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pulm.abpa.v1

Allergic Bronchopulmonary Aspergillosis (ABPA)

pulmonologychronicadult
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Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Confirm the ABPA scope: a predisposing condition (asthma OR CF) is OBLIGATORY — without asthma/CF this is not ABPA (consider chronic/invasive pulmonary aspergillosis, EGPA, eosinophilic pneumonia instead) (ISHAM-ABPA, Agarwal PMID 23889240)

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Advance rule
Set
Advance when

Predisposing asthma or CF confirmed; otherwise route to the appropriate non-ABPA engine

Patient inputs (16)

Adult ABPA pathway; biologic eligibility and azole TDM targets are age-aware

Eosinophil count must be interpreted steroid-naïve; prior OCS courses define glucocorticoid-dependent stage (ISHAM PMID 23889240)

Azoles are TERATOGENIC and contraindicated in pregnancy — drives steroid/omalizumab-only branch (azole label; ISHAM management PMID 23889240)

Azole CYP3A4 interactions (statins, DOACs, inhaled/systemic corticosteroid potentiation → iatrogenic Cushing/adrenal suppression) (Wark Cochrane PMID 15266440)

Predisposing condition is OBLIGATORY for ABPA — asthma vs CF changes thresholds and the CF-ABPA branch (ISHAM-ABPA PMID 23889240; Ashkenazi PMID 29950869)

OBLIGATORY diagnostic gate (>500, classically >1000 IU/mL) AND the principal treatment-response biomarker — 25–35% fall = response, ≥50% rise over baseline = exacerbation (Agarwal PMID 34503983 ~47.6% decline at response; PMID 23889240)

OBLIGATORY — A. fumigatus-specific IgE (or immediate-type skin test) elevation (ISHAM obligatory criterion PMID 23889240)

SUPPORTIVE radiology + staging — fleeting infiltrates, central bronchiectasis, high-attenuation mucus (HAM), mucoid impaction; defines serologic-ABPA vs ABPA-CB vs ABPA-CB-ORF (ISHAM PMID 23889240; Agarwal PMID 38154470)

A. fumigatus sputum growth (supportive, non-specific); distinguishes airway colonisation; Pseudomonas in established bronchiectasis (Agarwal PMID 23889240)

ISHAM/Patterson stage (remission vs exacerbation vs glucocorticoid-dependent vs end-stage) sets the prior for treatment selection (Agarwal PMID 23889240)

Differential — ANCA + multisystem + eosinophilia >1500 favours EGPA over ABPA (differential-as-data)

SUPPORTIVE — A. fumigatus-specific IgG / precipitins (ISHAM supportive criterion PMID 23889240)

SUPPORTIVE — peripheral eosinophilia >500/µL (steroid-naïve) (ISHAM supportive criterion PMID 23889240)

Mandatory therapeutic drug monitoring — itraconazole/voriconazole have erratic absorption + narrow therapeutic window; subtherapeutic troughs = treatment failure (Stevens NEJM 2000 PMID 10717010)

Lung-function decline tracks ABPA activity and bronchiectasis progression; secondary endpoint in ABPA RCTs (Agarwal PMID 26585431)

