Mucociliary Transport Research Articles

Assessment of pulmonary mucociliary transport using magnetic nanoparticles: influence of their surface potential

Objective(s): Inhaled aerocontaminants are removed from the lungs by pulmonary mucociliary transport (MCT) as an important defense mechanism. This study was undertaken to investigate the influence of the surface potential of magnetic nanoparticles (MNPs) on the MCT in murine lungs by use of magnetic particle imaging (MPI).Materials and Methods: Three kinds of MNPs (carboxymethyl dextran magnetite (CM), alkali-treated dextran magnetite (AM), and trimethylammonium dextran magnetite (TM)) with almost the same hydrodynamic diameters (50-55 nm) but different surface (zeta) potentials (−24 mV for CM, −15 mV for AM, and +2 mV for TM) were intratracheally injected to anesthetized ICR male mice at 10 weeks old using a nebulizing microsprayer containing 50 μL of MNPs. MPI images were acquired at 0.5, 6, 24, 72, and 168 hours after the injection of agents for each mouse. The retention value of the MNPs in the lungs was quantified from the average pixel value of the lungs in the MPI image. Results: The retention value of TM in the lungs was significantly greater than that of AM at 6 and 168 hours after the injection of agents, and was significantly greater than that of CM at 72 and 168 hours after injection. The retention value of AM was significantly greater than that of CM at 168 hours after injection.Conclusion: The surface potential of MNPs affects the clearance of MNPs from the lungs due to MCT, suggesting that the retention of MNPs in the lungs can be controlled by manipulating the surface potential of MNPs. MPI will be useful for the visual and quantitative assessment of MCT, because MPI allows for repeated and long-term studies with a single injection of MNPs and with no radiation exposure.

A glycopolymer improves vascoelasticity and mucociliary transport of abnormal cystic fibrosis mucus.

Cystic fibrosis (CF) is characterized by increased mucus viscosity and delayed mucociliary clearance that contributes to progressive decline of lung function. Mucus in the respiratory and GI tract is excessively adhesive in the presence of airway dehydration and excess extracellular Ca2+ upon mucin release, promoting hyperviscous, densely packed mucins characteristic of CF. Therapies that target mucins directly through ionic interactions remain unexploited. Here we show that poly (acetyl, arginyl) glucosamine (PAAG), a polycationic biopolymer suitable for human use, interacts directly with mucins in a Ca2+-sensitive manner to reduce CF mucus viscoelasticity and improve its transport. Notably, PAAG induced a linear structure of purified MUC5B and altered its sedimentation profile and viscosity, indicative of proper mucin expansion. In vivo, PAAG nebulization improved mucociliary transport in CF rats with delayed mucus clearance, and cleared mucus plugging in CF ferrets. This study demonstrates the potential use of a synthetic glycopolymer PAAG as a molecular agent that could benefit patients with a broad array of mucus diseases.

Evaluation of Cilia Function in Rat Trachea Reconstructed Using Collagen Sponge Scaffold Seeded with Adipose Tissue-Derived Stem Cells.

The tracheal lumen is essential for conducting air to the lung alveoli and for voice production. However, patients with severe tracheal stenosis and malignant tumors invading the trachea often require tracheal resection. Recently, various reported tissue engineering methods for tracheal reconstruction show that regeneration of ciliated epithelium in the reconstructed areas, as well as preservation of the luminal structure is possible. However, only few studies report on the mucociliary transport function in reconstructed tracheae. We investigated mucociliary transport function within rat tracheal epithelium, reorganized after autologous adipose tissue-derived stem cell (ASC) transplantation. Rat ASCs were expanded in culture, and then seeded in a collagen sponge, which was physically supported with a polypropylene framework. The ASC-seeded collagen sponge was transplanted into the rat tracheal defect. We then examined the motility and transport function of cilia generated in the transplanted area using ciliary beat frequency (CBF) and microsphere movement analyses. Our data suggested that autologous ASC transplantation promoted ciliogenesis, consistent with previous reports. The CBF analysis revealed that motility of the cilia generated in the ASC group was comparable to that observed in the normal rat tracheal epithelium. Transport function in the ASC group was higher than that in the control group. These data suggested that autologous ASC transplantation increased ciliated cells in the reconstructed area without significantly disrupting cilia motility, thereby promoting transport function regeneration. Autologous ASC transplantation is expected to be beneficial in morphological and functional regeneration of tracheal epithelium. Anat Rec, 303:471-477, 2020. © 2019 American Association for Anatomy.

