Lecture 7 - Mechanisms In Asthma Flashcards Preview

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Flashcards in Lecture 7 - Mechanisms In Asthma Deck (20):

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



- Antigen presentation -> IgE production -> mast cell degranulation and cytokine release -> clinical effects


Relievers of asthma: bronchodilator aerosols

- short acting B2 AR agonists
- Long acting B2 AR agonists
- Anticholinergics
- Theophylline: also preventer


Preventers (anti-inflammatory)

- cromones
- inhaled corticosteroids
- anti-leukotriene drugs
- Anti-IgE
- Anti- IL5, FDA approved, age-dependent and asthma linked to eosinophils


Example of corticosteroids

- most are inhaled
- beclomethasone, fluticasone, budesonide, ciclesonide
- treat severe exacerbations with short courses
- back to maintenance doses of inhaled corticosteroid
- patient should be assessed by a thoracic physician


Side effects of corticosteroids

- not common when using less than 100 ug/day
- oropharyngeal thrush (candida)
- dysphonia: 80-90% of drug via mucociliary transport into GIT, preventive measures: ringing and spacers

- immunosuppression, osteoporosis, muscle wasting, hyperglycemia, cataracts, bruising, moon face

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