WEEK 4 LUNGS: ASTHMA, COPD, IPF + SILICOSIS Flashcards
What are the 5 main respiratory conditions worldwide?
- COPD, Asthma, Acute LRI, TB, and lung cancer
What are the current respiratory health concerns?
- Climate change, and biological or chemical terrorism
What % of respiratory conditions makes up the burden of disease in AUS?
- 8%
- 6th leading contributer to global burden
Is asthma a long-term lung condition?
- YES
What are the symptoms for asthma?
Shortness of breath, tightness of chest, cough, difficulty breathing.
What is an example of a preventive medicine for asthma?
Flixotide
How many people in 10 in Aus have asthma?
- 1/10 (1 in 10)
When does thunderstorm asthma usually occur?
- During or immediately after a storm and generally with the hotter temperatures (e.g. 35 degrees)
What is thunderstorm asthma and why is it different to normal asthma?
- The moisture from the air goes into the rye grass pollen, these then ‘explode’ into the air
- These pollens are MUCH smaller than normal pollen and can get into the lungs easily
Who is at risk for thunderstorm asthma?
- Hayfever sufferers
is asthma triggered from only pollen?
- NO, from many other potential triggers e.g. air pollution
What are some potential preventive measures that the state government has taken to respond better to these thunderstorm asthma events in the future (especially since there were 10 deaths)?
- More money into predicting and responding to these events (forecasting system)
- Public health education campaign
- Clinical guidelines
- Revised state health emergency plan
Are brown coal mines used overseas?
- no, just domestically
How long did the Hazlewood mine fire burn for?
- 45 days
What are the two types of emergencies that could be considered for the Hazlewood mine fire?
- A fire emergency
- Public health emergency
From the Hazlewood fires, was there any significant relationships between the exposure to smoke and self reproted doctor diagnoses high BP, high LDL, CVD, diabetes or cancer?
- NO
What are potential reasons for an increase in medical symptoms in those exposed to smoke from the Hazlewood fires and no diagnosis?
- symptoms may have been sub-clinical
- participants may not have reported symptoms to GPs
- Symptom onset to diagnosis may be a long period of time (delayed)
Was there increased psychological stress in those in the hazlewood mine and if so, was it primarily children, adults, or both?
- YES and both
What is an explanation for the 2019 report that there was no effect on the hazlewood fires on asthma related symptoms, lung function or airway inflammation in adults?
- This means that people could be taking preventive medication properly (e.g. for asthma) so they are not showing those symptoms
What was the outcome of the Hazlewood fires investiagation on the miners?
- They were fined for not having proper procedures in place, not cutting back vegetation, not wetting the ground properly etc. (fined 2 million) `
What are the health effects of bushfire smoke in relation to the social determinants of health?
- Homelessness
- Povertty (loss of business/job)
- Social disruption/social isolation–> mental health
What can increased hospital presentations form bushfire smoke be due to?
- Asthma
- COPD
- Other respiratory infections
What are the effects of bushfire smoke on the body a part from the lungs?
- CV morbidity
- Psychological disorders
- Adverse birth outcomes
- Eye irritation
What was the controversy with the Fiskville training centre firefighters?
- b/w 1971 and 1999 firefighters training at this centre hd a SIR (obs/exp) =1.85 for all cancers
- Due to toxic chemical build up at the site (used the same site for a long time)
In the 2014 health study report for firefighters, what was the health of firefighters?
- Overall mortality lower
- No increase in CV or resp. mortality -
- Stat significant increase in prostate cancer for FT firefighters
- Significant increase in melanoma
Why , in the 2014 fire fighter health report, was the overall mortality lower?
- because these fire fighters are VERY fit
- When they are not working, they are training all the time - they don’t smoke
Is silicosis an occupational lung disease?
- YES
What are the symptoms of silicosis?
- breathing difficulties, cough, weight loss, tiredness
What does silicosis do to the lungs in broad terms?
- Damages the lung air sacs, causes scarring and fibrosis
Who is at risk for developing silicosis?
