Asthma in adults

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

Your Organizational Guidance

ebpracticenet urges you to prioritize the following organizational guidance:

Astma bij volwassenen: diagnose en monitoring in de eerste lijnPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2020Asthme chez l’adulte : diagnostic et surveillance en soins de santé primairesPublished by: Groupe de Travail Développement de recommmandations de première ligneLast published: 2020

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

initial treatment step 1: asthma symptoms 1-2 days per week or less and no risk factors for exacerbations

1st line – low-dose inhaled corticosteroid plus formoterol as needed

Back

1st line –

low-dose inhaled corticosteroid plus formoterol as needed

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3] The Global Initiative for Asthma (GINA) track 1 (preferred) approach is to start on as-needed low-dose ICS plus formoterol (ICS-formoterol).[3]

In GINA track 1, the decision to start steps 1-2 (i.e., as-needed low-dose ICS-formoterol) instead of step 3 (i.e., low-dose ICS-formoterol as Maintenance and reliever therapy [MART]) is determined by the absence of risk factors for exacerbation. These include daily symptoms, current smoking, low lung function, a recent severe exacerbation or history of life-threatening exacerbation, impaired perception of severity, severe airway hyperresponsiveness, or current exposure to an allergic trigger.[3]

Patient response should be reviewed 2-3 months after starting treatment, or earlier if clinically indicated, and should include checks of both treatment adherence and inhaler technique. Decisions made about further treatment changes should then follow the stepwise approach to ongoing management.[3]

Primary options

budesonide/formoterol inhaled: consult specialist for guidance on as-needed dose

2nd line – low-dose inhaled corticosteroid plus short-acting beta agonist as needed

Back

2nd line –

low-dose inhaled corticosteroid plus short-acting beta agonist as needed

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3]

The Global Initiative for Asthma (GINA) track 2 (alternative) approach is to start on low-dose ICS whenever a short-acting beta agonist (SABA) is taken, as either separate or combined inhalers.[3] Consider the likelihood of adherence to maintenance therapy before prescribing a SABA as a reliever. When choosing between steps 1 and 2 (track 2), taking an ICS whenever a SABA is taken is preferred over daily ICS plus as-needed SABA (track 2, step 2) to ensure that patients with infrequent symptoms receive an ICS dose.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

beclomethasone dipropionate inhaled: 80-240 micrograms/day

budesonide inhaled: 180-600 micrograms/day

ciclesonide inhaled: 80-160 micrograms/day

fluticasone propionate inhaled: 88-264 micrograms/day

mometasone inhaled: 200 micrograms/day

-- AND --

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

initial treatment step 2: asthma symptoms less than 3-5 days per week and normal (or mildly reduced) lung function

1st line – low-dose inhaled corticosteroid plus formoterol as needed

Back

1st line –

low-dose inhaled corticosteroid plus formoterol as needed

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3]

The Global Initiative for Asthma (GINA) track 1 (preferred) approach is to start on as-needed low-dose ICS-formoterol.[3]

Primary options

budesonide/formoterol inhaled: consult specialist for guidance on as-needed dose

2nd line – low-dose inhaled corticosteroid

Back

2nd line –

low-dose inhaled corticosteroid

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3]

The Global Initiative for Asthma (GINA) track 2 (alternative) approach is to start on daily low-dose ICS.[3] Consider the likelihood of adherence to maintenance therapy before prescribing a short-acting beta agonist (SABA) as a reliever. When choosing between steps 1 and 2 (track 2), taking an ICS whenever a SABA is taken is preferred over daily ICS plus as-needed SABA (track 2, step 2) to ensure that patients with infrequent symptoms receive an ICS dose.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

beclomethasone dipropionate inhaled: 80-240 micrograms/day

budesonide inhaled: 180-600 micrograms/day

ciclesonide inhaled: 80-160 micrograms/day

fluticasone propionate inhaled: 88-264 micrograms/day

mometasone inhaled: 200 micrograms/day

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

Note that the track 2 options tend to increase treatment complexity, requiring more inhalers. Consider the likelihood of adherence to maintenance therapy before prescribing a short-acting beta agonist as a reliever.

For patients using metered-dose inhalers, spacer devices improve drug delivery.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

initial treatment step 3: asthma symptoms most days (e.g., 4-5 days per week or more), or waking due to asthma once a week or more, low lung function, and risk factors for exacerbations

1st line – low-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Back

1st line –

low-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3]

The Global Initiative for Asthma (GINA) track 1 (preferred) approach is to start on daily low-dose ICS low-dose ICS-formoterol as maintenance and reliever therapy (MART).[3] In this regimen, the patient takes a regular fixed dose of the MART inhaler, plus uses the same inhaler as an as-needed reliever (maximum recommended formoterol dose of 72 micrograms/day).

In GINA track 1, the decision to start step 3 (i.e., low-dose ICS-formoterol as MART) instead of steps 1-2 (i.e., as-needed low-dose ICS-formoterol) is determined by the presence of risk factors for exacerbation. These include daily symptoms, current smoking, low lung function, a recent severe exacerbation or history of life-threatening exacerbation, impaired perception of severity, severe airway hyperresponsiveness, or current exposure to an allergic trigger.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Other combination formulations may be available; consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

2nd line – low-dose inhaled corticosteroid plus long-acting beta agonist

Back

2nd line –

low-dose inhaled corticosteroid plus long-acting beta agonist

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3] A Global Initiative for Asthma (GINA) track 2 (alternative) approach is to start on daily low-dose ICS plus a long-acting beta agonist (ICS-long-acting beta agonist [LABA]).[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

A Cochrane review comparing regular ICS-formoterol with ICS-salmeterol found both combinations to have a similar safety profile in patients with chronic asthma.[170]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

mometasone/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone propionate/salmeterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone furoate/vilanterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

2nd line – medium-dose inhaled corticosteroid

Back

2nd line –

medium-dose inhaled corticosteroid

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

beclomethasone dipropionate inhaled: >240-480 micrograms/day

budesonide inhaled: >600-1200 micrograms/day

ciclesonide inhaled: >160-320 micrograms/day

fluticasone propionate inhaled: >264-440 micrograms/day

mometasone inhaled: 400 micrograms/day

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

initial treatment step 4: daily asthma symptoms, waking at night once a week or more, and low lung function

1st line – medium-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Back

1st line –

medium-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

In an urgent care setting or where a patient presents with an acute exacerbation, please refer to guidance for managing Acute asthma exacerbation in adults.

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3] The Global Initiative for Asthma (GINA) track 1 (preferred) approach is to start on daily medium-dose ICS-formoterol as maintenance and reliever therapy (MART), using the same inhaler for both maintenance and reliever doses.[3]

The maintenance dose is increased by increasing the number of inhalations (e.g., 2 inhalations twice daily), but the reliever is still low-dose ICS-formoterol (1 inhalation). The maximum recommended formoterol dose is 72 micrograms/day.

