Week Two - Case One Flashcards
what are the three main characteristics of asthma
airflow limitation
airway hyper-responsiveness
inflammation of the bronchi
how many patients in the UK die a year from asthma
2000
what is associated with the inflammation of the bronchi
with infiltration by eosinophils, T cells and mast cells. there is associated plasma exudate, oedema, smooth muscle hypertrophy, mucus plugging and epithelial damage.
what often causes an asthmatic flare and what symptom does this bring
often flares up with viral infections which often causes a loud wheeze
who Is most likely to be affected before/after puberty
before puberty, boys are more likely to be affected
after puberty, girls are most likely to be affected
is asthma intrinsic or extrinsic
the disease can either be intrinsic (aka cryptogenic) where no causatory factor can be found, or extrinsic, where there is a definite external cause
when does intrinsic asthma often start
often starts in middle age, and is sometimes called late onset asthma.
no trigger can be identified
when does extrinsic asthma occur
in atopic individuals who have positive skin prick test results.
this type of asthma causes 90% of childhood cases, and 50% of adults with chronic asthma.
what is extrinsic asthma often accompanied by
eczema
how do non-atopic individuals develop asthma in later life
via sensitisation to occupational agents, aspirin, or as a result of taking Beta-blockers for hypertension or angina
what kind of reaction is extrinsic asthma
involves a type 1 hypersensitivity reaction to inhaled allergens
what other reaction happens with asthma
there is also a delayed phase reaction, type IV hypersensitivity which occurs hours-days after exposure
what does the term atopy describe
people who often have allergies/asthma/hayfever and where the trait runs in families
what gene is associated with airway hyper-responsiveness and airway remodelling
ADAM33
what gene is associated with increased IgE production
PHF11 gene
what antibodies do people have to many common allergens
IgE antibodies - these antibodies are present in 35% of the population
what is the hygiene hypothesis
this is a theory that states that growing up in a clean environment in the early years of life can cause atopy. if you grow up in a dirty environment and are exposed to various bacteria, this is thought to help direct your immune system away from recognising inert particles as allergens.
what are the allergens for asthma very similar to
very similar to the allergens that cause rhinitis.
what is rhinitis
is inflammation of the mucosal lining of the upper respiratory tract, particularly affecting areas near the nose
what can rhinitis cause
a constant runny nose
how can you test airway hyper-responsiveness
asking patient to inhale gradually increasing amounts of methacholine or histamine.
what is this test called
bronchial provovation test
what does this test induce
will induce transient airflow limitation in 20% of the population - and these are the patients that exhibit airway hyper-responsiveness
what are the features of non-atopic asthma
does not appear to be immunologically mediated - i.e there is not T cell involvement
associated with recurrent respiratory tract infection (viral)
skin tests are negative
bronchoconstriction due to airway hyper-responsiveness , not as much due to inflammation and leukocyte infliltration
what is the mechanism of aspirin induced asthma
mechanism is unknown but thought to be due to increased leukotrienes and decreased prostaglandins which leads to increased airway irritability
aspirin inhibits COX enzymes. This reduces the production of prostaglandins. However, prostaglandin E2 controls leukotriene production - thus in some patients this allows overproduction of leukotrienes and allows for an abnormal inflammatory reaction.
what kind of drug can this also occur with
NSAIDs such as ibuprofen.
what is a relative contra-indication
ibuprofen
what is occupational asthma
asthma induced by hypersensitivity to an agent at work - probably a combination of types I and IV hypersensitivity reactions
what products can cause asthma via an IgE-independent route
paints, varnishes and sprays
what do paints, varnishes and sprays do
bind directly to T cells (activating them) and other epithelial cells, without IgE
what kind of food diet can precipitate attacks
a high sodium and low magnesium diet
next questions are about pathology
what will happen to CD4 T cells when there is exposure to the antigen
CD4 T cells will differentiate into T helper cells (Th2 type, as opposed to Th1)
what will these T helper cells begin to secrete
IL4 and IL5
what will IL4 cause
IL-4 will cause B cells to become plasma cells and begin secreting IgE
what will IL-5 do
act on eosinophils and mast cells, making them reactive to the new antigen.
what does this IgE do
binds to mast cells in the mucosa
will this initial exposure cause an allergic reaction
no
what is this initial exposure
the IgE binding to the mast cells in the mucosa.
