Asthma

Question 1

Asthma

Answer 1

Chronic inflammatory condition of the airways that causes bronchoconstriction. It should be remembered that it is common for young children to wheeze when they develop a virus (‘viral-induced wheeze’). This makes the diagnosis of asthma in younger children difficult. This bronchoconstriction is caused by hypersensitivity of the airways and can be triggered by environmental factors.

Question 2

What is bronchoconstriction?

Answer 2

Bronchoconstriction is where the smooth muscles of the airways (the bronchi) contract causing a reduction in the diameter of the airways. Narrowing of the airways causes an obstruction to airflow going in and out of the lungs.

Question 3

Typical triggers of bronchoconstriction

Answer 3

Infection, night time or early morning, exercise, animals, cold/damp, dust, strong emotions.

Question 4

Presentation suggesting a diagnosis of asthma

Answer 4

• Episodic symptoms
• Diurnal variability. Typically worse at night.
• Dry cough with wheeze and shortness of breath
• A history of other atopic conditions such as eczema, hayfever and food allergies
• Family history
• Bilateral widespread “polyphonic” wheeze heard by a healthcare professional

Question 5

Atopic conditions meaning

Answer 5

Atopy is an exaggerated IgE-mediated immune response; all atopic disorders are type I hypersensitivity disorders. Allergy is any exaggerated immune response to a foreign antigen regardless of mechanism. genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema). Atopy is typically associated with heightened immune responses to common allergens, especially inhaled allergens and food allergens.

Question 6

Presentations indicating a diagnosis other than asthma

Answer 6

Wheeze related to coughs and colds more suggestive of viral induced wheeze
Isolated or productive cough
Normal investigations
No response to treatment
Unilateral wheeze. This suggests a focal lesion or infection.
Dyspnoea
Chest tiightness
Expiratory wheeze on auscultation.
Reduced peak expiratory flow rate (PEFR).

Question 7

Diagnosis

Answer 7

Perform spirometry with reversibility testing
Consider referral and investigating for other causes

NICE recommend assessment and testing at a “diagnostic hub” to establish a diagnosis. They specifically advise not to make a diagnosis clinically and require testing:

First line investigations:

Fractional exhaled nitric oxide
Spirometry with bronchodilator reversibility
If there is diagnostic uncertainty after first line investigations these can be followed up with further testing:

Peak flow variability measured by keeping a diary of peak flow measurements several times per day for 2 to 4 weeks
Direct bronchial challenge test with histamine or methacholine

Question 8

clinical diagnosis

Answer 8

clinical diagnosis: The estimated identification of the disease underlying a patient’s complaints based merely on signs, symptoms and medical history of the patient rather than on laboratory examination or medical imaging

Question 9

Long term Management

Short acting beta 2 adrenergic receptor agonists. –>Salbutamol

Answer 9

Short acting beta 2 adrenergic receptor agonists, for example salbutamol. These work quickly but the effect only lasts for an hour or two. Adrenalin acts on the smooth muscles of the airways to cause relaxation. This results in dilatation of the bronchioles and improves the bronchoconstriction present in asthma. They are used as “reliever” or “rescue” medication during acute exacerbations of asthma when the airways are constricting. Side effects include tremor.

Question 10

Long term management Inhaled corticosteroids (ICS)->Beclometasone

Answer 10

These reduce the inflammation and reactivity of the airways. These are used as ‘maintenance’ or ‘preventer’ medications and are taken regularly even when well.

Question 11

Long term management: Long-acting beta 2 agonists (LABA) –> Salmeterol

Answer 11

These work in the same way as short acting beta 2 agonists but have a much longer action.

Question 12

Long term management: Long-acting muscarinic antagonists (LAMA)

Answer 12

tiotropium. These block the acetylcholine receptors. Acetylecholine receptors are stimulated by the parasympathetic nervous system and cause contraction of the bronchial smooth muscles. Blocking these receptors leads to bronchodilation.

Question 13

Long term management: Leukotriene receptor antagonists, eg. montelukast

Answer 13

Leukotrienes are produced by the immune system and cause inflammation, bronchoconstriction and mucus secretion in the airways. Leukotriene receptor antagonists work by blocking the effects of leukotrienes.

Question 14

Long term management: Theophylline

Answer 14

This works by relaxing bronchial smooth muscle and reducing inflammation. Unfortunately it has a narrow therapeutic window and can be toxic in excess so monitoring plasma theophylline levels in the blood is required. This is done 5 days after starting treatment and 3 days after each dose changes.