Baseline + serial liver enzymes before/on azole — itraconazole/voriconazole hepatotoxicity (Wark Cochrane PMID 15266440)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningmassive_hemoptysis_from_bronchiectasis
    Massive hemoptysis (>200 mL/24 h or hemodynamic/airway compromise) from ABPA central bronchiectasis (Agarwal PMID 38154470)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereazole_hepatotoxicity_or_subtherapeutic_tdm
    On azole: transaminitis (>3–5× ULN) or jaundice = HEPATOTOXICITY → STOP azole, reassess; OR subtherapeutic trough (itraconazole bioassay <1 µg/mL; voriconazole <1 µg/mL) = TREATMENT FAILURE RISK → adherence/absorption review, dose adjust, or switch azole/escalate to biologic (Stevens NEJM 2000 PMID 10717010; Wark Cochrane PMID 15266440)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereazole_in_pregnancy_contraindicated
    ABPA requiring treatment in a pregnant or potentially-pregnant patient — triazoles (itraconazole/voriconazole) are TERATOGENIC and CONTRAINDICATED (azole embryopathy) (azole label; ISHAM management PMID 23889240)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateisham_criteria_bundle
    ISHAM-ABPA diagnostic bundle (Bayesian criteria-as-data) — PREDISPOSING (asthma OR CF; OBLIGATORY) + 2 OBLIGATORY (A. fumigatus-specific IgE elevated OR positive type-I skin test; AND total IgE >1000 IU/mL [>500 acceptable if all other criteria met]) + ≥2 of 3 SUPPORTIVE (A. fumigatus-specific IgG/precipitins positive; radiology consistent with ABPA — fleeting infiltrates / central bronchiectasis / high-attenuation mucus / mucoid impaction; absolute eosinophils >500/µL steroid-naïve) → ABPA confirmed (Agarwal Clin Exp Allergy 2013 PMID 23889240; modern review PMID 38154470)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateabpa_staging_bayesian
    ISHAM/Patterson staging as data — Stage 0 asymptomatic; I acute (symptomatic + infiltrates + IgE↑); II response (clinical/radiologic improvement + total IgE fall 25–35%); III exacerbation (≥50% rise in total IgE over baseline ± new infiltrates); IV remission (sustained off-treatment); V glucocorticoid-dependent (cannot taper / recurs on taper); VI end-stage fibrotic. Radiologic subtype: serologic-ABPA (no bronchiectasis) vs ABPA-CB (central bronchiectasis) vs ABPA-CB-ORF (other radiologic findings/fibrosis) (Agarwal PMID 23889240)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatetotal_ige_response_action_chain
    Total-IgE → action chain: establish patient baseline at diagnosis; recheck q6–8 wk. Fall of 25–35% from baseline + clinical/radiologic improvement = RESPONSE → begin/continue steroid taper. Rise ≥50% over the patient baseline (± new infiltrates/symptoms) = SEROLOGIC EXACERBATION → re-induce/escalate. Do NOT chase total IgE to normal — it rarely normalises and over-treatment causes steroid toxicity (Agarwal PMID 34503983 — mean ~47.6% decline at composite response; PMID 23889240)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatedifferential_abpa_vs_mimics
    §5.5.2 differential-as-data — ABPA vs: severe eosinophilic asthma (Asp-sIgE/IgG negative, total IgE not markedly elevated, no central bronchiectasis); chronic eosinophilic pneumonia (peripheral "photographic-negative" infiltrates, no Aspergillus serology, BAL eosinophilia); EGPA (ANCA+ ~40%, eosinophils typically >1500/µL, multisystem incl. mono/polyneuritis, asthma + sinus); CF (sweat chloride/CFTR — CF-ABPA distinct branch, total IgE less reliable, Ashkenazi PMID 29950869); invasive/chronic pulmonary aspergillosis (immunocompromise, cavitation, aspergilloma, weight loss → id.invasive-aspergillosis.core.v1); other (non-ABPA) bronchiectasis (no Aspergillus serology, no IgE gate). Pivots with test characteristics: Asp-specific IgE + total IgE >1000 are the high-LR ABPA discriminators; ANCA + eos >1500 + multisystem favours EGPA; cavitation/aspergilloma favours CPA/IA (Agarwal PMID 23889240/38154470)
    Trigger could not be auto-evaluated — needs clinician judgement.

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RISK_STRATIFICATIONoptionalDrives risk stratification
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Recommended regimen

ABPA stage-directed therapy — OCS induction → azole steroid-sparing → biologic (ISHAM-ABPA; Agarwal)
axis: abpa_stage_directedstep 1 - Step 1 — Acute-stage / exacerbation: oral corticosteroid induction (medium-dose)
Selected step "Step 1 — Acute-stage / exacerbation: oral corticosteroid induction (medium-dose)" — Acute-stage ABPA (ISHAM Stage I) or exacerbation (Stage III) — symptomatic with infiltrates and/or ≥50% rise in total IgE over baseline (Agarwal PMID 23889240/26585431)
  • prednisolone
    first line
    systemic_corticosteroid
    0.5 mg/kg/day (medium-dose Agarwal protocol) • PO • once daily (max: medium-dose protocol — high-dose NOT superior)
    triggers: acute_stage_abpa, abpa_exacerbation
    TAPER (encoded here, NOT a taper_plan field): medium-dose Agarwal protocol — 0.5 mg/kg/day × 1–2 wk, then 0.5 mg/kg every other day × 8 wk, then taper by 5 mg every 2 wk over ~3–5 months total, guided by symptoms + total IgE. Agarwal Eur Respir J 2015 (PMID 26585431): medium-dose vs high-dose RCT — exacerbation at 1 yr 50% vs 40.9% (p=0.59), glucocorticoid-dependent at 2 yr 14.6% vs 11.4% (p=0.88); cumulative dose + adverse effects significantly LOWER with medium-dose → medium-dose as effective and safer. RxCUI 8638 RxNav-verified IN
    rxcui 8638

outpatient playbook — drug actions (4)

