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A person&#8217;s degree of exposure to multiple environmental pollutants — reflected by their presence in the blood — may be used to predict <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) risk and survival, according to new research.
Greater exposure to these chemicals was associated with increased odds of an individual developing ALS, as well as a higher mortality risk among ALS patients in Michigan.
“Our results emphasize the importance of understanding the breadth of environmental pollution and its effects on ALS and other diseases,” Eva Feldman, MD, PhD, the study&#8217;s senior author and a professor at the University of Michigan (UM) and its medical school, said in a <a href="https://www.michiganmedicine.org/health-lab/drawing-tube-blood-could-assess-als-risk-environmental-toxin-exposure">university news story</a>.
“When we can assess environmental pollutants using available blood samples, that moves us toward a future where we can assess disease risk and shape prevention strategies,” added Feldman, also the director of the NeuroNetwork for Emerging Therapies at Michigan Medicine.
The study, &#8220;<a href="https://jnnp.bmj.com/content/early/2023/09/27/jnnp-2023-332121">Environmental risk scores of persistent organic pollutants associate with higher ALS risk and shorter survival in a new Michigan case/control cohort</a>,&#8221; was published in the <a href="https://jnnp.bmj.com/">Journal of Neurology, Neurosurgery &amp; Psychiatry</a>.
[recommended-reading id=75053]
<h3>Levels of 24 environmental pollutants found to impact survival in ALS</h3>
ALS is believed to arise from a combination of <a href="https://alsnewstoday.com/causes-of-als/">genetic and environmental risk factors</a>, such as exposure to pesticides, heavy metals, or electromagnetic fields.
The scientists previously found that concentrations of persistent organic pollutants (POPs) were <a href="https://alsnewstoday.com/news/pesticide-exposure-may-als-risk-factor/">higher in the blood of ALS patients</a> compared with the general population. POPs are hazardous chemicals that are widely distributed and live in the environment for a very long time. The most common ones are pesticides or insecticides used for agriculture.
In a follow-up study, the team found that high exposure to these pollutants was associated with <a href="https://alsnewstoday.com/news/exposure-to-environmental-pollution-reduces-survival-rates-of-als-patients-study-reports/">lower survival among ALS patients</a>.
Now, the scientists aimed to validate their findings in a new group of patients, using the information to develop an environmental risk score (ERS) based on these exposures that could predict ALS risk and survival.
The team examined blood levels of 36 different POPs among 164 ALS patients seen at UM&#8217;s Pranger ALS clinic, as well as 105 people from the general Michigan population, who served as controls.
Characteristics between the two groups were similar, except that the ALS patients were older, and had lower educational attainment than the controls. The ALS group also had a higher proportion of men.
Several individual pollutants were significantly associated with ALS. Still, the researchers found that the highest risk of the neurodegenerative disease didn&#8217;t arise from just one of them, but rather a mixture of several. That mixture was used to generate a risk score for predicting the likelihood of ALS.
The results showed that scores in the 75th percentile — the threshold for the highest 25% of exposure — were significantly linked to 2.58 times greater odds of developing ALS compared with patients in the 25th percentile, or the threshold for the lowest 25% of exposure.
“For the first time, we have a means collecting a tube of blood and looking at a person’s risk for ALS based on being exposed to scores of toxins in the environment,” said Stephen Goutman, MD, director of the Pranger Clinic, associate director of the ALS Center of Excellence at UM, and the study&#8217;s first author.
Overall, 24 of 36 POPs were found to have a negative effect on ALS survival. However, survival time was best predicted by taking into account all 36 of the toxins.
Survival ERSs based on exposure to all toxins indicated that greater exposure was associated with shorter survival, as expected.
Particularly, the 25% of patients with the highest exposure had a 2.31 times greater mortality risk than the 25% of those with the lowest exposure — corresponding to a survival benefit of 0.88 years for that group.
[quote=&#8221;center&#8221;]For the first time, we have a means collecting a tube of blood and looking at a person’s risk for ALS based on being exposed to scores of toxins in the environment.[/quote] 
Of the individual POPs, organochlorine pesticides, known as OCPs, were most strongly associated with ALS risk and survival, which the researchers noted is in line with multiple previous analyses. OCPs are a class of pesticides that have been used since the mid-1900&#8217;s for agriculture and mosquito control.
While many previous studies have estimated environmental exposures using geographical location or occupational history, the researchers believe that directly measuring their levels in the blood may be a more accurate and quantifiable way of assessing exposure.
Still, &#8220;replication in other non-Michigan cohorts is beneficial to determine the national and global distribution of this risk,&#8221; the researchers wrote.
The findings also highlight the possible use of ERSs for understanding the impact of environmental pollutants on human disease.
“Environmental risk scores have been robustly associated with other diseases, including cancers, especially when coupled with genetic risk. This is a burgeoning application that should be further studied as we deal with the consequences of pollutants being detected throughout the globe,” Feldman said.