- Stonecutters cutting artificial stone (engineered stone) for benchtops -crystalline silica or silica dust
What are the three forms of silicosis?
- Acute silicosis
- Accelerated silicosis
- Chronic silicosis
In what time frame does acute silicosis develop and what damage occurs?
Develops after a short exposure (a few weeks to years. to very high levels of silica dust.
- Causes severe inflammation and an outpouring of protein into the lung.
In what time frame does accelerated silicosis develop and what damage occurs?
- Develops after exposure 3 to 10 years to moderate to high levels of silica dust
- causes inflammation, protein in the lung and scarring of the lung (fibrotic nodules)
In what time frame does chronic silicosis develop and watch type of damage occurs?
- Develops after long-term exposure to lower levels of silica dust for example after 10 + years of exposure.
- Is known as the ‘classic silicosis’
Which two factors are key in preventing silicosis?
- Education
- OHS controls
Does silicosis generally occur in younger or older people?
- Young people
In terms of spirometry, what does the FEV1 mean?
- Forced expiratory volume in one second
- Measures how quickly the lungs can be emptied
- Volume expired in the first second of maximal expiration initiated at full inspiration (so you take your biggest breath in and exhale to your full capacity-measurement is within the first SECOND though)
In terms of spirometry, what is the FVC?
- Volume expired from full inspiration to full expiration
- this is compared to reference values (so compare normal lung function with the same age, sex, and height)
What are examples of obstructive diseases?
- Asthma and COPD
What are examples of restrictive diseases?
- IPF and Silicosis
If the FEV1/FVC ratio is less than the predicted lower limit of normal, then what does that mean?
- There is an airflow obstruction and they assess the severity of the obstruction by using the % predicted FEV1
What is teh FEV1 and FEV1/FVC ratio like in people with increased airway resistance?
- It is decreased
If a patient has a decreased FEV1 and FEV1/FVC, and measurements are taken again with the addition of a bronchodilator, then if they have asthma will the values improve or not?
- If they have asthma, then the values should improve BUT if they have COPD or fibrosis (e.g. IPF) then they won’t
What type of at home testing for lung function is available and what does it indicate?
- Peak Expiratory flow rate (L/min)
- Can be used to rule out clinically significant COPD if given before a bronchodilator
What are the normal adult values for males and females respectively for the PEF (peak expiratory flow rate)?
- Males: 450-700
- Females: 300-500
Does the PEF depend on age and time of day?
- YES it depends on age, height, weight and the reading is generally lower in the morning
How are most drugs delivered for lung diseases?
- Via the inhaled route because they are designed for deposit in lung
In terms of drugs for lung diseases, what feature of the body aids in systemic absorption for these drugs?
- The highly vascular pulmonary system
What 4 main things is the delivery and absorption of drugs for lung diseases dependent on?
- Inhaler technique
- Particle/droplet size
- Lipid solubility of the drug determining its duration of action
- Some of the drug may be swallowed which can cause systemic effects
A particle that is 5-10um in size is deposited on the ____ airways
- Deposited on the UPPER airways
A particle that is 0.5-5um in size is deposited in the ___ airways?
-Deposited in the SMALL airways
Any particle that is <2um in size will reach the ____ in lungs
- Will reach the alveoli in lungs
Which type of women are most at risk of dying form asthma?
- Baby boomer women
Why might the risk of dying from asthma be the greatest in the elderly?
- Because they may not be complying with their medication
What is a formal definition of asthma?
- “chronic inflammatory lung disease that leads to reversible narrowing of the airways, associated with increased airway hyperresponsiveness (AHR)”
- Imbalance between airway contraction and relaxation
What is a definition of asthma in terms of the symptoms experienced with it?
- Shortness of breath
- Wheezing, chest tightness
- Night-time or early morning coughing
What is the ‘extrinsic’ and more common form of asthma characterised by?
- ‘allergic’ (Th2 response immune system)
- Involving IgE antibodies/mast cell degranulation
- Triggered by re-exposure to an allergen e.g. pollen, house dust mite, pets
What is the ‘intrinsic’ and more severe form of asthma characterised by and what can it be caused by?
