Allergic bronchopulmonary aspergillosis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Airway persistence of Aspergillus antigens can provoke a strong type 2 inflammatory response, thick mucus, recurrent obstruction and bronchiectatic damage. ABPA should be considered when asthma becomes unexpectedly difficult to control, radiographic shadows migrate, brown plugs are expectorated, or a person with cystic fibrosis or bronchiectasis deteriorates without a sufficient bacterial explanation. Similar features may occur in other fungal-allergic airway disease, so the label should follow structured assessment.

Diagnosis is syndromic. The 2024 revised ISHAM criteria allow a predisposing condition—such as asthma, cystic fibrosis, bronchiectasis or COPD—or a compatible clinico-radiological presentation. Essential components are sensitisation to A. fumigatus and raised total IgE, followed by at least two supportive components: raised A. fumigatus-specific IgG, current or historical eosinophilia, or imaging consistent with ABPA. Results near a threshold deserve clinical interpretation, especially after systemic corticosteroids have suppressed IgE or eosinophils.

Treatment has two objectives: suppress damaging inflammation and reduce airway fungal burden while preserving airway clearance and background disease control. Response is judged through symptoms, exacerbations, imaging and total-IgE trajectory. Relapse, treatment-dependent disease and fixed fibrotic damage are different states; each needs a new assessment rather than automatic repetition of the last prescription.

Key points

ABPA is an exaggerated immune response to airway colonisation by Aspergillus, most often in asthma or cystic fibrosis; it is distinct from simple sensitisation and invasive aspergillosis.
The revised ISHAM framework requires compatible disease or presentation, Aspergillus fumigatus sensitisation and raised total IgE, with additional immunological or imaging evidence rather than one positive test alone.
Current diagnostic thresholds include A. fumigatus-specific IgE at least 0.35 kUA/L and total IgE usually at least 500 IU/mL, interpreted with steroid exposure, age and the clinical picture.
Central bronchiectasis, mucus plugging and transient pulmonary opacities support ABPA; high-attenuation mucus on CT is especially persuasive and can establish the diagnosis despite an otherwise incomplete criterion set.
A sputum culture growing Aspergillus neither proves allergic disease nor predicts activity, while a negative culture does not exclude the immunological syndrome.
Total IgE is useful as an individual trend: establish a post-treatment baseline and investigate a substantial rise alongside symptoms and imaging rather than trying to normalise it completely.
Acute symptomatic ABPA is commonly treated with a planned systemic corticosteroid course or an oral azole; recurrent disease may justify combination or steroid-sparing treatment under a specialist.
Azole treatment needs formulation-specific counselling, interaction screening, liver monitoring and usually therapeutic drug monitoring; prescribing it casually can cause toxicity or ineffective exposure.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Susceptible airways

Asthma and cystic fibrosis provide mucus-rich, structurally abnormal airways in which Aspergillus can persist without necessarily invading tissue.

Fungal sensitisation

Repeated exposure to airborne Aspergillus antigens drives exaggerated immediate and type 2 immune responses in a sensitised host.

Host predisposition

Atopy, impaired mucus clearance and selected immune or genetic factors increase risk, while fungal sensitisation alone remains more common than the full syndrome.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Airway colonisation
Inhaled spores germinate within retained bronchial mucus but usually remain confined to the airway lumen in immunocompetent patients.
2
Hypersensitivity inflammation
Fungal antigens trigger IgE-mediated and eosinophilic inflammation, causing bronchospasm, airway-wall oedema and systemic immunological activity, which helps produce the characteristic physiological impairment.
3
Mucoid impaction
Thick mucus, fungal material and inflammatory cells obstruct bronchi, producing transient opacities, segmental collapse and expectoration of plugs.
4
Structural damage
Repeated inflammation and obstruction remodel proximal bronchi, leading to central bronchiectasis, fixed airflow limitation and recurrent infection.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Difficult asthma pattern

Repeated steroid-requiring asthma attacks, persistent wheeze, falling lung function or poor control despite credible inhaler technique should prompt sensitisation testing, especially when imaging abnormalities are recurrent or fleeting.

Mucus plugging syndromeRed flag

Expectoration of tenacious brownish plugs, segmental collapse or finger-in-glove impaction suggests obstructing allergic mucin. Extensive plugging with hypoxaemia requires urgent airway and imaging assessment.

Structural lung context

A person with cystic fibrosis or established bronchiectasis may have ABPA superimposed on chronic sputum and infection. Look for a change in symptoms, new infiltrates and a coordinated immunological rise rather than attributing every decline to ABPA.

