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

ACUTE

stage 1: acute

1st line – oral corticosteroid

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ACUTE
|
stage 1: acute
1st line – 

oral corticosteroid

The mainstay of treatment for allergic bronchopulmonary aspergillosis is systemic corticosteroids to suppress the inflammatory response to A fumigatus. Evidence supporting this therapy is mostly from longitudinal case series.[7][45][46]

In one case series, all patients responded to corticosteroids with a significant decline in IgE and resolution of infiltrates on chest imaging.[45] The optimal dose for systemic corticosteroids is not known as there have been no prospective or randomised trials to guide dosing regimens.

Measurement of total serum IgE should be repeated after the initial 6-8 weeks of corticosteroid therapy, then every 8-12 weeks for 1 year.[47] Any rise in serum IgE >100% over baseline suggests an exacerbation. If the total serum IgE level does not drop by >35% over 2 months of therapy, the patient may not be taking the corticosteroid as instructed, or another diagnosis should be considered, such as infection.[48] A chest x-ray or computed tomography scan of the chest should be repeated after 4-8 weeks of therapy to document clearing of infiltrates.[47]

Primary options

prednisolone: 0.5 mg/kg/day orally for 7-14 days, then taper gradually according to response, maximum 60 mg/day

Plus – antifungal therapy

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ACUTE
|
stage 1: acute
Plus – 

antifungal therapy

Treatment recommended for ALL patients in selected patient group

The Infectious Disease Society of America recommends that first-line treatment of acute allergic bronchopulmonary aspergillosis (ABPA) should include a combination of a corticosteroid plus antifungal therapy.[26]

Azole antifungals (e.g., itraconazole, voriconazole, posaconazole) are effective against A fumigatus.

Itraconazole is used most commonly for the treatment of ABPA due to its better adverse-effect profile, tolerability, and because it is the most well studied. One RCT reported that prednisolone significantly increased the composite response rate, compared with itraconazole, in patients with ABPA (100% vs. 88%; P=0.007).[49] Similar results were found for both treatments for percent decline in IgE at 6 weeks and 3 months, number of patients with exacerbations at 1 and 2 years, time to exacerbation, and the improvement of lung function at 6 weeks.[49] However, adverse effects were significantly higher for patients treated with prednisolone.

Evidence suggests that voriconazole or posaconazole are reasonable second-line therapies for ABPA. One retrospective review of adult asthmatic patients who were refractory to or had developed adverse effects to itraconazole treatment with ABPA. Both voriconazole and posaconazole demonstrated similar results for clinical response at 3, 6, and 12 months, and reduction in total IgE at 9 and 12 months.[50]​ Treatment with voriconazole and posaconazole may also improve asthma control and reduce severity.[50]

Therapeutic drug monitoring is recommended with voriconazole in combination with corticosteroids. Marked adrenal suppression has been seen with concomitant use of systemic corticosteroids and azole antifungals; both agents can cause adrenal suppression in their own right due to metabolism through CYP450.[51][52]​​ In addition, azoles can increase the serum concentration of cystic fibrosis transmembrane conductance regulator modulators, which is important for drug monitoring in CF patients. 

If azole antifungals are unavailable or contraindicated, amphotericin-B deoxycholate and its lipid derivatives may be considered for initial therapy.[26]​ One systematic review concluded that amphotericin-B does not improve exacerbation-free status at 1 year, although some evidence suggested that amphotericin-B treatment delayed the time to first exacerbation compared with the control arm, this result was not statistically significant.[53]

Primary options

itraconazole: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release) twice daily on day 1, followed by 300 mg once daily

Tertiary options

amphotericin B deoxycholate: 1 to 1.5 mg/kg/day intravenously

OR

amphotericin B liposomal: 3-5 mg/kg/day intravenously

Plus – environmental control

Back
ACUTE
|
stage 1: acute
Plus – 

environmental control

Treatment recommended for ALL patients in selected patient group

Patients should be counselled to avoid exposure to Aspergillus fumigatus. Although ubiquitous in the environment, A fumigatus can be seen in particularly high quantities in, for example, dead and decaying organic matter such as compost, so activities such as gardening can increase exposure.

