An Investigation into Biomarkers for the Diagnosis of ABPA and Aspergillus Disease in Cystic Fibrosis

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease due to Aspergillus fumigatus (Af) which occurs in 10% of patients with cystic fibrosis (CF). ABPA is associated with increased morbidity and accelerated lung function decline; however, existing diagnostic criteria are nonspecific and diagnosis remains challenging. As ABPA is driven by Th2 inflammation, the aim of this study was to evaluate exhaled nitric oxide (FE ), eosinophilic cationic protein (ECP), peripheral eosinophil count, and bronchodilator response (BDR) in patients with CF.

Methods: A prospective observational cohort study of pediatric CF patients in a tertiary center. Patients had a clinical and serologic ABPA assessment, FE , serum ECP, peripheral eosinophil count, and assessment of BDR. Patients were stratified into three groups; ABPA, Af sensitized (AFS), and non-ABPA non-Af-sensitized (non-AFS).

Results: A total of 62 patients were included in the study: 13% ABPA, 19% AFS, and 68% non-AFS. Mean FE was higher in the ABPA group at 37.8 ppb compared to AFS 15.1 ppb (P = .05) and non-AFS 13.7 ppb (P = .04). Mean peripheral eosinophil count in ABPA group was also higher at 1000 cells/uL, compared to AFS 221 cells/uL (P = .03) and non-AFS 220 cells/uL (P = .03). Mean BDR in ABPA group was 13% compared to 5.5% in non-AFS (P = .01). Serum ECP was higher in patients with ABPA positive compared to the other groups, although this was not statistically significant.

Conclusion: In children with cystic fibrosis, FE and peripheral eosinophil counts are elevated in ABPA compared to those that are just sensitized to Aspergillus and may serve as useful diagnostic tests.