New Wheezing and Infiltrate in the Setting of Mild CF Lung Disease


Kenneth Coggins, MD

A 20 year-old male with a history of atopy and mild lung disease secondary to cystic fibrosis presented with a 3-week history of increased sputum production, dyspnea and wheezing. The patient's genotype was Delta F508/2789+5 G-T. He was pancreatic sufficient and had never required therapy with intravenous antibiotics. The patient had previously undergone allergy testing and had received immunotherapy for allergies to pet dander. He attributed his recent illness to an exacerbation of his allergies as a result of exposure to a dog while visiting relatives.

Past history included pancreatitis at age 17 requiring hospitalization, and major depression for which he had received treatment with sertraline in the past.

Physical examination was significant for crackles in the mid lung fields, and a prolonged expiratory phase with diffuse wheezing.
Laboratory investigations included a white blood cell count of 14,400 with 0.9% eosinophils and an elevated serum IgE level of 2840 IU. Spirometry performed pre-bronchodilator revealed an FEV1 of 3.15 liters (69% of predicted). Post-bronchodilator the FEV1 increased to 3.55 liters (77% of predicted). Chest x-ray revealed a patchy infiltrate in the superior segment of the right lower lobe. Based on this presentation, a further evaluation for allergic bronchopulmonary aspergillosis was performed.

An intracutaneous skin test using aspergillus antigen produced a wheal of 5 mm and a flare of 11mm. Serum was sent for examination for antibodies to A. fumigatus. Serum IgE for A. fumigatus was 9.21 and serum IgG was 2.39. A diagnosis of allergic bronchopulmonary aspergillosis was made. The patient was started on a course of therapy with Prednisone 40 mg per day, which he discontinued secondary to severe mood swings. On follow up, the patient had persistent dyspnea and wheezing on exam. A decision was made to start therapy with Itraconazole 100 mg per day and a lower dose of Prednisone (10 mg) per day. The patient tolerated the new therapeutic regimen well.

Allergic bronchopulmonary aspergillosis:

Allergic bronchoplumonary aspergillosis (ABPA) was initially reported in 1952 by Hinson and is characterized by recurrent chest roentgenographic infiltrates, peripheral eosinophilia and asthma. The incidence of ABPA in the adult patient with cystic fibrosis is approximately 2.3%. The diagnostic features of ABPA are: (1) asthma, (2) history of roentgenographic infiltrates, (3) immediate cutaneous sensitivity to A. fumigatus, (4) elevated total serum IgE, (5) precipitating antibodies to A. fumigatus, (6) peripheral blood eosinophilia, (7) elevated serum IgE and IgG to A. fumigatus (IgE-Af and IgG-Af, respectively) compared with sera from patients with asthma and cutaneous reactivity to Aspergillus who do not have ABPA, (8) proximal bronchiectasis. Because of the overlap between these features of ABPA and those of CF, the diagnosis in this setting is more difficult. Outside of CF, when all of the criteria are present, the diagnosis is straightforward and the patient is considered to have allergic bronchopulmonary aspergillosis with central bronchiectasis (ABPA-CB). In the absence of proximal bronchiectasis, the notation for seropositive ABPA is used (ABPA-S). The minimal diagnostic criteria in a patient with ABPA-S are asthma, immediate cutaneous reaction to A. fumigatus, elevated serum IgE-Af and IgG-Af, and an elevated total serum IgE. There are 5 stages of ABPA. Stage I (acute) is present when all of the classical findings are present. Stage II (remission) is noted after therapy with prednisone and is characterized by the absence of roentgenogrpahic infiltrates for at least 6 months. Stage III (exacerbation) occurs when new roentgenogrpahic infiltrates are noted in association with a marked elevation of total serum IgE. Stage IV (prednisone-dependent asthma) may occur when attempts are made to taper prednisone in patients with stage I or II disease resulting in uncontrolled asthma or new infiltrates. Patients with uncontrolled, prednisone-dependent asthma may have Stage IV ABPA. Stage V (fibrotic) occurs with repeated episodes of ABPA and is characterized by end stage fibrotic lung disease. The treatment of patients with acute ABPA consists of prednisone 0.5 mg/kg for 2 weeks with conversion to alternate day dosing for 2-3 months, and then tapering to the lowest dose necessary to control symptoms. Recent data from a multi-center randomized controlled trial support the addition of itraconazole as effective adjunctive therapy to systemic corticosteroids for patients with ABPA.

References:

  1. Stevens DA, Schwartz HJ, Lee JY, Moskovitz BL, Jerome DC, Catanzaro A, Bamberger DM, Weinmann AJ, Tuazon CU, Judson MA, Platts-Mill TA, Degraff AC. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. New England Journal of Medicine. 342(11): 756-62, 2000 Mar 16.
  2. Fraser R.S., Muller N.L., Colman N., Paré P.D. Fungi and Actinomyces. In Fraser and Paré's Diagnosis of Diseases of the Chest. Fourth edition: W.B. Saunders, Philadelphia. 875-961.
  3. Sharma OP, Chwogule R. Many faces of pulmonary aspergillosis. European Respiratory Journal. 12: 705-715, 1998.
  4. Noone P.G. and M.R. Knowles.1999. Standard therapy for cystic fibrosis lung disease. In Cystic Fibrosis in Adults. J.R. Yankaskas and M.R Knowles, editors. Lippincott-Raven, Philadelphia. 145-173.

 

 

 

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