Valenti et al. International Archives of Medicine 2013, 6:11 http://www.intarchmed.com/content/6/1/11 REVIEW Open Access Sidestream cigarette smoke and cardiac autonomic regulation Vitor E Valenti1*, Luiz Carlos M Vanderlei2, Celso Ferreira3, Fernando L A Fonseca4, Fernando R Oliveira3, Fernando H Sousa5, Luciano M Rodrigues4, Carlos B M Monteiro4, Fernando Adami4, Rubens Wajnsztejn4 and Luiz Carlos de Abreu4 Abstract Background: The literature has already demonstrated that cigarette influences the cardiovascular system. In this study, we performed a literature review in order to investigate the relationship between sidestream cigarette smoke (SSCS) and cardiac autonomic regulation. Methods: Searches were performed on Medline, SciELO, Lilacs and Cochrane databases using the crossing between the key-words: “cigarette smoking”, “autonomic nervous system”, “air pollution” and “heart rate variability”. Results: The selected studies indicated that SSCS exposure affects the sympathetic and parasympathetic responses to changes in arterial blood pressure. Moreover, heart rate responses to environmental tobacco smoke are increased in smokers compared to non-smokers. The mechanism involved on this process suggest increased oxidative stress in brainstem areas that regulate the cardiovascular system. Conclusion: Further studies are necessary to add new elements in the literature to improve new therapies to treat cardiovascular disorders in subjects exposed to sidestream cigarette smoke. Keywords: Autonomic nervous system, Cigarette smoking, Cardiovascular physiology, Air pollution Background Environmental tobacco smoke exposure was showed in the literature to be an important contributor to increased cardiovascular morbidity and mortality. The effects of cigarette smoke on respiratory and cardiovascular systems are a relevant matter in the reported several cardiovascu- lar impairment effects [1-3]. Cigarette smoke in the envi- ronment is divided into two categories. The sidestream cigarette smoke (SSCS) presents a great number of oxi- dants and other harmful components, its concentration is much higher than compared to the mainstream smoke. On the other hand, it is known that the mainstream smoke is inhaled by the active smokers and released on the environment while the SSCS is emitted from the cigarette and inhaled by so-called “passive smokers”. Pas- sive smokers are hence exposed to almost the same * Correspondence: vitor.valenti@gmail.com 1Department of Speech Language and Hearing therapy, Faculty of Philosophy and Sciences, UNESP, Av. Higyno Muzzi Filho, 737, Marilia, SP 17.525-900, Brazil Full list of author information is available at the end of the article © 2013 Valenti et al.; licensee BioMed Central Commons Attribution License (http://creativec reproduction in any medium, provided the or chemicals in cigarette smoke as active smokers are. Thus, passive smoking increases the risk of cardiac or other re- lated disease in nonsmokers [4]. Most effects of smoking on the autonomic regulation of the heart is attributed to nicotine, an active agent that cigarette triggers acute and chronic cardiovascular re- sponses by through sympathetic activation, resulting in the release of plasmatic catecholamines [5]. As a conse- quence, there is an increase in heart rate and systemic blood pressure, coronary spasm, increased workload and myocardial oxygen demand with concomitant reduction in this supply. It increases the propensity to arrhythmias and cardiac events in healthy subjects, these changes are attenuated by blocking alpha and beta adrenergic recep- tors, indicating that these effects are derived from sym- pathetic activation [6]. Although there are a large number of studies in the lit- erature that investigated the influence of smoking on the autonomic cardiac regulation, it lacks information re- garding the effects of SSCS on this mechanism. Thus, in this review we endeavored to gather evidences regarding Ltd. This is an Open Access article distributed under the terms of the Creative ommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and iginal work is properly cited. mailto:vitor.valenti@gmail.com http://creativecommons.org/licenses/by/2.0 Valenti et al. International