Effect of Swedish snuff on preterm birth

Är det farligt att snusa
vad vet vi idag?
Mats Wallström
Avd för käkkirurgi
3000 kemiska produkter
• Tobak
• Vatten
• Na-karbonate-Högt pH
• Salt
• Fuktämnen
• Smakämnen
• Nikotin
40-45%
45-60%
1.5-3.5%
1.5-3.5%
1.5-3.5%
< 1%
Nikotin-alkaloid
CNS-belöning
Autonoma
Ganglier
Adremalin Parasymp
VasomotoriskCenter
Binjurebarken
Adrenalin Ökad metabol effekt
Puls,O2, Arrth, Vasocon
Baroreceptorer
SkelettMuskelaturen.
Stim Blockad
Bolinder-1997
Tobaksspecifika nitrosaminer
23 st i snus
• TSNA Tobacco-specific N-nitrosamine
• NNN N-nitrosonornicotine
• NNK 4 (metylnitrosamino)-1-(3pyridyl)1-butanone
Cancerframkallande
pH är den avgörande faktor hur mycket
nikotin sommabsorberas genom slemhinnan
och med vilken hastighet
Tomar SL. Tob Control 1997 6(3):219-25.
Snuskonsumption
män %
kvinnor %
Sverige:
19
4
Norge:
11
2
USA
15?
2
Djurexperiment
Rat incisors
Lip canal filled
with snuff 10 h
per day
Surgically
created canal
in the lip
Snuff-induced lesions - A Clinical
and Experimental Study - Hirsch1983
Djurexperiment
Johansson Sl et al. Snuff-induced carcinogenisis:
Effect of snuff initiated with 4-nitrouinoline N-Oxide
Cancer research-1989
Larsson PA et al. Snuff tumorigenisis: effects of longterm snuff administrat after initiation with 4NQO and
Herpes simplex virus type 1. J Oral Pathol Med -1989
Park NH et al. Role of Virus in Oral CancinogenesisNIH publication-1993
Grasso. Smokeless Tobacco and Oral Cancer:
An Assessment of Evidence Derived from Laboratory
Animals. Food and Chem Toxicol - 1998
Effekter på kroppen
Lokala effekter
Slemhinnan
Parodontala
Karies
Allmänna
Vanebildande
Hjärta-kärl
Graviditet
Spädbarnsdöd
Diabetes
Cancer
Snus läsioner
1963 – Pindborg undersökte 12 kroniska
snusare. Inga dysplasier.
1976 – Axéll delade in snusläsionen i 4
olika kliniska grader.
1982 – Hirsch redogjorde för 50 kroniska
snusare. Lätt dysplasi i alla kliniska grader
1991 – Andersson biopserade 250 snusare.
Några dysplasier i materialet
2011 – Wallström undersökte reversibiliteten
efter 6 månaders snusstopp att läsionen
inte läkte ut.
Tandlossning
Gingivala retraktioner:
1965 - van Wyk noterad att angränsande
tänder hade gingival retraktioner.
1980 - Modeér en ökad gingivit trots
plackkontroll
1989 – Andersson fann att 23% vs 3% hade
gingiva retraktioner beroende på förpacknings
form
Tandlossning
2004, 2006, 2006. 3 svenska studier fann ingen
signifikant ökad bennedbrytning hos snusare
jmf med icke tobaksnyttjare
2005. Bland 12 000 snusare I en amerikansk studie
var det dubbelt så vanligt med avancerad tandlossning
jmf med icke tobaksnyttjare
Karies
USA
4 studier hos unga individer. En studie visade på positiv
korrelation mellan snusning-karies och gingivit.
Skandinavien
Hirsch-91
Snusare hade ett significant högre DMFT
Cancer
Cancer
The working group stated that
“there is sufficient evidence in
humans to establish
smokeless tobacco as
carcinogenic, i.e. smokeless
tobacco causes cancer of the
oral cavity and pancreas.”
Clinical data of the 15 patients
with snuff induced oral cancer
Case
G.S.
N.L.
F.A.
K-G.B.
S.W.
D.D.
B.W.
F.N.
S.E.
S.L.
H.G.
S-Å.G.
X.X.
R.F.
X.X.
Age
75
91
72
75
50
85
79
89
52
67
78
81
74
84
67
Location
Upper jaw
Upper jaw
Upper jaw
Upper jaw
Upper jaw
Upper jaw
Lower jaw
Upper jaw
Upper jaw
Upper jaw
Lower jaw
Upper jaw
Upper jaw
Upper jaw
Upper jaw
Snuff use (years)
61
70
42
71
8
20
45
69
20
18
66
40
30
49
Smoking
No
Not for 70 years
No
No
Prior to snuff use
No
Not for 30 years
No
Concomitant to snuff
Not for 18 years
No
No
No
No
Not for 48 years
ORAL CANCER IN SWEDISH SNUFF-DIPPERS Hirsch et al Submitted
Cancer
Years
Range
Mean age at time of diagnosis:
74,6
50-91
Median age at time of diagnosis:
75
Mean duration with the snuff habit:
43,5
Median duration with the snuff habit:
47
Mean age at start of snuff use:
30,8
Median age at start of snuff use:
31
8-71
4-65
Cancer
3 svenska studier
Schildt EB: Int J Cancer. 1998: Oral snuff, smoking habits and alcohol
consumption in relation to oral cancer in a Swedish case-control study.
