Table E-3.Descriptive Data from Case-Control Studies Included in the Qualitative Review

Table e-3.Descriptive data from case-control studies included in the qualitative review – EXPOSURE TO PESTICIDES

Source (Author, year [reference]) / Ethnicity / Study size (cases/controls) / Ascertainment of PD / Selection of controls / Matching criteria / Exposure assessment / Risk factor (pollutant) / Findings (OR [95%CI]) / Adjustments / Major sources of bias / Study quality (NOS score)
Ref. 28 / Swedish males / 91 cases / 75 controls / Neurologist-based / Inpatients with subarachonid hemorrage / sex and geographic area / Questionnaire / Agricultural chemicals exposure >15 days / 0,4 [0,1-1,4] / None / Selection / comparability of controls, self-reported data / 6
Ref. 29 / Chinese (care home residents) / 35 cases / 105 controls / Neurologist-based / Old age homes and geriatric day hospital controls / age (±3 years) / Person-to-person interview with a structured questionnaire of cases or spouse/relatives / Pesticides-herbicides / 3,6 [1,0-12,9] / None / Inclusion (outpatients excluded; non representative population) and recall bias (exposure self-reported [dementia?] or reported by spouse/relatives), limited number of cases / 4
Ref. 30 / Chinese (Beijing and Guangzhou) / 100 cases / 200 controls / Neurologist-based / Outpatients (neurology clinics) of the same hospitals / institution, gender and age (± 3 years) / Interview / Pesticides-herbicides (industrial chemicals) ≥1 year prior the onset of PD [or the matched age for controls]) / 2,39 [1,32-4,30] / Not reported / Selection / comparability of controls, and recall bias (exposure self-reported or reported by family members) / 6
Ref. 31 / USA (New Jersey) / 106 cases / 106 controls / Neurologist-based / Spouses of the patients / None / Questionnaire / Sprayed pesticides / 7,00 [1,61-63,46] / None / Selection / comparability of controls, self-reported data / 4
Ref. 32 / Canadian (British Columbia) / 57 cases / 122 controls / Neurologist-based / Community controls randomly selected from electoral rolls / Not reported / Questionnaire during a a face-to-face interview / Chemical spraying / 2,23 (p=0,30) / age and smoking (sex had no effect) / Self-reported data, limited number of cases / 7
Ref. 33 / USA Americans (Kansas) / 150 cases / 150 controls / Neurologist-based / Outpatients (neurology and medical clinics) of the same hospital / gender and age (± 2 years) / Questionnaire / Pesticides-herbicides / 1,05 [0,67-1,66] / None / Selection / comparability of controls, self-reported data / 6
Ref. 36 / USA Americans (Washington) / 34 cases / 25 controls / University Hospital Neurology Clinic / Neurology clinic patients with other diagnoses / Not reported / Questionnaire / Pesticides / Few patients reported the use. Data were sparse and no trends emerged / None / Selection / comparability of controls, self-reported data / 3
Ref. 37 / USA Americans (Kansas) / 38 cases with familial PD / 38 controls / Neurologist-based / General neurology and medicine clinics of the same hospital / age and sex / Interview / Pesticides-herbicides / 1,0 (p=1.0) / age and sex / Selection / comparability of controls, self-reported data, limited number of cases / 4
Ref. 38 / Spanish / 128 cases / 256 controls / Neurologist-based / Patients presenting to emergency room for minor, non-neurological ailments / age and sex / Questionnaire / Pesticides / 1,34 [0,85-2,16] / None / Selection / comparability of controls, self-reported data / 5
Ref. 39 / Canadian (Alberta) / 130 cases / 260 controls / Neurologist-based / Population-based / gender and age (± 2,5 years) / Interview / Pesticides use any for 10 years for 20 years for 30 years / 2,25 [1,27-3,99] 1,41 [0,73-2,73] 1,38 [0,53-3,57] 0,88 [0,29-2,99] / age and sex / Self-reported data / 7
Ref. e-1 / USA Americans (Kansas) / 63 cases / 76 controls / Neurologist-based / Recruited via news media releases (rural site) and from a university neurology clinic (urban syte) / no specific criteria but groups were similar in age and gender / Questionnaire / Pesticide or herbicide use ≥20 days per year for ≥5 years / 3,42 [1,27-7,32] / Neurologic disease family history and history of depression / Selection / comparability of controls, self-reported data / 4
