Impactos do fumo passivo no surgimento e na progressão da esclerose múltipla: uma revisão sistemática

Schlindwein, Marco Antônio Machado; Campos, Marcelo Henrique de Moura; Breis, Leticia Caroline; Chara, Beatriz Sordi; Scherer, Clara Sasse; Caminski, Vitória Augusta Piva; Matta, André; Gonçalves, Marcus Vinicius Magno

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Sumário

View and Review • Arq. Neuro-Psiquiatr. 82 (3) • 2024 • https://doi.org/10.1055/s-0044-1779271 copiar

Impactos do fumo passivo no surgimento e na progressão da esclerose múltipla: uma revisão sistemática

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

Antecedentes

Ao contrário do tabagismo ativo, o fumo passivo (FP) não é tão bem estabelecido como risco para o desenvolvimento de esclerose múltipla (EM) nem como um fator de risco para a progressão da doença.

Objetivo

Revisamos sistematicamente a associação entre FP e o risco de aparecimento e/ou progressão da EM.

Métodos

Fizemos uma triagem sistemática nas bases de dados MedLine/PubMed, Science Direct, LILACs e SciELO em busca de publicações entre 1° de janeiro de 2010 e 5 de julho de 2021 com as seguintes palavras-chave: "multiple sclerosis and smoking"; "multiple sclerosis and passive smoking"; "multiple sclerosis and secondhand smoking".

Resultados

Quinze artigos foram incluídos nesta revisão, que consistiu em revisões sistemáticas com metanálise (N = 2), revisões sistemáticas (N = 2) e estudos observacionais (N = 11). As metanálises relataram um impacto do FP no surgimento da EM entre fumantes passivos. Um revisão sistemática selecionou dois estudos observacionais mostrando a associação entre FP e desenvolvimento de EM, e um estudo que não encontrou associação significativa entre FP e o risco de desenvolvimento de EM. Outra revisão sistemática identificou oito artigos selecionados mostrando uma relação entre FP e EM. Sete estudos observacionais relataram maiores chances de aparecimento de EM quando associados a FP. Quatro estudos observacionais não mostraram uma relação entre FP e o desenvolvimento ou progressão da EM.

Conclusão

A maioria dos artigos mostrou uma associação positiva entre a exposição ao FP e o risco de desenvolver EM. Por outro lado, não foi possível estabelecer uma associação entre FP e maior risco de progressão da EM.

Palavras-chave
Esclerose Múltipla; Progressão da Doença; Poluição por Fumaça de Tabaco; Revisão Sistemática

