Academic journal article Environmental Health Perspectives

Association of Lead Exposure with Survival in Amyotrophic Lateral Sclerosis

Academic journal article Environmental Health Perspectives

Association of Lead Exposure with Survival in Amyotrophic Lateral Sclerosis

Article excerpt

BACKGROUND: Reasons for the variability in survival among ALS cases are unknown but may include exposure to environmental neurotoxicants.

OBJECTIVES: We aimed to determine whether lead exposure, assessed by measuring blood and bone lead levels, is associated with survival in amyotrophic lateral sclerosis (ALS).

METHODS: We evaluated the relationship of lead exposure to ALS survival in 110 cases from a case-control study conducted in New England in 1993-1996 that included measurements of blood and bone lead. We retrieved information on date and cause of death through 31 December 2003 from the National Death Index Plus and the Social Security Administration Death Index. We evaluated the relationship of survival to lead exposure using Cox proportional hazard analysis, with adjustment for age, sex, and smoking.

RESULTS: We found mortality data for 100 of 110 cases; 93 of 100 death certificates mentioned ALS. Median survival from diagnosis to death was 28 months. Shorter survival was associated with older age at diagnosis, female sex, bulbar onset, shorter interval between symptom onset and diagnosis, and reduced lung function. Shorter survival from diagnosis to death had a weak inverse association with blood lead (hazard ratio = 0.9; 95% confidence interval, 0.8-1.0) and a stronger inverse association with patella lead (0.5; 0.2-1.0) and tibia lead (0.3; 0.1-0.7); similar results were found for survival from symptom onset to death.

CONCLUSIONS: These results suggest that lead exposure is associated with longer survival in ALS cases and, if confirmed, may shed light on mechanisms involved in disease progression.

KEY WORDS: amyotrophic lateral sclerosis, lead, prognosis, survival. Environ Health Perspect 116:943-947 (2008). doi:10.1289/ehp.11193 available via [Online 2 April 2008]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the motor neurons of the spinal cord and brain. Typically, the disease is rapidly fatal; most individuals die within 2-3 years of diagnosis, often from respiratory failure (Mitchell and Borasio 2007). However, survival is variable, with some individuals living > 10 years (del Aguila et al. 2003). The reasons for this variability are largely unknown. Factors related to shorter survival include older age, female sex, bulbar onset, and decreased time from symptom onset to diagnosis (del Aguila et al. 2003), but other factors likely play a role.

The etiology of ALS is also not well understood, but the disease is generally considered to be a result of the interplay between genetic and environmental factors (Mitchell and Borasio 2007). Sporadic ALS is not strongly related to superoxide dismutase (SOD1) or other genes associated with familial ALS, although variation in these or other genes may increase susceptibility (Kunst 2004; Mitchell and Borasio 2007). No environmental exposure has been convincingly demonstrated to play a role in ALS (Armon 2003), but some evidence implicates smoking (Kamel et al. 1999), pesticides (McGuire et al. 1997), electromagnetic fields (Savitz et al. 1998), and heavy metals (Kamel et al. 2005).

In a previous study (Kamel et al. 2002), we found that ALS risk was associated with both blood and bone levels of lead as well as with occupational lead exposure. Other studies have also reported associations of ALS risk with lead exposure (reviewed by Kamel et al. 2005), and a recent study found a cluster of ALS cases in proximity to an active lead smelter in Missouri (Turabelidze et al. 2008). In the present study we followed cases from our previous study (Kamel et al. 2002) to evaluate the relationship of lead exposure to ALS mortality. Our expectation was that lead exposure would shorten survival; surprisingly, we found that lead exposure was associated with longer survival.

Materials and Methods

We conducted a case-control study in New England, USA, in 1993-1996 (Kamel et al. …

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