Real-Time PCR Detection of the Basidiomycetous Fungus <b><i>Bjerkandera adusta</i></b>: A Tool to Identify Itraconazole Responder Patients with Unexplained Chronic Cough

Abstract

Background: Filamentous basidiomycetes (f-BMs) are involved in some unexplained chronic cough (UCC) cases that can be improved by the administration of antifungal agents. The disease concept was termed fungus-associated chronic cough (FACC). The current diagnostic criteria warrant environmental fungi isolation from respiratory specimens, which is hardly conceivable for such fungi. Objectives: This study aimed to detect the f-BMs Bjerkandera adusta, the most common pathogen in FACC, from respiratory specimens of patients with UCC using real-time polymerase chain reaction (PCR). It also evaluated the applicability of the PCR system to detect antifungal agent responders among patients with unexplained cough. Methods: The PCR system specific to B. adusta was developed and its utility was evaluated using sputum samples from 23 patients with chronic cough. Results: B. adusta was detected in 10 out of 14 patients with UCC (71.4%), in contrast to only 2 out of 9 patients with non-UCC (22.2%; p < 0.05 with the Fisher’s exact test). The copy number of the samples correlated with the therapeutic impact score for cough symptoms following the oral administration of itraconazole. Conclusion: Development of the real-time PCR system enabled us to demonstrate that many patients with UCC might be influenced by B. adusta, a fact evidenced by the improvement of symptoms with itraconazole administration in most PCR-positive patients. This method would help in detecting itraconazole responders among patients with UCC when the isolation of f-BMs is not achievable.

Investigation of Filamentous Basidiomycetes in the Airway Is the Third Unmet Need in the Management of Unexplained Chronic Cough in Adults

“…UCC patients with BM colonization showing a good clinical response to antifungal drugs were diagnosed as having fungus-associated chronic cough (FACC), which has recently been introduced in the Japanese Respiratory Society Guidelines for the Management of Cough and Sputum 2019 [6, 7], and such patients were excluded from initial diagnosis of UCC [8]. In our preliminary studies, central suppressant therapies, such as pregabalin or gabapentin, were not always more efficacious on cough symptoms of FACC patients than antifungal drugs [9].…”