Abpa

allergic bronchopulmonary aspergillosis

1. Allergic Bronchopulmonary Aspergillosis (ABPA) Dr.Ravi Pokala PG in Pulmonary Medicine S.V.Medical College

2. 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

3. 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

4. Occurs primarily in patients with asthma (prevalence = 1-2%) or Cystic Fibrosis (prevalence = 1-15%) Most cases present in the 3 rd to 4 th decade No gender predilection Some patients have positive family history of ABPA Epidemiology

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. Can be normal Other possible findings include: Polyphonic wheezing Clubbing (16%) Coarse crackles (15%) Symptoms of pulmonary HTN and/or respiratory failure Physical Exam

12. 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/mm3 6) Infiltrates on CXR or HRCT 7) Central bronchiectasis on chest CT 8) Elevated specific serum IgE and IgG to A. fumigatus Diagnostic Criteria

13. 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

14. Parenchymal infiltrates (generally of upper lobes) Atelectasis due to mucous plugging Radiographic Features – Chest X Ray

15. 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

16. Findings in bronchiectasis “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

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

18. 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

19. 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.

20. 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

21. 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 disease Fibrotic, bullous , cavitary lung lesions, IgE may be normal Stages of ABPA (not necessarily progressive)

22. 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

23. 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

24. 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

25. 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

26. 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.