Koichiro Asano; Katsuhiko Kamei; Akira Hebisawa

doi:10.5415/apallergy.2018.8.e24

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Asano, Kamei, and Hebisawa: Allergic bronchopulmonary mycosis – pathophysiology, histology, diagnosis, and treatment

Current Review

Asia Pac Allergy 2018;8(3):e24.

Published online: 4 July 2018

DOI: https://doi.org/10.5415/apallergy.2018.8.e24

Allergic bronchopulmonary mycosis – pathophysiology, histology, diagnosis, and treatment

Koichiro Asano^1,^*, Katsuhiko Kamei², Akira Hebisawa³

¹Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan

²Medical Mycology Research Center, Chiba University, Chiba 263-8522, Japan

³Clinical Research Center, National Hospital Organization Tokyo National Hospital, Tokyo 152-8902, Japan

^*Correspondence to Koichiro Asano Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. Tel: +81-463-93-1121 Fax: +81-463-93-0381 E-mail: ko-asano@tokai-u.jp

Received 9 June 2018 Accepted 9 July 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Allergic bronchopulmonary mycosis (ABPM) develops mainly in patients with asthma or cystic fibrosis via types I and III hypersensitivity reactions to filamentous fungi. Aspergillus spp., especially Aspergillus fumigatus, is the major causative fungus because of its small conidia, thermophilic hyphae, and ability to secrete serine proteases. The cardinal histological feature of ABPM is allergic (eosinophilic) mucin-harboring hyphae in the bronchi, for which the formation of extracellular DNA trap cell death (ETosis) of eosinophils induced by viable fungi is essential. Clinically, ABPM is characterized by peripheral blood eosinophilia, increased IgE levels in the serum, IgE and IgG antibodies specific for fungi, and characteristic radiographic findings; however, there are substantial differences in the clinical features of this disease between East and South Asian populations. Systemic corticosteroids and/or antifungal drugs effectively control acute diseases, but recurrences are quite common, and development of novel treatments are warranted to avoid adverse effects and emergence of drug-resistance due to prolonged treatment with corticosteroids and/or antifungal drugs.

Keywords: Fungus, Aspergillus fumigatus, Eosinophils, Allergy

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Fig. 1.

Histology of allergic (eosinophilic) mucin in the bronchi. Mucus plugs packed in the bronchi of surgically-resected lungs from a patient with allergic bronchopulmonary mycosis demonstrate a fir tree-like structure (A: H&E, x5), which contain many eosinophils, Charcot-Leyden crystals, and fibrin exudates (B: H&E, x40). (C) Hyphae of fungi are sparsely found in mucus plugs (Grocott staining, x40).

Table 1.

Clinical characteristics of allergic bronchopulmonary aspergillosis (ABPA) in East and South Asia

Characteristic	East Asia						South Asia
Characteristic	Japan		Korea		China		India
Study
Author [reference number]	Tanimoto [39]	Ishiguro [36]	Oguma [7]	Kim [37]	Ye [40]	Zhang [41]	Behera [34]	Chakrabarti [35]	Prasad [38]	Agarwal [6]	Agarwal [33]
Publication year	2015	2016	2018	2012	2009	2017	1994	2002	2009	2010	2018
No. of cases	53	42	358	10	57	77	35	89	42	234	131
Age (yr)	57	57	64	63	41	42	34	36	31	34	37
Women	42%	–	57%	20%	42%	51%	60%	39%	36%	47%	47%
Asthma	79%	67%	81%	100%	–	96%	94%	80%	100%	100%	100%
Duration between onset of asthma and ABPA (yr)	31	–	14	15	–	–	11	12	12	6	12
Peripheral blood eosinophil counts (/µL)	580	–	1,075	1,198	–	–	–	–	–	847	1,271
Serum IgE levels (IU/mL)	1,170	–	1,913	927	–	–	–	–	–	5,015	10,540
Serum IgE levels > 1,000 IU/mL	–	81%	68%	50%	–	71%	–	–	–	–	100%
Specific IgE or immediate skin reaction to	100%	96%	100%	100%	–	89%	51%	82%	98%	100%	95%
Aspergillus antigen
Precipitins for Aspergillus antigen	–	77%	73%	–	–	57%	77%	72%	100%	83%	50%
Culture-positive for Aspergillus spp.	–	60%	59%	–	–	38%	–	63%	69%	–	–
Radiographic findings	–	–	–	–	–	–	–	–	–	–	–
Pulmonary opacities	–	100%	88%	20%	56%	79%	–	43%	95%	–	66%
Central bronchiectasis	–	98%	89%	80%	44%	81%	71%	69%	100%	77%	93%
High attenuation mucus	–	–	41%	–	–	–	–	–	–	21%	41%

Table 2.

Comparison of diagnostic criteria

Diagnostic criteria	Rosenberg-Patterson 1977	Greenberger-Patterson 1986	ISHAM 2013
Asthma or cystic fibrosis	●	●	●
Peripheral blood eosinophilia	●		○
Increased levels of IgE in serum	●	●	●
Immediate skin reaction to Aspergillus antigen	●	●	●
Specific IgE to Aspergillus fumigatus		●	●
Specific IgG to Aspergillus fumigatus		●	○
Precipitin to Aspergillus fumigatus	●		○
Pulmonary opacities	●		○
Central bronchiectasis	●	●	○
Positive sputum culture of Aspergillus fumigatus	△
Expectoration of brownish mucous plugs	△
Arthus-type skin reaction to Aspergillus antigen	△

Closed circles are mandatory components. In International Society for Human Animal Mycology (ISHAM) criteria, 2 out of 3 components (open circles) should also be fulfilled. Triangles are secondary components, further supporting the diagnosis of allergic bronchopulmonary aspergillosis.

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