Lecture 18: Asthma Flashcards
What is asthma?
chronic inflammatory disease of the airways.
- main feature = airway obstruction caused by bronchospasm
- very old disease first reported 3,500 years ago
What are the symptoms of asthma?
- wheezing
- cough
- sputum production
- chest tightness
- shortness of breath
- variable episodic air flow obstruction (reversible either spontaneously or with treatment)
How does asthma differ from COPD?
the airway obstruction in COPD is generally not reversible
What is the prevalence of asthma?
- 1/6 adults and 1/4 children have asthma symptoms
- most common cause of hospital admissions in children
- one of the highest ranking disease in DALYs lost in males and certain females
- male children and female adults have highest prevalence of asthma
What are the features of asthma?
- episodic. Symptom will vary from day to day and season to season
- generally worse in winter and night time
- chronic disease which could be life threatening
What are the 3 key differences in the airways between asthmatics and healthy people?
- airways are smaller
- airways are thicker
- oedema, swelling and lots of sputum
What are risk factors that trigger Asthma?
- exercise
- viral infection
- animal fur
- house dust mites (common in NZ)
- moulds, smoke, pollen
- changes in weather
- strong emotional expression (laughing or crying hard, breathing heavily)
- airborne chemicals or dust
What lab studies are used in the diagnosis of asthma?
- history of coughing, wheezing, chest tightedness
- lung function tests
- allergy tests and serologic studies
- radiographic studies to confirm diagnosis
Which lung function tests are used in the diagnosis of asthma?
-PEFR: this only measures difference of lung function. It cannot diagnose asthma, but is used to measure the efficacy of treatment
-FEV1 (spirometry) is a better measure for asthma. Often done before and after beta 2 agonist treatment
if FEV1 is reversible this strongly indicates asthma
How can a skin test help with asthma diagnosis?
helps to identify the allergen which sets off the asthma
What is the response to allergen challenge?
there are 3 main types:
- acute phase response - which occurs 5-10 min after exposure
- late phase response - which occurs 4-6 hours after the lung function reduces
- mixture of the 2 phases.
after the allergen challenge, lung function stops and becomes worse at around 1 hour. then at the late phase response, lung function reduces at 4 hours
What is the mechanism of asthma?
- the acute phase response stimulates the release of cytokines and inflammatory cells
- the late phase activates TH2 cells and IL-13 and IL-9. These activate B cells and cytokines to activate mast cells
What are the two main treatments of asthma?
preventors and relievers
What are the treatment goals for asthma?
- control chronic symptoms
- achieve normal activity levels for exercise
- maintain near normal pulmonary function
- prevent eacerbations
- minimise ED visits and hospitalisations
- avoid adverse effects of asthma medications
What is the difference between preventors and relievers?
preventors: do not provide relief from asthma attack but are long term control medications which have anti-inflammatory effects and therefore prevent asthma attacks
relievers: drugs which provide relief from asthma symptoms for acute asthma attacks
How to relievers work to treat asthma?
Beta 2 agonists bind to beta 2 adrenoreceptors which si a post membrane receptor.
- triggers adenylate cyclase to conver ATP -> cAMP which increase PKA levels to induce further functions
- Na/K ATPase is increased, pi hydrolysis is reduced
- Na/Ca exchanger is increased and MLCK is reduced
- Resulting in bronchial relaxation
What is the mechanism for side effects induced by relievers?
- There will be upregulation of the K+ channel (hypokalaemia)
- There are also beta 2 receptors in the heart which will cause increased HR, contractility and contraction (tachycardia)
- also increase contractility in skeletal muscles (tremors)
- activates alpha 1, beta 1 and beta 2 in fat cells resulting in lipolysis and thermogenesis
What are the different types of forms of relievers?
MDI dry powdered device spacer nebuliser oral
What are short acting relievers good for?
- they have a short duration but act quickly
- useful for EIB or non specific triggers
- acute and severe asthma
- normally used prn
Why should salbutamol be combined with an ICS?
- If you use salbtuamol more than 6x /day the effects of the drug is reduced.
- combined use with an ICS can help to recover some of the beta 2 receptors so they are used together in therpay to retain the potency of salbutamol
When are long acting relievers used?
- these have a long duration but will take some time to have onset
- cant last for more than 24 hours so are for regular use
How are anticholinergics used?
- these can also reduce smooth muscle contraction and increase secretion of glands
- majority of these agents are non selective
- ipratropium has a slow onset of 1-2 hours, and lasts fr 6-12 hours. It is used regularly with low side effect and can reduce the mucous
-tiotropium can last longer than 24 hours and has equal affinity for the M1, M2 and M3 receptors
What are the xanthines?
These are the nonselective phosphodiesterase inhibitors
- activation of histone deacetylase has an anti-inflammatory effect
- relaxes muscles too
- increases cAmp and PKA levels to inhibit inflammatory cells resulting in bronchodilation and increase ciliary beat frequency to help clear the mucous
What are the non respiratory effects of xanthines?
- improve CV performance
- decrease pulmonary pressure
- improve diuresis
