Allergic BronchoPulmonary Aspergillosis (ABPA) is an inflammatory lung disease caused by an allergic response to the fungus Aspergillus fumigatus. It mostly affects people with asthma or cystic fibrosis. ABPA is characterized by elevated IgE levels, eosinophilia, fleeting pulmonary opacities on imaging, and bronchial wall thickening or bronchiectasis. Diagnosis requires specific criteria involving immunological markers and radiological findings. Management involves use of oral steroids and antifungal azole drugs.

1. Allergic BronchoPulmonary
Aspergillosis
DR SANDEEP NAIN ,MD Respiratory Medicine

2. INTRODUCTION
Allergic bronchopulmonary aspergillosis (ABPA) is an idiopathic
inflammatory disease of the lung, characterized by an allergic
inflammatory response to colonization of the airways by Aspergillus
fumigatus or other fungi.
• Mostly in third to fifth decade of life
• Estimates :ABPA complicates
1.approximately 7%to 14% of cases of chronic steroid–dependent
asthma
2.approximately 7% to 15% of cases of cystic fibrosis (CF).
• No gender predisposition

3. Spectrum of Pulmonary Aspergillosis
Allergic
1. Aspergillus sensitized asthma
2. Allergic Aspergillus sinusitis
3. Allergic Bronchopulmonary aspergillosis
4. Hypersensitivity pneumonitis
Saprophytic
1. Aspergilloma
Invasive
1. Chronic necrotising pulmonary aspergillosis
2. Airway-invasive Aspergillosis
3. Angio-invasive Aspergillosis

5. Aspergillus Fumigatus
• Ubiquitous fungus
• Thermotolerant
• Reside in decaying organic matter and colonize most
domestic environments, including carpets and air ducts
• An opportunistic pathogen
• Size of conidia spores 2-5 micron equal to pores of alveoli
• Growth at 37 degree C
• Aspergillus spp. - Aspergillus fumigatus, Aspergillus
flavus, Aspergillus niger, etc

6. Genetic factors in the pathogenesis of ABPA
Defects in innate immunity
• Surfactant protein A2 gene polymorphisms
• Mannose-binding lectin gene polymorphisms
• Toll-like receptor 3,9 gene polymorphisms
Adaptive immunity
• HLA associations
• Interleukin 4,10,13,15 polymorphisms
• Tumour necrosis factor-α polymorphisms
• Transforming growth factor-β polymorphisms
Others
• CFTR gene mutation
• CHIT1 gene mutations
• Chitotriosidase 1

7. CFTR Gene Mutation
Decrease chloride secretion and increase sodium absorption at the
apical membrane of airway epithelial cells.
Decreased airway surface liquid (ASL) height and altered mucociliary
clearance
Chronic bacterial infection, airways inflammation, and damage to lung
tissue.
Activation of both innate and adaptive immune responses against these
antigens.
Development of lung injury and bronchiectasis over time.
Increases morbidity and mortality

8. Hypersensitivity reactions in ABPA
• Type I response (atopic, formation of IgE) The reaction of IgE
with Aspergillus antigens results in mast cell
degranulation with bronchoconstriction and increased capillary
permeability.
• Type III Hypersensitivity reactions- Immune complexes and
inflammatory cells are deposited within the mucous
membranes of the airways, leading to necrosis (tissue death)
and eosinophilic infiltration.
• Type IV hypersensitivity reactions- injury is caused by
activated macrophages.

9. Hypersensitivity reactions in ABPA

10. Conidia immunologically inert
because of the presence of surface
hydrophobin that prevents immune
recognition of fungal spores .
The immune response is a Th2 CD4+ T cell
response with IL-4, IL-5 and IL-13 cytokine
secretion.
profound inflammatory reaction with influx of
various inflammatory cells (including
neutrophils and eosinophils) and IgE (total and
A. fumigatus specific) synthesis
Airway macrophages recognize fungi
through pattern recognition receptors
(PRRs) such as toll-like receptors (TLRs)
and mannose-binding lectin (MBL), which
trigger secretion of pro-inflammatory
cytokines
hyphae forms are killed by neutrophils.
defective clearance of conidia which allows
them to germinate into hyphae which lead
to the release of antigens which are
presented by APCs
Exposures to high concentrations of spores
Inhalation of conidia spore
Normal person Asthma or cystic fibrosis patient
PATHOGENESIS

