Lecture 7 - Mechanisms In Asthma Flashcards
Asthma definition
- heterogenous chronic lung disease
- can be controlled but not cured
- Presence of both excessive variation in lung function and respiratory symptoms that vary over time and may be present or absent at any point in time
- simple definition: asthma is a syndrome whereby the airways narrow too much and too easily
Different asthma phenotypes
- Extrinsic asthma (most asthmatic): external triggers
- Intrinsic asthma (internally driven)
- mixed
- exercise-indiced bronchoconstriction
- Adult onset asthma
Prevalence of asthma
- 300 million worldwide
- 10% adults
- 15% children
- more indigenous, boys, and women
- poorer QOL
- 400 deaths annually (mostly elderly) -
- 40 thousand hospitalisation
- multiple phenotypes
Prevalence of astma and age
- Male: decline possibly due to increased airway size decreasing vulnerability to narrowing
- Females: change in hormone levels
Risk factors for asthma
- indoor allergens (house dust mites, pollution, pet dander)
- outdoor allergens (pollens and moulds)
- tobacco smoke
- chemical irritants in the workplace
- air pollution
- other triggers (cold air, extreme arousal, anger, fear, physical exercise)
Risk factors : dietary intervention
- asthmatic mothers prenattaly assessed
- control or prophylactic group
- 1 child in the prophylactic group had persistent asthma compared with 7 children in control group
Rate of lung dunction decline in asthma
- lung function declines with age in both asthmatic and non asthmatic, but higgher decline and more rapid in asthmatic
Direct provokers of Airway Smooth Muscle contraction
- MEthacholine: M3ACh receptors cause airway narrowing
- Histamine: H1 receptors: but cause indirect activation of the nerves - less commonly used
- PGF2alpha
Indirect provokers of ASM
- exercise induced bronchoconstriction
- hypertonic saline/mannitol
- beta-blocker
- Bradykinin
- Acid reflex - release of gut content into lung -> substance P etc…
BHR and asthma
- Provocation challenge test
- increase sensitivity (100x more in severe asthma)
- increase reactivity (slope)
- increase max response
Airway contraction induces remodelling
- sub epithelial reticular layer is thickened
- increase number of mucus cells
- thickening of collagen
- increase in muscle mass in airway
- so even in the short term the airway is remodelled
- everytime you challenge the airways -> remodelling happens
IMPLICATIONS: need to treat inflammation and bronchoconstriction in order to prevent adverse effects of airway remodelling
Summary of pathological changes that lead to thickened wall area of asthmatic airways
- inflammation
- increased smooth muscle
- hyperplasia of submucosal mucous glands and goblet cells
- laying down of ECM below the basement membrane
- angiogenesis
BHR: mechanism of action
- increased contraction via increased smooth muscle mass and amplification of contractile receptor acrtivation
- impaired relaxation of asthmatic airways due to activation of receptors that mediate relaxation
- decrease loafs that oppose airway narrowing
- impaired barrier to drug used for provocation of ASM
Treatment pyramid
1) SABA: short acting reliever
2) Corticosteroid : low dose preventer (recomended)
3) Corticosteroid/LABA: low dose preventer + long acting reliever
4) Corticosteroid/LABA: higher dose preventer + long acting reliever
5) Referral
Cells involved in pathogenesis
- macrophage/DC/ Mast cells respond to allergen
- activate Th2, eosinophils and neutrophils
- cause mucus hypersecretion, vasodilation, plasma leak edema, bronchoconstrictio
- Release of a LOT of cytokines - where costricosteroids act
