Flashcards in Lecture 22 - Smoking Deck (27):
When did smoking peak in the USA?
Epidemiology of smoking-related illness
Long latency between smoking and illness.
Stages of smoking-related illness epidemiology
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
Why 10-15% of adults still smoke in Australia
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.
Only treatment that reverses smoking-related damage
Cessation of smoking
Leading preventable cause of death in the USA
Major causes of smoking-related deaths (order of highest to lowest)
1) Lung cancer
2) Ischemic heart diesease
4) Other diagnoses
6) Other cancers
Proportion of lung cancers that are due to smoking
Proportion of lung cancer diagnoses that die within one year of diagnosis
5-year survival rate of lung cancer diagnoses
What leads to lung cancer in cigarette smoke?
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
Types of smoking-related lung cancer
1) 30-40% - Adenocarcinomas (slightly more common than squamous cell carcinomas)
2) 30-40% - Squamous cell carcinomas
Smoking-related lung cancer that has a genetic component
Adenocarcinomas. 15% of patients with adenocarcinoma are non-smokers (Asian, female)
Lung cancer type most strongly-associated with smoking
Squamous cell carcinoma
Features of transformed cells related to smoking
1) Deregulation of cellular energetics
2) Avoidance of immune destruction
3) Genome instability and mutation
4) Tumour-promoting inflammation
How does cigarette smoke modify inflammation to lead to tumours?
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
Primary cause of COPD
Proportion of smokers that develop COPD
Transcription factor induced by cigarette smoke
What does smoke-induced NF-kB activate?
1) Inflammatory gene transcription
2) Innate inflammation
3) Protease induction
Proportion of COPD patients with bacterial LRT colonisation
What can exacerbate COPD symptoms?
Active infective exacerbations
One effect of cigarette smoke exposure on proteins.
Irreversible reaction removed by degradation of carbonylated protein.
Effect of carbonylation of proteins on macrophages.
Impairs pseudopodia function (can't phagocytose properly)
Why does smoking lead to LRT bacterial colonisation?
Impairs airway cilia function. Mucociliary elevator doesn't work as well.
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