ASTHMA Flashcards
what is asthma?
Common condition inn which there is a HYPER-REACTIVITY of the airways and chronic inflammation
what are the symptoms of asthma
- wheeze
- tightness of chest
- NON-PRODUCTIVE cough
- shortness of breath, often worse at night
- cough that is worse in the mornings or at night
when is asthma most commonly diagnosed?
between ages of 3-5 where it can either worsen or get better with age
what are the 3 characterises of asthma.
1) airflow limitation
- reversible airflow obstruction
2) airway hyper-responsiveness
3) bronchial inflammation
what can asthma be classified according to?
1) its trigger factors
- Atopic or Non-atopic
- extrinsic or intrinsic
2) by age of onset
- adult onset
- childhood onset
3) by inflammatory subtypes
- Type 2 (characterised by TH2 lymphocytes)
- Non-type 2
4) Response to therapy
5) chronic or acute asthma
- chronic = asthma requiring long term maintenance
- acute = short term exacerbation
6) brittle asthma
= asthma in patients whose PEFR variability is significant despite considerable medical therapy
or
= sudden acute attacks without an obvious trigger on a background of good control
what does atopy mean?
- characteristic skin reactions to common allergens
- have circulating allergen specific antibodies (IgE)
- runs in families
what 2 factors affect serum total IgE levels?
1) genetic factors
2) environmental
airway hyper-responsiveness is a characteristic feature of asthma, so what 2 things could be done to demonstrate if you have it or not?
1) bronchial provocation tests
= inhale gradually increasing concentration of histamine or metha-choline
2) Exercise testing or inhalation of cold, dry air, mannitol or hypertonic saline.
How does inhaling gradually increasing concentrations of histamine and metha-choline work?
- they induce transient airflow limitation in susceptible individuals
- patients with asthma respond to very low doses of methacholine
how does exercise testing orinhalation of cold, dry air, mannitol or hypertonic saline work?
they are indirect tests that release endogenous mediators, e.g. histamine, prostaglandins and leukotrienes, which cause broncho-constriction.
what are the triggers for asthma?
1) allergens
- house dust mite
- pollen
- animal dander
- fungi
2) airborne irritants
- pollution
- tobacco smoke
- fumes
- cold air
- mould and damp
3) drugs
- NSAIDS = non-steroidal anti-inflammatory drugs
- beta blockers
4) infections
- upper respiratory tract infections
- acute bronchitis
5) foods
- eating lots of fruit and veg is meant to reduce your chances of getting asthma
6) physical activity
- exercise
why does exercise & cold, dry air cause asthma?
- exercise induced asthma doesn’t occur when exercising, but occurs afterwards
- during exercise, prostaglandins, histamine and leukotrienes are released and theres stimulation of neural reflexes when the epithelial lining flood of the bronchi becomes hyperosmolar owing to drying & cooling during exercise
what NSAID drugs trigger asthma?
- aspiring and propionic acid derivatives, such as indometaciin and ibuprofen
Why do NSAIDs drugs trigger asthma?
- the drugs BLOCK the COX-1 enzyme
- therefore decreasing the production of thromboxane & some anti-inflammatory prostaglandins
- this causes the over production of pro-inflammatory leukotriene
- causing severe exacerbations of asthma
- causing bronchoconstriction
does the inhibition of enzyme COX-2 trigger asthma?
no
- its only the inhibitors of COX-1 that triggers it
give an example of a beta blocker drug?
Pro-pranolol
do the airways have a direct parasympathetic or sympathetic interaction?
the airways have a direct PARASYMPATHETIC innervation, which causes bronchoCONSNTRICTION.
- there is no direct sympathetic innervation of bronchial smooth muscle
due to the airways having a direct parasympathetic innervation, what is the airway critically dependent upon circulating?
it is critically dependent upon circulating ADRENALINE, acting through BETA-2 RECEPTORS on the surface of smooth muscle cells.
therefore, what happens if there are beta-blockers?
- then there is inhibition of this effect
- causing broncho-constriction and airflow limitation
in allergen induced asthma, what are the 2 phases of an asthma attack?
