Acute Asthma Flashcards
What is asthma?
What are the common presenting features?
a chronic lung condition in which there is chronic inflammation of the airways, and hypersensitivity of the airways
symptoms include wheeze, cough, chest tightness and dyspnoea
it is often worse at night
What type of immune response is involved in asthma and how does this show on the lungs?
the immune response is CD4 mediated
the lungs will show an eosinophil infiltrate
What is the airflow obstruction like in asthma?
How is this different to in COPD?
airflow obstruction is varied over time and reversible
asthma exists where the obstruction is reversible by >15%
COPD exists where the obstruction is reversible by <15%
What are the typical characteristics of patients who fall into the grey area near the boundary between:
airway obstruction being reversible by >15% in asthma and <15% in COPD
and what is the usual diagnosis?
- patients are typically in their 30s and early 40s
- patients often have a history of smoking
- as their airway obstruction is reversible, they are usually given a diagnosis of asthma
- the actual diagnosis is more likely to be early stage COPD
- this is not too significant as the treatment is very similar
What similar treatment is used in both COPD and asthma and why?
inhalers
COPD is irreversible, but patients often get symptomatic relief from inhalers
(although the only way to improve prognosis is to stop smoking and give long-term oxygen therapy)
What are the 3 main characteristics of asthma?
AIRFLOW LIMITATION:
- usually reversible, either spontaneously, or with treatment
AIRWAY HYPER-RESPONSIVENESS:
- occurs to a wide range of stimuli
INFLAMMATION OF THE BRONCHI:
- with infiltration by eosinophils, mast cells and T cells
What other features are associated with inflammation of the bronchi in asthma?
- infiltration by eosinophils, T cells and mast cells
- associated plasma exudate
- oedema
- smooth muscle hypertrophy
- mucus plugging
- epithelial damage
What happens to asthma during viral infections?
asthma usually flares up with viral infections
this often causes a loud wheeze
What is the epidemiology of asthma like?
During what decade is prevalence highest and which gender is more likely to be affected?
- increasing in incidence, particularly in Western countries
- 10-20% of those in 2nd decade of life are affected (this is where prevalence is highest)
- boys are more likely to be affected in childhood
- girls are more likely to be affected after puberty
What % of individuals with childhood asthma will relapse in adulthood?
50% of those who have childhood asthma, but then “grow out of it” will relapse in adulthood
What are the 2 types of asthma?
INTRINSIC:
- no causatory factor can be found (i.e. cryptogenic)
EXTRINSIC:
- there is a definite external cause
At what age do people tend to be affected by intrinsic asthma?
What causes it?
- it often starts in middle age
- sometimes called late onset asthma
- no trigger can be identified
Who is usually affected by extrinsic asthma?
What is it often accompanied by?
- usually occurs in atopic individuals who have positive skin prick test results
- causes 90% of childhood cases and 50% of adults with chronic asthma
- often accompanied by eczema
How do non-atopic individuals tend to develop extrinsic asthma?
they develop asthma later in life via sensitisation
to e.g. occupational agents, aspirin,
or as a result of taking B-blockers for hypertension or angina
What is meant by sensitisation?
Encountering an allergen once is usually necessary to develop an allergy
sensitisation describes the process through which a person’s body becomes sensitive to a given allergen
What type of hypersensitivity reaction is involved in extrinsic asthma?
- it involves a type I hypersensitivity reaction to inhaled allergens
- there is also a delayed phase reaction ( type IV hypersensitivity ) which occurs hours to days after exposure
What is meant by atopy?
the genetic tendency to develop allergic diseases, such as
- allergic rhinitis
- asthma
- atopic dermatitis (eczema)
it is typically associated with heightened immune responses to common allergens
What is the difference between atopy and allergic disease?
- Atopy is the tendency to produce an exaggerated IgE immune response to otherwise harmless environmental substances
- allergic disease is defined as the clinical manifestations of the inappropriate IgE immune response
What genes tend to be involved in atopy?
- the ADAM33 gene is associated with airway hyperresponsiveness and airway remodelling
- the PHF11 gene is associated with increased IgE production
What is meant by the “hygiene hypothesis” that describes the development of atopy?
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 bacterial, fungal and viral proteins, this will direct the immune system away from recognising inert particles as allergens
How are asthma and allergic rhinitis similar?
