Respiratory & Sleep Disorders Flashcards
Define
Accelerated silicosis
an aggressive form of pneumoconiosis. It is caused by the inhalation of large amounts of respirable crystalline silica (very fine silica dust). This scars the lungs and causes progressive respiratory impairment.
Define
Acute silicosis
silicosis that happens after weeks or months of being around high levels of silica
Define
Asthma
Chronic inflammatory lung disease that leads to reversible narrowing of the airways, associated with increased airway hyperresponsiveness (AHR). Includes recurring episodes of breathing problems including shortness of breath, wheezing, chest tightness or night-time or early morning coughing
Define
Bronchodilator
a drug that relaxes bronchial muscle resulting in expansion of the bronchial air passages
Define
Bronchospasm
constriction of the air passages of the lung (as in asthma) by spasmodic contraction of the bronchial muscles
Define
Broncial thermoplasty
a procedure that applies directed heat to the airway walls, reducing the bulk of airway smooth muscle and thereby reducing the potential for airway constriction
Define
Calmodulin
a calcium-binding protein that mediates cellular metabolic processes (such as the contraction of muscle fibers) by regulating the activity of calcium-dependent enzymes
Define
Chronic obstructive pulmonary disease (COPD)
pulmonary disease (such as emphysema or chronic bronchitis) that is characterized by chronic typically irreversible airway obstruction resulting in a slowed rate of exhalation
Define
Chronic silicosis
silicosis that results from long-term exposure (more than 20 years) to low amounts of silica dust
Define
Dysphonia
defective use of the voice
Define
Extrinsic (allergic) asthma
asthma that is triggered by an allergen (such as dust mites, pet dander, pollen, or mold)
Define
Fibrosis
a condition marked by increase of interstitial fibrous tissue
Define
Forced expiration volume in one second (FEV1)
the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration
Define
Forced vital capacity (FVC)
the maximum amount of air a person can expel from the lungs after a maximum inhalation. It is equal to the sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume
Define
Iatrogenic Cushing’s syndrome
Cushing’s syndrome that is usually related to prolonged and/or high-dose oral or parenteral steroid use
Define
Inhaled corticosteroid (ICS)
the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2)
Define
Intrinsic (non-allergic) asthma
asthma that has a range of non-allergenic triggers, including weather conditions, exercise, infections, and stress
Define
Leukotriene receptor antagonists (LTRA)
a class of oral medication that is non-steroidal. They may also be referred to as anti-inflammatory bronchoconstriction preventors. They work by blocking a chemical reaction that can lead to inflammation in the airways
Define
Long-acting β2-adrenoeptor agonist (LABA)
usually prescribed for moderate-to-severe persistent asthma patients or patients with chronic obstructive pulmonary disease (COPD). They are designed to reduce the need for shorter-acting β2 agonists such as salbutamol (albuterol), as they have a duration of action of approximately 12 hours
Define
Mepolizumab
a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma. It recognizes and blocks interleukin-5, a signalling protein of the immune system
Define
Nebulisation
a drug delivery device used to administer medication in the form of a mist inhaled into the lungs
Define
Non-T2-type asthma
asthma that commonly has an older age of onset and is often associated with obesity and neutrophilic inflammation
Define
Obstructive lung disease
a type of lung disease that occurs due to blockages or obstructions in the airways. Blockages damage the lungs and cause their airways to narrow. This damage leads to difficulty breathing
Define
Omalizumab
an immunosuppressive drug that is a recombinant monoclonal antibody selectively binding to IgE to reduce allergic reactions and that is administered by subcutaneous injection especially in the treatment of asthma and chronic hives
Define
Prophylaxis
measures designed to preserve health (as of an individual or of society) and prevent the spread of disease
Define
Restrictive lung disease
a group of lung diseases that prevent the lungs from fully expanding with air. This restriction makes breathing difficult
Define
Salbutamol
a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing relaxation of airway smooth muscle
Define
Short-acting β2-adrenoeptor agonist (SABA)
a bronchodilator that targets the beta receptors that has a short half-life
Define
Silicosis
pneumoconiosis characterized by massive fibrosis of the lungs resulting in shortness of breath and caused by prolonged inhalation of silica dusts
Define
Spirometry
an instrument for measuring the air entering and leaving the lungs (as in determining lung function in the diagnosis of pulmonary disease)
Define
Sputum
matter expectorated from the respiratory system and especially the lungs that is composed of mucus but may contain pus, blood, fibrin, or microorganisms (such as bacteria) in diseased states
Define
T2-type asthma
asthma that is associated with Type 2 inflammation and typically includes allergic asthma and moderate-to-severe eosinophilic asthma
Define
Thunderstorm asthma
asthma that is triggered by a combination of grass pollen in the air and certain thunderstorm conditions
Definition
an aggressive form of pneumoconiosis. It is caused by the inhalation of large amounts of respirable crystalline silica (very fine silica dust). This scars the lungs and causes progressive respiratory impairment.
Accelerated silicosis
Definition
silicosis that happens after weeks or months of being around high levels of silica
Acute silicosis
Definition
Chronic inflammatory lung disease that leads to reversible narrowing of the airways, associated with increased airway hyperresponsiveness (AHR). Includes recurring episodes of breathing problems including shortness of breath, wheezing, chest tightness or night-time or early morning coughing
Asthma
Definition
a drug that relaxes bronchial muscle resulting in expansion of the bronchial air passages
Bronchodilator
Definition
constriction of the air passages of the lung (as in asthma) by spasmodic contraction of the bronchial muscles
Bronchospasm
Definition
a procedure that applies directed heat to the airway walls, reducing the bulk of airway smooth muscle and thereby reducing the potential for airway constriction
Broncial thermoplasty
Definition
a calcium-binding protein that mediates cellular metabolic processes (such as the contraction of muscle fibers) by regulating the activity of calcium-dependent enzymes
Calmodulin
Definition
pulmonary disease (such as emphysema or chronic bronchitis) that is characterized by chronic typically irreversible airway obstruction resulting in a slowed rate of exhalation
Chronic obstructive pulmonary disease (COPD)
Definition
silicosis that results from long-term exposure (more than 20 years) to low amounts of silica dust
Chronic silicosis
Definition
defective use of the voice
Dysphonia
Definition
asthma that is triggered by an allergen (such as dust mites, pet dander, pollen, or mold)
Extrinsic (allergic) asthma
Definition
a condition marked by increase of interstitial fibrous tissue
Fibrosis
Definition
the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration
Forced expiration volume in one second (FEV1)
Definition
the maximum amount of air a person can expel from the lungs after a maximum inhalation. It is equal to the sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume
Forced vital capacity (FVC)
Definition
Cushing’s syndrome that is usually related to prolonged and/or high-dose oral or parenteral steroid use
Iatrogenic Cushing’s syndrome
Definition
the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2)
Inhaled corticosteroid (ICS)
Definition
asthma that has a range of non-allergenic triggers, including weather conditions, exercise, infections, and stress
Intrinsic (non-allergic) asthma
Definition
a class of oral medication that is non-steroidal. They may also be referred to as anti-inflammatory bronchoconstriction preventors. They work by blocking a chemical reaction that can lead to inflammation in the airways
Leukotriene receptor antagonists (LTRA)
Definition
usually prescribed for moderate-to-severe persistent asthma patients or patients with chronic obstructive pulmonary disease (COPD). They are designed to reduce the need for shorter-acting β2 agonists such as salbutamol (albuterol), as they have a duration of action of approximately 12 hours
Long-acting β2-adrenoeptor agonist (LABA)
Definition
a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma. It recognizes and blocks interleukin-5, a signalling protein of the immune system
Mepolizumab
Definition
a drug delivery device used to administer medication in the form of a mist inhaled into the lungs
Nebulisation
Definition
asthma that commonly has an older age of onset and is often associated with obesity and neutrophilic inflammation
Non-T2-type asthma
Definition
a type of lung disease that occurs due to blockages or obstructions in the airways. Blockages damage the lungs and cause their airways to narrow. This damage leads to difficulty breathing
Obstructive lung disease
Definition
an immunosuppressive drug that is a recombinant monoclonal antibody selectively binding to IgE to reduce allergic reactions and that is administered by subcutaneous injection especially in the treatment of asthma and chronic hives
Omalizumab
Definition
measures designed to preserve health (as of an individual or of society) and prevent the spread of disease
Prophylaxis
Definition
a group of lung diseases that prevent the lungs from fully expanding with air. This restriction makes breathing difficult
Restrictive lung disease
Definition
a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing relaxation of airway smooth muscle
Salbutamol
Definition
a bronchodilator that targets the beta receptors that has a short half-life
Short-acting β2-adrenoeptor agonist (SABA)
Definition
pneumoconiosis characterized by massive fibrosis of the lungs resulting in shortness of breath and caused by prolonged inhalation of silica dusts
Silicosis
Definition
an instrument for measuring the air entering and leaving the lungs (as in determining lung function in the diagnosis of pulmonary disease)
Spirometry
Definition
matter expectorated from the respiratory system and especially the lungs that is composed of mucus but may contain pus, blood, fibrin, or microorganisms (such as bacteria) in diseased states
Sputum
Definition
asthma that is associated with Type 2 inflammation and typically includes allergic asthma and moderate-to-severe eosinophilic asthma
T2-type asthma
Definition
asthma that is triggered by a combination of grass pollen in the air and certain thunderstorm conditions
Thunderstorm asthma
What are the five main respiratory conditions effecting Australians?
