Treatment algorithm

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

ONGOING

age 0 to 5 years

1st line – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 1: infrequent viral wheezing episodes and no, or few, interval symptoms
1st line – 

short-acting beta agonist as needed

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

SABA-only therapy is still recommended for children ages ≤5 years with mild asthma.[1]

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 1: infrequent viral wheezing episodes and no, or few, interval symptoms
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – intermittent high-dose inhaled corticosteroid

Back
ONGOING
|
age 0 to 5 years
|
step 1: infrequent viral wheezing episodes and no, or few, interval symptoms
2nd line – 

intermittent high-dose inhaled corticosteroid

Children with intermittent viral-induced wheeze and no or few interval symptoms may benefit from intermittent high-dose inhaled corticosteroid (ICS), especially if there is underlying atopy.

Only prescribe when confident the ICS will be used appropriately and the child can be monitored for adverse effects.[1] 

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1][157][158]​ High-dose ICS therapy should also be limited to short-term use over a maximum of 3-6 months.

The benefit attributable to use of ICS may exceed the potential risk of a relatively small suppression in linear growth in children with asthma.[156][168]​​

Growth should be monitored in all children who take corticosteroids.[1] 

There is insufficient evidence for the use of a daily controller at step 1.[1]

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 1: infrequent viral wheezing episodes and no, or few, interval symptoms
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 1: infrequent viral wheezing episodes and no, or few, interval symptoms
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

1st line – low-dose inhaled corticosteroid

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
1st line – 

low-dose inhaled corticosteroid

Daily low-dose inhaled corticosteroids (ICS) are the preferred initial controller treatment in children ≤5 years with asthma.[1]​ GINA guidelines recommend that this initial treatment should be given for at least 3 months to establish its effectiveness.[1]​​

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156]​​ [ Cochrane Clinical Answers logo ] Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

Growth should be monitored in all children who take corticosteroids.[1]

When starting therapy with ICS, initial low dose is as effective as initial high dose with subsequent down-titration.[162]

If good control of asthma is not achieved with an initial treatment option, GINA recommends trialling the alternative step 2 treatments before moving up to step 3 therapy.[1]​​

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

budesonide inhaled: children ≥1 year of age: 500 micrograms/day nebulised

OR

fluticasone propionate inhaled: children ≥4 years of age: 50 micrograms/day

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – leukotriene receptor antagonist

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
2nd line – 

leukotriene receptor antagonist

Recommended as an alternative to inhaled corticosteroids (ICS) at step 2.[1]​​

One systematic review found that LTRA monotherapy compared with placebo reduced exacerbations and increased lung function, while another reported that adding LTRA to daily ICS in adolescents and adults with persistent asthma and suboptimal control led to improved lung function and asthma control.[188][189] [ Cochrane Clinical Answers logo ] ​ However, other reviews have reported the superiority of daily ICS over LTRA as monotherapy both in preschoolers with asthma or recurrent wheezing, and in adults and children with persistent asthma.[190][191]​​ One systematic review concluded that LTRA added to ICS does not reduce the need for rescue oral corticosteroid dosing in children and adolescents with mild to moderate asthma.[192]

LTRAs are of particular interest in paediatric chronic asthma due to their availability as a once-daily oral formulation, with potential adherence benefits.[187]

Montelukast as monotherapy for exercise-induced asthma is an option where exercise is not predictable and a regular medication is indicated.[148]

Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]​​ The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196][197]​ These include new-onset nightmares, behavioural 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 parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196][198]

If good control of asthma is not achieved with an initial treatment option, GINA recommends trialling the alternative step 2 treatments before moving up to step 3 therapy.[1]

Primary options

montelukast: children ≥1 year of age: 4 mg orally once daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – intermittent high-dose inhaled corticosteroid

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
2nd line – 

intermittent high-dose inhaled corticosteroid

Another option for preschool children with frequent viral-induced wheezing and interval asthma symptoms.[1]​​[141][143][219]​​​ This would usually consist of intermittent, short courses of high-dose inhaled corticosteroid (ICS) at the onset of respiratory illness.[1]​ A trial of daily low-dose ICS should be undertaken first.[1]​​[141][142][143]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​ Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1][157][158]​ High-dose ICS therapy should also be limited to short-term use over a maximum of 3-6 months.

The benefit attributable to use of ICS may exceed the potential risk of a relatively small suppression in linear growth in children with asthma.[156][168]​​​

Growth should be monitored in all children who take corticosteroids.[1]

If good control of asthma is not achieved with an initial treatment option, GINA recommends trialling the alternative step 2 treatments before moving up to step 3 therapy.[1]

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 2: symptoms consistent with asthma, poor control, or ≥3 exacerbations per year
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

1st line – medium-dose (or double low-dose) inhaled corticosteroid

Back
ONGOING
|
age 0 to 5 years
|
step 3: diagnosed asthma and poor control on low-dose inhaled
1st line – 

medium-dose (or double low-dose) inhaled corticosteroid

The preferred controller option at step 3 is daily medium-dose (or double low-dose) inhaled corticosteroid (ICS).[1]​​