Question 15

Maintenance and Reliever therapy (MART)

Answer 15

This is a combination inhaler containing a low dose inhaled corticosteroid and a fast acting LABA. This replaces all other inhalers and the patient uses this single inhaler both regularly as a “preventer” and also as a “reliever” when they have symptoms.

Question 16

BTS/SIGN stepwise ladder

Answer 16

• Add short-acting beta 2 agonist inhaler (e.g. salbutamol) as required for infrequent wheezy episodes.
• Add a regular low dose corticosteroid inhaler.
• Add LABA inhaler (e.g. salmeterol). Continue the LABA only if the patient has a good response.
• Consider a trial of an oral leukotriene receptor antagonist (i.e. montelukast), oral beta 2 agonist (i.e. oral salbutamol), oral theophylline or an inhaled LAMA (i.e. tiotropium).
• Titrate inhaled corticosteroid up to “high dose”. Combine additional treatments from step 4. Refer to specialist.
• Add oral steroids at the lowest dose possible to achieve good control.

Question 17

NICE guidelines for asthma management

Answer 17

-Add short-acting beta 2 agonist inhaler (e.g. salbutamol) as required for infrequent wheezy episodes.
-Add a regular low dose inhaled corticosteroid.
-Add an oral leukotriene receptor antagonist (i.e. montelukast).
-Add LABA inhaler (e.g. salmeterol). Continue the LABA only if the patient has a good response.
-Consider changing to a maintenance and reliever therapy (MART) regime.
Increase the inhaled corticosteroid to a “moderate dose”.
-Consider increasing the inhaled corticosteroid dose to “high dose” or oral theophylline or an inhaled LAMA (e.g. tiotropium).
Refer to a specialist.

Question 18

Risk factors and aetiology

Answer 18

personal or family history of atopy
antenatal factors: maternal smoking, viral infection during pregnancy (especially RSV)
low birth weight
not being breastfed
maternal smoking around child
exposure to high concentrations of allergens (e.g. house dust mite)
air pollution
‘hygiene hypothesis’: studies show an increased risk of asthma and other allergic conditions in developed countries. Reduced exposure to infectious agents in childhood prevents normal development of the immune system resulting in a Th2 predominant response.

Focusing on atopy, patients with asthma also suffer from other IgE-mediated atopic conditions such as:
atopic dermatitis (eczema)
allergic rhinitis (hay fever)

Question 19

occupational asthma

Answer 19

Finally, around 10-15% of adult asthma cases are related to allergens in the workplace. Occupational asthma is usually diagnosed by observing reduced peak flows during the working week with normal readings when not at work. Examples of common occupational allergens include isocyanates and flour.

Question 20

Spirometry

Answer 20

Spirometry is a test which measures the amount (volume) and speed (flow) of air during exhalation and inhalation. It is helpful in categorising respiratory disorders as either obstructive (conditions where there is obstruction to airflow, for example due to bronchoconstriction in asthma) or restrictive (where there is restriction to the lungs, for example lung fibrosis). Key metrics include:
FEV1: forced expiratory volume - volume that has been exhaled at the end of the first second of forced expiration
FVC: forced vital capacity - volume that has been exhaled after a maximal expiration following a full inspiration.
Typical results in asthma
FEV1 - significantly reduced
FVC - normal
FEV1% (FEV1/FVC) < 70%

Question 21

Inhaled corticosteroids: Beclometasone, diprp[ionnate, fluticasone, propionate.

Answer 21

Used in patients whose asthma is not controlled by SABA alone
Taken everyday, regardless of whether the patient has symptoms
When discussing with patients often termed ‘the preventer’
Side effects include oral candidiasis and stunted growth in children.

Question 22

Long acting beta-agonists (LABA): Salmeterol

Answer 22

LABAs, as their name suggests, are longer acting versions of SABAs
They are taken, like ICS, everyday, regardless of whether a patient has symptoms

Question 23

Leukotriene receptor antagonists

Answer 23

Monteleukast: oral medication.