In vitro intestinal toxicity of copper oxide nanoparticles in rat and human cell models

Human oral exposure to copper oxide nanoparticles (NPs) may occur following ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. This study assessed the cytotoxicity of Cupric (II) oxide (CuO) and Cu2O-polyvinylpyrrolidone (PVP) coated NPs and copper ions in rat (intestine epithelial cells; IEC-6) and human intestinal cells, two- and three-dimensional models, respectively. The effect of pretreatment of CuO NPs with simulated gastrointestinal (GI) fluids on IEC-6 cell cytotoxicity was also investigated. Both dose- and time-dependent decreases in viability of rat and human cells with CuO and Cu2O-PVP NPs and Cu2+ ions was observed. In the rat cells, CuO NPs had greater cytotoxicity. The rat cells were also more sensitive to CuO NPs than the human cells. Concentrations of H2O2 and glutathione increased and decreased, respectively, in IEC-6 cells after a 4-h exposure to CuO NPs, suggesting the formation of reactive oxygen species (ROS). These ROS may have damaged the mitochondrial membrane of the IEC-6 cells causing a depolarization, as a dose-related loss of a fluorescent mitochondrial marker was observed following a 4-h exposure to CuO NPs. Dissolution studies showed that Cu2O-PVP NPs formed soluble Cu whereas CuO NPs essentially remained intact. For GI fluid-treated CuO NPs, there was a slight increase in cytotoxicity at low doses relative to non-treated NPs. In summary, copper oxide NPs were cytotoxic to rat and human intestinal cells in a dose- and time-dependent manner. The data suggests Cu2O-PVP NPs are toxic due to their dissolution to Cu ions, whereas CuO NPs have inherent cytotoxicity, without dissolving to form Cu ions.

Mucociliary transport as a link between chronic rhinosinusitis and trace element dysbalance

Chronis rhinosinusitis is considered as a widespread public health issue with a prevalence of 10%. The disease significantly reduces quality of life and increases the risk of cardiovascular diseases as well as certain forms of cancer. Alteration of mucociliary clearance frequently observed in the patients and plays a significant role in disease pathogenesis. Certain studies have demonstrated that patients with chronic rhinosinusitis are characterized by significant reduction of essential trace elements and toxic metal overload. However, the particular mechanisms of the role of trace element dysbalance in chronic rhinosinusitis are unclear. We hypothesize that exposure to toxic trace elements (arsenic, nickel, cadmium) damages ciliary mucosal epithelium thus affecting mucociliary transport. In turn, altered mucociliary transport results in reduced removal of the inhaled metal-containing particles from nasal mucosa leading to their absorption and further aggravation of toxicity. Essential trace elements (zinc, selenium) play a significant role in regulation of mucociliary transport and immunity, thus their deficiency (either dietary or due to antagonism with toxic metals) may be associated with impaired functions and increased toxic metal toxicity. Therefore, a vicious circle involving metal accumulation and toxicity, essential element deficiency, impairment of mucociliary transport and metal particle removal, resulting in further accumulation of metals and aggravation of toxic effects is formed. The present hypothesis is supported by the findings on the impact of trace elements especially zinc and arsenic on mucociliary clearance, the role of mucociliary transport in heavy metal particles elimination from the airways, trace element dysbalance in chronic rhinosinusitis, as well as toxic and essential metal antagonism. The data from hypothesis testing and its verification may be used for development of therapeutic approach for management of chronic rhinosinusitis. Particularly, the use of essential elements (zinc, selenium) may reduce toxic metal toxicity thus destroying the vicious circle of heavy metal exposure, toxicity, alteration of mucociliary clearance, and aggravation of chronic rhinosinusitis. Essential element supplementation may be considered as a tool for management of chronic refractory rhinosinusitis. In addition, analysis of essential and toxic trace element status may provide an additional diagnostic approach to risk assessment of chronic rhinosinusitis in highly polluted environments.