11. Greenberg and Schwartz Diagnostic
Criteria ,1991

12. Predisposing Conditions
(1) Asthma, (2) Cystic Fibrosis
Obligatory Criteria (both need to be present)
(1) Type 1 Aspergillus skin test positive (immediate cutaneous hypersensitivity
reaction ) or elevated IgE levels against Aspergillus fumigatus.
(2) Elevated total IgE levels more than 1,000 IU/mL (unless all other criteria is
met, then total IgE levels can be less than 1,000 IU/mL)
Other criteria (two out of three at least)
(1) Presence of IgG antibodies against Aspergillus fumigatus or precipitating
antibodies.
(2) Presence of fleeting or radiograph pulmonary opacities consistent with
ABPA.
(3) Eosinophil count more than 500 cells/μL in steroid naive patient (may be a
historical value)
International society for Human and
Animal Mycology (ISHAM) Diagnostic
criteria,2013

13. Patterson and Rosenberg Diagnostic
Criteria ,1977
• Bronchial asthma
• Immediate cutaneous hypersensitivity
to A fumigatus antigen
• Serum total IgE levels (>1000 IU/mL)
• Serum A fumigatus specific IgG
and/or IgE levels more than twice the
mean plus two standard deviation
values in patients with Aspergillus
hypersensitive asthma
• Central bronchiectasis on HRCT chest
• Serum precipitins against A fumigatus
• Fleeting or fixed pulmonary opacities
on chest radiograph
• Peripheral blood eosinophil count
>1000 cells/µL
Major Criteria Minor Criteria
• Sputum cultures demonstrating growth
of A fumigatus
• Expectoration of brownish-black
mucus plugs
• Type III skin reactions to A
fumigatus antigen
The presence of 6 out of 8 major criteria makes the diagnosis almost certain.

14. RADIOLOGICAL FINDINGS
Chest Xray findings-
Transient
• Fleeting opacities
• Band-like shadows
-toothpaste opacities, appearance of a “V”, inverted “V” or a “Y” shaped shadow.
-finger-in-glove opacities (ovoid perihilar shadows with an expanded rounded distal end
• Consolidation
• Pseudo hilar adenopathy
• Atelectasis
Fixed
• Parallel line and ring shadows
• Cystic bronchiectasis
HRCT Findings-
• Signet ring
• String of pearls

15. PA chest X-ray shows hyperinflated lungs,
bronchial dilatation, and right lower lobe opacity
consistent with mucoid impaction.
Transient pulmonary infiltrates or fleeting
shadows that are characteristic of allergic
bronchopulmonary asperillosis

16. Chest radiograph shows mucoid
impaction with the classic finger-in-
glove pattern
Tram- line shadow parallel
linear shadows

17. Y shaped opacities- wine glass
shadow

18. Dilated central bronchus consistent with
cylindrical/central bronchiectasis.
Toothpaste shadows - mucoid
impaction of the bronchi

19. Tram- line shadow parallel linear shadows
extending from the hilum in bronchial
distribution and reflecting longitudinal views
of inflamed, edematous bronchi
Ring Shadows - dilated bronchi
with inflamed bronchial walls
seen on end

20. Radiological staging by Kumar
CATEGORY
ABPA-S
ABPA-CB
ABPA-CB-ORF
FEATURES
Patients meet the clinical, laboratory, and
serologic diagnostic criteria except central
bronchiectasis.
Patients meet diagnostic criteria along
with central bronchiectasis.
Patients meet diagnostic criteria and, in
addition to central bronchiectasis, they
also have other radiographic features such
as pulmonary fibrosis, scarring,
emphysematous changes, fibrocavitary
changes, and pleural changes.
SEVERITY
MILD
Mild to moderate airflow
obstruction
Aspergillus IgG precipitins
positive in 50%
MODERATE
Moderate to severe airflow
obstruction.
High IgE. Aspergillus IgG
precipitins positive in 66%
SEVERE
Severe airflow obstruction.
Very high eosinophil count
and IgE. Aspergillus IgG
precipitins positive in
100%

