Job-related Lead Exposure Linked to Shorter Survival After Diagnosis
Occupational exposure to lead — a heavy metal — prior to disease onset is associated with a more severe disease progression and lower survival among people with amyotrophic lateral sclerosis (ALS), according to a recent study.
“In survival analysis of an international cohort [group] of ALS cases, our results suggest that occupational lead exposure is associated with a faster rate of functional decline and shorter survival in ALS,” the researchers wrote. “This may suggest particular mechanistic pathways that may affect the course of ALS.”
The study, “Occupational lead exposure and survival with amyotrophic lateral sclerosis,” was published in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.
Environmental factors are thought to contribute to the risk of ALS development, and exposure to environmental toxins could influence later disease outcomes, like survival, in ALS patients. Lead is a well-established neurological toxin, the exposure to which has been associated with an increased risk of ALS development.
Two studies have evaluated whether blood or bone levels of lead influenced survival time in patients, but reached opposite conclusions. The studies were limited by the fact that later blood or bone levels of lead may not accurately reflect levels of original exposure to the toxin, the researchers wrote.
The new study examined the relationship between occupational or work-related lead exposure and survival in 135 ALS patients (64% male) who were enrolled in a prior study through the Clinical Research in ALS and Related Disorders Consortium (CReATe).
Patients completed an environmental questionnaire, including questions about their work history. Information from the survey was used to determine if participants had held an occupation associated with likely lead exposure prior to ALS symptom onset.
This data was compared with clinical information collected at the study’s start (baseline), and three months, six months, one year, and 18 months (a year and a half) thereafter.
The mean age of participants at symptom onset was 56.1 years, and the median time from symptom onset to completion of the environmental questionnaire was 3.2 years.
Among the 135 participants, 36 (27%) had held jobs with lead exposure, and the median time working these jobs was four years. Four cases were considered “high intensity” exposure, and 32 were deemed “low intensity” exposure. In 23 cases, military service accounted for the occupational lead exposure.
Over the course of follow-up, 38 patients (28%) reached a survival endpoint — either death or the use of permanent assisted ventilation. Eleven of 36 lead-exposed individuals (31%) reached an endpoint during follow-up, compared with 27 of 99 patients (27%) who were not exposed to lead.
After adjusting for other factors that could influence the relationship — like age of disease onset and prior military service — survival was significantly lower among lead-exposed individuals than those unexposed to lead.
Older age, bulbar site of disease onset (i.e. the first symptoms are speech and swallowing problems), and a shorter time between symptom onset and diagnosis were also significantly associated with a shorter survival.
Scores on the ALS Functional Rating Scale-Revised were examined to assess disease progression, with a lower score indicating functional decline. Results showed that the lead-exposed group showed faster score declines than the non-exposed group, suggestive of a faster disease progression.
“Our findings strengthen the conclusion that survival is shorter among those with lead exposure,” the researchers wrote.
One limitation of the study was the assignment of lead exposure based on job history alone, as people with the same occupation may not have had the same exposure, the researchers noted.
Still, the results suggest a relationship between occupational lead exposure and ALS survival.
While lead may contribute to disease exacerbations via several mechanisms, the researchers hypothesized that its ability to substitute for zinc in biological processes may play an important role. While zinc exists in only low amounts in the body, it is critical for the proper function of many enzymes, the creation of DNA, and supporting a healthy immune system, among other roles. Of note, the copper-zinc superoxide dismutase-1 (SOD1) gene is implicated in ALS.