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S moking r eduction S moking cessation? H arm reduction????

S moking r eduction S moking cessation? H arm reduction????. Philip Tønnesen,M.D, Dr.med., Chair of Pulmonary dept. Gentofte Hospital, Denmark. Smoking Reduction. Defintions Efficacy Motivation stategies. The aim of this talk. The concept Controlled trials in Smoking reduction

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S moking r eduction S moking cessation? H arm reduction????

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  1. Smoking reduction Smoking cessation? Harm reduction???? Philip Tønnesen,M.D, Dr.med., Chair of Pulmonary dept. Gentofte Hospital, Denmark Turkey 2005

  2. Smoking Reduction • Defintions • Efficacy • Motivation stategies Turkey 2005

  3. The aim of this talk • The concept • Controlled trials in Smoking reduction • Asthmatics • Epidemiological studies • Conclusion • Questions Turkey 2005

  4. Cigarette smoking • Its a chronic relapsing disease • (ICD-10) Tobacco (nicotine) dependence • Motivation to quit and reduce fluctuates over time • Quit several times before permanent ex-smoker • Use NRT/Bupropion in higher doses and in longer periods • Retreat every 2-4 months Turkey 2005

  5. SWEDEN: ”Snus” is used by 10-15% ! Smoking reduction =Harm reduction Turkey 2005

  6. Smoking Reduction Rationale • Aimed for smokers low in motivation to quit • Induction of permanent change in smoking habit • Compensation not 100 per cent • Will not interfere with smoking cessation Turkey 2005

  7. P-cotinine vs. cig/day (N=272)(Benowitz, NEJM 1983) Turkey 2005

  8. Smoking Reduction • Tools: • Cigarettes  + NRT long-term use • Cigarettes  + Bupropion long-term use • Cigarettes  + Snuff • Less toxic cigarettes = product modification • Smoke-less tobacco Turkey 2005

  9. Smoking reduction (RCT)BMJ 2000, Bolliger et al • 400 heavy smokers • mean 29 cig/day • unwilling or unable to quit but try to reduce • nicotine inhalers/placebo for up to 18 months Turkey 2005

  10. Smoking reductionBMJ 2000, Bolliger et al Definition: “arbitrary” Cigarettes/day < 50 % of entry numbers plus any decrease in CO (1 ppm or >) Turkey 2005

  11. Smoking reductionBMJ 2000, Bolliger et al Reduction (sustained): Active Placebo 4 months 26 % 9 % (p<0.001) 1-year 13 % 4 % (p<0.002) 2-years 10 % 3 % (p<0.05) Turkey 2005

  12. Smoking reductionBMJ 2000, Bolliger et al Cessation (point): Active Placebo 4 months 7 % 2 % (p<0.05) 2-years 11 % 9 % (NS) Turkey 2005

  13. Reduction in Cig/day and CO= compensation Smoking level=100 % Turkey 2005

  14. Smoking reductionBMJ 2000, Bolliger et al • Conclusion • A modest reduction rate of 10 % • A cessation rate of 10 %!!!!!!! • This IS clinical important • Any harm reduction ? Turkey 2005

  15. OWN REDUCTION STUDY Turkey 2005

  16. Smoking reductionWennike, Tønnesen et al. Addiction 2003 • 411 smokers • 24 cigarettes/day • Motivation to reduce on 10-cm VAS: 9 • Motivation to quit on 10-cm VAS: 5 • Nicotine gum for up to 12 months Turkey 2005

  17. Smoking reductionWennike, Tønnesen et al. 2001 • Visits: 30-60 minutes • Week 0, 2, 6, 10, • Month 4, 6, 9, 12, 24. • After 6 months advised to quit Turkey 2005

  18. Randomization Week: 2, 6, 10 Month: 4, 6, 9, 12,24 4 mg: 140 50 Week: 2, 6, 10 Month:4, 6, 912,24 Placebo: 138 42 Stratification Screening Inclusion: Week: 2, 6, 10 Month:4, 6, 9, 12, 24 Randomization 2 mg: 65 32 Week: 2, 6, 10 Month:4, 6, 9, 12, 24 Placebo: 68 29 DESIGN 278 590 411 133 133 Turkey 2005

  19. Smoking reductionWennike, Tønnesen et al. Addiction 2003 Reduction (sustained): Active Placebo 4-months 14 % 5 % (p<0.002) 1-year 8.8 % 1.5 % (p<0.001) 2-years 6.3 % 0.5 % (p<0.001) Turkey 2005

  20. Smoking reductionWennike, Tønnesen et al, Addiction 2003 Cessation (point): Active Placebo 4 months 6.3 % 0.5 % (p<0.001) 1-year 11.2 % 3.9 % (p<0.005) 2-years 9.3 % 3.4% (p<0.01) (2-year sust.) 2.9 % 0.0 % (p<0.015) Turkey 2005

