrometry.6 date the impact that SHS and SHA exposure have on the European population and how health impacts vary according to socioeco- Study 2. The TackSHS survey: a pan-European study on SHS and nomic and other demographic characteristics, with a particular SHA exposure (WP3) emphasis on specific vulnerable groups. This paper describes the specific objectives and methods of each study or ‘work-package’ This is a European cross-sectional study, led by the Istituto within the project. di Ricerche Farmacologiche Mario Negri IRCCS (Italy), that aims to: 1) estimate the prevalence and the determinants of smok- Method ing, e-cigarette use, and exposure to SHS and SHA; 2) analyse attitudes, perceptions and behaviours of the adult European pop- The TackSHS project is organised in 11 work-packages (WP) of ulation towards smoke-free policies in their countries; and 3) which eight are research-oriented and correspond to independent compare selected smoking-related data originated in this study studies, with a further three WPs involved in providing support and a previously conducted pan-European survey (i.e., the PPACTE (coordination, instrument calibration, and results dissemination) project).7 Approximately 12,000 individuals aged 15 years and during the 48 months of the project (November 2015 – October older will be enrolled in 12 EU countries (the same countries listed 2019). The overall structure of the project is depicted in Figure 1. for WP2 plus Latvia). The TackSHS survey will be representative of A summary of the WPs with the leading partners is provided in the country-specific population using a similar methodology of a Table I of the online Appendix. previous project.7 The sample size in each specific country (approx- imately n = 1000) will enable the estimation of prevalence in that Study 1. Environmental assessment of SHS exposure in private country with a standard error of ± 1.6%. The sampling methodology and outdoor settings in Europe (WP2) (in most of the countries multistage/stratified random sampling) will ensure the representativeness of the adult population in terms This is a European cross-sectional study, led by the Agència de of sex, age, geographic area and selected socioeconomic charac- Salut Pública de Barcelona (Spain), that aims to objectively assess teristics. A standard questionnaire developed ad hoc from existing SHS exposure across a range of different environments where validated questionnaires will be used to collect information on smoking was not regulated at the time this project was planned. cigarette smoking, use of e-cigarettes and emergent heated tobacco The study will be conducted in 11 European countries (Bulgaria, products. The questionnaire focuses particularly on the exposure E. Fernández et al. / Gac Sanit. 2020;34(1):77–82 79 WP1. Coordination & Management Advisory Board Advisory Board WP4. WP2. WP3. WP9. Intervention to Environmental Survey on SHS Attributable reduce exposure assessment of SHS in and electronic mortality to SHS in homes private and outdoor cigarettes settings WP10. Economic impact on health WP5. WP7. WP8. WP6. Effects SHS on Methods of Assessment of Acute effects of SHS lung diseases measurement of passive exposure to and e-cig aersol on SHS and e-cig e-cig aerosol in lung diseases aerosol real-life conditions WP11. Policy Recommendations & Dissemination Figure 1. TackSHS project structure and organisation of the work packages (WPs). SHS: Secondhand smoke; e-cig: electronic cigarettes. to SHS and the passive exposure to SHA from e-cigarettes in differ- effects that result from short-term SHS exposure among patients ent indoor and outdoor settings. WP3 will also examine compliance with asthma and chronic obstructive pulmonary disease (COPD). with the current country-specific smoke-free legislations, attitudes In many European countries, the introduction of smoke-free laws and perceptions towards various tobacco control policies, including has prompted the proliferation of outdoor areas where smoking smoking ban regulations that are already adopted, and an extension is permitted, and there exist places where non-smokers are still of these regulations to other (outdoor) public places. Finally, the exposed to some levels of SHS. The health effects of such expo- survey will explore participants’ knowledge of the harmful effects sures are uncertain as to date there is only anecdotal evidence; of SHS and SHA. some effects can be expected but it may be difficult to demonstrate unless in naturalistic, real-life conditions. This study will aim to Study 3. Air quality feedback to reduce SHS exposure in homes involve 60 patients (volunteers) from three European countries: the (WP4) Czech Republic, Ireland, and Spain (20 patients in each participat- ing country: 10 COPD and 10 asthma patients). The recruitment of This is an intervention study, led by the University of Stirling such patients will be done with the cooperation of patients’ organ- (Scotland, UK), aiming to encourage behaviour-change towards a isations in these countries which are affiliated with the European smoke-free home environment. The study will provide the par- Lung Foundation. Participants will be trained to keep a diary record ticipants (smokers who smoke