Radiographic migration

Transient consolidation, atelectasis or nodular branching shadows that clear and recur elsewhere are characteristic clues. Fixed advanced bronchiectasis or fibrosis may remain after immunological activity has settled.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
A. fumigatus-specific IgEFirst step
Why
Demonstrate fungal sensitisation as an essential diagnostic component.
Interpretation and limitations
A value at or above 0.35 kUA/L meets the revised ISHAM sensitisation threshold, but sensitisation alone is common in asthma and does not diagnose ABPA. A skin test may be used where specific IgE is unavailable.
02
Total serum IgE
Why
Support diagnosis and create an individual activity marker for follow-up.
Interpretation and limitations
A level at least 500 IU/mL usually fulfils the essential threshold. A lower value can occur after corticosteroids or in selected presentations, so a specialist may still diagnose ABPA when other evidence is compelling. Repeat after treatment to define a new baseline.
03
A. fumigatus-specific IgG
Why
Provide supportive immunological evidence of relevant exposure and response.
Interpretation and limitations
Use an assay-specific population reference range; a positive result is one supportive component, not proof by itself. Precipitin methods and modern immunoassays are not directly interchangeable.
04
Peripheral eosinophil count
Why
Identify type 2 inflammation and contribute a supportive criterion.
Interpretation and limitations
A current or historical count of at least 0.5 × 10^9/L supports ABPA. Normal eosinophils after oral corticosteroids, during acute illness or in advanced disease do not safely rule it out.
05
Thin-section chest CT
Why
Identify mucus, bronchiectasis and alternative pulmonary pathology.
Interpretation and limitations
Central or multilobar bronchiectasis and mucus impaction are supportive. Mucus denser than paraspinal skeletal muscle—high-attenuation mucus—is highly specific; cavitation or a fungal ball demands assessment for another aspergillus syndrome.
06
Sputum microbiology
Why
Find concurrent bacterial, mycobacterial or fungal organisms before immunosuppression.
Interpretation and limitations
Aspergillus isolation supports airway presence but is neither required nor sufficient for ABPA. Obtain routine and, when appropriate, mycobacterial cultures because infection can mimic relapse and influences steroid or biologic decisions.
07
Spirometry and baseline safety tests
Why
Measure airway impact and prepare for corticosteroid or azole treatment.
Interpretation and limitations
Record airflow obstruction and compare with the person's previous best. Before an azole, review liver tests, interacting medicines and cardiac history; the specialist service determines ECG, pregnancy and drug-level requirements.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Severe eosinophilic asthma

Eosinophilia and poor control overlap, but the combination of fungal sensitisation, markedly increased total IgE and compatible imaging supports ABPA.

Aspergillus sensitisation

Positive fungal-specific allergy tests without the broader immunological and radiological syndrome indicate sensitisation rather than ABPA.

Chronic pulmonary aspergillosis

Progressive cavities, fungal balls and systemic symptoms in structurally damaged lung suggest chronic infection rather than primarily allergic airway disease.

Eosinophilic granulomatosis with polyangiitis

Neuropathy, purpura, renal disease or other systemic vasculitic features distinguish eosinophilic vasculitis from lung-limited allergic disease.

Non-fungal bronchiectasis exacerbation

Purulent sputum and bacterial growth without rising allergic markers or new mucus impaction may represent ordinary infective deterioration.

Additional chapter-specific clues

Dangerous alternativeRed flag

Fever, pleuritic pain, cavitation, haemoptysis, neutropenia or major immunosuppression broadens the differential to bacterial pneumonia, chronic pulmonary aspergillosis or invasive fungal infection and should accelerate specialist review.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnoseAssemble concordant evidenceFirst stepUncontrolled asthma, unexplained mucus plugging or deterioration in cystic fibrosis or bronchiectasis raises suspicion of ABPA.

1Request A. fumigatus-specific IgE and total IgE, then add eosinophils, fungus-specific IgG and thin-section CT when sensitisation and clinical features make ABPA plausible.
2Apply current ISHAM criteria explicitly, recording whether each essential and supportive component is met and noting recent systemic steroid exposure that could suppress results.
3Exclude bacterial infection and other aspergillus syndromes, then agree the diagnosis and baseline activity measures with respiratory, CF or bronchiectasis specialists before starting prolonged treatment.

02TreatControl an acute episodeNewly diagnosed or relapsing ABPA is symptomatic, radiologically active or causing a meaningful functional decline.

1Stabilise severe airflow obstruction, restore airway clearance around plugs and address concurrent infection; do not use antifungal treatment as a substitute for emergency asthma care.
2Choose a time-limited oral corticosteroid or azole strategy according to severity, prior toxicity, recurrence, comorbidity and specialist guidance; document the intended duration and response checkpoint.
3Check symptoms, spirometry, imaging where abnormal and total IgE after initial therapy, then taper or stop according to the agreed plan rather than maintaining unreviewed treatment.