21. International Society for Human and Animal
Mycology(ISHAM) radiologic classification
FEATURES
ABPA-S All the diagnostic features of ABPA
but no evidence of bronchiectasis on CT
All findings of ABPA including bronchiectasis
on CT of the chest
All features of ABPA including HAM on CT of
the chest
ABPA with other radiologic features such as
pulmonary fibrosis, bleb, bullae,
pneumothorax, parenchymal scarring,
emphysematous change, multiple cyst,
fibrocavitary lesions, aspergilloma, pleural
thickening
CLASSIFICATION
ABPA-S (Serological)
ABPA-B (Bronchiectasis)
ABPA-HAM (high attenuation mucus)
ABPA-CPF (chronic pleuropulmonary
fibrosis).

22. Clinical Staging in patients with asthma by
ISHAM
Stage Definition Features
0 Asymptomatic No previous diagnosis of ABPA Controlled asthma .Fulfilling
the diagnostic criteria of ABPA.
1 Acute No previous diagnosis of ABPA Symptoms consistent with
ABPA Satisfying the diagnostic criteria of ABPA
1a With mucoid
impaction
Mucoid impaction observed on thoracic imaging
1b Without mucoid
impaction
Absence of mucoid impaction on thoracic imaging
2 Response Clinical and/or radiological improvement and decline in
serum total IgE by ≥25% of baseline at 8 wk
3 Exacerbation Clinical and/or radiological worsening and increase in
serum total IgE by at least 50% from the new baseline
established during response/remission

23. Continued…
Stage Definition Features
4 Remission Sustained clinical and radiological improvement and
serum total IgE levels persisting at or below baseline
for > 6 months off treatment.
5a Treatment-
dependent ABPA
Two or more exacerbations within six months of
stopping therapy or clinical and/or radiological
worsening, along with increase in serum total IgE
levels, on tapering oral steroids/azoles
5b Glucocorticoid
dependent asthma
Systemic glucocorticoids required for control of
asthma while the ABPA activity is controlled (as
indicated by serum total IgE and thoracic imaging)
6 Advanced ABPA Extensive bronchiectasis due to ABPA on chest
imaging along with either cor pulmonale and/or
chronic Type II respiratory failure

24. Allergic Aspergillus Sinusitis
• A chronic indolent disease, characterized by the presence of
'allergic mucin' in the sinuses .
• Patients having rhinosinusitis with a positive skin allergy test
to Aspergillus or other fungal antigens.
• Release of antigenic material from fungi cause chain of
immunologic reactions culminating in the development of
AAS.
Computed tomography of the paranasal
sinuses showing hyperdense lesions in the
ethmoid and maxillary sinuses, suggestive of
inspissated secretions.

25. DIAGNOSTIC
ALGORITHM

26. MANAGEMENT

27. Treatment protocols
1. Oral Glucocorticoids
Indications - First-line treatment of ABPA,
both in acute-stage and during exacerbation.

28. 2. Oral azoles
Itraconazole: 200 mg twice a day for 24 weeks
• Indication:
Second exacerbation of ABPA;
glucocorticoid-dependent ABPA;
alternative to glucocorticoids as first-line treatment of ABPA, especially in
those with increased propensity for glucocorticoid-related side effects.
• decrease the immune response by reducing the antigenic stimulus , Thus reduce
the need for glucocorticoids.
• RCT comparing monotherapy of itraconazole vs. prednisolone in ABPA (MIPA
study) is underway

29. 3. Other Therapies
• ABPA complicating CF - nebulized amphotericin and inhaled steroids.
• Omalizumab, a humanized monoclonal antibody against IgE, is a potential
approach
• Pulse doses of IV methylprednisolone – for severe exacerbations
• Voriconazole and posaconazole are also efficacious.

30. Follow up and monitoring
• History and physical examination, chest radiograph, spirometry and
measurement of total IgE levels every 8 wk (to determine the new
baseline IgE)
• A 25% decline in serum total IgE along with clinical and/or
radiological improvement, indicates a satisfactory response to
therapy
• A clinical or radiological worsening along with a ≥50% increase in
the new baseline IgE points to an ABPA exacerbation
• Worsening of symptoms in the absence of radiological or
immunological worsening (serum total IgE) suggests an asthma
exacerbation

31. THANK YOU