GINA recommends trying a minimum of 3 months of low-dose ICS before stepping up treatment. If that treatment fails to control symptoms, or exacerbations still occur, confirm that the symptoms are due to asthma, check inhaler technique and adherence, and exclude risk factors (e.g., allergen or tobacco smoke exposure) before stepping up treatment.[1]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​ Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1]​​[157][158]

At medium doses, the main adverse effects are local (e.g., candidiasis), or involve a transient slowing of growth. The benefits of ICS for asthma control are generally considered to outweigh the potential adverse effects on growth.[156]​

Growth should be monitored in all children who take corticosteroids.[1]

The child's response to medium-dose ICS should be assessed after 3 months of treatment.[1] The child should be referred to a specialist if symptom control remains poor or if exacerbations persist, or the child experiences adverse effects, or if adverse effects are suspected.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

budesonide inhaled: children ≥1 year of age: 1000 micrograms/day nebulised

OR

fluticasone propionate inhaled: children ≥4 years of age: 100 micrograms/day

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 3: diagnosed asthma and poor control on low-dose inhaled
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 3: diagnosed asthma and poor control on low-dose inhaled
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – low-dose inhaled corticosteroid plus leukotriene receptor antagonist

Back
ONGOING
|
age 0 to 5 years
|
step 3: diagnosed asthma and poor control on low-dose inhaled
2nd line – 

low-dose inhaled corticosteroid plus leukotriene receptor antagonist

An alternative option at step 3 is the addition of a leukotriene receptor antagonist (LTRA) to daily low-dose inhaled corticosteroid (ICS). This is based on data from older children.[1]​​

Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]​​ The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196][197]​ These include new-onset nightmares, behavioural 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 parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196][198]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

Growth should be monitored in all children who take corticosteroids.[1]

When starting therapy with ICS, initial low dose is as effective as initial high dose with subsequent down-titration.[162]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

budesonide inhaled: children ≥1 year of age: 500 micrograms/day nebulised

or

fluticasone propionate inhaled: children ≥4 years of age: 50 micrograms/day

-- AND --

montelukast: children ≥1 year of age: 4 mg orally once daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 3: diagnosed asthma and poor control on low-dose inhaled
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 3: diagnosed asthma and poor control on low-dose inhaled
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​​

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

1st line – continue controller treatment and refer for expert assessment

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
1st line – 

continue controller treatment and refer for expert assessment

The child's response to medium-dose inhaled corticosteroid (step 3 therapy) should be assessed after 3 months of treatment.[1]​

The child should be referred to a specialist if symptom control remains poor or if exacerbations persist, or the child experiences adverse effects of treatment, or if adverse effects are suspected.[1]​

Before referral, check the asthma diagnosis, check inhaler technique and adherence, and exclude risk factors (e.g., allergen or tobacco smoke exposure).[1]​​

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – high-dose inhaled corticosteroid

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
2nd line – 

high-dose inhaled corticosteroid

The best treatment for this patient group at step 4 has not yet been established.[1]​ GINA guidelines list several options that can be considered at this stage, provided the diagnosis of asthma has been confirmed, and specialist advice has been sought.[1]​​

One option is to further increase the dose of inhaled corticosteroid (ICS) for a few weeks until the child's asthma control improves, while monitoring for adverse effects.[1]​ 

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1][157][158]

Adrenal insufficiency is a potential complication with high cumulative doses of ICS.[169][170]​ Specialist pulmonary assessment should be sought before initiating this therapy.

Prospective cohort studies have shown that early life exposure to ICS before age 6 years was associated with reduced height but no change in bone density during continued therapy.[167] The benefit attributable to use of ICS may exceed the potential risk of a relatively small suppression in linear growth in children with asthma.[156][168]​​ 

Monitoring of adrenal function and growth is essential.

Other adverse effects that may be evident at high doses include cushingoid habitus (moon facies, buffalo hump, striae, and central obesity), behavioural problems, weight gain, diabetes, osteoporosis, cataracts, and hypertension.

There are no maximum doses for high-dose ICS therapy reported in the guidelines. Therefore, the dose should be increased gradually and cautiously according to patient response and adverse effects. It should be noted that the manufacturer's recommended maximum dose is lower than the doses suggested in the guidelines.

High-dose ICS therapy should also be limited to short-term use over a maximum of 3-6 months.

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – medium-dose inhaled corticosteroid plus leukotriene receptor antagonist

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
2nd line – 

medium-dose inhaled corticosteroid plus leukotriene receptor antagonist

The preferred treatment for this patient group at step 4 has not yet been established.[1]​ GINA guidelines list several options that can be considered at this stage, provided the diagnosis of asthma has been confirmed, and specialist advice has been sought.[1]​​

One option is to add a leukotriene receptor antagonist (LTRA) to the controller treatment that the child is already taking. This is based on evidence from older children.[1]​​

Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]​​ The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196][197]​ These include new-onset nightmares, behavioural 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 parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196][198]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

At medium doses, the main adverse effects are local (e.g., candidiasis), or involve a transient slowing of growth. The benefits of ICS for asthma control are generally considered to outweigh the potential adverse effects on growth.[156]​

