Assessment of Parkinson’s Disease symptoms and toxin exposures in reghters: a cross-sectional survey

BACKGROUND: Parkinson’s disease (PD) has been correlated with several environmental and toxic exposures. The frequency of PD in reghters is higher than the general population, which may be due to the high amounts of toxin exposures reghters experience on the job. There is a need to further address the high rates of PD among this subgroup. The purpose of this study is to improve our understanding of the relationship between toxin exposure in reghters and Parkinson’s Disease symptoms. METHODS: An anonymous survey distributed to Massachusetts reghters assessed risk factors for toxin exposure and presence of PD symptoms. Risk factors included frequency and duration of time spent reghting, number of res worked, and history of toxin exposure (i.e., pesticides). We collected the frequency of PD symptoms including tremors, muscle stiffness, REM behavior disorder, hyposmia, micrographia, and decreased walking pace. Analyses comparing toxin exposure and presence of PD symptoms were performed using Chi-square testing, p < 0.05 was considered signicant. RESULTS: Two hundred participants were included in the study. The number of years as a reghter, the number of days per week working, and the number of res worked correlated with higher reports of hyposmia, micrographia, and decreased walking pace. CONCLUSION: Fireghters have an increased risk for PD symptoms as a result of the toxin exposures that are frequently present in res.

Fire ghters experience heavy lead exposures as they encounter buildings heavily coated with lead-based paints and spotted with lead-comprised dust [4]. Lead exposure has shown to result in a two-fold increase in the risk for developing PD as it damages neurological pathways by inhibiting reuptake of Ca 2+ and decreasing the quantity of dopamine within vesicles [4,5]. Styrene or vinyl benzene is a crucial toxin encountered during res and has been shown to alter dopamine receptor functioning and damage central and peripheral nervous systems [6].
Benzopyrene has been shown to decrease dopamine neurotransmitter regeneration in the nucleus accumbens and hippocampus of rats [7]. A prior study found benzopyrene on re jackets, personal protective equipment of re ghters, as well as other tools and determined that current equipment cleaning standards do not eliminate benzopyrene contamination [8].
Polybrominated diphenyl ether (PBDE) is a neurotoxin used in ame-retardants and found in carpets, cushions, and home-insulating structures frequently handled by re ghters [9]. PBDE uses oxidative damage to inhibit dopamine transporters DAT and VMAT2 [4]. Many studies have established the correlation between carbon monoxide (CO) exposure and risk of PD [10,11]. Fire ghters frequently encounter CO as their own equipment known as self-contained breathing apparatuses (SCBAs) lead to elevated levels of CO found in compressed air [12].
Fire ghters are exposed to several environmental toxins that increase their risk for PD and there is a need to further address the high rates of PD diagnosis among this subgroup. This study utilized a retrospective analysis based on a survey assessing the incidence of environmental toxin exposure as well as Parkinson's symptoms among re ghters.

Methods
An anonymous online survey was distributed to re ghters > 18 years of age between January 2020 and August 2020 to the Professional Fire ghters of Massachusetts. Demographic data collected includes sex, age, race, and employment status (working, retired, volunteer, or family member of deceased re ghter).
Risk factors for toxin exposure were assessed surveying frequency and duration of time spent re ghting and use of protective gear. A history of toxin exposure was evaluated including prior work as a welder, consumption of well water, duration of military service, as well as exposure to Agent Orange, pesticides, and jet fuel. The presence and frequency of Parkinson Disease symptoms was collected, including tremors, muscle stiffness, REM behavior disorder (i.e., acting out dreams, talking during sleep), hyposmia, micrographia, and decreased walking pace. Analyses comparing toxin exposure and presence of Parkinson symptoms were performed using Chi-square testing, p < 0.05 was considered signi cant. This study was approved by the St. Elizabeth institutional review committee (IRB #EX064) and participants provided written informed consent to participate in the study.

