1. Allergic Bronchopulmonary Aspergillosis (ABPA)
CF cases are slightly different (eg, criteria for dx, lab values)

2. ABPA – Definition and Epidemiology
Hypersensitivity reaction d/t colonization of bronchi by Aspergillus  bronchial obstruction, inflammation, mucous plugging  bronchiectasis, fibrosis, resp failure
Occurs primarily in pts w/ asthma (prevalence = 1-2%) or CF (prevalence = 1-15%)
Most cases present in the 3rd to 4th decade
No gender predilection
Some pts have (+) family history of ABPA

3. Pathophyisology Incompletely understood
Genetic predisposition + inhalation of Aspergillus fumigatus spores (that later germinate into hyphae and release antigens) 
1) Airway barrier compromise (in part by dec’d mucociliary clearance, and action of proteolytic and mycotoxins)
2) Activation of innate lung immunity  Influx of inflammatory cells
3) Presentation of antigens to T cells  Activation of Th2 cells and inc’d production of Th2 cytokines (Il-4, -5, and -13)  Inc’d total and A fumigatus-specific IgE, mast cell degranulation, and eosinophilic response.
4) Also Type III (IgG and IgA) hypersensitivity reactions
“No apparent relation b/w intensity of exposure to airborne Aspergillus spores and rates of sensitization to the fungus as measured by skin testing”.

4. Pathology
Varies b/w different patients and w/in different lung ares w/in a pt
Typical Histology
Mucus, fibrin, Curschmann spirals, Charcot-Leyden crystals, inflammatory cells (primarily eosinophils).
Hyphae can often be seen in the bronchiectatic cavities
Other Possible Findings
Fungal growth in lung parenchyma
Non-caseating granulomas w/ eosinophils and multi-nucleated giant cells centered on airways
Invasive aspergillosis (rare)

5. Clinical Presentation
Common Sxs
Low-grade fever
Wheezing
Bronchial hyperactivity
Hemoptysis
Productive cough (often w/ expectoration of brownish black sputum)
Occasionally aSx’c and dx’d on routine screening (eg, 2/2 aSx’c consolidation).

6. Physical Exam Can be normal Other possible findings include:
Polyphonic wheezing
Clubbing (16%)
Coarse crackles (15%)
Sxs of pulmonary HTN and/or respiratory failure

7. Dx'c Criteria Major Criteria: (? 6 of 8 needed for dx) 2 Types
1) H/o asthma
2) Immediate skin test reactivity to Aspergillus antigens
3) Precipitating serum Abs to A. fumigatus
4) Serum total IgE > 1000 ng/mL (can be lower if on steroids)
5) Peripheral eosinophilia > /mm(3)
6) Infiltrates on CXR or HRCT
7) Central bronchiectasis on chest CT
8) Elev’d specific serum IgE and IgG to A. fumigatus
Other Common Findings -- Expectoration of mucous plugs. Aspergillus in sputum, late skin reactivity to Aspergillus Ag
2 Types
ABPA-CB (central bronchiectasis) -- 1, 2, 4, 7, 8
ABPA-S (seropositive) -- 1, 2, 3, 4 but NO accompanying central bronchiectasis
No one dx’c test. Criteria are controversial and continue to be modified d/t the lack of evidence on the # of criteria needed
Skin test -- Uses A fumigatus antigen. Test is read q 15 min x 1 hr and again at 6-8 hours. Interpretation
Type I ( 1 of the characteristic findings of ABPA) - (+) wheal and erythema after 1 min that reaches maximum intensity after min, and resolves w/in 1-2 hours. Indicates presence of A fumigatus specific IgE Abs
Type III (immune complex hypersensitivity) - Any amount of subcut edema after 6 hours.
Often do skin test first. If this is (-) as is intradermal reactivity to Aspergillus, ABPA is essentially excluded.
If skin prick is (+), check total serum IgE and precipitans to Aspergillus. If IgE < 1000 or if precipitans are (-), Aspergillus is excluded.