Archives of Medicine 2013, 6:11 Page 2 of 5 http://www.intarchmed.com/content/6/1/11 the effects of sidestream cigarette smoke on cardiac autonomic regulation. We aimed to add elements in the literature in order to better comprehend researchers and to contribute to new therapies. Method Search strategy and selection The revisions were made between September 2012 and January 2013. The Medline (via PubMed), Lilacs, Scielo and Cochrane databases were searched using the follow- ing subject keywords: “cigarette smoking”, “autonomic nervous system”, “air pollution” and “heart rate variabil- ity”. These words were defined by the Medical Subject Headings (MeSH). The studies were selected by a reviewer and supervised by a senior reviewer. Based on the titles and abstracts, we excluded manuscripts not clearly related to the sub- ject of the review. Thereafter, all the selected titles and abstracts were submitted to a final evaluation, which considered the inclusion criteria, and its reference lists independently checked to identify studies of possible relevance that were not found in the electronic search. We excluded studies that presented no abstract or full text in English between 2000 and 2012 and literature re- views. As inclusion criteria we considered clinical trials and basic studies that investigated the effects of auditory stimulation on the ANS. Results The electronic search yielded a total of 934 references. Among these references the first elimination resulted in the exclusion of 521 titles and abstracts, which were not clearly related to the subject of review. The titles of the remaining 413 abstracts were submitted to a final evalu- ation that took into account the inclusion criteria. After the final exclusion of studies that did not investigate the SSCS, we finished the review with five references. The investigation of the reference lists confirmed the absence of relevant documents. Summaries of the main studies analyzed were selected. Table 1 shows the levels of vari- ability and the main results and conclusions of the stud- ies included in this update. Table 1 Main studies regarding the effects of sidestream ciga Authors and year Valenti et al., 2010. Three weeks of exposure to SSC Valenti et al., 2010. SSCS exposure affected the sympathetic and parasym influenced th Cobb et al., 2012. Waterpipe smoking impairs heart rate variability. More Valenti et al., 2012. Exposure to SSCS impairs cardiovascular respo Ordoñana et al., 2012. Cardiovascular reaction to environmental tobacco smo responses to environmen WKY: Wistar Kyoto rats; SHR: Spontaneously Hypertensive Rats; 4th V: Fourth Cerebr Discussion Considering the small number of studies in the literature that investigated the association between SSCS and cardiac autonomic regulation, we endeavored to review recent studies from our group and others groups regarding this issue. The analysis of manuscripts selected for this review showed that exposure to SSCS impairs the autonomic regulation of the heart through the central nervous system and through the periphery. A first study from our group mentioned in this review failed to report changes in baroreflex function in Wistar rats exposed to SSCS during three weeks, five days per week for 180 minutes per day. The baroreflex sensitivity was compared between rats exposed to SSCS and rats exposed to fresh air [7]. Nevertheless, previous studies indicated that active smoking influences cardiovascular reflexes. It was indicated that cigarette smoking in active smokers increases sympathetic nerve activity through an effect mediated by the central nervous system and also through a direct peripheral mechanism [6]. In the study published by our group, Valenti et al. [7], there was no difference between rats exposed to SSCS and rats ex- posed to fresh air regarding tachycardic and bradycardic peak in response to decrease and increase in arterial blood pressure, respectively. Furthermore, it was not found difference in sympathetic and parasympathetic baroreflex gain. It is interesting to raise the hypothesis that the period of exposure to SSCS used in our pub- lished study (three weeks) was not enough to induce changes in baroreflex sensitivity in Wistar rats. Con- versely, a