Results
Two hundred participants were included in the study. Among participants, 96% are male, 99% are Caucasian, 1% are Hispanic, 62% are still employed, 37% are retired, and 12% have a family history of Parkinson's disease (Table 1). Table 1 shows the range of ages in survey participants with 42% of participants being ages 40-50 and 30% being ages 60-70. Figure 1 shows the communities of survey participants. The majority of our survey participants live in rural and suburban communities in Massachusetts with several living outside of Massachusetts. Family history of PD 25 (12%) Figure 2 demonstrates the frequency of common Parkinson Disease symptoms reported by all participants. 82% of survey participants reported muscle stiffness. 34% of participants reported tremors.
66% of participants reported REM behavior disorder. 36% of participants reported hyposmia. 15% of participants reported micrographia, and 38% of participants reported decreased walking pace.  Fig. 3 show the correlation of the number of years of being a re ghter with decreased walking pace, micrographia, and hyposmia. After 10 years of re ghting, participants were found to be 5 times more likely to have decreased walking pace. After 20 years, participants were 30 times more likely to have decreased walking pace and 5 times more likely to have micrographia. After 30 years, participants were twelve times more likely to have decreased walking pace and 5 times more likely to have hyposmia. Table 2: PD symptoms of decreased walking pace, micrographia, and hyposmia correlated with exposures using Chi-square analysis. * = statistically signi cant value with p < 0.05 considered to be signi cant. Table 2 and Fig. 4 show the correlation of the number of days per week working as a re ghter with decreased walking pace, micrographia, and hyposmia. Participants were thirty-three times more likely to have decreased walking pace if they had worked more than 2 days per week. Participants were eight times more likely to have micrographia if they had worked more than 1 day per week. They were ten times more likely to have micrographia if they had worked more than 2 days per week. Participants working more than 6 days per week were seven times more likely to have micrographia.
Using Chi-square analysis, Table 2 and Fig. 5 show the correlation between the number of 5-9 alarms res worked and decreased walking pace, micrographia, and hyposmia. Fire alarms are categorized based on the severity of the re with 5-9 re alarms being more severe. Participants who helped with 20 or more res were eight times more likely to have decreased walking pace and seventeen times more likely to have micrographia. Participants who have helped with 40 or more res were ve times more likely to have decreased walking pace, seven times more likely to have micrographia, and ve times more likely to have hyposmia. Participants who have helped with 100 or more res were four times more likely to have micrographia. Table 2 and Fig. 6 show the correlation of ghting in the Vietnam War with decreased walking pace, micrographia, and hyposmia. Participants who fought in the Vietnam War were six times more likely to have decreased walking pace and six times more likely to have micrographia. Table 2 and Fig. 7 show the correlation of exposure to pesticides with decreased walking pace, micrographia, and hyposmia. Participants who have been exposed to pesticides were seven times more likely to have decreased walking pace and ten times more likely to have micrographia.
Muscle stiffness was the most commonly reported symptom occurring in 82% of our survey responders. Several studies have discovered elevated baseline muscle pain in re ghters [13]. Dr.
Park and his team found that muscle pain was the second most common reported symptom amongst re ghters likely due to heavy personal protective equipment [14]. Thus, the muscle stiffness experienced by responders may be linked to the demands of their job or early symptoms of Parkinson's Disease.
Acting out dreams was reported by 66% of survey responders. This frequency was distinctly higher than other studies which have noted REM behavior disorder in only one third of Parkinson's patients [15].
Decreased walking pace and bradykinesia were reported by 38% of respondents. Hyposmia and tremors were the fourth and fth most reported Parkinson's symptoms at 36% and 34% respectively. Lastly, micrographia occurred in 15% of responders.

