Module 4.2 Flashcards
Thunderstorm Asthma (9 cards)
Appreciate how simple spirometry can be used to measure lung function and help diagnose respiratory disease.
Spirometry is the most commonly used pulmonary function test carried out by a device called a spirometer.
- Spirometry helps to differentiate between normal lung function and obstructive (asthma) or other restrictive disease patterns
- Steps to carry out spirometry:
- Measure RVC (relaxed vital capacity):
* The maximal amount of air exhaled in a relaxed expiration from full inspiration to residual volume (amount of air remaining in lungs after full expiration)
- Measure FVC (forced vital capacity):
* The total volume of gas forcibly exhaled from a position of full inspiration
* FEV1: volume of gas forcibly expelled after 1 second
- Note: pathology means disease
Describe the clinical manifestations of asthma, how it is diagnosed and the basic underpinning pathobiology.
- Note: Clinical manifestations means observable symptoms
- Note: pathobiology refers to the mechanisms of disease
Asthma: Inflammatory disease of the lungs, variable airflow obstruction due to smooth muscle bronchoconstriction
- Symptoms of asthma:
* Shortness of breath
* Chest tightness or pain
* Wheezing when exhaling (children commonly)
* Persistent cough when sleeping
- Diagnosis:
* Clinical history of recurrent wheezing and breathlessness, responsive to beta-agonist (salbutamol)
* Lung function testing - spirometry
- Disease mechanisms:
- Allergic and non-allergic pathways - context
* IgE (immunoglobulin E) is an antibody (a protein) that is produced by white blood cells and binds to harmful substances (antigens) to eliminate them, causing an allergic reaction.
* Mast cells are white blood cells found in connective tissue throughout the body and are part of the body’s innate immune response – they are the major producers of histamine
* Mast cells are part of your immune system and are made in the bone marrow and then move into bloodstream and tissues to help fight infections.
* Types of white blood cells in allergic reactions:
Mast cell – produces igE antibodies – release histamine
Eosinophils – fight parasites
Basophils – release enzymes like histamine, causing allergic reactions
* Serum is clear blood fluid after blood cells have been removed
Low serum conc – high blood cell concentration
- Allergic vs non-allergic pathways of asthma
* Eosinophilic asthma:
Type of asthma induced by allergen-specific and non-allergen-specific pathways - Eosinophilic inflammation is a type of asthma that occurs when the airways are filled with eosinophils, a type of white blood cell that helps fight infections
* Allergen:
Environmental triggers:
* Pollen – hayfever
* Grass pollen
* Dust mites
* Pet dander
* Non-allergic:
Exercise
Air pollution from smoke, industrial pollutants
Weather changes – cold air
Emotional stress
Discuss the current theories as to why allergic diseases are becoming more prevalent.
- “Hygiene” hypothesis: Westernised lifestyle, we are so protected from various pathogens/allergens that we over time have become sensitive to them.
- “Old Friends” hypothesis: diversity of organisms have been lost so no longer exposed to these organisms that have coevolved our immune systems
- Epithelial barrier hypothesis: exposure to chemicals/detergents leads to damage of the epithelium, permitting greater entry of some microorganism
Understand how allergic sensitisation can lead to asthmatic symptoms.
Allergic sensitisation is the process by which the immune system learns to identify a harmless substance as a threat, resulting in an allergy.
Note: a sensitised individual is someone that has become sensitive to a substance and reacts negatively (allergic response)
Steps to allergic sensitisation:
- Sensitised mast cells: The binding of IgE to IgE receptor on mast cell surfaces – sensitisation
- Mast cells contain mediators such as histamine
- IgE antibodies are on mast cells and basophils bound on Fc(epsilon)R1 receptor, and are ready to be released to encounter allergens when mast cells are sensitised
- An activated mast cell undergoes degranulation, where mediators are released (histamine produces allergic reaction – (also contains cytokines and eicosanoids)
Explain how grass pollen, climatic conditions and population density led to the TA event of November 2016.
- TA event November 2016:
- Grass pollen:
- Pollen contains the male gametes of conifers (pine trees etc.) and flowering plants
- Plants use either the wind or animals (or both) to carry pollen between individuals
- Pollen is a small powdery substance produced by certain types of plants as part of their process of sexual reproduction
- Thunderstorm + grass pollen affects:
- TA triggered by a combination of high grass pollen levels and a certain type of gusty thunderstorm
- The role of the thunderstorm is to fragment the pollen into smaller particles
- These smaller particles were able to deposit then deeper into the lower respiratory tract causing more severe asthmatic symptoms
- Population density:
- Increased allergen exposure and limited healthcare facilities due to overwhelming number of emergencies leading to healthcare burden exacerbating TA
Outline how drugs are discovered and examined for safety and efficacy with emphasis on drugs used to treat asthma.
- Features of useful medicines:
- Effective – have the therapeutic action for which they are indicated
- Convenient - e.g. once a day tablet
- Well-tolerated – few and manageable adverse (side) effects
- Safe – low risk of toxicity/drug allergy (consider current vaccine discussion (rare toxicity))
- Not too expensive
- How do medicines act in the body?
- Medicines (drugs) bind to proteins that are called receptors
- Drugs that stimulate the receptor protein function are called agonists
- Drugs that bind to the active region of the receptor protein but don’t stimulate the protein function are called antagonists
- Where do we get medicines?
- Nature – hormones produced by adrenal glands
- Stress hormones cortisol and adrenaline also protect against inflammation in acute allergic reactions such as anaphylaxis
- Atropine (from plants) – a xenobiotic antagonist binds to muscarinic receptors and prevents the actions of the endogenous agonist acetylcholine reducing its effects on bronchoconstriction
- High-throughput screening (HTS) – a brute-force methodology
- Target Identification: Identify and validate a biological target such as a receptor.
- Compound Library Preparation: Assemble a diverse library of compounds that can be tested for that biological target.
- Screening: Automate the screening process to test compounds against the assay.
- Data Analysis: Identify and analyze hits based on biological activity.
Consider the effects that climate change might have on the prevalence of allergic disease and TA events
- Improving patient morbidity and mortality in the future:
- Climate change carries risk:
Aeroallergen concentration: - Increasing air temperatures and CO2 concentrations are associated with increased pollen production (faster and larger growth of plants)
Frequency of extreme weather events: - Flooding, tropical cyclones: mould growth in homes
- Thunderstorm frequency
Impact: - Greater exposure to aeroallergen leading to a higher sensitisation/allergen response rate
- More frequent epidemic events
Industrial revolution: increased atmospheric greenhouse gases commencing since the 1750s with rapid changes over the last 50 years
Integrate how future TA events can be perhaps better managed through multiple approaches
Public education
Forecasting
Health professional training
Emergency response planning
Consider the different types of muscle that exist and how they are controlled by different
parts of the peripheral nervous system
- Skeletal muscle: responsible for movement and posture, attached to bones, controlled by somatic NS within PNS
- Smooth muscle: found in walls of hollow organs such as digestive tract and blood vessels, controlled by ANS
- Cardiac muscle: found in heart, controlled by ANS
