Asthma

Asthma is a reversible obstructive airway condition that has 2 distinct characteristics: airway inflammation and airway hyper-responsiveness (we will look at this further below).

🏘️ Epidemiology

Asthma is the most common lung condition, with an incidence of 160,000 annually. About 5.4 million people in the UK are currently receiving some form of treatment for asthma, costing the NHS £1 billion annually.

There are on average 3 deaths a day from asthma in the UK.

Pathophysiology

As mentioned previously, the 2 main components of asthma are inflammation and airway hyper-responsiveness. Let’s take a look at these further.

• Inflammation

An initial trigger (such as dust or animal fur) causes the release of inflammatory mediators which activates other inflammatory cells and causes migration of these cells.

It is a Th2 response that mediates the inflammatory reaction. It is characterised by the presence of CD4+ lymphocytes which secrete IL-4, IL-5 and IL-13, CCL11, TNF-a, LTB4 (leukotriene) and mast cell tryptase.

IL-5 is important in activating eosinophils, while IL-4 is important for isotope switching of antibodies to IgE for activation of mast cells.

Mast cells degranulate which induces bronchospasm, and increases vascular permeability and mucus production as well as leukocyte recruitment. These leukocytes release additional cytokines that initiate the late phase of asthma.

Eosinophils release mediators that damage the epithelium while neutrophils are important in near-fatal exacerbations of asthma.

• Airway hyper-responsiveness

The inflammatory mediators released with the inflammatory response induce smooth muscle contraction (through parasympathetic nerve fibre stimulation) → airway hyper-responsiveness.

This hyper-responsiveness has 2 different temporal elements:

1. Baseline fixed - which is persistent and presumably caused by airway remodelling due to chronic recurrent airway inflammation
2. Episodic variable - more acute which is associated with an episodic increase in airway inflammation due to environmental factors such as allergen exposure.

With the baseline AHR there is inflamed and thickened bronchiole walls due to remodelling, however, there is no bronchoconstriction as the smooth muscles are relaxed. With an acute episode (asthma attack) there is an additional component of smooth muscle contraction and additional inflammation which leads to worsened symptoms acutely

🔢 Classification

We can classify asthma as either allergic (extrinsic) or non-allergic (intrinsic). Extrinsic is more common.

⚠️ Risk factors

• Family history
• Exposure to triggers - may be triggered by viral infection, allergen exposure, NSAIDs/beta-blockers and/or exacerbated by exercise, cold air and emotion/laughter in children.
• History of atopy - such as eczema, atopic dermatitis or allergic rhinitis (this is the atopic triad). There is a progression known as the allergic/atopic march in which eczema/atopic dermatitis progresses → allergic rhinitis → asthma.
• Cigarette smoking or vaping
• Respiratory viral infection early in life

😷 Presentation

🔍 Investigations

It is necessary to remember that asthma can be diagnosed without confirmatory tests.

1. We need to perform an initial clinical assessments (algorithm A). This includes a structured clinical history. It is necessary to ask about
1. Wheeze, cough, breathlessness and daily/seasonal variation
2. Triggers that worsen symptoms
3. Personal or family history of atopy
2. Physical examination is the next step
1. Assess for an expiratory polyphonic wheeze
3. Order objective tests. The order and use of these tests differ depending on age (5, 5-16 or 17+):
1. <5 - manage symptoms but do not offer any diagnostic tests. When they reach the age of 5, then we can perform some objective tests
2. 5-16 - spirometry → bronchodilator reversibility (BDR) → FeNO → peak flow variability (check algorithm B).
3. 17+ - FeNO & spirometry → BDR → peak flow variability → bronchoprovocation/histamine challenge test/methacholine challenge test (check algorithm C).

Let’s take a closer look at what these tests include:

🌬️

Spirometry

Spirometry takes a look at the total amount of air inhaled and exhaled and plots this volume against time.

Spirometry enables us to calculate the FVC, FEV1, MVV:

• Forced vital capacity (FVC) - total volume of air exhaled during forced expiration.
• Forced expiratory volume in 1 second - total volume of air exhaled in the 1st second of the FVC.
• Maximum voluntary ventilation - measures the total ventilatory volume that a patient can produce in a given period of time (usually 1 minute).

The technique in spirometry involves taking a very deep breath and blowing out as forcefully and rapidly into the mouthpiece until no more air comes out.