Discussion
After conducting a thorough literature search, we identi ed the ve most common toxin exposures in res that have been shown to increase risk for PD. Through comparative analysis, we found that the number of years re ghting, number of days per week re ghting, number of 5-9 alarm res encountered, ghting in the Vietnam War, and exposure to pesticides all correlated with a signi cantly higher frequency of three Parkinsonian symptoms: micrographia, hyposmia, and decreased walking pace.
The number of years spent re ghting was broken down into 4 categories: 10 years or more, 20 years or more, 30 years or more, and 40 years or more. It is important to note that there was a small number of survey responders who had or have been re ghting for more than 40 years (n = 13). Nonetheless, the frequency of reported hyposmia and decreases in walking pace increased by an average of 5% and 7% per 10 years respectively. Meanwhile, the frequency of reported micrographia remained relatively unchanged. The duration of a re ghter's career has also been found to positively correlate with levels of epigenetic changes, namely hypomethylation, that could lead to developments of neurodegenerative diseases [16]. Alternatively, for the number of days worked per week, the frequency of reported micrographia and walking pace increased by 6% and 3% per day, respectively.
The comparative data for the number of 5-9 alarm res proved more di cult to gather due to the rarity of such alarm res with only 30 being reported in Boston within the past 10 years [17]. The frequency of micrographia increased by 1% per 20 5-9 alarm res.
Another key nding was that participation in the Vietnam War, which involved the toxin Agent Orange, was signi cantly correlated with decreased walking pace and micrographia. Those exposed to the Vietnam War more frequently reported decreased walking pace (88% vs. 41%), micrographia (38% vs. 6%), and hyposmia (50% vs. 34%). A number of different case studies on Vietnam War veterans have suggested that exposure to Agent Orange, speci cally its 2,4-Dichlorophenoxyacetic acid component, can signi cantly increase the risk of Parkinson's Disease [18].
Exposure to pesticides was signi cantly correlated with reported frequencies of decreased walking pace (53% vs. 32%), micrographia (30% vs. 11%), and hyposmia (45% vs. 34%). These trends align with previously conducted research which has found several pesticides and herbicides that are linked to increased susceptibilities to Parkinson's Disease. For example, one study with mice models showed that exposure to the herbicides Maneb and Paraquat can lead to mutations in genes responsible for neurogenesis which can in turn impact the development of PD [19]. Additionally, one notably deleterious pesticide, rotenone, has been shown to induce oxidative damage in dopaminergic regions of several rats [20].
Although this study provides ample data to help us understand the risks associated with re ghting, there were some limitations. The advertisement for this survey stated that the study's aim was to determine the link between re ghting and Parkinson's Disease. This may have increased the response rate of those concerned about or affected by Parkinson's Disease. This study has a relatively small sample size, but the demographics appear to represent the typical re ghters in Massachusetts. The demographics of the sample were 96% being male, 99% Caucasian, and 72% being between the ages of 40 and 70.
Hyposmia was reported by 36% of study participants. It is probable that the actual frequency of hyposmia is more than what was reported as this sensory symptom can be less noticeable than motor symptoms such as bradykinesia. Hyposmia is a commonly occurring symptom of Parkinson's Disease, reported in 80% of patients [21]. It is di cult, however, to determine whether the reported hyposmia in this study was due to the progression of Parkinson's Disease or chronic exposure to re and smoke. Research has shown that chronic smoke and toxic substance exposure can lead to irreversible hyposmia [22]. In one study, 47.5% of 102 Chicago city re ghters had signi cantly low scores for a sense of smell test [23].

Conclusions
The purpose of this study is to improve our understanding of the relationship between toxin exposure in re ghters and risk of Parkinson's Disease. Fire ghters have an increased risk for PD symptoms as a result of the toxin exposures that are frequently present in res. Our study showed that the number of years working as a re ghter, the number of days per week working, and the number of res worked correlated with higher reports of Parkinson symptoms such as hyposmia, micrographia, and decreased walking pace. It is important that the scienti c and re ghter community alike continue to develop studies aimed at determining the frequency of Parkinson's symptoms in re ghters as well as the speci c toxin exposures that are responsible for the progression of this disease.

Declarations
Ethics approval and consent to participate This study was approved by the St. Elizabeth institutional review committee (IRB #EX064). Participants provided written informed consent to participate in the study.

Consent for publication
The authors received written consent from Massachusetts re ghter Tim MacMillan who provided content for the background story.

Availability of data and materials
The datasets generated and/or analyzed during the current study are not publicly available due to privacy policies but are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
The authors have no sources of funding to declare.
Author's contributions RK contributed to the conception and design of the survey, acquisition of the background information, data analysis and interpretation of results, and writing of the manuscript. AC contributed to the acquisition of the background information, data analysis and interpretation of the results, and writing of the manuscript. HH contributed to the acquisition of the background information, data analysis and interpretation of the results, and writing of the manuscript. OV contributed to the conception and design of the survey, acquisition of the background information, and thorough editing of the manuscript. AH contributed to the conception and design of the survey, acquisition of the background information, and thorough editing of the manuscript. All authors read and approved the nal manuscript. Figure 1 Zip codes of participants.     Number of 5-9 alarm res helped put out and reported symptoms of hyposmia, micrographia, and decreased walking pace. Symptoms reported among those exposed to pesticides.