Question 24

Maintenance and reliever therapy (MART)

Answer 24

a form of combined ICS and LABA treatment in which a single inhaler, containing both ICS and a fast-acting LABA, is used for both daily maintenance therapy and the relief of symptoms as required
MART is only available for ICS and LABA combinations in which the LABA has a fast-acting component (for example, formoterol)

Question 25

Management of asthma has chchanged following 2017 NICE asthma guidelines. The main take-home points and are that all patients are:

Answer 25

patients on a SABA + ICS whose asthma is not well controlled should be offered a leukotriene receptor antagonist, not a LABA MART is now an option for patients with poorly controlled asthma

Question 26

What type of immune response is mediated in asthma and what do the lungs show?

Answer 26

The immune response is CD4 mediated, and the lungs will show an eosinophil infiltrate.

Question 27

What percentage of airflow obstruction is reversible in asthma vs copd?

Answer 27

asthma exists where the obstruction is reversible by >15%, and COPD exists where it is reversible by <15%.

Question 28

Three main characteristics of asthma

Answer 28

Airflow limitation – this is usually reversible, either spontaneously, or with treatment Airway hyper-responsiveness – this occurs to a wide range of stimuli 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. The disease often ‘flares up’ with viral infections – which often cause a loud wheeze.

Question 29

Determining factor between asthma and copd?

Answer 29

If the patients are in their 30s and 40s, and smoke or drink alcohol. Also, need to check if hasve inspiratory stridor or expiratory. Expiratory stridor is indicitive of asthma, where as inspiratory is indicative of airway obstruction. Ask ENT surgeon.

Question 30

Aetiology of asthma

Answer 30

The disease can either be intrinsic (aka cryptogenic); where no causatory factor can be found, or extrinsic, where there is a definite external cause. Intrinsic – this often starts in middle age, and is sometimes called late onset asthma. No trigger can be identified. Extrinsic – this usually occurs 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. It is often accompanied by eczema. Non-atopic individuals can develop asthma in later life via sensitisation to e.g. occupational agents, aspirin, or as a result of taking β-blockers for hypertension or angina. Extrinsic asthma involves a type I hypersensitivity reaction to inhaled allergens (there is also a delayed phase reaction, type IV hypersensitivity which occurs huors-days after exposure.

Question 31

Atopy meaning

Answer 31

This is a term used to describe people who often have allergies / asthma / hayfever, and where: The trait runs in families (i.e. genetic component).

Question 32

IgE antibody in asthma

Answer 32

The individuals have IgE antibodies to many common allergens – these antibodies are present in 30-40% of the UK population, and there is a strong correlation between the levels of IgE and the severity of asthma and airway hyper-responsivenessi

Question 33

Bronchial provocation test

Answer 33

You can test for this by asking the patient to inhale gradually increasing amounts of methacholine or histamine. This is known as a bronchial provocation test. This will induce transient airflow limitation in 20% of the population – and these are the patients that exhibit airway hyper-responsiveness.

Question 34

Pathology of asthma

Answer 34

Related to an individuals response to various antigens and to the amount of airway remodelling that occurs. Exposure to the antigen will make CD4 T cells differentiate into T helper cells (Th2 type, as opposed to Th1), and they will begin to secrete IL-4 and IL-5. IL-4 will cause B cells to become plasma cells and being 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. This IgE will bind to mast cells in the mucosa. This initial exposure will not cause an allergic reaction. The IgE sits there on the mast cell surface, waiting to come into contact with the antigen again, perhaps for years Upon re-exposure to the antigen, the mast cells will be activated, and will degranulate. This will release inflammatory mediators. There are increased numbers of mast cells in both the airway secretion, and the epithelial lining of lung in asthmatics – thus increased response to any antigens. This causes the initial asthma attack. This is mainly the result of histamine and prostaglandin (as well as leukotrienes; particularly LTC4) release by mast cells. This usually occurs within minutes of initial exposure to the antigen. Thus mast cells are responsible for the early attack.

Question 35

Histamine

Answer 35

causes smooth muscle contraction, increased bronchial secretions, and increased vascular permeability.

Question 36

Late phase reaction

Answer 36

occurs several hours after the initial reaction. It is caused by the accumulation of eosinophils (and some neutrophils – but these are much more numerous in COPD) at the site. The late phase reaction is a more sustained inflammation. The initial phase is more bronchoconstriction without as much underlying inflammation. Bronchodilators (the β-adrenergics) are good at treating the initial phase reaction; the late phase reaction tends not to respond well. Steroids (and other anti-inflammatories) are good for preventing the inflammation that causes the late phase reaction. The late phase reaction is more likely 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.