Ref. e-4 / Canadian (British Columbia) / 127 cases / 124 + 121 controls / Neurologist-based / Community controls (N=124) randomly selected from electoral rolls and chronic cardiac disease inpatients (N=121) / no specific criteria but groups were similar in age and gender / Questionnaire / Pesticides / Men: 2,32 [1,10-4,88] (voters); 2,03 [1,00-4,12] (cardiac disease) Women: 1,36 [0,48-3,85] (voters); 1,11 [0,32-3,80] (cardiac disease) / age / Self-reported data / 7
Ref. e-5 / Spanish / 74 cases / 148 controls / Neurologist-based / Patients presenting to emergency room for minor, non-neurological ailments / age and sex / Questionnaire / Pesticides (≥1 year) / 1,73 [0,98-3,03] / None / Selection / comparability of controls, self-reported data / 5
Ref. e-6 / Canadian (Alberta) / 40 cases / 101 controls / Neurologist-based / Population-based / gender and age (± 2,5 years) / Interview / Pesticides (during any period between the ages of 15-55 years) / 1,98 [0,80-4,88] / None / Self-reported data / 6
Ref. e-7 / Canadian / 87 cases / 2070 controls / Self-reported / Canadian Study of Health and Aging cohort: community (databasesof the provincial health insurance) and institutional sample (fromnursing homes, chronic care facilities and collectivedwellings) / None / Questionnaire / Pesticides / 1,81 [0,92-3,36] (occupational); 1,67 [0,67-3,63] (hobbies & sports) / Not reported / Selection / comparability of controls, self-reported data / 3
Ref. e-11 / German / 380 cases / 379 + 376 controls / Neurologist-based / Patients randomly selected among immediate neighborhood (N=379) and from electoral rolls (same urban & rural areas; N=376) / age (± 3 years), gender and urban/rural area / Interview / Pesticides (any type but unable to specify product name) / 1,5 [1,0-2,3] (neighborhood controls); 2,2 [1,4-3,4] (regional controls) / age, sex, education and smoking / 7
Ref. e-12 / Chinese (Taiwan) / 120 cases / 230 controls / Neurologist-based / Outpatients of the neurology clinic (headaches, peripheral neuropathy, back pain or cervical spondylosis) / gender, age (±2 years) & residence in Taiwan / Questionnaire / Pesticides and/or herbicides: Yes vs. No 1-19 years ≥20 years / ………………………………………… 2,89 [2,28-3,66] 1,41 [0,52-3,85] 6,72 [2,62-17,21] / age and gender (for exposed vs. non exposed) / Selection / comparability of controls, self-reported data / 6
Ref. e-13 / Chinese (Hong Kong) / 215 cases / 313 controls / Neurologist-based / Inpatients of the same hospitals / gender, age (± 10 years) & locality (hospital catchment area) / Questionnaire / Pesticides Crude Multiple adjusted / 1,80 [0,90-3,58] 0,75 [0,26-2,22] / age,sex, smoking, well water use, rural living, farming, vitamin supplements, tea and food items (times per week; raw vegetables, fruit and vegetables) consumption, duration of exposure to pesticides / Selection / comparability of controls, self-reported data / 6
Ref. e-14 / Italian / 100 cases / 200 controls / Neurologist-based / Outpatients (nephrology & haemostasis center) of the same hospital / sex / Questionnaire / Pesticides / 2,92 [1,38-6,14] / Not reported / Selection / comparability of controls, self-reported data / 4
Ref. e-17 / Australian (South East Queensland and Central West South Wales) / 224 cases / 310 controls / Neurologist-based / Population-based controls / age, gender, ethnicity, residential area and site of collection / Questionnaire / Pesticides or herbicides / 1,2 [0,8-1,5] / None / Self-reported data / 7
Ref. e-18 / Australian (south-east Quennsland and central west New South Wales) / 95 cases / 95 controls / Neurologist-based / Not described / None / Questionnaire / Pesticide use more than once weekly for ≥6 months / 2,3 [1,2-4,4] (no modyfing effect on risk was detected for GST polymorphism) / age, sex and family history / Selection / comparability of controls, self-reported data / 5
Ref. e-19 / Italian (Emilia Romagna) / 86 cases / 86 controls / Neurologist-based / Outpatients (cardiology, dermatology, nephrology, ophthalmology) of the same hospital / age and sex / Questionnaire / Pesticides-herbicides exposure ≥10 years / 1,15 [0,56-2,36] / None / Selection / comparability of controls, self-reported data / 6
Ref. e-20 / Swedish (southeastern area) / 113 cases / 263 controls / Prescription records review and by requesting doctors (diagnosis reviewed by a neurologist on defined criteria) / Population-based (randomly selected from the Population Register of the same county of the patients) / Municipality / Questionnaire / Pesticides (handling within any occupation) / 3,3 [1,0-10] (men) / age, sex, smoking and coffee consumption / Self-reported data / 8