Resistance exercise training improves mucociliary clearance in subjects with COPD: A randomized clinical trial

IntroductionElastic tubing was recently investigated as an alternative to the conventional resistance training (RT) in chronic obstructive pulmonary disease (COPD). The effects of RT on the mucociliary system have not yet been reported in the literature. ObjectiveThe aim of this study was to evaluate the effects of two RT programs on mucociliary clearance in subjects with COPD. MethodsTwentyeight subjects with COPD were randomly allocated by strata, according to individual strength of lower limbs, to defined groups: conventional resistance training (GCT) or resistance training using elastic tubing (GET). Nineteen subjects (GET: n=9; GCT: n=10) completed the study and were included in the analysis. The measurement of vital signs (blood pressure, heart rate and respiratory rate), lung function (spirometry) and the primary outcome mucociliary clearance analysis (saccharin transit time test (STT)) were performed before and after the 12 weeks of RT. ResultsIn relation to the mucociliary transportability analysis, no differences were observed between the baseline evaluations of the training groups (p=0.05). There was a significant reduction in the STT values in both training groups, GET (10.64±5.06 to 6.01±4.91) and GCT (12.07±5.10 to 7.36±2.54) with p=0.03. However, no differences between groups were observed on the magnitude of SST changes after interventions (GET: −43.51%; GCT: −38.94%; p=0.97). ConclusionThe present study demonstrated that both RT with elastic tubing and conventional training with weights promoted similar gains in the mucociliary transportability of subjects with COPD.

Challenges Facing Airway Epithelial Cell-Based Therapy for Cystic Fibrosis.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the life-limiting hereditary disease, cystic fibrosis (CF). Decreased or absent functional CFTR protein in airway epithelial cells leads to abnormally viscous mucus and impaired mucociliary transport, resulting in bacterial infections and inflammation causing progressive lung damage. There are more than 2000 known variants in the CFTR gene. A subset of CF individuals with specific CFTR mutations qualify for pharmacotherapies of variable efficacy. These drugs, termed CFTR modulators, address key defects in protein folding, trafficking, abundance, and function at the apical cell membrane resulting from specific CFTR mutations. However, some CFTR mutations result in little or no CFTR mRNA or protein expression for which a pharmaceutical strategy is more challenging and remote. One approach to rescue CFTR function in the airway epithelium is to replace cells that carry a mutant CFTR sequence with cells that express a normal copy of the gene. Cell-based therapy theoretically has the potential to serve as a one-time cure for CF lung disease regardless of the causative CFTR mutation. In this review, we explore major challenges and recent progress toward this ambitious goal. The ideal therapeutic cell would: (1) be autologous to avoid the complications of rejection and immune-suppression; (2) be safely modified to express functional CFTR; (3) be expandable ex vivo to generate sufficient cell quantities to restore CFTR function; and (4) have the capacity to engraft, proliferate and persist long-term in recipient airways without complications. Herein, we explore human bronchial epithelial cells (HBECs) and induced pluripotent stem cells (iPSCs) as candidate cell therapies for CF and explore the challenges facing their delivery to the human airway.

Mucus strands from submucosal glands initiate mucociliary transport of large particles.