1) immediate asthmatic reaction
2) dual & late phase reaction
what 2 factors play an important role in the severity of asthma?
1) airway inflammation
2) airway wall remodelling
what 4 cells are involved in airway inflammation?
1) mast clles
2) eosinophils
3) dendritic cells
4) lymphocytes
what do mast cells release that cause the asthmatic reaction?
They release mediators;
- histamine
- tryptase
- PGD2
- cysteinyl leukotrine
- cytokines
- chemokine
- growth factors
what are the 3 hallmarks of asthma?
1) basement membrane THICKENS
2) COLLAGEN DEPOSITED in the sub-mucosa
3) smooth muscle undergoes HYPERTROPHY
what happens to the epithelium during asthma?
- it is damaged and stressed
what is the epithelium a major source of?
its a major source of mediators, cytokines and growth factors that enhance inflammation and promote tissue remodelling
what does damage to the epithelium make it more vulnerable to?
more vulnerabel to infections bu common respiratory viruses and to the effects of air pollution
what investigations could be done?
1) Lung function tests
= PEAK FLOW
2) exercise tests
3) Histamine or methacholine bronchial provocation test
4) trial of corticosteroids
5) exhaled nitric oxide
6) skin tests
7) allergen provocation tests
what 2 lung function tests can be done?
1) peak expiratory flow rate (PEFR)
2) spirometer
when should the peak flow be carried out?
- when you wake up
- before you go to bed
- before you take your bronchodilator
- after you take your bronchodilator
what result in spirometry would you be able to diagnose asthma?
- reduced forced expiratory ratio (FEV1/FVC < 75%)
- if there is a GREATER THAN 15% improvement in FEV1 or PEFR following the inhalation of a bronchodilator
what does the test of histamine and methocholine bronchial provocation test indicate?
the presence of airway hyper-responsiveness
describe the asthma treatment pyramid.
1) shorting acting B2 agonists
2) INHALED STEROIDS
e.g. cromoglicate
+ CysLT1 Rec antagonists
+ LABA/LAMA
+ theophyline
+ Anti IgE / IL5
3) oral steroids
give examples of steroid sparing agents.
- methotrexate
- ciclosporin
- intravenous immunoglobulins
- anti-IgE monoclonal antibody
= omalizumab - etanercept
= infliximab
= lebrikizumab
if a patient has just occasional symptoms with 100% predicted PEFR, how would you treat them? STEP 1
- as required short acting B2 agonists
if the SABA is used more than once, theres daily symptoms of PEFR is <80% of predicted what would you do? STEP 2
- regular inhaled preventer therapy
= anti-inflammatory drugs - inhaled low dose corticosteroids
= leukotriene receptor antagonists (LTRA), theophyllinee & sodium cromoglicate
if that doesn’t control it, symptoms are severe or the PEFR is 50-80% of predicted what would you do?
STEP 3
- inhaled corticosteroids & long acting inhaled B2 agonists
= continue inhaled corticosteroids
= add regular inhaled (long acting) LABA
= if still not controlled add either LTRA, modified release oral theophylline or B2 agonists
if still not control, symptoms are uncontrolled even with high dose inhaled corticosteroid, what would you do?
STEP 4
- high dose inhaled corticosteroid and regular bronchodilator
= increase high dose corticosteroids up to 200microrgam daily
= plus regular long acting B2 agonists
= plus either LTRA or modified release theophylline or B2 agonists
is the symptoms deteriorate and PEFR is < 50% of predicted what would you do?
STEPS 5 & 6
- regular oral corticosteroids
or
- hospital admission
what do beta-adrenoceptor agonists do?
1) relax bronchial smooth muscle
2) effective in relieving symptoms
- but they DON’T AFFECT UNDERLYING AIRWAY INFLAMMATION
what sort of asthmatics should be using bronchodilator treatment ALONE.
only people with the MILDEST ASTHMA with only occasional intermittent attacks.
if an individual is using their B2-adrenoceptor agonists on a daily basis, what should they be started on?
they should be started onn inhaled corticosteroids.
if an individual has poorly controlled asthma and is on a standard dose of inhaled steroid what else should they be given?
they should also be on a LONG ACTING B2 ADRENOCEPTOR AGONISTS (LABA).
e.g. salmeterol or formoterrol
describe how LABAs should be taken, how often and how they work.