8. Radiographic Features - CXR
Parenchymal infiltrates (generally of upper lobes)
Atelectasis d/t mucous plugging
Findings c/w bronchiectasis
“Tram line” shadows d/t thickened non-dilated bronchial walls
“Parallel lines” d/t ectactic bronchi
Ring shadows d/t mucous filled bronchi or small abscesses
“Toothpaste shadows” d/t mucous plugging in 2nd to 4th order bronchi
“Gloved finger shadows” (branched tubular radiodensities, 2-3 cm long, 5-8 cm wide, extending from the hilum) d/t intrabronchial exudates w/ bronchial wall thickening

10. Ring shadows (long arrows) and tram lines (short arrow) seen on chest radiograph in an ABPA patient.

11. Radiographic Findings - HRCT
Widespread proximal cylindrical bronchiectasis (mostly of upper lobes)
Bronchial wall thickening
Mucous plugging
Atelectasis
Peripheral airspace consolidation
Ground-glass attenuation
Mosaic perfusion
Air trapping

12. Top R - Bilateral central bronchiectasis w/ centrilobular nodules & tree-in-bud opacities in L lung.
Top L - Bilateral central bronchiectasis w/ many mucus-filled bronchi.
Bottom L & R - High- attenuation mucoid impaction.

13. PFTs Not really used in dx’g ABPA but findings can show
Airflow obstruction
Mixed obstructive and restrictive pattern if bronchiectasis or fibrosis
Air trapping
Dec’d FEV1 and RV
(+) Bronchodilator response in < 50%

14. Stages of ABPA (not necessarily progressive)
Stage I = Acute flare
Infiltrates, markedly elev’d IgE
Stage II = Remisson
No infiltrates, off steroids > 6 mos, elev’d or NL IgE
Stage III = Recurrent exacerbations
Stage IV = Glucocorticoid-dependent asthma
Infiltrates present intermittently or not at all, elev’d or NL IgE
Stage V = Fibrotic (end stage) lung dz
Fibrotic, bullous, cavitary lung lesions, IgE may be normal

15. Tx - Goals
1) Early control of immunologic activity / inflammation to try to prevent progression to bronchiectasis and fibrosis
2) Monitoring for response and early detection of relapses
3) ?? Dec fungal burden in airways

16. Tx - Steroids
Doses vary depending on stage and prescriber preference. Higher dosages for longer durations may be more effective for tx’g flares.
Stages 1 & 3 – Prednisone mg/kg Qday x 14 days, then QOD x 6-8 wks, then taper by 5-10 mg q 2 weeks until d/c’d
Should see resolution of infiltrates and 35-50% dec in serum total IgE (measured q1-2 months during acute treatment)
Stage 2 – Steroids not needed. Monitor IgE q6 months x 1 year then q 1-2 years. Doubling of baseline IgE indicates relapse (stage 3)
Stage 4 – Steroid dependent. Aim for lowest possible dose
Stage 5 – Steroids not helpful
Steroid “prophylaxis” – Ca, Vit D, bisphosphonate
Need systemic form (inhaled form may help w/ underlying asthma but has no efficacy in ABPA)

17. Tx - Itraconazole
Dec’s antigenic stimulus for bronchial inflammation, possibly by dec;g specific Aspergillus IgG
Dec’d metabolism of steroids, so may be able to use lower dosages
16 week course + steroids  significant increased likelihood of clinical response (46 vs 19%)
200 TID x 3 days, then 200 BID x 16 wks, +/- Qday x 16 wks
Monthly LFTs

18. Resources
UpToDate – Allergic bronchopulmonary aspergillosis (Weller, PF)
Mason: Murray & Nadel's Textbook of Respiratory Medicine, 4th ed. Allergic Bronchopulmonary Aspergillosis, from MD Consult
Chest (135:3) - Argawal. Allergic Bronchopulmonary Aspergillosis.
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