1. Aspergillus & ABPA

2. Disease spectrum
IPA Invasive pulmonary aspergillosis

3. ABPA

4. ABPA – pathophysiology
conidia of Aspergillus trapped in mucous and narrowed airways of asthmatics/CF  germinate to form hyphae  release of soluble/particulate antigens  airway inflammation  epithelial damage  Antigen diffuses into interstitium  inflammatory mediators released  influx of inflammatory cells esp. E & Ag presented to Th2 cells  IL-4, IL-5 & IL-13 cytokines synthesized and secreted  IgE synthesis  mast cell degranulation  tissue injury  bronchial obstruction, inflammation, mucous plugging  bronchiectasis  fibrosis  respiratory failure

6. Diagnostic algorithm

7. Clinical Presentation
Asymptomatic patient with or without pulmonary infiltrates OR
Poorly controlled asthmatic patient
(more common)
Low-grade fever
Wheezing
Bronchial hyperactivity
Haemoptysis
Weight loss & malaise
Productive cough (often w/ expectoration of brownish black sputum)
Severe uncontrolled asthma
 with/out central bronchiectasis
 pulmonary fibrosis
 pulmonary hypertension
 Type 2 respiratory failure

8. Physical Exam Normal Other findings include: Polyphonic wheezing
Clubbing (16%)
Coarse crackles (15%)
Sx of pulmonary HTN and/or respiratory failure

9. Differential Diagnosis of ABPA

10. Asthma vs. ABPA vs. AH

11. Immunological Findings
Cutaneous hypersensitivity
Intradermal test > Skin prick test
Type 1 immediate +ve &
Type 3 delayed +ve
positive in virtually all ABPA
40% of asthmatics without ABPA also +ve

12. Immunological Findings
Total IgE
Cutoff >1000 IU/mL
With Rx
Reduction of often > 35% = REMISSION
levels do NOT reach normal values
repeated measurements needed to determine ‘new baseline’
Doubling of baseline = relapse

13. Radiographic Features - CXR
Parenchymal infiltrates (generally of upper lobes)
Transient vs. fixed
Atelectasis due to mucous plugging
Findings consistent with 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

14. 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

15. Diagnosis of ABPA

16. Diagnostic algorithm

18. Diagnosis
6/8 criteria
If not confirmed i.e. less than full compliment of dx criteria FU with 6/52 IgE  if increasing or >1000 IU/ml  Rx
ABPA-S (mild) vs. APBA-CB (moderate) vs. ABPA-CB-ORF
Recurrent episodes of remissions and relapses

19. Staging of ABPA

20. Remission No established definition Reduction of often >35%
Usually, by end of 6-9 months with a significant fall in IgE, patient said to be in remission i.e. Stage II (Remission)
‘Complete remission’ if no exacerbation for next 03 months after stopping Rx
FU with IgE every 6 months for 1st year, then annually

21. 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) ?? Decrease fungal burden in airways

22. 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

24. Regime 1 Regime 2 Dose Calculated dose Duration 0.5 mg/kg/day mg/day
2/52
0.5 mg/kg/alternate days
mg/alternate days
6-8/52
Reduce by 5mg
Every 2/52
FU every 6/52 with CXR & IgE
Total duration of treatment 6 – 12 months
Regime 1
Dose
Calculated dose
Duration
0.75 mg/kg/day
mg/day
6/52
0.5 mg/kg/day
Reduce by 5mg
Every 6/52
FU every 6/52 with CXR & IgE
Total duration of treatment 6 – 12 months
Regime 2

25. Total IgE levels
Date
Description
Load
IU/ml

26. Tx - Itraconazole
Decreases antigenic stimulus for bronchial inflammation, possibly by decreasing specific Aspergillus IgG
Decreased 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, +/- once day x 16 wks
LFTs: Twice weekly for 3 months  Monthly

28. Miscellaneous

29. SAM
The presence of concomitant allergic fungal sinusitis (AFS) and allergic bronchopulmonary mycosis in the same patient represents an expression of the same process of fungal hypersensitivity in the upper and lower airways. SAM syndrome: an acronym for sinobronchial allergic mycosis

30. Diagnostic Criteria chronic sinusitis involving multiple sinuses
asthma
total serum IgE levels are usually elevated as well
immediate cutaneous reactivity to fungal allergens
peripheral eosinophilia
radiographic evidence of bronchiectasis.
variety of chest radiographic abnormalities may occur: ranging from mass lesions to diffuse pulmonary infiltrates and even normal findings on chest radiographs.