ABPA

1. ABPA Allergic Bronchopulmonary Aspergillosis

2. Case – B.C. - chronology • 1983-Age 36, hx asthma. Persisting cough, mucous, sweats led to consultation and evaluation • CXR-LLL infiltrate w/ cavitation and RUL cavity • TEC 112 (on Prednisone) • ESR 30 – 50 • Fungal CF and Immunodiffusion neg.

3. 1983 • Bronchoscopy – Bx=Fibrosis and inflammatory debris. “A large number of inflammatory cells are eosinophils and macrophages” • Open lung biopsy rec. by Dr. Ed Goodman “Chronic bronchitis and bronchiolitis with acute bronchopneumonia-etiology not demonstrated.” Specifically no vasculitis, no granuloma, no mucoid impaction, and neg. AFB and Fungal stains.

4. 1983 • Negative AFB cultures from sputum, bronchoscopy, and OLBx. • Aspergillus species grew from sputum, bronchoscopy, and OLBx • No specific diagnosis made, no specific Rx given – on Vanceril, TheoDur, and Ventolin

5. Various Years • 1988 IgG, IgM, IgA, and Alpha-1 antitrypsin negative • 1990 TEC 400+ • 1991 Opinion from Dr. John Weissler at UTSWMS No information or letter received • 1994 TEC 400 • 1995 Evaluation by Dr. Gary Gross + Ragweed, molds, and animal dander. Rx Intal and nasal Atrovent. • 1998 Hospitaliztion for pneumonia • 1999 Outpatient pneumonia

6. 1999 • Opinion from Dr. Robert Sugarman, immunologist, for recurring pneumonias • Diff Dx – ABPA, ciliary dyskinesis, ASA hypersensitivity, Cystic Fibrosis • IgE 1810, RAST IgE and IgG for Aspergillus fumigatus elevated. • ABPA unifying diagnosis

7. More of the saga • 2000 – episode of pleurisy • 2001 – Sputum grew Mycobacterium avium complex…Rx EMB, RMP, Biaxin • 2001 - Right back/flank pain – H. zoster

8. 2003 • 4/03 CXR worsened • 5/03 CT – Bronchiectasis, Adenopathy, and pancreatic lesion • 5/03 Sputum grew Candida; AFB negative • 6/03 PET scan negative • 7/03 Bronchoscopy for Bx and Lavage. Bx=“chronic inflammation with eosinophilia.” Culture grew Aspergillus terreus. AFB negative. Spirometry: FVC 85%,FEV1 70%,FEF25-75 34% Bone Density: osteopenia

9. 2003 cont’d • 7/03 Rx: Prednisone 80-40-20, Sporanox 100 mg BID, Advair 500/50 BID • 9/03 FEV1 up to 2.1liters, Less cough, subjectively improved, TEC 100, HRT added by GYN, CXR/CT remarkably improved. Prednisone reduced to 20 QOD • 12/03 TEC 200, IgE 739. Prednisone reduced to 15 QOD, Advair to 250 due to hoarseness, and Sporanox continued

10. ABPA • Complex hypersensitivity reaction in patients with asthma that occurs when bronchi become colonized by Aspergillus • Repeated episodes of bronchial obstruction, inflammation, and mucoid impaction can lead to Bronchiectasis, Fibrosis, and respiratory compromise

11. ABPA Pathology • Mucoid impaction of bronchi, eosinophilic pneumonia, bronchocentric granulomatosis • Asthma • Septated hyphae with dichotomous branching may be seen in mucous, but do not invade the mucosa. • Culture + in 2/3 of patients

12. ABPA Physiology • No relationship between intensity of airborne exposure and rates of sensitization • Healthy individuals can eliminate fungal spores • Atopic individuals may form IgE and IgG antibodies. Vigorous IgE and IgG immune responses do not prevent this colonization. Fungal proteolytic enzymes and mycotoxins are released, in concert with Th2-mediated eosinophilic inflammation, may lead to airway damage and bronchiectasis

13. ABPA Clinical • Asthma • Bronchial obstruction • Fever, malaise • Expectoration of brownish mucous plugs • Eosinophilia • Hemoptysis • Wheezing +/-

14. ABPA Radiologic features • Upper lobe infiltrates • Atelectasis • “Tram lines” • “Parallel lines” • Ring shadows • “Toothpaste shadows” • “Gloved finger shadows” • Perihilar infiltrates may simulate adenopathy • Cylindrical bronchiectasis

15. ABPA PFTs • Airflow obstruction – reduced FEV1 • Air trapping – increased RV • Positive BD response in ½ • Mixed obst. and rest. if bronchiectasis and fibrosis present • Reduced DLCO if bronchiectasis present

16. ABPA Diagnosis • Hx Asthma • Skin test reactivity to Aspergillus • Ppt. serum antibodies to A. fumigatus • Serum IgE > 1000 ng/ml • Peripheral blood eosinophilia >500/mm3 • Pulmonary infiltrates • Central bronchiectasis • Elevated IgE and IgG to A. fumigatus

17. Pulmonary Eosinophilia • Drug and Toxin Induced • Helminthic and Fungal Infection • Acute Eosinophilic Pneumonia • Chronic Eosinophilic Pneumonia • Churg – Strauss Syndrome • Others-Hypereosinophilic Syndrome, Idiopathic Lung diseases, neoplasms, non-helminthic infections

18. ABPA vs. Asthma • ABPA in 6 – 30% of asthmatics with skin test reactivity to Aspergillus • Features of ABPA may be common in asthmatics without ABPA • Positive skin test to Aspergillus in 20-30% • Positive serum ppt.to Aspergillus in 10% asthmatics and 10% of nonasthmatic chronic lung disease patients • Recurrent Mucoid impaction and atelectasis • Peripheral blood eosinophilia and elevated IgE

19. ABPA and Bronchiectasis • Evaluate patients with Bronchiectasis for ABPA unless prior necrotizing pneumonia • CT characteristics of bronchiectasis have failed to differentiate ABPA from CF, ciliary dysfunction, hypogammaglobulinemia, or idiopathic causes.

20. ABPA Treatment • Corticosteroids • Inhaled steroids may help control symptoms of asthma but do not have documented efficacy in preventing acute episodes of ABPA • Itraconazole

21. ABPA Staging/Treatment • I – Acute flare – Rx 1mg/kg prednisone for 14 days with 3 – 6 month taper • II – Resolution of CXR with clinical improvement with 35% reduction in IgE • III – Recurrent exacerbations with 100% rise in IgE. May be asymptomatic • IV – Corticosteroid dependent asthma • V – Diffuse fibrotic lung disease due to repeated episodes

22. Itraconazole • Addition of itraconazole to corticosteroids in 55 patients for 16 weeks led to clinical response (46% vs. 19% with placebo)-reduced steroid dose 50%, 25% decrease in IgE, 25% improvement in FEV1 or exercise tolerance, or partial or complete resolution of pulm. Infiltrates. • May augment activity of methylprednisolone • May reduce specific aspergillus IgG NEJM 2000;342:756-762.