ABPA is a complex immunological lung disorder caused by hypersensitivity to Aspergillus fumigatus antigens in patients with asthma or cystic fibrosis. It presents as poorly controlled asthma, bronchiectasis, or recurrent lung infiltrates. Diagnosis requires elevated total IgE levels, positive skin test or specific IgE to A. fumigatus, and meeting two of three criteria including precipitating antibodies, chest imaging findings, or eosinophil count. Treatment involves oral steroids and long-term antifungal therapy to reduce IgE levels and control symptoms. The disease has a relapsing course and complications include worsening asthma and permanent lung damage if not treated early.

1. ABPA(Allergic Bronchopulmonary
Aspergillosis)
DR. NEELU CHUGH
PGY2 – PULMONARY MEDICINE
GGS MEDICAL COLLEGE HOSPITAL
FARIDKOT

2. INTRODUCTION
• ABPA is a complex immunological pulmonary
disorder caused by hypersensitivity to antigenic
products released by Aspergillus fumigatus
colonizing the tracheobronchial tree of patients
with Bronchial Asthma and Cystic Fibrosis (CF),
with resultant systemic immune activation.
• Mainly Presents as
a) Chronic Asthma/poorly controlled asthma
b) Bronchiectasis
c) Pulmonary Infiltrates(Recurrent)

3. Aspergillus species

4. Name comes from aspergillum of catholic ritual.
There are appx. 250 species of Aspergillus fumigatus but
only a few are known to be pathogenic for humans. Most
common are A. fumigatus, A. niger and A. flavus. They are
found in organic debris, dust, rotted leaves, indoor like
basement, beddings, mats, house dust, curtains.
Accounts for 0.1% - 22% of total sampled air
spores(worldwide).

5. CHARACTERS
• Filamentous, septate hyphae, appx. 3-7 µm wide
with Y shaped branching in tissue preparations.
• Thermotolerant – can grow at 37Ċ.
• Culture – Sabouraud’s agar medium.
• Spores – size appx. 2-3.5µm, grow into hyphae,
dispersed with wind.
• Swollen conidiophores
• Produce unknown substances that inhibit
phagocytosis and macrophages migration.

6. The Clinical, radiological and histological
manifestations of bronchopulmonary aspergillosis
are due to complex of interplay between following
factors:
1.Dose/numbers of spores inhaled
2.Virulence of the organisms
3.Host immunity
ABPM ( ABP Mycosis) is an ABPA like syndrome
caused numerous fungi other than A. fumigatus.

8. EPIDEMIOLOGY
• Prevalence varies from country to country. Higher in
Indian studies than outside.
• USA – Prevalence is 1-2% in Br. Asthma and 2-12% in CF.
• India – 5% (1.38 million people in 27.7 million asthmatics).
• India – a) In severe acute asthma in ICU, the prevalence of
AS(Aspergillus sensitization) and ABPA – 51% & 39% resp.
b)Br Asthma in OPD patients it is 39% and 21% in AS and
ABPA.

9. Pathogenesis

10. PATHOLOGY

11. Bronchiectasis is proximal ie. Involvement of segmental and
sub segmental bronchi with sparing of distal bronchi is
typical of ABPA.
Eosinophilic bronchitis, bronchocentric granulomatosis,
pattern similar to BOOP.
Recurrent to transient parenchymal opacities are generally
the result of eosinophillic pneumonia.
Host response limits the growth of fungi and severe tissue
destruction.
ABPA Bronchiectasis  Fungal hyphae Aspergilloma.

12. CLINICAL FEATURES

14. Laboratory Findings
• Aspergillus skin Test
• Total S. IgE levels
• Serum IgE specific to A. fumigatus
• Radiological Inv. – CXR, HRCT
• Serum precipitins(IgG Antibodies) – ELISA, FEIA, ImmunoCap.
• Peripheral Eosinophilia
• Sputum cultures for A. fumigatus
• PFTs
• Role of specific Aspergillus antigens
• Recent developments – Serum GM (galactomannan), TARC (Thymus
and activation regulated chemokine), CCL17 (chemoattractant to
Th2), Blood eosinophil CD203c (In CF) by FACS(fluorescence
activated cell sorting).

15. 1.Skin test: Two types SPT (Skin Prick Test) and Intradermal test. Ist
SPT if its neg then go for Intradermal. But Intradermal has more
sensitivity. Positive reaction is wheal and erythema within 1min., max
in 10-20 min., resolves within 1-2hr.
Dose: 0.2ml of 100PNU (Protein Nitrogen Unit)
Sensitivity 88-92%.
2. IgE: Pt. not taking steroids and having normal IgE means no ABPA
now. IgE >1000 IU/L is cut off taken . 25% Decrease in IgE levels at 8
weeks is taken as response. Always make new base line value of IgE
during remissions. Increase in IgE by 50% along with
clinical/radiological worsening means exacerbation.
3. Specific IgE: measured by FEIA( Fluorescent enzyme linked assay).
Levels are twice than AS. Cut off >0.35kUA/L is imp. Preferred test for
screening of ABPA in asthma but gold std.
Sensitivity is 100%.

