Asthma Flashcards
What are the three classic characteristics of asthma?
- Airflow limitation which is usually reversible spontaneously or with treatment
- Airway hyper-responsiveness to a wide range of stimuli
- Bronchial inflammation with T lymphocytes, mast cells, eosinophils with associated plasma exudation, oedema, smooth muscle hypertrophy, matrix deposition, mucus plugging and epithelial damage
What are the two main aetiological factors of asthma?
- Genetics
2. Environment
What are the genetic factors that predispose someone to develop asthma?
IL-4 and IL-13 strongly associated in asthma
What environmental factors can predispose someone to develop asthma?
There are different environmental influences on asthma:
- Early childhood exposure to allergens (hygiene hypothesis)
- Maternal smoking
- Intestinal bacteria
What factors can precipitate asthma?
- Occupational factors
- Cold air and exercise
- Atmospheric pollution and irritant dusts, vapours and fumes
- Diet - Increased intakes of fresh fruit and vegetables have been shown to be protective
- Emotion
- Drugs
What drives inflammation in asthma?
Th2-type T lymphocytes which facilitate IgE synthesis through the production of IL-4 and eosinophilic inflammation through IL-5
Late-stage asthma can be driven by Th1 response, triggering TNF-alpha
What cells are involved in the inflammatory response in asthma?
- Mast cells
- Eosinophils
- Dendritic cells and lymphocytes
Where in the airways can mast cells be found?
asthma
Increased in epithelium, smooth muscle and mucous glands
Where in the airways can eosinophils be found?
asthma
Found in large numbers in the bronchial wall
They are attracted to the airways by the eosinophilopoietic cytokines IL-3, IL-5 and GM-CSF
What do eosinophils do in asthma?
When activated, eosinophils release LTC4, and basic proteins such as major basic protein (MBP), eosinophil cationic protein (ECP) and eosinophils peroxidase (EPX) that are toxic to epithelial cells
Where in the airways can dendritic cells be found?
asthma
Mostly abundant in mucous membranes in the alveoli
What do dendritic cells do in asthma?
Dendritic cells have a role in the initial uptake and presentation of allergens to lymphocytes → T helper lymphocytes (CD4+) show evidence of activation and the release of their cytokines plays a key part in the migration and activation of mast cells (IL-3, IL-4, IL-9 and IL-13) and eosinophils
What are the remodeling changes that happen in asthma?
- Deposition of matrix proteins
- Swelling and cellular infiltration expand the submucosa beneath the epithelium so that for a given degree of smooth muscle shortening there is excess airway narrowing
- Swelling outside the smooth muscle layer spreads the retractile forces exerted by the surrounding alveoli over a greater surface area so that the airways close more easily
What are the principal symptoms of asthma?
- Wheezing attacks
2. Episodic shortness of breath
At what time of the day are asthma symptoms worst?
Symptoms are usually worst during the night, especially in uncontrolled disease