ABSTRACT
BACKGROUND: Neuropilin-1 (NRP1) is expressed on the surface epithelium of respiratory tract and immune cells, demonstrating its possible function in regulating the immune response in airway disease. However, its role in patient with chronic rhinosinusitis (CRS) remains unknown. This study aimed to elucidate the role of NRP1 in CRS with nasal polyps (CRSwNP). METHODS: Sinonasal biopsy specimens were immunohistochemically stained to investigate NRP1 expression. Double immunofluorescence, immunoblotting, and real-time polymerase chain reaction were performed to evaluate NRP1 in primary human nasal epithelial cells (hNECs). An NRP1 inhibitor was administered to a murine nasal polyp (NP) model. RESULTS: NRP1 was highly expressed in the epithelium in patients with CRSwNP compared to nasal tissue from controls and CRS without NP patients. NRP1 and vascular endothelial growth factor were upregulated in hNECs under hypoxia. Treatment with NRP1 inhibitor (EG00229) reduced the secretion of interleukin (IL)-1ß, IL-6, IL-8, and IL-33 cytokines, as well as inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2 in hNECs. We found that NRP1 was highly expressed in the airway epithelium in the murine NP model. The group treated with the NRP1 inhibitor had significantly fewer nasal polypoid lesions and reduced accumulations of immune cells. CONCLUSIONS: These findings reveal that NRP1 is upregulated in CRS and NP epithelium, and the inhibition of NRP1 may lead to a reduction in NP growth and immune cell infiltration. Our results suggest that NRP1 inhibition could be a novel possibility for treating nasal polyposis.
ABSTRACT
Objectives: The relationships among positional obstructive sleep apnea (POSA), obstructive sleep apnea (OSA), and periodic limb movement during sleep (PLMS) are unclear. We analyzed these relationships according to OSA severity and explored the underlying mechanisms. Methods: We retrospectively reviewed 6,140 eligible participants who underwent full-night diagnostic polysomnography in four clinical centers over a period of 5 years with eventsynchronized analysis. The PLMS index (PLMI) and periodic limb movements with arousal index (PLMAI) were evaluated. The effects of POSA on the PLMI, PLMAI, and PLMS were analyzed according to OSA severity. Results: The mean PLMI and PLMAI, as well as PLMS prevalence, were significantly lower in those with severe OSA than in those with mild and moderate OSA. The mean PLMI was higher in mild OSA group than in control group. The mean PLMI (4.80 ± 12.71 vs. 2.59 ± 9.82 events/h, p < 0.001) and PLMAI (0.89 ± 3.66 vs. 0.53 ± 3.33 events/h, p < 0.001), and the prevalence of PLMS (11% vs. 5.3%, p < 0.001) were higher in patients with POSA than patients with non-POSA. This trend was particularly marked in severe OSA group (OR 1.55, 95%CI [1.07-2.27]) and less so in mild (OR 0.56, 95%CI [0.30-1.03]) and moderate (OR 1.82, 95%CI [0.99-3.34]) OSA groups. Conclusion: The POSA group tended to have a higher prevalence of PLMS, particularly in those with severe OSA. If PLMS is prominent, diagnosis and treatment of POSA and OSA may be considered.