This is equivalent to step 4 in the GINA stepwise approach to ongoing management.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Other combination formulations may be available; consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Consider – short-course oral corticosteroid

Back

Consider –

short-course oral corticosteroid

Treatment recommended for SOME patients in selected patient group

Patients whose initial presentation is with severely uncontrolled asthma may need a short course of oral corticosteroids.[3]

Primary options

prednisone: 40-50 mg orally once daily for 5-7 days

2nd line – medium- or high-dose inhaled corticosteroid plus long-acting beta agonist

Back

2nd line –

medium- or high-dose inhaled corticosteroid plus long-acting beta agonist

In an urgent care setting or where a patient presents with an acute exacerbation, please refer to guidance for managing Acute asthma exacerbation in adults.

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3] A Global Initiative for Asthma (GINA) track 2 (alternative) approach is to start on daily medium- or high-dose ICS plus long-acting beta agonist (ICS-long-acting beta agonist [LABA]).[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

mometasone/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone propionate/salmeterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone furoate/vilanterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Consider – short-course oral corticosteroid

Back

Consider –

short-course oral corticosteroid

Treatment recommended for SOME patients in selected patient group

Patients whose initial presentation is with severely uncontrolled asthma may need a short course of oral corticosteroids.[3]

Primary options

prednisone: 40-50 mg orally once daily for 5-7 days

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

2nd line – high-dose inhaled corticosteroid

Back

2nd line –

high-dose inhaled corticosteroid

In an urgent care setting or where a patient presents with an acute exacerbation, please refer to guidance for managing Acute asthma exacerbation in adults.

Inhaled corticosteroid (ICS)-containing controller treatment should be initiated as soon as possible after the diagnosis of asthma is made.[3] A Global Initiative for Asthma (GINA) track 2 (alternative) approach recommended is to start on high-dose ICS therapy.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

beclomethasone dipropionate inhaled: >480 micrograms/day

budesonide inhaled: >1200 micrograms/day

ciclesonide inhaled: >320 micrograms/day

fluticasone propionate inhaled: >440 micrograms/day

mometasone inhaled: >400 micrograms/day

Consider – short-course oral corticosteroid

Back

Consider –

short-course oral corticosteroid

Treatment recommended for SOME patients in selected patient group

Patients whose initial presentation is with severely uncontrolled asthma may need a short course of oral corticosteroids.[3]

Primary options

prednisone: 40-50 mg orally once daily for 5-7 days

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

ONGOING

ongoing treatment step 1: patients using short-acting beta agonist (SABA) alone or with newly diagnosed asthma, with normal (or mildly reduced) lung function

1st line – low-dose inhaled corticosteroid plus formoterol as needed

Back

1st line –

low-dose inhaled corticosteroid plus formoterol as needed

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

A low-dose ICS with the long-acting beta agonist (LABA) formoterol (ICS-formoterol) used on an as-needed basis, for relief of symptoms and before exercise if needed, is the preferred controller treatment at step 1 (Global Initiative for Asthma [GINA] track 1).[3] This is based on evidence that low-dose ICS-formoterol as needed is superior to as-needed SABA use alone for prevention of asthma exacerbations.[145][146][147][148]

Although formoterol is a LABA, it has a fast onset of action suitable for reliever treatment.[147][149] 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.[150] [ ]

In GINA track 1, the decision to start steps 1-2 (i.e., as-needed low-dose ICS-formoterol) instead of step 3 (i.e., low-dose ICS-formoterol as maintenance and reliever therapy [MART]) is determined by the absence of risk factors for exacerbation. These include daily symptoms, current smoking, low lung function, a recent severe exacerbation or history of life-threatening exacerbation, impaired perception of severity, severe airway hyperresponsiveness, or current exposure to an allergic trigger.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

So far, all evidence for as-needed ICS-formoterol in mild asthma is with budesonide/formoterol.[3]

The recommended maximum daily usage of as-needed budesonide/formoterol corresponds to a total of 72 micrograms formoterol. However, in randomized controlled trials in mild asthma, such high usage was rarely seen, with average use around 3-4 doses per week.[3][161][253][254]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and associated with only mild local adverse effects.[143][144] See Complications.

Primary options

budesonide/formoterol inhaled: consult specialist for guidance on as-needed dose

2nd line – low-dose inhaled corticosteroid plus short-acting beta agonist as needed

Back

2nd line –

low-dose inhaled corticosteroid plus short-acting beta agonist as needed

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

A track 2 option recommended by Global Initiative for Asthma (GINA) for step 1 treatment is a low-dose ICS taken whenever a SABA is taken. This can include combination anti-inflammatory relievers.

The evidence for using an ICS and SABA at step 1 is indirect, being taken from small studies with separate or combination ICS and SABA inhalers in patients eligible for step 2 treatment.[151][152][153][154] Consider the likelihood of adherence to maintenance therapy before prescribing a SABA as a reliever. When choosing between steps 1 and 2 (track 2), taking an ICS whenever a SABA is taken is preferred over daily ICS plus as-needed SABA (track 2, step 2) to ensure that patients with infrequent symptoms receive an ICS dose.[3]

Even modest over-use of SABA increases the risk of severe exacerbations and asthma-related death, while and adding any ICS significantly reduces this risk.[3][147][156] High SABA use is associated with a significant increase in exacerbations and asthma-related healthcare utilization.[157][158] Patient populations most at risk for SABA over-reliance include older adults, smokers, and patients with low income.[158]

SABA use history should be obtained at every patient visit to identify usage patterns over time, which in turn, will guide treatment decisions; patient reassessment for possible over-use is suitable if ≥3 SABA inhalers are used in 1 year.[159][160]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and associated with only mild local adverse effects.[143][144] See Complications.

Examples of suitable drug regimens are given here; however, consult a local drug form

ulary for more options.

Primary options

beclomethasone dipropionate inhaled: 80-240 micrograms/day

budesonide inhaled: 180-600 micrograms/day

ciclesonide inhaled: 80-160 micrograms/day

fluticasone propionate inhaled: 88-264 micrograms/day

mometasone inhaled: 200 micrograms/day

-- AND --

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

ongoing treatment step 2: asthma not controlled on step 1 treatment

1st line – low-dose inhaled corticosteroid plus formoterol as needed

Back

1st line –

low-dose inhaled corticosteroid plus formoterol as needed

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

Inhaled low-dose ICS-formoterol on an as-needed basis for relief of symptoms and before exercise, if needed, is Global Initiative for Asthma (GINA's) preferred option at step 2 (track 1). This regimen decreases glucocorticoid exposure at the expense of some degree of symptom control, but is noninferior to low-dose ICS maintenance therapy in terms of prevention of exacerbation.[3][161]

So far, all evidence for as-needed ICS-formoterol in mild asthma is with budesonide/formoterol.[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and associated with only mild local adverse effects.[143][144] See Complications.

