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Clinical Investigations: HYPERSENSITIVITY |

Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis*: Role of Atopy and Response to Itraconazole

Ilynn B. Nepomuceno, MS; Silvia Esrig, MS; Richard B. Moss, MD, FCCP
Author and Funding Information

*From the Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA. Supported by the Ross Mosier Fund.



Chest. 1999;115(2):364-370. doi:10.1378/chest.115.2.364
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Study objectives: (1) To determine the relationship between IgE levels and the prevalence of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients, (2) to establish the usefulness of assessing atopy as an identifying risk factor for ABPA, (3) to evaluate the clinical course of patients receiving and not receiving itraconazole as reflected in oral steroid dose requirements and number of acute episodes of ABPA, and (4) to determine the role of acute episodes of ABPA in pulmonary exacerbations of CF.

Design: Retrospective review of online clinical database and medical records.

Setting: CF clinic and inpatient services of Lucile Salter Packard Children’s Hospital at Stanford.

Patients: One hundred seventy-two patients with CF for whom serial serum total IgE levels were measured over a 5-year study period, 1992 to 1996.

Interventions: We reviewed records of patients followed up at the CF Center at Stanford who had serum total IgE measured between January 1, 1992, and December 31, 1996. Total IgE and Aspergillus fumigatus (Af) specific IgE antibodies were measured by commercial fluorometric solid-phase immunoassay. Precipitating antibodies to Af were measured by double immunodiffusion. Patients who were diagnosed as having ABPA were treated with itraconazole unless significant liver dysfunction was present. Oral steroid dosing requirements and acute episodes of ABPA for days with vs days without itraconazole were compared.

Measurements and results: Serum total IgE was elevated (> 1 SD > geometric mean for age) in 51% of patients tested. IgE > 500 IU/mL, chosen as a screening cutoff for evaluating possible ABPA, was present in 19% of patients at some time during the study period. Atopy (defined as ≥ 1 IU/mL IgE antibody to ≥ 1 allergen) was present in 61% of 104 patients tested for specific allergen sensitization. ABPA was diagnosed in 16 patients (9%). ABPA occurred in 22% of atopic CF patients but only in 2% of nonatopic patients (p = 0.001). Six percent of pulmonary exacerbations requiring hospitalization were associated with acute episodes of ABPA. Over the study period, itraconazole use was associated with a reduced average daily oral steroid dose of 47% (p = 0.05) and a reduction in the number of acute ABPA episodes by 55% (p < 0.001).

Conclusions: Screening for atopy may be a cost-effective way to select CF patients for periodic monitoring with total serum IgE levels, since there is an increased risk of ABPA developing in atopic CF patients. Itraconazole treatment of ABPA is safe and associated with fewer acute episodes of ABPA despite reduction in average daily oral steroid dose.

Abbreviations: ABPA = allergic bronchopulmonary aspergillosis; Af = Aspergillus fumigatus; ALT = alanine transaminase; AST = aspartate transaminase; CF = cystic fibrosis; CFTR = cystic fibrosis transmembrane conductance regulator; LPCH = Lucile Packard Children’s Hospital; sIgE = specific IgE; tIgE = total IgE


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