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 BxFibrosis 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 complexRx
  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.
  Bxchronic inflammation with eosinophilia.
  Culture grew Aspergillus terreus. AFB negative.
  Spirometry FVC 85,FEV1 70,FEF25-75 34
• Bone Density osteopenia

9
2003 contd

• 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 gt 1000 ng/ml
• Peripheral blood eosinophilia gt500/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 2000342756-762.