at home and take care of at least of any noted changes and medication usage and perform pre- and one child) regular feedback in the form of personalised air qual- post-peak flow, spirometry, and carbon monoxide measurements. ity measurements made in their homes. This study will develop Such patients will wear personal monitors to continuously measure a targeted intervention with socioeconomically deprived smok- exposure to particulate matter (PM1 , PM2.5 , PM10 ) with continu- ers in four countries (Greece, Italy, Scotland, and Spain) based on ous geolocalisation monitoring with AirSpeck mobile wireless air a previously piloted intervention.8 The study will aim to recruit quality monitors and a RESpeck monitor to measure breathing rate 160 smokers (40 in each country). Participants will have particle and depth to detect any acute changes in breathing during or fol- counting instruments to measure in real time particulate matter lowing exposure to SHS at entertainment facilities. These novel concentration (PM2.5 ) installed in their homes for a period of 30 measurements will determine the individual level of SHS exposure days. These devices will allow data acquisition in real-time with a with spatially-resolved estimation of personal dosage of PM and 3G internet connection. During this period, personalised feedback the identification of acute respiratory effects from such exposure. will be provided to, and discussed with, the smoker along with There is also a recording of each breath sound which can be recog- target-setting and exploration of suitable methods of behaviour- nised and matched with time, location and level of exposure with change. Personalised feedback will be given via text messages to identification of any lags in time that may occur. mobile phones, email messages and through telephone calls. A final home visit will gather data on changes made while some Study 5. Impact of short-term second-hand exposure participants (10-20%) will take part in a further qualitative phone to e-cigarette aerosols (SHA) on the respiratory system (WP6) interview to gather data on their experience of the intervention. This study, led by the Hellenic Cancer Society (Greece), is aimed Study 4. Health effects of SHS exposure in outdoor smoking areas at characterizing exposure to e-cigarette aerosols among healthy in patients with COPD and asthma (WP5) non-smoker volunteers. An experimental study with cross-over design will be implemented in a laboratory. Three trial arms will This is a clinical research study, led by TobaccoFree Research be performed (no exposure vs. low e-cigarette aerosol exposure Institute Ireland, aiming to assess the acute respiratory health vs. high e-cigarette aerosol exposure) that will be differentiated 80 E. Fernández et al. / Gac Sanit. 2020;34(1):77–82 by the e-cigarettes’ battery power outputs. The study sample Study 9: Economic impact of SHS on morbidity and mortality and will consist of 40 adult volunteers that will be randomized to return on investment of interventions aiming at reducing SHS the sequence of three exposures to e-cigarette aerosol. In total, exposure (WP10) 120 person-exposures will take place, leading to 240 pre- and post- measurements. Recruitment will take place in Athens (Greece). This study, led by the Universidad Politécnica de Cartagena Exposures will last 30 minutes and will take place in a standardised (Spain), will produce economic models for the analysis of the return exposure chamber.9 Before and after exposure to aerosols origi- on investment of policies aimed at reducing SHS exposure in EU nated from e-cigarette use, the lung function of each participant countries. Available return on investment models for smoking ces- will be assessed through impulse oscillometry to assess respira- sation interventions (http://www.equipt.eu) will be considered. tory system impedance and resistance, exhaled nitric oxide levels Nevertheless, these models consider the effects of SHS exposure by and 8-isoprostane concentration in the exhaled breath condensate assuming that each successful quit contributes a fractional reduc- as a marker of oxidative stress.10 tion in the disease burden associated with SHS, they do not include policies specifically aimed at reducing SHS other than curbing smoking prevalence. The information on SHS exposure in European Study 6. Second-hand exposure to emissions from electronic countries obtained in the WP3 and the epidemiological evidence on cigarettes: personal and environmental assessment in confined attributable mortality and morbidity to SHS obtained in the WP9 spaces (WP8) will be combined with data on the cost consequences of disease to obtain country-specific versions of the return on investment This WP, led by the Institut Català d’Oncologia (Spain), models. The models will consider the lag between exposure and comprises three sub-studies to address three complementary effect and therefore will use appropriate short- and medium-term objectives. Firstly, a systematic review of the published studies horizons (2, 5, and 10 years) and long-term horizons (20 years and on passive exposure to e-cigarette aerosols will be performed. lifetime). With these models, the economic burden caused by SHS Secondly, environmental