what does the IgE do on the mast cell
it just sits there, waiting to come into contact with the antigen again, perhaps for years
what happens upon re-exposure to the antigen
the mast cell will be activated, and will degranulate.
what does this degranulation do
causes the release of inflammatory mediators
what are there increased numbers of in both the airway secretion and epithelial lining of lungs in asthmatics
increased numbers of mast cells.
what does this increased number of mast cells lead to
increased response to any antigens
what does this cause
the initial asthma attack
what is this initial asthma attack a result of
histamine and prostaglandin (as well as leukotrienes; particularly LTC4) release by mast cells.
what is responsible for the early attack
mast cells
what does histamine cause
smooth muscle contraction, increased bronchial secretions, and increased vascular permeability
what is the late phase reaction and when does it occur
occurs several hours after the initial reaction.
it is causes by the accumulation of eosinophils at the site
which phase is a more sustained inflammation
the late phase. the initial phase is more bronchoconstriciton without much underlying inflammation
what are good at treating the initial phase reaction
bronchodilators (beta-adrenergics)
what are good at preventing the inflammation that causes the late phase reaction
steroids and other anti-inflammatories
what may also happen in the late phase reaction
there may also be activation of platelets
what does activation of platelets lead to
micro thrombi in the lumen
what are the effects of bronchoconstriction on the distal airway
there will be distal airway hyperinflation and collapse (and reduced gaseous transfer to these regions)
what will happen in the bronchi
mucus plugging
what is this mucus plugging in the bronchi due to
increased number of goblet cells
what are Curschmann’s spirals
these are bits of epithelium that have been shed, and can be seen on histology of the mucous plugs
what are Charcot-Layden crystals
crystals that are formed as a result of eosinophil aggregation
what occurs via the process of remodelling
thickening of the bronchial basement membrane.
the submucosa becomes thickened, which means that when the smooth muscle does contract, there is an excessive narrowing of the airway and response to the contraction.
what are the effects of bronchoconstriction and inflammation on the epithelium
the epithelium loses many of its columnar ciliated cells, and these are replaced with over-active mucous secreting cells.
what does the mucosa release
lots of inflammatory proteins
what are the effects of bronchoconstriction and inflammation on smooth muscle
the smooth muscle is hypertrophied and also undergoes changes which make it more likely to contract, and more likely to stay contracted for longer
what does cold air and exercise do to the mucosa of the lungs
these both dry out the mucosa of the lung, which makes the lining hyperosmolar
what does this hyperosmolar lining lead to
causes mast cells to release histamine and prostaglandins, thus causing inflammation
what does atmospheric pollution do to asthma
large amounts of dust, cigarette smoke, car fumes and other allergens can trigger asthma in some individuals.
ozone has been a trigger in the past
what kind of diet is protective from asthma
high intake of fruit and vegetables possibly due to the large amounts of anti-oxidants
what its the ADAM33 gene thought to be responsible
for the release of factors by eosinophils
what are some of the factors released by eosinophils and what do they cause
MBP, ECP
these factors cause remodelling of the epithelium and stimulate growth of fibroblasts.
this increases the amount of smooth muscle present
what is the end result of these factors being released
increased airway hyperresponsiveness
what does the normal process of bronchoconstriction occur in response to
occurs in response to direct parasympathetic stimulation
what is antagonism to this effect produced by
freely circulating adrenaline that acts upon beta-receptors
what have been known to induce attacks in asthmatic patients
beta-blockers because they prevent adrenaline from doing its job
what are the 7 clinical features of asthma
Wheezing attacks
Periodic shortness of breath
Symptoms often worse during the night
Cough is frequent – and often misdiagnosed as bronchitis
Nocturnal cough alone can be a presenting feature
Some patients can have chronic symptoms
Attacks precipitated by a very wide range of triggers
what is thought to be the most useful test for asthma
twice daily measurements of PEF is probably the most useful test
what is PEF
the peak expiratory flow.