Growth should be monitored in all children who take corticosteroids.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

budesonide inhaled: children ≥1 year of age: 1000 micrograms/day nebulised

or

fluticasone propionate inhaled: children ≥4 years of age: 100 micrograms/day

-- AND --

montelukast: children ≥1 year of age: 4 mg orally once daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

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

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
2nd line – 

medium-dose inhaled corticosteroid plus long-acting beta agonist

The best treatment for this patient group at step 4 has not yet been established.[1]​ GINA guidelines list several options that can be considered at this stage, provided the diagnosis of asthma has been confirmed, and specialist advice has been sought.[1]​​

One option is to add a long-acting beta agonist (LABA) to the inhaled corticosteroid (ICS) that the child is already taking. This is based on data in children aged 4 years and older.[1]​​

The response to LABAs in children is different from that reported in adults and should not be extrapolated.[144][145] [ Cochrane Clinical Answers logo ] ​ There is a lack of evidence regarding the efficacy and safety of ICS-LABA available for the 0- to 4-year age group.[144]

Concerns about increased exacerbation rates with LABAs in children have been highlighted.​[144][181]​​ Paediatric recommendations should be strictly adhered to. Once-daily combined therapy is less efficacious than twice-daily regimens.[220]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]​​​

At medium doses, the main adverse effects are local (e.g., candidiasis), or involve a transient slowing of growth. The benefits of ICS for asthma control are generally considered to outweigh the potential adverse effects on growth.[156]​ 

Growth should be monitored in all children who take corticosteroids.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options. Proprietary combination inhaler formulations may be available.

Primary options

budesonide inhaled: children ≥1 year of age: 1000 micrograms/day nebulised

or

fluticasone propionate inhaled: children ≥4 years of age: 100 micrograms/day

-- AND --

salmeterol inhaled: children ≥4 years of age: 50 micrograms twice daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – medium-dose inhaled corticosteroid plus low-dose oral corticosteroid

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
2nd line – 

medium-dose inhaled corticosteroid plus low-dose oral corticosteroid

The best treatment for this patient group at step 4 has not yet been established.[1]​ GINA guidelines list several options that can be considered at this stage, provided the diagnosis of asthma has been confirmed, and specialist advice has been sought.[1]​​

One option is to add a low dose of oral corticosteroids, for a few weeks only, to the inhaled corticosteroid (ICS) that the child is already taking, until asthma control improves.[1]​ Children should be monitored for adverse effects.

There are concerns regarding systemic adverse effects of oral and inhaled corticosteroids, particularly at higher doses.​[168][172][221]​​ Oral corticosteroid bursts have been shown to decrease bone mineral accretion and increase the risk of osteopenia.[173]

In one systematic review, common adverse acute events related to oral corticosteroid use of ≤14 days' duration were vomiting, behaviour change, and sleep disturbance (incidence of 5.4%, 4.7%, and 4.3%, respectively).[174] Other less common but serious adverse events were infection (incidence of 0.9%), increased blood pressure (39%), hypothalamic-pituitary axis suppression (81%), and weight gain (28%).

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

At medium doses, the main adverse effects are local (e.g., candidiasis), or involve a transient slowing of growth. The benefits of ICS for asthma control are generally considered to outweigh the potential adverse effects on growth.[156]

Growth should be monitored in all children who take corticosteroids.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

budesonide inhaled: children ≥1 year of age: 1000 micrograms/day nebulised

or

fluticasone propionate inhaled: children ≥4 years of age: 100 micrograms/day

-- AND --

prednisolone: 1-2 mg/kg orally once daily, maximum 40 mg/day

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – medium-dose inhaled corticosteroid plus intermittent high-dose inhaled corticosteroid

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
2nd line – 

medium-dose inhaled corticosteroid plus intermittent high-dose inhaled corticosteroid

The best treatment for this patient group at step 4 has not yet been established.[1]​ GINA guidelines list several options that can be considered at this stage, provided the diagnosis of asthma has been confirmed, and specialist advice has been sought.[1]​​

If asthma exacerbations are the main problem, then one option is to add intermittent high-dose inhaled corticosteroid (ICS) at the onset of respiratory illnesses to daily medium-dose ICS.[1]​ Children should be monitored for side effects.

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​​​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]​ High-dose ICS therapy should also be limited to short-term use over a maximum of 3-6 months.

At medium doses, the main adverse effects are local (e.g., candidiasis), or involve a transient slowing of growth. The benefits of ICS for asthma control are generally considered to outweigh the potential adverse effects on growth.[156]

Growth should be monitored in all children who take corticosteroids.[1]

There are concerns regarding systemic adverse effects, particularly at higher ICS doses.[168][221]​​

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 0 to 5 years
|
step 4: asthma not well-controlled on medium-dose (or double low-dose) inhaled corticosteroid
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

age 6 to 11 years

1st line – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 1: infrequent symptoms 1-2 days a week or less
1st line – 

short-acting beta agonist as needed

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

The preferred treatment is as-needed SABA with low-dose inhaled corticosteroid (ICS) taken at the same time (combined or in separate inhalers). Daily maintenance low-dose ICS, plus as-needed SABA, is an alternative but risks poor adherence due to the infrequent symptoms.