COPD
Asthma
Acute lower respiratory tract infection
tuberculosis
lung cancer
Are respiratory conditions more common in men or women?
Similar
What are the symptoms of asthma?
shortness of breath, tightness of chest, cough, difficulty breathing
Which population of people are at risk for thunderstorm asthma even if they don’t usually have asthma?
Hayfever sufferers
What are the key findings to data from the Hazelhood Mine Fire Study?
Poorer perceived general health compared to no exposure group
Self-reported respiratory symptoms higher
No significant relationships between exposure to smoke and self-reported doctor-diagnosed high blood pressure, high cholesterol, any cardiovascular condition, diabetes or cancer.
Increase in medical symptoms but not an increase in diagnoses
No association between fetal growth and gestational maturity but some evidence of an increase in gestational diabetes
Increased psychological distress in both adults and children
no effect on asthma-related symptoms, lung function of airway inflammation in adults
Following the Hazelwood Mine Fire, why did we see an increase in medical symptoms but not an increase in diagnoses?
symptoms have been sub‐clinical, participants have not reported their symptoms to medical practitioners and the process from symptom onset to diagnosis may often be protracted.
Following the Hazelwood Mine Fire, why did we see no effect on asthma related symptoms?
Mowell residents seem to be on medium to high doses of preventers
Bushfire smoke causes increased hospital presentation of people with which conditions?
Asthma
COPD
Other respiratory infections
What did the Australian Firefighters health study find?
- Overall mortality lower (strong healthy worker effect and lower rates of smoking)
- No evidence of increase in cardiovascular or respiratory mortality
- Statistically significant increase in prostate cancer for full time, careers fire fighters - SIR 1.23 (1.10 - 1.37)
- Significant increase in melanoma - 1.45 (1.26 - 1.66)
Who is most at risk of silicosis?
Stonecutters
What are the three forms of silicosis?
Acute
Accelerated
Chronic
What exposure time period is typical for acute silicosis?
few weeks to years
What exposure time period is typical for accelerated silicosis?
3-10 years
What exposure time period is typical for chronic silicosis?
10+ years
What factors influence lung function?
- inflammation – airway and tissue
- changes to airway smooth muscle
- epithelial damage
- mucus plugging
- alveolar damage
- fibrosis – airway and tissue
- tumour
- obesity
What conditions are considered an obstructive lung condition? What would the spirometry look like for these conditions?
Asthma
COPD
What conditions are considered an restrictive lung condition? What would the spirometry look like for these conditions?
IPF
Silicosis
If FEV1/FVC is less than the predicted lower limit of normal what does that tell us?
Airway obstruction
Could be asthma or COPD
How do you determine whether an obstructive lung disease is asthma or COPD?
If the patient responds to a bronchodilator then it is probably asthma, otherwise it could be COPD
If FEV1/FVC is not less than the predicted lower limit of normal and FVC is also low what does that tell us?
Restrictive pattern
If FEV1/FVC is not less than the predicted lower limit of normal but FVC is not less than normal what does that tell us?
Normal spirometry
A peak expiratory flow rate variability of >20% is an indication of ________
A peak expiratory flow rate variability of >20% is an indication of asthma
What does delivery and absorption of drugs for lung diseases depend on?
- inhaler technique
- particle / droplet size
- 5-10 µm deposited on upper airways
- 0.5-5 µm deposited in small airways
- <2 µm reach alveoli
- lipid solubility of drug determines duration of action
Asthma is more common in ______ aged 0-14, but more common in _______ aged 15 and over
Asthma is more common in boys aged 0-14, but more common in females aged 15 and over
What causes thunderstorm asthma?
How does asthma effect COVID-19? What about the other way?
If infected with COVID-19, asthma attacks may be worse*
With more severe asthma, COVID-19 disease severity may be worse
What are the 2 types of asthma we previously used?
Extrinsic (allergic)
Intrinsic (non-allergic)
__________ asthma involves IgE antibodies / mast cell degranulation and is triggered by re-exposure to allergen e.g. pollen, house dust mite, pets
Extrinisic (allergic) asthma involves IgE antibodies / mast cell degranulation and is triggered by re-exposure to allergen e.g. pollen, house dust mite, pets
____________ asthma involves hyperresponsive airways, ‘non specific bronchial hyperreactivity’ and is triggered by cold, infection or exercise (but exercise can reduce frequency of attacks)
Intrinsic (non-allergic) asthma involves hyperresponsive airways, ‘non specific bronchial hyperreactivity’ and is triggered by cold, infection or exercise (but exercise can reduce frequency of attacks)
What is the current classification system for asthma?
What is the most common type of asthma?
Allergic
How is asthma diagnosed?
- Compatible respiratory symptoms including response to triggers AND Evidence of reversible airway obstruction (spirometry) OR Variable airflow obstruction (peak expiratory flow monitoring)
- If these criteria are not met, but asthma still suspected
- Bronchoprovocation with methacholine (some contraindications for this test; methacholine induces attack)
- Recent development - evaluation of inflammatory cells in sputum
Describe the pathogenesis of asthma
excessive mucus = obstruction & barrier to inhaler therapy
basement membrane thickening = fibrosis
more smooth muscle = increased contraction
What is the difference in airway resistance in response to an inhaled brochoconstrictor in a healthy person, severe-, and moderate asthma?
How does the immune system respond to aeroallergins in a healthy person?
CD4 cells release TH1 cytokines that recruits macrophages which engulf the allogen. No effect on airways
How does the immune system respond to aeroallergins in someone with asthma?
CD4 cells release TH2 cytokines that recruit eosinophils, mast cells and plasma cells which release a cocktail of cytokines and antibodies that causes constriction of airways
What are the four phases of asthma pathogenesis?
Induction phase (difficult to prevent)
- poorly understood, often (not always) related to acquisition of allergy
Inflammation (targeted by preventer medication)
- not completely understood, some mediators known
- e.g. IgE in allergic asthma, IL-5 in eosinophilic asthma
Airway remodelling (difficult to reverse)
- not completely understood, changes well characterised
Smooth muscle shortening (targeted by reliever / controller medication)
- well understood, most important mediators identified
- e.g. histamine, Cys-LTs
What causes the inflammation seen in allergic asthma and eosinophilic asthma?
Allergic: IgE
Eosinophilic: IL-5
What types of drugs are used to treat/control asthma?
Short-acting β2-adrenoeptor agonist (SABA)
Long-acting β2-adrenoeptor agonist (LABA)
Inhaled corticosteroid (ICS)
Leukotriene receptor antagonist
Monoclonal antibodies
Why do we use relievers in asthma?
Target immediate (acute) phase of asthma
Relieve airway smooth muscle spasm
Why do we use preventers (controllers) in asthma?
Target late (chronic) phase of asthma
Reduce inflammation
Which drugs are used to target the immediate phase of asthma?
SABAs
CysLT-receptor antagonists
Theophylline
Which drugs are used to target the late phase of asthma?
Glucocorticoids
How do relievers (glucocorticoids) target airway contraction?
Decreases contraction
- targets mediators of allergy (histamine leukotrienes
- targets parasympathetic vagal efferents (decreases)
Increases relaxation
- increases sympathetic efferents to adrenal medulla
- Available synthetic β2-adrenoeptor agonists (salbutamol)
How does histamine, cys leukotrienes and acetylcholine cause airway contraction in asthma?
