Aspergillus Precipitating Antibodies, IgG

CPT: 86606(x6)
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Test Includes

Aspergillus fumigatus, Aspergillus flavus, Aspergillus glaucus, Aspergillus niger, Aspergillus nidulans, and Aspergillus terreus


Expected Turnaround Time

4 - 5 days


Related Documents


Specimen Requirements


Specimen

Serum


Volume

0.3 mL


Minimum Volume

0.2 mL (Note: This volume does not allow for repeat testing.)


Container

Gel tube


Collection

Transfer separated serum to a plastic transport tube.


Storage Instructions

Room temperature


Test Details


Use

Detection of Aspergillus IgG Precipitins


Limitations

Although ABPA and CPA represent two distinct manifestations of Aspergillus-related lung disease, a patient can evolve with time from one category to the other, making the specific diagnosis challenging, particularly in the context of chronic lung disease.14,16,18,25,36 It should also be noted that in some patients with CPA, the Aspergillus IgG may remain negative even in the presence of symptoms, radiology, and laboratory diagnostics.25,28 Lastly, while the LabCorp Aspergillosis precipitins assay includes most species associated with Aspergillus-related lung disease, several other species not tested for have been implicated in aspergillosis in certain populations.


Methodology

Ouchterlony gel double-diffusion


Additional Information

Aspergillus species are ubiquitous environmental molds that grow on organic matter and aerosolize conidia.1,3 Humans inhale hundreds of conidia per day without adverse consequences, except for a small minority of people for whom infection with Aspergillus causes significant morbidity. The clinical manifestations of aspergillosis are determined by the host immune response to exposure with the spectrum ranging from a simple allergic response to local lung disease with mycelial balls to catastrophic systemic Aspergillus infection.

Aspergillus is a genus of molds that includes several hundred species that grow in nutrient-depleted environments.1,3 These obligate aerobes are ubiquitous and can be found in virtually every oxygen-rich setting. Aspergillus molds are saprophytes that thrive on decaying organic matter. They are often found as contaminants of starchy foods and other carbon-rich substrates. They are commonly found in soil and marine habitats as well as indoor environments and in drinking water.2 Of the hundred species identified, only a few have been associate with pathology in humans.2-4 Aspergillus fumigatus is the species most commonly associated with disease.5 Other species that have been linked to disease include A. flavus, A. glaucus, A. niger, A. nidulans and A. terreus.5-14

Aspergillus molds continuously disseminate spores (conidia) into the environment.2 Humans are constantly exposed to airborne Aspergillus spores which, once inhaled, can access the most distal airways of the lungs due to their size and durability.14 In immunocompetent individuals with healthy lungs, inhaled conidia are eliminated by the neutrophils and macrophages of the innate immune system and do not lead to disease.2,14 Illness only develops in a small proportion of patients with altered immune systems or underlying lung pathology.1,3,14-17 Non-invasive forms of Aspergillus-induced lung disease include Allergic Bronchopulmonary Aspergillosis (ABPA) and Chronic Pulmonary Aspergillosis (CPA).4,18 In severely immunocompromised individuals, Aspergillus infection of the respiratory system can spread to other organs in a condition referred to as Invasive Pulmonary Aspergillosis (IPA).2,3,15 Antibody testing is central to diagnosis of these conditions, with raised Aspergillus-specific IgG often seen in patients with ABPA and CPA. Antibody levels are also used to monitor treatment response in these syndromes.

