The effect of autosomal dominant polycystic kidney disease on mucociliary clearance.

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a renal disease with genetic transmisson. Mutations in the PKD1 and PKD2 genes, which encode integral membrane proteins of the cilia of primary renal tubule epithelial cells, are seen in ADPKD. The aim of this study was to evaluate the sinonasal epithelium, which is epithelium with cilia, by measuring the nasal mucociliary clearance time, and to investigate the effect of ADPKD on nasal mucociliary clearance. METHODS: The study included 34 patients, selected from patients followed up in the Nephrology Clinic, and 34 age and gender-matched control group subjects. The nasal mucociliary clearance time (NMCT) was measured with the saccharin test. RESULTS: The mean age of the study subjects was 47.15 ± 14.16 years in the patient group and 47.65 ± 13.85 years in the control group. The eGFR rate was determined as mean 72.06 ± 34.26 mL/min in the patient group and 99.79 ± 17.22 mL/min in the control group (p < 0.001). The NMCT was determined to be statistically significantly longer in the patient group (903.6 ± 487.8 s) than in the control group (580 ± 259 s) (p = 0.006). CONCLUSIONS: The study results showed that the NMCT was statistically significantly longer in patients with ADPKD compared to the control group, but in the linear regression analysis results, no correlation was determined between eGFR and NMCT.

The relationship between Covid-19 and mucociliary clearance.

BACKGROUND: The effect of Covid-19 infection on nasal mucociliary clearance (MCC) is unknown. AIMS/OBJECTIVES: The aim of this study is to investigate the relationship between Covid-19 and nasal MCC in terms of smoking, Covid-19 symptoms and treatment. METHODS: Thirty-six patients who were hospitalized in the pandemic ward due to Covid-19 and 36 volunteers (Covid-19 negative test result) who presented to the otolaryngology outpatient clinic with non-nasal symptoms were included in this study. The Saccharin test was performed in both groups to evaluate nasal MCC. RESULTS: The patients and control groups were not significantly different in terms of age and gender. The nasal MCC time was significantly higher in the patient group compared to the control group (19.18 ± 10.84 min and 13.78 ± 8.18 min, p = .003). CONCLUSIONS AND SIGNIFICANCE: In this study, we found that Covid-19 prolonged nasal MCC time regardless of age. We suggest that corticosteroids should be included in the treatment of Covid-19, both with its symptom reduction and its positive effect on MCC duration.

Rhinological manifestations of Sjögren's syndrome: a cohort-matched, prospective, cross-sectional, observational study.

OBJECTIVE: To assess the prevalence of abnormal rhinological findings in a Sjögren's syndrome population. METHODS: A cohort-matched, prospective, cross-sectional, observational study was conducted. Sixty-seven subjects (30 patients and 37 controls) were enrolled. Rhinological assessment including smell threshold was evaluated using a standardised, validated clinical test as part of a larger study. RESULTS: Smell thresholds were -4.4 and -5.4 in the Sjögren's syndrome and control groups, respectively (p = 0.001). Hyposmia (threshold values of less than -4.5) was demonstrated in the Sjögren's syndrome group (47 per cent). Smell was negatively correlated with age (p = 0.040). Nasal septal perforation was noted in 3 Sjögren's syndrome patients (10 per cent) and nasal mucosal dryness in 10 patients (33 per cent), but none of the control group were affected. CONCLUSION: Hyposmia in Sjögren's syndrome was demonstrated using the Smell Threshold Test. Nasal septal perforation and nasal mucosa dryness were also noted in patients with Sjögren's syndrome. A diagnosis of Sjögren's syndrome should be considered and investigated in smell deprivation and/or nasal septal perforation patients.

The relationship between nasal mucociliary clearance time and the degree of smoking dependence in smokers with obstructive sleep apnea syndrome.

INTRODUCTION: The aim of this study was to investigate the relationship between nasal mucociliary clearance time (NMCT), degree of smoking dependence, cumulative smoking burden and OSAS severity in smokers. MATERIAL AND METHODS: 123 patients (Group 1) with OSAS and 92 healthy controls (Group 2) were included in the study. Group 1 was divided into smokers (Group 1a) and non-smokers (Group 1b). In Group 1a, cumulative smoking burden and Fagerström nicotine dependence test (FNDT) were questioned. Saccharin test was applied to Groups 1 and 2. Student-t, Mann-Whitney-U, Anova, Kruskal-Wallis tests were used to compare the means. RESULTS: NMCT was higher in Group 1 than Group 2 (p = 0.005). The duration of NMCT was higher in Group 1A than Group 1B (p = 0.002). In Group 1a, NMCT values of mild and moderate OSAS patients were longer than in Group 1b (p = 0.02, p = 0.01, respectively). NMCT values of patients with mild dependence were shorter than those with moderate or severe dependence (p = 0.032, p < 0.001, respectively). CONCLUSION: Mucociliary clearance time was higher in smokers with OSAS than non-smokers. While OSAS has a negative effect on mucociliary clearance, smoking also exacerbates the condition.