- Hyperresponsive airways
- ‘non specific bronchial hyperactivity’
- Triggered by the cold and infection
- Triggered by exercise (but exercise can reduce the frequency of attacks)
What is the diagnosis of asthma (two main options)?
- Compatible respiratory symptoms including response to triggers AND evidence of reversible airway obstruction even (spirometry)
OR: - Variable airflow obstruction (peak expiratory flow monitoring)
If the main criteria for diagnosis of asthma are not met but asthma is still suspected, then what should be done?
- Bronchoprovocation with methacholine (but some contraindications)
- Newer research going into testing based on the sputum (white= healthy and yellow or green= not good)
In asthma, which part of the membrane undergoes fibrosis?
- But is that like reversible or not.
In asthma, what are the three main things occurring in its pathogenesis?
- Excessive mucus (obstruction and barrier to inhaler therapy)
- Basement membrane thickening (fibrosis)
- More smooth muscle contraction (increased contraction)
In the more severe form of asthma, what occurs with the ‘airway hyperresponsiveness’?
- Influence of inflammatory mediators and increased bulk of “sensitised” muscle leads to airways contracting “too easily and too much”
What type of T cell response occurs in healthy airways in response to aeroallergens?
- Th1 immune response (macrophage, low level th1, IFN-7, IL-2, TNF-a)
- Low level IgG
- Normal airway maintained
What type of T cell response occurs in asthmatic airways (allergic asthma) in response to aeroallergens?
- Th2 response
- IL-4, 5, 13
- Eosinophil activation, mast cells, and IgE
- Subepithelial fibrosis
- Goblet cell hyperplasia
- Airway edema
- Smooth muscle hyperplasia and/or hypertrophy
What are the 4 main phases in asthma pathogenesis?
- Induction phase
- Inflammation
- Airway remodelling
- Smooth muscle cell shortening
What occurs in the induction phase of asthma in general and is this hard to prevent ?
- This is poorly understood, often (not always) related to the acquisition of allergy.
- YES hard to prevent
What occurs in the inflammation phase of asthma?
- not completely understood, some mediators known
- e.g. IgE in allergic asthma, IL-5 in eosinophilic asthma
What occurs in the airway remodelling phase of asthma and is this phase difficult to reverse?
- Not completely understood, changes well characterised
- This is why we can’t cure it
- YES it is difficult to reverse
What occurs in the smooth muscle shortening of asthma pathogenesis?
- Well understood, most important mediators identified. e.g. Histamine, Cys-LTs
Which stage of the asthma pathogenesis can be targeted by preventing medication?
- The inflammation stage
Which stage of the asthma pathogenesis can be targeted by reliever or controller medication?
The smooth muscle shortening phase.
What are the 5 layers of asthma treatments today?
- SABA reliever only (e.g. short acting b receptor agonist - salbutamol)
- Add ICS preventer (inhaled corticosteroid)
- Change to ICS/LABA preventer (LABA= long acting b2 agonist)
- Increase dose of ICS/LABA preventer
- Specialised inc biologics (e.g. mAbs)
What is the point of using releivers for asthma?
- They target the immediate (acute) phase of asthma
- They relieve airway smooth muscle spasm
What is the point of using preventers (controllers) for asthma?
- They target the late (chronic) phase of asthma
- They REDUCE inflammation
What occurs in the late phase of asthma in terms of the immune system and what is it inhibited by?
- Infiltration of cytokine releasing Th2 cells and monocytes
- Activation of eosinophils
- Leads to epithelial damage which can increase the airway hyperactivity amd lead to bronchospasm, wheexing and coughing
- INHIBITED BY GLUCOCORTICOIDS
What occurs in the early (immediate) phase of asthma and what can reverse it?
- An allergen or non specific stimulus
- This leads to mast cells and mononuclear cells that cause bronchospasm
- B2 receptor agonists can reverse this or CysLT receptor antagonists, or theophylline
In general terms, what are the relievers targeting in terms of asthma?