The patient's home should be assessed for damp and water damage, which can encourage the growth of moulds of all types, including Aspergillus.[47][72] ​In practice, patients may be advised to keep indoor humidity below 50% as mould grows in humid environments. If mould is present in the home, professional remediation should be considered.

Plus – optimisation of management of cystic fibrosis, asthma and other comorbid conditions

Back
ACUTE
|
stage 1: acute
Plus – 

optimisation of management of cystic fibrosis, asthma and other comorbid conditions

Treatment recommended for ALL patients in selected patient group

Treatment of underlying asthma should be reviewed and optimised using a stepwise approach and standard agents. See Asthma in adults.

GORD treatment may benefit patients who have asthma, and GORD evaluation should be considered in patients who have poorly controlled asthma, especially with night-time symptoms. See Gastro-oesophageal reflux disease.​

Rhinitis or sinusitis symptoms or diagnosis should be evaluated in patients who have asthma, because the inter-relationship of the upper and lower airway suggests that therapy for the upper airway will improve asthma control. See Allergic rhinitis, Chronic rhinosinusitis without nasal polyps.

Treatment of underlying cystic fibrosis should be reviewed and optimised. This may involve the use of corticosteroids, long-acting beta-agonists, mucus-clearance agents, antibiotics, non-steroidal anti-inflammatory drugs, supplemental oxygen, and physiotherapy. See Cystic fibrosis.

stage 2: remission

1st line – optimisation of management of cystic fibrosis, asthma and other comorbid conditions

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ACUTE
|
stage 2: remission
1st line – 

optimisation of management of cystic fibrosis, asthma and other comorbid conditions

These patients are identified as generally being asymptomatic or stable, off prednisolone >6 months, with no infiltrates. Serum IgE may be elevated or normal.

Treatment of underlying asthma should be reviewed and optimised using a stepwise approach and standard agents. See Asthma in adults.

GORD treatment may benefit patients who have asthma, and GORD evaluation should be considered in patients who have poorly controlled asthma, especially with night-time symptoms. See Gastro-oesophageal reflux disease.​

Rhinitis or sinusitis symptoms or diagnosis should be evaluated in patients who have asthma, because the inter-relationship of the upper and lower airway suggests that therapy for the upper airway will improve asthma control. See Allergic rhinitis, Chronic rhinosinusitis without nasal polyps.

Treatment of underlying cystic fibrosis should be reviewed and optimised. This may involve the use of corticosteroids, long-acting beta-agonists, mucus-clearance agents, antibiotics, non-steroidal anti-inflammatory drugs, supplemental oxygen, and physiotherapy. See Cystic fibrosis.

Plus – environmental control

Back
ACUTE
|
stage 2: remission
Plus – 

environmental control

Treatment recommended for ALL patients in selected patient group

Patients should be counselled to avoid exposure to Aspergillus fumigatus. Although ubiquitous in the environment, A fumigatus can be seen in particularly high quantities in, for example, dead and decaying organic matter such as compost, so activities such as gardening can increase exposure.

The patient's home should be assessed for damp and water damage, which can encourage the growth of moulds of all types, including Aspergillus.[47][72]​ In practice, patients may be advised to keep indoor humidity below 50% as mould grows in humid environments. If mould is present in the home, professional remediation should be considered.

stage 3: exacerbation

1st line – oral corticosteroid

Back
ACUTE
|
stage 3: exacerbation
1st line – 

oral corticosteroid

Exacerbations may be diagnosed by an increase in total serum IgE >100% of baseline on routine monitoring or by clinical symptoms of cough, dyspnoea, increased sputum, and fever.[48] In practice, flares may be asymptomatic and only noted due to the rise in IgE or new infiltrates on chest imaging. Treatment is the same as for acute stage 1 allergic bronchopulmonary aspergillosis, usually with systemic corticosteroids in combination with antifungal therapy.

