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Cigarettes in the pathogenesis of asthma and COPD

Cigarettes in the pathogenesis of asthma and COPD. John Jay Shannon, M.D. Divisions of Pulmonary and Critical Care Medicine John H. Stroger, Jr. Hospital of Cook County. John Jay Shannon, M.D. Disclosure of Conflict of Interest Information I have no existing conflict

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Cigarettes in the pathogenesis of asthma and COPD

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  1. Cigarettes in the pathogenesis of asthma and COPD John Jay Shannon, M.D. Divisions of Pulmonary and Critical Care Medicine John H. Stroger, Jr. Hospital of Cook County

  2. John Jay Shannon, M.D. Disclosure of Conflict of Interest Information I have no existing conflict of information to disclose Disclosure information stated above is current as of March 15, 2007

  3. Early onset History of atopy Less smoking More wheezing More specific triggers Pronounced reversibility (lab or subjective) Greater response to corticosteroids Later onset Less atopy Heavy smoking hx Less wheezing Fewer specific triggers Less clear reversibility Less response to corticosteroids Asthma or COPD?

  4. Thomson Eur Respir J 2004; 24: 822

  5. Roles of tobacco exposure in asthma Tobacco exposure leads to… • Increased likelihood of development of asthma • Increased likelihood of persistence of asthma as a child grows • Increased likelihood of severe disease • Reduced effectiveness of most important medicines

  6. Effects of prenatal maternal smoking • Cohort of >18, 000 from UK • Incidence of wheezing illness by age 33 was 43% • Maternal smoking during pregnancy strongly associated with wheezing after age 16 • Current smoking additionally added to the risk Strachan BMJ 1999;312:1195

  7. Tobacco leads tothe development of asthma • Prospective study of 2609 children from 4th-7th grade • Regular smoking=7 cigs/day in week before and 300 cigs/year in year before annual interview • Regular smokers had RR 3.9 (95% CI 1.7-8.5) of developing asthma (higher if atopic) Gilliland AJRCCM 2006;175:1094

  8. Tobacco leads tothe development of asthma • Case control study of adults in Scotland, 39-45 years old • 102 adult-onset wheezers • Adult onset wheeze associated with: • Lower SES • Current smoking (RR 2.0) • Atopy • Family history of atopy Gilliland AJRCCM 2006;175:1094

  9. Tobacco leads to persistent asthma • Increased RR of exacerbations • Cassino AJRCCM 1999;159:1773 • Increased frequency and severity of symptoms • Sioux ERJ 2000;15:470

  10. Tobacco exposure increases the likelihood of severe asthma • Prospective cohort study of 451 nonsmoking adults with asthma • Increasing exposure to ETS was associated with • Worse quality of life (general and asthma-specific) • More urgent and ER visits Eisner AJRCCM 1998;158:170

  11. Tobacco exposure increases asthma exacerbations RR for asthma exacerbations was 1.8 (1.4-2.2) for those exposed –either by self-report or cotinine levels Chilmonczyk NEJM 1993;328:1665

  12. Increased loss of FEV1 in Asthma Male non-smokers P <0.001 Height-adjusted FEV1 (litres) No asthma (n= 5480) Asthma (n= 314) Age (years) Lange P et al, NEJM 1998

  13. Smoking reduces effectiveness of corticosteroids 14 smokers 10 ex-smokers 26 never smokers All with asthma and bronchodilator response Two weeks of oral prednisone 40 mg daily Active smokers: no change in physiology or asthma control score; ex-smokers in between Chaudhuri Am J Respir Crit Care Med 2003; 168:1308

  14. Smoking Modulates Outcomes of Glucocorticoid Therapy in Asthma (SMOG) • randomized, double-dummy, crossover trial of treatment with an ICS or an LTRA. • primary outcome: change in pre-bronchodilator FEV1 • Non-smokers • increases in FEV1 (170ml) • FEV1% predicted (5%) • PEF (28 L/m) • PC20 (0.63) • smokers no such effects (except for daily AM PEF)   Wechsler (ACRN) ATS 2006 (under review)