Primary options

budesonide/formoterol inhaled: consult specialist for guidance on as-needed dose

2nd line – low-dose inhaled corticosteroid

Back

2nd line –

low-dose inhaled corticosteroid

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

A regular, daily low-dose ICS plus as-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) is an alternative option at step 2 (track 2).[1][3]

There is a large body of evidence from randomized controlled trials and observational studies that severe exacerbations, hospitalizations, and mortality are reduced with daily low-dose ICS. However, adherence with maintenance ICS in patients with mild asthma is very low.[3] Consider the likelihood of adherence to maintenance therapy before prescribing a short-acting beta agonist (SABA) as a reliever. When choosing between steps 1 and 2 (track 2), taking an ICS whenever a SABA is taken is preferred over daily ICS plus as-needed SABA (track 2, step 2) to ensure that patients with infrequent symptoms receive an ICS dose.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and associated with only mild local adverse effects.[143][144] See Complications.

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

beclomethasone dipropionate inhaled: 80-240 micrograms/day

budesonide inhaled: 180-600 micrograms/day

ciclesonide inhaled: 80-160 micrograms/day

fluticasone propionate inhaled: 88-264 micrograms/day

mometasone inhaled: 200 micrograms/day

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

The use of inhaled corticosteroid (ICS)-short-acting beta agonist (SABA) for as-needed therapy is based on studies with separate or combination ICS and SABA inhalers that showed no difference in exacerbation rates compared with daily ICS.[151][152][153][154]

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

2nd line – low-dose inhaled corticosteroid plus short-acting beta agonist as needed

Back

2nd line –

low-dose inhaled corticosteroid plus short-acting beta agonist as needed

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

Low-dose ICS taken whenever a short-acting beta agonist (SABA) is taken is another option at step 2 (track 2).[3][111]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC); Cloutier MM, Baptist AP, Blake KV, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70. The ICS and SABA can be given in single or combination inhalers. This is based on studies with separate or combination ICS and SABA inhalers, showing no difference in exacerbations compared with daily ICS.[151][152][153][154]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and associated with only mild local adverse effects.[143][144] See Complications.

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

beclomethasone dipropionate inhaled: 80-240 micrograms/day

budesonide inhaled: 180-600 micrograms/day

ciclesonide inhaled: 80-160 micrograms/day

fluticasone propionate inhaled: 88-264 micrograms/day

mometasone inhaled: 200 micrograms/day

-- AND --

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

ongoing treatment step 3: asthma not controlled on steps 1-2 treatment (track 1) or step 2 treatment (track 2), with risk factors for exacerbations

1st line – low-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Back

1st line –

low-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

Global Initiative for Asthma (GINA’s) preferred option at step 3 is low-dose ICS-formoterol as maintenance therapy and low-dose ICS-formoterol as reliever therapy (track 1).[3] In the maintenance and reliever therapy (MART) regimen, the patient takes a regular fixed dose, plus uses the same inhaler as an as-needed reliever.[3]

ICS-formoterol as MART is GINA's preferred option at step 3 because this treatment reduces exacerbations and provides similar levels of asthma control at relatively low doses of ICS compared with either regular, fixed-dose ICS-long-acting beta agonist plus short-acting beta agonist (SABA) as needed or a higher dose of ICS plus SABA as needed.[163][164][165][166][167][168][169]

MART regimens are the recommended option at step 3 in the 2020 US guidelines.[111]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC); Cloutier MM, Baptist AP, Blake KV, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.

In patients with uncontrolled asthma receiving a GINA track 2 treatment (i.e., maintenance ICS-long-acting beta agonist [LABA] plus reliever SABA), a meta-analysis has shown that switching to GINA track 1 (i.e., MART) is associated with a longer time to first severe asthma exacerbation compared with stepping up or continuation of track 2 options at steps 3-5.[172]

For patients taking ICS-formoterol as MART, the maximum recommended dose of formoterol in a single day is 72 micrograms metered dose (equivalent to 54 micrograms delivered dose) for budesonide/formoterol.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and associated with only mild local adverse effects.[143][144] See Complications.

Other combination formulations may be available; consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite low-dose inhaled corticosteroid (ICS)-formoterol.[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Serious neuropsychiatric events have been reported in patients taking LTRAs, particularly montelukast.[128] These include new-onset nightmares, headache, behavioral problems (e.g., agitation, hyperactivity, irritability, nervousness, aggression), and suicidal ideation.

Healthcare professionals are advised to consider the benefits and risks of montelukast before prescribing, to have an open discussion about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[3]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

2nd line – low-dose inhaled corticosteroid plus long-acting beta agonist

Back

2nd line –

low-dose inhaled corticosteroid plus long-acting beta agonist

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

The main alternative to ICS-formoterol as maintenance and reliever therapy in Global Initiative for Asthma (GINA) guidance is low-dose ICS plus long-acting beta agonist (LABA) as regular treatment with as-needed short-acting beta agonist (SABA) or as-needed ICS-SABA as a reliever (track 2). Adding a LABA to ICS in a combination inhaler leads to improved symptoms and lung function, and a reduced risk of exacerbations.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

In traditional ICS plus LABA treatment, the drugs are prescribed as a fixed-dose combination inhaler.[3]

A Cochrane review comparing regular ICS-formoterol with ICS-salmeterol found both combinations to have a similar safety profile in patients with chronic asthma.[170]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and associated with only mild local adverse effects.[143][144] See Complications.

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

mometasone/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone propionate/salmeterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone furoate/vilanterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

The evidence for including as-needed inhaled corticosteroid (ICS)-short-acting beta agonist (SABA) comes from a multinational, phase 3, double-blind, randomized trial evaluating the efficacy and safety of albuterol/budesonide, compared to albuterol alone, used as rescue drug in patients with uncontrolled moderate-to-severe asthma receiving ICS-containing maintenance therapies that remained unchanged throughout the study (step 3 therapy).[171] This showed that the risk of severe asthma exacerbation was significantly lower with as-needed use of the fixed-dose albuterol/budesonide combination than with as-needed albuterol alone.[171] Note that this track 2 option can be considerably more complex than the track 1 option, typically requiring multiple inhalers.

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite low-dose inhaled corticosteroid (ICS)-long-acting beta agonist (LABA).[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

2nd line – medium-dose inhaled corticosteroid

Back

2nd line –

medium-dose inhaled corticosteroid

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

Increasing the ICS to a medium dose is another second-line option (track 2), but this is less efficacious than adding a long-acting beta agonist to low-dose ICS.[3]

For patients using metered-dose inhalers, spacer devices improve delivery of the drug and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and associated with only mild local adverse effects.[143][144] See Complications.