In one case series, all patients responded to corticosteroids with a significant decline in IgE and resolution of infiltrates on chest imaging.[45] The optimal dose for systemic corticosteroids is not known as there have been no prospective or randomised trials to guide dosing regimens.

Measurement of total serum IgE should be repeated after the initial 6-8 weeks of corticosteroid therapy, then every 8-12 weeks for 1 year.[47] Any rise in serum IgE >100% over baseline suggests an exacerbation. If the total serum IgE level does not drop by >35% over 2 months of therapy, the patient may not be taking the corticosteroid as instructed, or another diagnosis should be considered, such as infection.[48]​ A chest x-ray or computed tomography scan of the chest should be repeated after 4-8 weeks of therapy to document clearing of infiltrates.[47]

Primary options

prednisolone: 0.5 mg/kg/day orally for 7-14 days, then taper gradually according to response, maximum 60 mg/day

Plus – antifungal therapy

Back
ACUTE
|
stage 3: exacerbation
Plus – 

antifungal therapy

Treatment recommended for ALL patients in selected patient group

The Infectious Disease Society of America recommends that first-line treatment of acute allergic bronchopulmonary aspergillosis (ABPA) should include a combination of a corticosteroid plus antifungal therapy.[26]

Azole antifungals (e.g., itraconazole, voriconazole, posaconazole) are effective against A fumigatus.

Itraconazole is used most commonly for the treatment of ABPA due to its better adverse-effect profile, tolerability, and because it is the most well studied. One RCT reported that prednisolone significantly increased the composite response rate, compared with itraconazole, in patients with ABPA (100% vs. 88%; P=0.007).[49] Similar results were found for both treatments for percent decline in IgE at 6 weeks and 3 months, number of patients with exacerbations at 1 and 2 years, time to exacerbation, and the improvement of lung function at 6 weeks.[49] However, adverse effects were significantly higher for patients treated with prednisolone.

Evidence suggests that voriconazole or posaconazole are reasonable second-line therapies for ABPA. One retrospective review of adult asthmatic patients who were refractory to or had developed adverse effects to itraconazole treatment with ABPA. Both voriconazole and posaconazole demonstrated similar results for clinical response at 3, 6, and 12 months, and reduction in total IgE at 9 and 12 months.[50]​ Treatment with voriconazole and posaconazole may also improve asthma control and reduce severity.[50]

Therapeutic drug monitoring is recommended with voriconazole in combination with corticosteroids. Marked adrenal suppression has been seen with concomitant use of systemic corticosteroids and azole antifungals; both agents can cause adrenal suppression in their own right due to metabolism through CYP450.[51][52]​​ In addition, azoles can increase the serum concentration of cystic fibrosis transmembrane conductance regulator modulators, which is important for drug monitoring in CF patients. 

If azole antifungals are unavailable or contraindicated, amphotericin-B deoxycholate and its lipid derivatives may be considered for initial therapy.[26]​ One systematic review concluded that amphotericin-B does not improve exacerbation-free status at 1 year, although some evidence suggested that amphotericin-B treatment delayed the time to first exacerbation compared with the control arm, this result was not statistically significant.[53]

Primary options

itraconazole: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release) twice daily on day 1, followed by 300 mg once daily

Tertiary options

amphotericin B deoxycholate: 1 to 1.5 mg/kg/day intravenously

OR

amphotericin B liposomal: 3-5 mg/kg/day intravenously

Plus – environmental control

Back
ACUTE
|
stage 3: exacerbation
Plus – 

environmental control

Treatment recommended for ALL patients in selected patient group

Patients should be counselled to avoid areas of possible exposure to Aspergillus fumigatus. Although ubiquitous in the environment, A fumigatus can be seen in particularly high quantities in dead and decaying organic matter such as compost piles.

The patient's home should be assessed for damp and water damage, which can encourage the growth of moulds of all types, including Aspergillus.[47][72]​ In practice, patients may be advised to keep indoor humidity below 50% as mould grows in humid environments. If mould is present in the home, professional remediation should be considered.

