Paraquat e doença de Parkinson: revisão sistemática e metanálise de estudos observacionais
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Data
2017-07-28
Autores
Vaccari, Carolina [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A doença de Parkinson (DP) é uma condição neurodegenerativa progressiva que tem como possíveis fatores de risco o envelhecimento, a suscetibilidade genética e a exposição a certos agentes químicos. Nas últimas décadas, estudos epidemiológicos e experimentais têm sugerido associação entre exposição a praguicidas e o desenvolvimento da DP. No total, nove revisões sistemáticas (RS) da literatura foram realizadas desde 2005 para verificar a associação entre exposição ao herbicida paraquat e a DP. A maioria dessas revisões apresentou limitações metodológicas, como restrições de idioma (apenas artigos em inglês), de bases de dados, de período de publicação dos estudos, e principalmente, não avaliou a qualidade metodológica dos estudos por ferramentas consistentes. Dentre as RS seguidas de metanálise, a maioria apresentou resultados positivos e estatisticamente significativos, apesar de ter identificado alto nível de heterogeneidade (I²) entre os estudos. Assim, justificou-se a realização de nova RS da literatura e metanálise que apresentassem menos limitações operacionais que as detectadas nas RS existentes. Para isso, foram selecionados estudos coortes, caso-controle e transversais comparativos que incluíssem quaisquer participantes expostos ambiental e/ou ocupacionalmente ao paraquat, sem restrição quanto à dose ou período de exposição. Os desfechos considerados foram a DP diagnosticada por especialistas ou relatada pelos participantes em entrevistas e/ou questionários. As bases de dados pesquisadas foram: PubMed, EMBASE, LILACS, TOXNET e Web of Science, sem restrição de idioma ou período de publicação. A heterogeneidade entre os estudos foi avaliada pelo teste I², sendo o odds ratio (OR) a medida de estimativa de efeito, com intervalo de confiança 95%. O risco de viés foi avaliado pelas ferramentas modificadas do NewCastle Otawa. Como resultados, foram incluídos 15 estudos na RS e 12 estudos na metanálise, que resultou em um OR de 1,40 (IC 95% 1,16-1,70; I² 15%), demonstrando associação positiva entre exposição ao paraquat e DP. Essa associação pareceu ser mais evidente em indivíduos suscetíveis, expostos ocupacionalmente ao paraquat em coexposição a outros pesticidas e que fizeram pouco uso de equipamentos de proteção. No entanto, a maioria dos estudos incluiu pequeno número de participantes expostos e apresentou alto risco de viés. Assim, novos estudos prospectivos que documentem cuidadosamente a exposição ao herbicida, com maior número de indivíduos potencialmente expostos, ainda são necessários para consolidar a associação positiva observada. Também, a análise de genes específicos que aumentam a predisposição à DP, e coexposições a outros praguicidas que podem estar relacionados a essa doença, poderão contribuir para a identificação de fatores que modulam a sua ocorrência.
Parkinson's disease (PD) is a progressive neurodegenerative condition whose possible risk factors are aging, genetic susceptibility and exposure to certain chemical agents. In the last decades, epidemiological and experimental studies have suggested an association between pesticide exposure and the development of PD. In total, nine systematic reviews (SRs) of the literature have been conducted since 2005 in order to verify the association between exposure to the herbicide paraquat and PD. However, most of them presented methodological limitations, such as language restrictions (only articles in English), databases, period of publication of the studies, and mainly, they did not evaluate their methodological quality by consistent tools. From the SRs followed by meta-analysis, the majority presented positive and statistically significant results, although a high level of heterogeneity (I²) was identified among studies. Thus, the conception of a new SR of the literature and meta-analysis that presented less operational limitations than those detected in the existing SRs was justified. For this, cross-sectional, cohort and case-control studies enrolling any participant exposed to environmental and/or occupational exposure to paraquat, without restrictions regarding dose or period of exposure, were selected. Outcomes considered were PD diagnosed by specialists or reported by the participants themselves in interviews and/or questionnaires. The searched databases were: PubMed, EMBASE, LILACS, TOXNET and Web of Science, without language or publication period restrictions. The heterogeneity among studies was evaluated by the I² test. Data were summarized as odds ratios with their respective 95% confidence intervals. Risk of bias was assessed by modified tools from the NewCastle Otawa Scale. As results, 15 studies were included in the SR and 12 studies included in the meta-analysis. An OR of 1.40 (95% CI 1.16-1.70, I² 15%) was obtained, demonstrating a positive association between exposure to paraquat and PD. This association appeared to be more evident in susceptible individuals, occupationally exposed to paraquat in coexposure to other pesticides, lacking use of protective equipment. However, most studies included a small number of exposed participants and presented a high risk of bias. Thus, new prospective studies that carefully document the herbicide exposure, with a greater number of potentially exposed individuals, are still necessary to consolidate the positive association observed. Also, the analysis of specific genes that increase predisposition to PD, and coexposure to other pesticides that may be related to this disease, may contribute to the identification of factors that modulate its occurrence.
Parkinson's disease (PD) is a progressive neurodegenerative condition whose possible risk factors are aging, genetic susceptibility and exposure to certain chemical agents. In the last decades, epidemiological and experimental studies have suggested an association between pesticide exposure and the development of PD. In total, nine systematic reviews (SRs) of the literature have been conducted since 2005 in order to verify the association between exposure to the herbicide paraquat and PD. However, most of them presented methodological limitations, such as language restrictions (only articles in English), databases, period of publication of the studies, and mainly, they did not evaluate their methodological quality by consistent tools. From the SRs followed by meta-analysis, the majority presented positive and statistically significant results, although a high level of heterogeneity (I²) was identified among studies. Thus, the conception of a new SR of the literature and meta-analysis that presented less operational limitations than those detected in the existing SRs was justified. For this, cross-sectional, cohort and case-control studies enrolling any participant exposed to environmental and/or occupational exposure to paraquat, without restrictions regarding dose or period of exposure, were selected. Outcomes considered were PD diagnosed by specialists or reported by the participants themselves in interviews and/or questionnaires. The searched databases were: PubMed, EMBASE, LILACS, TOXNET and Web of Science, without language or publication period restrictions. The heterogeneity among studies was evaluated by the I² test. Data were summarized as odds ratios with their respective 95% confidence intervals. Risk of bias was assessed by modified tools from the NewCastle Otawa Scale. As results, 15 studies were included in the SR and 12 studies included in the meta-analysis. An OR of 1.40 (95% CI 1.16-1.70, I² 15%) was obtained, demonstrating a positive association between exposure to paraquat and PD. This association appeared to be more evident in susceptible individuals, occupationally exposed to paraquat in coexposure to other pesticides, lacking use of protective equipment. However, most studies included a small number of exposed participants and presented a high risk of bias. Thus, new prospective studies that carefully document the herbicide exposure, with a greater number of potentially exposed individuals, are still necessary to consolidate the positive association observed. Also, the analysis of specific genes that increase predisposition to PD, and coexposure to other pesticides that may be related to this disease, may contribute to the identification of factors that modulate its occurrence.
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Palavras-chave
Paraquat, Doença de Parkinson, Revisão sistemática, Metanálise