16. 4. RADIOLOGICAL:
A) CXR: Fleeting- Gloved fingers opacities, consolidation like
opacities, tram line/parallel line, tooth paste like, ring
shadows, fibrosis, collapse of up. Lobe esp., cavitation,
bronchiectasis, perihilar infiltrates, nodules, pleural
effusion and pleural thickening.
B) HRCT: Replaced bronchography. Shows central
bronchiectasis (40% it may be up to periphery) of >= 3
lobes with peripheral tapering of bronchi, mucoid
impaction, centrilobular nodules and tree in bud
appearance. CB has sensitivity of 37% only so removed
from ISHAM Criteria. HAM( Hyper attenuated Mucus)
100% specific for ABPA bronchiectasis- marks severe
disease and high risk of recurrence.
C) MRI – pregnancy and children.

17. 5. Serum precipitins : IgG antibodies, not specific but
supports the diagnosis. Increasing titres marks the
progression to CPA.
6. Peripheral Eosniphilia: >500cells/µl in 75% of cases,
>1000cells/µl in 40% of cases.
7. Sputum Culture: supportive, Positive in 39%-60% cases.
Not routinely required, done to see susceptibility to azoles.
So better to get before you start azoles.
8. PFTs: not diagnostic, only for monitoring of asthma.
Shows obstructive pattern with decrease diffusion capacity.
9. Role of specific Aspergillus antigens: rAsp f4 and f6 are
specific markers for ABPA, rAsp f1 abd f3 for AS.
10. Recent developments:

19. Diagnosis and Diagnostic Criteria
• Rosenberg Patterson criteria – 6 criteria.
• IgE levels, AEC, Specific IgE levels varies a lot but
studies have found 100% specificity (but sensitivity
is 70%) at 
• IgE = 2347IU/ml, AEC = 507cells/µL, Specific IgE=
1.91 kUA/L.

21. Conventional diagnostic criteria for ABPA
(Rosenberg-Patterson Criteria)
Primary/Major
1. Episodic bronchial obstruction (asthma)
2. Peripheral blood eosinophilia
3. Immediate skin reactivity to Aspergillus antigen
4. Elevated serum precipitins against As. Antigens
5. Elevated serum IgE concentrations
6. Elevated specific IgG/E to A. fumigatus
7. Fleeting pulmonary infiltrates (transient or fixed)
8. Central bronchiectasis

22. Secondary/Minor
1. Aspergillus fumigatus in sputum (by repeated
culture or microscopic examination)
2. History of expectoration of brown plugs or flecks
3. Delayed skin reactivity to Aspergillus fumigatus
antigen.

23. Why need for a new criteria
• Due to lack of gold standard the criteria could not
be validated.
• Cut off values for different serological tests was not
defined.
• It imparted same importance to all of 7 features
whereas subsequent research has shown few of
them are clinically more relevant than others.

24. New diagnostic criteria
(ISHAM-ABPA working Group Criteria)
Predisposing conditions
• Bronchial asthma, cystic fibrosis
Obligatory criteria (both should be present)
• Type I Aspergillus skin test positive (immediate
cutaneous hypersensitivity to Aspergillus antigen) or
elevated IgE levels against Aspergillus fumigatus
• Elevated total IgE levels (> 1000 IU/mL)
Other criteria (at least two of three)
• Presence of precipitating or IgG antibodies against A.
fumigatus in serum
• Radiographic pulmonary opacities consistent with
ABPA
• Total eosinophil count > 500 cells/lL in steroid naive
patients.

30. • The sensitivity and specificity of different
tests were as following:
1. Aspergillus skin test positivity - 94.7% & 79.7%.
2. S.IgE >1000 IU/ml - 97.1% & 37.7%.
3. A.fumigatus specific IgE level >0.35kUA/L - 100% &
69.3%.
4. Eosinophil count >1000cells/cc - 29.5% & 93.1%.
5. Bronchiectasis - 91.9% & 80.9%.
6. HAM - 39.7% & 100%.

31. Natural History and Staging
• It is characterized by recurrent episodes of
remissions and relapses. Most often ABPA is non
acute, very rarely acute, that lingers on for years
before the diagnosis is made.
• For better understanding we need to know clinical
and radiological staging of ABPA.