Mucus produced by submucosal glands is a key component of respiratory mucociliary transport (MCT). When it emerges from submucosal gland ducts, mucus forms long strands on the airway surface. However, the function of those strands is uncertain. To test the hypothesis that mucus strands facilitate transport of large particles, we studied newborn pigs. In ex vivo experiments, interconnected mucus strands moved over the airway surface, attached to immobile spheres, and initiated their movement by pulling them. Stimulating submucosal gland secretion with methacholine increased the percentage of spheres that moved and shortened the delay until mucus strands began moving spheres. To disrupt mucus strands, we applied reducing agents tris-(2-carboxyethyl)phosphine and dithiothreitol. They decreased the fraction of moving spheres and delayed initiation of movement for spheres that did move. We obtained similar in vivo results with CT-based tracking of microdisks in spontaneously breathing pigs. Methacholine increased the percentage of microdisks moving and reduced the delay until they were propelled up airways. Aerosolized tris-(2-carboxyethyl)phosphine prevented those effects. Once particles started moving, reducing agents did not alter their speed either ex vivo or in vivo. These findings indicate that submucosal glands produce mucus in the form of strands and that the strands initiate movement of large particles, facilitating their removal from airways.

СОСТОЯНИЕ МЕРЦАТЕЛЬНОГО ЭПИТЕЛИЯ БРОНХОВ И МУКОЦИЛИАРНОГО ТРАНСПОРТА ПРИ ХРОНИЧЕСКОМ БРОНХИТЕ НА ФОНЕ ДЛИТЕЛЬНОГО КУРЕНИЯ

The objective of the study : to compare the state of mucociliary clearance and bronchial ciliated epithelium in smokers and non-smokers suffering from chronic bronchitis. Subjects and methods . 80 chronic bronchitis patients with exacerbation were examined; they were divided into 2 groups: Group 1 included 40 active smokers and Group 2 comprised of 40 patients who had never smoked. The comparison group included 10 non-smokers with no respiratory disorders. All chronic bronchitis patients had certain examinations including bronchoscopy with biopsy and consequent ultrastructural tests of biopsy specimens and aerosol scintigraphy of the lungs for mucociliary clearance assessment. Results. Morphological and functional changes in the mucociliary transport system were detected in case of chronic bronchitis versus those healthy. Those changes were more profound in the smokers compared to non-smokers. Thus, the smokers with chronic bronchitis were diagnosed with a significant reduction of mucociliary clearance corresponding to degree II of mucociliary transport system failure, which was down to 16.60 ± 2.40% (down to 23.91 ± 2,11% in non-smokers, while it was 34.82 ± 2.14% in health) with concurrent diffuse bilateral bronchitis deformans and significant amount of very viscous mucosal or mucopurulent discharge according to the endoscopy data. The ultrastructural testing of biopsy specimens detected the significant damage of bronchial ciliated epithelium in the form of diffuse atrophy, focal metaplasia, which was one of the obvious causes of significant impairment of mucociliary transport.

Relationship between deviations of nasal septum and mucociliary transport time using saccharin test

Relationship between deviations of nasal septum and mucociliary transport time using saccharin test

Nebulized hypertonic saline in noncystic fibrosis bronchiectasis: a comprehensive review.

Bronchiectasis occurs as a result of a vicious circle consisting of an impaired mucociliary transport system, inflammation, and infection and repair of the airways. Damage to the mucociliary system prevents secretion elimination and facilitates bacterial growth and bronchial inflammation. To facilitate mucociliary clearance, current guidelines recommend the use of hypertonic saline (HS) solutions in patients with bronchiectasis not secondary to cystic fibrosis (CF), although the evidence of efficacy in this pathology is sparse. A high percentage of patients with CF and bronchiectasis tolerate HS solutions, but often patients report cough, dyspnoea, throat irritation, or salty taste after inhalation. These adverse effects negatively impact adherence to treatment, which sometimes must be discontinued. Some studies have shown that the addition of hyaluronic acid increases the tolerability of HS solutions, both in patients with CF and in bronchiectasis of other etiologies. We aimed to review the benefits and safety of HS solutions in patients with bronchiectasis. The reviews of this paper are available via the supplemental material section.