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

beclomethasone dipropionate inhaled: >240-480 micrograms/day

budesonide inhaled: >600-1200 micrograms/day

ciclesonide inhaled: >160-320 micrograms/day

fluticasone propionate inhaled: >264-440 micrograms/day

mometasone inhaled: 400 micrograms/day

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

Much of the evidence for including as-needed inhaled corticosteroid (ICS)-short-acting beta agonist (SABA) comes from a multinational, phase 3, double-blind, randomized trial evaluating the efficacy and safety of albuterol/budesonide, compared to albuterol alone, used as rescue drug in patients with uncontrolled moderate-to-severe asthma receiving ICS-containing maintenance therapies that remained unchanged throughout the study (step 3 therapy).[171] This showed that the risk of severe asthma exacerbation was significantly lower with as-needed use of the fixed-dose albuterol/budesonide combination than with as-needed albuterol alone.[171] Note that this track 2 option can be considerably more complex than the track 1 option, typically requiring multiple inhalers.

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite medium-dose inhaled corticosteroid (ICS).[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

ongoing treatment step 4: asthma not controlled on step 3 treatment

1st line – medium-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Back

1st line –

medium-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

Medium-dose ICS-formoterol as maintenance therapy and low-dose ICS-formoterol as reliever therapy is Global Initiative for Asthma (GINA’s) preferred option at step 4 (track 1).[3]

For adults and adolescents with asthma, combination ICS-formoterol as maintenance and reliever therapy (MART) is better at reducing exacerbations than the same dose of maintenance ICS-long-acting beta agonist or high doses of ICS.[167] For MART, the same inhaler should be used for both maintenance and reliever doses. The maintenance dose can be increased by increasing the number of inhalations, but the reliever is still low-dose ICS-formoterol.[3]

MART regimens are the recommended option at step 4 in the 2020 US guidelines.[111]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC); Cloutier MM, Baptist AP, Blake KV, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Long-term therapy with a low- to medium-dose ICS is safe and mainly associated with mild local adverse effects (e.g., oral or oropharyngeal candidiasis and dysphonia/hoarseness); treatment is not associated with increased risks of upper or lower respiratory tract infection (including influenza) or of fractures and changes in bone mineral density.[143][144] Patients exposed to high-dose ICS are more susceptible to osteoporosis, cataracts, glaucoma, and adrenal suppression.[175] See Complications. High-dose ICS are only recommended for short-term use (e.g., 3-6 months).[3]

Other combination formulations may be available; consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite medium-dose inhaled corticosteroid (ICS)-formoterol.[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

Consider – long-acting muscarinic antagonist

Back

Consider –

long-acting muscarinic antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on long-acting muscarinic antagonists (LAMAs), such as tiotropium, glycopyrrolate, or umeclidinium, may be considered if asthma is persistently uncontrolled despite medium-dose inhaled corticosteroid (ICS)-long-acting beta agonist (LABA).[3]

Compared with medium-dose ICS alone, medium-dose ICS with either a LAMA or LABA both improve treatment response and reduce moderate-to-severe exacerbations.[111]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC); Cloutier MM, Baptist AP, Blake KV, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.[144][176] Compared with medium-dose ICS-LABA, switching to medium- or high-dose ICS-LABA-LAMA modestly improves lung function and time to severe exacerbations requiring oral corticosteroids, but not quality of life or mortality, with benefit seen primarily in patients with a history of exacerbations in the previous year.[177][178][179][180][181][182]

LAMAs can be given as a separate inhaler or in a combination ("triple") inhaler that contains ICS, LABA, and LAMA. Inhaler availability varies by country. Combination inhalers are not detailed here - consult your local drug formulary for details on available inhalers and doses.

Primary options

tiotropium inhaled: 2.5 micrograms inhaled once daily

umeclidinium inhaled: 62.5 micrograms inhaled once daily

2nd line – medium-dose inhaled corticosteroid plus long-acting beta agonist

Back

2nd line –

medium-dose inhaled corticosteroid plus long-acting beta agonist

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

For patients taking daily low-dose ICS plus long-acting beta agonist (LABA) with as-needed short-acting beta agonist (SABA) or as-needed ICS-SABA at step 3 (track 2), then a step-up option for track 2 is an increase to daily medium-dose ICS plus LABA with as-needed SABA or as-needed ICS-SABA at step 4.[3][174]

In ICS plus LABA treatment, the drugs are prescribed as a fixed-dose combination inhaler where possible.[3]

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

A Cochrane review comparing regular ICS-formoterol with ICS-salmeterol found both combinations to have a similar safety profile in patients with chronic asthma.[170]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

High-dose ICS are only recommended for short-term use (e.g., 3-6 months).[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

mometasone/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone propionate/salmeterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone furoate/vilanterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid [ICS]-short-acting beta agonist[SABA]) should also be prescribed.[3]

Global Initiative for Asthma (GINA) does not recommend inhaled corticosteroid (ICS)-formoterol as the reliever for patients taking combination ICS-long-acting beta agonist (LABA) drugs with a different LABA. For these patients, their as-needed reliever inhaler should be a short-acting beta agonist (SABA) or ICS-SABA.[3]

The evidence for including as-needed ICS-SABA comes from a multinational, phase 3, double-blind, randomized trial evaluating the efficacy and safety of albuterol/budesonide, compared to albuterol alone, in a sub-population of patients taking maintenance medium-dose ICS-LABA or high-dose ICS (step 4 therapy).[171] This showed that there was a significant decrease in risk of severe exacerbations with as-needed high-dose ICS-SABA compared with as-needed SABA.[171] Note that this track 2 option can be considerably more complex than the track 1 option, typically requiring multiple inhalers.

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite medium-dose inhaled corticosteroid (ICS)-long-acting beta agonist (LABA).[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

Consider – long-acting muscarinic antagonist

Back

Consider –

long-acting muscarinic antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Primary options

tiotropium inhaled: 2.5 micrograms inhaled once daily

umeclidinium inhaled: 62.5 micrograms inhaled once daily

2nd line – high-dose inhaled corticosteroid plus long-acting beta agonist

Back

2nd line –

high-dose inhaled corticosteroid plus long-acting beta agonist

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

Increasing to high-dose inhaled corticosteroid plus long-acting beta agonist (ICS-LABA) is an option at step 4 (track 2), but clinicians and patients should consider the potential increase in adverse effects relating to ICS.[3] The increased dose of ICS rarely provides substantial extra benefit compared with a medium dose, and the risk of adverse effects is increased. Systemic adverse effects relating to long-term, high-dose ICS include easy bruising, an increased risk of osteoporosis, cataracts, glaucoma, and adrenal suppression. Local adverse effects of ICS include oropharyngeal candidiasis (oral thrush) and dysphonia.[3]

A suitable ICS-LABA combination formulation inhaler should be used whenever possible. However, if the high dose of ICS is not achievable with the combination formulation (in order to not go above the maximum LABA dose), a separate ICS inhaler can be added to the combination formulation to achieve the necessary ICS dose.