  21. Change in cig/day,CO,cotinine,thiocyanatein subjects on nicotine gum (% of base) 100 %= smoking level Turkey 2005

  22. Biomarkers after 2 years Absolute values Turkey 2005

  23. Motivation to quit Turkey 2005

  24. Motivation toreducein failures high motivation low Turkey 2005

  25. Conclusion This study shows that - by using the concept of smoking reduction in this group of smokers not motivated or able to quit smoking - nicotine gum combined with clinic visits increased both short-term and long-term smoking cessation (point prevalence). Turkey 2005

  26. Conclusion (A) • Modest cessation and reduction rate • Modest decease in biomarkes up to 1-year • Compensation occurs • Clinical relevance ? YES! • Harm reduction ? Turkey 2005

  27. Conclusion : Smoking reduction (B) • Reduction possible long-term • Reduction leads to cessation • Relative low efficacy and variable effect of NRT • Motivation to quit not decreased • Recruitment of new segment of smokers Turkey 2005

  28. Smoking reduction Pt.No.5 Turkey 2005

  29. Smoking reduction Pt.No.6 Turkey 2005

  30. Smoking reduction Pt.No.7 Turkey 2005

  31. Effect of smoking reduction with NRT (N=19 trials)% = reduction in CPD =cigarettes per day( ) = number of cigarettes 1 100 % 80 % 60 % 40 % 20 % 0 % 20 56% (23)5(23)6% 25% (8) 26% (8) 13% (3) NRT Control Turkey 2005

  32. ASTHMATICS AND SMOKING REDCUTION Turkey 2005

  33. 220 Asthmatics • 3 groups: • Quit smoking • Reduce to less than 7 cig/day • Unchanged smoking • 4 months follow-up • Asthma regulation • Smoking cessation and reduction Turkey 2005

  34. Cessation and reduction rates4 months Turkey 2005

  35. Biomarkers Turkey 2005

  36. PF in asthmatics Turkey 2005

  37. Bronchial reactivity Turkey 2005

  38. PC20-Histamine BPT for quitters(27), reducers(33) and smokers(50) (asthmatics) change in dose Tønnesen et al, 2005 Turkey 2005

  39. Conclusion : Smoking reduction • Reduction possible long-term • Reduction leads to cessation • Relative low efficacy • Motivation to quit not decreased • Recruitment of new segment of smokers Turkey 2005

  40. Conclusion : What have we learned? New studies • Long-term NRT needed ? • Nicotine gum and inhaler best choice • 2-year follow-up needed • Use point prevalence cessation • Some behavioural support is needed • The cut-off <7 cig/day or 50% ? • 7. Other biomarkers/meassures Turkey 2005

  41. Epidemiological studies Turkey 2005

  42. 1976-1981 Copenhagen study Population study Observation 5-years follow-up 3.791 smokers Nina Gotfredsen Preventive Medicine 2001;33:46-52 Predictors of smoking reduction/cessation Turkey 2005

  43. Men Reduction: 13 % 31(12) to 16(9) cig/d. Cessation: 9 % Women Reduction: 9 % 27(11) to 13(7) cig/d. Cessation: 7 % Predictors of smoking reduction/cessation (5-years) Turkey 2005

  44. Smoking reduction/cessation CIG/DAY Turkey 2005

  45. Smoking reduction/cessation CIG/DAYCIG Turkey 2005

  46. Predictors • Reduction Cessation • +25 cig/day 15-24 cig/day • FEV1< 50 % pred. FEV1< 50 % • Gender Male • Conclusion: Different subgroups of smokers who reduce or quit ! Turkey 2005

  47. B: Reduction and risk of admission COPDThorax 2002 Godtfredsen et al.[N =19,709, followed 14 yrs.] Adjusted hazard ratio, reducers: 0.93 (0.73-1.18)95% CI 832 reducers and 1454 quitters Turkey 2005

  48. Reduction and risk of admission COPDThorax 2002 Godtfredsen et al.Lowest baseline tertile FEV1 (N =1,354) Adjusted hazard ratio, reducers: 1,49 (1.00-2.23)95% CI - first 5 years: 1.15 (0.65-2.04) Turkey 2005

  49. Reduction and Mortality AM J Epidemiol 2002 Godtfredsen et al.Followed for 16 years (N =19,732) NS for reducers; All causes and Cancers Signif. Diff from smokers. Turkey 2005

  50. Reduction and Myocardial Infarction Godtfredsen et al.2003Hazard ratios Reducers: 1,15 (0.94-1.40); Quitters+light smokers sign. Diff. Turkey 2005

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