The impact of nasal adhesions on airflow and mucosal cooling - A computational fluid dynamics analysis.

Nasal adhesions are a known postoperative complication following surgical procedures for nasal airway obstruction (NAO); and are a common cause of surgical failure, with patients often reporting significant NAO, despite relatively minor adhesion size. Division of such nasal adhesions often provides much greater relief than anticipated, based on the minimal reduction in cross-sectional area associated with the adhesion. The available literature regarding nasal adhesions provides little evidence examining their quantitative and qualitative effects on nasal airflow using objective measures. This study examined the impact of nasal adhesions at various anatomical sites on nasal airflow and mucosal cooling using computational fluid dynamics (CFD). A high-resolution CT scan of the paranasal sinuses of a 25-year-old, healthy female patient was segmented to create a three-dimensional nasal airway model. Virtual nasal adhesions of 2.5 mm diameter were added to various locations within the nasal cavity, representing common sites seen following NAO surgery. A series of models with single adhesions were created. CFD analysis was performed on each model and compared with a baseline no-adhesion model, comparing airflow and heat and mass transfer. The nasal adhesions resulted in no significant change in bulk airflow patterns through the nasal cavity. However, significant changes were observed in local airflow and mucosal cooling around and immediately downstream to the nasal adhesions. These were most evident with anterior nasal adhesions at the internal valve and anterior inferior turbinate. Postoperative nasal adhesions create local airflow disruption, resulting in reduced local mucosal cooling on critical surfaces, explaining the exaggerated perception of nasal obstruction. In particular, anteriorly located adhesions created greater disruption to local airflow and mucosal cooling, explaining their associated greater subjective sensation of obstruction.

Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19.

The upper respiratory tract is compromised in the early period of COVID-19, but SARS-CoV-2 tropism at the cellular level is not fully defined. Unlike recent single-cell RNA-Seq analyses indicating uniformly low mRNA expression of SARS-CoV-2 entry-related host molecules in all nasal epithelial cells, we show that the protein levels are relatively high and that their localizations are restricted to the apical side of multiciliated epithelial cells. In addition, we provide evidence in patients with COVID-19 that SARS-CoV-2 is massively detected and replicated within the multiciliated cells. We observed these findings during the early stage of COVID-19, when infected ciliated cells were rapidly replaced by differentiating precursor cells. Moreover, our analyses revealed that SARS-CoV-2 cellular tropism was restricted to the nasal ciliated versus oral squamous epithelium. These results imply that targeting ciliated cells of the nasal epithelium during the early stage of COVID-19 could be an ideal strategy to prevent SARS-CoV-2 propagation.

ATF4-mediated GDF15 suppresses LPS-induced inflammation and MUC5AC in human nasal epithelial cells through the PI3K/Akt pathway.

AIMS: Growth and differentiation factor 15 (GDF15) is a stress-related factor, which implicated in various diseases. This study aimed to investigate the role of GDF15 in LPS-mediated inflammation and to explore the potential underlying molecular mechanisms in human nasal epithelial cells (HNEpCs). MAIN METHODS: HNEpCs were treated with LPS. GDF15 loss-of-function and gain-of-function experiments were performed. The expression of GDF15 by quantitative real-time PCR (RT-qPCR). The mRNA levels and secretion of inflammatory cytokines and MUC5AC were assessed by RT-qPCR and ELISA kits. LY294002 (PI3K inhibitor) and 740Y-P (PI3K agonist) were utilized to interfere with PI3k/Akt pathway. The relationship between GDF15 and ATF4 was identified by chromatin immunoprecipitation (ChIP) and luciferase reporter assay. KEY FINDINGS: We observed that LPS triggered GDF15 expression. GDF15 ablation reduced the mRNA levels and secretion of inflammatory cytokines. GDF15 silencing led to the reduction of the MUC5AC mRNA level, protein level and secretion in response to LPS. Enhanced expression of GDF15 showed the opposite results. Furthermore, we found that GDF15 deficiency inhibited activation of the PI3K/Akt pathway, LY294002 treatment further enhanced the role of GDF15 suppression in inflammation and MUC5AC expression, while 740Y-P administration partly reversed the biological activities of GDF15 silencing. ATF4 could bind to the promoter of GDF15 and positively regulate GDF15 expression. Depression of ATF4 diminished the secretion of inflammatory cytokines and MUC5AC via regulation of GDF15. SIGNIFICANCE: Our data suggest that GDF15 is regulated by ATF4 and suppresses LPS-induced inflammation and MUC5AC in human nasal epithelial cells through the PI3K/Akt pathway.