previous investigation that used a similar protocol to expose rats to mainstream cigarette smoke reported that chronic exposure induces cardiac remodel- ing that is characterized by a decrease in ventricular functional capacity [8]. Taken together, based on the studies cited above, we may propose that cigarette smoke exposure during three weeks is able to damage cardiac function without influence the autonomic regu- lation of the heart. Another investigation cited in the review published by our group evaluated the effects of SSCS exposure on sympathetic and parasympathetic responses induced by rette smoking on cardiac autonomic regulation Main conclusions S did not affect baroreflex function in Wistar rats. pathetic responses to changes in blood pressure in WKY rats while it e sympathetic reaction in SHR. over, exposure to smoke components different from nicotine causes the similar effects. nses through its influence on catalase mechanism into the 4th V. ke is associated with individual craving in smokers. Psychophysiological tal tobacco smoke are increased in smokers. al Ventricle. Valenti et al. International Archives of Medicine 2013, 6:11 Page 3 of 5 http://www.intarchmed.com/content/6/1/11 decrease and increase in arterial blood pressure in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) [9]. At this time, it was found that SSCS ex- posure over three weeks attenuated the sympathetic and parasympathetic responses in WKY whereas it attenu- ated the sympathetic responses in SHR. The exposure protocol used in this study indicated that SSCS reduced tachycardic peak, bradycardic reflex and heart rate range in WKY rats, while it influenced the heart rate range and tachycardic peak in SHR. These findings support the suggestion that a period of cigarette exposure lower than 30 days is enough to induce changes in the sympathetic nervous activity on the heart with no alterations on baseline arterial blood pressure. The protocol applied in rats to activate parasympathetic and sympathetic re- sponses induced by changes in arterial blood pressure is well accepted in the literature [9,10]. The method is based on intravenous phenylephrine that enhances arter- ial pressure and activates the parasympathetic nervous system, leading to the bradycardic reflex and then the bradycardic baroreflex gain is calculated. The intraven- ous sodium nitroprusside decreases arterial blood pres- sure and activates the sympathetic nervous system, leading to the tachycardic reflex [11-13]. The difference between the results from this cited study and the other reported in Wistar rats regarding autonomic cardiac re- sponses to SSCS is possible due to the difference be- tween WKY and Wistar rats, since WKY rats come from normotensive offspring of SHR that the NIH investiga- tors acquired from a colony in Kyoto [14]. According to one of the selected manuscripts in this review, Ordoñana and coworkers [15] indicated that ex- posure to environmental tobacco smoke caused a stable intensification in skin conductance levels and heart rate responses. Furthermore, the authors reported that this intensification was consistently increased in smokers than non-smokers. According to the authors, smokers subjects presented an increase in heart rate that contin- ued regularly higher than their basal levels. The distinc- tion between smokers and no-smokers subjects was more apparent at the end of the exposure to environ- mental tobacco smoke when the smoke density was the highest, and non-smokers did not present an appropriate response to this stimulation. Previous studies regarding cue-reactivity reported that heart rate enhanced when smokers were exposed to drug-related vs. drug-neutral stimulation [16,17]. It is suggested that this reaction is dependent on the degree of nicotine dependence or the deprivation level [18]. Additionally, Ordonãna and co- workers [15] reported that the increase in heart rate in response to environmental tobacco smoke positively cor- related with subjective craving. In a very elegant and well conducted study, Cobb and colleagues [19] published a cross-over study design with 32 participants that investigated the effects of toxicant exposure to waterpipe smoking on heart rate variability. Heart