  1. 1. prednisolone
    rxcui 8638
    0.5 mg/kg/day (medium-dose Agarwal protocol) • PO • once daily then taper over ~3–5 months
    trigger: Acute-stage or exacerbation ABPA
    Medium-dose as effective and safer than high-dose (Agarwal RCT PMID 26585431)
  2. 2. itraconazole
    rxcui 28031
    200 mg BID (TDM-guided) • PO • BID with food + acid for absorption
    trigger: Glucocorticoid-dependent / steroid-sparing indicated
    Steroid-sparing; response 46% vs 19% placebo (Stevens NEJM 2000 PMID 10717010); mandatory TDM + LFTs
  3. 3. omalizumab
    rxcui 302379
    Per weight × baseline IgE table • SC • q2–4 weeks
    trigger: Glucocorticoid-dependent / azole-refractory or intolerant
    Biologic steroid-sparing in asthma-ABPA (Eraso PMID 33050821)
  4. 4. amphotericin B (nebulised)
    rxcui 732
    10 mg nebulised BID • inhaled • BID maintenance
    trigger: Recurrent ABPA exacerbations despite the above
    Exacerbation prevention 8.3% vs 66.7% at 1 yr (Ram pilot RCT PMID 26666774)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Poorly-controlled or steroid-dependent asthma — screen for ABPA (ISHAM-ABPA; Agarwal Clin Exp Allergy 2013 PMID 23889240); Cystic fibrosis with clinical/spirometric deterioration — CF-ABPA screen (ISHAM-ABPA; CF-ABPA distinct entity, Ashkenazi PMID 29950869); Expectoration of brownish/black mucus plugs (characteristic of ABPA mucoid impaction; Agarwal review PMID 38154470).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Allergic Bronchopulmonary Aspergillosis (ABPA)** (pulm.abpa.v1).
Phenotype framing: §5.5.2 differential-as-data — ABPA vs severe eosinophilic asthma (no Asp-sIgE/IgG, IgE not markedly ↑, no central bronchiectasis) vs chronic eosinophilic pneumonia (peripheral photographic-negative infiltrates, no Asp serology) vs EGPA (ANCA, eos >1500, multisystem/neuropathy) vs CF (sweat chloride/CFTR — CF-ABPA is a distinct branch) vs invasive/chronic pulmonary aspergillosis (immunocompromise/cavitation/aspergilloma) vs other bronchiectasis (no Asp serology, no IgE gate) — IgE/IgG/eosinophil/HRCT pivots with test characteristics (Agarwal PMID 23889240)
Scope: Confirm the ABPA scope: a predisposing condition (asthma OR CF) is OBLIGATORY — without asthma/CF this is not ABPA (consider chronic/invasive pulmonary aspergillosis, EGPA, eosinophilic pneumonia instead) (ISHAM-ABPA, Agarwal PMID 23889240)

No severity triggers fired against current inputs.

Plan

Regimen axis: **ABPA stage-directed therapy — OCS induction → azole steroid-sparing → biologic (ISHAM-ABPA; Agarwal)** — step "Step 1 — Acute-stage / exacerbation: oral corticosteroid induction (medium-dose)".
1. prednisolone 0.5 mg/kg/day (medium-dose Agarwal protocol) PO once daily (systemic_corticosteroid, first line) — TAPER (encoded here, NOT a taper_plan field): medium-dose Agarwal protocol — 0.5 mg/kg/day × 1–2 wk, then 0.5 mg/kg every other day × 8 wk, then taper by 5 mg every 2 wk over ~3–5 months total, guided by symptoms + total IgE. Agarwal Eur Respir J 2015 (PMID 26585431): medium-dose vs high-dose RCT — exacerbation at 1 yr 50% vs 40.9% (p=0.59), glucocorticoid-dependent at 2 yr 14.6% vs 11.4% (p=0.88); cumulative dose + adverse effects significantly LOWER with medium-dose → medium-dose as effective and safer. RxCUI 8638 RxNav-verified IN