and bystanders’ exposure to e-cigarette exposure and the return on investment of some interventions will aerosols in controlled conditions in a car and a room will be inves- be estimated. Different perspectives (health system, overall pub- tigated through an experimental study which will involve two lic sector and wider society) will be adopted. The model outcomes volunteers exposed to SHA and an e-cigarette user to produce it. will comprise not only standard cost-effectiveness and cost-utility Airborne nicotine and PM2.5 will be measured for environmental ratios but also a fully disaggregated list of health outcomes and exposure and nicotine, cotinine and tobacco-specific nitrosamines resource use consequences so that the budgetary impact of imple- in saliva for personal exposure assessment. Thirdly, a cross- mentation at local, regional and national scale will be appraised. sectional study will be conducted to investigate environmental and bystanders’ exposure to SHA in real-life conditions at homes of e- cigarette users, in four European countries (Greece, Italy, Spain, Supportive WP: Instruments’ calibration (WP7) and the UK). Based on the differences detected in a previous pilot study11 and standard assumptions, this study will aim to include This WP, led by the Fondazione IRCCS Istituto Nazionale dei 250 participants. Airborne nicotine and PM2.5 will be measured Tumori (Italy), will investigate the best methods and procedures during one week and saliva and urine samples will be collected for real-time measurement of SHS and SHA using optical particle for the determination of nicotine, cotinine and tobacco-specific counters. All devices of the project Partners used in WP4, WP5, WP6 nitrosamines. Airborne nicotine samples will be analysed by gas and WP8 (Dylos DC1700, SidePak AM150, and AirVisual Pro) will chromatography/mass spectrometry;6,12 while saliva and urine be tested and individually calibrated through comparison with one analysis will be performed using high-resolution chromatogra- Beta Attenuation Monitor (BAM-1020). phy/mass spectrometry;13,14 and PM2.5 will be measured by means The Dylos DC1700 is an optical particle counter instrument that of an optical portable counter.15 counts the small and large particles present in the surrounding environment. The TSI SidePak AM510 Personal Aerosol Monitor is a laser photometer that measures a variety of particle sizes Study 8. Attributable mortality and morbidity to SHS in Europe (PM1 , PM2.5 , PM10 ). The AirVisual Pro is a low-cost optical parti- (WP9) cle counter, measuring PM2.5 , PM10 , carbon dioxide, temperature and relative humidity. All these devices are portable and station- The objectives of this WP, led by the Istituto per lo Studio, ary, capable to operate and memorise the data with or without la Prevenzione e la Rete Oncologica (Italy), are: 1) to review the connection to the internet. methods used in the literature, with special focus on Europe, to cal- For calibration, comparison of different measurements will culate attributable mortality and morbidity to SHS and the results be performed by the generation of exposures using a range of published to date for EU countries; 2) to develop algorithms of cal- cigarettes and e-cigarettes in a real-life environment in a room culation of attributable mortality and morbidity to SHS; and 3) to of 48 m3 . The BAM-1020 will be operated and the optical parti- update attributable mortality and morbidity to SHS for EU countries cle counters will be calibrated in parallel for the time necessary based on SHS exposure prevalence collected in the WP3. to simulate concentration changes in order to verify the accuracy In order to estimate attributable mortality and morbidity to SHS, and precision of the instruments within the whole range of mea- mortality and morbidity data (asthma, COPD, lung cancer, stroke, surements specified by the manufacturers and to compensate for ischaemic heart disease, breast cancer and diabetes in adults; low coincidence losses. birth weight, lower respiratory infections, otitis media, asthma and sudden infant death syndrome in children) will be collected from 28 EU countries on SHS-related diseases, along with information Conclusion on prevalence of SHS exposure in EU countries. For attributable mortality and morbidity estimates, data on the prevalence of SHS The TackSHS project involves a comprehensive and innovative exposure will be used from two sources: information collected in approach to develop a scientific understanding of second-hand the WP3 of this project and from Eurobarometer surveys. Finally, exposure to smoke from cigarettes and aerosols from e-cigarettes. sensitivity analyses of attributable mortality and morbidity to SHS For the first time, this project will consider the integration of will be conducted. data on SHS exposure from a validated, homogenous survey, as E. Fernández et al. / Gac Sanit. 