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Allergic Bronchopulmonary Aspergillosis (ABPA). ABPA – Definition and Epidemiology Hypersensitivity reaction d/t colonization of bronchi by Aspergillus.

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Presentation on theme: "Allergic Bronchopulmonary Aspergillosis (ABPA). ABPA – Definition and Epidemiology Hypersensitivity reaction d/t colonization of bronchi by Aspergillus."— Presentation transcript:

1 Allergic Bronchopulmonary Aspergillosis (ABPA)

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 3 rd to 4 th 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 decd 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 incd production of Th2 cytokines (Il-4, -5, and -13) Incd total and A fumigatus-specific IgE, mast cell degranulation, and eosinophilic response. 4) Also Type III (IgG and IgA) hypersensitivity reactions

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 aSxc and dxd on routine screening (eg, 2/2 aSxc 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) 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 > 500-1000/mm(3) 6) Infiltrates on CXR or HRCT 7) Central bronchiectasis on chest CT 8) Elevd 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

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 2 nd to 4 th 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 dxg ABPA but findings can show Airflow obstruction Mixed obstructive and restrictive pattern if bronchiectasis or fibrosis Air trapping Decd FEV1 and RV (+) Bronchodilator response in < 50%

14 Stages of ABPA (not necessarily progressive) Stage I = Acute flare Infiltrates, markedly elevd IgE Stage II = Remisson No infiltrates, off steroids > 6 mos, elevd or NL IgE Stage III = Recurrent exacerbations Infiltrates, markedly elevd IgE Stage IV = Glucocorticoid-dependent asthma Infiltrates present intermittently or not at all, elevd 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 txg flares. Stages 1 & 3 – Prednisone 0.5-1.0 mg/kg Qday x 14 days, then QOD x 6-8 wks, then taper by 5-10 mg q 2 weeks until d/cd 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

17 Tx - Itraconazole Decs antigenic stimulus for bronchial inflammation, possibly by dec;g specific Aspergillus IgG Decd 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. _18/lesson17.php _18/lesson17.php

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