SABA-only therapy is no longer recommended for children aged ≥6 years with mild asthma.[1]

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Plus – low-dose inhaled corticosteroid whenever short-acting beta agonist is taken

Back
ONGOING
|
age 6 to 11 years
|
step 1: infrequent symptoms 1-2 days a week or less
Plus – 

low-dose inhaled corticosteroid whenever short-acting beta agonist is taken

Treatment recommended for ALL patients in selected patient group

The preferred option is taking a low-dose inhaled corticosteroid (ICS) whenever short-acting beta agonist (SABA) is taken.[1] This is based on indirect evidence from step 2 studies with separate inhalers.[222][223]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

Growth should be monitored in all children who take corticosteroids.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

beclometasone inhaled: 50-100 micrograms/day (extrafine particle); 100-200 micrograms/day (standard particle)

OR

budesonide inhaled: 100-200 micrograms/day via inhaler; 250-500 micrograms/day nebulised

OR

fluticasone propionate inhaled: 50-100 micrograms/day

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 1: infrequent symptoms 1-2 days a week or less
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – low-dose inhaled corticosteroid

Back
ONGOING
|
age 6 to 11 years
|
step 1: infrequent symptoms 1-2 days a week or less
2nd line – 

low-dose inhaled corticosteroid

An alternative option at step 1 is daily low-dose inhaled corticosteroid (ICS) plus as-needed short-acting beta agonist (SABA).[1]​ However, there is a risk of poor adherence in children with infrequent symptoms.[1]​​

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

Growth should be monitored in all children who take corticosteroids.[1]

When starting therapy with ICS, initial low dose is as effective as initial high dose and subsequent down-titration.[162]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

beclometasone inhaled: 50-100 micrograms/day (extrafine particle); 100-200 micrograms/day (standard particle)

OR

budesonide inhaled: 100-200 micrograms/day via inhaler; 250-500 micrograms/day nebulised

OR

fluticasone propionate inhaled: 50-100 micrograms/day

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 1: infrequent symptoms 1-2 days a week or less
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

The preferred treatment is as-needed SABA with low-dose ICS taken at the same time (combined or in separate inhalers). Daily maintenance low-dose ICS, plus as-needed SABA, is an alternative, but risks poor adherence due to the infrequent symptoms.

SABA-only therapy is no longer recommended for children ages ≥6 years with mild asthma.[1]

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 1: infrequent symptoms 1-2 days a week or less
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.​[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

1st line – low-dose inhaled corticosteroid

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
1st line – 

low-dose inhaled corticosteroid

Daily low-dose inhaled corticosteroids (ICS) are the preferred initial and ongoing controller treatment option at step 2 for children in this patient group.[1]​ This is usually in children with asthma symptoms or need for reliever medication twice a month or more.[1]​​

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

Growth should be monitored in all children who take corticosteroids.[1]

When starting therapy with ICS, initial low dose is as effective as initial high dose with subsequent down-titration.[162]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

beclometasone inhaled: 50-100 micrograms/day (extrafine particle); 100-200 micrograms/day (standard particle)

OR

budesonide inhaled: 100-200 micrograms/day via inhaler; 250-500 micrograms/day nebulised

OR

fluticasone propionate inhaled: 50-100 micrograms/day

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
2nd line – 

short-acting beta agonist as needed

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]

​​Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Plus – low-dose inhaled corticosteroid whenever short-acting beta agonist is taken

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
Plus – 

low-dose inhaled corticosteroid whenever short-acting beta agonist is taken

Treatment recommended for ALL patients in selected patient group

An alternative controller option at step 2 for children with symptoms or need for reliever use at least twice a month (but not daily) is low-dose inhaled corticosteroid (ICS) whenever short-acting beta agonist (SABA) is taken.[1]​ This is based on indirect evidence from step 2 studies with separate inhalers.[222][223]

Taking low-dose ICS whenever SABA is taken is also an alternative initial treatment for this patient group.[1]​​

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

Growth should be monitored in all children who take corticosteroids.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

beclometasone inhaled: 50-100 micrograms/day (extrafine particle); 100-200 micrograms/day (standard particle)

OR

budesonide inhaled: 100-200 micrograms/day via inhaler; 250-500 micrograms/day nebulised

OR

fluticasone propionate inhaled: 50-100 micrograms/day

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – leukotriene receptor antagonist

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
2nd line – 

leukotriene receptor antagonist

Recommended as an alternative controller option at step 2 for children with symptoms or need for reliever use at least twice a month (but not daily).[1]Daily leukotriene receptor antagonist (LTRA) is also an alternative initial treatment for this patient group.[1]​​

One systematic review found that LTRA monotherapy compared with placebo reduced exacerbations and increased lung function, while another reported that adding LTRA to daily ICS in adolescents and adults with persistent asthma and suboptimal control led to improved lung function and asthma control.[188][189] [ Cochrane Clinical Answers logo ] ​​​ However, other reviews have reported the superiority of daily ICS over LTRA as monotherapy both in preschoolers with asthma or recurrent wheezing, and in adults and children with persistent asthma.[190][191]​​​ One systematic review concluded that LTRA added to ICS does not reduce the need for rescue oral corticosteroid dosing in children and adolescents with mild to moderate asthma.[192]