They bind to a GCPR which causes a cascade resulting in calcium release which interacts with the myosin light chain resulting in contraction
Which endogenous molecules cause airway contraction?
Histamine
Leukotrienes
Acetylcholine
Which exogenous drugs can be used to induce airway relaxation?
β2-adrenoeptor agonists
Salbutamol
Phosphodiesterase (PDE) inhibitor
Theophylline
Which endogenous molecule can induce airway relaxation?
Adrenaline
What is the mechanism by which a β2-adrenoeptor agonist inhibits airway contraction in asthma?
The β2-adrenoeptor agonist binds to a GPCR which causes ATP to be coverted to cAMP which is converted into protein kinase A (PKA) which inhibits the release of calcium and converts myosin light chain into the inactive form
What is the first step in the treatment of asthma?
Salbutomol/albuterol (Ventolin)
administered via inhalation leads to bronchodilation
What are the other positive effects of SABAs?
- decrease release of inflammatory mediators from mast cells
- stimulate mucociliary clearance
What are the adverse effects of SABAs?
- tachycardia (β1-mediated)
- muscle tremor (β2-mediated)
- potential for tolerance with overuse or infection (receptor downregulation / desensitization)
- no effect on remodelling
- reduced efficacy with smoking/ infection
Why have LABAs been linked to increased mortality?
They mask symptoms of inflammation
How are LABAs used?
used only for prophylaxis, only in conjunction with inhaled steroids (Step 3)
alternative to increased steroid dose
Beta-adrenoceptor ____________ are contraindicated in asthma
Beta-adrenoceptor antagonists are contraindicated in asthma
What is step 2 of treating asthma?
Reliever as required, add daily low dose ICS alone
What is step 3 of treating asthma?
Change to ICS/LABA combination
Why are controllers (ICS) not useful for acute attacks?
They effect the sythensis of inflammatory factors which takes time to take effect
What is the mechanism of action for ICS?
Transactivation: Increase anti-inflammatory proteins
Transrepression: Decrease pro-inflammatory proteins
- reduced cytokine synthesis
- decreased eosinophil activation
- reduced activity of PLA2 (via 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
- BUT NO ACUTE EFFECT ON BRONCHOSPASM
What are the adverse effects of corticosteroids?
Most relate to chronic oral use
- suppress endogenous glucocorticoid synthesis
- iatrogenic Cushing’s syndrome
- suppress response to infection and injury
- behavioural disturbances
- cataracts, glaucoma
- metabolic effects
- growth suppression - use cautiously in children
What are leukotriene receptor antagonists (LTRAs)?
- i.e. Montelukast, Zafirlukast
- orally active, prophylactic use only (preventers)
- modest bronchodilatation (about half that of β2-agonists)
- efficacy in chronic asthma in combined therapy with ICS / LABA
- indicated for aspirin- and exercise-induced asthma
- limited side effects - liver function may be impaired in some patients
What is step 5 for the treatment of severe, persistent allergic asthma?
Omalizumab
recombinant monoclonal antibody against immunoglobulin E (IgE)
inhibits IgE-induced release of mast cell mediators - histamine, cys LTs
subcutaneous administration every 2-4 weeks by health provider
What is step 5 for the treatment of eosinophilic asthma?
Mepolizumab
recombinant monoclonal antibody against IL-5
inhibits eosinopilia
subcutaneous administration every 4 weeks by health provider
How do you manage life-threatening acute asthma?
- consider anaphylaxis and manage if suspected
- treat with adrenaline if patient unable to inhale salbutamol
- administer salbutamol by continuous nebulisation
- subsequent treatment depends is there marked, some or no improvement or worsening?
- may require
- ventilation
- i.v. magnesium sulfate
- nebulised SABA/SAMA
- i.v. salbutamol
Define
Alpha-1-antitrypsin
a protein belonging to the serpin superfamily. As a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase
Define
Chronic bronchitis
a persisting infection and inflammation of the larger airways of the lungs – the bronchi
Define
Elastase
an enzyme from the class of proteases (peptidases) that break down proteins and elastin, an elastic fibre that, together with collagen, determines the mechanical properties of connective tissue
Define
Emphysema
a type of chronic obstructive pulmonary disease. The air sacs in the lungs become damaged and stretched. This results in a chronic cough and difficulty breathing
Define
Idiopathic pulmonary fibrosis (IPF)
a type of rare lung disease that causes the tissue around the air sacs (alveoli) within the lungs to become thickened and scarred – this is called fibrosis. This scarring makes the lungs stiff which makes it increasingly difficult to breathe deeply.
Define
Long-acting muscarinic receptor antagonist (LAMA)
result in bronchodilation with a duration of action of 12 to 24 hours, depending on the agent and are mainly prescribed for people with COPD
Define
Nintendanib (Ofev)
an oral medication used for the treatment of idiopathic pulmonary fibrosis. It has been shown to slow down decrease in forced vital capacity, and it also improves people’s quality of life. It interferes with processes like fibroblast proliferation, differentiation and laying down extracellular matrix
Define
Pirfenidone (Esbriet)
a medication used for the treatment of idiopathic pulmonary fibrosis. It works by reducing lung fibrosis through downregulation of the production of growth factors and procollagens I and II.
Define
Short-acting muscarinic receptor antagonist (SAMA)
used both in the acute and chronic management of COPD. Blocks muscarinic receptors and is effective within minutes
Define
TGF-B
a multifunctional cytokine belonging to the transforming growth factor superfamily. Plays a role in immune and stem cell regulation
Definition
a protein belonging to the serpin superfamily. As a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase
Alpha-1-antitrypsin
Definition
a persisting infection and inflammation of the larger airways of the lungs – the bronchi
Chronic bronchitis
Definition
an enzyme from the class of proteases (peptidases) that break down proteins and elastin, an elastic fibre that, together with collagen, determines the mechanical properties of connective tissue
Elastase
Definition
a type of chronic obstructive pulmonary disease. The air sacs in the lungs become damaged and stretched. This results in a chronic cough and difficulty breathing
Emphysema
Definition
a type of rare lung disease that causes the tissue around the air sacs (alveoli) within the lungs to become thickened and scarred – this is called fibrosis. This scarring makes the lungs stiff which makes it increasingly difficult to breathe deeply.
Idiopathic pulmonary fibrosis (IPF)
Definition
result in bronchodilation with a duration of action of 12 to 24 hours, depending on the agent and are mainly prescribed for people with COPD
Long-acting muscarinic receptor antagonist (LAMA)
Definition
an oral medication used for the treatment of idiopathic pulmonary fibrosis. It has been shown to slow down decrease in forced vital capacity, and it also improves people’s quality of life. It interferes with processes like fibroblast proliferation, differentiation and laying down extracellular matrix
Nintendanib (Ofev)
Definition
a medication used for the treatment of idiopathic pulmonary fibrosis. It works by reducing lung fibrosis through downregulation of the production of growth factors and procollagens I and II.
Pirfenidone (Esbriet)
Definition
used both in the acute and chronic management of COPD. Blocks muscarinic receptors and is effective within minutes
Short-acting muscarinic receptor antagonist (SAMA)
Definition
a multifunctional cytokine belonging to the transforming growth factor superfamily. Plays a role in immune and stem cell regulation
TGF-B
What drug types are used in both COPD and asthma but are more commonly used for COPD?
SAMA
LAMA
What drug types are used in both COPD and asthma equally?
SABA
LABA
ICS
What type of drug is salbutamol?
SABA
What are the five risk factors for COPD?
- Genetic reasons (alpha-1 antitrypsin deficiency)
- Occupational dust and chemicals
- Indoor smoke from wood, coal, cow dungs, crop residues used for cooking
- Frequent lung infections as a child
- Smoking and passive smoking
Which gender is COPD more common in?
Males
What are the major features of COPD?
- progressive decline in lung function
- chronic bronchitis
- excessive phlegm/sputum, cough
- emphysema
- breakdown of alveolar walls, driven by elastase-induced damage
- most patients have both
What is the difference between healthy and COPD lung pathology?
What cytokine do macrophages produce that stimulate neutrophils to produce elastase in COPD?
IL-8
How is COPD different to asthma?
COPD:
Progressively worsening airflow obstruction
Often presents in 6th decade of life or later in patients
More permanent airflow obstruction; less reversibility and less normalisation of airflow obstruction
Cellular inflammation: neutrophils, macrophages, eosinophils and mast cells may occur
Emphysema frequently found
What are the typical symptoms and lung function of someone with mild COPD?
