Occupational pesticide exposure and the risk of death in patients with Parkinson's disease: an observational study in southern Brazil

Márcio Schneider Medeiros, Sumanth P Reddy, Mariana P Socal, Artur Francisco Schumacher-Schuh, Carlos Roberto Mello Rieder, Márcio Schneider Medeiros, Sumanth P Reddy, Mariana P Socal, Artur Francisco Schumacher-Schuh, Carlos Roberto Mello Rieder

Abstract

Background: Multiple studies have suggested that various pesticides are associated with a higher risk of developing Parkinson's disease (PD) and may influence the progression of the disease. However, the evidence regarding the impact of pesticide exposure on mortality among patients with PD is equivocal. This study examines whether pesticide exposure influences the risk of mortality among patients with PD in Southern Brazil.

Methods: A total of 150 patients with idiopathic PD were enrolled from 2008 to 2013 and followed until 2019. In addition to undergoing a detailed neurologic evaluation, patients completed surveys regarding socioeconomic status and environmental exposures.

Results: Twenty patients (13.3%) reported a history of occupational pesticide exposure with a median duration of exposure of 10 years (mean = 13.1, SD = 11.2). Patients with a history of occupational pesticide exposure had higher UPDRS-III scores, though there were no significant differences in regards to age, sex, disease duration, Charlson Comorbidity Index, and age at symptom onset. Patients with occupational pesticide exposure were more than twice as likely to die than their unexposed PD counterparts (HR = 2.32, 95% CI [1.15, 4.66], p = 0.018). Occupational pesticide exposure was also a significant predictor of death in a cox-proportional hazards model which included smoking and caffeine intake history (HR = 2.23, 95% CI [1.09, 4.59], p = 0.03)) and another which included several measures of socioeconomic status (HR = 3.91, 95% CI [1.32, 11.58], p = 0.01).

Conclusion: In this prospective cohort study, we found an increased all-cause mortality risk in PD patients with occupational exposure to pesticides. More studies are needed to further analyze this topic with longer follow-up periods, more detailed exposure information, and more specific causes of mortality.

Keywords: Environmental exposure; Mortality; Occupational exposure; Parkinson; Pesticides.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Survival curve comparing patients with (n = 20) and without (n = 130) self-reported occupational pesticide exposure (n = 150, p-value from log-rank test)
Fig. 2
Fig. 2
Impact of occupational pesticide exposure on mortality when controlling for smoking, caffeine intake, sex, and age (Multivariable cox proportional hazards model; n = 150, concordance = 0.60, SE = 0.04. Global Schoenfeld residual is p > 0.05))
Fig. 3
Fig. 3
Impact of occupational pesticide exposure on mortality when controlling for sex, age, and socioeconomic status - employment history, average historical monthly income (when employed), insurance status, race, and education level (Multivariable cox proportional hazards model; n = 105, concordance = 0.60, se = 0.06 Global Schoenfeld residual is p > 0.05))