LTRAs are of particular interest in paediatric chronic asthma due to their availability as a once-daily oral formulation, with potential adherence benefits.[187]

Montelukast as monotherapy for exercise-induced asthma is an option where exercise is not predictable and a regular medication is indicated.[148]

Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]​ The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196][197]​ These include new-onset nightmares, behavioural 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 parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196][198]

Primary options

montelukast: children <6 years of age: 4 mg orally once daily; children ≥6 years of age: 5 mg orally once daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 2: symptoms 2-5 days a week
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

1st line – medium-dose inhaled corticosteroid

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
1st line – 

medium-dose inhaled corticosteroid

Medium-dose inhaled corticosteroid (ICS) - after checking inhaler technique, adherence to treatment, and addressing any risk factors - is one of three preferred controller options for children with troublesome symptoms most days, or waking due to asthma at least once a week.[1]

Taking daily medium-dose ICS, with SABA as needed, is also a preferred initial treatment for this patient group, especially if the child has risk factors.[1]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

At medium doses, the main adverse effects are local (e.g., candidiasis) or involve a transient slowing of growth. The benefits of ICS for asthma control are generally considered to outweigh the potential adverse effects on growth.[156]

Growth should be monitored in all children who take corticosteroids.[1]

There are concerns regarding systemic adverse effects, particularly at higher ICS doses.[168][221] 

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

beclometasone inhaled: >100-200 micrograms/day (extrafine particle); >200-400 micrograms/day (standard particle)

OR

budesonide inhaled: >200-400 micrograms/day via inhaler; >500-1000 micrograms/day nebulised

OR

fluticasone propionate inhaled: >100-200 micrograms/day

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

1st line – low-dose inhaled corticosteroid plus long-acting beta agonist

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
1st line – 

low-dose inhaled corticosteroid plus long-acting beta agonist

Low-dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA) - after checking inhaler technique, adherence to treatment, and addressing any risk factors - is one of three preferred controller options for children with troublesome symptoms most days, or waking due to asthma at least once a week.[1]

Taking low-dose ICS plus LABA regularly, with short-acting beta agonist (SABA) as needed, is also a preferred initial treatment for this patient group, especially if the child has risk factors.[1]

The generalisable response to LABAs in children is different from that reported in adults and should not be extrapolated.[144][145] [ Cochrane Clinical Answers logo ] ​​ Additional concerns about increased exacerbation rates with LABAs in children have also been highlighted.[144][181]​​​ Until more appropriate paediatric evidence exists, paediatric recommendations should be strictly adhered to. Once-daily combined therapy is less efficacious than twice-daily regimens.[220]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1][157][158]

Growth should be monitored in all children who take corticosteroids.[1]

​When starting therapy with ICS, initial low dose is as effective as initial high dose with subsequent down-titration.[162]

​Examples of suitable drug regimens are given here. Consult a local drug formulary for more options. Proprietary combination inhaler formulations may be available.

Primary options

beclometasone inhaled: 50-100 micrograms/day (extrafine particle); 100-200 micrograms/day (standard particle)

or

budesonide inhaled: 100-200 micrograms/day via inhaler; 250-500 micrograms/day nebulised

or

fluticasone propionate inhaled: 50-100 micrograms/day

-- AND --

salmeterol inhaled: 50 micrograms twice daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

1st line – very low dose inhaled corticosteroid plus formoterol as maintenance and reliever therapy

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
1st line – 

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

Very low dose inhaled corticosteroid (ICS) plus formoterol as maintenance and reliever therapy (MART) - after checking inhaler technique, adherence to treatment, and addressing any risk factors - is one of three preferred controller options for children with troublesome symptoms most days, or waking due to asthma at least once a week.[1]

Taking a very low dose of ICS-formoterol as MART is also a preferred initial treatment for this patient group, especially if the child has risk factors.[1]

In the MART regimen, the same inhaler is used as both a controller and a reliever.

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1][157][158]

Growth should be monitored in all children who take corticosteroids.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options. The total daily dose of formoterol should not exceed 48 μg when prescribed ICS-formoterol as MART.

Primary options

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

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

2nd line – low-dose inhaled corticosteroid plus leukotriene receptor antagonist

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
2nd line – 

low-dose inhaled corticosteroid plus leukotriene receptor antagonist

An alternative option at step 3 is daily low-dose inhaled corticosteroid (ICS) plus a leukotriene receptor antagonist (LTRA) plus short-acting beta agonist (SABA) when required.[1]​ However, there is little evidence for adding LTRA to low dose ICS in children.[146]​​

Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]​​ The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196][197] These include new-onset nightmares, behavioural 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 parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196][198]​​

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1][157][158]

Growth should be monitored in all children who take corticosteroids.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options.