What is rhinitis?
rhinitis is the inflammation of the mucosal lining of the URT, particularly affecting areas near the nose, thus causing a constant runny nose
the allergens for asthma are very similar to those that cause rhinitis
What is meant by “airway hyperresponsiveness”?
the predisposition of the airways of patients to narrow excessively in response to stimuli that would produce little or no effect in healthy individuals
What test is used to assess for airway hyperresponsiveness?
How is a positive diagnosis made?
BRONCHIAL PROVOCATION TEST
patient is asked to gradually inhale increasing amounts of methacholine or histamine
this will induce transient airflow limitation in 20% of the population - these exhibit airway hyperresponsiveness
What happens to the immune system when a patient with asthma is exposed to the antigen?
exposure to the antigen makes CD4+ T cells differentiate into T helper cells
these are Th2 type opposed to Th1
the Th2 helper cells begin to secrete IL-4 and IL-5
What are the roles of IL-4 and IL-5 that are released from Th2 type helper cells?
- IL-4 will cause B cells to become plasma cells and begin secreting IgE
- IL-5 will act on eosinophils and mast cells, making them reactive to the new antigen
- other factors are also released that are chemotaxic for eosinophils
What happens to IgE after it is released by plasma cells?
What cell does it bind to?
the IgE binds to mast cells in the mucosa
!!! this initial exposure does NOT cause an allergic reaction !!!
the IgE sits on the mast cell surface, perhaps for years, waiting to come into contact with the antigen again
What happens once IgE on the surface of mast cells is re-exposed to the initial antigen?
upon re-exposure to the antigen, the mast cells are activated and will degranulate
this leads to the release of inflammatory mediators
Why do asthmatics have increased inflammatory responses to any antigens?
there are increased numbers of mast cells in both the airway secretion and the epithelial lining of the lung
What inflammatory mediators are involved in the initial asthma attack?
When does this occur?
initial asthma attack is mainly the result of histamine and prostaglandin
(as well as leukotrienes - particularly LTC4)
these are released by mast cells when they degranulate
this response occurs within minutes of initial exposure to the antigen
What are the actions of histamine in the initial asthma attack?
it causes…
- smooth muscle contraction
- increased bronchial secretions
- increased vascular permeability
When does the late phase reaction occur in asthma?
What cell causes this?
the late phase reaction occurs several hours after the initial reaction
it is caused by the accumulation of eosinophils at the site
(there are also some neutrophils - but these are more numerous in COPD)
What is the main difference between the late phase reaction and the initial phase?
- the late phase is a more sustained inflammation
- the initial phase is more bronchoconstriction without as much underlying inflammation
What is the difference in treatments for the initial phase and the late phase reaction?
Initial phase:
- the main treatment is bronchodilators (B-adrenergics)
- the late phase does not respond well to these
Late phase:
- the main treatment is steroids (& other anti-inflammatories) to prevent the inflammation associated with this reaction
In what types of patients is the late phase reaction more likely to occur?
What is an associated risk with this phase occurring?
it is more likely to occur in poorly controlled / chronic asthma where there is already a reasonable aggregation of eosinophils in the mucosa
in this phase, there may also be activation of platelets, which can lead to microthrombi in the lumen
What are the 3 immediate main effects of bronchoconstriction and inflammation on lung function?
- distal airway hyperinflation and collapse and reduced gaseous transfer to these regions
-
mucus plugging of the bronchi
- occurs due to an increased number of goblet cells, which secrete more than normal goblet cells
- bronchial inflammation
What can be seen on the histology of mucus plugs from the bronchi of an asthmatic?
Curschmann’s spirals
these are bits of epithelium that have been shed
they are spiral-shaped and are found in the sputum of asthmatics
What are Charcot-Leyden crystals?
crystals that are formed as a result of eosinophil aggregation
they are microscopic crystals composed of eosinophil protein galectin-10
What happens to the bronchial basement membrane as a result of bronchoconstriction and inflammation?
Why is this significant?
there is thickening of the bronchial basement membrane
this occurs via the process of remodelling
the submucosa becomes thickened, meaning that when the smooth muscle does contract, there is excessive narrowing of the airway in response to contraction
What are the effects of bronchoconstriction and inflammation on the lung epithelium?
- epithelium loses many of its columnar ciliated cells
- these are replaced with over-active mucous secreting cells
- the mucosa also releases lots of inflammatory proteins
- it is likely to get damaged in inflammatory processes, and this (along with the excess mucous production) increases risk of infection
What are the effects of bronchoconstriction and inflammation on smooth muscle?
