[A MULTICENTER CLINICAL SURVEY ABOUT THE PREVALENCE OF JAPANESE CYPRESS POLLINOSIS AND THE EFFICACY OF SUBLINGUAL IMMUNOTHERAPY WITH JAPANESE CEDAR POLLEN EXTRACT DURING JAPANESE CYPRESS POLLEN DISPERSAL PERIOD].

BACKGROUND: Little is known whether sublingual immunotherapy using Japanese cedar pollen extract (cedar SLIT) is effective for not only Japanese cedar pollinosis but also Japanese cypress pollinosis. We investigated the prevalence rate of Japanese cypress pollinosis, efficacy of cedar SLIT on cypress pollinosis and patients' wish to receive cypress SLIT. METHODS: We investigated a multi-center (31 institutions), cross-sectional survey using a self-administrated questionnaire with four questions for patients received cedar SLIT aged from 5 to 69 years old. RESULTS: 2523 subjects were enrolled for analysis. 83.4% of them had pollinosis symptoms during cypress season before cedar SLIT. In such patients, 37.4% experienced lessened efficacy of cedar SLIT during cypress season. Both the prevalence of cypress pollinosis and the lessened efficacy of cedar SLIT on cypress pollinosis were significantly seen in western Japan as compared to eastern Japan. 76.1% of the subject having cypress pollinosis before SLIT wished to receive cypress SLIT if it is available. CONCLUSION: A lessened efficacy of cedar SLIT during cypress season was broadly seen in Japan, and further showed a regional difference. Together with the finding of high wish by patients, these results suggest a development of cypress SLIT is desirable.

Preliminary Clinical Trial of Biomarkers to Predict Response to Sublingual Immunotherapy for Japanese Cedar Pollinosis.

BACKGROUND: As part of the planning for a future multicenter study, this preliminary clinical trial used serum samples from patients to identify biomarkers for predicting the therapeutic effects of sublingual immunotherapy (SLIT) for Japanese cedar pollinosis (JCP). METHODS: This prospective study included patients undergoing SLIT for JCP at our hospital. All enrolled patients (N = 17) started SLIT between June and November of 2015. With informed consent from the patients, blood samples were obtained in January, March, and June of 2016, and patients completed the Japan rhino-conjunctivitis quality of life questionnaire (JRQLQ). On the basis of the JRQLQ results, the 6 patients with the best outcomes were included in the high-response group (HRG), and the 5 patients with the worst outcomes were included in the poor-response group (PRG). We then compared serum data between the two groups, to identify useful biomarkers. RESULTS: IL-12p70 and VEGF levels tended to be higher in the HRG than in the PRG in January, March, and June (0.10 > p > 0.05). In addition, the June IL-17 level was significantly higher (p < 0.05) in the HRG than in the PRG. CONCLUSIONS: IL-12p70 and VEGF may be useful biomarkers for predicting the effects of SLIT. In addition, although IL-17 does not appear to be useful as a biomarker for evaluating treatment response at the start of SLIT, it may be useful as a biomarker after the beginning phase of SLIT.

Anti-Inflammatory Effects of EM900 on Cultured Human Nasal Epithelial Cells.

OBJECTIVES: Macrolide therapy is an important conservative therapy for chronic rhinosinusitis, especially in Japan. The mechanism underlying this therapy involves anti-inflammatory and not antimicrobial activity. However, the administration of long-term low-dose macrolides (LTLMs) causes an increase in the number of antibiotic-resistant bacteria. EM900 is a derivative of erythromycin (EM), with anti-inflammatory but not antibacterial effects. It does not induce macrolide-resistant bacteria as shown by LTLM. In the present study, we analyzed the inhibitory effects of EM900 in comparison with those of clarithromycin (CAM) on inflammatory cytokine production in human nasal epithelial cells (HNEpCs). METHODS: After HNEpCs were cultured for 4 days, CAM or EM900 was added into the culture, followed by stimulation with tumor necrosis factor (TNF)-α. Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) levels were measured using real-time polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). RESULTS: Both the ELISA and RT-PCR showed that EM900 and CAM significantly inhibited IL-8 production in HNEpCs. In contrast, EM900 and CAM did not suppress the increased VEGF production when HNEpCs were stimulated with TNF-α. CONCLUSION: EM900 showed an anti-inflammatory effect, such as that of CAM, due to the inhibitory effect on IL-8 production in HNEpCs.