Small inhaled particles, which are entrapped by the mucous layer that is maintained by mucous secretion via mucin exocytosis and fluid secretion, are removed from the nasal cavity by beating cilia. The functional activities of beating cilia are assessed by their frequency and the amplitude. Nasal ciliary beating is controlled by intracellular ions (Ca²⁺, H⁺ and Cl⁻), and is enhanced by a decreased concentration of intracellular Cl⁻ ([Cl⁻]_i) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which increases the ciliary beat amplitude. A novel method to measure both ciliary beat frequency (CBF) and ciliary beat distance (CBD, an index of ciliary beat amplitude) in cHNECs has been developed using high-speed video microscopy, which revealed that a decrease in [Cl⁻]_i increased CBD, but not CBF, and an increase in [Cl⁻]_i decreased both CBD and CBF. Thus, [Cl⁻]_i inhibits ciliary beating in cHNECs, suggesting that axonemal structures controlling CBD and CBF may have Cl⁻ sensors and be regulated by [Cl⁻]_i. These observations indicate that the activation of Cl⁻ secretion stimulates ciliary beating (increased CBD) mediated via a decrease in [Cl⁻]_i in cHNECs. Thus, [Cl⁻]_i is critical for controlling ciliary beating in cHNECs. This review introduces the concept of Cl⁻ regulation of ciliary beating in cHNECs.

The effects of the isoflavone daidzein on the ciliary beat distance (CBD, which is a parameter assessing the amplitude of ciliary beating) and the ciliary beat frequency (CBF) were examined in ciliated human nasal epithelial cells (cHNECs) in primary culture. Daidzein decreased [Cl⁻]_i and enhanced CBD in cHNECs. The CBD increase that was stimulated by daidzein was mimicked by Cl⁻-free NO₃⁻ solution and bumetanide (an inhibitor of Na⁺/K⁺/2Cl⁻ cotransport), both of which decreased [Cl⁻]_i. Moreover, the CBD increase was inhibited by 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, a Cl⁻ channel blocker), which increased [Cl⁻]_i. CBF was also decreased by NPPB. The rate of [Cl⁻]_i decrease evoked by Cl⁻-free NO₃⁻ solution was enhanced by daidzein. These results suggest that daidzein activates Cl⁻ channels in cHNECs. Moreover, daidzein enhanced the microbead transport driven by beating cilia in the cell sheet of cHNECs, suggesting that an increase in CBD enhances ciliary transport. An [Cl⁻]_i decrease enhanced CBD, but not CBF, in cHNECs at 37 °C, although it enhanced both at 25 °C. Intracellular Cl⁻ affects both CBD and CBF in a temperature-dependent manner. In conclusion, daidzein, which activates Cl⁻ channels to decrease [Cl⁻]_i, stimulated CBD increase in cHNECs at 37 °C. CBD is a crucial factor that can increase ciliary transport in the airways under physiological conditions.

Invasive fungal rhinosinusitis (FRS) is a rare but intractable infectious disease of the sinonasal region with destructive direct infiltration into surrounding tissues, such as the bone, orbit and brain, and potential dissemination to systemic organs. Symptomatic assessments and imaging are frequently not sufficiently diagnostic, and histopathological examination is essential for definite diagnosis of FRS. We herein report a case of chronic invasive FRS (CIFRS) in a 58-year-old Japanese male with end-stage diabetic nephropathy that required maintenance dialysis after graft rejection of living kidney transplantation. His initial main clinical presentation was sinus gangrene, which gradually progressed from the paranasal sinus to the nasal septum and oral palate, but not towards the intracranial or orbital region, for two months. The patient was first strongly suspected to have extranodal natural killer/T cell lymphoma (ENKTL), nasal type, a subtype of malignant lymphoma, based on the macroscopic appearance of the gangrene, expansion pattern and high serum soluble interleukin-2 level; however, repeated biopsies and eventual resection led to diagnosis of CIFRS due to Aspergillus niger and Mucor. The disease was improved by surgical resection in combination with antifungal pharmacologic treatment with liposomal amphotericin B and voriconazole. CIFRS typically occurs in immunocompetent patients and shows intracranial progression, but this case shows that atypical CIFRS with an uncommon expansion pattern can occur in an immunodeficient patient.