dependent asthma as well as in patients with CF who have a progressive pulmonary function decline.

Laboratory Evaluation

Skin Testing

Immediate cutaneous hypersensitivity to Aspergillus antigens is a classic fnding in ABPA and part of the current diagnostic criteria. The test can be performed with a skin prick test or an intradermal injection. Development of a wheal and erythema within 1 min of administration of the antigen re ects the presence of immediate cutaneous hypersensitivity. In ABPA, the sensitivity of a positive result to antigens derived from Aspergillus fumigatus is around 90% [49].

Serum Precipitins

The presence of precipitating IgG antibodies against extracts of Aspergillus fumigatus in patients with ABPA was frst described by Pepys et al. in 1959 [50]. Longbottom and Pepys further refned the signifcance of the presence of serum precipitins with an agar gel double-diffusion test and immunoelectrophoresis on Aspergillus in a study comparing the serum from 60 presumed normal controls, 397 asthma patients, 93 asthma patients with transitory pulmonary infltrations and blood eosinophilia, 66 patients with radiographic, surgical, or postmortem evidence of mycetoma, and 185 patients with other pulmonary diseases [51]. A higher percentage (63%) of the patients with asthma with transitory pulmonary infltrations and blood eosinophilia had positive and stronger precipitation reactions compared to patients with only asthma (9%). An additional study found positive Aspergillus fumigatus precipitins in 69% of patients with similar ABPA-type features [52].

Eosinophil Count

Peripheral eosinophilia is a common fnding in ABPA. It is incorporated into the diagnostic criteria, but its presence is not obligatory to make a diagnosis. The cutoff value for elevated peripheral eosinophil count is >500 cells/μL in a corticosteroid-­naïve patient [46]. Sputum eosinophilia is also present in ABPA with increasing levels of sputum eosinophilia demonstrated to correlate with the severity of bronchiectasis present on a high-resolution CT scan (HRCT) [53].

Total Serum Immunoglobulin E Levels

In 1972, Patterson et al. demonstrated that elevated total serum IgE levels may aid in diagnosis of ABPA and that they were associated with acute ares of disease [54]. Total serum IgE levels are incorporated as part of the formal diagnosis of ABPA with a level > 1000 IU/mL the criteria for a positive result; although if a patient meets all other ABPA criteria, a lower level may be acceptable [46]. The earliest measure-

ment of total serum IgE should be used in the diagnosis of ABPA as levels may decline with treatment. Of note, serum IgE levels are often reported in different units around the world, leading to misapplied cutoff values and misinterpretation of the normalcy of results (1 IU/mL is equivalent to 2.4 ng/mL) [46]. Total serum IgE levels very often do not return to normal ranges even when patients are in remission. Serial monitoring of total serum IgE levels should be done while following patients, as an increase in the IgE levels may signal an impending exacerbation.

Serum Antibodies Speci c to Aspergillus fumigatus

An elevated level of Aspergillus fumigatus-specifc IgE is a characteristic fnding of ABPA and is included as part of the diagnostic criteria. Experts recommend a value >0.35 kUA/L as positive [46]. The presence of Aspergillus fumigatus-­ specifc IgG is also included in the diagnostic criteria; however, it is not required for the diagnosis of ABPA if the other additional criteria are present [46]. Aspergillus fumigatus-­ specifc IgG is not specifc to ABPA and can be found in other Aspergillus-related pulmonary diseases.

Recombinant Antigens

New technology permits the cloning of specifc proteins of Aspergillus fumigatus, allowing for the creation of recombinant antigens rather than crude extracts of Aspergillus. Studies have demonstrated that antibodies against the recombinant antigens rAsp f1, rAsp f3, rAsp f4, and rAsp f6 are elevated in patients with ABPA [55, 56]. Their use in the diagnosis of ABPA is under investigation.

Radiographic Imaging

Chest radiographs with eeting pulmonary opacities and bronchiectasis should raise a suspicion for ABPA, especially in patients with underlying asthma or CF. Pulmonary opacities can re ect eosinophilic infltration as well as mucus plugging, atelectasis, bronchoceles (mucus-flled dilated bronchi), or lobar collapse [57]. HRCT more precisely characterizes the pulmonary fndings in ABPA compared to chest radiographs. HRCT classically shows consolidation with central cystic or varicose bronchiectasis involving multiple lobes (Fig. 4.3) and mucus-flled bronchi (Fig. 4.4) [58]. Bronchiectasis is defned as central if it is confned to the medial two-thirds or the medial half of the lungs [59]. Although central bronchiectasis is a characteristic fnding in ABPA, bronchiectasis may extend to the periphery in some cases. Bronchiectasis typically involves the upper lobes. Centrilobular nodules, tree-in-bud opacities, and mosaic attenuation are other radiographic fndings, which may be observed. Transient airuid levels may be seen in dilated

bronchi. Varying appearances of mucus plugging can occur, which have been described as “V,” inverted “V,” and “Y”-shaped shadows, toothpaste shadows, and fnger-in-­ glove opacities [59]. High attenuation mucus, in which the mucus plug is visually denser than the paraspinal skeletal muscle or has a density of 100–170 Hounsfeld units, is a characteristic radiologic sign in ABPA. High attenuation mucus was the most specifc fnding in the diagnosis of ABPA in a study of more than 300 patients [49]. In a setting of untreated or progressive disease, extensive bronchiectasis with airway cavitation and pleuropulmonary fbrosis can develop.

Pulmonary Function Testing

Pulmonary function test fndings are nonspecifc in ABPA, given the high frequency of additional pulmonary pathology [60]. Air ow obstruction is a common fnding, but spirometry may also be normal. Partially reversible air ow obstruction is often noted in early or mild ABPA with fxed air ow obstruction seen in more advanced diseases. Decreased lung volumes can be seen if interstitial fbrosis has developed. The diffusing capacity may be normal or decreased. The primary role of pulmonary function testing in ABPA is to monitor disease progression over time.