Journal of Neurology

, 256:577 | Cite as

Smoking is associated with progressive disease course and increased progression in clinical disability in a prospective cohort of people with multiple sclerosis

  • Fotini Pittas
  • Anne-Louise Ponsonby
  • Ingrid A. F. van der Mei
  • Bruce V. Taylor
  • Leigh Blizzard
  • Patricia Groom
  • Obioha C. Ukoumunne
  • Terry Dwyer
ORIGINAL COMMUNICATION

Abstract

Background

Multiple sclerosis has a variable disease course. The contribution of modifiable lifestyle factors to disease course has not been well studied, although one cohort has reported that smoking is associated with conversion to secondary progressive MS course and another that smoking is not.

Methods

We conducted a prospective cohort study of people with MS in Southern Tasmania from 2002 to 2004 with 78 % (203/259) of eligible participating and 198 with one or more reviews and confirmed MS. The cohort had a high retention rate (90 % (183/203)). The median follow- up time was 909 days. Smoking data were collected at baseline and six-monthly reviews. Clinical disability assessments were conducted annually in conjunction with a real time clinical notification system for relapses. A repeated measures analysis and other statistical methods were used.

Results

Cumulative pack-years (p-y) smoked after cohort entry was associated with an increase in longitudinal MSSS (p < 0.001). Relative to the 0 pack years (p-y) category (in the year prior to the MSSS measure) those in the 0 to 1 p-y category had an adjusted mean difference in MSSS of 0.34 (95 % CI 0.28, 0.66); those in the 1 to 2 p-y category had a 0.41 (95 % CI −0.03, 0.85) increase; and those in the 2 or more p-y category had a 0.99 (95 % CI 0.41, 1.58) increase in MSSS. Similar results were found using a variety of statistical approaches or EDSS as a clinical outcome. Smoking during the cohort period was not associated with relapse (cumulative pack years smoked after cohort entry, HR 0.94 (0.69, 1.26) per pack year).

Conclusion

A better understanding of the mechanisms underlying smoking and multiple sclerosis, particularly progressive forms of the disease, may provide new insights for the eventual goal of better treatment and prevention of multiple sclerosis.

