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2020 Allergic Bronchopulmonary Aspergillosis Clinical Care Guidelines | CF Foundation

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Allergic Bronchopulmonary Aspergillosis

Clinical Care Guidelines
Allergic bronchopulmonary aspergillosis is a hypersensitivity lung disease that results
from exposure to Aspergillus fumigatus and occurs primarily in people with asthma or with
cystic brosis. These guidelines were developed via a consensus conference of experts in
2003. 

Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis Clinical Care

Guidelines
Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri
R, Brody AS, Light M, Skov M, Maish W, Mastella G, and participants in the Cystic Fibrosis
Foundation Consensus Conference. Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis-
State of the Art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003 Oct; 37
(Suppl 3), S225-64.PMID: 12975753

The 2003 recommendations addressed diagnostic criteria, screening, imaging, and treatment
recommendations. Since 2003, there has been advancement in diagnostic ability via serology
and immunologic testing. Most advancement has occurred in the treatment options. There has
been more clarity in steroid dosing, but additional treatment options, including intravenous (IV)
pulse steroids, systemic and inhaled antifungals, and anti-immunoglobulin E (IgE) therapy, have
been explored. Future directions include the need for improved animal models as well as
controlled treatment studies.

Purpose and Background

Allergic bronchopulmonary aspergillosis (ABPA), a lung disease of hypersensitivity to Aspergillus
fumigatus (A. fumigatus) that primarily occurs in people with asthma or with cystic brosis, is
seen in 2 to 19 percent of people with CF. People with CF may be predisposed to ABPA because
of abnormal airway surface liquid and CF mucus. The disease is characterized by a variety of
clinical and immunologic responses to A. fumigatus antigens. Clinical manifestations include:

Wheezing
Pulmonary in ltrates (usually mucoid impaction)
Bronchiectasis
Fibrosis

The diagnosis of ABPA in people with CF is di cult and often delayed because of shared clinical
features. ABPA has been associated with accelerated deterioration in lung disease, so timely

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diagnosis and treatment are imperative. 

Methodology
An expert panel was convened and a consensus conference held in 2001. The panel used the
United States Preventive Services Task Force, 1989 grading methodology.

Recommendations

Diagnosis: Classic Case

Recommendations Evaluation of the Evidence

1. Acute or subacute clinical deterioration Consensus

(cough, wheeze, exercise intolerance,
exercise-induced asthma, decline in
pulmonary function, increased sputum) not
attributable to another etiology.

2. Serum total IgE concentration of >1000 IU Consensus

per mL unless patient is receiving systemic
corticosteroids (if so, retest when steroid
treatment is discontinued).

3. Immediate cutaneous reactivity to Consensus

Aspergillus (prick skin test wheal of ≥3 mm in
diameter with surrounding erythema, while
the patient is not being treated with
systemic antihistamines) or in vitro presence
of serum IgE antibody to A. fumigatus.

4. Precipitating antibodies to A. fumigatus or Consensus

serum IgG antibody to A. fumigatus by an in
vitro test.

5. New or recent abnormalities on chest Consensus

radiography (in ltrates or mucus plugging)
or chest CT (bronchiectasis) that have not
cleared with antibiotics and standard
physiotherapy.

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Minimal Diagnostic Criteria

Recommendations Evaluation of the Evidence

6. Acute or subacute clinical deterioration Consensus

(cough, wheeze, exercise intolerance,
exercise-induced asthma, change in
pulmonary function, or increased sputum
production) not attributed to another
etiology.

7. Total serum IgE concentration of >500 IU Consensus

per mL. If ABPA is suspected and the total
IgE level is 200-500 IU per mL, repeat testing
in one to three months is recommended. If
patient is taking steroids, repeat when
steroid treatment is discontinued.

8. Immediate cutaneous reactivity to Consensus

Aspergillus (prick test wheal >3 mm with
surrounding erythema, o systemic
antihistamines) or in vitro demonstration of
IgE antibody to A. fumigatus.

9. One of the following: Consensus

a. Precipitins to A. fumigatus  or in vitro

demonstration of IgG antibody to A.
fumigatus

b. New or recent abnormalities on chest

radiography (in ltrates or mucus
plugging) or chest CT (bronchiectasis)
that have not cleared with antibiotics and
standard physiotherapy 

Screening for ABPA

Recommendations Evaluation of the Evidence

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10. Maintain a high level of suspicion for ABPA Consensus

in patients >6 years of age.

11. Determine the total serum IgE Consensus

concentration annually. If the total serum
IgE concentration is >500 IU per mL,
determine immediate cutaneous reactivity
to A. fumigatus or use an in vitro test for IgE
antibody to A. fumigatus. If results are
positive, consider diagnosis on the basis of
minimal criteria.

12. If the total serum IgE concentration is 200- Consensus

500 IU per mL, repeat the measurement if
there is increased suspicion for ABPA, such
as by a disease exacerbation, and perform
further diagnostic tests (immediate skin test
reactivity to A. fumigatus, in vitro test for IgE
antibody to A. fumigatus, A. fumigatus
precipitins, or serum IgG antibody to A.
fumigatus and chest radiography).