Primary options

beclometasone inhaled: 50-100 micrograms/day (extrafine particle); 100-200 micrograms/day (standard particle)

or

budesonide inhaled: 100-200 micrograms/day via inhaler; 250-500 micrograms/day nebulised

or

fluticasone propionate inhaled: 50-100 micrograms/day

-- AND --

montelukast: children <6 years of age: 4 mg orally once daily; children ≥6 years of age: 5 mg orally once daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 3: symptoms 4-5 days a week or waking due to asthma at least once a week
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

1st line – medium-dose inhaled corticosteroid plus long-acting beta agonist

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
1st line – 

medium-dose inhaled corticosteroid plus long-acting beta agonist

Medium-dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA) is one of two preferred controller options for children with severely uncontrolled asthma.[1]

Taking daily medium-dose ICS plus LABA regularly, with short-acting beta agonist (SABA) as needed, is also a preferred initial treatment for this patient group.[1]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​ Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

At medium doses, the main adverse effects are local (e.g., candidiasis) or involve a transient slowing of growth. The benefits of ICS for asthma control are generally considered to outweigh the potential adverse effects on growth.[156]

Growth should be monitored in all children who take corticosteroids.[1]

There are concerns regarding systemic adverse effects, particularly at higher ICS doses.[168][221]​ 

​The generalisable response to LABAs in children is different from that reported in adults and should not be extrapolated.[144][145] [ Cochrane Clinical Answers logo ] ​​​ Additional concerns about increased exacerbation rates with LABAs in children have also been highlighted.[144][181]​​​​ Until more appropriate paediatric evidence exists, paediatric recommendations should be strictly adhered to. Once-daily combined therapy is less efficacious than twice-daily regimens.[220]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options. Proprietary combination inhaler formulations may be available.

Primary options

beclometasone inhaled: >100-200 micrograms/day (extrafine particle); >200-400 micrograms/day (standard particle)

or

budesonide inhaled: >200-400 micrograms/day via inhaler; >500-1000 micrograms/day nebulised

or

fluticasone propionate inhaled: >100-200 micrograms/day

-- AND --

salmeterol inhaled: 50 micrograms twice daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

Consider – refer for expert assessment and advice

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

refer for expert assessment and advice

Additional treatment recommended for SOME patients in selected patient group

If asthma is not well controlled on medium-dose inhaled corticosteroid, GINA recommends referral for expert assessment and advice.[1]​​

Consider – leukotriene receptor antagonist

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

leukotriene receptor antagonist

Additional treatment recommended for SOME patients in selected patient group

If not trialled before, a leukotriene receptor antagonist (LTRA) could be added at step 4.[1]

Note that it is preferable to change only one medication at a time in chronic management, in order to see which medication had an effect.

LTRAs are of particular interest in paediatric chronic asthma due to their availability as a once-daily oral formulation, with potential adherence benefits.[187]

Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]​​ The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196][197] These include new-onset nightmares, behavioural 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 parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196][198]

Primary options

montelukast: children <6 years of age: 4 mg orally once daily; children ≥6 years of age: 5 mg orally once daily

Consider – tiotropium

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

tiotropium

Additional treatment recommended for SOME patients in selected patient group

Tiotropium, a long-acting muscarinic antagonist, may be used as an add-on therapy in children aged 6 years and older.[1]​

Note that it is preferable to change only one medication at a time in chronic management, in order to see which medication had an effect.

One systematic review found that add-on tiotropium reduced exacerbations and led to a modest improvement in lung function.[224]

Primary options

tiotropium inhaled: 5 micrograms once daily

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

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
1st line – 

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

Low-dose inhaled corticosteroid (ICS) plus formoterol as maintenance and reliever therapy (MART) is one of two preferred controller options for children with severely uncontrolled asthma.[1]

Taking daily low-dose ICS plus formoterol as MART is also a preferred initial treatment for this patient group.[1]

In the MART regimen, the same inhaler is used as both a controller and a reliever.[1]​ 

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] Adverse effects may be minimised by using the lowest dose to achieve good control, by using a spacer (limiting oropharyngeal deposition), and by rinsing the mouth after medication delivery.[1]​​[157][158]

Growth should be monitored in all children who take corticosteroids.[1]

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options. The total daily dose of formoterol should not exceed 48 μg when prescribed ICS-formoterol as MART.

Primary options

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

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

Consider – refer for expert assessment and advice

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

refer for expert assessment and advice

Additional treatment recommended for SOME patients in selected patient group

If asthma is not well controlled on low-dose inhaled corticosteroid plus formoterol as maintenance and reliever therapy, GINA recommends referral for expert assessment and advice.[1]

Consider – leukotriene receptor antagonist

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

leukotriene receptor antagonist

Additional treatment recommended for SOME patients in selected patient group

If not trialled before, a leukotriene receptor antagonist (LTRA) could be added at step 4.[1]

Note that it is preferable to change only one medication at a time in chronic management, in order to see which medication had an effect.

LTRAs are of particular interest in paediatric chronic asthma due to their availability as a once-daily oral formulation, with potential adherence benefits.[187]

Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]​​ The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196][197]​ These include new-onset nightmares, behavioural 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 parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196][198]

Primary options

montelukast: children <6 years of age: 4 mg orally once daily; children ≥6 years of age: 5 mg orally once daily

Consider – tiotropium

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

tiotropium

Additional treatment recommended for SOME patients in selected patient group

Tiotropium, a long-acting muscarinic antagonist, may be used as an add-on therapy in children aged 6 years and older.[1]​

Note that it is preferable to change only one medication at a time in chronic management, in order to see which medication had an effect.