- smooth muscle is hypertrophied
- it undergoes changes which make it more likely to contract, and more likely to stay contracted for longer
What are the stages involved in the pathology of an asthma attack?
- excess mucous is produced
- muscle bands constrict to narrow the airway
- irritants which triggered the attack are stuck within the mucus
- tissue within the bronchiole swells
What are the effects of cold air and exercise on an asthmatic?
When does the asthma attack occur?
- these both dry out the mucosa of the lung, which makes the lining hyperosmolar
- this causes mast cells to release histamine & prostaglandins, causing inflammation
- typically, the asthma attack does NOT occur during exercise, but afterwards
How can atmospheric pollution influence asthma?
large amounts of dust, cigarette smoke, car fumes and other allergens can sometimes trigger asthma
ozone has also been known to be a trigger
How can diet influence asthma?
high intake of fruit and vegetables is protective against asthma
this is probably due to the large amounts of anti-oxidants that they contain
genetic variations affecting antioxidant production can also affect severity of disease
What is the role of the ADAM33 gene?
it is thought to be responsible for the release of factors by eosinophils, including:
- major basic protein (MBP)
- eosinophilic cationic protein (ECP)
What are the roles of major basic protein (MBP) and eosinophilic cationic protein (ECP) released by eosinophils?
these factors can cause remodelling of the epithelium and stimulate growth of fibroblasts
this increases the amount of smooth muscle present
and makes the smooth muscle more likely to contract in response to the release of inflammatory factors
!!! this increases airway hyperresponsiveness !!!
What usually stimulates bronchoconstriction?
What is the antagonist to this effect?
- bronchoconstriction occurs in response to direct parasympathetic stimulation
- antagonism of this effect is produced by freely circulating adrenaline that acts upon B-receptors
What type of drug is known to induce asthma attacks in patients and why?
BETA BLOCKERS
e.g. atenolol
these can induce asthma attacks as they prevent adrenaline from acting as an antagonist to the process of bronchoconstriction
What medication is given to asthmatic patients to lessen the effects of bronchoconstriction?
BETA AGONISTS
e.g. salbutamol
these will stimulate the same receptors that adrenaline uses (B2) to cause bronchodilation
What are the clinical features of intrinsic asthma?
- wheezing attacks
- periodic shortness of breath
- symptoms often worse during the night
- frequent cough
- nocturnal cough alone can be a presenting feature
- attacks precipitated by a very wide range of triggers
What is the specific diagnostic test used to diagnose asthma?
there is no specific diagnostic test for asthma
the most useful test is the variability shown through twice daily measurements of peak expiratory flow (PEF)
What is the most useful test in asthma?
How should it be performed?
PEAK EXPIRATORY FLOW (PEF)
- patients should take 2 readings per day, to show the variability of the disease
- in patients with suspected asthma, they should take 2 weeks of measurements whilst at work, and 2 weeks whilst at home to prove the cause of the disease
How can spirometry be used to show the presence of asthma?
there should be demonstration of 15% improvement in FEV1 or PEF following the inhalation of a bronchodilator
Why is spirometry not the gold standard test for asthma?
in some patients, it may not be possible to show reversibility through spirometry
e.g. those in remission or those with particularly severe chronic asthma
How can nitrous oxide sometimes be used as a test for asthma?
for an unknown reason, levels of nitrous oxide are raised in the breath of those with asthma
What test is usually used in children to diagnose asthma?
How is this performed?
EXERCISE TESTS
- child runs on a treadmill for UP TO 6 minutes - enough to increase the heart rate to at least 160 bpm
- peak flow is tested before and after
- test every 15 minutes after running, looking for 15% improvement
- negative test does not rule out asthma
What test is used to identify hyper-responsiveness of the airway?
What type of patients is this good for?
histamine or metacholine bronchial provocation test
this indicates hyper-responsiveness which is found in most asthmatics
it is useful for diagnosing patients whose main/only symptom is cough
How is the histamine or metacholine bronchial provocation test carried out?
the dose of the drug needed to produce a 20% drop in FEV1 is noted
patients with airway hyperresponsiveness require only a very small dose to acheive this
(<11 umol of metacholine)
this is dangerous and is only really done for research purposes
What drugs are often trialled for children at first presentation for asthma?
corticosteroids
- children are trialled on 20mg prednisolone for several days
- or 30mg for up to 2 weeks in adults
- the initial dose is a one-off
How does trialling children (or adults) on corticosteroids assist in their diagnosis of asthma?