Plus – optimisation of management of cystic fibrosis, asthma and other comorbid conditions

Back
ACUTE
|
stage 3: exacerbation
Plus – 

optimisation of management of cystic fibrosis, asthma and other comorbid conditions

Treatment recommended for ALL patients in selected patient group

Treatment of underlying asthma should be reviewed and optimised using a stepwise approach and standard agents. See Asthma in adults

GORD treatment may benefit patients who have asthma, and GORD evaluation should be considered in patients who have poorly controlled asthma, especially with night-time symptoms. See Gastro-oesophageal reflux disease.​

Rhinitis or sinusitis symptoms or diagnosis should be evaluated in patients who have asthma, because the inter-relationship of the upper and lower airway suggests that therapy for the upper airway will improve asthma control. See Allergic rhinitis, Chronic rhinosinusitis without nasal polyps.

Treatment of underlying cystic fibrosis should be reviewed and optimised. This may involve the use of corticosteroids, long-acting beta-agonists, mucus-clearance agents, antibiotics, non-steroidal anti-inflammatory drugs, supplemental oxygen, and physiotherapy. See Cystic fibrosis.

stage 4: corticosteroid-dependent asthma

1st line – oral corticosteroid

Back
ACUTE
|
stage 4: corticosteroid-dependent asthma
1st line – 

oral corticosteroid

This occurs when the patient is unable to be weaned off oral corticosteroids and/or there is persistent elevation of serum IgE, along with obstructive and restrictive lung changes.

Treatment is daily oral corticosteroids, which may need to be given indefinitely.[20][47][75]​​

Multiple asthmatic exacerbations in an allergic bronchopulmonary aspergillosis patient suggest that corticosteroid therapy should be used, usually at a dose of ≥10 mg/day of prednisolone, although with the aim of using the minimal dose that will stabilise the patient.

The decision to gradually reduce the dose of corticosteroids should be made on an individual basis, depending on the clinical course.

Primary options

prednisolone: 10-40 mg orally once daily or on alternate days

Plus – antifungal therapy

Back
ACUTE
|
stage 4: corticosteroid-dependent asthma
Plus – 

antifungal therapy

Treatment recommended for ALL patients in selected patient group

Antifungal therapy is recommended to help patients wean off corticosteroids.

Azole antifungals (e.g., itraconazole, voriconazole, posaconazole) are effective against A fumigatus.

Itraconazole is used most commonly for the treatment of allergic bronchopulmonary aspergillosis (ABPA) due to its better adverse-effect profile, tolerability, and because it is the most well studied. One RCT reported that prednisolone significantly increased the composite response rate, compared with itraconazole, in patients with ABPA (100% vs. 88%; P=0.007).[49] Similar results were found for both treatments for percent decline in IgE at 6 weeks and 3 months, number of patients with exacerbations at 1 and 2 years, time to exacerbation, and the improvement of lung function at 6 weeks.[49] However, adverse effects were significantly higher for patients treated with prednisolone.

Evidence suggests that voriconazole or posaconazole are reasonable second-line therapies for ABPA. One retrospective review of adult asthmatic patients who were refractory to or had developed adverse effects to itraconazole treatment with ABPA. Both voriconazole and posaconazole demonstrated similar results for clinical response at 3, 6, and 12 months, and reduction in total IgE at 9 and 12 months.[50]​ Treatment with voriconazole and posaconazole may also improve asthma control and reduce severity.[50]

Therapeutic drug monitoring is recommended with voriconazole in combination with corticosteroids. Marked adrenal suppression has been seen with concomitant use of systemic corticosteroids and azole antifungals; both agents can cause adrenal suppression in their own right due to metabolism through CYP450.[51][52]​​ In addition, azoles can increase the serum concentration of cystic fibrosis transmembrane conductance regulator modulators, which is important for drug monitoring in CF patients. 