Author	Study Design, country, and year	Population	Main findings	Study limitations
Poorolajal et al.¹²12 Poorolajal J, Bahrami M, Karami M, Hooshmand E. 2017Effect of smoking on multiple sclerosis: A meta-analysis. J. Public Heal. (United Kingdom). https://doi.org/10.1093/pubmed/fdw030 https://doi.org/10.1093/pubmed/fdw030...	Meta-analysis, Iran, 2017.	−	The study indicated that both former and current smokers are predisposed to develop Multiple Sclerosis (MS). The risk increases proportionally to the number of cigarettes smoked per day. The meta-analysis selected 3 studies that show the association between MS and environmental tobacco smoke (ETS). Among second-hand smokers, the estimated Odds Ratio (OR) of MS was 1.12, when compared with nonsmokers.	Does not identify which studies had the association between MS and ETS. Data regarding environmental tobacco smokers was not detailly provided. Does not detailly described selected studies. Limited number of studies in some subgroups. (V) The majority of articles selected were low-quality studies.
Zhang et al.¹³13 Zhang P, Wang R, Li Z, et al. The risk of smoking on multiple sclerosis: a meta-analysis based on 20,626 cases from case-control and cohort studies. Peer J 2016;4:e1797. Doi: 10.7717/peerj.1797 https://doi.org/10.7717/peerj.1797...	Meta-analysis, China, 2016.	−	The study shows that smoking is an environmental risk to MS. The meta-analysis also identified three studies containing four study populations that show the association between ETS and MS, reporting an overall OR of 1.24.	The study did not use a technique for assessing the risk of bias in the individual studies included.
McKay et al.¹⁴14 McKay KA, Jahanfar S, Duggan T, Tkachuk S, Tremlett H. Factors associated with onset, relapses or progression in multiple sclerosis: A systematic review. Neurotoxicology 2017;61:189-212. Doi: 10.1016/j.neuro.2016.03.020 https://doi.org/10.1016/j.neuro.2016.03....	Systematic review, Canada, 2017.	−	Three studies selected evaluate the correlation between ETS and MS. Hedström et al. (2011), reported an OR of 1.3 for MS among never-smoker patients who were exposed to ETS. A French study, by Mikaeloff et al. (2007) reported an association between parental smoking and the early onset of MS in their children (OR 2.12), with a higher risk in older children, when compared to younger ones. Gardener et al. (2009) showed that children whose parents used to smoke at home had an increased risk of MS; however, when restricted to the cases that were non-smokers as adults, it was not statistically significant (OR 1.2, CI 0.90-1.5).	The vast literature present in the study limited the full discussion of some papers included, for example the strengths and limitations of each study.
Degelman and Herman.¹⁵15 Degelman ML, Herman KM. Smoking and multiple sclerosis: A systematic review and meta-analysis using the Bradford Hill criteria for causation. Mult Scler Relat Disord 2017;17:207-216. Doi: 10.1016/j.msard.2017.07.020 https://doi.org/10.1016/j.msard.2017.07....	Systematic review, Canada, 2017.	−	Four out of the eight articles analyzed, which cited the correlation between ETS and MS, demonstrated a statistically significant association. Meta-analysis was not performed due to heterogeneity among studies.	Studies included regarding the association between ETS and MS were not described in detail. Quality of study evidence for each outcome was either low or very low.
Oturai et al.¹⁶16 Oturai DB, Bach Søndergaard H, Koch-Henriksen N, et al. Exposure to passive smoking during adolescence is associated with an increased risk of developing multiple sclerosis. Mult Scler 2021; 27(02):188-197. Doi: 10.1177/1352458520912500 https://doi.org/10.1177/1352458520912500...	Case-control, Denmark, 2021.	N = 2,589. First cohort analyzed was composed by never-smokers (cigarettes), with 342 cases and 590 controls. The second was composed by individuals who started cigarette smoking above the age of 19, with 577 cases and 1,080 controls.	The association between exposure to ETS during adolescence (10-19 years of age) and MS was evaluated. In males, ETS exposure was not correlated to MS in neveractive smoking subjects. However, for those who became cigarette smokers in adulthood, previous ETS exposure history showed up with an OR of 1.593 for MS. ETS exposure in female neveractive smoking subjects demonstrated an OR of 1.43. There was no correlation between ETS in adolescence and MS in female patients that became active smokers after the age of 19 years.	Selection of blood donors as controls. Recall bias may be present, as subjects were asked about their experience and habits. Authors considered ETS exposure only in the workplace or at home and did not consider the experience in other places, for example while outdoors.
