3 Asthma: Diagnosis, Monitoring, Pathophysiology and Management Flashcards
Define asthma
It is an auto-immune chronic airway hyper-responsiveness and airway inflammation with a history of respiratory symptoms such as wheeze, SoB, chest tightness and cougj
What are the symptoms of asthma?
more than one of…
- Wheeze
- Chest tightness
- Cough
Variable airflow obstruction
What are the identifiable changes in the FEV1:FVC observed in asthma?
- It is characterised by reversible decreases in FEV1:FVC
less than 70-80% suggests increases in airway resistance
Important features
e.g. to distinguish from COPD
The airflow obstruction is reversible, whereas in COPD it is irreversible
Variations in the PEF, which can be improved with B2 agonist
Clinical features of asthma
- Wheezing
- Breathlessness
- Tight chest
- Cough (worse at night/exercise)
- Decreases in FEV1, reversed by a B2-agonist
What can provoke an asthmatic attack?
genetic predisposition
- Allergens
- Cold air
- Viral infections
- Smoking
- Excercise
- Drug-induced asthma
What are the observable differences in the FEV1 and a volume/time curve?
- lower FEV1
- the graph will have a less steep slope but will eventually reach TLC
It is an obstructive deficit
What are the objective tests available for diagnosis of asthma (in adults, young people, and children aged 5 and over)
(and what to expect for a positive test for obstructive airway disease)
- Offer a FeNO (fractional exhaled nitric oxide) test to adults (17 and over)
- Blood test (eosinophil level), to look for eosinophilic airway inflammation or atopy
- offer spirometry
(regard FEV1/FVC ratio of less than 70% as a positive test for obstructive airway disease) - offer a BDR (bronchodilator reversibility) test to adults with obstructive spirometry.
(regard an improvement in FEV1 of 12% or more, together with an increase in the volume of 200ml or more, as a positive test of obstructive airway disease
How do you use a peak flow meter to Monitor asthma
PEF is one’s maximum ability to breathe out air
- Useful for monitoring disease than making an initial diagnosis
- track the PEF over a few weeks (taking 2/3 times daily measurements, and asking patients to keep a record of the measurements)
What is the pathophysiology of Asthma
- Immunoglobulin IgE likelihood of asthma increases with serum concentrations
- Body first exposed to the allergen, leading to the production of allergen-specific IgE
- Re-exposure occurs, where the allergen binds to IgE molecule on the surface of mast cells
- Degranulation occurs, with the release of inflammatory mediators such as histamines, prostaglandins, and leukotrienes (from mast cells)
Describe the early phase of asthma
- Infiltration by eosinophils, T-cells, and mast cells
- Goblet cells produce mucus (causes wheeze, where the air is trying to push through constricted and mucus-filled airways
- T cells release cytokines
(late phase airways become more responsive to triggers)
Asthma is steroid-responsive
- Long term damage is untreated
What are the aims of treatment for asthma?
- No day-time symptoms
- No night-time awakening due to asthma
- No need for rescue medication
- No asthma attacks
- No limitations of activity, including exercise
- Normal lung function (PEF>80%)
- Minimum side-effects of medication
What 3 questions can you ask a patient to assess the control of their asthma (and the medications)
In the last week (month):
- Have you had difficulty sleeping because of asthma symptoms (cough?)?
- Have you had your usual daily activities?
Yes, to any, implies uncontrolled asthma
What is the approach to management for asthma?
-Start treatment at level most appropriate severity
-Achieve early control
-Maintain control by:
o Increasing treatment as necessary
o Decreasing treatment when control is good
What is the first-line treatment all asthmatics get?
B2-adrenoceptor agonists
(SABA as reliever therapy
Give examples of B2-adrenoceptor agonists, and how they are used
Short-acting beta-agonists (SABA) - used as a reliever
- e.g. Salbutamol, terabutaline
Long-acting beta-agonists (LABA) - stay on receptor longer
- LABAs are given as add-on therapy for long-term prevention and long-term control (overnight)
[long-term use, especially of LABA, may lead to receptor down-regulation]
Describe how SABA’s work, and give features of it
Inhale short-acting beta-agonists as required
- this step only manages symptoms and does not control the underlying inflammation
- SABA works more quickly and/or with fewer side effects than the tablet/syrup alternatives
Give the mechanism of action of Salbutamol (SABA)
Activation of Beta-2 adrenergic receptors on airway smooth muscle:
- leads to the activation of Adenyl Cyclase (through the G-protein coupled receptor activation)
- And leads to an increase in concentration in cAMP.
