People who are smokers at the time of their ALS diagnosis are unlikely to survive as long as people who have already quit smoking or never started, according to a report in the September 21 Journal of Neurology, Neurosurgery, and Psychiatry. The correlation between between smoking and disease prognosis, which is largely independent of respiratory status at diagnosis, suggests that smoking plays a role in ALS beyond increasing the risk of developing the disease, commented lead author Adriano Chiò of the Neuroscience Institute of Torino in Turin, Italy. The study did not address whether quitting upon diagnosis improves ALS outcomes.
The study data was drawn from the Piemonte and Valle d’Aosta Registry for ALS, which has been collecting information on ALS patients in the region since 1995 (Chiò et al., 2014). All patients diagnosed between 2007 and 2011 were included in the current study. Smoking status was classified as current smoker, i.e. smoker at the time of symptom onset, former smoker (prior to symptom onset), or never smoker. In order to assess the potential survival impact of respiratory diseases frequently associated with smoking on ALS prognosis, pulmonary function tests were performed at diagnosis. These included forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and the ratio of the two, which is used to determine severity of the respiratory disease chronic obstructive pulmonary disorder (COPD).
Complete data, including demographic and clinical characteristics, were available for 650 patients, including 19% current smokers, 28% former smokers, and 53% who had never smoked. 44 patients (7%) met the criteria for COPD. In 81% of patients, data was available on the patients’ genetic status with respect to common ALS mutations, including SOD1, TDP-43, and expanded repeats in C9ORF72. Kaplan-Meier analysis of median survival for each group revealed that current smokers lived on average 1.9 years after symptoms onset, compared to 2.3 years for former smokers and 2.7 years for never smokers (p=0.001). Smoking status was also correlated to the average monthly decrease in scores on the revised ALS Functional Rating Scale (ALSFRS-R). The effect of smoking was seen in both men and women, and was unaffected by age at onset, site of onset, or C9ORF72 gene status.
Despite the likely effects of smoking on respiratory function, the trend was still significant after correcting for FVC, FEV1 and COPD status. In addition, Cox multivariable analysis revealed COPD as an independent factor that negatively impacts ALS survival.
“We know smoking increases the risk of ALS,” Chiò said, with the best estimates suggesting that smokers are up to 44% more likely to develop the disease (Alonso et al., 2010; Wang et al., 2011). But why smoking is a risk factor is unknown. Epigenetic modifications have been shown to occur in smokers (Ambatipudi et al., 2016), and may contribute to differences in prognosis between ALS patients who are smokers and those who have never smoked, Chiò speculated. Epigenetics could also potentially explain the intermediate survival effect on former smokers, since such modifications may revert over time, however, Chiò emphasized that there is no substantial evidence to support or refute this idea.
Considerable evidence suggests a protective effect for smoking on development of Parkinson’s disease (Chen et al., 2010; Wirdefelt et al., 2011), but it is unclear whether there is a direct benefit conferred by substances in cigarette smoke, or rather personality changes that occur prior to onset of PD (“premorbid personality”) that affect smoking behavior, as some studies suggest (Poewe et al., 1983). In ALS, Chiò said, unlike in PD, there has as yet been no study of premorbid personality traits that might explain smoking’s link to risk of developing ALS.
“The study adds to our understanding of the connection between smoking and ALS,” commented Bjorn Oskarsson of the University of California, Davis, who was not involved in the study. He added that while the analysis showed that COPD at diagnosis could not explain much of the effect on survival, there may be other factors, including risk for pneumonia, and even heart attack and stroke, which could partially account for the effect of smoking on survival and were not captured in the analysis. A direct effect of smoking on ALS is also possible.
Chiò was not able to ascertain whether quitting smoking at the time of diagnosis offers any survival benefit, as the group of patients who have done so is too small for analysis. “We recommend it to all our patients who smoke,” he said, and most take the advice. But not all, he added, noting that some say they prefer to maintain a habit that brings them pleasure. Oskarsson agreed, and added that although he recommends that patients discontinue smoking upon diagnosis, this study does not address whether quitting improves prognosis.
Calvo A, Canosa A, Bertuzzo D, Cugnasco P, Solero L, Clerico M, De Mercanti S, Bersano E, Cammarosano S, Ilardi A, Manera U, Moglia C, Marinou K, Bottacchi E, Pisano F, Mora G, Mazzini L, Chiò A. Influence of cigarette smoking on ALS outcome: a population-based study. J Neurol Neurosurg Psychiatry. 2016 Sep 21. ePub ahead of print. [Pubmed]
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