For patients using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

A Cochrane review comparing regular ICS-formoterol with ICS-salmeterol found both combinations to have a similar safety profile in patients with chronic asthma.[170]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Patients exposed to high-dose ICS are more susceptible to osteoporosis, cataracts, glaucoma, and adrenal suppression.[175] See Complications. High-dose ICS are only recommended for short-term use (e.g., 3-6 months).[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

mometasone/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone propionate/salmeterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone furoate/vilanterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

The evidence for including as-needed inhaled corticosteroid (ICS)-short-acting beta agonist (SABA) comes from a multinational, phase 3, double-blind, randomized trial evaluating the efficacy and safety of albuterol/budesonide, compared to albuterol alone, in a sub-population of patients taking maintenance medium-dose ICS-long-acting beta agonist (LABA) or high-dose ICS (step 4 therapy).[171] This showed that there was a significantly decreased risk of severe exacerbations with high-dose as-needed ICS-SABA compared with as-needed SABA.[171]

Note that this track 2 option can be considerably more complex than the track 1 option, typically requiring multiple inhalers.[171]

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite high-dose inhaled corticosteroid (ICS)-long-acting beta agonist (LABA).[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

Consider – long-acting muscarinic antagonist

Back

Consider –

long-acting muscarinic antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on long-acting muscarinic antagonists (LAMAs), such as tiotropium, glycopyrrolate, or umeclidinium, may be considered if asthma is persistently uncontrolled despite high-dose inhaled corticosteroid (ICS)-long-acting beta agonist (LABA).[3]

Primary options

tiotropium inhaled: 2.5 micrograms inhaled once daily

umeclidinium inhaled: 62.5 micrograms inhaled once daily

2nd line – high-dose inhaled corticosteroid

Back

2nd line –

high-dose inhaled corticosteroid

All patients should receive an inhaled corticosteroid (ICS) as part of their treatment.

Increasing the ICS to a high dose is another second-line option (track 2), but this is less efficacious than adding a long-acting beta agonist to medium-dose ICS.[3]

The increased dose of ICS rarely provides substantial extra benefit compared with a medium dose, and the risk of adverse effects is increased. Systemic adverse effects relating to long-term, high-dose ICS include easy bruising, an increased risk of osteoporosis, cataracts, glaucoma, and adrenal suppression.[3]

For patients using metered-dose inhalers, spacer devices improve delivery of the drug and, for ICS, reduce the risk of local adverse effects (e.g., dysphonia and oral candidiasis).[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

beclomethasone dipropionate inhaled: >480 micrograms/day

budesonide inhaled: >1200 micrograms/day

ciclesonide inhaled: >320 micrograms/day

fluticasone propionate inhaled: >440 micrograms/day

mometasone inhaled: >400 micrograms/day

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

The evidence for including as-needed inhaled corticosteroid (ICS)-short-acting beta agonist (SABA) comes from a multinational, phase 3, double-blind, randomized trial evaluating the efficacy and safety of albuterol/budesonide, compared to albuterol alone, in a sub-population of patients taking maintenance medium-dose ICS-long-acting beta agonist (LABA) or high-dose ICS (step 4 therapy).[171] This showed that there was no significant increase in time to first severe exacerbation with as-needed ICS-SABA compared with as-needed SABA.[171] Note that this track 2 option can be considerably more complex than the track 1 option, typically requiring multiple inhalers.

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite high-dose inhaled corticosteroid (ICS).[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

Consider – long-acting muscarinic antagonist

Back

Consider –

long-acting muscarinic antagonist

Treatment recommended for SOME patients in selected patient group

Change only one drug at a time in chronic management.

Compared with medium-dose ICS alone, medium-dose ICS with either a LAMA or long-acting beta agonist (LABA) both improve treatment response and reduce moderate-to-severe exacerbations.[111]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC); Cloutier MM, Baptist AP, Blake KV, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.[144][176] Compared with medium-dose ICS-LABA, switching to medium- or high-dose ICS-LABA-LAMA modestly improves lung function and time to severe exacerbations requiring oral corticosteroids, but not quality of life or mortality, with benefit seen primarily in patients with a history of exacerbations in the previous year.[177][178][179][180][181][182]

Primary options

tiotropium inhaled: 2.5 micrograms inhaled once daily

umeclidinium inhaled: 62.5 micrograms inhaled once daily

ongoing treatment step 5: asthma not controlled on step 4 treatment and patient reviewed by specialist

1st line – consider high-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Back

1st line –

consider high-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

If a patient with asthma has persistent symptoms or exacerbations despite taking step 4 treatment with good adherence and correct inhaler technique, and after trialing or considering other step 4 controller options, then they should be referred to a specialist in severe asthma.[3] Global Initiative for Asthma (GINA) has released a separate pocket guide on difficult-to-treat and severe asthma. GINA: diagnosis and management of difficult-to-treat and severe asthma Opens in new window

Following specialist assessment and optimization of existing treatment, high-dose inhaled corticosteroid (ICS)-formoterol as maintenance therapy and low-dose ICS-formoterol as reliever therapy may be considered on a trial basis for 3-6 months at step 5 (GINA track 1).[3]

For the maintenance and reliever therapy (MART) regimen, the same inhaler should be used for both maintenance and reliever doses. The maintenance dose can be increased by increasing the number of inhalations, but the reliever is still low-dose ICS-formoterol.[3]

Other combination formulations may be available; consult a local drug formulary for more options.

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

High-dose ICS therapy increases the potential for osteoporosis, cataracts, glaucoma, and adrenal suppression.[175] Patients need to be counseled on, and monitored for, these adverse effects.[175][184][185] When using metered-dose inhalers, spacer devices improve drug delivery and, for ICS, reduce the risk of local adverse effects. Consider therapy to prevent osteoporosis.[3][175] See Complications.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite high-dose inhaled corticosteroid (ICS)-formoterol.[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Serious neuropsychiatric events have been reported in patients taking LTRAs, particularly montelukast.[128] These include new-onset nightmares, behavioral problems (e.g., agitation, hyperactivity, irritability, nervousness, aggression, and headache), and suicidal ideation.

