A recent collaborative study from Italian universities and research institutes has shed light on Amyotrophic Lateral Sclerosis (ALS). The reports from the study have established that cigarette smoking may accelerate the progression of ALS.
Cigarette smoking may also raise the risk of ALS, according to the study that adds new evidence to the growing link between smoking and the rare muscle-wasting disease. This will lead to decreased survival in ALS patients.
The results from studies done in the past have been conflicting or involved only a limited number of ALS patients participating which did not provide satisfactory results. The epidemiological studies supporting the hypothesis that cigarette smoking as a risk factor for ALS have been small and mostly retrospective.
ALS is a fatal degenerative disorder of upper and lower motor neurons that affects muscle functions, including breathing, speaking and swallowing. With the death of motor neurons, ALS patients lose the ability to initiate and regulate muscle movement which is attributed to the resulting paralysis and eventually death.
In half of all reported cases, ALS also is associated with cognitive impairment ranging from Frontotemporal Dementia (FTD) to milder forms of impairment. The median survival time from onset of ALS ranges from two to five years after diagnosis. However, 10 to 20 percent of patients survive longer than 10 years.
ALS occurs in two forms, one, Familial ALS occurs in families that have ALS in their history where several genes linked to ALS that have been spotted and mapped to a particular region of a chromosome occur. However, it has been observed that only about 10 percent of patients have a positive family history for ALS. Secondly, in most cases ALS appears sporadically in the population. Sporadic ALS which develops independent of family relationships.
Researchers claim that the cause of ALS is unknown in about 90 percent of cases. However, there is evidence suggesting that age, gender and underlying health issues are risk factors for the devastating disorder. It has also been established that there are genetic variations that vulnerability to development of ALS, in as much as the genetic differences cannot be associated with the disease.
More than 5,500 people each year are diagnosed with ALS in the U.S. As it is, there is no cure, and there are limited treatment options for the disease, which causes rapid muscle deterioration. This makes ALS patients dependent on medications such as Riluzole that will alleviate symptoms such as muscle spasms and mechanical breathing aid devices.
The study which was investigating the influence of cigarette smoking on ALS outcome in a population-based study was conducted. It was published in the Journal of Neurology Neurosurgery and Psychiatry.
In an effort to examine the prognostic influence of premorbid smoking habits and vascular risk profile in the development of ALS researchers conducted a population-based cohort study. It involved 650 Italian patients with ALS and the research team was led by Adriano Chio, MD, medical and scientific director of the Department of Neuroscience at the University of Turin in Italy, and colleagues.
The researchers collected data on ALS patients’ smoking habits and also investigated Chronic Obstructive Pulmonary Disease (COPD) among these patients. At the time of ALS diagnosis, approximately 19 percent of the ALS patients were regular smokers, 28 percent were former smokers and about 53 percent had never indulged in smoking.
Cigarette smoking has been attributed to the development of Chronic Cough commonly referred to as Smoker’s Cough. It is seen to lead to breathing difficulties in one out of five smokers. It has remained a medical mystery how 80 percent of smokers escape complications from long-term smoking such as COPD. On the other hand, 20 percent develop severe airway damage, resulting in high morbidity and mortality. It has been estimated that COPD is the third most common cause of death in the U.S.
It was suggested in the past that genetic composition may elaborate on how different people respond to the many toxins and chemicals released into the body of a smoker. However, the details of the genes associated with this phenomenon were elusive until research conducted by scientists at Weill Cornell Medical College explained the pathogenesis of COPD, and how some genetically susceptible individuals develop compromised pulmonary functioning in their lives.
In the study, COPD was diagnosed in 44 ALS patients. Half of these patients were former smokers. It was seen that patients with COPD had a shorter lifespan in comparison to those without the disease. The researchers also found that cigarette smoking appeared to shorten lives of ALS patients irrespective of whether or not they had COPD when ALS diagnosis was made.
The ALS patients who were current smokers had a notable shorter median survival of 1.9 years compared with former smokers who has 2.3 years and those who never smoked with 2.7 years. To add on, current smokers were younger in age than others when their ALS was diagnosed.
The researchers concluded the study indicated that environmental factors and personal habits were representative risk factors for onset of ALS and could also play a role in its phenotype and prognosis. They further mentioned that, the discovery of the mechanisms, either genetic or epigenetic, by which exogenous factors influence disease phenotype is of great significance in an objective approach to cure of and fight against ALS.
The Cancer Prevention Study II (CPS II) cohort of the American Cancer Society, comprising over 1 million Americans (22), provided the opportunity to assess prospectively the relation between cigarette smoking and ALS mortality among men and women. The study looked at the relationship between cigarette smoking and ALS in five different long-term studies involving 1.1 million people, 832 of whom developed ALS.
In the study the researchers discovered that current or former cigarette smokers were likely to develop ALS by nearly 50 percent in comparison to people who had never smoked. Cigarette smoking status was ascertained by the question, “Do you now or have you ever smoked cigarettes, at least one a day for one year’s time?”
Ever smokers were then asked questions on the average number of cigarettes they smoked per day, the age when they started smoking, and the total number of years they smoked. Former smokers were also asked the age at which they quit smoking. Data on the covariates considered in the analyses were also obtained from responses to the questionnaire.
The results indicated that current smokers were 42 percent more likely to be diagnosed with ALS and former smokers had a 44 percent higher risk. Among current or former smokers, the risk of ALS increased as the age at which they started smoking reduced.
It was established that, although the risk of ALS increased by 10 percent for each increment of 10 cigarettes smoked per day and by 9 percent for each 10 years of smoking, these associations were no longer evident when the group of those who never smoke was exempted from the analysis.
The researchers noted that significant trends in the risk of ALS were observed with the duration of smoking and the number of cigarettes smoked per day, but these trends were highly influenced by the low ALS risk among those who had never smoked. They said that further studies were necessary to confirm the association between ALS and cigarette smoking.
It was discovered that there are several probable ways in which cigarette smoking may increase the risk of ALS. For instance, nitric oxide or other toxic components such as residues of pesticides used in tobacco cultivation, of cigarette smoke could lead to direct damage to the neurons.
Also, the chemicals in tobacco were capable of generating free radicals that could also damage cells associated with ALS. Therefore, cigarette smoking might contribute to the risk of ALS either by a direct neurotoxic effect on motor neurons or by increasing oxidative stress.
The constant exposure to formaldehyde, a by-product of the combustion process of tobacco smoking, has been reported to be linked to an increased risk of ALS. Additionally, inhibition of Vascular Endothelial Growth Factor (VEGF) has also been proposed as a probable explanation for smoke-related effects on neurons.
In spite of the fact that a recent review suggested that smoking can be considered an established risk factor for ALS, there have been significantly few studies and results have been conflicting. A positive association between smoking and ALS has been reported in some but not all case-control studies. These disparities may be explained by small sample sizes and possible survival, selection, and recall bias.
In a study analysis including 621 ALS deaths, cigarette smoking was associated with an increased ALS mortality in women, but not in men. The probability of effect modification, not only by hormones and oral contraceptive use but also by other factors that might relate to the absence of effect among the men.
The lack of linkage between smoking and ALS in men was thereafter ascertained in a cohort of male construction workers in Sweden, 160 of whom died of ALS. On the other hand, in a recent multi-centred prospective study in Europe, including 118 participants with ALS, current smokers had two-fold increased rates of ALS compared to those who had never smoked, with no notable differences by gender.