patients should take two readings per day, to show the variability of the disease
what should you get patients who have suspected asthma to do
get them to take two weeks worth of measurements whilst at work, and 2 weeks whilst at home, to prove the cause of the disease
what is the spirometry test you can do to show the presence of asthma
demonstrate a 15% improvement in FEV1 or PEF following the inhalation of a bronchodilator
what will the picture be of
an obstructive disease
what would the carbon monoxide transfer test show in an asthmatic
nothing, it would be normal
what happens to nitrous oxide levels in asthmatic’s breath
levels of NO are raised
what test is often used to diagnose children with asthma
the exercise test
describe how to perform an exercise test
the child should run on a treadmill for a max of 6 minutes
- enough to increase the heart rate till at least 160bpm
then test the peak flow before and after
test every 15 minutes after, again looking for a 15% difference
does a negative test rule out asthma
no
what does the histamine or metacholine bronchial provocation test indicate
hyper-responsiveness - which is found in most asthmatics
what is the histamine or metacholine bronchial provocation test most useful for
diagnosing patients who’s main or only symptom is a cough
what does the dose of the drug in the histamine or metacholine bronchial provocation test need to produce
needs to produce a 20% drop in FEV1 and is called the PD20 FEV1
patients with airway hyperresponsiveness require only a very small dose to achieve this
who should the histamine or metacholine bronchial provocation test not be performed on
those with brittle asthma, or those who have an FEV1<1.5L
what improvement in the FEV1 always demonstrates the presence of asthma
> 15% improvement
what test is not diagnostic on its own but may help form your diagnosis
blood and sputum tests that you can test for high number of eosinophils
what will a CXR of an asthmatic show
this will be normal, unless they are having a particularly bad exacerbation, in which case, overinflation may be present
what is the CXR good at doing
excluding the possibility of a pnevumothorax
when should you perform skin prick tests
should perform these on all newly diagnosed asthmatics to help find a cause
what is an absolute contra-indication for asthmatics
taking beta-blockers in any form
what is step one, mild intermittent and exercise induced asthma defined as (6 things)
Symptoms ≤2 times a week
Asymptomatic and normal peak expiratory flow (PEF) between attacks
Attacks are brief with varying intensity
Night-time symptoms ≤2 times a month
Forced expiratory flow at 1 second (FEV1) or PEF ≥80% of predicted
PEF variability <20%.
what is sufficient alone to treat mild intermittent asthma or exercise induced asthma (step1)
the use of a SABA as required is sufficient alone.
what is step 2, mild persistent asthma defined as (5 things)
Symptoms >2 times a week but <1 time a day
Exacerbations may affect activity
Night-time symptoms >2 times a month
FEV1 ≥80% of predicted
PEF variability between 20% and 30%.
what are added if control is not achieved with SABA in type 2, mild persistent asthma
low dose inhaled corticosteroids are added.
what can be used in step 2 asthma (mild persistent) instead of inhaled corticosteroids
either sodium cromoglicate, leukotriene receptor antagonists (LRTA), nedocromil or theophylline.
what is step 3, moderate persistent asthma defined as (7 things)
Daily symptoms
Use of short-acting beta agonists daily
Attacks affect activity
Exacerbations ≥2 times a week and may last for days
Night-time symptoms >1 time a week
FEV1 greater than 60% to less than 80% of predicted
PEF variability >30%.
what is added in treatment for step 3, moderate persistent asthma
adds LABA to step 2 therapy (SABA and low-dose ICS)
OR
increase low dose ICS to medium dose ICS.
what are second line alternatives to either increasing ICS dose or adding a LABA
combine SABA as needed and ICS with either LRTA’s, theophylline or zileuton
what is step4-6, severe persistent asthma defined as (6 things)
Continual symptoms
Limited physical activity
Frequent exacerbations
Frequent night-time symptoms
FEV1 ≤60% of predicted
PEF variability >60%.
what is the preferred combination of treatment for step 4, severe persistent asthma
medium-dose ICS plus LABA plus SABA as needed.