Healthcare professionals are advised to consider the benefits and risks of montelukast before prescribing, to have an open discussion with patients about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[3]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

Consider – long-acting muscarinic antagonist

Back

Consider –

long-acting muscarinic antagonist

Treatment recommended for SOME patients in selected patient group

Compared with medium-dose ICS alone, medium-dose ICS with either a LAMA or long-acting beta agonist (LABA) both improve treatment response and reduce moderate-to-severe exacerbations.[144]

Compared with medium-dose ICS-LABA, switching to medium- or high-dose ICS-LABA-LAMA modestly improves lung function and time to severe exacerbations requiring oral corticosteroids, but not quality of life or mortality, with benefit primarily seen in patients with a history of exacerbations in the previous year.[176][177][178][180][181]

LAMAs can be given as a separate inhaler or in a combination ("triple") inhaler that contains ICS, LABA, and LAMA. Inhaler availability varies by country.[3] Combination inhalers are not detailed here - consult your local drug formulary for details on available inhalers and doses.

Primary options

tiotropium inhaled: 2.5 micrograms inhaled once daily

umeclidinium inhaled: 62.5 micrograms inhaled once daily

Consider – biologic agent

Back

Consider –

biologic agent

Treatment recommended for SOME patients in selected patient group

Global Initiative for Asthma (GINA) recommends biologic (type 2-targeted) therapy for severe asthma only after existing treatment has been optimized, regardless of regulatory approvals, advising that an initial trial should last at least 4 months (tracks 1 and 2).[3] In general, biologics reduce the need for oral corticosteroids and reduce the exacerbation rate in patients with severe uncontrolled asthma.[185][191][192][193][194]

Biologic therapy is typically well tolerated, safe, and can help reduce steroid-associated adverse effects; however, long-term safety data are lacking for some agents and there is usually a trade-off for increased all-cause adverse effects compared with standard therapy.[195][196][197] Minor injection site reactions are common, but hypersensitivity reactions may occur.

Several monoclonal antibodies are available. Although direct comparisons are complicated by a lack of consistent patient groups and outcome measures among trials, minimal differences are expected in clinical efficacy and safety when biologics are used according to their indications; where comparisons have been attempted, no single agent has shown superiority over another.[191][198][199][200][201][202][203]

Omalizumab (anti-IgE) is approved as add-on maintenance therapy in adults and adolescents (ages ≥12 years) with severe allergic asthma, elevated IgE levels, and positive testing for a perennial aeroallergen.[3][196][204][205][206][207] Factors associated with response include a history of childhood-onset asthma and a clinical history suggesting allergen-driven symptoms.[3] Baseline IgE and blood eosinophil levels are often used to select patients who may benefit from treatment.[3][208][209][210] The presence of multiple allergic comorbidities or atopic dermatitis may be more reliable predictors of outcome.[211]

Mepolizumab (anti-IL-5) is approved as add-on maintenance therapy in adults and adolescents (ages ≥12 years) with severe asthma and an eosinophilic phenotype.[3][213][214] Mepolizumab may also be given as a fixed-dose regimen, regardless of body weight or body mass index.[216] Factors associated with response include high sputum eosinophil count at baseline, high number of severe exacerbations in the last year, adult-onset asthma, nasal polyps, maintenance oral corticosteroid requirement, and low lung function (FEV₁ <65% predicted).[3][217]

Reslizumab (anti-IL-5) is approved as add-on maintenance therapy only for adults (ages ≥18 years) with severe asthma and an eosinophilic phenotype.[3][212][219] Factors associated with response include high sputum eosinophil count at baseline, high number of severe exacerbations in the last year, adult-onset asthma, nasal polyps, maintenance oral corticosteroid requirement, and low lung function (FEV₁ <65% predicted).[3]

Benralizumab (anti-IL-5R-alpha) is approved as add-on maintenance therapy in adults and adolescents (ages ≥12 years) with severe asthma and an eosinophilic phenotype.[3][196][212][220][221][222][223] Factors associated with response include high sputum eosinophil count at baseline, high number of severe exacerbations in the last year, adult-onset asthma, nasal polyps, maintenance oral corticosteroid requirement, and low lung function (FEV₁ <65% predicted).[3]

Dupilumab (anti-IL-4R-alpha) is approved as add-on maintenance therapy in adults and adolescents (ages ≥12 years) with moderate-to-severe asthma, an eosinophilic phenotype, or oral corticosteroids-dependent asthma.[3][196][224][225][226][227] Factors associated with response include higher blood eosinophils and higher FeNO levels.[3]

Tezepelumab (anti-thymic stromal lymphopoietin) is approved as add-on maintenance therapy in adults and adolescents (ages ≥12 years) with severe asthma.[3][230][231][232][233][234][235] Clinical utility has been shown in severe uncontrolled asthma regardless of phenotype, offering a safe and effective option for patients without eosinophilic or allergic asthma.[236][237] Factors associated with response include higher blood eosinophils and higher FeNO levels.[3]

Some biologics are suitable for self-administration at home after appropriate training.[240]

Asthma therapy may be stepped down in patients with severe asthma who show good response to biologic (type 2-targeted) therapy.[3] This should prioritize reducing and stopping maintenance oral corticosteroids.[241][242] Evidence also suggests that the maintenance inhaled corticosteroid (ICS) dose can be reduced slowly while still maintaining asthma control in patients receiving benralizumab, indicating that switching to a low-dose maintenance and reliever therapy (MART) may be possible.[242]

Stopping biologic therapy is associated with a high risk of relapse.[243][244][245][246][247] A trial withdrawal should not generally be considered until at least 12 months of treatment, only if: asthma remains well controlled on medium-dose inhaled corticosteroid (ICS) therapy; and exposure to a previously well-documented allergic trigger can be avoided.[3]

Careful monitoring is needed when a trial withdrawal is attempted. One double-blind randomized controlled trial reported that patients who stopped mepolizumab experienced more exacerbations and reduced asthma control over the subsequent 12-month period than patients who continued treatment.[245]

Primary options

omalizumab: dose depends on baseline serum IgE level and patient weight; consult specialist for guidance on dose

mepolizumab: 100 mg subcutaneously every 4 weeks

reslizumab: 3 mg/kg intravenous infusion every 4 weeks

benralizumab: 30 mg subcutaneously every 4 weeks for the first 3 doses, followed by 30 mg every 8 weeks thereafter

dupilumab: 400 mg subcutaneously initially, followed by 200 mg every other week; or 600 mg subcutaneously initially, followed by 300 mg every other week

tezepelumab: 210 mg subcutaneously every 4 weeks

Consider – bronchial thermoplasty

Back

Consider –

bronchial thermoplasty

Treatment recommended for SOME patients in selected patient group

This bronchoscopic procedure is a potential add-on option at step 5 (tracks 1 and 2) for patients ages ≥18 years when asthma remains uncontrolled despite optimized pharmacologic therapy.[3]

Bronchial thermoplasty involves the application of controlled thermal energy to the airway wall to decrease smooth muscle.