Allergic Bronchopulmonary Aspergillosis (ABPA)

ABPA is a relatively uncommon allergic reaction to Aspergilli that almost exclusively affects individuals with asthma or cystic fibrosis.4,14,15,19 ABPA typically causes bronchospasm and mucus buildup resulting in coughing, breathing difficulty and airway obstruction. Bronchiectasis can develop resulting in worsening lung function and increased risk of infection. ABPA in patients with poorly controlled asthma has also been referred to as Severe Asthma with Fungal Sensitization (SAFS).20

The diagnostic criteria for ABPA include the presence of a predisposing condition (asthma or cystic fibrosis) and positive allergen specific IgE to aspergillus species and a total IgE >1000 IU/mL.21,37-39 Serum aspergillus IgG precipitins and a blood eosinophil count >500 cells/L in corticosteroid naive patients support the diagnosis of ABPA.21 A positive precipitin reaction against A. fumigatus can be demonstrated in 69-90% of patients with ABPA.37,38 but also in 10% of asthmatics without ABPA39 and in semi-invasive forms of aspergillosis like CPA.

Chronic Pulmonary Aspergillosis (CPA)

CPA is an uncommon, slowly destructive pulmonary disease characterized by progressive lung cavitation, fibrosis, and pleural thickening caused by Aspergillus infection of the pulmonary parenchyma in subjects with normal or mildly suppressed immunity and underlying structural lung disease.6,14-17, 22-27 Predisposing conditions include pulmonary tuberculosis, nontuberculous mycobacterial infection, sarcoidosis, pneumothorax, chronic obstructive pulmonary disease, surgically treated lung cancer and other cavitating or bullous lung conditions. Patients with CPA can present with chronic productive cough, weight loss and hemoptysis with nodules, cavities or fungal balls (aspergilloma) on chest imaging.

The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), defined as one or more pulmonary cavities that may or may not contain solid or liquid material or a fungal ball with significant pulmonary or systemic symptoms and overt radiographic progression.2,23 Untreated, CCPA can progress to chronic fibrosing pulmonary aspergillosis (CFPA).25 A less common manifestation of CPA is the simple aspergilloma, a fungal ball consisting of Aspergillus hyphae, fibrin and other debris, formed within a pre-existing area of pulmonary scar or cavity that has been colonized by Aspergillus.15,22,25

Guidelines for the diagnosis and management of CPA were published in 2016 jointly by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Respiratory Society (ERS), and the European Confederation of Medical Mycology (ECMM).25 Also, the Infectious Diseases Society of America (IDSA) established recommendations for the diagnosis of CPA in the same year.23 According to these guidelines, the diagnosis of CPA requires one or more cavities with or without a fungal ball or nodules present on thoracic imaging for ≥ 3 months, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus specie(s), and exclusion of alternative diagnoses.25 Several studies support the utility of measuring Aspergillus precipitins for diagnosing CPA.5,24,28-30 A recent study indicated that the test was positive in more than 95% of cases32 while another study indicated 89.3% positivity compared to only 50% with Aspergillus galactomannan antigen ELISA tests.31 The Aspergillus IgG precipitins test has been reported to have a positive predictive value of 100% in differentiating infected and colonized individuals.25,33 If antibody testing is not positive, then other evidence of Aspergillus infection is required.25

Invasive Pulmonary Aspergillosis (IPA)

Chronic and allergic forms of aspergillosis are much more common than IPA.34,35 Aspergillus infection in severely immunocompromised patients, such as individuals with hematological cancers or organ/stem cell transplant recipients, can lead to IPA, the most serious entity on the spectrum of pulmonary aspergillosis.17,23 This life threatening disease is characterized by invasion of lung tissue by Aspergillus hyphae and subsequent spread into the lung parenchyma and associated vasculature.14 IPA can lead to intravascular thrombosis and hemorrhagic pulmonary infarction15 and has a relatively rapid progression (ranging from days to a few weeks) with a very high mortality rate.14,17,23,30 Aspergillus IgG precipitins testing is generally not useful in the diagnosis of IPA due to the lack of antibody production in severely immunocompromised patients.15,23,28


