Lung Disease- Asthma Flashcards
What is Asthma?
Atopic disease: Allergic disease
Immune response elicited to inherently innocuous antigens
Epidodic
Severity of disease increases with time
Can be fatal
What are the types of Asthma
Apotic- Allergic disorder
Non-apotic (non-allergic) causes also exist but later onset and much rarer
Why do symptoms of Asthma typically occur?
Following exposure to an allergen/trigger
e.g. dust mite, animal hair, cold air, exercise, pollutants
What are the clinical symptoms of asthma?
Shortness of breath
Wheezing
Cough
During an asthma attack (exacerbation) symptoms get suddenly worse
What is airflow obstruction caused by
Bronchoconstriction
Mucus hyper-secretion
Airway hyper-responsiveness
What is brochoconstriction?
Leads to airflow obstruction
Smooth muscle contracts, airway lumen narrows (diameter decreases)
Excessive mucus secretion which blocks to limit airflow
How does airway hyper-responsiveness take place?
Occurs due to airway remodeling
Permanent alterations to airway structure
Airflow limitation is only partially reversible
Exaggerated airway narrowing in response to innocuous stimuli
What is key to Asthma pathogenesis and symptoms?
Asthma is a chronic inflammatory disorder of the conducting airways
Airway inflammation is key to disease pathogenesis and symptoms
What are the phases of atopic asthma?
- Sensitisation to allergen
- Early phase response (<1h)
- Late phase response (3-8 hours)
- Airway remodeling (ongoing, years)
What happens in the sensitisation phase?
Requires that the individual inhales an allergen into the lungs
The allergen is internalised by dendritic cells (APC’s)
Survey the environment for pathogens
Extend the processes into the airway lumen
Once internalised, what happens to the allergen?
The allergen is broken down into smaller fragments (peptides)
These are transported to the cell surface via MHC class 2 molecules
Dendritic cells present the antigen to lymphocytes (T cells)
T cell receptors on T lymphocytes recognise the antigen
T cells are activated
What is produced by T cells during sensitisation?
IL-4 (cytokine) is produced
IL-4 activates B cells (lymphocytes to produce antibodies (IgE) against the inhaled allergen
Where are mast cells located?
In the airway wall
Resident immune cells
Increase in mast cell numbers in asthmatics
What are mast cells filled with?
Inflammatory mediators
What binds to mast cells during sensitisation?
IgE binds to mast cells in the lungs
Mast cells are sensitised
NO symptoms at this stage
What happens during the early and late phase?
Re-exposure to the allergen stimulates an inflammatory response
Triggers asthma symptoms
2 phases in this response: early and late
What happens in the early phase?
Following inhalation the allergen binds to IgE on mast cells
This stimulates mast cell degranulation Exocytosis of pro-inflammatory mediators from granules
What are the effects of Mast cell generated mediators?
Bronchoconstrictors and mucus secretion
Inflammation
Cytokines: activate immune system
What happens during the late phase?
Eosinophils are responsible for symptoms at late phase of asthma
Recruited to the airways following mast cell activation
Granules release inflammatory mediators which stimulate bronchoconstriction and mucus production
What cells are involved in asthma at what stages?
Sensitisation- APC’s, lymphocytes, mast cells
Inflammation- Mast cells (early phase) and Eosinophils (late phase)
What happens during airway remodelling?
Following exposure to an allergen airways narrow due to bronchoconstriction and mucus secretion
Inflammatory mediators released from mast cells and eosinophils
Symptoms recurrent, but reversible
What happens over time with airway remodelling?
progressively worse with age
Airflow limitation becomes only partially reversible
Over time the airway becomes hyper responsive to a variety of stimuli
What is airway hyper-responsiveness caused by?
AHR is caused by inflammation that drives permanent structural changes in the airway wall
Characterised by narrowing of airways
Airway wall thickening
Increase in epithelial and muscle cell size and number
Airway obstruction
Mucus hypersecretion
How is asthma diagnosed?
Measure Peak Expiratory Flow
What are the 2 main strategies to treat asthma?
Anti inflammatory agents: to supress airway inflammation
Bronchodilators: to relieve bronchoconstriction
Combination of both usually used
What are Bronchodilators?
Relax airway smooth muscle
Increase airflow to lungs
What are the three main categories of bronchodilators
Beta receptor agonists
Methylxanthines
Leukotriene antagonists
What do B2 agonists do?
B2 receptor agonists
Cause airway smooth muscle relaxation by blocking signals produced by nerves
What do Methylxanthines do?
Inhibit the activity of phosphodiesterase (PDE) in smooth muscle cells
Increases cyclic AMP concentration in smooth muscle cells
Causes smooth muscle cell relaxation
What are the anti-inflammatory agents in asthma?
Corticosteroids
Leukotriene antagonists
Mast cell degranulation inhibitor
Neutralisation of IgE
What do Leukotriene antagonists prevent?
prevent the production of leukotrienes by cells OR inhibit LT receptor activation
How can drugs be used to affect mast cells?
Drugs can inhibit mast cell degranulation
Mediators not released
Prevents mast cell mediated bronchoconstriction and inflammation
What novel therapies are under development for asthma?
Antibodies that bind to IgE to decrease allergen binding to mast cells
Reduces mast cell activation
