26 May 2022

8/3/20 Chronic fibrosing pulmonary aspergillosis

At Goldstein Report, PGY3 Percy Genyk presented a case of a 66 y/o M with history of orthotopic heart transplant in 2004 complicated by cardiac allograft vasculopathy, HFpEF (EF 67%, G3DD), HTN, RCC s/p R partial nephrectomy in 2018, bronchiectasis of unknown etiology and CKD Stage IV presents with dyspnea on exertion x1 week, dry cough x2 weeks and new onset small volume hemoptysis x2 episodes. ROS otherwise negative for chest pain, orthopnea, PND, LE edema or recent sick contact/travels. Home medications include amlodipine, clonidine, febuxostat, furosemide, labetalol, levothyroxine, mycophenolate mofetil, and tacrolimus. Vital signs stable and physical exam only significant for diminished respiratory sounds, L>R.

CBC: WBC 5.1>Hb 10.4/Hct 32.9<Plt 312
Na 133/K 4.4/Cl 101/HCO3 18/BUN 49/Cr 3.3 <Glucose 201 (Baseline Cr 2.4)
ALP 101>T.protein 6.9/Albumin 3.9/AST 15/ALT 17/Tbili 0.4


Tacrolimus level: 12.9 ng/mL

pBNP: 5595 (normal <124)
IgE 41.0 (normal <100)
IgG 1172 (normal: 700-1600)

Infectious workup:

  • COVID-19 negative
  • HIV, RPR negative
  • Hepatitis panel negative
  • Sputum Cx showed normal respiratory flora
  • Sputum AFB smear and culture negative x3
  • Fungal Blood culture negative
  • Serum cryptococcal Ag negative
  • Serum coccidioides Ag/Ab negative
  • Serum galactomannan negative
  • Serum Aspergillus Ag <0.5
  • Serum CMV/EBV PCR negative
  • Urine histoplasma Ag negative
  • PCP DFA negative
  • Respiratory viral panel negative

Renal workup:

  • UA Spec Grav 1.010, pH 5.0, Protein 30, negative leuk esterase/nitrite, negative blood
  • FeNa 0.9%, FeUrea 30.2
  • Uprotein/cr 2.4
  • US renal showed small echogenic kidneys consistent with chronic medical renal disease

CT Thorax w/o contrast:


Thoracentesis performed with following results:

  • pH: 7.0
  • Cell Count: total cells 100 (97% neutrophils)
  • Glucose 186
  • Protein 2.9 (Serum protein 6.3)
  • LDH 67 (Serum LDH 222)
  • Albumin 1.8 (Serum albumin 3.3)
  • ADA <1.6
  • Fluid Culture negative to date
  • Fluid AFB culture negative to date
  • Cytology showed reactive mesothelial cells and chronic inflammation. No malignant cells identified.

Bronchoscopy with transbronchial biopsy performed:


  • CMV DNA +, 2.87 log IU/mL
  • Aspergillus Ag not detected
  • Pathology: fragments of bronchial wall showing mucosal granulation tissue with associated marked acute and chronic inflammation, including focally abundant eosinophils and focal early squamous metaplasia of respiratory epithelium. Detached clusters of fungal hyphae, compatible with aspergillus

Treatment: Patient was diagnosed with chronic fibrosing pulmonary aspergillosis and started on voriconazole.

Take home points:

  1. Chronic cavitary pulmonary aspergillosis (CCPA) left untreated will lead to chronic fibrosing pulmonary aspergillosis which is extensive fibrosis with fibrotic destruction of at least two lobes of lung, leading to a major loss of lung function.
  2. Symptoms of chronic pulmonary aspergillosis include weight loss, cough usually productive, SOB, hemoptysis, moderate to severe fatigue/malaise, chest pain and rarely fever.
  3. Diagnostic criteria only requires one of the following:
    1. Aspergillus IgG or precipitins positive
    2. Strongly positive Aspergillus Ag or DNA in respiratory fluids
    3. Percutaneous or excision biopsy showing fungal hyphae on microscopy or growing Aspergillus spp from a cavity
  4. Treatment of choice is usually itraconazole or voriconazole with duration of therapy of at least 6 months. Follow up imaging in 3-6months.
  5. Given the patient being on immunosuppression, will need to adjust cellcept and tacrolimus dosing when placed on azole therapy.

Sentinel Article:
Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management

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