Allergic Bronchopulmonary

Aspergillosis (ABPA)

Dr.Ravi PokalaPG in Pulmonary

MedicineS.V.Medical College

Allergic Bronchopulmonary Aspergillosis (ABPA) is an idiopathic inflammatory lung disease characterised by an allergic inflammatory response to the colonisation of Aspergillus or other fungi.

Definition

Aspergillus species are ubiquitous, thermotolerant organisms that reside in decaying organic matter.

There are more than 150 species ,Common are A.fumigatus, A.niger, A.flavus

Occurs primarily in patients with asthma (prevalence = 1-2%) or Cystic Fibrosis (prevalence = 1-15%)

Most cases present in the 3rd to 4th decade

No gender predilection

Some patients have positive family history of ABPA

Epidemiology

At microscopic level ABPA is characterized by an intense eosinophilic and mononuclear cell inflammatory response that leads to airway injury and bronchiectasis.

A role of Type I hypersensitivity is strongly suggested by elevated serum levels of total and aspergillus-specific IgE.

Pathogenesis

Type III hypersensitivity is suggested by the presence of aspergillus precipitins and circulating immune complexes during disease exacerbation.

A Type IV cell mediated immune reaction may also be at work based on the finding of dual (immediate and delayed) cutaneous reactions

Genetic predisposition + inhalation of Aspergillus fumigatus spores (that later germinate into hyphae and release antigens) 1) Airway barrier compromise (in part by decreased mucociliary clearance, and action of proteolytic and mycotoxins)

Pathophyisology

2) Activation of innate lung immunity Influx of inflammatory cells

3) Presentation of antigens to T cells Activation of Th2 cells and increased production of Th2 cytokines (Il-4, -5, and -13) increased total and A fumigatus-specific IgE, mast cell degranulation, and eosinophilic response.

4) Also Type III (IgG and IgA) hypersensitivity reactions

Pathophyisology

Varies between different patients and in different lung areas in a patient

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 with eosinophils and

multi-nucleated giant cells centered on airways◦ Invasive aspergillosis (rare)

Pathology

Common Symptoms◦ Low-grade fever◦ Wheezing◦ Bronchial hyperactivity◦ Hemoptysis◦ Productive cough (often w/ expectoration of

brownish black sputum)

Occasionally asymptomatic and diagnosed on routine screening.

Clinical Presentation

Can be normal

Other possible findings include:◦ Polyphonic wheezing◦ Clubbing (16%)◦ Coarse crackles (15%)◦ Symptoms of pulmonary HTN and/or respiratory

failure

Physical Exam

Major Criteria: (6 of 8 needed for diagnosis)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 > 1000/mm36) Infiltrates on CXR or HRCT 7) Central bronchiectasis on chest CT 8) Elevated specific serum IgE and IgG to A.

fumigatus

Diagnostic Criteria

Other Common Findings -- Expectoration of mucous plugs. Aspergillus in sputum, late skin reactivity to Aspergillus Ag

2 TypesABPA-CB (central bronchiectasis) -- 1, 2, 4, 7, 8ABPA-S (seropositive) -- 1, 2, 3, 4 but NO

accompanying central bronchiectasis

Parenchymal infiltrates (generally of upper lobes)

Atelectasis due to mucous plugging

Radiographic Features – Chest X Ray

Findings in bronchiectasis.

“Tram line” shadows due to thickened non-dilated bronchial walls

“Parallel lines” due to ectactic bronchi

Ring shadows due to mucous filled bronchi or small abscesses

Radiographic Features – Chest X Ray

Findings in bronchiectasis

“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

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

Widespread proximal cylindrical bronchiectasis (mostly of upper lobes)

Bronchial wall thickening

Mucous plugging

Atelectasis

Peripheral airspace consolidation

Ground-glass attenuation

Mosaic perfusion

Air trapping

Radiographic Findings - HRCT

Top L- Bilateral central bronchiectasis with centrilobular nodules & tree-in-bud opacities in L lung.

Top R - Bilateral central bronchiectasis with many mucus-filled bronchi.

Bottom L & R - High-attenuation mucoid impaction.

Not really used in diagnosing ABPA but findings can show Airflow obstruction Mixed obstructive and restrictive

pattern if bronchiectasis or fibrosis Air trapping Decreased FEV1 and RV (+) Bronchodilator response in < 50%

PFTs

Stage I = Acute flare Infiltrates, markedly elevated IgE

Stage II = Remisson No infiltrates, off steroids > 6 mos, elevated

or normal IgE Stage III = Recurrent exacerbations

Infiltrates, markedly elevated IgE Stage IV = Glucocorticoid-dependent asthma

Infiltrates present intermittently or not at all, elevated or normal IgE

Stage V = Fibrotic (end stage) lung diseaseFibrotic, bullous, cavitary lung lesions, IgE may

be normal

Stages of ABPA (not necessarily progressive)

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) To Decrease fungal burden in airways

Treatment- Goals

Doses vary depending on stage and prescriber preference. Higher dosages for longer durations may be more effective for treating flares.

Stages I & III– Prednisone 0.5-1.0 mg/kg/day for 14 days, then 0.5 mg/kg every other day for 6-8 weeks, then taper by 5-10 mg every 2 weeks over the ensuing 3 months.

Treatment - Steroids

Stage II– Steroids not needed. Monitor IgE every 6 months for 1 year then every 1-2 years. Doubling of baseline IgE indicates relapse (stage 3)

Stage IV– Steroid dependent. Aim for lowest possible dose

Stage V – Steroids not helpful

“prophylaxis” – Ca, Vit D, bisphosphonate

Decreases antigenic stimulus for bronchial inflammation, possibly by decreasing specific Aspergillus IgG

Decreases metabolism of steroids, so may be able to use lower dosages

200 mg/day or every other day is generally recommended.

Treatment - Itraconazole

In addition to medical therapy patients with ABPA should avoid areas and environmental conditions associated with high mould count such as decomposing organic materials and moldy indoor environments.

One should consider the use of HEPA filter devices if such exposures are unavoidable.