If azole antifungals are unavailable or contraindicated, amphotericin-B deoxycholate and its lipid derivatives may be considered for initial therapy.[26]​ One systematic review concluded that amphotericin-B does not improve exacerbation-free status at 1 year, although some evidence suggested that amphotericin-B treatment delayed the time to first exacerbation compared with the control arm, this result was not statistically significant.[53]

Primary options

itraconazole: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release) twice daily on day 1, followed by 300 mg once daily

Tertiary options

amphotericin B deoxycholate: 1 to 1.5 mg/kg/day intravenously

OR

amphotericin B liposomal: 3-5 mg/kg/day intravenously

Plus – environmental control

Back
ACUTE
|
stage 4: corticosteroid-dependent asthma
Plus – 

environmental control

Treatment recommended for ALL patients in selected patient group

Patients should be counselled to avoid areas of possible exposure to Aspergillus fumigatus. Although ubiquitous in the environment, A fumigatus can be seen in particularly high quantities in dead and decaying organic matter such as compost piles.

The patient's home should be assessed for damp and water damage, which can encourage the growth of moulds of all types, including Aspergillus.[47][72]​ In practice, patients may be advised to keep indoor humidity below 50% as mould grows in humid environments. If mould is present in the home, professional remediation should be considered.

Plus – optimisation of management of cystic fibrosis, asthma and other comorbid conditions

Back
ACUTE
|
stage 4: corticosteroid-dependent asthma
Plus – 

optimisation of management of cystic fibrosis, asthma and other comorbid conditions

Treatment recommended for ALL patients in selected patient group

Treatment of underlying asthma should be reviewed and optimised using a stepwise approach and standard agents. See  Asthma in adults.

GORD treatment may benefit patients who have asthma, and GORD evaluation should be considered in patients who have poorly controlled asthma, especially with night-time symptoms. See Gastro-oesophageal reflux disease.

Rhinitis or sinusitis symptoms or diagnosis should be evaluated in patients who have asthma, because the inter-relationship of the upper and lower airway suggests that therapy for the upper airway will improve asthma control. See Allergic rhinitis, Chronic rhinosinusitis without nasal polyps.

Treatment of underlying cystic fibrosis should be reviewed and optimised. This may involve the use of corticosteroids, long-acting beta-agonists, mucus-clearance agents, antibiotics, non-steroidal anti-inflammatory drugs, supplemental oxygen, and physiotherapy. See  Cystic fibrosis.

Consider – biological therapy

Back
ACUTE
|
stage 4: corticosteroid-dependent asthma
Consider – 

biological therapy

Additional treatment recommended for SOME patients in selected patient group

In practice, off-label use of biologics as a corticosteroid-sparing therapy may be used for patients with corticosteroid-dependent asthma who cannot taper off oral corticosteroids despite a course of antifungal therapy. Evidence from a retrospective chart review suggests that omalizumab, mepolizumab, dupilumab, or benralizumab may reduce the dose of, or eliminate the need for, corticosteroid treatment.[56]

Biological therapy may also be used in preference to antifungal therapy as a corticosteroid-sparing therapy for patients in whom antifungal treatment is contraindicated, such as those with liver disease, or those taking other treatments that interact with CYP450 inhibitors.[57][58]​​​​ 

Omalizumab, a monoclonal antibody directed against IgE that prevents IgE binding to receptors on effector cells, is used for patients with allergic asthma who have asthma exacerbations despite maximal standard therapy. Case reports of its use in allergic bronchopulmonary aspergillosis (ABPA) in patients with corticosteroid-dependent cystic fibrosis showed it to be a corticosteroid-sparing therapy with associated clinical improvements.[59][60][61]​​ Trials of omalizumab in patients with asthma and ABPA demonstrated reductions in exacerbations of asthma and oral corticosteroid requirements, but in one study it did not improve spirometry.[62][63]​​ However, there is a lack of evidence for the efficacy and safety of anti-IgE therapy for people with CF and APBA.[64]