- taken by inhalation and are effective for up to 12 hours
- given once or twice a day
- they improve symptoms and lung function and reduce exacerbations in patients
can LABAs be taken on their own?
LABA CANNOT be taken on their own, but always in combination with an inhaled corticosteroid
give examples of non-selective anti-muscarinic bronchodilator drugs and what do they do in asthma treatment?
- non-selective muscarinic antagonists;
= ipratropium bromide
= oxitropium bromide - useful in asthma exacerbations
- less helpful in stable asthma
what do the drugs sodium cormoglicate and nedocromil sodium do?
they are anti-inflammatory cells, preventing activation of inflammatory cells by blocking a specific chloride channel, which in turn prevents chloride influx
what sorts of patients are anti-inflammatory drugs used in?
patients with milder asthma
- used in step 2
in what sorts of asthmatics should an inhaled corticosteroid be used?
- used in people with regular persistent symptoms (even mild symptoms)
what are tithe most commonly used inhaled steroids?
= BECLOMETASONE
- budesonide
- fluticasone propionate
- fluticasone furcate
- mometasone furcate
- triamcinolone
up to what dose do beclometasonne and budesonide not seem to present a risk?
up to 800micrograms/days
what are some unwanted side effects of corticosteroids?
how could you reduce these side effects?
- oral candidiasis
- hoarseness
- osteoporosis is less likely than with oral steroids but can occur with high dose inhaled corticosteroids (beclometasone and budesonide > 800 micrograms).
- candidiasis and GI absorption minimised by using a spacer, mouth washing and teeth cleaning after use
when should oral corticosteroids be used?
they should be used for individuals who are not controlled by inhaled corticosteroids.
STEP 5.
- dose should be kept as low as possible to minimise side effects.
what do the leukotriene receptor antagonists target?
they target the cysteinyl LT1 receptor.
give examples of the types of drugs in the leukotriene receptor antagonists category and state how they are given?
- montelukast
- pranklukast
- zafirlukast
= they are given orally.
when should leukotriene receptor antagonist theory be tried?
in patients who is NOT controlled on low to medium dose of inhaled steroids.
do they work along with LABAs or by themselves?
LTRAs action is additive to LABAs.
when is LTRA therapy useful?
- patents requiring high dose inhaled or oral corticosteroids
- people with aspirin intolerant asthma
- asthmatic smokers
give 2 examples of monoclonal antibodies that could be used?
- omalizumab
- lebrikizumab
what does omalizumab do?
- it is directed against IgE, chelates free IgE and down-regulates the number & activity of mast cells and basophils.
when is omalizumab useful?
useful in patents with frequent exacerbations & hospital admissions.
what does lebrikizumab target?
targets IL13
why are asthma attacks most commonly caused?
- by lack of treatment adherence
- respiratory virus infection associated with the common cold
- exposure to allergen or triggering drug e.g. NSAIDS
what are the 4 things that indicate someone is having an acute severe asthma attack?
1) inability to complete a sentence in one breath
2) a respiratory rate of >25 breaths/min
3) tachycardia of > 110 bpm
4) PEFR < 50% of predicted normal or best
features of life threatening attacks?
1) a silent chest, cyanosis or feeble respiratory effort
2) exhaustion, confusion, coma
3) bradycardia or hypotension
4) PEFR < 30% or predicted normal or best
what stats suggest a life-threatening attack?
- high PaCO2 > 6kPa
- severe hyperaemia < 8kPa despite treatment with oxygen
- low and or falling arterial pH
how would you manage a severe or life threatening asthma attack?
- nebuliser Short acting bronchodilators
- oxygen 40%-60%
- prednisolone (40-60mg daily) given orally
- nebuliser anti-muscarinics (e.g. ipratropium)
- magnesium sulfate are given IV
- ventilation for patients whoa deteriorate
