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ABPA Allergic Bronchopulmonary Aspergillosis. Case – B.C. - chronology 1983-Age 36, hx asthma. Persisting cough, mucous, sweats led to consultation and.

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Presentation on theme: "ABPA Allergic Bronchopulmonary Aspergillosis. Case – B.C. - chronology 1983-Age 36, hx asthma. Persisting cough, mucous, sweats led to consultation and."— Presentation transcript:

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 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.

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