Ref. e-21 / Finnish / 123 cases / 256 controls / Neurologist-based / Population-based controls / gender, age (± 2 years) & municipality / Interview / Pesticides Regular Occasional Any / 0,65 [0,33-1,29] 1,23 [0,74-2,04] 1,02 [0,63-1,65] / age, sex and municipality / Self-reported data, cases were restricted to those having a disease duration <7 years / 6
Ref. e-22 / USA Americans (Massachussets) / 140 cases / 147 controls / Neurologist-based / Friends or in-laws of the patients / None / Questionnaire during a a face-to-face interview / Pesticides (for increasing exposure in years) / 1,02 [0,90-1,17] / sex, birth cohort, smoking, education, familiy history of PD and tremors, well water, place of living and herbicides / Selection / comparability of controls, self-reported data / 6
Ref. e-24 / Brazilian / 92 cases / 110 controls / Neurologist-based / Inpatients or outpatients (rheumatology, neurology) of the same hospital / gender, age (± 2 years) / Questionnaire during a a face-to-face interview / Pesticides and/or herbicides ( for ≥15 years) / 2,49 [0,53-13,14] / None / Selection / comparability of controls, self-reported data / 5
Ref. e-25 / French (Limousin province) / 140 cases / 280 controls / Neurologist-based / Inpatients or outpatients (endocrinology, rheumatology, ear-nose-throat, ophthalmology) of the same hospital / age (± 5 years) / Interview / Pesticides-herbicides / 1,2 [0,7-2,3] / age, family history of PD, tea and coffee consumption, smoking and living in urban area / Selection / comparability of controls, self-reported data / 5
Ref. e-27 / Israelian (south area) / 93 cases / 93 controls / Neurologist-based / Outpatients (dermatology, neurology, internal medicine clinics) of the same hospital / gender & age (± 2 years) / Questionnaire / Pesticides / 6,81 [0,75-64,89] / smoking, work in mechanical factory or in construction, country of birth & peptic disease / Selection / comparability of controls, self-reported data / 6
Ref. e-29 / European (13 academic centers) / 203 sibling pairs / Neurologist-based / Siblings / None / Questionnaire during a a face-to-face interview / Pesticides (mixing, handling or applying) / Not significant (p=0.31) and could not be retrieved or calculated / None / Cases were non representative of the PD population (restricted to farmers and related jobs), selection / comparability of controls, self-reported data / 5
Ref. e-31 / Italian (north-east) / 136 cases / 272 controls / Neurologist-based / Neurology clinics outpatients / gender and age (± 3 years) / Questionnaire during a a face-to-face interview / Pesticides / 1,6 [1,0-2,4] / age, sex and smoking (pack-years) / Selection / comparability of controls, self-reported data / 6
Ref. e-32 / Italian / 1316 cases / 4383 controls / Neurologist-based / Population-based (Italian Longitudinal Study Health cohort) / None / Questionnaire / Pesticides-use license / 3,68 [1,57-8,64] gender-specific analyses: 4,41 [1,84-10,56] (men; there were no PD cases among women) / age, sex, years of schooling and smoking / Self-reported data / 7
Ref. e-33 / French (Gironde and Dordogne) / 84 cases / 252 controls / Neurologist-based / Population-based controls (PAQUID study cohort) / gender and age (± 1 year) / Questionnaire / Pesticides any use Dose exposure: 1st quartile 2nd quartile 3rd quartile 4th quartile / 2,20 [1,11-4,34] ……… ……… 2,4 [0,7-7,9] 1,8 [0,5-5,9] 6,6 [1,7-25,0] 0,7 [0,1-3,7] / age, sex, education and smoking / Cases were non representative of the PD population (restricted to aged 70 years or over); self-reported data / 6
Ref. e-34 / Chinese (Beijing) / 114 cases / 205 controls / Neurologist-based (on two consecutive visits) / Residents in the same areas included in a PD prevalence survey / gender, race, residence categories (urban-rural) / Questionnaire / Pesticides-herbicides / 1,19 [0,54-2,61] / age, gender, alcohol & tea consumption, fertilizers, head injury, well water drinking, farming and organic solvent use / Self-reported data / 8
Ref. e-35 / Turkish (Kızılcaboluk & Denizli) / 36 cases / 108 controls / Neurologist-based / Population-based controls / age and sex / Questionnaire / Pesticides (>20 days per year for ≥10 years) / 2,96 [1,31-6,69] / None / Self-reported data, limited number of cases / 7
Ref. e-37 / Australian / 393 cases / 389 controls / Neurologist-based / Spouses of the patients and volunteers / None / Questionnaire / Pesticides (regular use) / 1,33 [0,63-2,83] (for positive exposure in metabolizer according to genetic analysis of CYP2D6 polymorphism; in poor metabolizers: heterozygotes, 3,27 [1,21-8,80]; homozygotes, 8,41 [1,01-69,8]) / age, gender, smoking, and positive family history / Selection / comparability of controls, self-reported data / 5