An FEV1/FVC ratio may be calculated using this information. An FEV1/FVC ratio of <70% is indicative of obstructive disease.

🌬️

Fractional exhaled nitric oxide (FeNO)

Nitric oxide is produced by 3 types of nitric oxide synthase enzymes. One of which is inducible NOS. It’s levels tend to rise in inflammatory cells (particularly eosinophils), therefore levels of nitric oxide tend to correlate with levels of inflammation.

• Adults - >40 parts per billion is considered positive for asthma.
• Children - >35 parts per billion is considered positive for asthma.

Steroids should not be taken for 2 weeks prior to the test as this can give us a false negative

🌬️

Peak flow variability

This test measures how rapidly you can breathe out after maximal inspiration. It is sometimes known as the peak expiratory flow rate (PEFR).

The patient will be asked to perform the test 3 times and the best score will be noted.

Diagnosis is made if there is >20% PEFR variability on >3 days per week for 2 weeks.

💯 Grading

We can grade asthma from moderate all the way up to near-fatal asthma:

⚠️ High pCO2 is worrisome as it is indicative of the patient becoming tired. It is normal for them to hyperventilate to breathe in more oxygen, however, they simultaneously blow off more CO2 and become hypocapnic as a result. A normal or high CO2 can be concerning as it means they are not breathing as much.

🧰 Management

The aims of asthma management are to control the disease. Complete control of asthma is defined as:

• No daytime symptoms
• No night-time awakening due to asthma
• No need for rescue medication
• No asthma attacks
• No limitations on activity
• Normal lung function
• Minimal side effects from medication

The 3 RCP questions can help us identify if it is well controlled:

1. Have you had difficulty sleeping because of your asthma symptoms (including cough)?
2. Have you had your usual asthma symptoms during the day (cough, wheeze, chest tightness or breathlessness)?
3. Has your asthma interfered with your usual activities (for example, housework, work/school, etc.)?

Let’s discuss the management of asthma in <5, 5-16 and adults (17+) and then we will discuss the management of acute asthma in children and adults:

Management of chronic asthma in adults >17 years of age [BTS, 2019]

• Reliever therapy - short-acting ß2 agonist (SABA). This may be used at any step to provide relief. It is the “blue inhaler”.
• Salbutamol

• Maintenance therapy:

1. Start on a low-dose inhaled corticosteroid (ICS) - budesonide, beclametasone, fluticasone.
2. If not enough, add an inhaled long-acting ß2 agonist (LABA) to the ICS as a fixed-dose regimen or a maintenance and reliever therapy (MART) which is essentially the ICS + LABA in a single inhaler.
1. Salmeterol, formoterol are the 2 most common LABAs. It is the “brown inhaler”.
2. Fostair (beclametasone + formoterol) is a MART that is often described as the “purple inhaler”.
3. If this is not enough, consider increasing the ICS from a low dose to medium dose. Or we can add a leukotriene receptor antagonist (LTRA) instead on top of the low-dose ICS and LABA
1. [Medium-dose ICS + LABA] OR [low-dose ICS + LABA + LTRA]
2. Montelukast is the LTRA.
4. If this is still not sufficient → refer to specialist.

NICE (2017) differs slightly by suggesitng:

1. Low-dose ICS
2. Add LTRA
3. Add LABA
4. Switch to MART instead of fixed dose ICS and LABA. The MART regimen may or may not contain the LTRA.
5. Increase ICS to moderate-dose
6. There are 3 options:
1. Increase ICS to high-dose
2. Trial theophylline
3. Trial LAMA
7. Refer to specialist.

Management of chronic asthma in children 5-16 years of age [BTS, 2019]

• Reliever therapy - short-acting ß2 agonist (SABA). This may be used at any step to provide relief. It is the “blue inhaler”.
• Salbutamol

• Maintenance therapy

1. Start on paediatric-dose ICS
2. Add inhaled LABA or LTRA
3. Consider increasing ICS to low-dose ICS and adding LTRA or LABA (i.e. low-dose ICS + LTRA/LABA). If there is no response to the LABA, consider stopping it.
4. If not sufficient → refer to specialist.