Setting playbook (outpatient) — Confirm ABPA by the ISHAM criteria bundle, stage it, induce remission with medium-dose OCS, minimise steroid exposure with azole/biologic, and prevent bronchiectasis progression (Agarwal PMID 23889240; PMID 38154470)
2. prednisolone 0.5 mg/kg/day (medium-dose Agarwal protocol) PO once daily then taper over ~3–5 months — Acute-stage or exacerbation ABPA (Medium-dose as effective and safer than high-dose (Agarwal RCT PMID 26585431))
3. itraconazole 200 mg BID (TDM-guided) PO BID with food + acid for absorption — Glucocorticoid-dependent / steroid-sparing indicated (Steroid-sparing; response 46% vs 19% placebo (Stevens NEJM 2000 PMID 10717010); mandatory TDM + LFTs)
4. omalizumab Per weight × baseline IgE table SC q2–4 weeks — Glucocorticoid-dependent / azole-refractory or intolerant (Biologic steroid-sparing in asthma-ABPA (Eraso PMID 33050821))
5. amphotericin B (nebulised) 10 mg nebulised BID inhaled BID maintenance — Recurrent ABPA exacerbations despite the above (Exacerbation prevention 8.3% vs 66.7% at 1 yr (Ram pilot RCT PMID 26666774))

Non-pharmacologic actions:
- Airway-clearance technique + treat colonising organisms in ABPA-CB (Agarwal PMID 38154470)
- Environmental Aspergillus exposure reduction counselling
- Vaccination (influenza, pneumococcal, COVID) given chronic steroid/immunosuppression
- Severe-asthma / pulmonology referral for glucocorticoid-dependent disease (ATS/ERS severe asthma)

AVOID / contraindication checks:
- Azole_teratogenic_contraindicated_in_pregnancy_use_steroid_or_omalizumab (azole label; ISHAM management Agarwal PMID 23889240)
- Azole_cyp3a4_potentiates_inhaled_and_systemic_corticosteroid_iatrogenic_cushing_adrenal_suppression (Wark Cochrane PMID 15266440)
- Azole_cyp3a4_statin_interaction_avoid_simvastatin_lovastatin_dose_limit_atorvastatin (azole label)
- Azole_doac_interaction_increased_bleeding_risk_review_anticoagulant (azole label)
- Itraconazole_negative_inotrope_avoid_in_decompensated_heart_failure (itraconazole label)
- Azole_mandatory_TDM_trough_itraconazole_>=1ugml_voriconazole_1_to_5p5ugml_subtherapeutic_equals_failure (Stevens NEJM 2000 PMID 10717010)
- Azole_hepatotoxicity_baseline_and_serial_LFTs_stop_on_transaminitis_or_jaundice (Wark Cochrane PMID 15266440)
- Chronic_OCS_minimise_bone_glycaemia_adrenal_axis_screen_on_taper_medium_dose_preferred (Agarwal PMID 26585431)
- Cf_abpa_distinct_total_IgE_unreliable_monitor_omalizumab_benefit_not_demonstrated (Ashkenazi PMID 29950869)

Monitoring

Regimen monitoring:
- Total IgE — baseline then q6–8 wk: 25–35% fall = response (do NOT chase to normal); ≥50% rise over the patient baseline = serologic exacerbation (Agarwal PMID 34503983 ~47.6% decline at response; PMID 23889240)
- Azole trough TDM at steady state — itraconazole bioassay ≥1 µg/mL; voriconazole 1–5.5 µg/mL; subtherapeutic = treatment failure (Stevens NEJM 2000 PMID 10717010)
- LFTs — baseline, 1 month, then periodically on azole; stop azole on transaminitis/jaundice (Wark Cochrane PMID 15266440)
- HRCT chest — serial for central bronchiectasis / high-attenuation mucus / fibrosis progression (Agarwal PMID 23889240)
- Absolute eosinophils + spirometry (FEV1) to track ABPA activity and bronchiectasis decline (Agarwal PMID 26585431)
- OCS taper supervision — adrenal-axis awareness; medium-dose protocol preferred (cumulative dose + adverse effects lower vs high-dose, Agarwal PMID 26585431)
- Glucose + bone health on corticosteroid; counsel + monitor for steroid toxicity driving step-up to azole/biologic