Ref. e-38 / French / 190 cases / 419 controls / Neurologist-based / Community subjects (enrolled in the French health insurance organizationfor farmers and related job categories) / age, sex & region of residency / Questionnaire (occupation screening). In professional user exposure was reviewed by an insurance physician (home interview) and interviews reviewed by epidemiologists, occupational health physicians and an agronomist / Pesticides (gardening / professional use) / 1,50 [0,92-2,43] (for positive exposure in metabolizer according to genetic analysis of CYP2D6 polymorphism; in poor metabolizers, 3,28 [1,16-9,27]) / age, sex , region of residency and smoking / Cases were non representative of the PD population (restricted to farmers and related jobs); self-reported data / 7
Ref. e-40 / Italian (Tuscany) / 190 cases / 190 controls / Neurologist-based / Population-based controls / age, sex, socio-cultural factors & same area of residency / Questionnaire / Pesticides 1-10 years 11-20 years 21-30 years >30 years Any / 0,82 1,00 0,90 1,12 (0,94 [0,63-1,40]) / None / Self-reported data / 7
Ref. e-42 / USA Americans (western WashingtonState) / 250 cases / 388 controls / Neurologist-based / Population-based controls / sex & age (in 10-year categories) / Interview-administered structured questionnaire / Pesticides (any type, ≥6 months) / 0,95 [0,66-1,37] / age, sex and smoking / Self-reported data / 7
Ref. e-43 / Taiwanese / 125 cases / 162 controls / Neurologist-based / Outpatients of the neurology clinic (back pain or cervical spondylosis) / age and sex / Questionnaire during a a face-to-face interview / Pesticides / 1,72 [1,07-2,75] (for exposure ≥35 years: 2,14 [1,23-3,71]) / Not reported / Selection / comparability of controls, self-reported data / 4
Ref. e-45 / French / 247 cases / 676 controls / Neurologist-based / Community subjects (enrolled in the French health insurance organization
for farmers and related job categories) / age, sex & region of residency / Questionnaire (occupation screening). In professional user exposure was reviewed by an insurance physician (home interview) and interviews reviewed by epidemiologists, occupational health physicians and an agronomist / Pesticides (gardening & professional use) / 1,6 [1,0-2,4] / age (in quartiles) and education / Cases were non representative of the PD population (restricted to farmers and related jobs); self-reported data / 7
Ref. e-49 / USA Americans (Missouri and Illinois) / 102 cases / 133 controls / Neurologist-based / Community subjects (recruited from adult living complexes, community centers,fraternal organizations, volunteer offices, and olderadult services programs) / age and ethnicity / Questionnaire / Pesticides (occupational exposure) / 1,2 [0,3-4,8] / marital status, smoking, rural living, farm living, family history of PD and essential tremor, head trauma, farming and orchard employment / Self-reported data / 5
Ref. e-50 / Australian / 306 cases / 321 controls / Neurologist-based / Spouses of patients and volunteers collected from patient neighbourhoods and from community organizations / None / Questionnaire / Pesticides any exposure regular exposure (at least weekly for sixmonths) / 1,50 [1,09-2,05] 2,87 [1,57-5,24] / None / Selection / comparability of controls, self-reported data / 4
Ref. e-51 / USA Americans (Minnesota) / 149 cases / 129 controls / Through the medical records-linkage system of the Rochester Epidemiology Project / Population-based / age, sex & county of residence / Telephone interview-administered structured questionnaire (with patients or proxies) / Pesticides: Any From farming Men (smoking adjust.) Women / 1,5 [0,8-2,9] 1,3 [0,6-3,1] 2,2 [0,8-6,0] 2,5 [1,1-5,7] 0,2 [0,02-1,9] / age and sex / Cases were identified by means of medical-record linkage / 8
Ref. e-52 / USA Americans (Washington) / 293 cases / 395 controls / Neurologist-based / Community subjects (volunteers belonging to the GroupHealthCooperativeCenter for Health Studies database) / age (birth decade) and sex / Interview-administered structured questionnaire / Pesticides / 1,63 [0,52-5,15] (for positive exposure in low risk genotype carriers according SLC6A3 polymorphism; in high risk carriers, 5,66 [1,73-18,5]) / age, education and smoking status / Self-reported data / 6