- This increase in cAMP leads to relaxation of the smooth muscles in the airways
This causes bronchodilation
How to give the LABA (salmeterol), and why?
In asthma, LABA needs to be given with a corticosteroid
- Salmeterol (LABA) do not have any anti-inflammatory properties
(it control the symptoms, but doesn’t affect the inflammation)
Give an example of a corticosteroid used to treatment in Asthma (as well as a feature)
e. g. Beclomethasone (inhaled corticosteroid - ICS)
- or prednisolone (oral)
What is the mechanism of action of the corticosteroids?
Anti-inflammatory actions by:
- activation of intracellular receptors, leading to altered gene transcription (decrease in cytokine production) and production of lipocortin
- They decrease the production of prostaglandins (which trigger the release of inflammatory mediators), by inhibiting the arachidonic acid pathway
What is the appropriate dosage for ICS?
Lower does give a higher response (whereas, the increasing dose does not give additional clinical benefit, whilst increasing adverse effects)
What are the side effects of Inhaled Corticosteroids?
- Hoarseness, dysphonia, throat infections, oral candidiasis
- Higher doses reduce bone density, skin thinning, bruising
- Increased risk of pneumonia
High dose of ICS - increased risk of diabetes
What is the procedure to follow in a patient whose asthma is uncontrolled whilst on a low dose of ICS as maintenance therapy?
Offer the patient a Leukotriene-receptor antagonist (LTRA), in addition to the ICS, and review the response to treatment in 4-8 weeks
What is a leukotriene receptor antagonist, and give features and examples of it
e. g. Montelukast, zafirlukast
- Oral option for adults (10mg), children (5mg), who do not respond to a LABA, and have poor control with a steroid + LABA
After an LTRA, what is the next choice treatment available for asthma?
Exchange and MART (SMART)
- Maintenance and reliever therapy
What is MART?
Maintenance and reliever therapy (MART) is a form of combined ICS and LABA treatment in a single inhaler, containing both ICS + fast-acting LABA (formoterol)
- used for both daily maintenance therapy
- and relief of symptoms as required
What is the 5th line treatment for asthma?
Methylxanthines
Give features of methylxanthines, with an example too
It is hardly used in Asthma
- Need to be careful in dosage - as it has a narrow therapeutic range
- It also has lots of interactions with other drugs
- If prescribed to a patient who smokes, the dosage of theophylline (methylxanthine) needs to be halved
What are the signs of toxicity of methylxanthine
- Cardiac dysrhythmia
- seizure
- GI disturbances
What is the mechanism of action of theophylline (methylxanthines)
- Theophylline works to stop the breakdown of cAMP
- It inhibits the enzyme phosphodiesterase (PDE - which breaks down cAMP to AMP)
Describe the use of monoclonal antibodies in the treatment of asthma
- IgE antibodies - only prescribed by top consultants
e.g. Omalizumab (mAb)
It is used in the management of allergic asthma
e.g. Benralizumab is another mAb used for treating severe eosinophilic asthma
What is the mechanism of action of monoclonal antibodies?
- They are directed against free IgE, but not bound to IgE
- They prevent IgE from binding to immune cells and basophils
- Hence, decreases the release of allergic mediators
Describe the use of mast cell stabilisers in the treatment of asthma
It used to be used, but not anymore (due to its side effects)
e.g. Cromoglycate (sodium cromoglicate) is given by inhalation
It is used as a prophylactic anti-inflammatory drug
What is the mechanism of action of a cromone (like cromoglycate)?
- Their effect is on the mast cells that are rich in histamine and other inflammatory mediators by preventing their activation to initiate inflammatory responses
What is the contraindication between NSAIDs and asthma
- Non-steroidal inflammatory drugs (NSAIDs) are good at treating pain and inflammation from prostaglandins (as they inhibit the production of prostaglandins)
e. g. aspirin, ibuprofen - BUT, NSAID’s may provoke asthma by increasing leukotriene production