Few symptoms
Breathless on moderate exertion
Recurrent chest infections
Little or no effect on daily activities
FEV1 = 60-80% predicted
What are the typical symptoms and lung function of someone with moderate COPD?
Breathless walking on level ground
Increasing limitation of daily activities
Cough and sputum production
Exacerbations requiring oral corticosteroids and/or antibiotics
FEV1 = 40-59% predicted
What are the typical symptoms and lung function of someone with severe COPD?
Breathless on minimal exertion
Daily activities severely curtailed
Experiencing regular sputum production
Chronic cough
Eacerbations of increasing frequency and severity
FEV1 < 40% predicted
What are some non-pharmacological interventions for COPD?
Risk reduction: smoking cessation, flu shot
Optimise function: encourage exercise, review nutrition
Consider co-morbitities: especially CVD, mental illness and lung diseases
Refer to pulmonary rehabilitation for sympomatic patients
Oxygen therapy for moderate to severe patients
What is typical of a spirometry graph for someone with COPD?
Slower rate of expiration, decreased FEV1
Reduced peak expiratory flow and extreme coving
In terms of pharmacological treatment, what drugs are introduced first to manage COPD?
SAMA
SABA
In terms of pharmacological treatment, what drugs are introduced second to manage COPD?
Add long acting bronchodilators:
LAMA
LABA
In terms of pharmacological treatment, what drugs are introduced third to manage COPD?
Consider adding anti-inflammatory agent:
ICS
What are the main effects of the M3 antagonists (SAMA/LAMA)?
Both oppose tonic parasympathetic drive (ACh)
Both reduce mucous
What are the main effects of Beta-2-adrenoceptor agonists (SABA/LABA) in COPD?
Oppose all constrictors
Stimulate mucosiliary clearance
Inhibit release of inflammatory mediators from mast cells
How do M3 antagonists decrease contraction?
Competetively inhibits the ACh receptors preventing the calcium release that leads to contraction
Which contraction signalling molecule is the most important in COPD?
ACh
What are the adverse-effects of M3 antagonists?
dry throat (local anti-SLUD)
acute infection
flu-like symptoms
trouble breathing
What are the features of corticosteroid use in COPD?
less effective in COPD than in asthma, but still widely prescribed
poor efficacy in reducing inflammation due to macrophages and neutrophils (compared to effective inhibition of eosinophils in allergic asthma)
do not affect symptoms
inhaled route - may reduce frequency and severity of exacerbations
oral route - used to treat exacerbations
What are the triggers and therapies used for COPD?
Triggers:
- Viruses
- Bacteria
- Pollutants
Therapy
- Antibiotics
- Steroids
- Bronchodilators
- Pulmonary rehab
Which cell type do corticosteroids particularly target in COPD?
Eosinophils
When should ICS be prescribed to patients with COPD?
When they have a high eosinophil count
What are the two most cost effective ways to prevent/treat COPD?
Flu vaccines
Smoking cessation
How does alpha1-antitrypsin deficiency lead to COPD?
What possibly caused the spike in deaths from marijuana vaping?
Pesticide contamination
True or False:
IPF is relatively rare
True
What are the causes/implications of IPF?
Cause:
Unknown
Implications:
Smoking
Certain animal exposures
Certain viruses/bacteria
Acid reflux disease
Genetics
Radiation
Certain medicine/antibiotics
Describe the pathophysiology of IPF?
What are the symptoms of IPF?
Shortness of breath
Persistent, dry, hacking cough
Fatigue
Clubbing of fingers
What causes the clubbing of fingers seen in IPF?
Increased growth factors and decreased oxygen
Why don’t we use dilators to treat IPF?
Symptoms are not due to brochoconstriction
Bronchodilators have little or no benefit in relieving symptoms
Why don’t we use anti-inflammatories to treat IPF?
Previously combination treatment with prednisone (a corticosteroid), azathioprine (an immunosuppressive) and N‑acetyl cysteine (NAC; a mucolytic)
NOW RECOMMENDED AGAINST DUE TO ADVERSE OUTCOMES
How is pirfenidone administered?
Orally
What is the mechanism of action for pirfenidone?
not completely defined
inhibits TGFβ
- anti-inflammatory
- anti-fibrotic
What are the adverse effects of pirfenidone?
- upper gastrointestinal symptoms (take with food)
- anorexia
- photosensitivity
- skin rash
- liver toxicity (need to monitor function)
How is nintedanib administered?
Orally
What is the mechanism of action of nintedanib?
- not completely defined
- inhibits tyrosine kinase
- reduces signaling of multiple growth factors
- TGFβ, PDGF, FGF, VEGF
- anti-fibrotic
- TGFβ, PDGF, FGF, VEGF
Which signalling pathways does nintedanib interfere with?
What are the adverse effects of nintedanib?
arterial thromboembolic events including myocardial infarction (caution with coronary artery disease, myocardial ischaemia)
liver toxicity (need to monitor function)
What are the final options for IPF?
Lung transplantation
Pallative care
What causes silicosis?
Inhaled respirable crystalline silicon dioxide dust particles
What occupations have seen silicosis cases?
Mining
Denim sandblasting
Stone cutting
What happens when a macorphage injects a silica molecule?
Since it’s inert it results in apoptosis of the macrophage causing the silica to be released
What cytokines do macrophages release in response to silica ingestion?
TNF-a
IL-1B
TGF-B
How does TGF-B cause increased collagen and elastin production in silicosis?
Stimulates fibroblast cells to produce ECM
Causes epithelial cells to become fibroblast-like and produce ECM
How is whole lung lavage used to treat silicosis?
- May be used in early stages after high exposure to reduce silica load in the lung
- Up to 10 litres of saline is added to and removed from the lung • Requires anaesthesia, ICU monitoring
- Allows the level of exposure to be measured – grams of silica collected
- not all silica removed (repeat procedure?)
- Being trialled in Queensland (<10 cases to date)
How is relaxin used to treat silicosis?
Relaxin is a RXFP1 agonist which inactivates the TGF-B receptor preventing the production of ECM
It also acts as a vaso- and bronchodilator
Define
Actigraphy
a non-invasive method of monitoring human rest/activity cycles
Define
Acute respiratory distress syndrome (ARDS)
a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath, rapid breathing, and bluish skin coloration. For those who survive, a decreased quality of life is common
Define
Airborne
disease transmission through small particulates that can be transmitted through the air over time and distance
Define
Alpha waves
neural oscillations in the frequency range of 8–12 Hz arising from the synchronous and coherent electrical activity of thalamic pacemaker cells in humans. Typical of sleepy wakefulness
Define
Basic reproduction number (R0)
the reproduction number (R) when the entire population is susceptible.
Define
Beta waves
periodic and repeating fluctuations heard in the intensity of a sound when two sound waves of very similar frequencies interfere with one another. Typical of wakefulness
Define
Cluster
an aggregation of cases grouped in place and time that are suspected to be greater than the number expected
Define
Convalescent plasma
the liquid part of blood that contains antibodies
Define
COVID-19
an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first identified in December 2019 in Wuhan, China, and has since spread globally, resulting in an ongoing pandemic
Define
Delta waves
a high amplitude brain wave with a frequency of oscillation between 0.5 and 4 hertz. Typical of slow wave sleep
Define
Dexamethasone
a type of corticosteroid medication. It is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, and along with antibiotics in tuberculosis. Being explored as an option for COVID-19
Define
Direct transmission
when there is physical contact between an infected person and a susceptible person.
Define
Endemic
the constant presence of a disease or infectious agent in a population within a geographic area
Define
Epidemic
an increase, often sudden, in the number of cases above what is normally expected in that population in that area
Define
Fomites
objects or materials which are likely to carry infection, such as clothes, utensils, and furniture
Define
Incubation stage
the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent
Define
Indirect transmission
refers to the transfer of an infectious agent from a reservoir to a host by suspended air particles, inanimate objects (vehicles), or animate intermediaries (vectors).
Define
Infectious disease
diseases caused by pathogenic microorganisms, such as bacteria, viruses, parasites or fungi; the diseases can be spread, directly or indirectly, from one person to another
Define
K complex
a waveform that may be seen on an electroencephalogram (EEG). It occurs during stage 2 of NREM sleep. It is the “largest event in healthy human EEG”
Define
Latent period
the period between infection with a virus or other microorganism and the onset of symptoms, or between exposure to radiation and the appearance of a cancer.
