Lecture 23 - Smoking and lung health Flashcards Preview

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Flashcards in Lecture 23 - Smoking and lung health Deck (40):

Smoking rates are ___ in some countries



Smoking results in long diease latency:

What are the challenges of reducing the burden of Cigarette smoke?

Large proportion of the golbal population is still in early stages of smoking epidemic (i.e education and government intervention are not yet established)

Current golbal smoking trends in developing countries will impact on dealth reates for over 50-80 years...


Can smoking reates be reduced to below 10% in developed countries?

Consider New phase of anti-smoking educational programs

Further restrict sophisticated, cynical marketing targeting the young


Why are 10-15% adult population still smoking in Australia?

nicotine is highly addictive affeting CND dopamine please/reinforcement and executuve centres

Addition and smoking behavious may have a genetic basis: where nicotinic Ach receptor genetic variants govern smoking dose

Nicotine is a major appetite suppresant - people use it for weight loss


What are the therapeutic intervention to combat nicotine addiciton?

nicotine replacement therapy, nicotine receptor blockers and partial agonists


true or false

Cigarette use is the leading preventable cause of death in the US



What cancers other than lung can be caused by smoking?

Liver, rectum and stomach


COPD, ischemic heart disease and lung cancer are each what percentage of smoking related deaths?


so the remaining quarter is made up of other cancers, stroke and other stuff


What percentage of lung cancer cases are due to long-term exposure to tobacco smoke?



What percentage of patients have metastatic disease at lung cancer diagnosis?

over 50% - majority will die in the first year of diagnosis


What is the role of nicotine in lung cancer?

Not directly mutagenic BUT

The gene variants of the Ach receptor are strongly associated with nicotine dependence

So smoking behaviours is driven by genetic and will cause an increased uptake of nicotine in smoke AND consequently a greater present of lung carcinogens


smoke contains __ known carcinogens that can covalently bind to DNA to form DNA adducts



Cigarette smoke is also a contains ___



What are the types of non-small cell lung cancers (which account for 70-80% of cases)

30-40% - Adenocarcinomas - originate in peripheral airway (associated with non-smokers, particularly female asians)

30-40% Squamous cell carcinomas - originate in central airways - strongly associated with smoking history (so declining is AUS, but increased amounts in developing countries


Lung cancers relating to smoking have a different mutation profile to...

non-smoking related lung cancers


We need therapies/targets to treat squamous cell carcinoma because...

Alternative FGFR1 gene amplication pathways are moreso responsible

This is in contrast to adenocarcinomas which rely on activating mutations in K-RAS signalling molecules

FGFreceptor1 inhibitors are currently being assessed in SCC patients that are positive for FGFR1 amplification


Cigarette smoke may also drive tumour promoting..

inflammation and avoidance of immune destruction:

- This inflammation can be tumour promoting


inflammatory cells can release ROS, meaning...

they are actively mutagenic for nearby cancer cells, accelerating their malignancy potential


Cigarette smoke also drives lung inflammatio that causes the developmnt of____


10-15% smokers develop COPD

risk of developing COPD increase with age, and is an issue in developing countries in the future


Chronic inflammation can cause ___ ______ in the same way ___ ______ causes chronic inflammation

oxidative stress

increase in neutrophils, macropaghes - innate immunity is exaggerated in COPD as well as adaptive


Smoke-induced NFkB controls inflammatory gene programs

How does NFkB contribute to smoking pathology

NFkB can be activated by cigarette smoke

It then drives expression of inflammatory mediators including TNF-a and GM-CSF

Also induces protease expression - promotes further recruiting of inflammatory cells by remodelling the matrix


COPD exacerbations are very related to...

bacterial and viral infections - this really drives disease progression


How does smoking contribute to COPD exacerbations via infections

Defective innate immunity - Smoking damages the mucosal linging, leading to imapied muco-ciliary clearance

Can also directly interfere with the function of phagocytic leukocytes (so the pathogen sticks around)

this then causes increased expression of Protases and ROS, causes airways injury and the cycle continues


Carbonylation is markedly induced in Cigarette smoke exposure - what does this mean?

metal catalysed oxidation of susceptible proteins

attacks the amino acid side chain of Pro, Lys Arg and Thr residues

Typically irreversible reaction removed by degradation


Pseodopdoai are important in Macrophage fucntion, it means...

sensing the pathogen

carbonylated macrophages don't do this as well - can be prevented using anti-oxidants


What are some known carbonylation targets?

Actin - disrupts cytoskeleton

Sp - A/D 9increase susceptiility to pneumonia)

a1-antitrypsin (anti-protease, so can lose the protease balance)


A reduced ability to clear apoptotic cells what will happen

will go down the necrotic pathway and release contents unsafely (including protease)


Whats are the efects of secondary smoke?

especially bad for children

40% of chilren worldwide were exposed to second hand smoke in 2004

Smoke exposure and early life respiratory infections are major risk factors for developing asthma


Cigarette smoking is pro-____: promotes activation of inflammatory transcription factors to initiate recruitment of ______ into the airway

Cigarette smoking is pro-inflammatory: promotes activation of inflammatory transcription factors to initiate recruitment of leukocytes (macrophages) into the airway


How does smoking alter normal functioning of mucosal immune cells

M2 skewing of alveolar macrophages (alternative phenotype)

Suppress NK cells function required for efficient tumour clearance


Cigarette smoke physically damages mucosal linging leading to...

impaired mucociliary clearance = bacterial colonisation


Macrophages and important defense molecules are susceptible to oxidative modificaion in the form of ____ _______

protein carbonylation


impaired macrophage fucntion leads to deficient microbial clearance and impaired efferocytosis (safe clearance of damaged tissue, necrotic pathways instead), which leads to....

increase inflammation and damage


How is cigarette smoking causally related to CVD?

Associated with acelerated atherosclerosis and increased risk of acute myocardial infarction, stroke and peripheral artery disease

oxidising chemicals in smoke are systemically absorbed, increasing lipid peroxidation which promotes endothelial dysfunction, inflammation and platelet acivation

Carbon monoxide reduces oxygen delivery to heart

atherosclerotic plaques appear to be important in smokers - where clots can embolise in narrowed vessels

Weakened vessels can also blow-out or rupture


Smoking ____ continue to rise in developing countries including the western pacific region



It is very difficult to reduce smoking rates in developed countries below ___



Genetic polymorphisms of CHRA5 nicotinic receptor linked to...

nicotine addiciton


___% of children worldwide are exposed to second-hand smoke - this increases the risk of...


increases risk of developing a serious lower respiratory infection


What damages tissue, dNA and initiates cancer, promotes inflammation and damages to essential host immunity in smoke?

Toxic chemicals, oxidants and mutagens prsent in vapour


Cessation rapidly reduced risk. Are there any other known preventions or cures?


only medicines that aid cessation