410p/410c OR 0.7 CI 95% 0.4-1.1
Rosenqvist K: Use of Swedish moist snuff, smoking and alcohol consumption
in the aetiology of oral and oropharyngeal squamous cell carcinoma.
A population-based case-control study in southern Sweden.
135p/320c
OR 1.1 CI 95% 0.5-25
Lewin F: Cancer. 1998: Smoking tobacco, oral snuff, and alcohol in
the etiology of squamous cell carcinoma of the head and neck:
a population-based case-referent study in Sweden.
605p/756c
RR 4.7 for ever users CI 95% 1.6-13.8
Cancer
2 svenska studier
Roosaar A et al. 2008 Int J Cancer Cancer and mortality among users and
nonusers of snus. Cohort 9976p 1973-2002.
Ökad cancerrisk oral och orofaryngeal RR 3.1 CI 95% 1.5-6.6
Ökad dödlighet: HR 1.10 CI 95% 1.01-1.21
Luo J et al. 2007 Lancet: Oral use of Swedish moist snuff (snus) and risk for
cancer of the mouth, lung, and pancreas in male construction workers: a
retrospective cohort study. 279897p
Pancreascancer RR 2.0 CI 95% 1.2-3.3
1 norsk studie
Boffetta P. 2005- In J Cancer . Smokeless tobacco use and risk of cancer of
the pancreas and other organs. Cohort 10136p
Pancreas cancer: RR 1.67 CI 95% 1.12-2.5
Long-term use of smokeless of
smokeless tobacco
Målsättning:
Öka kunskapen om snusningens hälsoeffekter,
Främst avseende risken för hjärt- och
kärlsjukdom
Bolinder G, Avhandling -97
Long-term use of smokeless of
smokeless tobacco
Material och metod:
1971-78 hälsoundersöktes totalt 135 036
byggnadsarbetare av bygghälsan.
- 32 546 hade aldrig nyttjat tobak
- 14 983 rökte > 15cig/dag
- 6 297 var enbart snusare
Bolinder G, Avhandling -97
Long-term use of smokeless of
smokeless tobacco
1. Symptom, sjukfrånvaro och förtidspensionering hos snusare
jämfört med rökare och tobaksfria I byggbranschen.
2. Ökad risk för död I hjärt-och kärl sjukdom hos snusare.
3. Fysisk arbetsförmåga vid långvarigt snusbruk.
4. Metabola riskfaktorer för hjärt-kärlsjukdom vid snusning.
5. Snusning och åderförkalkning-ultraljudsundersökning av
intima-media-tjocklek I arteria carotis.
6. 24-timmars blodtrycksmätning hos snusare, rökare och
icke-tobaksbrukare.
Bolinder G, Avhandling -97
Long-term use of smokeless of
smokeless tobacco
En av slutsatserna:
50% av alla dödsfall beror på hjärtkärl –sjukdommar.
Vid en måttlig riskökning med en relativ risk på 1.4 och
då 20% av svenska män snusar betyder det att ca 1300
dödsfall om året kan tillskrivas snusningen.
Bolinder G, Avhandling -97
Hjärt-kärlsjukdomar
Scandinavien
Cohort studie
Bolinder-94
OR
CI
34-54år Angina-typ
Stroke
H-K död
2.0
1.9
2.1
1.49-2.9
0.6-5.7
1.5-2.9
55-64år Angina
Stroke
H-K död
1.2
1.2
1.0
1.0-1.5
0.7-1.8
1.0-1.4
Fall-kontroll studier
MONICA 2 studier som inte visade på någon ökad risk för snusare att få
hjärtinfarkt jmf med icke-snusare
Hjärt-kärlsjukdomar
Kliniska epidemiologiska studier fokuserar på hjärt-kärlsjukdommar,
Hjärtinfarkt, aterioskleros, stroke, högt blodtryck och metabola syndrom.
Boffetta P, Straif K 2009 Lancet. Use of smokeless tobacco and risk of
myocardial infarction and stroke: systematic review with meta-analysis.
Dödlig hjärtinfarkt RR 1.13 95% CI 1.06-1.21 Dödlig stroke 1.40 1.281.54
Hergens 2007 J I Medicin Long-term use of Swedish moist snuff and the
risk of myocardial infarction amongst men.
Dödlig myocard RR 1.96 95% CI 1.08-3.58
Henley 2005 Cancer Causes Contro. lTwo large prospective studies of
mortality among men who use snuff or chewing tobacco.
Ökad dödlighet HR 1.17 1.11-1.23, HR 1.18 1.08-1.29
Metabolt syndrom/ diabetes
Norberg, 2006, Scand J Public Health. Contribution of Swedish moist
snuff to the metabolic syndrome: a wolf in sheep's clothing?
