Lecture 22 - Smoking

Question 1

When did smoking peak in the USA?

Answer 1

1960s

Question 2

Epidemiology of smoking-related illness

Answer 2

Long latency between smoking and illness.

Question 3

Stages of smoking-related illness epidemiology
1)
2)
3)
4)

Answer 3

Stage 1 - Low smoking prevalence (under 20%). Little increase in smoking-related illness.
Stage 2 - Smoking over 50% of men, increasing in women. Some smoking-related illness, tobacco control initiatives not widespread.
Stage 3 - Smoking declines, but smoking-related deaths increase. Better smoking control policies.
Stage 4 - Increasing decline in smoking. Smoking-related deaths decline in males, Female deaths continue to rise

Question 4

Why 10-15% of adults still smoke in Australia
1)
2)
3)

Answer 4

1) Nicotine highly-addictive.
2) Nicotinic acetylcholine receptor mutants might confer greater susceptibility to nicotine addiction
3) Nicotine is an appetite suppressant. Some smoke to lose weight.

Question 5

Only treatment that reverses smoking-related damage

Answer 5

Cessation of smoking

Question 6

Leading preventable cause of death in the USA

Answer 6

Smoking

Question 7

Major causes of smoking-related deaths (order of highest to lowest)
1)
2)
3)
4)
5)
6)

Answer 7

1) Lung cancer
2) Ischemic heart diesease
3) COPD
4) Other diagnoses
5) Stroke
6) Other cancers

Question 8

Proportion of lung cancers that are due to smoking

Answer 8

80-90%

Question 9

Proportion of lung cancer diagnoses that die within one year of diagnosis

Answer 9

60%

Question 10

5-year survival rate of lung cancer diagnoses

Answer 10

15%

Question 11

What leads to lung cancer in cigarette smoke?
1)
2)
3)
4)

Answer 11

1) Over 50 known carcinogens in smoke.
2) Carcinogens bind to DNA to form DNA adducts
3) Polycyclic aromatic hydrocarbons lead to GC->AT mutation
4) N-nitrosamines lead to GC-> TA and GC-> AT mutations
5) Cigarette smoke is a potent source of free radicals. Leads to lipid peroxidation, DNA adducts

Question 12

Types of smoking-related lung cancer

Answer 12

1) 30-40% - Adenocarcinomas (slightly more common than squamous cell carcinomas)
2) 30-40% - Squamous cell carcinomas

Question 13

Smoking-related lung cancer that has a genetic component

Answer 13

Adenocarcinomas. 15% of patients with adenocarcinoma are non-smokers (Asian, female)

Question 14

Lung cancer type most strongly-associated with smoking

Answer 14

Squamous cell carcinoma

Question 15

Features of transformed cells related to smoking 
1)
2)
3)
4)

Answer 15

1) Deregulation of cellular energetics
2) Avoidance of immune destruction
3) Genome instability and mutation
4) Tumour-promoting inflammation

Question 16

How does cigarette smoke modify inflammation to lead to tumours?
1)
2)
3)
4)

Answer 16

1) Inflammatory cells release ROS (mutagenic for nearby cells)
2) Formation of M2 macrophages. These release factors that promote tumour growth and invasion.
3) Smoke inhibits NK cell function
4) CD8+ T cell function might be compromised by smoke

Question 17

Primary cause of COPD

Answer 17

Cigarette smoke

Question 18

Proportion of smokers that develop COPD

Answer 18

10-15%

Question 19

Transcription factor induced by cigarette smoke

Answer 19

NF-kB

Question 20

What does smoke-induced NF-kB activate?
1)
2)
3)

Answer 20

1) Inflammatory gene transcription
2) Innate inflammation
3) Protease induction

Question 21

Proportion of COPD patients with bacterial LRT colonisation

Answer 21

30-50%

Question 22

What can exacerbate COPD symptoms?

Answer 22

Active infective exacerbations

Question 23

One effect of cigarette smoke exposure on proteins.

Answer 23

Carbonylation.

Irreversible reaction removed by degradation of carbonylated protein.

Question 24

Effect of carbonylation of proteins on macrophages.

Answer 24

Impairs pseudopodia function (can’t phagocytose properly)

Question 25

Why does smoking lead to LRT bacterial colonisation?

Answer 25

Impairs airway cilia function. Mucociliary elevator doesn’t work as well.

Question 26

Outcome of poor macrophage pseudopodia funciton

Answer 26

Macrophages don’t clear dead neutrophils from airways. This leads to an increase in neutrophil elastase release, which increases inflammation

Question 27

How is cigarette smoke causally-linked to cardiovascular disease?
1)
2)
3)
4)
5)

Answer 27

1) Associated with accelerated atherosclerosis, increased risk of stroke, acute myocardial infarction, peripheral artery disease
2) Oxidising chemicals lead to lipid peroxidation, which promotes endothelial dysfunction, inflammation, platelet activation
3) Carbon monoxide reduces oxygen delivery to heart, which can aggravate peripheral artery disease
4) Atherosclerotic plaques important in smokers, as clots can embolise in narrowed blood vessels
5) Weakened vessels from inflammatory elastolysis can blow out (aneurysm) or rupture (bleeding stroke)