PH2113 - Asthma Flashcards
What is asthma caused by?
Lung inflammation
What are the steps in asthma development?
- sensitisation
- exposure
- inflammatory response
- bronchoconstriction (asthma attack)
Describe the airways during an asthma attack
During an asthma attack, the airway is constricted due to smooth muscle contracting
What is resistance to air flow proportional to?
1 / airway radius^4
What is mucus plugging?
Airways completely blocked by mucus
What causes a decreased airway diameter?
Airway smooth muscle contraction + increased mucus production
What does airway resistance affect?
Airflow
What determines airflow?
Respiratory drive
- metabolism
How is airflow measured?
Spirometry
- peak flow
- FEV1 - the amount of air you can force from your lungs in one second
What generates the pressure gradient in the lungs?
At rest - diaphragm
During exercise - diaphragm, internal and external intercostals
What is resistance to airflow determined by?
Airway diameter
What is peak flow?
Maximum rate of exhalation
What is FEV1?
Volume of air that can be forcibly exhaled in 1 second
What is the function of a reliever inhaler?
- cause bronchodilation (relieve acute asthma symptoms)
- no anti-inflammatory action (does not affect disease progression)
What is the function of a preventer inhaler?
- do not cause bronchodilation (no acute relief from symptoms)
- anti-inflammatory action (limits disease progression)
Which class of drugs are primarily in preventer inhalers?
Corticosteroids
- beclametasone
- fluticasone
What is a combi-inhaler?
- contains both preventer (steroid) and reliever (long acting beta-agonist)
- provides long-term bronchodilation and prophylaxis
How many people in the UK have asthma?
5.4 million people
What proportion of households are affected by asthma?
1/5
How many people die each day from asthma?
3 people a day die from asthma
What percentage of asthma hospital admissions are avoidable?
75%
What percentage of asthma deaths are preventable?
90%
Why are asthma statistics so bad?
Poor asthma control
- increase rates of morbidity and mortality
Asthma is controlled by preventers (corticosteroids)
- corticosteroids are not effective? (steroid resistance)
- patients do not take their medication (poor adherence)
- as low as 50%
- confuse anabolic steroids and corticosteroids
- patients do not take their medication correctly (poor inhaler technique)
- needs to go to the bottom of the lung
What type of hypersensitivity reaction is asthma?
Type 1
What are the two main types of asthma phenotype?
Extrinsic
- allergen induced
Intrinsic
- non-allergen induced
Give examples of extrinsic asthma triggers
- pollen
- house dust mite
- mould
- ragweed
Give examples of intrinsic asthma triggers
- viral infection
- cold, dry air
- environmental pollution
- aspirin
- cigarette smoke
- exercise
What are the two phases of an asthma attack?
- early phase
- late phase
What happens in the early phase of an asthma attack?
Immediate response to release of inflammatory mediators from mast cells
What happens in the late phase of an asthma attack?
Continuation of inflammation characterised by an influx of eosinophils into the lungs
What is hyperresponsiveness?
Increased response of the target cells (receptors)
How does asthma sensitisation take place?
An allergen (foreign protein) triggers a dendritic cell (resident in the lungs) which migrates into the lymph nodes The dendritic cell presents the antigen to the Th0 helper lymphocytes which differentiate into Th2 lymphocytes This activates B cells which generates IgE antibodies
Upon re-exposure, the IgE receptors on mast cells in the lungs bind the IgE which starts the inflammation process
What happens to mast cells when they are activated by an allergen binding to IgE?
Degranulation
- release of histamine and other mediators
Describe the process of sensitisation
- allergen is recognised as foreign by dendritic cell
- dendritic cells migrate to lymph nodes where they display the allergen to undifferentiated population of T cells
- This then causes the T cells to differentiate into TH2 lymphocytes which then activate B cells.
- B cells generate IgE immunoglobulins
- IgE then binds to high affinity receptors on mast cells
- preexposure of the allergen causes cross linking between multiple IgE binded to the mast cell which triggers mast cell degranulation
What are the outcomes of the inflammatory cascade?
- bronchoconstriction
- vasodilation
- increased mucus production
- increased vascular permeability
- leukocyte recruitment
What are the late phase responses of an asthma attack?
Continuation of the inflammatory response
- oedema begun during early phase is more prominent
- sensory nerve fibres release inflammatory agents that can cause bronchoconstriction
- increased parasympathetic activation ACh and M3 receptors which cause bronchoconstriction
What causes and drives asthma progression?
Inflammation
What is airway remodelling?
Airway remodelling is an ongoing structural change caused by asthma that leads to thickened airway walls and the narrowing of the airway
Driven by chronic inflammation Generally makes airway thicker - reducing diameter of airway - increased obstruction of airway - increased resistance to airflow Lung less stretch - reduced capacity of lung - reduced elastic rebound when exhaling Chronic inflammation - more mucus from goblet cells Pulmonary angiogenesis - new blood vessels Smooth muscle hypertropy
