Allergic Bronchopulmonary Aspergillosis (ABPA)
Alan Baptist, MD
Andrew Singer, MD
This site will cover the basics of ABPA in regards to definition, epidemiology,
pathogenesis, diagnosis, clinical findings, radiographic findings, differential diagnosis,
and treatment.
Definition – ABPA is a disorder arising from an allergic response to multiple antigens
expressed by Aspergillus fumigatus colonizing the bronchial mucus of certain asthmatic
patients.1 The first case was described in 1952 in the United Kingdom.2 A fumigatus is a
thermotolerant fungi that grows on decomposing organic matter including soil, grass,
mulch, wood chips, and decaying vegetation. Figure 1 shows a picture of A fumigatus.
There are Aspergillus-associated diseases other than ABPA (Table 1), and these are
covered in detail elsewhere.3-5
Epidemiology – The prevalence of asthma in the United States is thought to be 4.5 –
6.8%, accounting for approximately 16 million people.6, 7 Of all patients with chronic
asthma, the prevalence of ABPA is estimated at approximately 2%.8 Studies of referrals
to asthma specialists have shown the prevalence to be much greater in this select
population.9 In patients with cystic fibrosis (CF), the prevalence is thought to be 215%.10, 11 While ABPA can develop at any age, it most commonly develops in the third
and fourth decades of life.
Pathogenesis – Current ideas regarding the pathogenesis of ABPA are summarized in
Table 2.12-17 ABPA is thought to involve IgE, IgG, Th2 lymphocytes, eosinophils, and
numerous cytokines, but many questions still remain regarding the pathogenesis of
ABPA. For example, the reasons why certain asthmatics develop ABPA while others do
not is currently unknown. In addition, it is unknown why A fumigatus is able to colonize
the airways of patients with ABPA, while it is cleared in those asthmatics that do not go
on to develop ABPA. Patients who develop ABPA likely have an underlying genetic
predisposition, possibly relating to certain HLA-DR2 alleles.18
Diagnosis – The diagnostic criteria for ABPA was originally established in 1977, but has
been modified since that time.19 There are currently 5 criteria considered essential for the
diagnosis of classic ABPA, while 3 other criteria are supportive but not essential. Table
3 lists the criteria for ABPA, indicating which are essential and which are not. It is
important to note that not all criteria may be present at the time of presentation,
depending on which stage a patient is in (see below). Therefore, continued diagnostic
testing may be required for years to fulfill all criteria.1 The diagnosis of ABPA in
patients with CF is slightly different, and is based on the work of the Consensus
Conference of the Cystic Fibrosis Foundation.20
Consider formal evaluation for ABPA if any of the following are present: sputum
positive for Aspergillus, increasingly severe asthma, CXR infiltrates, peripheral blood
eosinophilia, or bronchiectasis on radiographic imaging.21
Clinical Findings – There are no specific clinical or physical examination findings to
ABPA. Symptoms can range from recurrent asthma exacerbations with cough, wheeze
and shortness of breath to systemic features with fever, anorexia, and malaise.22 Patients
will often complain of expectoration of brownish mucous plugs. Asthma is typically
present for 5 to 10 years prior to diagnosis,23 and can be of varying severity. Physical
exam findings can range from a normal examination to end-stage fibrotic lung disease
(clubbing, cor pulmonale, fine crackles). If pulmonary infiltrates are present at the time
of examination, lung examination may reveal egophony, crackles or bronchial breath
sounds.
Lab testing typically done in ABPA include tests that are part of the diagnostic
criteria, as listed in Table 3. Additionally, PFTs can be done, and will often reveal
airflow obstruction and air trapping, with a reduced FEV1 and increased residual volume.
If fibrosis or bronchiectasis has occurred, the PFTs can also show a fibrotic pattern or a
reduction in DLCO.24
Radiographic findings – Pulmonary infiltrates will often correlate with clinical
symptoms; however in 33% of cases infiltrates are present in asymptomatic patients.23
On CXR, findings are usually seen in the upper and middle lung fields (Figure 2).