rate variability is a well accepted method that pro- vides information regarding RR interval, i.e. the interval time between each heart beat [20-23]. Cobb et al. [11] reported that waterpipe smoking acutely impaired heart rate variability, they also concluded that exposure to smoke constituents other than nicotine causes the same malefic effects on the cardiac autonomic regulation. The results cited above support previous studies that evalu- ated the acute effects of smoking a single cigarette [24-26]. It was observed an increase in the low fre- quency/high frequency ratio after smoking a single cigarette, the baseline levels of this index recovered around 20 minutes after smoking cessation. In order to investigate the physiological mechanisms involved in SSCS induced cardiovascular responses our group tried to evaluate the effects of catalase inhibition into the fourth cerebral ventricle on cardiovascular re- sponses in rats exposed to SSCS [27]. It was reported that central catalase inhibition increased heart rate dur- ing the first 5 minutes in rats exposed to fresh air while it increased heart rate and attenuated bradycardic peak during the first 15 minutes in rats exposed to SSCS. As a main conclusion, it was suggested that SSCS exposure increased the cardiovascular responses caused by cata- lase inhibition into the fourth cerebral ventricle, propos- ing a central mechanism that involve oxidative stress. In this context, a previous study reported that exogenous H2O2 into the fourth cerebral ventricle influenced heart rate and arterial blood pressure [28]. The results ob- served in this study support the hypothesis of the nose anatomy, which is based on the transport of exogenous agents into the brain [29]. The dendritic buttons and protuberant cilia of the olfactory bulb make contact with its surface area. The olfactory cells are first-order neu- rons that send axons to the brain without intervening synapse. However, it was not possible to confirm which brainstem area was affected by SSCS exposure. According to the anatomy of the fourth cerebral ven- tricle, a drug injected in this are present a preference for the parasympathetic activity on the heart rate [30]. Fu- ture investigations are necessary to confirm this hypothesis. Another important issue to be addressed is the rela- tionship between SSC smoke and endothelial function in the cardiac autonomic regulation. Distinct types of regu- lation are suggested such as autonomic and hormonal modulation. The variation of regulatory processes im- plies in interactions [31]. In this context, nitric oxide is produced in the endothelium and in the heart, it is indi- cated that the triggering type is involved in the role of this substance in the cardiovascular system, affecting both the heart and the endothelium [32]. Also, nitric Valenti et al. International Archives of Medicine 2013, 6:11 Page 4 of 5 http://www.intarchmed.com/content/6/1/11 oxide production is influenced by the expression of cal- cium/calmodulin-dependent kinase IV, which regulates blood pressure [33]. Masahiko et al. [34] failed to find a significant effect of passive smoke exposure on the fore- arm vascular responses induced by vasodilators in non- smokers subjects. On the other hand, Argacha and co- workers [35] reported that tobacco SSCS extract im- paired endothelium-dependent relaxation in the isolated aorta of rats. The authors observed that it was related to increased oxidative stress and to tobacco and the in- creased superoxide production was not accompanied with changes in acetylcholine-induced relaxation. The genetic polymorphism is an important mechanism that is worth to be referred. Gairola and colleagues [36] in- vestigated the effects of SSCS exposure on atheroscler- otic lesions in apoE−/− mice. The authors reported an elevation of atherosclerotic injury progress induced by SSCS in this strain, suggesting that a genetic component is also involved. Taken together, it is suggested that the interaction between autonomic and endocrine systems may be involved in the induced-SSCS cardiovascular injuries. Our study presents some points that are worth to be pointed. As a study review, it does not add new elements in the literature. Nonetheless, it