Longitudinell cohort 16492p efter 10 år.
Metsy bland snusare OR 1.6 (1.26-2.15)
höga triglycerider OR 1.6 (1.30-1.95), obesitas 1.7 (1.36-2.18)
Persson, 2000 J Intern Med.. Cigarette smoking, oral moist snuff use and
glucose intolerance. J Intern Med. 2000
Cross sectional study 3128 män där 52% hade en ärftlig belastning
Mer än 3 dosor/vecka OR 2.7 (1.3-5.5)
Eliasson M, Rodu B. 2004 J Intern Med. Influence of smoking and snus on
the prevalence and incidence of type 2 diabetes amongst men: the
northern Sweden MONICA study.
Snusare OR 1.34 (0.65-2.)7 and Har snusat OR 1.18 (0.48-2.9)
Effect of Swedish snuff on preterm birth
OBJECTIVE:
To compare the effects of Swedish snuff and cigarette
smoking on risks of preterm birth.
DESIGN:
Population-based cohort study.
All live, singleton births in Sweden 1999-2006.
MAIN OUTCOME MEASURES:
Very (<32 weeks) and
moderately (32-36 weeks) preterm birth.
Wikström AK et al 2010. BJOG 2010 Jul;117(8):1005-10. Epub 2010 May 11.
Effect of Swedish snuff on preterm birth
METHODS:
Odds ratios (OR) with 95% confidence intervals (CI) were
used to estimate relative risks for preterm birth in
snuff users (n = 7607),
light smokers (1-9 cigarettes/day; n = 41 436)
heavy smokers (ten or more cigarettes/day; n = 16 951)
non-tobacco users (n = 503 957) as reference.
Wikström AK et al 2010. BJOG 2010 Jul;117(8):1005-10. Epub 2010 May 11.
Effect of Swedish snuff on preterm birth
RESULTS:
Compared with non-tobacco users,
snuff users had increased risks of both
very (adjusted OR 1.38; 95% CI 1.04-1.83) and
moderately (adjusted OR 1.25; 95% CI 1.12-1.40) preterm
birth.
Wikström AK et al 2010. BJOG 2010 Jul;117(8):1005-10. Epub 2010 May 11.
Effect of Swedish snuff on preterm birth
CONCLUSIONS:
The use of Swedish snuff was
associated with increased risks of very
and moderately preterm birth with both
spontaneous and induced onsets.
Swedish snuff is not a safe alternative to
cigarette smoking during pregnancy.
Wikström AK et al 2010. BJOG 2010 Jul;117(8):1005-10. Epub 2010 May 11.
Maternal use of Swedish snuff (snus)
and risk of stillbirth.
BACKGROUND:
Swedish snuff has been discussed internationally as a safer
alternative to tobacco smoking. International cigarette
manufacturers are promoting new snuff products, and the use of
Swedish snuff is increasing, especially among women of
childbearing age. The effect of Swedish snuff on pregnancy
complications is unknown.
Maternal use of Swedish snuff and risk
of stillbirth.
METHODS:
In this population-based cohort study, we estimated the risk of
stillbirth in
snuff users (n = 7629),
light smokers (1-9 cigarettes/day; n = 41,488), and
heavy smokers (≥10 cigarettes/day; n = 17,014),
using nontobacco users (n = 504,531) as reference.
Maternal use of Swedish snuff and risk
of stillbirth.
RESULTS:
Compared with nontobacco users,
snuff users had an increased risk of stillbirth
(adjusted OR= 1.6 [95% CI= 1.1-2.3]);
the risk was higher for preterm (<37 weeks) stillbirth
(2.1 [1.3-3.4]).
For light smokers, the adjusted odds ratio of stillbirth
was 1.4 (1.2-1.7) and the corresponding risk for
heavy smokers was 2.4 (2.0-3.0).
Wikstrom AK Epidermiology 2010 Nov;21(6):772-8.
Maternal use of Swedish snuff and risk
of stillbirth.
CONCLUSIONS:
Use of Swedish snuff during pregnancy was associated with a
higher risk of stillbirth. The mechanism behind this increased
risk seems to differ from the underlying mechanism in
smokers. Swedish snuff does not appear to be a safe
alternative to cigarette smoking during pregnancy.
Wikstrom AK Epidermiology 2010 Nov;21(6):772-8.
Harm reduction
Definition:
A product is harm reducing if it lowers total
tobacco – related mortality and morbidity
Even though use of that product may involve
Continued exposure to tobacco toxicants
Clearing the Smoke., Assessing the Scienece Base for Tobacco Harm Reduction
Interventionsstudier
Farmakologiska studier:
Buprion - 1 studie
NRT - 2 studie (tuggimmi)
NRT – 3 studier (plåster)
CI 95%
OR 1.0 0.23-4.37
OR 0.98 0.59-1.63
OR 1.16 0.88-1.54
Betendevetenskapliga studier:
Ind/grupp – 8 studier
OR 2.42 1.79-3.24
Cochrane 2007