Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis.
BACKGROUND
The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity of various paraclinical parameters in the diagnosis of ABPA in patients with CF.


METHODS
Accumulated data from a 5-year period in 238 CF patients were used to divide patients into two groups designated the ABPA group (n=26) and the non-ABPA group (n = 35). Patients in both groups were colonized with Aspergillus fumigatus (Af.), but only the ABPA group consistently demonstrated specific IgE antibodies and specific precipitins. Patients without A. fumigatus colonization were not assigned to either of these groups (n = 177). By this selection as the true diagnosis, 10 patients were selected from the ABPA group and 10 patients from the non-ABPA group.


RESULTS
The groups were comparable as to age, sex, lung function (P=0.6), and presence of chronic Pseudomonas aeruginosa infection (P>0.1). No significant difference between the groups in unspecific atopic parameters such as eosinophil count (P=0.9) or eosinophil cationic protein (ECP) in sputum, plasma, or serum (P=0.9, P=0.59, and P = 0.9, respectively) was demonstrated. Total IgE was significantly higher in the ABPA group (P<0.01). The groups were comparable in skin prick test (SPT) positivity to a standard panel of aeroallergens (pollen, dander, molds, and mites) (P>0.2). Statistically significantly higher levels in the ABPA group were demonstrated in specific IgE to Af. (P < 0.05), SPT positivity to Af. (P < 0.02), and Af. precipitins (P < 0.05). Histamine release (HR) to Af. tended to be higher (P=0.075) in the ABPA group. Specific IgE to Af. was determined by Magic Lite (ML), CAP, and Maxisorp (in-house RAST). The CAP level was one to two classes higher than the ML level; however, the results were comparable (r=0.66, P<0.005). IgE to Af. measured by CAP was the test which offered the highest positive predictive value (PPV) and negative predictive value (NPV). Optimal diagnostic cutoff levels for the diagnosis of ABPA were determined: class 2 for HR to Af., 200 kIU/l for total IgE, and 3.5 (titer) for precipitating antibodies to Af., and class 2 for IgE to Af. (by CAP System).


CONCLUSIONS
Unspecific atopy markers were of limited value for the diagnosis of ABPA. Patients with ABPA do not seem to be more atopic to other aeroallergens than non-ABPA patients. The most valid parameters for the diagnosis of ABPA in CF are SPT to Af., IgE to Af. in combination with precipitating antibodies to Af., and/or total IgE.
Skov
M
M
Department of Pediatrics, National University Hospital, Copenhagen, Denmark.
Koch
C
C
Reimert
C M
CM
Poulsen
L K
LK
D000293:Adolescent; D000328:Adult; D000908:Antibodies, Fungal / Q000097:blood; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000175:diagnosis* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology / Q000302:isolation & purification; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications*; D003718:Denmark; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D011233:Precipitin Tests; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D012882:Skin Tests
D000908:Antibodies, Fungal; D011933:Reagent Kits, Diagnostic; D007073:Immunoglobulin E