Asthma is a common chronic inflammatory disorder of the airways.
Approximately, 12% of the UK population have a diagnosis of asthma and 5.4 million are receiving treatment for the condition.
Clinically it presents with classical features including cough, wheeze, chest tightness, and shortness of breath. It can present acutely as an 'exacerbation of asthma', which may be life-threatening. It is characterised by:
Over the last decade, the approach to the diagnosis and management of asthma has been changing rapidly. There are currently two broad guidelines for the management of asthma (NICE and BTS/SIGN).
Asthma is an enormously complex condition that may present at any age.
Many factors can contribute to the development of asthma, understanding these is key to effective management.
Atopy is a genetic predisposition to IgE-mediated allergen sensitivity. Atopic individuals are predisposed to the following three conditions:
The hygiene hypothesis was first developed from epidemiological data showing increased autoimmune and allergic disease in western countries.
It postulates that reduced exposure to infectious pathogens at a young age predisposes individuals to such diseases. In simple terms, this environment is thought to encourage Th2 predominant response - one that produces IgE.
A small subset of patients with asthma are affected by a sensitivity to aspirin. Ingestion is capable of triggering an attack. These patients exhibit Samter’s triad:
Around 15% of cases of asthma in adults are related to occupational exposure. Asthma may be induced or exacerbated by such exposure. Hundreds of sensitisers have been identified. They may be categorised as:
Peak expiratory flow diaries during periods of work and holiday are key to the diagnosis of occupational asthma.
In this variant asthma is triggered by strenuous physical activity. The aetiology is complex but exposure to cold air and environmental pollutants contributes.
Asthma is the result of aberrant airway inflammation and bronchospasm, which contribute to an increase in airway resistance.
Inhalation of allergens results in an immediate (type 1) hypersensitivity reaction in the airways.
Sensitisation occurs during the allergen exposure causing the release of IgE antibodies from plasma cells. IgE bind to high affinity receptors on mast cells.
Subsequent exposure to antigens cause mast cell degranulation and histamine release. These mediators cause smooth muscle contraction and bronchoconstriction whilst inflammation contributes to airway obstruction.
The initial early phase reaction may be followed by a late response hours later. During the late phase, recruitment of a variety of inflammatory cells (e.g. polymorphonuclear cells, T-cells) occurs.
The late response is more complex than the early response involving multiple additional processes. Beta-agonists do not cause complete reversal of the late response.
In response to persistent chronic inflammation, the airways lay down fibrous tissue. Over time airway remodelling occurs and manifests as fixed airway obstruction - i.e. airway narrowing that is irreversible.
Characteristic features of asthma include cough, shortness of breath and an expiratory polyphonic wheeze.
Between acute exacerbations, some patients may experience little in the way of signs and symptoms whereas others may have chronic disabling breathlessness.
Asthma is a chronic disease who's course may be interrupted by acute deteriorations or 'attacks'. These attacks are characterised by:
In more severe attacks patients have signs of respiratory failure:
These features can be used to categorise the severity of an asthma attack as seen in the below table.
Spirometry should always be performed at the time of diagnosis to assess airway obstruction.
Spirometry measures the flow and volume of air during inhalation and exhalation:
The following changes are seen in obstructive lung disease:
Reversibility may be demonstrated by performing spirometry before and after the administration of a bronchodilator.
Asthma demonstrates characteristic variability on PEFR diaries. It usefulness in the diagnosis of asthma is limited.
It is considered non-specific as variability may be seen in other conditions. It may be used to categorise acute asthma attacks and can be key to the diagnosis of occupational asthma.
FeNO testing is typically offered to patients being investigated for asthma at the same time as spirometry. FeNO is a newer way of testing for eosinophilic airway inflammation. FeNO is measured in parts per billion and a level >25 ppb at 50 ml/sec is seen in 70-80% of patients with untreated asthma. Eosinophilic airway inflammation has been linked to the response to corticosteroids.
In the NICE guidelines (NG80) FeNO has an important role in the diagnosis of asthma in adults. In the BTS/SIGN guidelines it is more targeted to patients with an intermediate risk of asthma. Based on NICE guidance, we can think of FeNO measurements in three groups.
BTS, SIGN & NICE have all produced guidelines for the diagnosis and management of asthma.
These guidelines provide broadly similar advice for the diagnosis and treatment in adults. However, due to the methodology used in the creation of these guidelines, there are key differences relating to both diagnosis and management. Consequently, all three have committed to producing a joint guideline, which should help unify the management of asthma.
The Global Initiative for Asthma (GINA) have recently produced a report on recommendations for the management and prevention of asthma in 2021. This highlighted the overuse of short-acting beta agonists (e.g. salbutamol) and made suggestions for the step-wise treatment of asthma that differs from the previous NICE and BTS/SIGN guidelines. Unfortunately, this continues to add to the confusion of the optimum treatment of asthma.
Asthma is diagnosed in the presence of indicative clinical features and the exclusion of alternate diagnoses.
The diagnosis and subsequent investigations for suspected asthma in adults may differ between the NICE and BTS/SIGN guidelines.
Initially, it is important that all patients have a structural clinical assessment including history and examination to determine the probability of asthma. This is true between both guidelines. Here, we discuss the BTS/SIGN guidelines.
BTS/SIGN guidelines advise categorisation of patients based upon the probability of asthma being the correct diagnosis. From here the choice of further investigations may be made.
Investigate and treat for alternative, more likely, diagnosis. If alternative diagnosis unlikely, investigate as an intermediate probability of asthma.
Refer for lung function testing (e.g. spirometry and bronchodilator reversibility). Additional testing may be considered to assess for variability and eosinophilic inflammation.
