Asthma in adults

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

For information specific to management of exacerbations, see Acute asthma exacerbation in adults.

The main goal of asthma treatment is to achieve maximum control of symptoms with the fewest medications. The British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) define complete control of asthma as:[55]

No daytime symptoms
No night-time waking due to asthma
No need for rescue medication
No asthma attacks/exacerbations
No limitations on activity, including exercise
Normal lung function (in practical terms forced expiratory volume at 1 second [FEV₁] and/or peak expiratory flow [PEF] more than 80% predicted or best)
Minimal adverse effects from medication

The National Institute for Health and Care Excellence (NICE) defines uncontrolled asthma as any one of:[56]

Three or more days a week with symptoms
Three or more days a week with required use of a short-acting beta agonist (SABA) for symptomatic relief
One or more nights a week with waking due to asthma

In practice, complete control of asthma may require a regimen that is inconvenient for the patient and may lead to adverse effects. The goal of complete control should therefore be balanced with the patient's lifestyle and their tolerance for adverse effects.

Once control of symptoms is achieved, attempt to reduce the doses of medications while maintaining optimal control and minimising any adverse effects.

Education and environmental control

Ensure all patients at all steps of therapy have access to a self-management programme, which should include a written personalised asthma action plan and education.[1][55][56][85] [ ] This should be supported by regular professional review.[55][56] Advise the patient to take environmental control measures (e.g., reduce exposure to indoor and outdoor air pollution, tobacco smoke, and occupational and domestic allergens).[1][55][56] If you suspect an occupational cause, see Occupational asthma.

Consider breathing exercise programmes as part of an integrated approach to management, alongside pharmacological treatment, to improve the patient's quality of life and reduce symptoms.[1][55]

Approaches used in practice include the Papworth method and the Buteyko method.[55] These techniques involve instruction by a trained therapist in exercises to reduce respiratory rate and minute volume, and to promote nasal, diaphragmatic breathing.
Breathing exercises can lead to modest improvements in asthma symptoms and quality of life, and reduce bronchodilator requirement in adults with asthma, but have little effect on lung function or airway inflammation.[55][86][87][88][89] More studies are needed.[88] [ ]

Exercise-induced bronchoconstriction

Always review the patient's regular treatment and check their inhaler technique and adherence if they are experiencing exercise-induced symptoms; breakthrough exercise-induced bronchoconstriction may indicate poorly controlled asthma, potentially requiring stepping up of treatment (see Stepwise therapy for long-term management).[55] [ ]

If exercise induces symptoms (e.g., shortness of breath, wheezing) in patients whose asthma is otherwise well controlled with an inhaled corticosteroid (ICS) or other stepwise therapy (see below), advise the patient to use an inhaled SABA immediately before exercise.[55] In addition, consider adding one of the following to their usual medication:[55]

Leukotriene receptor antagonist (LTRA)
Long-acting beta agonist (LABA)
Sodium cromoglicate or nedocromil[90]
Theophylline[91]

The Medicines and Healthcare products Regulatory Agency (MHRA) warns of serious behaviour- and mood-related adverse effects with montelukast (an LTRA), and advises that healthcare professionals:[92]

Be alert for neuropsychiatric reactions in patients taking montelukast, including but not limited to sleep disturbances, depression and agitation, disturbances of attention or memory, speech impairment (stuttering), and obsessive-compulsive symptoms.
Advise patients and their carers to read carefully the list of neuropsychiatric reactions in the patient information leaflet and seek medical advice immediately should they occur.
Evaluate carefully the risks and benefits of continuing treatment if neuropsychiatric reactions occur.

Stepwise therapy for long-term management

Guidelines recommend that asthma severity and control be viewed as a ladder in which medication can be stepped up or stepped down based on the severity of the disease and adequacy of the control.

The patient's symptoms should be assessed and recorded on at least an annual basis in a clinical review by a healthcare professional with appropriate training in asthma management. These reviews can be undertaken in primary and/or secondary care according to local availability and clinical need.[55] For more information on annual reviews, see Monitoring section.

When assessing the patient's symptoms, use specific questions, such as the Royal College of Physicians' '3 Questions' (RCP3Q):[55]

'In the last month, have you had difficulty sleeping because of asthma symptoms (including cough)?'[93]
'Have you had your usual asthma symptoms during the day?'[93]
'Has your asthma interfered with your usual activities (e.g., housework, work, etc.)?'[93]

Positive responses to RCP3Q should prompt further assessment with a validated questionnaire to measure symptomatic asthma control, for example the Asthma Control Questionnaire (ACQ) or Asthma Control Test (ACT).[2][55][56][94] [ ]

The stepwise approach is meant to assist, not replace, the clinical decision making required to meet individual patient needs.