Objective measurement and patient-reported evaluation of the nasal airway: Is correlation dependent on symptoms or on nasal airflow?

BACKGROUND: Evidence has shown that the sensation of nasal breathing is related to variations in nasal mucosa temperature produced by airflow. An appropriate nasal airflow is necessary for changing mucosal temperature. Therefore, the correlation between objective measurements of nasal airflow and patient-reported evaluation of nasal breathing should be dependent on the level of nasal airflow. OBJECTIVES: To find if the correlation between patient-reported assessment of nasal breathing and objective measurement of nasal airflow is dependent on the severity of symptoms of nasal obstruction or on the level of nasal airflow. METHODS: The airway of 79 patients was evaluated using NOSE score and peak nasal inspiratory flow (PNIF). Three subgroups were created based on NOSE and three subgroups were created based on PNIF level to find if correlation was dependent on nasal symptoms or airflow. RESULTS: The mean value of PNIF for the 79 patients was 92.6 L/min (SD 28.1 L/min). The mean NOSE score was 48.4 (SD 24.4). The correlation between PNIF and NOSE was statistically significant (P = .03), but with a weak association between the two variables (r = -.248). Evaluation of correlation based on symptoms demonstrated a weak or very weak association in each subgroup (r = -.250, r = -.007, r = -.104). Evaluation of correlation based on nasal airflow demonstrated a very weak association for the subgroups with middle-level and high PNIF values (r = -.190, r = -.014), but a moderate association for the subgroup with low PNIF values (r = -.404). CONCLUSIONS: This study demonstrated a weak correlation between NOSE scores and PNIF values in patients non-selected according to symptoms of nasal obstruction or to airflow. It demonstrated that patients with symptoms of nasal obstruction have different levels of nasal airflow and that low nasal airflow prevents the sensation of good nasal breathing. Therefore, patients with symptoms of nasal obstruction may require improving nasal airflow to improve nasal breathing sensation.

Role of α-Tocopherol Acetate on Nasal Respiratory Functions: Mucociliary Clearance and Rhinomanometric Evaluations in Primary Atrophic Rhinitis.

Primary atrophic rhinitis is a disease of the nose and of paranasalsinuses characterized by a progressive loss of function of nasal and paranasal mucosa caused by a gradual destruction of ciliary mucosalepithelium with atrophy of serous-mucous glands and loss of bonestructures.The aim of this study was to evaluate the therapeutic effects of topic α-tochopherol acetate (vitamin E) in patients with primary atrophicrhinitis based on subjective and objective data.We analyzed 44 patients with dry nose sensation and endoscopic evidence of atrophic nasal mucosa. We analyzed endoscopic mucosascore, anterior rhinomanometry, and nasal mucociliary clearance before and after 6 months of topic treatment with α-tochopherol acetate. For statistical analysis, we used paired samples t test (95% confidence interval [CI], P < .05) for rhinomanometric and muciliary transit time evaluations and analysis of variance 1-way test (95% CI, P < .05) for endoscopic evaluation. All patients showed an improvement in "dry nose" sensation and inperception of nasal airflow. Rhinomanometric examination showed increase of nasal airflow at follow-up (P < .05); nasal mucociliaryclearance showed a reduction in mean transit time (P < .05); and endoscopic evaluation showed significative improvement of hydration of nasalmucosa and significative decreasing nasal crusts and mucusaccumulation (P < .05). Medical treatment for primary atrophic rhinitis is not clearly documented in the literature; in this research, it was demonstrated that α-ochopherol acetate could be a possible treatment for atrophic rhinitis.

Dry Eye and Dry Nose Caused by the Effect of Allergic Rhinitis on Tear and Nasal Secretion Osmolarity.