Sakoda et al.¹⁷17 Sakoda A, Matsushita T, Nakamura Y, et al. Environmental risk factors for multiple sclerosis in Japanese people. Mult Scler Relat Disord 2020;38:101872. Doi: 10.1016/j.msard.2019.101872 https://doi.org/10.1016/j.msard.2019.101...	Case-control, Japan, 2020.	N = 227. Patients with MS: 103. Controls: 124.	MS patients were evaluated regarding environmental exposure risk factors. A history of exposure to ETS was observed to have a positive correlation with MS, with an OR of 1.31.	Small sample size study. Recall bias may be present, as subjects were asked about their past experience and habits. Cases were hospital-based and at various clinical stages, potentially producing selection bias and heterogeneity between MS subjects Not possible to distinguish patients exposed to ETS as current smokers, ex-smokers, or never-smokers
Lavery et al.¹⁸18 Lavery AM, Collins BN, Waldman AT, et al. The contribution of secondhand tobacco smoke exposure to pediatric multiple sclerosis risk. Mult Scler 2019;25(04):515-522. Doi: 10.1177/1352458518757089 https://doi.org/10.1177/1352458518757089...	Case-control, United States of America, 2019.	N = 297. All subjects aged less than 16 years; 216 children with monophasic acquired demyelinating syndromes (ADS); 81 children with MS.	The study concluded that ETS exposure was 37% more common in MS, in comparison to monophasic acquired demyelinating syndromes (29.5%); however, it was not an independent factor. When associated with the presence of HLADRB1*15, an OR of 3.7 for MS was reached.	Recall bias may be present, as subjects were asked about their past experience and habits. Authors considered ETS exposure only at home and did not consider the experience in other places, for example while outdoors.
Abdollahpour et al.¹⁹19 Abdollahpour I, Nedjat S, Sahraian MA, Mansournia MA, Otahal P, van der Mei I. Waterpipe smoking associated with multiple sclerosis: A population-based incident case-control study. Mult Scler 2017;23(10):1328-1335. Doi: 10.1177/1352458516677867 https://doi.org/10.1177/1352458516677867...	Case-control, Iran, 2017.	N = 1,604. Subjects with MS: 547; Controls: 1,057.	This article demonstrated that active waterpipe (OR 1.77), cigarette (OR 1.69) or secondhand (OR 1.85) tobacco smoking exposure is associated with increased MS risk. Regarding passive smoking, a much stronger association was found in exposures after the age of 20 years (OR∼2.2).	Recall bias may be present, as subjects were asked about their past experience and habits. Authors considered ETS exposure only at home and did not consider the experience in other places, for example while outdoors or workplace.
Hedström et al.²⁰20 Hedström AK, Olsson T, Alfredsson L. Smoking is a major preventable risk factor for multiple sclerosis. Mult Scler 2016;22(08): 1021-1026. Doi: 10.1177/1352458515609794 https://doi.org/10.1177/1352458515609794...	Case-control, Sweden, 2016.	N = 7,791. Among cases exposed to ETS: 457 never-smokers; 775 smokers. Among controls exposed to ETS: 1,115 never-smokers; 1,321 smokers.	The study assessed the impact of smoking and ETS on MS risk. The exposure to ETS in neversmokers was associated with the occurrence of MS in a dose-dependent manner, with an obtained OR of 1.1 for 1-20 years of exposure and 1.4 for more than 20 years of exposure	Recall bias may be present, as subjects were asked about their experience and habits. Authors considered ETS exposure only in the workplace or at home and did not consider the experience in other places, for example while outdoors.
Hedström et al.²¹21 Hedström AK, Bäärnhielm M, Olsson T, Alfredsson L. Exposure to environmental tobacco smoke is associated with increased risk for multiple sclerosis. Mult Scler 2011;17(07):788-793. Doi: 10.1177/1352458511399610 https://doi.org/10.1177/1352458511399610...	Case-control, Sweden, 2011.	N = 2,330. Patients with MS: 695. Controls: 1,635. All subjects reported that they had never smoked before the year of MS onset.	This case-control study considered the exposure to ETS before the year of MS onset for cases and during the same period in the corresponding controls. Subjects who were exposed to ETS were found to be 30% more susceptible to develop MS. Furthermore, the exposure time was directly correlated with risk, when greater than or equal to 20 years, the obtained OR was 1.8, compared to individuals who had never been exposed.	Recall bias may be present, as subjects were asked about their experience and habits. Authors considered ETS exposure only in the workplace or at home and did not consider the experience in other places, for example while outdoors.