References

    1. Ball N, Teo WP, Chandra S, Chapman J. Parkinson’s disease and the environment. Front Neurol. 2019;10:218. doi: 10.3389/fneur.2019.00218.
    1. Caudle WM. Occupational exposures and parkinsonism. Handb Clin Neurol. 2015;131:225–239. doi: 10.1016/B978-0-444-62627-1.00013-5.
    1. Paul KC, Sinsheimer JS, Cockburn M, Bronstein JM, Bordelon Y, Ritz B. Organophosphate pesticides and PON1 L55M in Parkinson's disease progression. Environ Int. 2017;107:75–81. doi: 10.1016/j.envint.2017.06.018.
    1. Kaur K, Kaur R. Occupational pesticide exposure, impaired DNA repair, and diseases. Ind J Occup Environ Med. 2018;22:74–81. doi: 10.4103/ijoem.IJOEM_45_18.
    1. Tangamornsuksan W, Lohitnavy O, Sruamsiri R, et al. Paraquat exposure and Parkinson's disease: a systematic review and meta-analysis. Arch Environ Occup Health. 2019;74:225–238. doi: 10.1080/19338244.2018.1492894.
    1. Nandipati S, Litvan I. Environmental exposures and Parkinson's disease. Int J Environ Res Public Health. 2016;13.
    1. Pezzoli G, Cereda E. Exposure to pesticides or solvents and risk of Parkinson disease. Neurology. 2013;80:2035–2041. doi: 10.1212/WNL.0b013e318294b3c8.
    1. Priyadarshi A, Khuder SA, Schaub EA, Shrivastava S. A meta-analysis of Parkinson’s disease and exposure to pesticides. Neurotoxicology. 2000;21:435–440.
    1. Gunnarsson LG, Bodin L. Parkinson’s disease and occupational exposures: a systematic literature review and meta-analyses. Scand J Work Environ Health. 2017;43:197–209. doi: 10.5271/sjweh.3641.
    1. Priyadarshi A, Khuder SA, Schaub EA, Priyadarshi SS. Environmental risk factors and Parkinson's disease: a metaanalysis. Environ Res. 2001;86:122–127. doi: 10.1006/enrs.2001.4264.
    1. van der Mark M, Brouwer M, Kromhout H, Nijssen P, Huss A, Vermeulen R. Is pesticide use related to Parkinson disease? Some clues to heterogeneity in study results. Environ Health Perspect. 2012;120:340–347. doi: 10.1289/ehp.1103881.
    1. Van Maele-Fabry G, Hoet P, Vilain F, Lison D. Occupational exposure to pesticides and Parkinson's disease: a systematic review and meta-analysis of cohort studies. Environ Int. 2012;46:30–43. doi: 10.1016/j.envint.2012.05.004.
    1. Gamache PL, Haj Salem I, Roux-Dubois N, Le Bouthillier J, Gan-Or Z, Dupre N. Exposure to pesticides and welding hastens the age-at-onset of Parkinson’s disease. Can J Neurol Sci. 2019:1–6.
    1. Caballero M, Amiri S, Denney JT, Monsivais P, Hystad P, Amram O. Estimated residential exposure to agricultural chemicals and premature mortality by Parkinson's disease in Washington state. Int J Environ Res Public Health. 2018;15.
    1. Macleod AD, Taylor KS, Counsell CE. Mortality in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29:1615–1622. doi: 10.1002/mds.25898.
    1. Brouwer M, Koeman T, van den Brandt PA, et al. Occupational exposures and Parkinson's disease mortality in a prospective Dutch cohort. Occup Environ Med. 2015;72:448–455. doi: 10.1136/oemed-2014-102209.
    1. Ritz B, Yu F. Parkinson’s disease mortality and pesticide exposure in California 1984-1994. Int J Epidemiol. 2000;29:323–329. doi: 10.1093/ije/29.2.323.
    1. Coelho FEA, Lopes LC, Cavalcante RMS, Correa GC, Leduc A. Brazil unwisely gives pesticides a free pass. Science. 2019;365:552–553.
    1. Rieck M, Schumacher-Schuh AF, Altmann V, et al. DRD2 haplotype is associated with dyskinesia induced by levodopa therapy in Parkinson's disease patients. Pharmacogenomics. 2012;13:1701–1710. doi: 10.2217/pgs.12.149.
    1. CNF: Cadastro Nacional de Falecidos. Brasil: CNF; 2019. Resultados da Pesquisa. . [cited 2019 Jul 1].
    1. Lamarca R, Alonso J, Gomez G, Munoz A. Left-truncated data with age as time scale: an alternative for survival analysis in the elderly population. J Gerontol A Biol Sci Med Sci. 1998;53:M337–M343. doi: 10.1093/gerona/53A.5.M337.
    1. Korn EL, Graubard BI, Midthune D. Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale. Am J Epidemiol. 1997;145:72–80. doi: 10.1093/oxfordjournals.aje.a009034.
    1. Yan D, Zhang Y, Liu L, Shi N, Yan H. Pesticide exposure and risk of Parkinson's disease: dose-response meta-analysis of observational studies. Regul Toxicol Pharmacol. 2018;96:57–63. doi: 10.1016/j.yrtph.2018.05.005.
    1. Krueger PM, Tran MK, Hummer RA, Chang VW. Mortality attributable to low levels of education in the United States. PLoS One. 2015;10:e0131809. doi: 10.1371/journal.pone.0131809.
    1. Rogers RG, Everett BG, Zajacova A, Hummer RA. Educational degrees and adult mortality risk in the United States. Biodemography Soc Biol. 2010;56:80–99. doi: 10.1080/19485561003727372.
    1. Sichieri R, de Lolio CA, Correia VR, Everhart JE. Geographical patterns of proportionate mortality for the most common causes of death in Brazil. Rev Saude Publica. 1992;26:424–430. doi: 10.1590/S0034-89101992000600008.
    1. Rogot E, Sorlie PD, Johnson NJ. Life expectancy by employment status, income, and education in the National Longitudinal Mortality Study. Public Health Rep. 1992;107:457–461.
    1. Yang F, Johansson AL, Pedersen NL, Fang F, Gatz M, Wirdefeldt K. Socioeconomic status in relation to Parkinson's disease risk and mortality: A population-based prospective study. Medicine (Baltimore) 2016;95:e4337. doi: 10.1097/MD.0000000000004337.
    1. Beard JD, Steege AL, Ju J, Lu J, Luckhaupt SE, Schubauer-Berigan MK. Mortality from amyotrophic lateral sclerosis and Parkinson's disease among different occupation groups - United States, 1985-2011. MMWR Morb Mortal Wkly Rep. 2017;66:718–722. doi: 10.15585/mmwr.mm6627a2.
    1. Costa J, Lunet N, Santos C, Santos J, Vaz-Carneiro A. Caffeine exposure and the risk of Parkinson’s disease: a systematic review and meta-analysis of observational studies. J Alzheimers Dis. 2010;20(Suppl 1):S221–S238. doi: 10.3233/JAD-2010-091525.
    1. Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J. Coffee and tea consumption and the risk of Parkinson’s disease. Mov Disord. 2007;22:2242–2248. doi: 10.1002/mds.21706.
    1. Abbott RD, Ross GW, White LR, et al. Environmental, life-style, and physical precursors of clinical Parkinson’s disease: recent findings from the Honolulu-Asia Aging Study. J Neurol. 2003;250(Suppl 3):III30–III39.
    1. Hernan MA, Takkouche B, Caamano-Isorna F, Gestal-Otero JJ. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Ann Neurol. 2002;52:276–284. doi: 10.1002/ana.10277.
    1. Palacios N, Gao X, McCullough ML, et al. Caffeine and risk of Parkinson’s disease in a large cohort of men and women. Mov Disord. 2012;27:1276–1282. doi: 10.1002/mds.25076.
    1. Paul KC, Chuang YH, Shih IF, et al. The association between lifestyle factors and Parkinson’s disease progression and mortality. Mov Disord. 2019;34:58–66. doi: 10.1002/mds.27577.
    1. Ma C, Liu Y, Neumann S, Gao X. Nicotine from cigarette smoking and diet and Parkinson disease: a review. Transl Neurodegener. 2017;6:18. doi: 10.1186/s40035-017-0090-8.
    1. Ferguson LW, Rajput AH, Rajput A. Early-onset vs. late-onset Parkinson's disease: a clinical-pathological study. Can J Neurol Sci. 2016;43:113–119. doi: 10.1017/cjn.2015.244.

Source: PubMed

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