Patients may start at any step of the ladder, according to their initial severity, and medications can be added (stepped up) if needed.
Stepping up of treatment may be needed at any time in a patient with poor symptom control and/or exacerbations despite taking asthma treatment. Before stepping up, always check the patient's inhaler technique and adherence to treatment, confirm the diagnosis of asthma, work with the patient to reduce or remove any triggers (e.g., smoking), and address comorbidities where feasible.[55][95] [ ] In the UK, NICE recommends allowing 4 to 8 weeks to assess the patient's response before making a decision on whether a step up to the next level of treatment is needed.[96]
Increasing use of a SABA (if prescribed) or use >2 days a week for symptom relief (not prevention of exercise-induced bronchoconstriction) generally indicates inadequate control and the need to step up treatment.

Regularly assess the patient's asthma control, with the aim of stepping down the ladder if their symptoms have been well controlled for at least 3 months.[56] Ongoing regular review of patients as treatment is decreased is important.[55]

When deciding which drug to decrease first and at what rate, take into account: the severity of asthma, the adverse effects of the treatment, time on current dose, the beneficial effect achieved, and the patient's preference.[55]
Patients should be maintained at the lowest possible dose of ICS. Reduction in dose should be slow as patients deteriorate at different rates. Reductions should be considered every 3 months, decreasing the dose by approximately 25% to 50% each time.[55]

The management of asthma has been the subject of debate among the major UK guideline authorities, with differences in the details of their step-up pharmacological options. Recommendations in this topic are based primarily on the BTS/SIGN guideline, which was last updated in July 2019, but a summary of the NICE guideline is also provided towards the end of this section. Follow the recommended approach in your region.

[Figure caption and citation for the preceding image starts]: Summary of management in adults; reproduced from BTS/SIGN “British guideline on the management of asthma”British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. First published 2003. Revised edition published July 2019; used with permission [Citation ends]. com.bmj.content.model.Caption@2779438c

BTS/SIGN: step 1 - initial therapy for control of asthma

SABA

Prescribe an inhaled SABA (e.g., salbutamol), as short-term therapy, to be used as needed to relieve symptoms in symptomatic patients.[55]

In practice, only a very limited number of patients will need occasional use of SABAs alone with no preventer therapy. Most patients will also need regular preventer therapy with ICS.
SABAs work more quickly and/or with fewer adverse effects than the alternatives (ipratropium, theophylline).[55][97]

If the patient needs more than one short-acting bronchodilator inhaler device a month, arrange urgent assessment of their asthma and take measures to improve asthma control if this is poor.[55]

High SABA use is associated with a significant increase in exacerbations and asthma-related healthcare utilisation.[98][99] Overuse of SABAs is also a risk factor for fatal asthma.[55]
Patient populations most at risk for SABA over-reliance include older adults, smokers, and patients with lower socioeconomic status.[99]

Low-dose ICS

Consider adding low-dose ICS to SABA if the patient has any of the following asthma-related features:[55]

Acute asthma attack (requiring oral corticosteroids) in the past 2 years
Using inhaled SABA three times a week or more
Symptomatic three times a week or more
Waking one night a week

Although alternatives are available (e.g., sodium cromoglicate, nedocromil, theophylline), ICSs are the most effective preventer drug for achieving overall treatment goals.[100][101][102][103] Adding ICS to SABA significantly reduces the risk of severe exacerbations and asthma-related death associated with overuse of SABA.[1][104][105]

Start the patient at a reasonable starting dose of ICS appropriate to the severity of their asthma.[55]

Titrate to the lowest dose at which effective control of asthma is maintained.[55]
Higher doses might be needed in patients who smoke or used to smoke.[55]

BTS/SIGN: step 2 - initial add-on therapy

If the patient's symptoms are not adequately controlled with low-dose ICS alone, BTS/SIGN recommend to add a LABA, either as a fixed-dose regimen (with SABA as needed) or as combination maintenance and reliever therapy in a single inhaler (MART).[55]

The addition of an inhaled LABA to ICS alone improves lung function and symptoms, and decreases asthma attacks.[106]

