Lecture 22 - Smoking Flashcards Preview

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Flashcards in Lecture 22 - Smoking Deck (27):
1

When did smoking peak in the USA?

1960s

2

Epidemiology of smoking-related illness

Long latency between smoking and illness.

3

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

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

4

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

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.

5

Only treatment that reverses smoking-related damage

Cessation of smoking

6

Leading preventable cause of death in the USA

Smoking

7

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

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

8

Proportion of lung cancers that are due to smoking

80-90%

9

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

60%

10

5-year survival rate of lung cancer diagnoses

15%

11

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

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

12

Types of smoking-related lung cancer

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

13

Smoking-related lung cancer that has a genetic component

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

14

Lung cancer type most strongly-associated with smoking

Squamous cell carcinoma

15

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

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

16

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

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

17

Primary cause of COPD

Cigarette smoke

18

Proportion of smokers that develop COPD

10-15%

19

Transcription factor induced by cigarette smoke

NF-kB

20

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

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

21

Proportion of COPD patients with bacterial LRT colonisation

30-50%

22

What can exacerbate COPD symptoms?

Active infective exacerbations

23

One effect of cigarette smoke exposure on proteins.

Carbonylation.
Irreversible reaction removed by degradation of carbonylated protein.

24

Effect of carbonylation of proteins on macrophages.

Impairs pseudopodia function (can't phagocytose properly)

25

Why does smoking lead to LRT bacterial colonisation?

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

26

Outcome of poor macrophage pseudopodia funciton

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

27

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

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)