- The airway contraction leading to relaxation via the sympathetic efferents to adrenal medulla / synthetic b2 adrenoceptor agonists (e.g. salbutamol, short acting)
In terms of asthma, what is innervating the contraction of the bronchioles?
- Parasymp vagal efferents (Ach via M3 receptors)
What is an example of receptor antagonists that oppose the actions of HA (histamine), Cys-LTs (leukotreines) and Ach on the GPCR in terms of asthma and bronchoconstriction?
- M receptor antagonists e.g. Ipratropium
- This is known as competitive antagonism
What are examples of dilators that allow for functional antagonism?
- B2 adrenoceptor agonists–> adrenaline (endogenous), salbutamol, PDE inhibitor (theophylline)
Are reliever medications good at preventing against attacks?
- no
Via which pathway do beta agonists work to allow for muscular contraction?
- Via a GPCR
- ATP –> cAMP –> PKA (protein kinase A)
- PKA inhibits calcium release from sarc reticulum
- Due to this decrease, Ca2+ is then reduced which leads to reduced contraction
- MLC is de P’d (via phosphatase)
What is the mechanism of action of contraction in the smooth muscle bronchioles?
- Ach, histamine and Cys-LTs
- Phospholipase signalling (IP3)
- Increased release of intracellular Ca2+ release from SR
- P of MLC (Myosin light chain)
What are two positives that come from SABA?
- decrease the release of inflammatory mediators from mast cells
- stimulate mucociliary clearance
What are the adverse effects/limitations of SABA?
- Tachycardia (B1- mediated)
- Muscle tremor (B2 mediated)
- Potential for tolerance with overuse or infection (receptor downregulation/desensitization)
- No effect on remodelling
- Reduced efficacy with smoking/infection
What is another name for the asthma controllers?
- LABA
- Long acting B2 adrenoceptor agonists
What are examples of controllers (LABAs) ?
- Salmeterol (12 hour duration and rapid onset)
- Eformoterol (12 hour duration and rapid onset)
- clenbuterol /bambuterol
- Masks symptoms of inflammation and linked to increased mortality.
What are the indications for the use of LABAs?
- to only be used for prophylaxis!
- Also only with inhaled steroids (Step 3)
- Can be an alternative to an increased steroid dose
What can LABAs protect against?
- Exercise-induced/nocturnal asthma
What is an example of a medicaton that is contra-indicated in asthma?
- B adrenoceptor antagonists (Beta blockers-hypertension)
- b1 selective antagonists still can’t be used because of potential non specificity
- Could also cause bronchoconstriction
What are examples of other bronchodilators?
- Ipratropium (short acting M3 antagonist)
- Theophylline (Active component of aminophylline)
How do the short and long acting M3 antagonists work? (e.g. Ipratropium and Tropropium)
- Blocking vagal tone (bronchodilation and decreases mucous secretions)
How does Theophylline (brondecon, Neulin) work?
- Has variable pharmacokinetics/ narrow TI
- PDE inhibitor INHIBITING cAMP breakdown (leading to bronchodilation)
- Increases the effectiveness of the beta agonist
What type of drug is theophylline?
PDE inhibiting drug
What are two things that ICS (inhaled glucocorticoids) can do?
- Reduce mucus and swelling
- Prevent muscle spasm
- These can both reduce the severity of an asthma attack
What is the mechanism of action of ICS (Inhaled corticosteorids) ?
- Glucocorticoids enter cell via glucocortocoid receptor (GR)
- Enter nucleus and binds to TFs to transactivate - increase the anti-inflammatory proteins (e.g. annexin A1)
- ALso binds to TFs that repress that NFkB TF thus decreasing pro-inflammatory proteins such as COX-2, PLA2, IL-1, TNFa
What are 5 things that occur with the preventer/controller mechanism?