Footnotes

1. Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011 Sep 1;20(121):156-174.21881144
2. Paulussen C, Hallsworth JE, Álvarez-Pérez S, et al. Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. Microb Biotechnol. 2017 Mar;10(2):296-322.27273822
3. Mousavi B, Hedayati MT, Hedayati N, Ilkit M, Syedmousavi S. Aspergillus species in indoor environments and their possible occupational and public health hazards. Curr Med Mycol. 2016 Mar;2(1):36-42.28681011
4. Maghrabi F, Denning DW. The Management of Chronic Pulmonary Aspergillosis: The UK National Aspergillosis Centre Approach. Curr Fungal Infect Rep. 2017;11(4):242-251.29213345
5. Denning DW. Chronic forms of pulmonary aspergillosis. Clin Microbiol Infect. 2001;7 Suppl 2:25-31.11525215
6. Barac A, Kosmidis C, Alastruey-Izquierdo A, Salzer HJF, CPAnet. Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1;57(Supplement_2):S104-S109.30816975
7. Perfect JR, Cox GM, Lee JY, et al. The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clin Infect Dis. 2001 Dec 1;33(11):1824-1833.11692293
8. Steinbach WJ, Marr KA, Anaissie EJ, et al. Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH Alliance registry. J Infect. 2012 Nov;65(5):453-464.22898389
9. Enoch DA, Ludlam HA, Brown NM. Invasive fungal infections: a review of epidemiology and management options. J Med Microbiol. 2006 Jul;55(Pt 7):809-818.16772406
10. Gupta K, Gupta P, Mathew JL, et al. Fatal Disseminated Aspergillus penicillioides Infection in a 3-Month-Old Infant with Suspected Cystic Fibrosis: Autopsy Case Report with Review of Literature. Pediatr Dev Pathol. 2016 Nov/Dec;19(6):506-511.26579953
11. Balajee SA, Kano R, Baddley JW, et al. Molecular identification of Aspergillus species collected for the Transplant-Associated Infection Surveillance Network. J Clin Microbiol. 2009 Oct;47(10):3138-3141.19675215
12. Balajee SA, Houbraken J, Verweij PE, et al. Aspergillus species identification in the clinical setting. Stud Mycol. 2007;59:39-46.18490954
13. Lass-Flörl C, Griff K, Mayr A, et al. Epidemiology and outcome of infections due to Aspergillus terreus: 10-year single centre experience. Br J Haematol. 2005 Oct;131(2):201-207.16197450
14. Yii AC, Koh MS, Lapperre TS, Tan GL, Chotirmall SH. The emergence of Aspergillus species in chronic respiratory disease. Front Biosci (Schol Ed). 2017 Jan 1;9:127-138.27814579
15. Kanj A, Abdallah N, Soubani AO. The spectrum of pulmonary aspergillosis. Respir Med. 2018 Aug;141:121-131.30053957
16. Sehgal IS, Choudhary H, Dhooria S, et al. Diagnostic cut-off of Aspergillus fumigatus-specific IgG in the diagnosis of chronic pulmonary aspergillosis. Mycoses. 2018 Oct;61(10):770-776.29920796
17. Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018 May;24 Suppl 1:e1-e38.29544767
18. Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax. 2015 Mar;70(3):270-277.25354514
19. Shah A, Panjabi C. Allergic Bronchopulmonary Aspergillosis: A Perplexing Clinical Entity. Allergy Asthma Immunol Res. 2016 Jul;8(4):282-297.27126721
20. Greenberger PA. When to suspect and work up allergic bronchopulmonary aspergillosis. Ann Allergy Asthma Immunol. 2013 Jul;111(1):1-4.23806451
21. Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013 Aug;43(8):850-873.23889240
22. Hayes GE, Novak-Frazer L. Chronic Pulmonary Aspergillosis-Where Are We? and Where Are We Going? J Fungi (Basel). 2016 Jun 7;2(2).29376935
23. Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60.27365388
24. Izumikawa K. Recent advances in chronic pulmonary aspergillosis. Respir Investig. 2016 Mar;54(2):85-91.26879477
25. Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016 Jan;47(1):45-68.26699723
26. Schweer KE, Bangard C, Hekmat K, Cornely OA. Chronic pulmonary aspergillosis. Mycoses. 2014 May;57(5):257-270.24299422
27. Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J. 2011 Apr;37(4):865-872.20595150
28. Page ID, Richardson M, Denning DW. Antibody testing in aspergillosis--quo vadis? Med Mycol. 2015 Jun;53(5):417-439.25980000
29. Kohno S, Izumikawa K, Ogawa K, et al. Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis: a multicenter trial in Japan. J Infect. 2010 Nov;61(5):410-418.20797407
30. Zmeili OS, Soubani AO. Pulmonary aspergillosis: a clinical update. QJM. 2007 Jun;100(6):317-334.17525130
31. Kitasato Y, Tao Y, Hoshino T, et al. Comparison of Aspergillus galactomannan antigen testing with a new cut-off index and Aspergillus precipitating antibody testing for the diagnosis of chronic pulmonary aspergillosis. Respirology. 2009 Jul;14(5):701-708.19659648
32. Nam HS, Jeon K, Um SW, et al. Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases. Int J Infect Dis. 2010 Jun;14(6):e479-482.19910234
33. Uffredi ML, Mangiapan G, Cadranel J, Kac G. Significance of Aspergillus fumigatus isolation from respiratory specimens of nongranulocytopenic patients. Eur J Clin Microbiol Infect Dis. 2003 Aug;22(8):457-462.12898283
34. Denning DW, Pleuvry A, Cole DC. Global burden of chronic pulmonary aspergillosis complicating sarcoidosis. Eur Respir J. 2013 Mar;41(3):621-626.22743676
35. Denning DW, Pleuvry A, Cole DC. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol. 2013 May;51(4):361-370.23210682
36. Agarwal R, Dua D, Choudhary H, et al. Role of Aspergillus fumigatus-specific IgG in diagnosis and monitoring treatment response in allergic bronchopulmonary aspergillosis. Mycoses. 2017 Jan;60(1):33-39.27523578
37. Dhooria S, Agarwal R. Diagnosis of allergic bronchopulmonary aspergillosis: a case-based approach. Future Microbiol. 2014;9(10):1195-1208.25405888
38. Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013 Aug;43(8):850-873.23889240
39. Agarwal R, Aggarwal AN, Gupta D, Jindal SK. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis. Int J Tuberc Lung Dis. 2009 Aug;13(8):936-944.19723372