In people with severe asthma, this procedure improves asthma-specific quality of life, with a reduction in severe exacerbations and healthcare use in the posttreatment period.[249][250][251]

Approval was based on strict criteria including a history of poorly controlled asthma despite high-dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA) treatment, FEV₁ >60% of predicted, no history of life-threatening exacerbations, and fewer than three exacerbations in the past year. Bronchial thermoplasty performed outside these criteria is considered experimental.

A follow-up of 45% of patients from three randomized controlled trials found that the efficacy of bronchial thermoplasty, in terms of proportions of severe exacerbations, quality of life, and spirometry, was sustained for 10 years or more, with a small proportion of patients developing mild or moderate bronchiectasis.[252] The 2020 US guidelines on asthma conditionally recommend against bronchial thermoplasty, except where patients place a low value on harms and a high value on potential benefits.[111]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC); Cloutier MM, Baptist AP, Blake KV, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.

Consider – azithromycin

Back

Consider –

azithromycin

Treatment recommended for SOME patients in selected patient group

An option for patients ages 18 years and older with severe asthma.[3][186] Secondary analysis of data from the AMAZES (Asthma and Macrolides: the Azithromycin Efficacy and Safety) clinical trial supports this approach in a significant proportion of people with persistent symptomatic asthma.[187][188]

One Cochrane review found macrolides superior to placebo in reducing severe exacerbations and improving symptoms of chronic asthma, but concluded that more robust clinical trial evidence was needed for definite conclusions to be drawn.[189]

Concerns remain over the frequency of potential adverse effects, including increased risks of cardiovascular and noncardiovascular deaths.[187][189][190]

Before starting azithromycin, assess the following: sputum for atypical mycobacteria, the risk of antimicrobial resistance, EKG for a long QTc interval (re-check a month after starting treatment), and audiogram for hearing function (repeat if change reported).[3]

Primary options

azithromycin: 500 mg orally three times weekly

Consider – low-dose oral corticosteroid

Back

Consider –

low-dose oral corticosteroid

Treatment recommended for SOME patients in selected patient group

Reserved for patients with poor symptom control and/or frequent exacerbations (track 1 or track 2) despite: correct inhaler technique and; good adherence with other step 5 treatments; having excluded contributory factors; and having tried other add-on treatments, including biologic agents (where appropriate).[3]

Increased markers of type 2 inflammation (i.e., high blood eosinophils and fractional exhaled nitric oxide values) predict response to oral corticosteroids.[248]

Oral corticosteroids increase the potential for osteoporosis, cataracts, glaucoma, and adrenal suppression.[175] Patients need to be counseled on, and monitored for, these adverse effects.[175][184][185] Consider therapy to prevent osteoporosis.[3][175] See Complications.

Primary options

prednisone: ≤7.5 mg orally once daily

2nd line – consider high-dose inhaled corticosteroid plus long-acting beta agonist

Back

2nd line –

consider high-dose inhaled corticosteroid plus long-acting beta agonist

Following specialist assessment and optimization of existing treatment, high-dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA) may be considered on a trial basis for 3-6 months at step 5 (GINA track 2). However, the increased dose of ICS rarely provides substantial extra benefit compared with a medium dose.

The patient must also take a short-acting beta agonist (SABA) as needed.[3]

An ICS-LABA combination inhaler should be used whenever possible. However, if the high dose of ICS is not achievable with the combination formulation, a separate ICS inhaler can be added to the combination formulation to avoid exceeding the maximum LABA dose and achieve the necessary ICS dose.

A Cochrane review comparing regular ICS-formoterol with ICS-salmeterol found both combinations to have a similar safety profile in patients with chronic asthma.[170]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Examples of suitable drug regimens are given here; however, consult a local drug formulary for more options.

Primary options

budesonide/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

mometasone/formoterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone propionate/salmeterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

fluticasone furoate/vilanterol inhaled: dose depends on brand and formulation; consult product literature for guidance on dose

Plus – short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Back

Plus –

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Treatment recommended for ALL patients in selected patient group

As-needed short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) should also be prescribed.[3]

The evidence for including as-needed inhaled corticosteroid (ICS)-short-acting beta agonist (SABA) comes from a multinational, phase 3, double-blind, randomized trial evaluating the efficacy and safety of albuterol/budesonide, compared to albuterol alone, in a sub-population of patients taking maintenance medium-dose ICS-long-acting beta agonist (LABA) or high-dose ICS (step 4 therapy).[171] This showed that there was no significant increase in time to first severe exacerbation with as-needed ICS-SABA compared with as-needed SABA.[171] Note that this track 2 option can be considerably more complex than the track 1 option, typically requiring multiple inhalers.

For patients using metered-dose inhalers, spacer devices improve delivery of the drug.[3]

Potency is not equivalent between ICS drugs labeled "low dose," "medium dose," and "high dose"; a switch between brands may, therefore, represent a clinically significant dose change.[3]

Primary options

albuterol inhaled: 90-180 micrograms every 4-6 hours when required

levalbuterol inhaled: 45-90 micrograms every 4-6 hours when required

albuterol/budesonide inhaled: 180 micrograms (albuterol)/160 micrograms (budesonide) when required, maximum 12 inhalations/day

Consider – leukotriene receptor antagonist

Back

Consider –

leukotriene receptor antagonist

Treatment recommended for SOME patients in selected patient group

Add-on leukotriene receptor antagonist (LTRA) may be considered if asthma is persistently uncontrolled despite medium- or high-dose inhaled corticosteroid (ICS)-long-acting beta agonist (LABA).[3] LTRAs are less effective than ICS, but may be considered in combination with ICS-based therapy.[3][173]

Primary options

montelukast: 10 mg orally once daily

zafirlukast: 20 mg orally twice daily

Consider – long-acting muscarinic antagonist

Back

Consider –

long-acting muscarinic antagonist

Treatment recommended for SOME patients in selected patient group

Add-on long-acting muscarinic antagonists (LAMAs), such as tiotropium, glycopyrrolate, or umeclidinium, may be considered if asthma is persistently uncontrolled despite medium- or high-dose inhaled corticosteroid (ICS)-long-acting beta agonist (LABA).

Compared with medium-dose ICS alone, medium-dose ICS with either a LAMA or LABA both improve treatment response and reduce moderate-to-severe exacerbations.[144]

LAMAs can be given as a separate inhaler, or in a combination ("triple") inhaler that contains ICS, LABA, and LAMA. Inhaler availability varies by country.[3] Combination inhalers are not detailed here - consult your local drug formulary for details on available inhalers and doses.