OBJECTIVE: Allergic rhinitis is a type 1 hypersensitivity reaction of immunoglobulin E in the rhino-ocular mucosa. This study was planned to demonstrate in patients with allergic rhinitis to evaluate changes in tear, nasal secretions, and blood osmolarity compared to healthy individuals. METHOD: Forty allergic rhinitis patients, 25 patients with acute upper respiratory tract infections, and 26 healthy participants were included in the study. Positive patients with allergic symptoms and skin prick test results were included in the allergic rhinitis group. Tear, nasal secretion, and blood osmolarity values were examined for the 3 groups. RESULT: In patients with allergic rhinitis, tear and nasal secretion osmolarity values were significantly higher in patients with acute upper respiratory tract infections and those of the healthy participants (P = .001, P = .038). In blood osmolarity measurements, there was no statistical difference between the groups (P = .489). In patients with allergic rhinitis, Schirmer test results were significantly shorter than patients who had acute upper respiratory tract infection and those of the healthy participants (P = .001, P = .001). Patients with allergic rhinitis and acute upper respiratory tract infections had significantly shorter Schirmer test results than in healthy participants (P = .001, P = .001). CONCLUSION: Tear osmolarity was increased in allergic rhinitis patients, and this was thought to lead to dry eye findings. In the presence of allergic rhinitis, nasal secretions were found more hyperosmolar than tears. Nasal secretion osmolarity was higher in allergic rhinitis patients than in patients with acute upper respiratory tract infections and control group.

Regional Peak Mucosal Cooling Predicts Radiofrequency Treatment Outcomes of Nasal Valve Obstruction.

OBJECTIVES/HYPOTHESIS: Low energy radiofrequency may offer effective treatment for narrow or obstructed nasal valve, yet its precise mechanism is not fully understood. STUDY DESIGN: Prospective, nonrandomized, case series. METHODS: Twenty prospective patients with internal nasal valve obstruction underwent office-based Vivaer treatment (Aerin Medical, Inc) under local anesthesia. Computational fluid dynamics (CFD) models were constructed based on the pre- and 90 days post-procedure computed tomography (CT) scans to identify salient changes in nasal airflow parameters. RESULTS: Patients' Nasal Obstruction Symptom Evaluation score (NOSE: pre-treatment 78.89 ± 11.57; post-treatment 31.39 ± 18.30, P = 5e-7) and Visual Analog Scale of nasal obstruction (VAS: pre-treatment 6.01 ± 1.83; post-treatment 3.44 ± 2.11, P = 1e-4) improved significantly at 90 days after the minimally invasive approach. Nasal airway volume in the treatment area increased ~7% 90 days post-treatment (pre-treatment 5.97 ± 1.20, post-treatment 6.38 ± 1.50 cm3 , P = .018), yet there were no statistically significant changes in the measured peak nasal inspiratory flowrate (PNIF, pre-treatment: 60.16 ± 34.49; post-treatment: 72.38 ± 43.66 ml/s; P = .13) and CFD computed nasal resistance (pre-treatment: 0.096 ± 0.065; post-treatment: 0.075 ± 0.026 Pa/(ml/s); P = .063). As validation, PNIF correlated significantly with nasal resistance (r = 0.47, P = .004). Among all the variables, only the peak mucosal cooling posterior to the nasal vestibule significantly correlated with the NOSE at baseline (r = -0.531, P = .023) and with post-treatment improvement (r = 0.659, P = .003). CONCLUSION: Minimal remodeling of the nasal valve (7% in this study) may have a profound effect on perceived nasal obstruction, despite little effect on nasal resistance, or PNIF. The results corroborated our previous findings that subjective relief of nasal obstruction correlates with regional mucosal cooling rather than nasal resistance or peak flow rate, a potential target for future effective, personalized therapeutic approaches. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1760-E1769, 2021.

Protection and regeneration of esophageal, pharyngeal, and laryngeal mucosa as a major element in therapy of patients with esophageal and extraesophageal reflux symptoms.

Treatment of esophageal and extraesophageal reflux syndromes is mainly focused on inhibiting the secretion of hydrochloric acid. In spite of the high efficacy of proton pump inhibitors, approx. 30-60% of GERD patients experience daily symptoms. Beside acid reflux, other factors such as abnormal esophageal peristalsis, visceral hypersensitivity, ineffective esophageal clearance mechanisms, and impaired mucosal barrier also play an important role in generating GERD symptoms. An additional therapeutic proposition is a procedure aimed at improving the defense mechanisms of esophageal mucosa rather than inhibiting the damage-inducing factors. The preparation consisting of hyaluronic acid (HA), chondroitin sulfate (SC) and poloxamer 407 protects against harmful factors (hydrochloric acid, pepsin) and accelerates mucosal healing and regeneration, constituting a substantial element of monotherapy or add-on therapy in patients with gastroesophageal reflux disease.