The addition of mepolizumab, an interleukin (IL)-5 antagonist monoclonal antibody, at conventional doses for patients with severe asthma complicated by ABPA led to a significant decrease in peripheral eosinophil counts, an increase in FEV1, improvement in asthma control scores, and a significant reduction in exacerbations and oral corticosteroid dose.[65]​ In another small study of nine patients with ABPA, some of whom had failed treatment with antifungal therapy or omalizumab, all patients treated with an IL-5 antagonist had decreased exacerbations compared to the prior year, improved asthma-related quality of life, and reduced oral corticosteroid dose.[66]​ Reductions in IgE levels and mucus plugging have also been noted with the use of mepolizumab for treatment of ABPA.[67]

Evidence from one case study demonstrates that dupilumab, an IL-4 antagonist monoclonal antibody, successfully treated patients with ABPA, often those who have failed conventional therapies or other biologics.[68]​ A multi-centre randomised clinical trial testing the efficacy of dupilumab in ABPA has been completed and results are currently being analysed.[69]

Evidence from case series suggests that benralizumab, an IL-5 antagonist monoclonal antibody, successfully treats ABPA, and may be more effective than mepolizumab (another IL-5 antagonist) at clearing bronchial mucus plugs.[70][71]

Primary options

omalizumab: 150-375 mg subcutaneously every 2-4 weeks, adjust dose according to serum IgE levels and body weight, maximum 150 mg/injection site

OR

mepolizumab: 100 mg subcutaneously every 4 weeks

OR

dupilumab: 400-600 mg subcutaneously as a single dose on day 1, followed by 200-300 mg subcutaneously every 2 weeks

OR

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

stage 5: end-stage fibrosis

1st line – supportive care

Back
ACUTE
|
stage 5: end-stage fibrosis
1st line – 

supportive care

Stage 5 disease occurs when the patient is unable to be weaned off oral corticosteroids and there are obstructive and restrictive lung changes. Clinically, patients are dyspneic and appear cyanotic, with fibrotic, bullous, or cavitary lesions on chest imaging. Serum IgE may be normal. In practice, it is unlikely that end-stage fibrosis will respond to any immunomodulation. Patients may benefit from pulmonary rehabilitation, and oxygen supplementation as needed. A referral to a lung transplant centre should be considered.

Plus – environmental control

Back
ACUTE
|
stage 5: end-stage fibrosis
Plus – 

environmental control

Treatment recommended for ALL patients in selected patient group

Patients should be counselled to avoid areas of possible exposure to Aspergillus fumigatus. Although ubiquitous in the environment, A fumigatus can be seen in particularly high quantities in dead and decaying organic matter such as compost piles.

The patient's home should be assessed for damp and water damage, which can encourage the growth of moulds of all types, including Aspergillus.[47][72]​ In practice, patients may be advised to keep indoor humidity below 50% as mould grows in humid environments. If mould is present in the home, professional remediation should be considered.

Plus – optimisation of management of cystic fibrosis, asthma and other comorbid conditions

Back
ACUTE
|
stage 5: end-stage fibrosis
Plus – 

optimisation of management of cystic fibrosis, asthma and other comorbid conditions

Treatment recommended for ALL patients in selected patient group

Treatment of underlying asthma should be reviewed and optimised using a stepwise approach and standard agents. See Asthma in adults.

GORD treatment may benefit patients who have asthma, and GORD evaluation should be considered in patients who have poorly controlled asthma, especially with night-time symptoms. See Gastro-oesophageal reflux disease.

Rhinitis or sinusitis symptoms or diagnosis should be evaluated in patients who have asthma, because the inter-relationship of the upper and lower airway suggests that therapy for the upper airway will improve asthma control. See Allergic rhinitis, Chronic rhinosinusitis without nasal polyps.

Treatment of underlying cystic fibrosis should be reviewed and optimised. This may involve the use of corticosteroids, long-acting beta-agonists, mucus-clearance agents, antibiotics, non-steroidal anti-inflammatory drugs, supplemental oxygen, and physiotherapy. See Cystic fibrosis.

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Choose a patient group to see our recommendations

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

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