Findings can be transient (infiltrates, consolidation, mucoid impaction) or permanent
(parallel line and ring shadows indicating bronchiectasis, parenchymal fibrosis). Of note,
a normal CXR appearance does not exclude the diagnosis of ABPA.25
CT scans in ABPA can show central bronchiectasis, with upper lobe
predominance and bronchial wall thickening. While some patients may not have central
bronchiectasis (i.e. ABPA-S patients), the presence of bronchiectasis on CT scan
warrants further evaluation for ABPA. In addition to changes due to central
bronchiectasis, CT scans can show parenchymal infiltrates, bronchial wall thickening,
pulmonary fibrosis, or mucoid impaction.26 Figure 3 shows a CT scan of a patient with
ABPA. Of note, high resolution CT scans (HRCT) are sometimes necessary to detect
radiographic changes due to ABPA that may be missed by conventional CT scans.
Stages of ABPA – The natural history of ABPA is difficult to predict.27 A staging
system has been developed to try and classify patients for appropriate therapy and to
better understand the disease. Table 4 shows the 5 stages of ABPA, as characterized by
serum IgE, serum precipitins, blood eosinophilia, CXR findings, and serum IgE-Af/IgGAf. It is important to note that patients do not necessarily progress from stage I through
stage V, but may jump from one stage to another and never reach certain stages (such as
stage IV or V).28 In addition, as shown in Table 4, the stage a person is in may determine
which diagnostic criteria are present (for example, in stage II many criteria may be
absent).
Differential Diagnosis – Syndromes associated with bronchiectasis or eosinophilia
should be considered in the work up of a patient with ABPA. Table 5 is an incomplete
list of some of the disease entities on the differential diagnosis for ABPA.
Treatment – The goal of treatment in ABPA is to control acute inflammation and limit
progressive lung injury (bronchiectasis, fibrosis). The two main targets of ABPA at this
time are inflammation (treated with corticosteroids) and fungal colonization (treated with
antifungals).1
Corticosteroids – Currently oral steroids are the cornerstone of therapy in ABPA.
Steroids are able to suppress inflammation, and this is reflected in a resolution of
clinical symptoms, clearance of CXR infiltrates, and a return to stable IgE level.26
Of note, the IgE level in patients with stable ABPA is often elevated above that of
patients without ABPA, and the goal of therapy with steroids should not be to try
and normalize the IgE level. Usual starting dose is 0.5mg/kg/day for 2 weeks,
then 0.5mg/kg QOD for 2 weeks, then taper to off. IgE levels and CXR should be
checked 2 months later. Every 2 months (for at least 1 year) an IgE level should
be checked to establish a stable baseline level. In addition, PFTs, CXR/CT scan,
and clinical symptoms should be monitored as needed.29 If a patient suffers an
ABPA flare, they shoud receive another course of corticosteroids. Some patients
are very difficult to wean off steroids as they will have a flare of their asthma each
time the steroids are stopped (i.e. stage IV patients). In this population, try to
wean the steroids down to the lowest alternate day dose tolerated, and every few
months consider trying a trial off steroids.
Antifungals – Numerous antifungal agents have been tried in ABPA, including
nystatin, amphotericin B, natamycin, ketoconazole, and itraconazole.30-32 Of
these, amphotericin B and ketoconazole did show efficacy but were limited by
toxicity.33 On the other hand, itraconazole has been shown effective in modifying
the immunologic activation in ABPA with a low degree of side effects.34 It is
currently used in some ABPA patients as adjunctive therapy with steroids. The
dose is usually 200mg BID x 4-6 months, then taper over 4-6 months.1 Use of
itraconazole as monotherapy has not been studied to date.
Other therapies – As with any asthmatic patient, it is important to optimize
baseline asthma. Inhaled steroids do not have efficacy in preventing acute
episodes of ABPA, but may help to reduce long term oral steroid dosage and are
often important in baseline asthma control.35 While the role of environmental
exposure has not been well studied in ABPA, areas with high concentrations of
mold should be avoided (crawl spaces, decaying organic material, etc). No
controlled studies have looked at the use of immunotherapy in ABPA. However,
fungal immunotherapy is know to have a high incidence of side effects,36 and
until further studies are done immunotherapy should be avoided as treatment for
ABPA.
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