Define
Myocarditis
an inflammation of the heart muscle. Itcan affect your heart muscle and your heart’s electrical system, reducing your heart’s ability to pump and causing rapid or abnormal heart rhythms (arrhythmias)
Define
NREM sleep
dreamless sleep. During this phase, the brain waves on the electroencephalographic (EEG) recording are typically slow and of high voltage, the breathing and heart rate are slow and regular, the blood pressure is low, and the sleeper is relatively still
Define
Outbreak
a noticeable, often small but sudden, increase over the expected number of epidemiologically linked cases
Define
Pandemic
an epidemic with a P ( p for passport) ‐ A new pathogen that spreads from person to person across the globe”.
Define
Phasic REM
REM that is characterized by PGO waves and actual “rapid” eye movements
Define
Polysomnography
a test used to diagnose sleep disorders. It records your brain waves, the oxygen level in your blood, heart rate and breathing, as well as eye and leg movements during the study
Define
REM sleep
a unique phase of sleep in mammals and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the sleeper to dream vividly
Define
Remdesivir
a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein
Define
Reproduction number (R)
the average number of new infections caused by 1 infected individual
Define
SARS-COV2
the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), a respiratory illness. It is a positive-sense single-stranded RNA virus.
Define
Sawtooth waves
a kind of non-sinusoidal waveform. It is so named based on its resemblance to the teeth of a plain-toothed saw with a zero rake angle
Define
Sleep spindles
bursts of neural oscillatory activity that are generated by interplay of the thalamic reticular nucleus (TRN) and other thalamic nuclei during stage 2 NREM sleep in a frequency range of ~11 to 16 Hz (usually 12–14 Hz) with a duration of 0.5 seconds or greater (usually 0.5–1.5 seconds)
Define
Sporadic
a disease that occurs infrequently and irregularly
Define
Theta waves
a neural oscillatory pattern that can be seen on an electroencephalogram, recorded either from inside the brain or from electrodes attached to the scalp. Typical of sleep onset or light sleep
Define
Tonic REM
REM that is characterized by theta rhythms in the brain
Define
Two Process Model of Sleep-Wake Regulation
posits that the interaction of its two constituent processes, a sleep/wake dependent homeostatic Process S and a circadian Process C, generates the timing of sleep and waking
Define
Vector-borne
illnesses that are transmitted by vectors, which include mosquitoes, ticks, and fleas
Define
Vehicle-borne
an indirect transmission process during which the pathogen is indirectly transferred from a reservoir, source or host to another host by inanimate intermediary vehicle objects
Define
Virus shedding
occurs when a virus replicates inside your body and is released into the environment. at that point, it may be contagious
Definition
a non-invasive method of monitoring human rest/activity cycles
Actigraphy
Definition
a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath, rapid breathing, and bluish skin coloration. For those who survive, a decreased quality of life is common
Acute respiratory distress syndrome (ARDS)
Definition
disease transmission through small particulates that can be transmitted through the air over time and distance
Airborne
Definition
neural oscillations in the frequency range of 8–12 Hz arising from the synchronous and coherent electrical activity of thalamic pacemaker cells in humans. Typical of sleepy wakefulness
Alpha waves
Definition
the reproduction number (R) when the entire population is susceptible.
Basic reproduction number (R0)
Definition
periodic and repeating fluctuations heard in the intensity of a sound when two sound waves of very similar frequencies interfere with one another. Typical of wakefulness
Beta waves
Definition
an aggregation of cases grouped in place and time that are suspected to be greater than the number expected
Cluster
Definition
the liquid part of blood that contains antibodies
Convalescent plasma
Definition
an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first identified in December 2019 in Wuhan, China, and has since spread globally, resulting in an ongoing pandemic
COVID-19
Definition
a high amplitude brain wave with a frequency of oscillation between 0.5 and 4 hertz. Typical of slow wave sleep
Delta waves
Definition
a type of corticosteroid medication. It is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, and along with antibiotics in tuberculosis. Being explored as an option for COVID-19
Dexamethasone
Definition
when there is physical contact between an infected person and a susceptible person.
Direct transmission
Definition
the constant presence of a disease or infectious agent in a population within a geographic area
Endemic
Definition
an increase, often sudden, in the number of cases above what is normally expected in that population in that area
Epidemic
Definition
objects or materials which are likely to carry infection, such as clothes, utensils, and furniture
Fomites
Definition
the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent
Incubation stage
Definition
refers to the transfer of an infectious agent from a reservoir to a host by suspended air particles, inanimate objects (vehicles), or animate intermediaries (vectors).
Indirect transmission
Definition
diseases caused by pathogenic microorganisms, such as bacteria, viruses, parasites or fungi; the diseases can be spread, directly or indirectly, from one person to another
Infectious disease
Definition
a waveform that may be seen on an electroencephalogram (EEG). It occurs during stage 2 of NREM sleep. It is the “largest event in healthy human EEG”
K complex
Definition
the period between infection with a virus or other microorganism and the onset of symptoms, or between exposure to radiation and the appearance of a cancer.
Latent period
Definition
an inflammation of the heart muscle. Itcan affect your heart muscle and your heart’s electrical system, reducing your heart’s ability to pump and causing rapid or abnormal heart rhythms (arrhythmias)
Myocarditis
Definition
dreamless sleep. During this phase, the brain waves on the electroencephalographic (EEG) recording are typically slow and of high voltage, the breathing and heart rate are slow and regular, the blood pressure is low, and the sleeper is relatively still
NREM sleep
Definition
a noticeable, often small but sudden, increase over the expected number of epidemiologically linked cases
Outbreak
Definition
an epidemic with a P ( p for passport) ‐ A new pathogen that spreads from person to person across the globe”.
Pandemic
Definition
REM that is characterized by PGO waves and actual “rapid” eye movements
Phasic REM
Definition
a test used to diagnose sleep disorders. It records your brain waves, the oxygen level in your blood, heart rate and breathing, as well as eye and leg movements during the study
Polysomnography
Definition
a unique phase of sleep in mammals and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the sleeper to dream vividly
REM sleep
Definition
a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein
Remdesivir
Definition
the average number of new infections caused by 1 infected individual
Reproduction number (R)
Definition
the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), a respiratory illness. It is a positive-sense single-stranded RNA virus.
SARS-COV2
Definition
a kind of non-sinusoidal waveform. It is so named based on its resemblance to the teeth of a plain-toothed saw with a zero rake angle
Sawtooth waves
Definition
bursts of neural oscillatory activity that are generated by interplay of the thalamic reticular nucleus (TRN) and other thalamic nuclei during stage 2 NREM sleep in a frequency range of ~11 to 16 Hz (usually 12–14 Hz) with a duration of 0.5 seconds or greater (usually 0.5–1.5 seconds)
Sleep spindles
Definition
a disease that occurs infrequently and irregularly
Sporadic
Definition
a neural oscillatory pattern that can be seen on an electroencephalogram, recorded either from inside the brain or from electrodes attached to the scalp. Typical of sleep onset or light sleep
Theta waves
Definition
REM that is characterized by theta rhythms in the brain
Tonic REM
Definition
posits that the interaction of its two constituent processes, a sleep/wake dependent homeostatic Process S and a circadian Process C, generates the timing of sleep and waking
Two Process Model of Sleep-Wake Regulation
Definition
illnesses that are transmitted by vectors, which include mosquitoes, ticks, and fleas
Vector-borne
Definition
an indirect transmission process during which the pathogen is indirectly transferred from a reservoir, source or host to another host by inanimate intermediary vehicle objects
Vehicle-borne
Definition
occurs when a virus replicates inside your body and is released into the environment. at that point, it may be contagious
Virus shedding
What are the unique features of infectious diseases?
Case is a source of infection for others
- Failure to detect early and treat is detrimental
Urgency in response
- Prompt response is important. Surveillance and preparedness is key
Multiple prevention measures is critical
- Prevent exposure and transmission
- Treatment is a key prevention
- Increase resilience of population
Immunity
- Prior exposure may confer immunity.
- Vaccination is important measure
- Heard immunity
How are infectious diseases transmitted?
Direct transmission
- Direct physical contact
Indirect transmission
- Vehicle‐borne
- Contaminated inanimate materials or objects (fomites).