Ways of enhancement of the surgical treatment efficacy in treatment of patients, suffering pulmonary tumors

Objective. Efficacy of endoscopic bronchosanation for prophylaxis of preoperative and postoperative complications in patients with pulmonary tumors.
 Маterials and methods. There was studied the efficacy of endoscopic photodynamic therapy in accordance to procedure, elaborated by the authors, including injection of the water solution of a methylene blue dye in concentration 0.04% into tracheobronchial tree, irradiated by laser with the wave length 0.63 mcm, independently and in conjunction with a standard anti-inflammatory therapy as preoperative preparation of tracheobronchial tree in patients, suffering pulmonary cancer. In the investigation 181 patients were included, suffering pulmonary cancer Stages II-III, morphologically confirmed, and with coexistent endobronchitis.
 Results. In accordance to analysis of the pathogenic microflora titer and character in lumen of bronchial tree after preoperative preparation there was established, that while application of independent endoscopic bronchosanation in 55 (87%) observations the pathogenic microflora was absent. While combination of photodynamical bronchosanation in accordance to standard therapy a pathogenic microflora was not revealed in 52 patients. While conduction of a standard preparation without application of a laser therapy microflora was not revealed only in 44.8% observations. Together with the bronchial mucosa metaplasia in some investigated patients the dysplastic changes of bronchial epithelium of various severity degree were registered. Independent endoscopic bronchosanation have leaded to trustworthy lowering of a general rate of the bronchial epithelial dysplasia in the patients tо 36.1%, together with standard anti-inflammatory therapy - tо 42.4%.
 Conclusion. Application of endoscopic photodynamic bronchosanation in accordance to the proposed procedure in preoperative period in the patients with objective to correct a concomitant endobronchitis, as independent option or together with standard anti-inflammatory therapy, leads to reduction of the endobronchial complications rate after operative treatment for pulmonary cancer, comparing with a control group. Еndoscopic bronchosanation is accompanied by significant lowering of severity of endoscopic signs of coexistent endobronchitits and improvement of mucociliary transport. In accordance to microbiological tests in 87 - 88% of patients a complete sanation of bronchial tree and elimination of main histological criteria of inflammation were noted, while in 67.2 - 100% patients – restoration of normal structure of the bronchial tree mucosa.

Esomeprazole Increases Airway Surface Liquid pH in Primary Cystic Fibrosis Epithelial Cells.

Respiratory failure, driven by airways mucus obstruction, chronic inflammation and bacterial infections, is the main cause of mortality and morbidity in people with cystic fibrosis (CF) due to defects in the Cl- and transport activity of the CF Transmembrane conductance Regulator (CFTR). Most recent pre-clinical and clinical studies have focused on restoring CFTR function by enhancing its trafficking or transport activity and show promising results. However, there are a significant number of patients that will not benefit from these CFTR-targeted therapies and it is therefore important to identify new non-CFTR targets that will restore lung function, by-passing CFTR dysfunction. The H+/K+-ATPase, ATP12A, has recently been identified as a potential novel target for CF therapies, since its acute inhibition by ouabain was shown to help restore mucus viscosity, mucociliary transport, and antimicrobial activity using in vitro CF airway models, and this effect was linked to an increase in the pH of the airway surface liquid (ASL). Here, we have evaluated the potential therapeutic use of ouabain by investigating the effect of chronically treating fully differentiated CF primary human airway epithelial cells (hAECs) with ouabain, under thin film conditions, resembling the in vivo situation. Our results show that although chronic treatment increased ASL pH, this correlated with a deleterious effect on epithelial integrity as assessed by LDH release, transepithelial electrical resistance, fluorescein flux, and ion transport. Since ATP12A shares approximately 65% identity with the gastric H+/K+-ATPase (ATP4A), we investigated the potential of using clinically approved ATP4A proton pump inhibitors (PPIs) for their ability to restore ASL pH in CF hAECs. We show that, despite not expressing ATP4A transcripts, acute exposure to the PPI esomeprezole, produced changes in intracellular pH that were consistent with the inhibition of H+ secretion, but this response was independent of ATP12A. More importantly, chronic exposure of CF hAECs to esomeprazole alkalinized the ASL without disrupting the epithelial barrier integrity, but this increase in ASL pH was consistent with a decrease in mRNA expression of ATP12A. We conclude that PPIs may offer a new approach to restore ASL pH in CF airways, which is independent of CFTR.