Primary options

tiotropium inhaled: 2.5 micrograms inhaled once daily

umeclidinium inhaled: 62.5 micrograms inhaled once daily

Consider – biologic agent

Back

Consider –

biologic agent

Treatment recommended for SOME patients in selected patient group

Global Initiative for Asthma (GINA) recommends biologic (type 2-targeted) therapy for severe asthma only after existing treatment has been optimized, regardless of regulatory approvals, advising that an initial trial should last at least 4 months (tracks 1 and 2).[3] In general, biologics reduce the need for oral corticosteroid treatment and reduce the exacerbation rate in patients with severe uncontrolled asthma.[185][191][192][193][194]

Biologic therapy is typically well tolerated, safe, and can help reduce steroid-associated adverse effects; however, long-term safety data are lacking for some agents and there is usually a trade off for increased all-cause adverse effects compared with standard therapy.[195][196][197] Minor injection site reactions are common, but hypersensitivity reactions may occur.

Mepolizumab (anti-IL-5) is approved as add-on maintenance treatment in adults and adolescents (ages ≥12 years) with severe asthma and an eosinophilic phenotype.[3][213][214][215] Mepolizumab may also be given as a fixed-dose regimen, regardless of body weight or body mass index.[216] Factors associated with response include high sputum eosinophil count at baseline, high number of severe exacerbations in the last year, adult-onset asthma, nasal polyps, maintenance oral corticosteroid requirement, and low lung function (FEV₁ <65% predicted).[3][217]

Some biologics are suitable for self-administration at home after appropriate training.[240]

Stopping biologic therapy is associated with a high risk of relapse.[243][244][245][246][247] A trial withdrawal should not generally be considered until at least 12 months of treatment, only if: asthma remains well controlled on medium-dose ICS therapy; and exposure to a previously well-documented allergic trigger can be avoided.[3]

Careful monitoring is needed when a trial withdrawal is attempted. One double-blind randomized controlled trial reported that patients who stopped mepolizumab experienced more exacerbations and reduced asthma control over the subsequent 12 month period than patients who continued treatment.[245]

Primary options

omalizumab: dose depends on baseline serum IgE level and patient weight; consult specialist for guidance on dose

mepolizumab: 100 mg subcutaneously every 4 weeks

reslizumab: 3 mg/kg intravenous infusion every 4 weeks

benralizumab: 30 mg subcutaneously every 4 weeks for the first 3 doses, followed by 30 mg every 8 weeks thereafter

dupilumab: 400 mg subcutaneously initially, followed by 200 mg every other week; or 600 mg subcutaneously initially, followed by 300 mg every other week

tezepelumab: 210 mg subcutaneously every 4 weeks

Consider – bronchial thermoplasty

Back

Consider –

bronchial thermoplasty

Treatment recommended for SOME patients in selected patient group

This bronchoscopic procedure is a potential add-on option at step 5 (tracks 1 and 2) for patients ages ≥18 years when asthma remains uncontrolled despite optimized pharmacologic therapy.[3]

Bronchial thermoplasty involves the application of controlled thermal energy to the airway wall to decrease smooth muscle. In people with severe asthma, this procedure improves asthma-specific quality of life, with a reduction in severe exacerbations and healthcare use in the posttreatment period.[249][250][251]

Consider – azithromycin

Back

Consider –

azithromycin

Treatment recommended for SOME patients in selected patient group

An option for patients ages 18 years and older with severe asthma.[3][186]

Secondary analysis of data from the AMAZES (Asthma and Macrolides: the Azithromycin Efficacy and Safety) clinical trial supports this approach in a significant proportion of people with persistent symptomatic asthma.[187][188]

Concerns remain over the frequency of potential adverse effects, including increased risks of cardiovascular and noncardiovascular deaths.[187][189][190]

Primary options

azithromycin: 500 mg orally three times weekly

Consider – low-dose oral corticosteroid

Back

Consider –

low-dose oral corticosteroid

Treatment recommended for SOME patients in selected patient group

Reserved for patients with poor symptom control and/or frequent exacerbations (track 1 or track 2) despite: correct inhaler technique; good adherence with other step 5 treatments; having excluded contributory factors; and having tried other add-on treatments, including biologic agents (where appropriate).[3]

Increased markers of type 2 inflammation (i.e., high blood eosinophils and fractional exhaled nitric oxide values) predict response to oral corticosteroids.[248]

Primary options

prednisone: ≤7.5 mg orally once daily

Use of this content is subject to our disclaimer

Asthma in adults

Treatment algorithm

Your Organizational Guidance

initial treatment step 1: asthma symptoms 1-2 days per week or less and no risk factors for exacerbations

low-dose inhaled corticosteroid plus formoterol as needed

Primary options

low-dose inhaled corticosteroid plus short-acting beta agonist as needed

Primary options

initial treatment step 2: asthma symptoms less than 3-5 days per week and normal (or mildly reduced) lung function

low-dose inhaled corticosteroid plus formoterol as needed

Primary options

low-dose inhaled corticosteroid

Primary options

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Primary options

initial treatment step 3: asthma symptoms most days (e.g., 4-5 days per week or more), or waking due to asthma once a week or more, low lung function, and risk factors for exacerbations

low-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Primary options

low-dose inhaled corticosteroid plus long-acting beta agonist

Primary options

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Primary options

medium-dose inhaled corticosteroid

Primary options

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Primary options

initial treatment step 4: daily asthma symptoms, waking at night once a week or more, and low lung function

medium-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Primary options

short-course oral corticosteroid

Primary options

medium- or high-dose inhaled corticosteroid plus long-acting beta agonist

Primary options

short-course oral corticosteroid

Primary options

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Primary options

high-dose inhaled corticosteroid

Primary options

short-course oral corticosteroid

Primary options

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Primary options

ongoing treatment step 1: patients using short-acting beta agonist (SABA) alone or with newly diagnosed asthma, with normal (or mildly reduced) lung function

low-dose inhaled corticosteroid plus formoterol as needed

Primary options

low-dose inhaled corticosteroid plus short-acting beta agonist as needed

Primary options

ongoing treatment step 2: asthma not controlled on step 1 treatment

low-dose inhaled corticosteroid plus formoterol as needed

Primary options

low-dose inhaled corticosteroid

Primary options

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Primary options

low-dose inhaled corticosteroid plus short-acting beta agonist as needed

Primary options

ongoing treatment step 3: asthma not controlled on steps 1-2 treatment (track 1) or step 2 treatment (track 2), with risk factors for exacerbations

low-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Primary options

leukotriene receptor antagonist

Primary options

low-dose inhaled corticosteroid plus long-acting beta agonist

Primary options

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Primary options

leukotriene receptor antagonist

Primary options

medium-dose inhaled corticosteroid

Primary options

short-acting beta agonist (or inhaled corticosteroid-short-acting beta agonist) as needed

Primary options

leukotriene receptor antagonist

Primary options

ongoing treatment step 4: asthma not controlled on step 3 treatment

medium-dose inhaled corticosteroid plus formoterol as maintenance therapy and low-dose inhaled corticosteroid plus formoterol as reliever therapy

Primary options

leukotriene receptor antagonist

Primary options

long-acting muscarinic antagonist