What are the other benefits to doing this?
- corticosteroids will reduce their symptoms
- it will also mean that they respond better to bronchodilators
- if they respond to treatment, then you know it is asthma and you can start them on a normal management plan
- this is just a bronchodilator (e.g. salbutamol) to begin with
What is it important to do before and after the course of corticosteroids?
What result will suggest asthma in adults?
- lung function must be measured immediately before and after the course of steroids
- >15% improvement in FEV1 demonstrates the presence of asthma
What type of blood / sputum test may be performed in someone with asthma?
blood / sputum tests are tested for high numbers of eosinophils
this helps to form the diagnosis, but is not diagnostic on its own
Why is chest X-ray performed in patients with suspected asthma?
What will it look like?
- CXR is used to exclude the possibility of pneumothorax, which can be a complication of asthma
- CXR should be normal
- in a particularly bad exacerbation, overinflation may be present
Why might a skin prick test be performed in suspected asthma?
skin prick tests are performed on all newly diagnosed asthmatics to help find a cause
allergen provocation tests are also performed, but only in cases of occupational asthma
What is the main advice given to patients for management of extrinsic factors that may trigger their asthma?
it is important to try and reduce the risk of a person coming into contact with a provocating factor
dust mite faeces is a major cause, so changing bedding regularly is a good way to manage this risk
Which medication is an absolute contraindication in asthma?
beta blockers
patients should avoid taking beta blockers in any form
Which group of medications are effective for treating asthma which patients are often scared to take?
asthma is a chronic inflammatory condition
patients are often scared, but should take anti-inflammatories, such as steroids
What is the underlying treatment approach to asthma?
What is the main goal of treatment?
- main goal is to achieve maximum control of symptoms with the fewest medications
- the goal for optimal control is to have the patient as asymptomatic as possible with as normal PEF as possible
- once a state of control is reached, an attempt should be made to reduce the doses of medications
What do guidelines describe the management of asthma to be like?
Stepwise management of asthma
medication can be stepped up or stepped down the ladder based on the severity of the disease and adequacy of the control
What generally indicates a need to step up the ladder in management of asthma control?
increasing use of a short-acting beta agonist (SABA)
or use >2 days a week for symptom relief
this generally indicates inadequate control and the need to step up treatment
When is stepping down the ladder in the stepwise management of asthma recommended?
there should be regular assessments of the patient’s asthma
if the disease has been well controlled for at least 3 months, then the aim is to step down the treatment
What is STEP 1 in the stepwise management of asthma?
What is PEFR in this step and what is treatment?
occasional symptoms - less frequent than daily
PEFR:
- 100% predicted
Treatments:
- PRN bronchodilators ( “2 puffs as required” )
- these will deliver a dose of around 200ug
What is STEP 2 in the stepwise approach to asthma management?
What is PEFR and what is treatment?
symptoms more than 3x a week
PEFR:
- equal to or less than 80% predicted
Treatment:
- low dose inhaled corticosteroid
- start at 200-400ug but can be increased up to 800ug
- OR sodium cromoglicate
What is STEP 3 in the stepwise management of asthma?
What is PEFR and what is treatment?
severe symptoms
PEFR:
- 50 - 80% predicted
Treatment:
- add a long-acting B2 agonist
- e.g. sertide and symbicort are combinations of LABAs and corticosteroids
What is STEP 4 in the stepwise management of asthma?
What is PEFR and what is treatment?
severe symptoms not controlled by high dose corticosteroids
PEFR:
- 50 - 80% predicted
Treatments:
- give a higher dose corticosteroid - up to 2000ug
- consider leukotriene receptor antagonist - such as montelukast
- or theophyline
What is STEP 5 in the stepwise approach to asthma management?
What is PEFR and what is treatment?
severe symptoms that are deteriorating
PEFR:
- <50% predicted
Treatment:
- add prednisolone 40mg daily
What is STEP 6 in the stepwise approach to asthma management?
What is PEFR and what is treatment?
severe symptoms that are deteriorating despite prednisolone
PEFR:
- <30% predicted
Treatment:
- hospital admission
How is step 1:
mild intermittent and exercise induced asthma
defined in terms of symptoms?
- symptoms 2 times or less per week
- asymptomatic and normal PEFR between attacks
- attacks are brief with varying intensity
- night-time symptoms 2 times or less per month