raises important hypoth- esis for further investigation regarding this issue. Al- though great part of the selected studies was performed in animals, the mechanisms observed are currently sup- ported, however, it needs additional clarification for im- provement in clinical application. We decided to not select all studies linking cigarette and cardiovascular sys- tem in order to focus our objective that was to investi- gate the relationship between SSCS and autonomic regulation of the heart. Conclusion This review showed that SSCS exposure produces changes on autonomic nervous system components that regulate the heart rate, indicating that there is a reduction of a parasympathetic system activity. Nevertheless, the results about the sympathetic activity are inconclusive. Further studies are necessary to clarify this mechanism. Competing interests The authors declare that they have no competing interests. Authors’ contributions All authors participated in the acquisition of data and revision of the manuscript. All authors determined the design, interpreted the data and drafted the manuscript. All authors read and gave final approval for the version submitted for publication. Acknowledgements This manuscript received financial support from UNESP. The funding body provided financial support to make all procedures and in the decision to submit the manuscript for publication. Author details 1Department of Speech Language and Hearing therapy, Faculty of Philosophy and Sciences, UNESP, Av. Higyno Muzzi Filho, 737, Marilia, SP 17.525-900, Brazil. 2Post-graduation Program in Physiotherapy, Faculty of Sciences and Technology, UNESP, Rua Roberto Simonsen, 305, Presidente Prudente, SP 19060-900, Brazil. 3Post-graduation Program in Cardiology, UNIFESP, Rua Napoleão de Barros, 715, São Paulo, SP 04024-002, Brazil. 4Department of Morphology and Physiology, School of Medicine of ABC, Av. Príncipe de Gales, 821, Santo André, SP 09060-650, Brazil. 5Faculty of Sciences, UNESP, Av. Eng. Luiz Edmundo Carrijo Coube, 14-01, Bauru, SP 17033-360, Brazil. Received: 26 February 2013 Accepted: 4 March 2013 Published: 7 March 2013 References 1. Varela-Carver A, Parker H, Kleinert C, Rimoldi O: Adverse effects of cigarette smoke and induction of oxidative stress in cardiomyocytes and vascular endothelium. Curr Pharm Des 2010, 16:2551–2558. 2. Huxley RR, Woodward M: Cigarette smoking as a risk factor for coronary heart disease in women compared with men. a systematic review and meta-analysis of prospective cohort studies. Lancet 2011, 378:1297–1305. 3. Gaemperli O, Liga R, Bhamra-Ariza P, Rimoldi O: Nicotine addiction and coronary artery disease: impact of cessation interventions. Curr Pharm Des 2010, 16:2586–2597. 4. Marchetti F, Rowan-Carroll A, Williams A, Polyzos A, Berndt-Weis ML, Yauk CL: Sidestream tobacco smoke is a male germ cell mutagen. Proc Natl Acad Sci USA 2010, 108:12811–12814. 5. Balakumar P, Kaur J: Is nicotine a key player or spectator in the induction and progression of cardiovascular disorders? Pharmacol Res 2009, 60:361–368. 6. Shinozaki N, Yuasa T, Takata S: Cigarette smoking augments sympathetic nerve activity in patients with coronary heart disease. Int Heart J 2008, 49:261–272. 7. Valenti VE, Abreu LC, Saldiva PH, Carvalho TD, Ferreira C: Effects of sidestream cigarette smoke exposure on baroreflex components in spontaneously hypertensive rats. Int J Environ Health Res 2010, 20:431–437. 8. Castardeli E, Paiva SA, Matsubara BB, Matsubara LS, Minicucci MF, Azevedo PS, Campana AO, Zornoff LA: Chronic cigarette smoke exposure results in cardiac remodeling and impaired ventricular function in rats. Arq Bras Cardiol 2005, 84:320–324. 9. Valenti VE, de Abreu LC, Imaizumi C, Petenusso M, Ferreira C: Strain differences in baroceptor reflex in adult Wistar Kyoto rats. Clinics (Sao Paulo) 2010, 65:203–208. 10. Valenti VE, De Abreu LC, Sato MA, Saldiva PH, Fonseca FL, Giannocco G, Riera AR, Ferreira C: Central N-acetylcysteine effects on baroreflex in juvenile spontaneously hypertensive rats. J Integr Neurosci 2011, 10:161–176. 11. Valenti VE, De Abreu LC, Sato MA, Fonseca FL, Riera AR, Ferreira C: Catalase inhibition into the fourth cerebral ventricle affects bradycardic parasympathetic response to increase in arterial pressure without changing the baroreflex. J Integr Neurosci 2011, 10:1–14. 