A research group including Specially Appointed Assistant Professor Naoto Adachi, Assistant Professor Masanori Kidoguchi, and Professor Shigeharu Fujieda of the School of Medical Sciences at the University of Fukui, along with Professor Emiko Noguchi of the Faculty of Medicine at the University of Tsukuba, in collaboration with Northwestern University in the U.S. and Dokkyo Medical University, has clarified the involvement of fungi in "eosinophilic chronic rhinosinusitis (ECRS)". ECRS is an intractable form of sinusitis previously thought to occur without fungal infection.
Using high-sensitivity analysis with next-generation sequencing, the team confirmed the resident presence of fungi in all subjects, including healthy individuals. They discovered that cases where Alternaria (a type of mold) was detected had a 2.81-fold higher rate of nasal polyp recurrence compared to non-detection cases. This breakthrough is expected to lead to the formulation of new therapeutic strategies. The findings were published in the American Journal of Respiratory and Critical Care Medicine on May 27.
Provided by the University of Fukui
ECRS is designated as an intractable medical condition in Japan. It causes multiple polyps to form within the nasal cavity, leading to severe nasal congestion and loss of smell. It is also frequently accompanied by asthma or otitis media (middle ear inflammation). Even after the surgical removal of nasal polyps via endoscopic sinus surgery, the condition recurs with high probability. The underlying mechanism behind this recurrence has long been unknown.
ECRS has conventionally been classified as a disease that does not involve fungi. However, because fungi are known to induce Type 2 inflammation in the upper respiratory tract mucosa, their involvement in ECRS had been suspected. Traditional detection methods relied on cultivation techniques, which had limitations in sensitivity, leaving the truth unverified.
To address this, the research group comprehensively analyzed intranasal fungi based on fungal DNA sequences using next-generation sequencing. Specifically, they identified fungal species by analyzing the ITS (internal transcribed spacer) region of samples obtained from middle meatus swabs of 168 individuals in total: 81 ECRS cases, 53 non-ECRS cases, and 34 healthy controls.
As a result, fungi were detected in almost all subjects, including the healthy controls. The team successfully identified seven major genera: Malassezia, Candida, Cladosporium, Aspergillus, Alternaria, Trametes, and Schizophyllum. Malassezia was detected in nearly all subjects, while Candida was found in 51% and Alternaria in 20% of the participants.
Next, the team investigated the relationship between fungal species and disease recurrence. They found that the ECRS group in which Alternaria was detected experienced significantly higher postoperative recurrence than the non-detection ECRS group, with Candida showing a similar trend. In the Alternaria-detected ECRS group, approximately 75% experienced a recurrence within one year after surgery, compared to only about 25% in the non-detection group.
Furthermore, multivariate analysis revealed that Alternaria alone was significantly correlated with postoperative nasal polyp recurrence. Alternaria was revealed to be an independent postoperative recurrence factor with a hazard ratio of 2.81 and P = 0.002.
Patients in the Alternaria-detected ECRS group exhibited significantly higher fungal diversity compared to the non-detection ECRS group, suggesting that this diversity may play a role in the pathophysiology of the disease. Additionally, it was revealed that the expression of IL-33, an inflammatory cytokine, was significantly higher in the Alternaria-detected patient group.
IL-33 is known to trigger allergic Type 2 inflammation via group 2 innate lymphoid cells. It is hypothesized that Alternaria acts on nasal mucosal epithelial cells to stimulate the production of IL-33, thereby exacerbating Type 2 inflammation and causing postoperative recurrence.
Adachi stated: "Moving forward, more precise diagnosis and individualized treatment for this fungal-latent type of ECRS may become necessary. For example, performing a fungal test prior to surgery could serve as a vital guide for postoperative follow-up, allowing us to implement additional postoperative drug treatments or topical therapies if Alternaria is detected."
Journal Information
Publication: American Journal of Respiratory and Critical Care Medicine
Title: Association Between Fungi and Postoperative Recurrence in Eosinophilic Chronic Rhinosinusitis
DOI: 10.1093/ajrccm/aamag254
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.