Two cases of Schizophyllum asthma: Is this a new clinical entity or a precursor of ABPM?

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Abstract

Background

There is a close link between fungal sensitization and asthma severity. Although Schizophyllum commune (S. commune, “suehirotake” in Japanese), one of the basidiomycetous (BM) fungi, is a fungus that can cause allergic bronchopulmonary mycosis (ABPM) and allergic fungal sinusitis (AFS), whether the fungus causes or sensitizes subjects to asthma is unclear.

Methods

The bronchial provocation test using S. commune antigen was performed in two asthmatics who had demonstrated positive skin reactions to the S. commune antigen, and low dose of itraconazole (50 mg/day) was prescribed as an adjunctive therapy for 2 weeks. The allergological features and clinical manifestations of these patients are herein evaluated and discussed.

Results

Case 1 was a 71-year-old female, and case 2 was a 69-year-old male. Both patients demonstrated positive reactions to the inhalation test. A diagnosis of AFS or ABPM was excluded in both patients because of the lack of a history of pulmonary infiltrates, central bronchiectasis, a history of expectoration of brown plugs or flecks, or sinusoidal findings. Although the efficacy of itraconazole in our cases was unclear, the elevated titer of the specific IgG-for S. commune in case 2 gradually decreased during the period of antifungal therapy.

Conclusions

The two patients described herein were diagnosed to have bronchial asthma caused by S. commune; so-called Schizophyllum asthma. S. commune may also be a causative fungal antigen of bronchial asthma.

Introduction

There has been increasing interest in the relationship between severe asthma and fungal sensitization [1], [2], [3]. Therefore, testing in adults with asthma that does not respond to first-line treatments should include not only such routine investigations as lung function, sinus CT scanning, sensitization to common inhalant allergens or evaluation of evidence for allergic bronchopulmonary aspergillosis (ABPA) [4], but should also include an evaluation for evidence of colonization with a range of fungi, including Alternaria, Candida, and Trichophyton, as well as Aspergillus species [5].

Recent research has focused on the possible role of basidiomycetous (BM) fungi as a fungal aeroallergen [6], and allergic fungal respiratory diseases [7] caused by BM fungi have been increasingly reported [8], [9], [10]. Although it is well-known that Schizophyllum commune (S. commune), one of the BM fungi, causes mucoid impaction of bronchi (MIB) [11], allergic bronchopulmonary mycosis (ABPM) [12] and allergic fungal sinusitis (AFS) [13], however, it remains unclear whether this fungus really causes or triggers asthma symptoms similar to Aspergillus species [14].

This report describes two patients with bronchial asthma caused by S. commune; so-called Schizophyllum asthma. Except for the criteria of pulmonary involvement, such as central bronchiectasis and mucoid impaction, both cases met the criteria for ABPM caused by S. commune. Therefore, it was difficult to distinguish Schizophyllum asthma from eosinophilic bronchitis involved in ABPM caused by S. commune.

This raises the question of whether the proposed Schizophyllum asthma is actually a new clinical entity similar to both Trichophyton asthma [15], [16] and Candida asthma [17], or is instead a precursor of ABPM caused by S. commune.

Section snippets

Preparation of the antigenic solution of S. commune

One liter of Sabouraud’s dextrose broth in 3 L flasks was sterilized. Five milliliters of a S. commune spore suspension (105 spores per ml) in sterile physiological saline from 14 day-old Sabouraud’s dextrose agar culture were used to inoculate a flask. The flask was shaken at 25 °C at 150 rpm in a rotary shaker incubator for 14 days. Mycelia were separated by filtration, and centrifuged. The supernatants were dialyzed against 5 mM ammonium bicarbonate and lyophilized.

Intradermal skin test and serological test

The antigenic solution

Discussion

It is important to elucidate the etiological agents and the exacerbating factors involved in allergic fungal respiratory diseases (AFRD) [7]. In particular, there has been increasing interest in the association between severe asthma and fungal sensitization [1], [2], [3]. Recently, it was stated in the Global Initiative for Asthma (GINA) 2009 that describing patients as having allergic asthma is usually of little benefit, unless a single specific trigger can be identified [21]. However, in

Conflict of interest

All authors declare that they have no competing interests that might be perceived to influence the results and discussion reported in the present manuscript.

Acknowledgments

The authors wish to thank Dr. Masakatsu Seo (Seo Laboratory) for extending his help in the macroscopic identification of the fungal species, and Dr. Kazuo Akiyama (Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital) for preparing the antigenic solution. This study was supported in part by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports Science and Technology - Japan (No. 17607003).

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