Before stepping up to a new drug, always check the patient's inhaler technique and adherence to treatment, confirm the diagnosis of asthma, work with the patient to reduce or remove any triggers (e.g., smoking), and address comorbidities where feasible.[55]

Option A: fixed-dose LABA + low-dose ICS + SABA as needed

Prescribe a fixed-dose combination ICS/LABA inhaler.[55]

LABAs should never be used without ICS.[55]
- LABA monotherapy is associated with an increased risk of adverse events, life-threatening asthma, and asthma hospitalisation events.[107][108]
Experience in clinical practice shows that combination inhalers not only help patient adherence but also ensure that the LABA is not taken without the ICS.[55]

The patient should continue with their intermittent reliever therapy (usually an inhaled SABA; see step 1: initial therapy for control of asthma), used as needed.[55]

Option B: MART (LABA + low-dose ICS)

Consider MART, particularly if the patient has a history of asthma attacks on a fixed-dose LABA and a low-dose ICS.[55]

MART allows for the rapid onset of a reliever effect with formoterol; by also including a dose of ICS, MART ensures that the dose of preventer medication increases as the need for a reliever increases.[55] Therefore, a comprehensive self-management plan must be provided with a MART regimen.[55]
MART may also lower the overall dose of ICS needed to prevent asthma attacks.[55]

The patient should not use intermittent reliever therapy (e.g., an inhaled SABA) alongside MART.[55]

One Cochrane review of serious adverse events when taking ICS with and without regular formoterol found no difference in risk of death in adults taking ICS-formoterol versus ICS alone.[109] [ ]

BTS/SIGN: step 3 - additional controller therapies

If symptom control remains suboptimal after initial add-on therapy, BTS/SIGN recommend either increasing the ICS to medium dose or adding an LTRA.[55]

Before stepping up treatment, always check the patient's inhaler technique and adherence to treatment, confirm the diagnosis of asthma, work with the patient to reduce or remove any triggers (e.g., smoking), and address comorbidities where feasible.[55]

Option A: medium-dose ICS

If there was some improvement when a LABA was added as initial add-on therapy, but symptom control remains suboptimal, continue with the LABA and consider increasing the dose of ICS from low to medium (either as MART or a fixed-dose regimen).[55]

Consider stopping the LABA before increasing the ICS dose if there was no improvement when a LABA was added.[55] Bear in mind that in clinical practice, the LABA is very rarely stopped so proceed cautiously if considering this.

If the patient is taking a fixed-dose LABA, they should continue with their intermittent reliever therapy (usually an inhaled SABA; see step 1: initial therapy for control of asthma), used as needed. The patient should not use intermittent reliever therapy (e.g., an inhaled SABA) alongside MART.[55][56]

Option B: add LTRA

If there was some improvement when a LABA was added as initial add-on therapy, but symptom control remains suboptimal, continue with the LABA and consider adding an LTRA (e.g., montelukast).[55]

BTS/SIGN recommend to consider stopping the LABA before starting the LTRA if there was no improvement when a LABA was added.[55] In clinical practice, the LABA is usually continued so proceed with caution if considering this.

If on a fixed-dose regimen, the patient should continue with their intermittent reliever therapy (usually an inhaled SABA; see step 1: initial therapy for control of asthma), used as needed.[55]

The MHRA warns of serious behaviour- and mood-related adverse effects of montelukast, and advises that healthcare professionals:[92]

Be alert for neuropsychiatric reactions in patients taking montelukast, including but not limited to sleep disturbances, depression and agitation, disturbances of attention or memory, speech impairment (stuttering), and obsessive-compulsive symptoms
Advise patients and their carers to read carefully the list of neuropsychiatric reactions in the patient information leaflet and seek medical advice immediately should they occur
Evaluate carefully the risks and benefits of continuing treatment if neuropsychiatric reactions occur.

BTS/SIGN: step 4 - specialist therapies

If the patient has severe poorly controlled asthma despite step 3 treatment, with good adherence and correct inhaler technique, BTS/SIGN recommend referring to a specialist.[55]

There are very few clinical trials in this specific patient group to guide management. Recommendations are largely based on extrapolation from trials of add-on therapy to ICS alone.[55]

The specialist might try a number of approaches including:[55]

Increasing the ICS from medium- to high-dose
Adding a long-acting muscarinic antagonist (LAMA)
Adding theophylline
Oral corticosteroids
Biological agents
Bronchial thermoplasty.