One systematic review found that add-on tiotropium reduced exacerbations and led to a modest improvement in lung function.[224]

Primary options

tiotropium inhaled: 5 micrograms once daily

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

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
2nd line – 

high-dose inhaled corticosteroid plus long-acting beta agonist

Another controller option at step 4 in this patient group is increasing to high-dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA).[1]

The generalisable response to LABAs in children is different from that reported in adults and should not be extrapolated.[144][145] [ Cochrane Clinical Answers logo ] ​​ Additional concerns about increased exacerbation rates with LABAs in children have also been highlighted.[144][181]​​​ Until more appropriate paediatric evidence exists, paediatric recommendations should be strictly adhered to. Once-daily combined therapy is less efficacious than twice-daily regimens.[220]

The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155][156] [ Cochrane Clinical Answers logo ] ​​​ Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1][157][158]​ High-dose ICS therapy should also be limited to short-term use over a maximum of 3-6 months.

Adrenal insufficiency is a potential complication with high cumulative doses of ICS.[169][170]​​ Specialist pulmonary assessment should be sought before initiating this therapy.

Prospective cohort studies have shown that early life exposure to ICS before age 6 years was associated with reduced height but no change in bone density during continued therapy.[167] The benefit attributable to use of ICS may exceed the potential risk of a relatively small suppression in linear growth in children with asthma.[156][168]​​​ 

Monitoring of adrenal function and growth is essential.

Other adverse effects that may be evident at high doses include cushingoid habitus (moon facies, buffalo hump, striae, and central obesity), behavioural problems, weight gain, diabetes, osteoporosis, cataracts, and hypertension.

There are no maximum doses for high-dose ICS therapy reported in the guidelines. Therefore, the dose should be increased gradually and cautiously according to patient response and adverse effects. It should be noted that the manufacturer's recommended maximum dose is lower than the doses suggested in the guidelines.

Examples of suitable drug regimens are given here. Consult a local drug formulary for more options. Proprietary combination inhaler formulations may be available.

Primary options

beclometasone inhaled: >200 micrograms/day (extrafine particle); >400 micrograms/day (standard particle)

or

budesonide inhaled: >400 micrograms/day via inhaler; >1000 micrograms/day nebulised

or

fluticasone propionate inhaled: >200 micrograms/day

-- AND --

salmeterol inhaled: 50 micrograms twice daily

Plus – short-acting beta agonist as needed

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Plus – 

short-acting beta agonist as needed

Treatment recommended for ALL patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to step up treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]​​

Primary options

salbutamol inhaled: (100 micrograms/dose metered-dose inhaler) 100-200 micrograms (1-2 puffs) every 4-6 hours when required

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

Consider – leukotriene receptor antagonist

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

leukotriene receptor antagonist

Additional treatment recommended for SOME patients in selected patient group

If not trialled before, a leukotriene receptor antagonist (LTRA) could be added at step 4.[1]​

Note that it is preferable to change only one medication at a time in chronic management, in order to see which medication had an effect.

LTRAs are of particular interest in paediatric chronic asthma due to their availability as a once-daily oral formulation, with potential adherence benefits.[187]

Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]​​ The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196][197]​ These include new-onset nightmares, behavioural 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 parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196][198]

Primary options

montelukast: children <6 years of age: 4 mg orally once daily; children ≥6 years of age: 5 mg orally once daily

Consider – tiotropium

Back
ONGOING
|
age 6 to 11 years
|
step 4: symptoms daily or most days, waking with asthma at least once a week, and low lung function
Consider – 

tiotropium

Additional treatment recommended for SOME patients in selected patient group

Tiotropium, a long-acting muscarinic antagonist, may be used as an add-on therapy in children aged 6 years and older.[1]

Note that it is preferable to change only one medication at a time in chronic management, in order to see which medication had an effect.

One systematic review found that add-on tiotropium reduced exacerbations and led to a modest improvement in lung function.[224]

Primary options

tiotropium inhaled: 5 micrograms once daily

1st line – continue controller treatment and refer for phenotypic assessment

Back
ONGOING
|
age 6 to 11 years
|
step 5: persistent symptoms and/or exacerbations despite appropriate therapy
1st line – 

continue controller treatment and refer for phenotypic assessment

If the child has persistent symptoms and/or exacerbations despite correct inhaler technique and good adherence with step 4 treatment, and if other controller options have been considered, then the child should be referred to a specialist for investigation and management of severe asthma.[1]​​[147]

The child should continue with their existing inhaled corticosteroid (ICS)-containing controller treatment, plus short-acting beta agonist (SABA) when required (if not on a maintenance and reliever [MART] regimen), until their specialist assessment.[1]​​[147]