33. Radiological staging
• Greenberger et al. proposed ABPA-S as the earliest
stage of ABPA with less severe immunological
findings compared to ABPA –CB. However in their
study, only A. fumigatus-specific IgG levels were
higher in ABPA-CB, while the other immunological
parameters (total and A. fumigatus specific IgE) were
similar in the two groups.
• Thereafter, Kumar et al. classified ABPA into three
groups namely ABPA-S, ABPA-CB and ABPA-CB with
other radiological findings (ABPA-CBORF) and they
propose ABPA CB ORF being the severe most form of
the disease.

36. Treatment regimens
1. Oral glucocorticoids : INDICATIONS:
ABPA with mucoid impaction
ABPA with significant deterioration of lung function attributed
to worsening asthma or ABPA (and not intercurrent infection)
would require treatment with glucocorticoids.
• Regimen 1
Prednisolone 0.5 mg/kg/day for one to two weeks, then on
alternate days for six to eight weeks. Then taper by 5–10 mg
every 2 weeks and discontinue.
• Regimen 2
Prednisolone, 0.75 mg/kg for 6 weeks, 0.5 mg/kg for 6 weeks,
then tapered by 5 mg every 6 weeks to continue for a total
duration of at least 6–12 months

37. Aim of therapy is to decrease IgE levels 25-50% by 6wks –
3months. In remission check IgE every 3-6 months for 1year
and then yearly. Remission can be sustained by low dose
steroids, azoles, neb. Amphotericin B, monthly methylpred
pulses. Recurrent relapses are common in HAM, Extensive
bronchiectasis, Aspergilloma.
In those with mucoid impaction and proximal collapse,
assessment should be made at 3
weeks and if the collapse has not resolved, therapeutic
bronchoscopy should be performed.
Response is also assessed by decrease in CSTs dose by 50%,
Increase in exercise tolerance by 25%, PFTs improved by
25%,

38. Higher dose is associated with higher remission
rate and lower incidence of steroid dependent
asthma [13.5% in comparison to 45% in a
historical cohort where lower dose of steroid was
used].
2. Inhaled glucocorticoids: Currently it is believed that ICS
has no role in ABPA. But beneficial in control of asthma once
oral steroids dose is reduced.

39. 3. Oral itraconazole (with or without concomitant
steroids)
a) First Relapse of ABPA
OR
ABPA with recurrent exacerbations (to prevent
exacerbations after controlling the exacerbation with
glucocorticoids)
b) Glucocorticoid-dependent ABPA
Dose: ITRACONAZOLE: 200 mg twice a day, with therapeutic drug
monitoring for at least 16 weeks. Response often takes longer than 16
weeks. Recurrent short courses of 4-6 months or long term therapy.
Other azoles- Voriconazole and posaconazole are used in itraconazole
failure or resistance or intolerant.

40. ITRACONAZOLE:
Less toxic and more effective.
S/E : Prolongs QT interval, Inhibits the metabolism of
methylpred but not prednisolone so be cautious.
Even cases of adrenal insufficency has been reported
with inhaled steroids (least with fluticasone) and
azoles.
Voriconazole: Causes Skin Cancer.
Immunosuppressant : Methotrexate can be used
esp. where CSTs are absolute C/I like Cystoid macular
edema.

42. Follow up and monitoring
• The patients are followed up with a history and
physical examination, chest radiograph, total IgE levels
and quality of life, questionnaire every 8 weeks.
• A ≥ 25% decline in IgE level along with clinico-
radiological improvement signifies satisfactory
response to therapy.
• If the patient cannot be tapered off
prednisolone/azole then the disease has evolved into
stage 4. Management should be attempted with
alternate-day prednisone/azole in the least possible
dose.
• Monitor for adverse effects of treatment.

43. Advanced/Future Therapies
• Monoclonal antibodies against IgE - Omalizumab
• Monoclonal antibodies a/g Th2 cytokine IL-5
• Monoclonal antibodies a/g IL-13
• Vitamin D – acts on Th2 pathway.

44. Anti IgE therapy for ABPA

45. Differential Diagnosis
• Pulmonary Tuberculosis
• Pneumonia
• Pulmonary inflammatory disorders like
• Eosinophilic pneumonia
• Bronchocentric granulomatosis
• Churg-strauss syndrome

46. COMPLICATIONS
• Recurrent Asthma exacerbations
• Bronchiectasis
• Collapse
• Pulmonary Hypertension
• Type2 Respiratory failure
• Cor pulmonale
• Chronic pulmonary aspergillosis(Pulmonary fibrosis,
cavitation, collapse, pleural fibrosis)
• Amyloidosis

47. Take home message
• All patients with asthma should be screened for
aspergillus sensitivity.
• Early initiation of therapy may prevent permanent
damage to lung.
• New revised diagnostic criteria help in this regard,
but validation studies are needed.
• Role of antifungal and its exact place in treatment
algorithm is yet to be defined.
Aim is not to bring IgE levels within normal but
decline of 25-50% in 6wks-3months.