- Vector‐borne
- Mechanical: No multiplication of agent (i.e. fly) in vector
- Biological: Multiplication of agent (i.e. Mosquitoes) in vector
Airborne
- Droplet
- Microbial aerosols usually the respiratory tract.
- Dust
- The small particles from soil clothes, bedding or contaminated floors by wind or mechanical agitation.
Rank these terms in increasing magnitude of impact:
Cluster, epidemic, outbreak and pandemic
Cluster < outbreak < epidemic < pandemic
What happens when the reproduction number of an illness is greater than and less than 1?
R >1: epidemic progresses
R <1: epidemic wanes
SARS-CoV-2 is the third known zoonotic coronavirus disease. What are the other two?
SARS-CoV
MERS-CoV
Whole‐genome comparison shows Covid‐19 shares 96% of genetic material with ____________coronavirus
Whole‐genome comparison shows Covid‐19 shares 96% of genetic material with bat coronavirus
Which coronavirus cluster does SARS-CoV-2 belong to?
Beta
What is the natural and intermediate host of SARS-CoV?
Natural: Bats
Intermediate: Civet cats
What is the natural and intermediate host of MERS-CoV?
Natural: Bats
Intermediate: Camels
What is the natural and intermediate host of SARS-CoV-2?
Natural: Bats
Intermediate: Unknown
What is the incubation period of COVID 19?
1-14 days
How can SARS-CoV-2 be transmitted?
- Direct or indirect contact
- Fomites - remains on surfaces
- Aerosol - respiratory droplets
- Fecal-oral route - virus shedding in 41%
- Body fluid and sexual activity - not fully understood
What do we know about the pathophysiology of COVID-19?
- Virus binds to the angiotensin‐converting enzyme‐2 (ACE2) receptor in humans [24]
- Downregulate ACE2, leading to a toxic over accumulation of plasma angiotensin‐II, which may induce acute respiratory Distress syndrome (ARDS) and myocarditis [25,26].
- ACE 2 is present in respiratory tract, endothelium of vessels and in several organs
- Explains extra pulmonary manifestations associated with infection ( e.g. heart, oesophagus, kidneys, bladder, and ileum) [27].
- COVID‐19 is hypothesised to be a disease of the endothelium.
- In autopsy pulmonary artery obstruction by thrombotic material at both the macroscopic and microscopic levels has been identified.
- Histopathologic of brain showed hypoxic changes but no encephalitis due to virus.
- Endotheliopathy and platelet activation are likely to be associated with coagulopathy, critical illness and death
Which receptor does SARS-CoV-2 target?
ACE2
Why is SARS-CoV-2 less common in children?
Low ACE2 in the nasal epithelium of children ages <10 years compared with adults
Explains why COVID‐19 is less prevalent in children [28].
What are the risk factors for COVID-19?
Age
Sex
Obesity
Co-morbidities
Ethnicity?
Genetics
Viral factors
Immune factors
Which cytokine is particularly upregulated in moderate and severe COVID-19?
IL6
What is the clinical diagnositic criteria for mild COVID-19?
- Symptomatic patients meeting the case definition for COVID‐19 without evidence of hypoxia or pneumonia
- Common symptoms include fever, cough, fatigue, anorexia, dyspnoea, and myalgia.
- Nonspecific Symptoms include sore throat, nasal congestion, headache, diarrhoea, nausea/vomiting, and loss of smell/taste.
What is the clinical diagnositic criteria for moderate COVID-19?
Clinical signs of pneumonia but no Signs of severe pneumonia including blood oxygen saturation levels (SpO₂) ≥90% on room air.
What is the clinical diagnositic criteria for severe COVID-19?
Clinical signs of severe pneumonia and severe respiratory distress and blood oxygen saturation levels (SpO₂) <90% on room air.
What is the clinical diagnositic criteria for critical COVID-19?
Presence of acute respiratory distress syndrome (ARDS), sepsis, or septic shock. May have acute pulmonary embolism, acute coronary syndrome, acute stroke, and delirium.
What tests are used to detect COVID-19?
Virus detection
- Nasopharyngeal specimens or lower respiratory samples ‐ RT‐PCR
Antibody detection
- Tells about a past infection.
- SARS‐CoV‐2 immunoglobulin G (IgG)/IgM antibodies in serum, plasma, or whole blood
Laboratory tests
Imaging
Where are COVID-19 sufferers cared for?
- Asymptomatic or mild disease can be managed at home
- Patients with moderate or severe disease in hospital
- Patients with critical disease require intensive care.
What is the current treatment approach for COVID-19?
- Supportive care according to the clinical presentation.
- Oxygen therapy, high‐flow nasal oxygen, non‐invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.
- Intravenous fluids, venous thromboembolism prophylaxis
- Antibiotics if there is clinical suspicion of bacterial infection.
- Low‐dose dexamethasone (steroid)
What are the current experimental therapies for COVID-19?
- remdesivir, Lopinavir / ritonavir
- Convalescent plasma
What is the difference between quarantine and isolation?
Isolation separates people with coronavirus (COVID‐19) from people who do not have the virus.
Quarantine separates and restricts the movement of people who have been or may have been exposed to coronavirus (COVID‐19)
What are the four main functions of sleep?
Conserve energy
Enhance survival / adaptation
Restorative / repair of injury (NREM)
Aid learning / memory consolidation (REM)
What are the current findings on how much sleep we need?
- Adults should sleep 7 or more hours per night on a regular basis to promote optimal health.
- Sleeping less than 7 hours per night on a regular basis is associated with adverse health outcomes, including weight gain and obesity, diabetes, hypertension, heart disease and stroke, depression, and increased risk of death. Sleeping less than 7 hours per night is also associated with impaired immune function, increased pain, impaired performance, increased errors, and greater risk of accidents.
- Sleeping more than 9 hours per night on a regular basis may be appropriate for young adults, individuals recovering from sleep debt, and individuals with illnesses. For others, it is uncertain whether sleeping more than 9 hours per night is associated with health risk.
How does loss of sleep effect performance and alertness?
The more sleep we lose, the worse both out performance and alertness are. However, performance suffers more than our perception of how alert we are which can be dangerous
What are the objective and subjective ways of measuring sleep?
Objective
- Polysomnography
- Actigraphy
Subjective
- Sleep diary
- Self-report questionnaires
What are the two distinct stages of sleep?
REM
NREM
How many stages of NREM sleep are there?
3
What is the best way to measure sleep?
Polysomnography
What are the main recording parameters of polysomnography?
Brain waves - Electroencephalogram (EEG)
Eye movement – Electrooculogram (EOG)
Muscle activity – Electromyogram (EMG)
Breathing or airflow
Heart rate and rhythm – Electrocardiogram (ECG)
Oxygen saturation – pulse oximetry (SpO2)
What does an EEG measure?
Difference in electrical potential between pairs of electrodes placed on the scalp.
List the common brainwaves in order of decreasing frequency
(Gamma)
Beta
Alpha
Theta
Delta
________waves: 4 – 7 Hz/cps - Sleep onset, light sleep
___________waves: 0.5 – 3 Hz/cps - Deep sleep
________waves: 14-26 Hz/cps - Alert waking activity, arousal from sleep
_________-waves: 8 – 13 Hz/cps - Relaxed waking, eyes closed, arousal from sleep
Theta waves: 4 – 7 Hz/cps - Sleep onset, light sleep
Delta waves: 0.5 – 3 Hz/cps - Deep sleep
Beta waves: 14-26 Hz/cps - Alert waking activity, arousal from sleep
Alpha waves: 8 – 13 Hz/cps - Relaxed waking, eyes closed, arousal from sleep
Score sleep in 30 sec sequential ________commencing at the start of the study
Score sleep in 30 sec sequential epochs commencing at the start of the study
If 2 or more stages coexist in an epoch, what do we assign it as?
Assign the stage comprising the greatest portion of the epoch
What is the typical brain activity of someone who is vigilantly wakeful?
Beta activity
Desynchronized
High frequency (15-20 Hz)
Low amplitude
What is the typical EEG, EOG and EMG activity of someone who is relaxed wakeful?
EEG: low voltage, mixed frequency; rhythmic alpha activity (8-13 Hz)
EOG: REMs or none, SEMs when drowsy
EMG: relatively high level of tonic activity, affected by voluntary movements
What is the typical EEG, EOG and EMG activity of someone who is in stage N1 sleep?