Imaging

Recommendations Evaluation of the Evidence

13. Bronchiectasis a. Grade II-2

b. Grade II-2
a. Central predominance, common in ABPA
without CF, is rare in CF c. Grade III
b. Lobar distribution of bronchiectasis is
similar in both diseases
c. Central varicose bronchiectasis suggests
ABPA

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14. Pulmonary in ltrates a. Grade III

b. Grade III
a. In ltrates are common in both ABPA and
CF
b. In ltrates are more likely to partially or
completely clear in response to steroids
in ABPA, or CF with ABPA, than in CF
without ABPA, although this response is
variable

15. Mucus plugging a. Grade III

b. Grade II-2
a. High attenuation mucus plugs have been
reported in ABPA and not in CF c. Grade II-3
b. Mucus plugs are common in CF and in
ABPA
c. Centrilobular nodules are seen in CF and
in ABPA

16. Pleural thickening Grade III

a. Pleural thickening is seen in ABPA and in

advanced CF

17. Imaging modality Grade III

a. All imaging features described above are

best identi ed with CT

Treatment

Recommendations Evaluation of the Evidence

18. First line: systemic steroids -- prednisone Grade II-3

0.5-2.0 mg per kg per day, one to two weeks
-- then attempt to taper within two to three
months.

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19. Second line: antifungal -- oral itraconazole 5 Grade III

mg per kg per day (max 400 mg per day) for
three to six months (if slow or poor
response to steroids, relapse, or steroid
toxicity).

a. Therapeutic drug monitoring, liver

function tests

20. Bronchodilators, inhaled steroids, Grade III

antiasthma drugs only if indicated for
asthma.

Unanswered Questions
New animal models are needed to better represent ABPA in CF. For example, Urb et al.
developed a promising murine model for chronic Aspergillus airway infection (Infect Immun
2015, 83, 3590).

New and/or validated ways to better classify and distinguish Aspergillus lung phenotypes (i.e.,
colonization, infection/bronchitis, sensitization, and ABPA) are needed. For example, Baxter et
al. added sputum Aspergillus PCR and galactomannan to standard serologic assays (J Allergy Clin
Immunol 2013, 132, 560-6.e10). Gernez et al. showed diagnostic accuracy of basophil activation
test (Eur Resp J 2016, 47, 177).

There is continued need for randomized placebo-controlled trials testing the e cacy of
antifungals and Th2-directed biologics in people with ABPA CF.

Further Reading
Relevant manuscripts published after the original guidelines are listed below. These manuscripts
have not been reviewed or endorsed by the guidelines committee.

Diagnostics
Tracy MC, Okorie CUA, Foley EA, Moss RB. Allergic Bronchopulmonary Aspergillosis. J. Fungi.
2016 Jun;2(2), 17.
Agarwal R, Chakrabarti A, Shah A, Gupta D, Meis JF, Guleria R, Moss R, Denning DW; ABPA
complicating asthma ISHAM working group. Allergic bronchopulmonary aspergillosis: a
review of literature and proposal of new diagnostic and classi cation criteria. Clin Exp Allergy.
2013 Aug;43(8):850-73.PMID: 23889240

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Phuyal S, Garg MK, Agarwal R, Gupta P, Chakrabarti A, Sandhu MS, Khandelwal N. High-
attenuation mucus impaction in patients with allergic bronchopulmonary aspergillosis:
objective criteria on high-resolution computed tomography and correlation with serologic
parameters. Curr Probl Diagn Radiol. 2016 May-Jun;45(3):168-73. Epub 2015 Aug 10.PMID:
26323654

Treatment
First-line treatment: Oral glucocorticosteroids: Agarwal R, Aggarwal AN, Dhooria S, Singh
Sehgal I, Garg M, Saikia B, Behera D, Chakrabarti A. A randomised trial of glucocorticoids in
acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Resp J. 2016
Feb;47(2):490-8. Epub 2015 Nov 19.PMID: 26585431
IV pulse glucocorticosteroids: Cohen-Cymberknoh M, Blau H, Shoseyov D, Mei-Zahav M,
Efrati O, Armoni S, Kerem E. Intravenous monthly pulse methylprednisolone treatment for
ABPA in patients with cystic brosis. J Cyst Fibros. 2009 Jul;8(4):253-7. Epub 2009 May
15.PMID: 19447081
Systemic antifungals: Elphick HE, Southern KW. Antifungal therapies for allergic
bronchopulmonary aspergillosis in people with cystic brosis. Cochrane Database System Rev
2016, 11, CD002204.PMID: 27820955
Inhaled amphotericin: Ram B, Aggarwal AN, Dhooria S, Sehgal IS, Garg M, Behera D,
Chakrabarti A, Agarwal R. A pilot randomized trial of nebulized amphotericin in patients with
allergic bronchopulmonary aspergillosis. J Asthma. 2016 Jun;53(5):517-24. Epub 2016 Jan
22.PMID: 26666774
Omalizumab: Clinicaltrials.gov identi er NCT00787917-
https://clinicaltrials.gov/ct2/show/NCT00787917
Omalizumab: Voskamp AL, Gillman A, Symons K, Sandrini A, Rolland JM, O'Hehir RE,
Douglass JA. Clinical e cacy and immunologic e ects of omalizumab in allergic
bronchopulmonary aspergillosis. J Allergy Clin Immunol Pract. 2015 Mar-Apr;3(2):192-9. Epub
2015 Jan 29.PMID: 25640470
Omalizumab: Jat KR, Walia DK, Khairwa A. Anti-IgE therapy for allergic bronchopulmonary
aspergillosis in people with cystic brosis. Cochrane Database System Rev. 2015 Nov 4;
(11):CD010288.PMID: 26545165

This executive summary was prepared by:

Caroline Okorie, M.D., MPH and Richard B. Moss, M.D. (Stanford University)

The guidelines were published in October 2003, they were reviewed in April 2019 and it was
determined that no update is needed at this time.

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