Hedström et al.²²22 Hedström AK, Bomfim IL, Barcellos LF, et al. Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk. Int J Epidemiol 2014;43(06):1791-1798. Doi: 10.1093/ije/dyu195 https://doi.org/10.1093/ije/dyu195...	Case-control, Sweden, 2014.	N = 2,879. All subjects with MS. All subjects were never-smokers. Cases (never-smokers exposed to ETS): 1,311. Controls (never-smokers not exposed to ETS): 1,568.	This study evaluated the development of MS in groups of individuals who carried HLA-DRB115 and lacked HLA-A02, which are genetic conditions that increase the susceptibility of MS (OR of 4.5). These patients presented a 7.7- fold higher chance of developing MS if exposed to ETS when compared to non-smokers never exposed to ETS without these HLA genotypes.	Recall bias may be present, as subjects were asked about their experience and habits. Authors considered ETS exposure only in the workplace or at home and did not consider the experience in other places, for example while outdoors.
Toro et al.²³23 Toro J, Reyes S, Díaz-Cruz C, et al. Vitamin D and other environmental risk factors in Colombian patients with multiple sclerosis. Mult Scler Relat Disord 2020;41:101983. Doi: 10.1016/j. msard.2020.101983 https://doi.org/10.1016/j.msard.2020.101...	Cross-sectional, Colombia, 2020.	N = 174. Subjects with MS: 87. Subjects without MS: 87.	In the analysis, neither cigarette nor ETS history had a statistically significant association with an increased risk for MS.	Recall bias may be present, as subjects were asked about their past experience and habits. No detailed quantitative data on ETS amounts. Subjects were asked about ETS exposure only considering when they were 19-25 years old
Abbasi et al.²⁴24 Abbasi M, Nabavi SM, Fereshtehnejad SM, et al. Risk factors of multiple sclerosis and their relation with disease severity: A cross-sectional study from Iran. Arch Iran Med 2016;19(12): 852-860	Cross-sectional, Iran, 2016.	N = 660. All subjects with MS.	From the total of 660 patients with MS included in the study, most were female, with a median age of 37 years, and with relapsing-remitting MS clinical features. The analysis showed no association between ETS and MS severity.	No detailed data on quantitative ETS amount. Recall bias may be present, as subjects were asked about their experience and habits.
Mandia et al.²⁵25 Mandia D, Ferraro OE, Nosari G, Montomoli C, Zardini E, Bergamaschi R. Environmental factors and multiple sclerosis severity: a descriptive study. Int J Environ Res Public Health 2014;11(06): 6417-6432. Doi: 10.3390/ijerph110606417 https://doi.org/10.3390/ijerph110606417...	Cross-sectional, Italy, 2014.	N = 131. All subjects with MS.	The study examined factors that may be associated with the evolution of MS. There was no significant correlation between cigarette smoking status or exposure to ETS and the severity of MS.	Small sample size study. Recall bias may be present, as subjects were asked about their past experience and habits. Not possible to distinguish patients exposed to ETS as current smokers, ex-smokers, or never-smokers. The study only considered the exposure to ETS 12 months prior to data collection.
Ramagopalan et al.²⁶26 Ramagopalan SV, Lee JD, Yee IM, et al. Association of smoking with risk of multiple sclerosis: a population-based study. J Neurol 2013;260(07):1778-1781. Doi: 10.1007/s00415-013-6873-7 https://doi.org/10.1007/s00415-013-6873-...	Case-control, Canada, 2013.	N = 3,913. MS cases: 3,157. Controls (spouses): 756.	MS cases and spouses were asked about cigarette smoking and ETS exposure. There was no correlation between ETS and MS in never-smoking patients. Exposure to ETS at home presented an OR of 0.87, whereas at the workplace the OR was 0.99.	Recall bias may be present, as subjects were asked about their experience and habits. No quantitative data on ETS amounts. Small control sample, possibly underpowered to detect relevant effects. Authors considered ETS exposure only in the workplace or at home and did not consider the experience in other places, for example while outdoors. The study did not collect information on paternal smoking.

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[1] Address for correspondence Marcelo Henrique de Moura Campos (email: marcelo.campos88@hotmail.com)