High-dose ICS

A specialist may consider increasing the ICS to a high dose; this should only be done as part of a fixed-dose regimen, with a SABA used as a reliever therapy.[55][56]

LAMA

If the patient's asthma does not respond to ICS plus LABA, the addition of a LAMA (e.g., tiotropium) to ICS is a possible alternative a specialist might consider.[55]

There is insufficient evidence to suggest that addition of tiotropium to ICS in patients inadequately controlled on ICS alone has any benefit over addition of LABA to ICS.[55]

Theophylline

Oral theophylline is a bronchodilator which may improve lung function and symptoms, but is associated with adverse effects including headache, nausea, and vomiting.[55]

Plasma theophylline concentration should be checked 5 days after starting treatment and at least 3 days after any dose adjustment. Be aware that smoking increases the clearance of theophylline (therefore, the drug is less effective in people who smoke).

Oral corticosteroids

Some patients with very severe asthma not controlled with high-dose ICS, and who have also been trialled or are still taking LABA, LTRA, LAMA, or theophylline, may require regular long-term oral corticosteroids.[55]

In practice, only a small number of patients will have symptoms that remain uncontrolled despite high-dose therapies. For these patients, daily oral corticosteroids should only be used at the lowest dose providing adequate control.[55]
All patients requiring frequent or continuous use of oral corticosteroids should be under the care of a specialist asthma service.[55]

Biological agents

If the patient has severe persistent asthma that continues to be uncontrolled despite other step 4 therapies, a specialist in a tertiary care centre may consider biological agents as an add-on to optimised standard therapy. Optimised standard therapy is defined as a full trial of, and if tolerated, documented compliance with, high-dose ICS, LABA, LTRA, theophylline, oral corticosteroids, and smoking cessation if clinically appropriate.[55] Add-on biological agents a specialist may consider include:

Omalizumab: for patients with severe persistent allergic immunoglobulin E (IgE) mediated asthma who have:[55][110][111][112][113][114][115]
- A positive skin test or in vitro reactivity to a perennial aeroallergen
- Reduced lung function (FEV₁ less than 80%)
- Frequent daytime symptoms or night-time awakenings
- Multiple documented severe exacerbations despite daily high-dose ICS plus a LABA.
Mepolizumab: for severe refractory eosinophilic asthma if:[55][114][116]
- The patient's blood eosinophil count has been recorded as ≥300 cells per microlitre and they had at least 4 exacerbations needing systemic corticosteroids in the previous 12 months, or the patient has had continuous oral corticosteroids of at least the equivalent of prednisolone 5 mg/day over the previous 6 months, or
- The patient's blood eosinophil count has been recorded as ≥400 cells per microlitre and they have had at least 3 exacerbations needing systemic corticosteroids in the previous 12 months (so the patient is also eligible for either benralizumab or reslizumab - see below).
Reslizumab: for severe eosinophilic asthma that is inadequately controlled despite maintenance therapy with high-dose ICS plus another drug, only if:[55][114][117]
- The patient's blood eosinophil count has been recorded as 400 cells per microlitre
- The patient has had at least 3 severe asthma exacerbations needing systemic corticosteroids in the previous 12 months.
Benralizumab: for treating severe eosinophilic asthma that remains uncontrolled despite maintenance therapy with high-dose ICS and LABA, only if:[55][114][118][119]
- The patient's blood eosinophil count has been recorded as ≥300 cells per microlitre and the person has had 4 or more exacerbations needing systemic corticosteroids in the previous 12 months, or has had continuous oral corticosteroids of at least the equivalent of prednisolone 5 mg/day over the previous 6 months (i.e., the patient is eligible for mepolizumab), or
- The patient's blood eosinophil count has been recorded as ≥400 cells per microlitre with 3 or more exacerbations needing systemic corticosteroids in the past 12 months (i.e., the patient is eligible for reslizumab).
Dupilumab: for patients with severe asthma with type 2 inflammation that is inadequately controlled, despite maintenance therapy with high-dose ICS and another maintenance treatment, only if:[120][121]
- The patient has a blood eosinophil count of ≥150 cells per microlitre and fractional exhaled nitric oxide of ≥25 parts per billion, and has had at least 4 or more exacerbations in the previous 12 months.
- The patient is not eligible for mepolizumab, reslizumab, or benralizumab, or has asthma that has not responded adequately to these biological therapies.
Tezepelumab: for severe asthma when treatment with high-dose ICS plus another maintenance treatment has not controlled symptoms, only if:[122][123]
- The patient has had 3 or more exacerbations in the previous year, or
- The patient is taking maintenance oral corticosteroids.

