An investigation into biomarkers for the diagnosis of ABPA and aspergillus disease in cystic fibrosis

Abstract

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 NO), 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, FENO, 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 FENO 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, FENO and peripheral eosinophil counts are elevated in ABPA compared to those that are just sensitized to Aspergillus and may serve as useful diagnostic tests.

Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches

“…However, a positive culture for Aspergillus from sputum does not imply the development of ABPA because of the heterogeneity of the interaction between the fungus and the host. In fact, allergy to Aspergillus antigens detected by skin prick test is described in almost 50% of CF patients, whilst the prevalence of ABPA is estimated to be between 10% and 25% depending on the studies [ 10 , 11 , 12 , 13 , 14 ]. However, ABPA may be often underdiagnosed due to the lack of standardized diagnostic criteria.…”

A Peculiar Case of Pneumonia due to Mycoplasma pneumoniae in a Child with Cystic Fibrosis and Sensibilization to Aspergillus fumigatus

“…Sometime, bronchospasms are present. In CF patients, ABPA is not a rare disease; in most studies, it was reported that it was diagnosed in approximately 10% of cases [6,7]. Despite its relative frequency, the significant clinical manifestations and the characteristic laboratory findings, ABPA is frequently underdiagnosed, and diagnosis is frequently made several months or years after the onset of signs and symptoms.…”

Allergic bronchopulmonary aspergillosis in children

“…of ABPA in CF. 5,6 It has been assessed that an early disease recognition may prevent the progression of ABPA, and accordingly, clinical and radiographic stages of ABPA progression have been proposed. 3,7 The radiographic findings of ABPA on chest-X-ray are not specific, but pulmonary infiltrates, consolidation, and macronodular densities are commonly reported at the early-stage disease, whereas central bronchiectasis, ring shadows, and pulmonary fibrosis are reported at the end-stage.…”

“…Patients with ABPA show a severe progression in all lung function parameters, and FEF at 50% VC (FEF 50 ), the volume of trapped gas, and specific airway resistance as the best predictors have been reported 1,2,4 . Recently, exhaled nitric oxide (FE NO ) has been proposed as biomarker for the diagnosis of ABPA in CF 5,6 . It has been assessed that an early disease recognition may prevent the progression of ABPA, and accordingly, clinical and radiographic stages of ABPA progression have been proposed 3,7 .…”