- reduced cytokine synthesis (thus decreased eosinophil activation)
- Reduced activity of PLA2 (vias increased annexin A1)
- Reduced COX-2 synthesis (decreased generation of prostaglandins/leukotrienes)
- Reduced IgE synthesis by B cells (decreased mast cell activation, less histamine release)
- Decreased symptoms of secretions; swelling; inflammation
NO ACUTE EFFECT ON BRONCHOSPASM
Can ICS (inhaled corticosteroids) have an acute effect on bronchospasms?
- NO
When are ICS used/reserved for?
- As a rescue medication
- Has dose limiting adverse effects
- need to wean patients off chronic use to avoid withdrawal
What are some of the adverse events related to corticosteroid use?
- Suppressing endogenous glucocorticoid synthesis
- cushings
- suppressing response to infection or injury
- behavioral symptoms
- cataracts
- metabolic effects (increased abdominal fat, easy bruising)
- growth suppression
What are LTRAs?
- Leukotriene receptor antagonists
- e.g. Montelukast, Zafirlukast
What do LTRAs do?
- Orally active
- PROPHYLACTIC USE ONLY (preventers)
- Modest bronchodilation (1/2 compared to B2 agonists)
- Has efficacy in asthma in combined therapy with ICS/LABA
What are LTRAs indicated for?
- Asprin and exercise induced asthma
What is Omalizumab?
- It is a mAb (monoclonal antibody) against IgE
- Inhibits IgE induced release of mast cell mediators- histamine, cys LTs
- ## Needs to be administered subcutaneously every 2-4 weeks by health provider.
In which situations is Omalizumab rezerved for in asthma?
- Severe, persistent allergic asthma that is uncontrolled even with high doses of coroicosteroids
- There is a low potential for anaphylaxis
What is the mAb Mepolizumab targeting in severe asthma treatment?
- IL-5
- Inhibits eosinophilia
- Subcutaneous administration every 4 weeks by health provider
- So only to be used for severe eosinophilic asthma!
If a patient is undergoing life-threatening acute asthma and can’t inhale salbutamol, then what should be done?
- Adrenaline should be administered and can administer salbutamol by continuous nebulisation
- could also require ventilation, i.v. magnesium sulfate, nebulised SABA/SAMA
What is COPD characterised by?
- Progressive decline in lung function
- Chronic bronchitis (excessive phlegm/sputum, cough) - emphysema –> breakdown of alveolar walls, riven by elastase-induced damage
- most patients have both (bc of smoking as well)
What is the reason why there is gas trapping in emphosema?
- Tethering forces are destroyed (what the alveoli are attached by)
What do I mean when I sat ‘blue bloater’?
- This is to do with chronic bronchitis in COPD
- Daily cough
- Overweight and person is also cyanotic due to lack of O2. They have higher hemoglobin, peripheral edema and bronchi and wheezing
What do I mean when I say ‘pink puffer’?
- This is to do with emphysema with COPD
- People are generally older and thin
- Have severe shortness of breath
- quiet chest
- Have hyperinflation on X-ray with flattened diaphragms
What type of remodelling occurs in COPD?
- Increased muscle
- Fibrosis
- Emphysema
What type of inflammation occurs in COPD?
- Macrophage and neut based inflamm (neutrophil elastase), IL-8 (neut recruiter), Fibroblasts
- mucus
What are the 3 classifications of COPD?
- Mild ( few symptoms, moderate exertion breathlessness, chest inflections, no effect on daily activities- FEV1 60-80%)
- Moderate ( exacerbations that need coticosteroids and/or antibiotics etc FEV1 40-59%)
- Severe ( minimal exertion breathlessness, chronic cough, regular sputum production- FEV1 <40%)
What is a characteristic COPD PEF and FEV1?
- They will both bee decreased
- FEV1 will be lower due to decreased rate of expiration
- PEF (peak expiratory flow rate) and extreme coving (someone can’t breathe out) = OBSTRUCTION
What are some non-pharmacological treatments for COPD?
- Assess the severity
- Identify/avoid risk factors
- cease smoking
- flu vaccine
- treat comorbidities
- Assess exercise capacity