2020;34(1):77–82 81 an instrument for the subjectively perceived exposure by wide supported by the Instituto de Salud Carlos III, Government of Spain populations in several EU countries, together with its objective (INT16/00211 and INT17/00103), co-funded by the European assessment using environmental and biological markers. Whilst Regional Development Fund (FEDER). A. Lugo was supported by this is the core objective of the TackSHS project, additional WPs an AIRC fellowship for Italy. The work of S. Gallus was partially will address specific questions regarding exposure to SHS and SHA, funded by the Italian League Against Cancer (LILT, Milan). including its impact on health and its economic burden in spe- cific populations and patients with chronic lung and respiratory Conflicts of interests diseases. At the societal level, we aim to raise awareness of the risks from The authors declare no conflicts of interests. Specifically, they SHS exposure and their associated health burden. The project will declare not receiving, directly or indirectly, funding from tobacco also provide new evidence to further inform the debate about the manufacturers or their affiliates. scale of risk from SHA exposure. TackSHS team will also invest con- siderable effort in disseminating the obtained results, not only to the scientific community, policy makers and stakeholders, but also Annex. The TackSHS project investigators to patient and consumer organisations at the national and European level. Catalan Institute of Oncology (ICO), Bellvitge Biomedical The initial publication plan includes 20 papers with the main Research Institute (IDIBELL), Spain: Esteve Fernández, Yolanda findings, considered as priority publications. Further publications, Castellano, Marcela Fu, Montse Ballbè, Beladenta Amalia, Olena with results at the country level and combining the results from Tigova; Public Health Agency of Barcelona (ASPB), Spain: María different studies will be produced after the initial primary publica- José López, Xavier Continente, Teresa Arechávala, Elisabet Hen- tions. In addition, a comprehensive report, as well as policy briefs, derson; Istituto di Ricerche Farmacologiche Mario Negri IRCCS will be launched in the final conference and distributed to stake- (IRFMN), Italy: Silvano Gallus, Alessandra Lugo, Xiaoqiu Liu, Cristina holders, including policymakers, patients, the scientific community Bosetti, Enrico Davoli; Istituto DOXA, Worldwide Independent and the general public. Network/Gallup International Association, Italy: Paolo Colombo; University of Stirling (UNISTIR), UK: Sean Semple, Rachel O’Donnell, Editor in charge Ruaraidh Dobson; TobaccoFree Research Institute Ireland (TFRI), Ireland: Luke Clancy, Sheila Keogan, Shashsa Li, Elizabeth Bres- Carlos Álvarez-Dardet. lin, Hannah Byrne; Hellenic Cancer Society - George D. Behrakis Research Lab (HCS), Greece: Panagiotis Behrakis, Anna Tzortzi, Constantine Vardavas, Vergina Konstantina Vyzikidou, Stephanie Authorship contributions Teloniatis, Gerasimos Bakelas, George Mattiampa; Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Italy: Roberto Boffi, Ario E. Fernández and M.J. López designed the overall framework of Ruprecht, Cinzia De Marco, Alessandro Borgini, Chiara Veronese, the project protocol. E. Fernández, M.J. López, S. Gallus, S. Sem- Martina Bertoldi, Andrea Tittarelli; Istituto per lo Studio, la Pre- ple, L. Clancy, P. Behrakis, A. Ruprecht, G. Gorini, C. Radu-Loghin, venzione, e la Rete Oncologica (ISPRO), Italy: Giuseppe Gorini, J.B. Soriano and A. López-Nicolás developed detailed protocols of Giulia Carreras, Barbara Cortini, Simona Verdi, Alessio Lachi, Elisa- the corresponding studies they coordinate. All the TackSHS project betta Chellini; Polytechnic University of Cartagena (UPCT), Spain: investigators have participated in different phases of the project, Ángel López Nicolás, Marta Trapero-Bertran, Daniel Celdrán Guer- contributed to this manuscript and gave final approval. E. Fer- rero; European Network on Smoking and Tobacco Prevention nández prepared a first complete draft of this manuscript; all (ENSP), Belgium: Cornel Radu-Loghin, Dominick Nguyen, Polina authors critically reviewed it and contributed with significant and Starchenko; Fundación para la Investigación Biomédica del Hos- important suggestions. All authors have participated in writing the pital Universitario La Princesa (IISP), Spain: Joan B. Soriano, Julio manuscript, its critical review and have approved the final ver- Ancochea, Tamara Alonso, María Teresa Pastor, Marta Erro, Ana sion. All of them are jointly responsible for adequate revision and Roca, Patricia Pérez. discussion of all aspects included in the manuscript. Acknowledgements Appendix A. Supplementary data We thank Ms. Cristina Rajo, formerly at the Research Support Supplementary data associated with this article can be found, in Office of the Catalan Institute of Oncology, for her valuable help the online version, at doi:10.1016/j.gaceta.2019.07.002. throughout the process for the grant application and negotiation. We also thank Ana Navas-Acién, Dan Smith, Armando Peruga and References James Repace for accepting being members of the Scientific Advi- sory Board, and Fèlix Bosch for accepting being the External Ethics 1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; Vol. 83. Tobacco smoke and involuntary smoking. Lyon: International Agency for Advisor of the project. Research on Cancer; 2004. In memory of Dr. Manel Nebot (1957-2012) and Dr. Giovanni 2. 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