Environmental pollutants in blood linked to ALS risk, survival

An earlier start to noninvasive ventilation (NIV) could help to improve respiratory function and prolong survival for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), according to a small clinical trial in Spain.
While many of the study&#8217;s findings failed to reach statistical significance, the researchers believe the data still support the adoption of earlier ventilation assistance to improve ALS outcomes.
The study, &#8220;<a href="https://content.iospress.com/articles/journal-of-neuromuscular-diseases/jnd221658">Impact of Early Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A multicenter Randomized Controlled Trial</a>,&#8221; was published in the <a href="https://content.iospress.com/journals/journal-of-neuromuscular-diseases/Pre-press/Pre-press">Journal of Neuromuscular Diseases</a>.
[recommended-reading id=85375]
In ALS, weakness in muscles needed for breathing can lead to <a href="https://alsnewstoday.com/symptoms-of-als/#Breathing_difficulties">respiratory difficulties</a> for many patients. Respiratory failure is the main cause of death for about 80% of patients.
NIV can help support better breathing for people living with the neurodegenerative disease. With the approach, oxygen is delivered to a person&#8217;s airways using a mask or similar device, often initially worn at nighttime.
While it has become recognized that NIV can help to prolong survival and boost life quality, the appropriate time to start a patient on NIV has not been definitively established. Still, it is generally agreed that NIV should be initiated before severe respiratory muscle weakness occurs.
In Spain, where the study was conducted, NIV is typically begun once patients have reached a forced forced vital capacity (FVC) that&#8217;s less than 50% of what is predicted for one&#8217;s age and sex, according to the researchers.
A standard measure of lung function, FVC assesses the maximum amount of air a person can forcibly exhale from the lungs. A score higher than 80% of predicted is generally considered normal.
Some studies suggest NIV could have greater benefits when initiated at earlier stages of lung function decline, when FVC is at around 65-75% of predicted. But no randomized trials have directly compared the outcomes of ALS patients who started NIV earlier versus later in their disease course.
<h3>Randomized, controlled clinical trial</h3>
To address that, the scientists conducted a <a href="https://classic.clinicaltrials.gov/ct2/show/NCT01641965">randomized controlled clinical trial (NCT01641965)</a> to evaluate the impacts of earlier NIV initiation on ALS prognosis. The findings from the trial, which was conducted from 2012-2014, were described in the recent publication.
A total of 42 ALS patients were recruited at ALS centers in Spain, all of whom were in the initial phase of respiratory muscle weakness, defined as having an FVC at or less than 75% of expected, but with a previous FVC over 75% recorded in the last six months.
Participants were assigned randomly to an early NIV group, where NIV was initiated immediately, or a standard NIV group, which started NIV when their FVC reached less than 50%, they experienced shortness of breath when lying down, or a daytime buildup of carbon dioxide in the bloodstream.
All participants were using <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">Rilutek</a> (riluzole) throughout the trial, and were followed for a median of 16-18.5 months. Overall disease severity at the start of the study was similar between groups.
<h3>Study&#8217;s main goal</h3>
The study&#8217;s main goal was to evaluate differences in survival between the early and standard NIV groups.
Data showed that the median survival time since diagnosis in the early NIV group was longer than in the standard NIV group — 25.2 months compared with 19.4 months. But the differences were not found to be statistically significant, meaning the trial failed to meet its main goal.
Still, a statistically significant association was observed between FVC values throughout the study and death, which &#8220;suggests a protective effect of [higher] FVC%,&#8221; the researchers wrote.
Overall disease progression was similar between the two groups throughout the study, as were measures of sleep and life quality. Other measures of respiratory function tended to favor the early NIV group, although there were no significant differences.
Rates of NIV-related side effects were similar between groups, the most common of which was dry mouth.
Overall, the researchers believe the findings highlight that the optimal time to start NIV is when FVC values are about 75%, and respiratory muscles are slightly affected.
&#8220;This is when NIV can do its job: maintaining muscle strength, slowing the decline in FVC, and preventing nocturnal hypoventilation [nighttime breathlessness] and respiratory complications, and thus prolonging survival,&#8221; the scientists wrote.
<h3>Some patients hesitant to start NIV earlier</h3>
While compliance to treatment was good in the study, the team noted that many patients may be hesitant to start NIV because it implies deterioration. Doctors should thus be mindful of how they approach the topic with their patients and in monitoring compliance.
The researchers believe the failure of the trial to reach its main goal may be that not enough trial participants were recruited (only 42 of the expected 72 participants). This was mostly due to competing clinical trials that were run at the ALS centers at the same time, they said.
&#8220;It’s important to highlight the difficulty in conducting studies like this, both now and in the future,&#8221; they wrote, noting that few studies like this are likely to be conducted in the future, partly because many centers are already adopting an earlier start to NIV.

Tag: ALS survival outcomes

Environmental pollutants in blood linked to ALS risk, survival

Starting noninvasive ventilation sooner may yield survival benefit