12. Valenti VE, Ferreira C, Meneghini A, Ferreira M, Murad N, Ferreira Filho C, Correa JA, Abreu LC, Colombari E: Evaluation of baroreflex function in young spontaneously hypertensive rats. Arq Bras Cardiol 2009, 92:205–215. 13. Cisternas JR, Valenti VE, Alves TB, Ferreira C, Petenusso M, Breda JR, Pires AC, Tassi N, de Abreu LC: Cardiac baroreflex is already blunted in eight weeks old spontaneously hypertensive rats. Int Arch Med 2010, 3:2. 14. Okamoto K, Aoki K: Development of a strain of spontaneously hypertensive rats. Jpn Circ J 1963, 27:282–293. 15. Ordoñana JR, González-Javier F, Gómez-Amor J: Psychophysiological reactivity to environmental tobacco smoke on smokers and non- smokers. Addict Behav 2012, 37:838–843. 16. Upadhyaya HP, Drobes DJ, Thomas SE: Reactivity to smoking cues in adolescent cigarette smokers. Addict Behav 2004, 29:849–856. 17. Upadhyaya HP, Drobes DJ, Wang W: Reactivity to in vivo smoking cues in older adolescent cigarette smokers. Nicotine Tob Res 2006, 8:135–140. 18. Carpenter MJ, Saladin ME, DeSantis S, Gray KM, LaRowe SD, Upadhyaya HP: Laboratory-based, cue-elicited craving and cue reactivity as predictors of naturally occurring smoking behavior. Addict Behav 2009, 34:536–541. Valenti et al. International Archives of Medicine 2013, 6:11 Page 5 of 5 http://www.intarchmed.com/content/6/1/11 19. Cobb CO, Sahmarani K, Eissenberg T, Shihadeh A: Acute toxicant exposure and cardiac autonomic dysfunction from smoking a single narghile waterpipe with tobacco and with a “healthy” tobacco-free alternative. Toxicol Lett 2012, 1:70–5. 20. Vanderlei FM, Rossi RC, de Souza NM, de Sá DA, Gonçalves TM, Pastre CM, Abreu LC, Valenti VE, Vanderlei LC: Heart rate variability in healthy adolescents at rest. J. Hum. Growth Dev 2012, 22:173–178. 21. Dias de Carvalho T, Marcelo Pastre C, Claudino Rossi R, de Abreu LC, Valenti VE, Marques Vanderlei LC: Geometric index of heart rate variability in chronic obstructive pulmonary disease. Rev Port Pneumol 2011, 17:260–265. 22. Carvalho TD, Pastre CM, de Godoy MF, Fereira C, Pitta FO, de Abreu LC, Ramos EM, Valenti VE, Vanderlei LC: Fractal correlation property of heart rate variability in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2011, 6:23–28. 23. Abreu LC: Heart rate variability as a functional marker of development. J. Hum. Growth Dev 2012, 22:279–282. 24. Hayano J, Yamada M, Sakakibara Y, Fujinami T, Yokoyama K, Watanabe Y, Takata K: Short- and long-term effects of cigarette smoking on heart rate variability. Am J Cardiol 1990, 1:84–8. 25. Karakaya O, Barutcu I, Kaya D, Esen AM, Saglam M, Melek M, Onrat E, Turkmen M, Esen OB, Kaymaz C: Acute effect of cigarette smoking on heart rate variability. Angiology 2007, 5:620–4. 26. Kobayashi F, Watanabe T, Akamatsu Y, Furui H, Tomita T, Ohashi R, Hayano J: Acute effects of cigarette smoking on the heart rate variability of taxi drivers during work. Scand J Work Environ Health 2005, 31:360–366. 27. Valenti VE, de Abreu LC, Sato MA, Ferreira C, Adami F, Fonseca FL, Xavier V, Godoy M, Monteiro CB, Vanderlei LC, Saldiva PH: Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle. BMC Cardiovasc Disord 2012, 12:22. 28. Máximo Cardoso L, de Almeida Colombari DS, Vanderlei Menani J, Alves Chianca D Jr, Colombari E: Cardiovascular responses produced by central injection of hydrogen peroxide in conscious rats. Brain Res Bull 2006, 71:37–44. 29. Doty RL: The olfactory vector hypothesis of neurodegenerative disease: is it viable? Ann Neurol 2008, 63:7–15. 30. Colombari E, Sato MA, Cravo SL, Bergamaschi CT, Campos RR Jr, Lopes OU: Role of the medulla oblongata in hypertension. Hypertension 2001, 38:549–54. 31. Beaulieu P, Lambert C: Peptidic regulation of heart rate and interactions with the autonomic nervous system. Cardiovasc Res 1998, 37:578–85. 32. Casadei B, Sears CE: Nitric-oxide-mediated regulation of cardiac contractility and stretch responses. Prog Biophys Mol Biol 2003, 82:67–80. 33. Santulli G, Cipolletta E, Sorriento D, Del Giudice C, Anastasio A, Monaco S, Maione AS, Condorelli G, Puca A, Trimarco B, Illario M, Iaccarino G: CaMK4 Gene Deletion Induces Hypertension. J Am Heart Assoc 2012, 1:e001081. 