Setting (outpatient) monitoring:
- Total IgE q6–8 wk — 25–35% fall = response; ≥50% rise over baseline = exacerbation (Agarwal PMID 34503983)
- Azole trough TDM + LFTs on azole therapy (Stevens NEJM 2000 PMID 10717010; Wark Cochrane PMID 15266440)
- Serial HRCT for bronchiectasis/fibrosis progression (Agarwal PMID 23889240)
- Spirometry + eosinophils at review

Follow-up plan: Relapse surveillance (clinical + total-IgE + radiology); complete the corticosteroid taper; long-term bronchiectasis care (airway clearance, exacerbation plan, anti-pseudomonal if colonised); biologic step-down only in sustained remission; vaccination; environmental Aspergillus exposure counselling (Agarwal PMID 38154470; PMID 23889240)
- Close-out criterion: Relapse plan + taper completion + long-term bronchiectasis care documented

Monitoring phase: Total IgE trend (baseline then q6–8 wk: 25–35% fall = response, ≥50% rise over the patient baseline = serologic exacerbation — do NOT chase IgE to normal — Agarwal PMID 34503983 ~47.6% decline at response); azole trough TDM + LFTs on therapy; serial HRCT for bronchiectasis progression; eosinophils + spirometry (Wark Cochrane PMID 15266440; Agarwal PMID 23889240)

Disposition

Current setting: outpatient — Confirm ABPA by the ISHAM criteria bundle, stage it, induce remission with medium-dose OCS, minimise steroid exposure with azole/biologic, and prevent bronchiectasis progression (Agarwal PMID 23889240; PMID 38154470)

Disposition criteria:
- Continue outpatient management if responding (IgE falling, symptoms/imaging improving)
- Refer to pulmonology/severe-asthma or CF clinic for glucocorticoid-dependent / end-stage disease

Escalation triggers (move to higher acuity):
- Massive hemoptysis from bronchiectasis → inpatient/IR (registry workup.hemoptysis)
- Severe ABPA exacerbation with respiratory compromise → admit
- Azole hepatotoxicity (transaminitis/jaundice) → stop azole, admit if severe (Wark Cochrane PMID 15266440)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Massive hemoptysis (>200 mL/24 h or hemodynamic/airway compromise) from ABPA central bronchiectasis (Agarwal PMID 38154470)
- [SEVERE] On azole: transaminitis (>3–5× ULN) or jaundice = HEPATOTOXICITY → STOP azole, reassess; OR subtherapeutic trough (itraconazole bioassay <1 µg/mL; voriconazole <1 µg/mL) = TREATMENT FAILURE RISK → adherence/absorption review, dose adjust, or switch azole/escalate to biologic (Stevens NEJM 2000 PMID 10717010; Wark Cochrane PMID 15266440)
- [SEVERE] ABPA requiring treatment in a pregnant or potentially-pregnant patient — triazoles (itraconazole/voriconazole) are TERATOGENIC and CONTRAINDICATED (azole embryopathy) (azole label; ISHAM management PMID 23889240)

Citations

- ISHAM-ABPA working group diagnostic + staging criteria (Agarwal, Clin Exp Allergy 2013) + 2023 modern review (Agarwal/Muthu/Sehgal, Semin Respir Crit Care Med) — ABPA RCT evidence base (Agarwal PGIMER program) + Cochrane azoles [PMID:23889240](https://pubmed.ncbi.nlm.nih.gov/23889240/)
- Cited evidence (PMID 38154470) [PMID:38154470](https://pubmed.ncbi.nlm.nih.gov/38154470/)
- Cited evidence (PMID 37062874) [PMID:37062874](https://pubmed.ncbi.nlm.nih.gov/37062874/)
- Cited evidence (PMID 26585431) [PMID:26585431](https://pubmed.ncbi.nlm.nih.gov/26585431/)
- Cited evidence (PMID 10717010) [PMID:10717010](https://pubmed.ncbi.nlm.nih.gov/10717010/)

Last reconciled with current guidelines: 2026-05-16.
References
  • ISHAM-ABPA working group diagnostic + staging criteria (Agarwal, Clin Exp Allergy 2013) + 2023 modern review (Agarwal/Muthu/Sehgal, Semin Respir Crit Care Med) — ABPA RCT evidence base (Agarwal PGIMER program) + Cochrane azoles — PMID:23889240
  • Cited evidence (PMID 38154470) — PMID:38154470
  • Cited evidence (PMID 37062874) — PMID:37062874
  • Cited evidence (PMID 26585431) — PMID:26585431
  • Cited evidence (PMID 10717010) — PMID:10717010