The first epidemiological study of a suspected cluster of amyotrophic lateral sclerosis (ALS) among civilian workers at Kelly Air Force base in Texas has found no evidence that ALS mortality is any higher than would be expected.
However, because many workers and former workers are still alive and younger than when symptoms typically appear, an advisory panel that reviewed the study design and results recommended re-examining mortality rates in five or 10 years.
Independently conducted for the Air Force by Applied Epidemiology of Amherst, MA, the investigation was assisted by several other interested parties, including the ALS Association (ALSA), its South Texas chapter, the San Antonio Metropolitan Health District, and the Texas Department of Health. Although the Air Force paid for the study, active and retired service members were not included.
The review of death certificates found 3,264 deaths among nearly 32,000 employees who had worked at Kelly for at least one year between 1981 and 2000, 13 of which were categorized as motor neuron disease, which includes ALS. This rate was lower than the standardized mortality ratio (SMR) for the US and Texas.
Normal ALS mortality for the 20-year study period would have been between one and two deaths per year. The only notable difference was among Hispanic men, where five ALS deaths were confirmed. Hispanics typically have lower ALS rates than the general population. The results were published in the November 2002 Journal of Occupational and Environmental Medicine (44(11): 989–996).
“The study cohort worked at the base for a long time – three-quarters for 10 years and half for 20 years or more,” said Carmel Armon, MD, Professor of Neurology at Loma Linda University in California, who serves on ALSA's Medical Advisory Panel. “Most of the workers are still alive and younger than we usually see at onset. We recognize this as an inherent limitation of the study and recommend examining mortality again in five years,” he said. “Even if a full-scale study is not warranted in five years' time, we advise that one be performed in 10 years.”
UNUSUAL HIGH INCIDENCE REPORTED
Concern was raised after media reports of what appeared to be unusually high incidence of ALS among base workers who met at a support group sponsored by the San Antonio ALSA chapter. In 1999, the South Texas chapter of the ALSA reported a suspected cluster of cases to the Air Force and regional health authorities. The Air Force Institute for Environment, Safety, and Occupational Health Risk Analysis and the San Antonio Metropolitan Health District then launched an investigation into mortality from all causes at the base, including cancer and ALS.
An initial informal survey by the ALSA chapter found 39 workers and former workers with ties to Kelly who said they or a family member had been diagnosed with ALS or ALS-like symptoms. Ultimately, Kelly families reported 140 deaths from ALS but the researchers were unable to confirm most cases because ALS was not cited on the death certificates. Including these would have biased the study because national and state comparison figures were exclusively based on death certificate data, Dr. Armon explained.
Mary Lyon, PhD, ALSA's Vice President of Patient Services, said the organization is very pleased with the cooperation and openness with which the study was conducted and believes additional research will further clarify the issue. A separate study is now under way examining shared characteristics and providing descriptive information about confirmed ALS patients. The results are expected later this year.
“This started out as face-to-face encounters at the support group,” Dr. Lyon said. “People began to meet each other and the local chapter developed a [basic] questionnaire. A case series is now in progress based on the questionnaire, and more than 100 persons have reported symptoms or a diagnosis of ALS over an unlimited time period, but there's no guarantee of ascertainment.”
The Air Force has created a more extensive questionnaire, but ALS is “very difficult to investigate,” she added. “We at ALSA are very pleased the study was done. From our point of view, it is most important to answer this basic question of excess mortality. Like any study, there were limitations, but we are grateful the study was even conducted in the open way that it was.”
OTHER EXPLANATIONS POSSIBLE
Air Force officials worried that an ALS cluster – if one did exist at Kelly – might have been caused by exposure to unknown toxic chemicals, radiation, or environmental contamination from the base.
Over the past decade, several studies have examined reports of elevated neuromuscular disease rates among Gulf War veterans and servicemen exposed to Agent Orange and other defoliants in Vietnam. A 2001 Veterans Administration study found ALS incidence in Persian Gulf combatants was twice that for non-combatants, but the paper describing those results has not yet been published (Neurology Today 2002; 2(11): 1,6,8).
