Brain disorders affect over one billion people globally, presenting significant challenges for effective treatment due to the limited drug bioavailability in the brain. The graphical abstract was created with BioRender.

Background: Chronic rhinosinusitis with nasal polyp (CRSwNP) is a typical type 2 inflammation involving interleukin (IL)‐4 and IL‐13. Dupilumab is a fully human monoclonal antibody targeting IL‐4 receptor α subunit, thereby blocking signaling by both cytokines. Our hypothesis was that IL‐4 and IL‐13, by inducing a severe epithelial dysregulation, are involved in CRSwNP pathogenesis. This study aimed to evaluate the in vitro direct effect of IL‐4, IL‐13, and dupilumab on nasal epithelial functions.Methods: Nasal polyps and control mucosa from 28 patients, as well as human nasal epithelial cells (HNEC) from 35 patients with CRSwNP were used. Three major epithelial functions were investigated: the epithelial barrier function (characterized by transepithelial electrical resistance measurements and tight junction protein expression), the ciliary motion (characterized by the ciliary beating efficiency index), and wound healing (characterized by the wound repair rate) under various stimulations (IL‐4, IL‐13, and dupilumab). The main outcome was a significant change in epithelial functions following exposure to IL‐4, IL‐13, and dupilumab for 48 h in the basal media.Results: IL‐4 (1, 10, and 100 ng/mL) but not IL‐13 induced a significant decrease in occludin and zonula‐occludens protein expression, ciliary beating efficiency, and wound repair rate in HNEC. Dupilumab (0.04 mg/mL) had no effect on HNEC and specifically restored all epithelial functions altered when cells were exposed to a 48‐h IL‐4 stimulation.Conclusion: Dupilumab, in vitro, restored epithelial integrity by counteracting the effect of IL‐4 on the epithelial barrier (increased epithelial permeability, decreased ciliary beating efficiency, and decreased wound repair rate).

Background: Internal valve collapse is a frequent cause of nasal obstruction but remains poorly understood and is sometimes treated inappropriately as a result. No functional or imaging test for the condition has been validated and the reference diagnostic technique is physical examination. The objective of this study was to evaluate the potential of four‐phase rhinomanometry as a diagnostic test for internal valve collapse.Methods: In a case–control diagnostic accuracy study, the nostrils of adult patients consulting for chronic nasal obstruction were classified as “collapsed” or “non‐collapsed” based on clinical findings. Four‐phase rhinomanometry was performed in all patients. The area defined by the path of the flow/pressure curve in the two phases of inspiration (the “inspiratory loop area” or “hysteresis loop area”) was calculated for both nasal cavities and the threshold value with the highest Youden index was identified.Results: Sixty‐six patients (132 nostrils) were included with 72 nostrils classified as collapsed and 60 as non‐collapsed. Before nasal decongestion, the inspiratory loop area with the highest Youden index was 17.3 Pa L s⁻¹ and the corresponding sensitivity and specificity were 88.3% (95% confidence interval, 80.0–95.0%) and 89.9% (82.6–95.7%), respectively.Conclusions: In these patients, a cutoff inspiratory loop area in four‐phase rhinomanometry data reproduced clinical diagnoses of internal valve collapse with high sensitivity and specificity. This method may offer a firmer basis for treatment indications than subjective physical examinations.Level of evidence: Level 4.

FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium. Only three studies evaluated the potential toxicity of biologics’ intranasal delivery, and they all showed that it was safe. This systematic review confirmed that FcRn is expressed in the nasal airway and the olfactory epithelium, and that FcRn may play a role in IgG and/or IgG-derived molecule-transcytosis across the airway epithelium. However, additional research is needed to better characterize the pharmacokinetic and pharmacodynamic properties of biologics after their intranasal delivery.