The effect of the nasal packing material on nasal epithelial cells

Objective:The aim of this study is to investigate the effect of polyethylene glycol acrylate hybrid hydrogel degradation substance on nasal mucociliary transport system. Method:In our experiment, the complex hydrogel were formed by the combination of different ratios of polyethyleneglycol diacrylate, chitosan and polyvinyl alcohol. The experiment was divided into four groups according to the international standard of medical devices. DMEM/F12∶BEGM culture medium was used for each packing material extraction, DMEM/F12∶BEGM culture medium was used as control. Human nasal uncinate tissue, gas liquid interface culture of human nasal mucociliary epithelium cells. The high frequency digital microscope video imaging system was used to detect the ciliary wiggle frequency. The baseline state (0 min) and 1 h,1 d, 2 d, 3 d of CBF were measured after dosing. Result:①In the experimental group and the control group, with the increase of the number of days, the ciliary beat frequency increased first and then slowed down. ②Compared with the other groups, Polyethylene glycol acrylate hybrid hydrogel group increase on CBF (P<0.05). There was no significant difference between the maximum increase and the maximum decrease in B, C and D groups (P>0.05). Therefore, it can be concluded that absorbable gelatin sponge material and absorbable chitosan material had no effect on nasal mucociliary activity. Conclusion:Polyethylene glycol diacrylate composite hydrogel material can increase the frequency of ciliary wounded nasal mucosa epithelial cells cultured in air-liquid interface in vitro, and enhanced the activity of nasal mucosa cilia. Therefore, it can meet the safety requirements of clinical application of the new material.

The relevance of the application mukoactive preparations in patients with inflammatory pathology of ent organs

The mucous membrane of the respiratory tract is the first line of protection of the human body from various damaging agents. This function is provided by mucociliary clearance and its component by mucociliary transport. Optimum work of ciliated epithelium is possible only with normal rheology of mucous secretion - viscosity, elasticity, adhesiveness. The development of mucociliary dysfunction is the main pathogenetic mechanism of almost all inflammatory diseases of the respiratory tract and middle ear. The main areas of treatment for patients with infectious and inflammatory diseases of the respiratory tract and ear are evacuation of the pathological secretion, restoration of the synthesis of physiological mucus and a positive effect on the restructuring of the respiratory epithelium. The effectiveness of a mucoactive drug is determined by its ability to directly affect several components of mucociliary clearance - regulation of viscosity and secretion composition, its formation processes and evacuation rate. These characteristics correspond to carbocysteine.

Mucociliary Transport in Healthy and Cystic Fibrosis Pig Airways.

Cystic fibrosis (CF) lung disease is the major cause of morbidity and mortality in people with CF. Abnormal mucociliary transport has been the leading hypothesis for the underlying pathogenesis of CF airway disease. However, this has been difficult to investigate at very early time points. A porcine CF model, which recapitulates many features of CF disease in humans, enables studies to be performed in non-CF and CF pigs on the day that they are born. In newborn CF pigs, we found that under basal conditions, mucociliary transport rates in non-CF and CF pigs are similar. However, after cholinergic stimulation, which stimulates submucosal gland secretion, particles become stuck in the CF airways owing to a failure of mucus strands to release from submucosal glands. In this review, we summarize these recent discoveries and also discuss the morphology, composition, and function of mucins in the porcine lung.

Functional Anatomic Imaging of the Airway Surface.