03ReassessSeparate relapse from mimicSymptoms recur, IgE rises, steroid reduction fails or repeated treatment is being considered.

1Compare total IgE with the patient's stable post-treatment value and look for new symptoms or imaging change; an isolated fluctuation is insufficient to declare relapse.
2Re-culture sputum, review adherence and airway clearance, and investigate asthma, bacterial infection, NTM, fixed bronchiectatic damage or another aspergillus phenotype as competing explanations.
3Refer treatment-dependent or repeatedly relapsing disease for specialist azole, combination or biologic consideration with toxicity prevention and a defined steroid-sparing objective.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Suppresses allergic airway inflammation in a newly diagnosed episode or clinically confirmed relapse and can relieve mucus-associated obstruction.

Prednisolone for active ABPA

Use a respiratory-specialist, time-limited regimen with a planned taper; the starting dose, duration and reduction schedule must reflect severity, comorbidity and the current local ABPA protocol.

Confirm activity before repeating a course. Assess glucose, blood pressure, infection risk, mood, bone and gastrointestinal risks, cumulative exposure and adrenal suppression; provide steroid safety advice and prophylaxis where indicated.

Reduces airway fungal burden and may be used as an alternative in selected acute disease or to reduce corticosteroid dependence in recurrent ABPA.

Itraconazole as antifungal or steroid-sparing treatment

Dose and formulation must follow the specialist ABPA protocol and product information, with therapeutic drug monitoring when indicated; capsules and oral solution have different administration and absorption requirements.

Check liver function and the full medicines list for potent CYP3A and P-glycoprotein interactions. Consider negative inotropy, neuropathy and gastrointestinal effects; poor absorption or subtherapeutic levels can mimic non-response.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Progressive bronchiectasis

Repeated mucus obstruction and inflammation permanently dilate bronchi, establishing impaired clearance and a cycle of bacterial infection.

Fixed airflow obstruction

Chronic airway remodelling can reduce reversibility and leave persistent breathlessness despite control of current allergic activity.

Recurrent lobar collapse

Large mucus plugs can occlude segmental or lobar bronchi, producing atelectasis, infection and acute worsening of gas exchange.

Treatment toxicity

Repeated systemic corticosteroids cause metabolic, skeletal and infectious harm, while antifungal medicines introduce hepatic effects and interactions.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record a multidimensional baseline: symptoms, recent exacerbations, spirometry, radiographic abnormality, total IgE, eosinophils and current oral-steroid exposure.
Reassess after initial treatment using clinical improvement plus IgE trajectory and targeted imaging; complete normalisation of total IgE is neither expected nor required.
Once stable, retain the lowest post-treatment total IgE as the comparator and investigate a substantial rise only in conjunction with symptoms, function or new radiographic change.
During itraconazole treatment, follow liver biochemistry, interactions, adverse effects and drug exposure according to specialist and laboratory protocol.
For recurrent disease, audit cumulative corticosteroid toxicity, bone protection, vaccination, adrenal-risk counselling and whether a genuinely steroid-sparing plan is working.
Continue surveillance of the underlying asthma, cystic fibrosis or bronchiectasis because structural airway care remains necessary even when ABPA is immunologically quiet.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Sensitisation is the gateway

A. fumigatus-specific IgE is an essential starting point, but many sensitised people never develop ABPA; additional immune and radiological evidence prevents overdiagnosis.

High attenuation matters

High-attenuation mucus is more specific than ordinary mucus plugging and can secure the diagnosis in an otherwise compatible case that falls short on another criterion.

IgE is personal

The useful comparator is the individual's stable value after treatment, not the laboratory upper limit; persistent elevation does not automatically mean persistent active disease.

Steroids blur the evidence

Recent systemic corticosteroids can reduce eosinophils and total IgE, so record exposure and recover historical results before dismissing a strongly suggestive presentation.

Not every shadow is allergy

People with damaged airways commonly develop bacterial consolidation, NTM disease or chronic aspergillus infection, each of which may worsen if reflexively treated as ABPA relapse.

11Common pitfallsFrequent interpretation and management errors.

01
Calling a positive Aspergillus sputum culture ABPA without demonstrating sensitisation and the wider diagnostic pattern.
02
Excluding the diagnosis because eosinophils are normal after systemic corticosteroid treatment.
03
Restarting prednisolone for an isolated total-IgE rise without checking symptoms, imaging and infection.
04
Prescribing itraconazole without reconciling interactions, formulation instructions, liver monitoring or drug-level arrangements.
05
Treating chronic fixed bronchiectasis as ongoing allergic activity and allowing cumulative steroid harm to grow.
06
Assuming ABPA is invasive aspergillosis, or overlooking invasive disease in a genuinely immunocompromised patient.