34. Kato M, Roberts-Thomson P, Phillips BG, Narkiewicz K, Haynes WG, Pesek CA, Somers VK: The effects of short-term passive smoke exposure on endothelium-dependent and independent vasodilation. J Hypertens 1999, 17:1395–401. 35. Argacha JF, Fontaine D, Adamopoulos D, Ajose A, van de Borne P, Fontaine J, Berkenboom G: Acute effect of sidestream cigarette smoke extract on vascular endothelial function. J Cardiovasc Pharmacol 2008, 52:262–7. 36. Gairola CG, Drawdy ML, Block AE, Daugherty A: Sidestream cigarette smoke accelerates atherogenesis in apolipoprotein E−/− mice. Atherosclerosis 2001, 156:49–55. doi:10.1186/1755-7682-6-11 Cite this article as: Valenti et al.: Sidestream cigarette smoke and cardiac autonomic regulation. International Archives of Medicine 2013 6:11. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Abstract Background Methods Results Conclusion Background Method Search strategy and selection Results Discussion Conclusion Competing interests Authors’ contributions Acknowledgements Author details References << /ASCII85EncodePages false /AllowTransparency false /AutoPositionEPSFiles true /AutoRotatePages /PageByPage /Binding /Left /CalGrayProfile (Dot Gain 20%) /CalRGBProfile (sRGB IEC61966-2.1) /CalCMYKProfile (U.S. Web Coated \050SWOP\051 v2) /sRGBProfile (sRGB IEC61966-2.1) /CannotEmbedFontPolicy /Error /CompatibilityLevel 1.4 /CompressObjects /Tags /CompressPages true /ConvertImagesToIndexed true /PassThroughJPEGImages true /CreateJobTicket false /DefaultRenderingIntent /Default /DetectBlends true /DetectCurves 0.0000 /ColorConversionStrategy /LeaveColorUnchanged /DoThumbnails true /EmbedAllFonts true /EmbedOpenType false /ParseICCProfilesInComments true /EmbedJobOptions true /DSCReportingLevel 0 /EmitDSCWarnings false /EndPage -1 /ImageMemory 1048576 /LockDistillerParams true /MaxSubsetPct 100 /Optimize true /OPM 1 /ParseDSCComments true /ParseDSCCommentsForDocInfo true /PreserveCopyPage true /PreserveDICMYKValues true /PreserveEPSInfo true /PreserveFlatness true /PreserveHalftoneInfo false /PreserveOPIComments false /PreserveOverprintSettings true /StartPage 1 /SubsetFonts true /TransferFunctionInfo /Apply /UCRandBGInfo /Preserve /UsePrologue false /ColorSettingsFile () /AlwaysEmbed [ true ] /NeverEmbed [ true ] /AntiAliasColorImages false /CropColorImages true /ColorImageMinResolution 300 /ColorImageMinResolutionPolicy /OK /DownsampleColorImages true /ColorImageDownsampleType /Bicubic /ColorImageResolution 300 /ColorImageDepth -1 /ColorImageMinDownsampleDepth 1 /ColorImageDownsampleThreshold 1.50000 /EncodeColorImages true /ColorImageFilter /DCTEncode /AutoFilterColorImages true /ColorImageAutoFilterStrategy /JPEG /ColorACSImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /ColorImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000ColorACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000ColorImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasGrayImages false /CropGrayImages true /GrayImageMinResolution 300 /GrayImageMinResolutionPolicy /OK /DownsampleGrayImages true /GrayImageDownsampleType /Bicubic /GrayImageResolution 300 /GrayImageDepth -1 /GrayImageMinDownsampleDepth 2 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /GrayImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000GrayACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000GrayImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasMonoImages false /CropMonoImages true /MonoImageMinResolution 1200 /MonoImageMinResolutionPolicy /OK /DownsampleMonoImages true /MonoImageDownsampleType /Bicubic /MonoImageResolution 1200 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict << /K -1 >> /AllowPSXObjects false /CheckCompliance [ /None ] /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile (None) /PDFXOutputConditionIdentifier () /PDFXOutputCondition () /PDFXRegistryName () /PDFXTrapped /False /CreateJDFFile false /Description << /ARA /BGR /CHS /CHT /CZE /DAN /DEU /ESP /ETI /FRA /GRE /HEB /HRV /HUN /ITA /JPN /KOR /LTH /LVI /NLD (Gebruik deze instellingen om Adobe PDF-documenten te maken voor kwaliteitsafdrukken op desktopprinters en proofers. 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