Expression, Distribution and Role of Aquaporins in Various Rhinologic Conditions.

Aquaporins (AQPs) are water-specific membrane channel proteins that regulate cellular and organismal water homeostasis. The nose, an organ with important respiratory and olfactory functions, is the first organ exposed to external stimuli. Nose-related topics such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS) have been the subject of extensive research. These studies have reported that mechanisms that drive the development of multiple inflammatory diseases that occur in the nose and contribute to the process of olfactory recognition of compounds entering the nasal cavity involve the action of water channels such as AQPs. In this review, we provide a comprehensive overview of the relationship between AQPs and rhinologic conditions, focusing on the current state of knowledge and mechanisms that link AQPs and rhinologic conditions. Key conclusions include the following: (1) Various AQPs are expressed in both nasal mucosa and olfactory mucosa; (2) the expression of AQPs in these tissues is different in inflammatory diseases such as AR or CRS, as compared with that in normal tissues; (3) the expression of AQPs in CRS differs depending on the presence or absence of nasal polyps; and (4) the expression of AQPs in tissues associated with olfaction is different from that in the respiratory epithelium.

Restraint stress increased the permeability of the nasal epithelium in BALB/c mice.

Stress seems to affect the onset and evolution of diverse illnesses with an inflammatory substrate. Whether physiological or psychological, stress increases epithelial permeability. In the mucosa of the nasal cavity and upper respiratory tract, the epithelial barrier is regulated in large part by bicellular and tricellular tight junctions (bTJs and tTJs, respectively). The junctional complexes are composed of multiple membrane proteins: claudins, tight-junction-associated MARVEL proteins (TAMs: occludin, tricellulin and marvelD3), and scaffolding proteins such as ZO-1, -2 and -3. The aim of the present study was to examine the possible modification of nasal permeability and TJ protein expression in a mouse model of acute psychological stress (a 4-h immobility session). Serum corticosterone was quantified from plasma samples to verify the onset of stress. Evaluation was made of the relative concentration of key proteins in nasal mucosa by using Western blot, and of changes in permeability by analyzing FITC-Dextran leakage from the nose to the blood. Compared to the control, the stressed group showed a greater epithelial permeability to FITC-Dextran, a reduced expression of occludin and tricellulin, and an elevated expression of ZO-2 and claudin-4. This evidence points to increased paracellular flow of large molecules through an altered structure of tTJs. Apparently, the structure of bTJs remained unchanged. The current findings could provide insights into the relation of stress to the onset/exacerbation of respiratory infections and/or allergies.

Upper Airway Cough Syndrome in Pathogenesis of Chronic Cough.

Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing.Upper airway cough syndrome (UACS) - previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.

Evaluation of nasal mucociliary clearance time in children with celiac disease.

OBJECTIVES: Celiac disease is an autoimmune disorder that develops because of sensitivity to gluten-containing grains in genetically disposed individuals. Nasal mucociliary clearance is the most important protective factor that protects the upper and lower airways from foreign particulates. This study aimed to investigate the effect of celiac disease on nasal mucociliary clearance. METHODS: The study included patients with celiac disease and healthy children. Nasal mucociliary clearance time was measured using the saccharin test. The children's saccharin taste time was recorded in seconds. RESULTS: Overall, 65 children were included: 43 patients with celiac disease (66.2%) and 22 healthy children (33.8%). Of all the children, 42 (64.6%) were female, and the average age was 11.8 ± 4 years. Nasal mucociliary clearance time of patients with celiac disease (531 ± 155 s) was significantly prolonged in comparison to that of healthy children (448 ± 80 s) (p = 0.006). No relationships were found between the diagnosis age, celiac type, and histopathological phase and compliance with the gluten-free diet and nasal mucociliary clearance time of patients with celiac disease. CONCLUSIONS: This study showed that nasal mucociliary clearance was prolonged in patients with celiac disease. A defect in nasal mucociliary clearance increases the risk of infection and inflammation in small airways. Studies reported a high prevalence of respiratory tract infection in patients with celiac disease, which was associated with malnutrition, vitamin deficiency, and hyposplenism. The findings of the present study indicated that impairment of nasal mucociliary clearance could play a role in the development of frequent lung infections in patients with celiac disease.