EEG: low amplitude, mixed frequency; mainly theta activity (4-7 Hz), vertex sharp waves
EOG: SEMs are often seen
EMG: tonic activity, may be slight decrease from waking
What is the typical EEG, EOG and EMG activity of someone who is in stage N2 sleep?
EEG: Low amplitude, mixed frequency (8-15 Hz) Sleep spindles (11-16 Hz, ≥ 0.5 sec): waxing and waning spindle shape K complex: negative sharp wave followed immediately by slower positive component (≥ 0.5 sec)
EOG: occasionally SEMs
EMG: tonic activity, low level, usually less than N1
What is this brainwave called? When is it seen?
K complex
Stage N2 sleep
What is this brainwave called? When is it seen?
Sleep spindle
Stage N2 Sleep
What is the typical EEG, EOG and EMG activity of someone who is in stage N3 sleep?
EEG: ≥ 20% of epoch, high amplitude (>75µv), slow wave activity (delta) (≤ 2 Hz)
EOG: none
EMG: tonic activity, low leve
What type of waves are these? What stage of sleep is this?
Delta waves
Stage N3 sleep
What is the typical EEG, EOG and EMG activity of someone who is in REM sleep?
EEG: low amplitude, mixed frequency (similar to N1). Sawtooth waves may occur
EOG: Bursts of EOG activity – rapid eye movements = phasic REM Epochs of no EOG activity = tonic REM
EMG: Chin EMG drops to its lowest level • Reflective of the inhibition of motor activity and loss of muscle tone which occurs in REM
Bursts of EOG activity – rapid eye movements = _______REM
Epochs of no EOG activity = ______REM
Bursts of EOG activity – rapid eye movements = phasic REM
Epochs of no EOG activity = tonic REM
What stage of sleep is this?
REM sleep
What is the order of sleep stages in a typical sleep cycle?
Awake
Stage N1
Stage N2
Stage N3
REM
Which stage of sleep is also called slow wave sleep?
Stage N3
What part of the night is stage N3 sleep more prominent? What about REM?
Stage 3/4 (N3) more prominent in first third
REM more prominent in second half
How long is a typical sleep cycle?
90 minutes
Which stages of sleep change the most as we age?
Increased wake after sleep onset (WASO)
Decreased slow wave sleep (N3)
Peak in circadian drive for wakefulness in the __________.
Peak in circadian drive for sleep in the ___________.
Peak in circadian drive for wakefulness in the evening.
Peak in circadian drive for sleep in the early morning.
_________drive for wakefulness opposes __________drive for sleep in the evening (just prior to normal bedtime) – helps maintain wakefulness.
Circadian drive for wakefulness opposes homeostatic drive for sleep in the evening (just prior to normal bedtime) – helps maintain wakefulness.
Define
Apnea
the cessation of breathing
Define
Apnea-hypopnea index (AHI)
the number of apneas or hypopneas recorded during the study per hour of sleep
Define
Continuous positive airway pressure (CPAP)
a type of positive airway pressure, where the air flow is introduced into the airways to maintain a continuous pressure to constantly stent the airways open, in people who are breathing spontaneously
Define
Endotype
A subtype of a condition that has a distinct functional or pathobiological mechanism
Define
Hypoglossal nerve stimulator
an implanted medical device that reduces the occurrence of OSA by electrically stimulating the hypoglossal nerve, which causes tongue movement
Define
Hypopnea
abnormally slow or shallow breathing
Define
Loop gain
a function of how much output is fed back to the input. Considered as a ratio of the controller gain (i.e., ventilatory response to CO2), the plant gain (i.e., blood gas response to a change in ventilation), and feedback gain (i.e., the speed [cardiac output] of feedback signal [CO2] back to the controller). Under normal non-REM sleep conditions, small (<2 mm Hg) changes in Pco2 are promptly recognized by the chemoreceptors, maintaining stable ventilation. This tightly controlled, and rapidly responsive, negative feedback system between the brain and the lungs allows for stable ventilation with miniscule changes in CO2 levels.
Define
Mandibular advancement devices
Devices that prevent upper airway collapse by protruding the mandible forward, thus altering the jaw and tongue position
Define
Maxillo-mandibular advancement
surgery that moves the upper (maxilla) and lower (mandible) jaws forward, and it effectively enlarges the airway in both the palate and tongue regions
Define
Obstructive sleep apnea (OSA)
occurs when the muscles that support the soft tissues in your throat, such as your tongue and soft palate, temporarily relax. When these muscles relax, your airway is narrowed or closed, and breathing is momentarily cut off
Define
Oral pressure therapy
a treatment for obstructive sleep apnea (OSA) that uses negative pressure in the mouth to shift the soft palate and tongue forward
Define
Waking hypersomnolence
a condition where a person experiences significant episodes of sleepiness, even after having 7 hours or more of quality sleep
Definition
the cessation of breathing
Apnea
Definition
the number of apneas or hypopneas recorded during the study per hour of sleep
Apnea-hypopnea index (AHI)
Definition
a type of positive airway pressure, where the air flow is introduced into the airways to maintain a continuous pressure to constantly stent the airways open, in people who are breathing spontaneously
Continuous positive airway pressure (CPAP)
Definition
A subtype of a condition that has a distinct functional or pathobiological mechanism
Endotype
Definition
an implanted medical device that reduces the occurrence of OSA by electrically stimulating the hypoglossal nerve, which causes tongue movement
Hypoglossal nerve stimulator
Definition
abnormally slow or shallow breathing
Hypopnea
Definition
a function of how much output is fed back to the input. Considered as a ratio of the controller gain (i.e., ventilatory response to CO2), the plant gain (i.e., blood gas response to a change in ventilation), and feedback gain (i.e., the speed [cardiac output] of feedback signal [CO2] back to the controller). Under normal non-REM sleep conditions, small (<2 mm Hg) changes in Pco2 are promptly recognized by the chemoreceptors, maintaining stable ventilation. This tightly controlled, and rapidly responsive, negative feedback system between the brain and the lungs allows for stable ventilation with miniscule changes in CO2 levels.
Loop gain
Definition
Devices that prevent upper airway collapse by protruding the mandible forward, thus altering the jaw and tongue position
Mandibular advancement devices
Definition
surgery that moves the upper (maxilla) and lower (mandible) jaws forward, and it effectively enlarges the airway in both the palate and tongue regions
Maxillo-mandibular advancement
Definition
occurs when the muscles that support the soft tissues in your throat, such as your tongue and soft palate, temporarily relax. When these muscles relax, your airway is narrowed or closed, and breathing is momentarily cut off
Obstructive sleep apnea (OSA)
Definition
a treatment for obstructive sleep apnea (OSA) that uses negative pressure in the mouth to shift the soft palate and tongue forward
Oral pressure therapy
Definition
a condition where a person experiences significant episodes of sleepiness, even after having 7 hours or more of quality sleep
Waking hypersomnolence
What is considered mild, moderate and severe sleep apnea?
Mild: 5-15 events/hour
Moderate: 15-30 events/hour
Severe: >30 events/hour
What are the risk factors for obstructive sleep apnea?
Obesity
Increasing age
Male gender
Anatomic abnormalities of upper airway
Family history
Alcohol/sedative use
What is the pathogenesis of obstructive sleep apnea?
What are the neurocogitive clinical consequences of OSA?
- Waking Hypersomnolence
- Decreased quality of life
- Increased automobile crashes
- Increased risk of mental illness
What are the cardiovascular clinical consequences of OSA?
- Systemic hypertension
- Arrthymias
- Increased incidence of congestive heart failure, stroke, and myocardial infarction
What is the first line treatement for OSA?
CPAP
What percentage of patients continue to use CPAP beyond 3 months?
50%
What are the current OSA therapies for individuals intolerant to CPAP?
Behavioral (i.e. weight loss, positional therapy)
Medical (i.e. oral appliance, expiratory resistance valves, suction devices)
Surgical (i.e. UPPP, hypoglossal nerve stimulation)
What are some examples of OSA behavioural interventions?
Weight Loss
Avoid Supine sleep
Avoid alcohol and sedatives before bed
What has a greatest effect on OSA: Diet, exercise or both?
Combined reduces both BMI and AHI
Diet lead to no change in either
Exercise decreased AHI
What is the major challenge and benefit of recommending weight loss for OSA?