Dr. Armon called the Kelly study a “benchmark” for future collaborative research efforts, adding that there might be other explanations for the appearance of a cluster at Kelly. The patients could be living longer as a result of better-than-average supportive treatment, while a comparison of local mortality to national figures may understate the rate of disease occurrence over the short term, he explained. In addition, greater attention to ALS among the Kelly cohort could also mean a diagnosis of ALS would be more likely to appear on their death certificate than would national and local populations.
INCIDENCE AND PREVALENCE
ALS researcher and neurology professor Hiroshi Mitsumoto, MD, Director of the Eleanor and Lou Gehrig MDA/ALS Center at Columbia-Presbyterian Medical Center in New York City, said a mortality study at this stage resolves little.
“I don't think these findings are conclusive. A death certificate-based study may not capture a significant portion of patients, and many may have developed the disease but left the area. We need to see all incidence and prevalence cases, as well as deaths.”
The incidence of ALS in the United States is estimated at two new cases per 100,000 persons each year, while its prevalence is believed to be about six cases per 100,000. Incidence is the rate at which new ALS cases occur in a population over a specific period, while prevalence is the proportion of a population that is affected at any given time. An estimated 5,000 new cases are reported each year and there are up to 30,000 people with ALS at any given time.
Dr. Mitsumoto believes ALS is a syndrome rather than a single disease – a number of diseases rather than just one. “Because of this, epidemiological studies just can't capture true incidence; you have to look at all the subsets. It is like a diagnosis of headache – it could be fatigue, inflammation, or eye strain, but it could also be a tumor or a stroke; it could even be psychosomatic.”
“ALS remains an enigma,” said Dr. Armon. “Even in the five to 10 percent of individuals who have inherited a gene for the disease we don't know how the gene triggers disease onset. We don't understand what causes the delayed development of the disease over a person's lifetime, or why there are acute and chronic versions. Whether ALS can be caused by environmental exposure to neurotoxins is still in the hypothesis stage. For the nearly 95 percent of patients who have ‘sporadic’ ALS, the mystery is baffling and frustrating.”
Dr. Mitsumoto, who has published numerous studies on ALS, said he is “passionate” about learning more about genetic susceptibility to ALS and possible environmental triggers, emphasizing that he believes science is on the cusp of a much fuller understanding of the syndrome and its causes.
“Large, multicenter DNA studies of ALS patients and families will also shed light on other possible genetic variables that might predispose persons to developing ALS,” he added. Dr. Mitsumoto and other researchers met with National Institute of Environmental Health and Safety in November to discuss the need for a large-scale genetic study of ALS. “The agency committed to a national study of the genetics, a case-control study using DNA samples. Some people may consider it a fishing expedition, but I see it as a start. If 20 years from now we have genetic data on, say, 2,000 ALS patients, we're going to have answers to some of these questions.”
ARTICLE IN BRIEF:
✓ The first epidemiological study of a suspected cluster of amyotrophic lateral sclerosis (ALS) among civilian workers at Kelly Air Force base in Texas found no evidence that ALS mortality is any higher than would be expected.
✓ However, because many workers and former workers are still alive and younger than when symptoms typically appear, an advisory panel that reviewed the study design and results recommended re-examining mortality rates in five or 10 years.
✓ Dr. Carmel Armon of Loma Linda University, who reviewed the data, said there could be other reasons for the appearance of a cluster at Kelly. The patients could be living longer as a result of better-than-average supportive treatment, while a comparison of local mortality to national figures may understate the rate of disease occurrence over the short term.
✓ Dr. Hiroshi Mitsumoto, Director of the Eleanor and Lou Gehrig MDA/ALS Center, believes the mortality study findings would not be conclusive, however, and said researchers need to see all incidence and prevalence cases, as well as deaths.