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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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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

of information to disclose

Disclosure information stated above is current as of March 15, 2007

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?

Thomson Eur Respir J 2004; 24: 822

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

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

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

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

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

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

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

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

Smoking reduces


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


Am J Respir Crit Care Med

2003; 168:1308

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)

-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

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:

    • Baltimore169%

    • Chicago/CHIRAH249%

    • Chicago/Sinai311-59% (5 comm.)

  • 1Eggleston Ann All Asthma Immunol 2005;95:518

  • 2Kumar 2007 (in preparation)3Whitman 2004

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

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

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

…and mortality.Overall risk to smokers and never-smokers

Never smoked






Current cigarette




% Alive

7.5 years













Doll et al BMJ 1994

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


Short-term changes in airway caliber

Reversible airflow obstruction


Airway inflammation: eosinophils, lymphocytes


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.




Sustained quitters


Post bronchodilator FEV1

Continuing smokers










Years of follow-up

JAMA 1994;272(19):1497-505

Effect of inhaled corticosteroids in post-bronchodilator FEV1 (FEV<50% pred)

Sutherland Thorax 2003;58:937

Effect of inhaled corticosteroids on exacerbations in COPD

Sin DD JAMA 2003;290:2301

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).

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

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

Cost-effectiveness of Smoking Cessation Intervention

JAMA 1997;278:1759

Cigarette consumption in the modern era

MacKenzie NEJM 1994; 330: 975

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