Challenge: The improvement in OSA with weight loss is unpredictable and non-linear – true for weight-loss via diet or surgery
Benefit: There is no downside to weight loss – it bestows significant cardiovascular risk reduction benefits (even if no improvement in OSA)
What are some examples of OSA medical interventions?
Oral appliances (or Mandibular advancement devices)
Expiratory resistance valves
Suction devices
How do expiratory resistance valves work?
The positive pressure they create causes the airway and lungs to expand
What are the limitations of expiratory resistance valves?
Don’t work if you mouth breathe
Tolerance in real world appears poor
Cost is high in long term (have to keep purchasing them)
What are some examples of OSA surgical interventions?
Maxillo-mandibular advancement
Soft tissue surgery
Stimulate the upper airway muscles:
What are the limitations of the main CPAP alternative treatments?
Large variability in efficacy – Work for some, but not for others
Expensive (and invasive) to ‘test-drive’
Need robust ways to predict who will respond to therapy – How do we define a ‘responder’?
Stable upper airways lead to no OSA but highly collapsible upper airways lead to OSA. What about vulnerable upper airways?
Depends on the non-anatomical traits (e.g. Loop gain, muscle responsiveness and arousal threshold)
What are the non-anatomical traits that contribute to OSA?
Loop gain
Muscle responsiveness
Arousal threshold
How do we measure the OSA endotypes?
‘Gold-standard’ technique involves manipulating CPAP and measuring ventilation
What non-CPAP interventions are recommended for individuals with a small, collapsible upper airway?
Weight loss
Positional therapy
Oral appliances
Surgery
What interventions are recommended for individuals with oversensitive ventilatory control systems?
Supplemental O2/CO2
Acetazolamide
What interventions are recommended for individuals with poor pharygeal muscle responses?
Hypoglossal nerve stimulation
Noradrenergic/anti-muscarinic drugs
Training?
What interventions are recommended for individuals with low arousal threshold?
Sedative/hypnotics
Do oral appliances alter the non-anatomical traits?
No, only alter the passive collapsibility
Which two factors are major predictors of response to OSA oral appliance therapy?
Low collapsibility
Low loop gain
__________ predicts response to supplemental CO2 and O2
Loop gain predicts response to supplemental CO2 and O2
How do we predict successful sedative treatment?
What factors would make OSA endotyping clinicallly useful?
- Non-invasively determined
- Determined using currently collected clinical data
- In-laboratory diagnostic PSG/CPAP titrations
- Amenable to automation
What clincal variables are used to assess the anatomy/collapsibility endotype
CPAP level
Negative expiratory pressure
Negative pressure pulses
What clincal variables are used to assess the arousal threshold endotype
3 PSG characteristics [AHI82.5%. and %hypopneas >58.3%]
What clincal variables are used to assess the loop gain endotype?
Breath-hold duration
Chemoreflex test
__________ predicts response to combination therapy (O2+sedative)
CPAP level predicts response to combination therapy (O2+sedative)
___________ also predicts response to Hypoglossal Nerve Stimulation (HGNS)
CPAP level also predicts response to Hypoglossal Nerve Stimulation (HGNS)
True or False:
Collapsibility alone isnot a predictor of response to surgery
True
Even though surgery improves collapsibilty, loop gain is a better predictor
__________ predicts response to surgery
Loop gain predicts response to surgery
What combination of endotypes predicted a positive response to supplemental oxygen?
Mild collapsibility
High loop gain
Good muscle compensation
What combination of endotypes predicted a positive response to oral appliances?
Mild/moderate collapsibility
Low loop gain and high arousal threshold
Weaker muscle compensation
Which of the following three features are seen in allergic asthma?
a) High IgE, high eosinophils, high Th2 cytokines
b) High IgE, low eosinophils, high Th2 cytokines
c) Low IgE, high eosinophils, low Th2 cytokines
d) Low IgE, low eosinophils, low Th2 cytokines
Which of the following three features are seen in allergic asthma?
a) High IgE, high eosinophils, high Th2 cytokines
b) High IgE, low eosinophils, high Th2 cytokines
c) Low IgE, high eosinophils, low Th2 cytokines
d) Low IgE, low eosinophils, low Th2 cytokines
Salbutamol, a short-acting β2 adrenoceptor agonist (SABA) causes airway relaxation by:
a) blocking calcium channels
b) antagonising muscarinic receptors
c) increasing synthesis of cAMP
d) inhibiting phosphodiesterase
Salbutamol, a short-acting β2 adrenoceptor agonist (SABA) causes airway relaxation by:
a) blocking calcium channels
b) antagonising muscarinic receptors
c) increasing synthesis of cAMP
d) inhibiting phosphodiesterase
Mepolizumab:
a) should be used in asthmatics with high levels of neutrophils
b) is administered via the inhaled route
c) is the first choice if SABA are being used more than twice a week
d) is a recombinant monoclonal antibody against IL-5
Mepolizumab:
a) should be used in asthmatics with high levels of neutrophils
b) is administered via the inhaled route
c) is the first choice if SABA are being used more than twice a week
d) is a recombinant monoclonal antibody against IL-5
Which of the following pathological features is seen in COPD but not asthma?
a) increased mucous
b) airway fibrosis
c) airway inflammation
d) emphysema
Which of the following pathological features is seen in COPD but not asthma?
a) increased mucous
b) airway fibrosis
c) airway inflammation
d) emphysema
Inhaled glucocorticoids (ICS) are less effective antiinflammatories in COPD than asthma because:
a) higher levels of airway mucous in COPD reduces ICS bioavailability
b) people with asthma are more compliant and better at using inhalers than those with COPD
c) increased eosinophils in asthma but not increased neutrophils in COPD are targeted by ICS
d) smoking increases metabolism of ICS
Inhaled glucocorticoids (ICS) are less effective antiinflammatories in COPD than asthma because:
a) higher levels of airway mucous in COPD reduces ICS bioavailability
b) people with asthma are more compliant and better at using inhalers than those with COPD
c) increased eosinophils in asthma but not increased neutrophils in COPD are targeted by ICS
d) smoking increases metabolism of ICS
In the treatment of idiopathic pulmonary fibrosis, pirfenidone :
a) Should only be used in combination with inhaled glucocorticoids
b) Reverses established fibrosis
c) Inhibits both fibrosis and inflammation
d) Inhibits tyrosine kinase to exert its anti-fibrotic actions
In the treatment of idiopathic pulmonary fibrosis, pirfenidone :
a) Should only be used in combination with inhaled glucocorticoids
b) Reverses established fibrosis
c) Inhibits both fibrosis and inflammation
d) Inhibits tyrosine kinase to exert its anti-fibrotic actions
As we fall asleep, typically the start of the Non REM stage 1 state is characterized by the disappearance of:
a) Theta waves
b) Alpha waves
c) Delta waves
d) Beta waves
As we fall asleep, typically the start of the Non REM stage 1 state is characterized by the disappearance of:
a) Theta waves
b) Alpha waves
c) Delta waves
d) Beta waves
Brad has been up late preparing the BMS3052 theme test on respiratory and sleep disorders. Due to being tired he does not set his alarm which enables him to get a full 8 hours sleep. Whilst Brad was asleep, which sleep stage would he LIKELY spend the MOST % asleep in?
a) N1
b) N2
c) N3
d) REM
Brad has been up late preparing the BMS3052 theme test on respiratory and sleep disorders. Due to being tired he does not set his alarm which enables him to get a full 8 hours sleep. Whilst Brad was asleep, which sleep stage would he LIKELY spend the MOST % asleep in?
a) N1
b) N2
c) N3
d) REM
George Konstanza has recently been diagnosed with sleep apnoea. According to the latest evidence, which treatment option would be the least effective to reduce the apnoea-hypopnea index (AHI)?
a) CPAP
b) Exercise
c) Oral device
d) Weight loss
George Konstanza has recently been diagnosed with sleep apnoea. According to the latest evidence, which treatment option would be the least effective to reduce the apnoea-hypopnea index (AHI)?
a) CPAP
b) Exercise
c) Oral device
d) Weight loss
Which of the following forms of obstructive sleep apnoea (OSA) does not have variable rates of success for responders to oral appliances?
a) All OSA
b) Mild OSA
c) Moderate OSA
d) Severe OSA
Which of the following forms of obstructive sleep apnoea (OSA) does not have variable rates of success for responders to oral appliances?
a) All OSA
b) Mild OSA
c) Moderate OSA
d) Severe OSA