Some biologics are suitable for self-administration at home after appropriate training.[124]

Bronchial thermoplasty

This bronchoscopic procedure aims to reduce bronchial smooth muscle mass, therefore reducing the capacity for bronchoconstriction. In the UK, only a few specialist centres offer this treatment, which has considerable resource implications.[55]

Any patients being considered for bronchial thermoplasty should be assessed to confirm the diagnosis of asthma, that uncontrolled asthma is the cause of their ongoing symptoms, and that they are adherent with current treatment.[55]
An asthma specialist with expertise in bronchial thermoplasty should assess patients prior to undergoing treatment, and treatment should take place in a specialist centre with the appropriate resources and training, including access to an intensive care unit.[55]
In people with severe asthma, bronchial thermoplasty improves asthma-specific quality of life, with a reduction in severe exacerbations and healthcare use in the post-treatment period.[125][126]
In the UK, patients undergoing bronchial thermoplasty should have their details entered onto the Severe Asthma Registry. Bronchial thermoplasty is an invasive procedure and is associated with a high rate of adverse respiratory events in the short term.[127]

NICE

Although the evidence base informing the BTS/SIGN and NICE guidelines was broadly the same, the methodologies employed by the two guideline development groups were substantially different, leading to discrepancies in the recommendations for management of asthma. NICE's approach is summarised in the flowchart below and the text that follows.

[Figure caption and citation for the preceding image starts]: Pharmacological treatment of chronic asthma in adults aged 17 and over; reproduced from NICE “Asthma: diagnosis, monitoring and chronic asthma management”National Institute for Health and Care Excellence. Algorithm F: Pharmacological treatment of chronic asthma in adults aged 17 and over. 2017 [internet publication]; used with permission [Citation ends]. com.bmj.content.model.Caption@6ed60d0f

Step 1 - initial therapy for control of asthma

NICE advocates the use of SABA reliever therapy alone, to be used as needed to relieve symptoms in symptomatic patients if the patient has infrequent, short-lived wheeze and normal lung function.[56]

In practice, only a very limited number of patients will need occasional use of SABAs alone with no preventer therapy. Most patients will also need regular preventer therapy with ICS.

NICE recommends to consider adding low-dose ICS to SABA if the patient has any of the following asthma-related features:[56]

Acute asthma attack (requiring oral corticosteroids) in the past 2 years
Using inhaled SABA three times a week or more
Symptomatic three times a week or more
Waking one night a week.

Step 2 - initial add-on therapy

If asthma is uncontrolled in adults on low-dose ICS as preventer therapy, NICE recommends an LTRA in addition to the ICS; review the response to treatment in 4 to 8 weeks.[56]

If the patient’s symptoms remain uncontrolled on a low dose of ICS and an LTRA as preventer therapy, NICE recommends to give a LABA in combination with the ICS and review LTRA treatment by:[56]

Discussing with the patient whether or not to continue LTRA treatment
Taking into account the degree of response to LTRA treatment.

NICE recommends that the patient can continue to use intermittent reliever therapy (usually an inhaled SABA) as needed throughout all the steps outlined above.[56]

If symptoms remain uncontrolled on a low dose of ICS and a LABA (with or without an LTRA), NICE recommends to consider changing the patient's ICS and LABA maintenance therapy to a low-dose LABA and ICS MART regimen.[56]

NICE states that the patient should continue with an LTRA alongside a MART regimen if they had a response to the LTRA at the previous step.[56]

NICE advises that the patient should not use intermittent short-acting reliever therapy (e.g., an inhaled SABA) alongside MART.[56]

Step 3 - additional controller therapies

If the patient's symptoms remain uncontrolled on a MART regimen with a low-dose LABA/ICS, with or without an LTRA, NICE recommends to consider increasing the ICS dose to medium (either continuing on a MART regimen or changing to a fixed dose of an ICS and a LABA, with a SABA as a reliever therapy).[56]

Step 4 - specialist therapies

If the patient's symptoms remain uncontrolled despite a medium maintenance ICS dose with a LABA (either as MART or a fixed-dose regimen), with or without an LTRA, NICE recommends to consider one of the following approaches:[56]

Increasing the ICS to a high maintenance dose (this should only be offered as part of a fixed-dose regimen, with a SABA used as a reliever therapy)
A trial of an additional drug (e.g., a LAMA or theophylline)
Seeking advice from a healthcare professional with expertise in asthma.

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