Key words

multiple sclerosis tobacco smoke prospective cohort repeated measures disability 

Abbreviations

25(OH) D

25 hydroxy vitamin D

AOR

adjusted odds ratio

CI

confidence interval

DNA

deoxyribonucleic acid

EDSS

expanded disability status scale

HR

hazard ratio

OR

odds ratio

MRI

magnetic resonance imaging

MS

multiple sclerosis

MSSS

multiple sclerosis severity score

PP

primary progressive course

p-y

pack-years

RR

relapsing remitting course

SP

secondary progressive course

UVR

ultraviolet radiation

References

  1. 1.
    Hernan MA, Jick SS, Logroscino G, Olek MJ, Ascherio A, Jick H (2005) Cigarette smoking and the progression of multiple sclerosis. Brain 128(Pt 6): 1461–1465CrossRefPubMedGoogle Scholar
  2. 2.
    Koch M, van Harten A, Uyttenboogaart M, De Keyser J (2007) Cigarette smoking and progression in multiple sclerosis. Neurology 69(15):1515–1520CrossRefPubMedGoogle Scholar
  3. 3.
    Emre M, de Decker C (1987) Nicotine and CNS. Neurology 37(12):1887–1888PubMedGoogle Scholar
  4. 4.
    Emre M, de Decker C (1992) Effects of cigarette smoking on motor functions in patients with multiple sclerosis. Arch Neurol 49(12):1243–1247PubMedGoogle Scholar
  5. 5.
    Pekmezovic T, Drulovic J, Milenkovic M, Jarebinski M, Stojsavljevic N, Mesaros S, et al. (2006) Lifestyle factors and multiple sclerosis: A case-control study in Belgrade. Neuroepidemiology 27(4):212–216CrossRefPubMedGoogle Scholar
  6. 6.
    Ghadirian P, Dadgostar B, Azani R, Maisonneuve P (2001) A case control study of the association between socio-demographic, lifestyle and medical history factors and multiple sclerosis. Can J Public Health 92:281–285PubMedGoogle Scholar
  7. 7.
    Zorzon M, Zivadinov R, Nasuelli D, Dolfini P, Bosco A, Bratina A, et al. (2003) Risk factors for multiple sclerosis: a case-control study. Neurol Sci 24:242–247CrossRefPubMedGoogle Scholar
  8. 8.
    Riise T, Nortvedt MW, Ascherio A (2003) Smoking is a risk factor for multiple sclerosis. Neurology 61(8):1122–1124PubMedGoogle Scholar
  9. 9.
    Hernan MA, Olek MJ, Ascherio A (2001) Cigarette smoking and incidence of multiple sclerosis. Am J Epidemiol 154(1):69–74CrossRefPubMedGoogle Scholar
  10. 10.
    van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Simmons R, Taylor BV, et al. (2003) Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ (Clinical research ed.) 327(7410):316CrossRefPubMedGoogle Scholar
  11. 11.
    White V, Hill D, Siapush M, Bobevsky I (2003) How has the prevalence of cigarette smoking changed among Australian adults? Trends in smoking prevalence between 1980 and 2001. Tobacco Control 12(Suppl II):ii67–ii74PubMedGoogle Scholar
  12. 12.
    Laaksonen M, Luoto R, Helakorpi S, Uutela A (2002) Associations between Health-Related Behaviors: A 7-Year Follow-up of Adults. Prev Med 34(2):162–170CrossRefPubMedGoogle Scholar
  13. 13.
    Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231CrossRefPubMedGoogle Scholar
  14. 14.
    McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50(1):121–127CrossRefPubMedGoogle Scholar
  15. 15.
    van der Mei IA, Blizzard L, Ponsonby AL, Dwyer T (2006) Validity and reliability of adult recall of past sun exposure in a case-control study of multiple sclerosis. Cancer Epidemiol Biomarkers Prev 15(8):1538–1544CrossRefPubMedGoogle Scholar
  16. 16.
    Dwyer T, Muller HK, Blizzard L, Ashbolt R, Phillips G (1998) The use of spectrophotometry to estimate melanin density in Caucasians. Cancer Epidemiol Biomarkers Prev 7(3):203–206PubMedGoogle Scholar
  17. 17.
    Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, et al. (2005) Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology 12; 64(7):1144–1151PubMedGoogle Scholar
  18. 18.
    PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group (1998) Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/ remitting multiple sclerosis. Lancet 352(9139):1498–1504Google Scholar
  19. 19.
    Goldstein H (2003) Multilevel Statistical Models 3rd ed. London: Hodder ArnoldGoogle Scholar
  20. 20.
    Petzold A, Eikelenboom MI, Keir G, et al. (2006) The new global multiple sclerosis severity score (MSSS) correlates with axonal but not glial biomarkers. Mult Scler 12(3):325–328CrossRefPubMedGoogle Scholar
  21. 21.
    Kleinbaum DG, Klein M (2005) Survival Analysis: a self-learning text. 2nd Ed. New York: Springer, pp 331, 390Google Scholar
  22. 22.
    Perneger TV (1998) What’s wrong with Bonferroni adjustments. BMJ 316(7139):1236–1238PubMedGoogle Scholar
  23. 23.
    Hawkes CH (2007) Smoking is a risk factor for multiple sclerosis: a metanalysis. Multiple sclerosis (Houndmills, Basingstoke, England) 13(5):610–615CrossRefPubMedGoogle Scholar
  24. 24.
    Costenbader KH, Karlson EW (2006) Cigarette smoking and autoimmune disease: what can we learn from epidemiology? Lupus 15(11):737–745CrossRefPubMedGoogle Scholar
  25. 25.
    Charil A, Filippi M (2007) Inflammatory demyelination and neurodegeneration in early multiple sclerosis. J Neurol Sci 259(1–2):7–15CrossRefPubMedGoogle Scholar
  26. 26.
    Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, et al. (1999) Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol 46(3):296–304CrossRefPubMedGoogle Scholar
  27. 27.
    Inglese M, Benedetti B, Filippi M (2005) The relation between MRI measures of inflammation and neurodegeneration in multiple sclerosis. J Neurol Sci 233(1–2):15–29CrossRefPubMedGoogle Scholar
  28. 28.
    Filippi M, Bozzali M, Rovaris M, Gonen O, Kesavadas C, Ghezzi A, et al. (2003) Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 126(Pt 2):433–437CrossRefPubMedGoogle Scholar
  29. 29.
    Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Bruck W (2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125 (Pt 10):2202–2212CrossRefPubMedGoogle Scholar
  30. 30.
    Inglese M, Mancardi GL, Pagani E, Rocca MA, Murialdo A, Saccardi R, et al. (2004) Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation. J Neurol Neurosurg Psychiatry 75(4):643–644PubMedGoogle Scholar
  31. 31.
    Trapp BD, Bo L, Mork S, Chang A (1999) Pathogenesis of tissue injury in MS lesions. J Neuroimmunol 98(1):49–56CrossRefPubMedGoogle Scholar
  32. 32.
    Smith KJ, Kapoor R, Hall SM, Davies M (2001) Electrically active axons degenerate when exposed to nitric oxide. Ann Neurol 49(4):470–476CrossRefPubMedGoogle Scholar
  33. 33.
    Kapoor R, Davies M, Blaker PA, Hall SM, Smith KJ (2003) Blockers of sodium and calcium entry protect axons from nitric oxide-mediated degeneration. Ann Neurol 53(2):174–180CrossRefPubMedGoogle Scholar
  34. 34.
    Suemaru K, Kawasaki H, Gomita Y, Tanizaki Y (1997) Involvement of nitric oxide in development of tailtremor induced by repeated nicotine administration in rats. Eur J Pharmacol 335(2–3):139–143CrossRefPubMedGoogle Scholar
  35. 35.
    Lee TJ, Zhang W, Sarwinski S (2000) Presynaptic beta(2)-adrenoceptors mediate nicotine-induced NOergic neurogenic dilation in porcine basilar arteries. Am J Physiol 279(2):H808–H816Google Scholar
  36. 36.
    Tonnessen BH, Severson SR, Hurt RD, Miller VM (2000) Modulation of nitric-oxide synthase by nicotine. J Pharmacol Exp Therapeutics 295(2): 601–606Google Scholar
  37. 37.
    Jack C, Antel J, Bruck W, Kuhlmann T (2007) Contrasting potential of nitric oxide and peroxynitrite to mediate oligodendrocyte injury in multiple sclerosis. Glia 55(9):926–934CrossRefPubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2009

Authors and Affiliations

  • Fotini Pittas
    • 1
  • Anne-Louise Ponsonby
    • 1
    • 2
  • Ingrid A. F. van der Mei
    • 1
  • Bruce V. Taylor
    • 1
  • Leigh Blizzard
    • 1
  • Patricia Groom
    • 1
  • Obioha C. Ukoumunne
    • 2
    • 3
  • Terry Dwyer
    • 1
    • 2
  1. 1.The Menzies Research InstituteUniversity of TasmaniaTasmaniaUSA
  2. 2.Murdoch Childrens Research InstituteRoyal Children’s HospitalMelbourneUSA
  3. 3.Dept. of PaediatricsUniversity of MelbourneMelbourneUSA

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