NICE (2017) differs slightly by suggesting:

1. Low-dose ICS as first-line maintenance therapy.
2. Add LTRA to the ICS and review in 4-8 weeks.
3. If insufficient, stop the LTRA and starting a LABA in combination with the ICS.
4. If insufficient, then consider changing to a MART regimen which contains a paediatric low-dose ICS.
5. If insufficient, consider increasing the ICS to a paediatric moderate-dose (as MART or with fixed-dose ICS + LABA).
6. If not sufficient, consider trialling an additional drug (theophylline) or increasing the ICS to a paediatric high-dose (alone without LABA). LAMAs are not used in the 5-16 age group.
7. Refer to specialist.

Management of chronic asthma in children <5 of age [BTS, 2019]

• Reliever therapy - short-acting ß2 agonist (SABA). This may be used at any step to provide relief. It is the “blue inhaler”.
• Salbutamol

• Maintenance therapy

1. Start on LTRA
2. Add paediatric-dose ICS
3. Refer to specialist

NICE differs slightly by suggesting:

1. Consider paediatric moderate-dose ICS trial for 8 weeks.
2. After 8 weeks stop treatment and monitor the symptoms.
1. If symptoms do not resolve then review if an alternative diagnosis is likely.
2. If symptoms resolved and reoccurred within 4 weeks then restart the ICS at a paediatric low-dose as first-line maintenance.
3. If symptoms resolved but reoccurred after 4 weeks of stopping the ICS, repeat the 8 week trial.
3. If suspected asthma is uncontrolled in children <5 on paediatric low-dose ICS, consider adding an LTRA on top of it.
4. If not enough, stop the LTRA and refer to specialist.

Maintenance therapy is considered if symptoms clearly indicate the need for maintenance therapy (e.g. asthma-related symptoms >3 times a week, or waking up a night due to symptoms) OR if the asthma is uncontrolled with SABA alone.

🚨

Management of an acute asthma attack [BTS, 2019]

• 🥇Admit to hospital if life-threatening or near-fatal asthma attack.
• According to the NICE guidelines, you should admit a patient if there are features of a severe attack and these persist after a trial of bronchodilators.
• NICE also recommends a lower threshold (moderate asthma exacerbation) for admission with certain patients, such as:
• Pregnant women - even if they respond well to initial treatment.
• Age under 18 years.
• Poor treatment adherence.
• Living alone/social isolation.
• Psychological problems such as depression, and alcohol or drug misuse.
• Physical or learning disability.
• Previous severe asthma attack.
• Exacerbation despite an adequate dose of oral corticosteroids before presentation.
• Presentation in the afternoon or at night.
• Recent nocturnal symptoms.
• Recent hospital admission.

• 🥇 Nebulisers
• Salbutamol - up to 10mg/hour
• Add ipratropium bromide (SAMA) - 500mcg (up to 4 hourly) if salbutamol is not enough.
• 🥇 Steroids - prednisolone if they can swallow. It should be given for 3-5 days.
• Oxygen to patients who are hypoxaemia (maintaining 94-98% SpO2). Do not delay oxygen administration in the absence of pulse oximetry but commence monitoring of SpO2 as soon as it is available.
• Antibiotics - if indicated, but not routinely recommended.
• Magnesium sulphate - given IV to patients with PEFR <50% (severe asthma) who did not respond to inhaled bronchodilators.
• Aminophylline - not recommended in children with mild-moderate acute asthma but may be considered in children with severe or life-threatening asthma who are unresponsive to a maximal dose of steroids and bronchodilators.

When discharged from hospital, patients should have:

• Been on discharge medication for 12-24 hours and have had inhaler technique checked and recorded.
• Prior to discharge, been referred to the respiratory nurse specialists for education and inhaler technique if they have been admitted with a new diagnosis or exacerbation of asthma.
• PEF >75% of best or predicted and PEF diurnal variability <25% unless discharge is agreed with respiratory physician.
• Treatment with prednisolone until recovery - minimum of 5 days and inhaled steroids in addition to bronchodilators. Patients should have inhaled corticosteroid therapy started if new diagnosis or treatment increased if poorly controlled prior to admission. This will usually be guided by respiratory nurses.
• Own peak flow meter and written asthma action plan.
• GP follow up arranged within 2 working days.
• Follow up appointment in respiratory clinic within 4 weeks.

[ADD SECTION ON INHALER TECHNIQUE]

[ADD SECTION ON ASTHMA MIMICS/DIFFERENTIAL DIAGNOSIS]

[LINK OCCUPATIONAL ASTHMA FROM CCC ON OCCUPATIONAL LUNG DISEASES]