Consider – reliever medication

Back
ONGOING
|
age 6 to 11 years
|
step 5: persistent symptoms and/or exacerbations despite appropriate therapy
Consider – 

reliever medication

Additional treatment recommended for SOME patients in selected patient group

All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief.[1]​​

Children on a maintenance and reliever therapy (MART) regimen should use their ICS-formoterol inhaler, rather than a SABA, as their reliever.[1]​​

Use of a SABA inhaler on average more than twice a week over 1 month indicates the need to consider additional treatment.[1]​​

Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]

Consider – management of exercise-induced bronchoconstriction

Back
ONGOING
|
age 6 to 11 years
|
step 5: persistent symptoms and/or exacerbations despite appropriate therapy
Consider – 

management of exercise-induced bronchoconstriction

Additional treatment recommended for SOME patients in selected patient group

A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1][8][148][149]​​​​​ 

For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.​[1][8]​​​​ Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1][150]​​​​ 

The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148] Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]

Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1][148]​​​​ There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]

Consider – tiotropium

Back
ONGOING
|
age 6 to 11 years
|
step 5: persistent symptoms and/or exacerbations despite appropriate therapy
Consider – 

tiotropium

Additional treatment recommended for SOME patients in selected patient group

Tiotropium, a long-acting muscarinic antagonist, may be used as an add-on therapy in children aged 6 years and older.[1]​

Note that it is preferable to change only one medication at a time in chronic management, in order to see which medication had an effect.

One systematic review found that add-on tiotropium reduced exacerbations and led to a modest improvement in lung function.[224]

Primary options

tiotropium inhaled: 5 micrograms once daily

Consider – biological agent

Back
ONGOING
|
age 6 to 11 years
|
step 5: persistent symptoms and/or exacerbations despite appropriate therapy
Consider – 

biological agent

Additional treatment recommended for SOME patients in selected patient group

In patients aged ≥6 years with evidence of allergic sensitisation and an elevated immunoglobulin E (IgE) serum level, omalizumab should be considered.[1]​

Note that it is preferable to change only one medication at a time in chronic management, in order to see which medication had an effect.

Omalizumab is a monoclonal antibody (anti-IgE) that interferes with the binding of IgE to receptors on basophils and eosinophils.[212] Pain and bruising are reported in 5% to 20% of patients. Risk of anaphylaxis is approximately 0.2%. Dose depends on the patient's weight and pretreatment serum IgE level.

In patients aged ≥6 years with evidence of elevated eosinophils, mepolizumab could be considered.[1][209][225]​​​​ Mepolizumab is an interleukin (IL)-5 antagonist monoclonal antibody that directly binds to IL-5. While its efficacy in reducing asthma exacerbations (but not quality of life or lung function) has been shown in older children (aged >12 years), efficacy in younger children has not been documented. Headaches are a common known adverse event.[226]​​

Dupilumab is approved in the US for children aged 6 to 11 years with moderate-to-severe asthma characterised by an eosinophilic phenotype or with oral corticosteroid dependent asthma.

Primary options

omalizumab: consult specialist for guidance on dose

OR

mepolizumab: consult specialist for guidance on dose

OR

dupilumab: consult specialist for guidance on dose

Consider – low-dose oral corticosteroid

Back
ONGOING
|
age 6 to 11 years
|
step 5: persistent symptoms and/or exacerbations despite appropriate therapy
Consider – 

low-dose oral corticosteroid

Additional treatment recommended for SOME patients in selected patient group

Some patients may benefit from low-dose oral corticosteroids, but long-term systemic adverse effects are common and serious.[1]​​​

Oral corticosteroids should be considered for children with severe asthma not adequately controlled with maximal therapy.

Long-term oral corticosteroid use is less common in children/adolescents than adults (9.9% vs. 22.4%).[172]​ Short courses of oral corticosteroids may be needed to achieve control of exacerbations, while long-term low-dose oral corticosteroids may be needed as part of chronic asthma management for children with severe asthma not adequately controlled on maximal therapy.[1]

There are concerns regarding systemic adverse effects of oral and inhaled corticosteroids, particularly at higher doses.​[168][172][221]​​ Oral corticosteroid use is more frequently associated with hypothalamic-pituitary axis suppression, growth retardation, and weight gain.[174][175]​​ Adrenal insufficiency is a potential complication with high cumulative doses of ICS.[169][170]​​ Oral corticosteroid bursts have been shown to decrease bone mineral accretion and increase the risk of osteopenia.[173]

In one systematic review, common adverse acute events related to oral corticosteroid use ≤14 days' duration were vomiting, behaviour change, and sleep disturbance (incidence 5.4%, 4.7%, and 4.3%, respectively).[174] Other less common but serious adverse events were infection (incidence of 0.9%), increased blood pressure (39%), hypothalamic-pituitary axis suppression (81%), and weight gain (28%).[174] Another systematic review of oral corticosteroid treatment for ≥ 15 days reported incidence rates for weight gain (22.4%), cushingoid features (20.6%), and growth retardation (18.9%), together with increased susceptibility to infection that could result in death.[175]

Cataracts have been reported in 15% to 35% of children receiving oral corticosteroids for more than 1 year.[166]

Primary options

prednisolone: 1-2 mg/kg orally once daily, maximum 40 mg/day

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