what can LABA be substituted for
either LRTA, theophylline or zileuton
what happens in step 5
changes medium-dose ICS to high-dose ICS
what can also be considered in stage 5 for patients with allergies
immunodilators such as omalizumab
what happens in step 6
adds oral corticosteroids to existing treatments
what may be added to the use of beta2 agonists in an acute asthma attack
theophylline and aminohpyline (aminophyline is metabolised to theophylline)
what is omalizumab
a drug that forms completes with free IgE, and prevents it binding to inflammatory cells
what is status asthmatics
this is asthma that has failed to resolve within 12 hours of therapy use
we now use the term acute severe asthma
what are the features of acute severe asthma
inability to complete a sentence in one breath
RR>25
tachycardia >110bpm
PEF<50% predicted
what are the features of a life threatening attack
silent chest
feeble respiratory effort
cyanosis
exhaustion
bradycardia
hypotension
confusion or coma
PEF <30% predicted normal or best (approx 150L/min in adults)
what is pulsus paradoxis
on inspiration, the diastolic pressure decreases by 10mmHg. this is present in about 45% of cases
what is the hospital management for a severe acute asthma attack
(Do an ABG – it may be life-threatening if:
CO2 > 5kPa (high)
O2 <8kPa (low)
Low pH
Start on 100% O2 (non-rebreathing mask) with the patient sat upright in bed
Give 5mg salbutamol with 0.5mg ipratropium bromide via nebulizer on 100% O2
Give hydrocortisone 100mg IV or 50mg prednisolone orally. Give both if very unwell
Do CXR to exclude pneumothorax
what are the 4 steps if life threatening steps are present
Inform ITU and seniors
Give magnesium sulphate 1.2-2g IV over 20 minutes
Change the nebulized salbutamol every 15 minutes, or give 10mg continuously per hour. Only give more ipratropium every 4-6 hours
Repeat PEF every 15-30 minutes to assess the situation. If improving then gradually reduce O2 and nebs. If not, try and find senior, keep giving nebs, and consider aminophyline.
Check pulse oximetry – aiming for sats >92%
Check blood gases every 2 hours, and definitely within 2 hours of admission
Record PEF’s and β-agonists when given / carried out
A maximum of 60mg/day of prednisolone can be given (orally)
You can give 200mg hydrocortisone every 4 hours for a max of 24 hours
Give oral prednisolone for 5 days after they are starting to recover
Ventilation is an option – you would have to call an anaesthetist
Patients have to have >75% predicted PEF for discharge
what should be continued after a severe asthma attack
oral corticosteroids should be continued until the PEF rate is at least 80% of the patient’s previous best
what is brittle asthma
catastrophic sudden severe asthma
what do steroids cause an increased risk for
peptic ulcers
can anaemia cause breathlessness
yes, especially in younger patients including young females who may have menorrhagia leading to anaemia which can cause breathlessness
what tests do you run to confirm diagnosis of asthma as demonstrated in NICE guidelines
-peak flow
- peak flow diary
- exhaled nitric oxide
- spirometry
how are patients predicted peak flows calculated
you need to know the gender, age, and height to calculate the Patient’s predicted peak flow
what do normal adult peak flow scores range between
400-700 litres per minute
how long before exercise should you use a SABA (salbutamol - blue inhaler)
15 mins
if someone is waking frequently at night what also may a GP prescribe as well as a SABA
a low dose ICS inhaler
what is in a low-dose corticosteroid inhaler
beclomethasone diproprionate
what does beclomethasone dipropriate do and how fast does it work (QVAR)
QVAR (beclomethasone dipropionate) is an inhaled corticosteroid and acts to reduce inflammation in the airways. As a result it is classed as a preventer medication as it doesn’t have an immediate effect and may take weeks to work and is used to prevent ongoing asthma symptoms, by reducing airway inflammation and thereby bronchial hyperreactivity to stimuli like cold air.
what are two examples of SABAs (short acting)
salbutamol
terbutaline
what is an example of a LABA (long acting)
salmeterol
what are 4 examples of inhaled corticosteroids
beclometasone
fluticasone
ciclesonide
budesonide
what are the 3 types of inhaler devices
metred dose inhalers (MDI)
- inhale slow and steady
dry powdered inhalers (DPI)
- inhale quickly and deep
breath actuated inhalers (BAI)
look up video on how to perform spirometry
In what other medical conditions can you hear a wheeze in
cardiac failure
eosinophilic lung disease
COPD
foreign body aspiration
OPD
define the term Peak Expiratory Flow Rate
the PEFR is the rate of maximal volume of air that a person can exhale during a short maximal expiratory effort after a full inspiration
how do you record serial readings of PEFR and for how long
for diagnosis 2-4 weeks, twice daily
for occupational asthma it may require 2-4 hourly readings over several weeks