References

Agarwal R, Aggarwal AN, Sehgal IS, Dhooria S, Behera D, Chakrabarti A. Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis. Mycoses. 2016 Jan;59(1):1-6.26575791
Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol. 1988 Apr;81(4):646-650.3356845
Hogan C, Denning DW. Allergic bronchopulmonary aspergillosis and related allergic syndromes. Semin Respir Crit Care Med. 2011 Dec;32(6):682-692.22167396
Izumikawa K, Yamamoto Y, Mihara T, et al. Bronchoalveolar lavage galactomannan for the diagnosis of chronic pulmonary aspergillosis. Med Mycol. 2012 Nov;50(8):811-817.22568603
Knutsen AP, Bush RK, Demain JG, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol. 2012 Feb;129(2):280-291; quiz 292-293.22284927
Schweer KE, Bangard C, Hekmat K, Cornely OA. Chronic pulmonary aspergillosis. Mycoses. 2014 May;57(5):257-270.24299422
Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008 Feb 1;46(3):327-360.18177225

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
606846 Aspergillus Precipitins 660092 Aspergillus fumigatus IgG 19726-9
606846 Aspergillus Precipitins 660068 Aspergillus flavus IgG 19725-1
606846 Aspergillus Precipitins 660050 Aspergillus niger IgG 19727-7
606846 Aspergillus Precipitins 660167 Aspergillus nidulans IgG 47426-2
606846 Aspergillus Precipitins 660159 Aspergillus glaucus IgG 46157-4
606846 Aspergillus Precipitins 607015 Aspergillus terreus IgG 95543-5

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