Treatment can then be instigated based on the results of investigations
Trial of treatment and reassess using lung function testing or a validated scoring system.
When the diagnosis of Asthma is unclear, further investigations or specialist referral may be required.
At any point during the diagnostic algorithm within the BTS/SIGN guidelines, there may be need for further investigations or specialist referral.
Criteria for referral:
Features suggesting alternative diagnosis:
Asthma management is a step-wise process with advancement indicated by ongoing symptoms.
The general principles of asthma management are to start at the most appropriate level of therapy, achieve early control and then maintain control.
Each of the guidelines (BTS/SIGN, NICE, GINA) outline different stepwise treatment recommendations. We have outlined below the BTS/SIGN guidelines, which are widely used in clinical practice. It is important that you know some of the key differences between the guidelines.
Control is defined as:
There are many different inhalers that can be used in the treatment of asthma. Inhalers may contain a single drug (e.g. beta-agonist) or combination of drugs (e.g. beta-agonist and corticosteroid).
Inhalers may deliver drugs by different mechanisms
Pharmacological treatment of asthma follows a step-wise algorithm.
Traditionally, all patients are offered a short-acting beta-2 agonist (SABAs) such as salbutamol (a reliever). This is prescribed as needed (PRN) and if use exceeds three times a week consider 'stepping up' therapy. However, newer guidelines focus on early initiation of an ICS. It is important to only prescribe inhalers following training on how to use the device and demonstration of satisfactory technique.
The first step in the SIGN/BTS guidelines is an ICS with SABA as needed. Alternatively, a patient may use a LABA (e.g. formoterol) combined with an ICS as part of a maintenace and reliever inhaler (i.e. MART). These LABAs are relatively short-acting and can be taken for relief of symptoms as required and reduce the need for multiple inhalers.
The below stepwise algorithm follows the SIGN/BTS guidelines. We also mention the newer recommendations on chronic asthma management recommended by GINA.
Prescribe an inhaled corticosteroid (ICS) as part of a monitored trial in those with suspected asthma or to those formally diagnosed with asthma. Examples include Fluticasone and Beclomethasone.
Add inhaled long-acting beta agonist (LABA) in addition to low dose ICS. Can consider fixed doses or use of maintenance and reliever therapy (MART), which refers to a combined inhaler. Fostair is an example of a MART that contains formoterol/beclometasone.
A MART should be used daily as maintenance, but can also be used when patients develop symptoms. If patients are using a MART they should not be dually prescribed a SABA (e.g. salbutamol).
Consider increasing ICS to medium dose or adding a leukotriene receptor antagonist (LTRA) like montelukast. One of the major differences in the NICE guidelines refers to the role of LRTAs (they recommend this at step 2).
If ongoing symptoms despite previous therapies, consider specialists referral.
GINA have advised their own step-wise recommendations that follows two tracks depending on the role of the 'reliever' inhaler:
A severe acute asthma attack represents a medical emergency. Prompt recognition and management is required.
The severity of an acute asthma attack is based on symptoms, observations and the PEFR, this is described in the table in the 'Clinical features' chapter. Patients will generally receive their initial therapy in A&E Resus or majors depending on presenting features. ITU/HDU input should be arranged early in those with severe features.
The below algorithm is based on SIGN/BTS 158 guideline on the management of asthma. Patients not responding to first line therapies need senior clinician review and discussion with HDU/ICU.
Salbutamol nebulisers, 2.5 - 5mg (preferably driven by oxygen) should be administered in adults. They may be repeated every 15 to 30 minutes. If there is no access to nebulisers back to back inhalers should be given. IV beta-2 agonists should be reserved for those in whom inhaled therapy is not possible.
Oxygen should be started immediately in severe attacks and is typically titrated to saturations of 94-98%. An arterial blood gas should be considered if saturation < 92% or life-threatening features. The development of hypercapnia indicates a near-fatal attack, specialist and anaesthetic involvement is required.
Steroids should be started. Either PO with prednisolone 40-50mg daily or IV with hydrocortisone 100mg six hourly. They should be continued for at least five days. In cases where IV hydrocortisone has been used, switch to oral prednisolone when appropriate.
Ipratropium bromide nebulisers, 0.5 mg 4-6 hourly, are given to most patients admitted with an acute asthma attack. However, it is advised for patients with severe or life-threatening asthma not responding to nebulised salbutamol.
There is a body of evidence indicating magnesium sulfate has bronchodilator effects. Discussion with senior staff is necessary, a dose of 1.2 - 2 g IV magnesium sulfate may be given over 20 minutes in adults.
In patients still not responding B2 agonist infusions may be started.
In an acute attack, there is little evidence IV aminophylline will result in additional bronchodilation.
It is often still used and requires senior input. A 5mg/kg loading dose (over 20 minutes) is followed by a continuous infusion. Aminophylline levels should be checked daily.
Patients who have suffered a near-fatal acute exacerbation of asthma require specialist follow-up indefinitely.
The SIGN/BTS guidelines provide information about appropriate discharge of patients from the emergency department who present with an acute exacerbation of asthma.
If require nebulised beta-2 bronchodilators prior to presentation, consider extended period of observation.
NOTE: Once admitted to hospital the key parameter to determine discharge is peak flow. The aim should be a peak flow >75% of best or predicted with a diurnal variability <25% before discharge (unless agreed otherwise by a respiratory clinician).
All patients with a peak flow <50% of best or predicted on admission require prednisolone 40-50 mg/day until recovery with a minimum of five days. It is essential to check inhaler technique and ensure supply. Will need GP follow-up within two days of discharge and a referral to asthma specialist nurse clinic. If the patient was admitted to hospital, they will require a respiratory clinic appointment within four weeks.
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