Ref. e-53 / European (Scotland, Italy, Sweden, Romania and Malta) / 767 cases / 1989 controls / Neurologist-based / Mixed hospital inpatients and outpatients and community controls / age, sex & geography / Interview-administered structured questionnaire (exposure review by an occupational hygienist) / Pesticides exposure: Any Low High / …………………... 1,25 [0,97-1,61] 1,09 [0,77-1,55] 1,39 [1,02-1,89] / age, sex , country, tobacco use, ever knocked unconscious and family history of PD / Selection / comparability of controls, self-reported data / 6
Ref. e-55 / Taiwanese / 153 cases / 155 controls / Neurologist-based / Community individuals recruited from the samehospital in the health examination clinic / age, sex and birthplace / Questionnaire during a a face-to-face interview / Pesticides (for risk genotypes according to MnSOD and NQO1 poly-morphisms): Low risk One high risk Two high risk / ………...... ………… 2,62 [0,95-7,26] 2,69 [1,17-6,24] 4,09 [1,34-10,64] / age, sex, smoking and genetic susceptibility / Selection / comparability of controls, self-reported data / 5
Ref. e-26 / USA Americans (Iowa and North Carolina) / 86 cases / 79557 controls / Self-reported / Persons certified to use restricted-use pesticides and spouses (Agricultural Health Study) / None / Questionnaire / Pesticides (mixing or applying). Ever use of any Cumulative lifetime use: 0-64 days 65-200 days 201-396 days ≥397 / ……...... …………… 0,5 [0,2-1,1] ……………………… ………… reference 0,7 [0,3-1,3] 0,7 [0,4-1,5] 0,8 [0,4-1,5] / age, state and type of participant / Inclusion (non representative population of cases; spouses as major controls source) and recall bias (exposure self-reported) / 5
Ref. e-58 / USA Americans (Wisconsin, Iowa, South Dakota, or North Dakota) / 833 cases / 833 controls / Neurologist-based / Unaffected siblings and unrelated control subjects (by random digit
dialing (age <65 years) or from the Centers for
Medicare and Medicaid Services lists (ages >65 years) / Geography / Interview-administered structured questionnaire / Pesticides / 1,10 [0,88-1,37] / age, sex and SNCA REP1 genotype / Selection / comparability of controls, self-reported data / 7
Ref. e-57 / Brazilian / 72 early-onset cases / 81 controls / Neurologist-based / Outpatients of the same clinic / age / Interview / Pesticides and/or herbicide and/or solvents (at least 1 day per month for ≥2 continuous years before onset) / 5,47 [1,14-26,21] / None / Cases were non representative of the PD population (restricted to early-onset PD), selection / comparability of controls, self-reported data / 4
Ref. e-60 / USA Americans / 319 cases / 326 controls / Neurologist-based / Sibling, parents and spouses of the patients / Geography / Interview-administered structured questionnaire / Pesticides use any for <11 years for 11-26 years for >26 years / 1,61 [1,13-2,29] 1,68 [1,01-2,80] 1,35 [0,84-2,19] 1,87 [1,17-3,00] / age, sex , caffeine consumption and smoking / Selection / comparability of controls, self-reported data / 7
Ref. e-61 / Danish (Faroe Islands] / 79 cases / 154 controls / Neurologist-based / Population-based controls (Faroese Population Registry) / sex and age / Face-to-face interview / Pesticides …………………………………………………………………….……………………… / 6,00 [0,62-57,68] (men; no exposure was reported by women); ………………….. / age, sex and smoking / Self-reported data on exposure. / 6
Ref. e-62 / USA Americans (California) / 368 cases / 341 controls / Neurologist-based / Population-based controls / place of residence / Combination of data on agricultural application
of restricted-use pesticides, historical electronic maps of land use and
crop type, historical occupational / residential
addresses / Pesticides (likely occupational): / ………………… 1,52 [1,08-2,14] / None / 7
Ref. e-63 / French / 224 cases / 557 controls / Neurologist-based / Community subjects (enrolled in the French health insurance organization
for farmers and related job categories) / age, sex & region of residency / Questionnaire (occupation screening). In professional user exposure was reviewed by an insurance physician (home interview) and interviews reviewed by epidemiologists, occupational health physicians and an agronomist / Pesticides Gardening use Professional use / 1,4 [0,9-2,3] 1,7 [1,0-2,9] / age and sex (additionally for smoking & cognition in professional user) / Cases were non representative of the PD population (restricted to farmers and related jobs); self-reported data / 8