  15. -no significant changes were seen between smokers and nonsmokers in effects of ICS on airway hyper-responsiveness or changes in sputum eosinophils Lazarus AJRCCM 2007 Epub

  16. Exposure/reduction of environmental tobacco smoke • Few studies directly analyzing this as main study question; small in size, varied methodologies • No clear effective strategy or outcomes • Exposure of asthmaticchildren: household ETS proportions: • Baltimore1 69% • Chicago/CHIRAH2 49% • Chicago/Sinai3 11-59% (5 comm.) • 1Eggleston Ann All Asthma Immunol 2005;95:518 • 2Kumar 2007 (in preparation)3Whitman 2004

  17. Effects of smoking cessation-asthma • 10 quitters compared to 10 continued smokers • within 3 weeks quitters had • improved FEV1 • Improved asthma control score • decreased sputum neutrophils Chaudhuri AJRCCM 2006;174:127

  18. Roles of tobacco exposure in chronic obstructive pulmonary disease Tobacco ….. • exposure in utero leads to impaired lung development • is the leading cause of COPD in the developed world • continued use once a diagnosis is made is associated with earlier death

  19. Tobacco use is associated with COPD…. • NHANES III-COPD seen in • 12.5% current smokers • 9.4% former smokers • 5.8% lifelong non-smokers • Nurses Health Study (n>74,000) • RR for chronic bronchitis 2.85 in smokers

  20. …and mortality.Overall risk to smokers and never-smokers Never smoked 100 regularly 80 80 80 Current cigarette 59 smokers 60 % Alive 7.5 years 40 33 33 20 12 0 40 55 70 85 100 Age Doll et al BMJ 1994

  21. Causes of smoking-related mortality Cigarette smoking causes an estimated 438,000 deaths, or about 1 of every 5 deaths, each year. • lung cancer (124,000) • heart disease (108,000) and • chronic lung diseases (90,000) …..are responsible for the largest number of smoking-related deaths CDC. MMWR 2005: 54(25) 625

  22. Asthma Short-term changes in airway caliber Reversible airflow obstruction Hyperresponsiveness Airway inflammation: eosinophils, lymphocytes COPD Long-term changes in airway caliber Less-reversible airflow obstruction No (or infrequent) hyperresponsiveness Airway inflammation: neutrophils Key Points of Definition Magnussen H, et al. Clin Exp Allergy. 1998;28(suppl 5):187-194.

  23. CHANGE IN FEV1 BY SMOKING STATUS 2.9 2.8 Sustained quitters 2.7 Post bronchodilator FEV1 Continuing smokers 2.6 2.5 2.4 5 Screen 1 2 3 4 Years of follow-up JAMA 1994;272(19):1497-505 depqumch.tc

  24. Effect of inhaled corticosteroids in post-bronchodilator FEV1 (FEV<50% pred) Sutherland Thorax 2003;58:937

  25. Effect of inhaled corticosteroids on exacerbations in COPD Sin DD JAMA 2003;290:2301

  26. Manage Stable COPD Key Points • Regular treatment with inhaled glucocorticoids should only be prescribed for symptomatic COPD patients with: • documented spirometric response or • those with an FEV1 < 50% predicted and repeated exacerbations (Evidence B).

  27. Smoking decreases effects of inhaled corticosteroids in COPD • In ISOLDE, current smoking was associated with a lower FEV1 response to inhaled corticosteroids: +35 ml vs. +74 ml (p<0.01) Burge Thorax 2003;58:654

  28. Cessation: Behavioral Intervention Studies • Pregnancy, acute illness is a good time to intervene • Brief counseling works better than simple advice to quit • Counseling with self-help materials offered by a trained clinician can improve cessation rates by 30% to 70% • Intervention works best for moderate (<20 cigarettes/day) smokers

  29. Cost-effectiveness of Smoking Cessation Intervention JAMA 1997;278:1759

  30. Cigarette consumption in the modern era MacKenzie NEJM 1994; 330: 975

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