The airway surface functional microanatomy, including the ciliated airway epithelium and overlying mucus layer, is a critical component of the mucociliary escalator apparatus, an innate immune defense that helps to maintain a clean environment in the respiratory tract. Many genetic and acquired respiratory diseases have underlying pathophysiological mechanisms in which constituents of the airway surface functional microanatomy are defective. For example, in cystic fibrosis, mutations in the cystic fibrosis transmembrane conductance regulator gene, which normally produces a secretory anion channel protein, result in defective anion secretion and consequent dehydrated and acidic mucosal layer overlying the airway epithelium. This thick, viscous mucus results in depressed ciliary beating and delayed mucociliary transport, trapping bacteria and other pathogens, compromising host defenses and ultimately propagating disease progression. Thus, developing tools capable of studying the airway surface microanatomy has been critical to better understanding key pathophysiological mechanisms, and may become useful tools to monitor treatment outcomes. Here, we discuss functional imaging tools to study the airway surface functional microanatomy, and how their application has contributed to an improved understanding of airway disease pathophysiology.

TLR7 agonist attenuates acetylcholine-induced, Ca2+ -dependent ionic currents in swine tracheal submucosal gland cells.

What is the central question of this study? Does Toll-like receptor 7 (TLR7) have any direct effects on Ca2+ -dependent physiological function of tracheal submucosal gland cells? What is the main finding and its importance? TLR7 is co-localized with SERCA2 in tracheal submucosal gland cells and causes a rapid attenuation of acetylcholine (ACh)-induced, Ca2+ -dependent ionic currents through the activation of SERCA2-dependent Ca2+ clearance. TLR7 is abundantly expressed in the airways of both swine and healthy human subjects, but is significantly downregulated in chronic obstructive pulmonary disease (COPD) airways. These findings suggest that a dysfunction of TLR7 in COPD removes the brake on ACh-induced serous secretion during viral infections, resulting in prolonged airway hypersecretion, and that it is one of the triggers of COPD exacerbations. Airway surface fluids are mainly secreted from submucosal glands (SMGs) and play important roles in the defence of airways via the activation of mucociliary transport. Toll-like receptor 7 (TLR7) recognizes and eliminates single stranded RNA (ssRNA) viruses through the induction of innate immunity. However, there is no obvious connection between TLR7 and mucus secretion, aside from TLR7 recognizing ssRNA viruses, which are often associated with airway hypersecretion in chronic obstructive pulmonary disease (COPD). Here, we investigated whether TLR7 has any direct effects on the Ca2+ -dependent physiological function of tracheal SMG cells. Patch-clamp analyses revealed that TLR7 ligand inhibited the acetylcholine (ACh)-induced ionic currents in isolated tracheal SMG cells. Intracellular calcium assays and pharmacological analyses revealed that TLR7 attenuated the transient rises in the intracellular calcium concentration evoked by ACh by activating sarco/endoplasmic reticulum Ca2+ -ATPase 2 (SERCA2). Immunofluorescence staining and immunohistochemical staining revealed that TLR7 was co-localized with SERCA2. These findings suggest that the activation of TLR7 during viral infections contributes to the rapid attenuation of ACh-induced ionic currents through an increase in SERCA2-dependent Ca2+ clearance in healthy airway SMG cells. Our study also revealed that TLR7 expression was significantly downregulated in COPD airways. Based on these findings, we speculate that a dysfunction of TLR7 may not only have an adverse effect on the elimination of these viruses but also remove the brake on ACh-induced serous secretion, resulting in prolonged hypersecretion and acting as one of the triggers of COPD exacerbations.

Assessment of nasal functions and their relationship with cholesteatoma formation in patients with unilateral chronic otitis media.

To evaluate the nasal functions of patients with unilateral chronic otitis media using rhinomanometry, comparing chronic otitis media sides with healthy sides, chronic otitis media patients with cholesteatoma and without cholesteatoma, and patients with healthy individuals. This prospective study included 102 patients with unilateral chronic otitis media (48 with and 54 without cholesteatoma). The control group comprised 40 individuals without any ear or nasal pathologies. All patients underwent active anterior rhinomanometry to measure nasal airway resistance and a saccharin test to measure mucociliary transport times. There were no significant differences in nasal airway resistance and mucociliary transport time between the chronic otitis media sides and unaffected sides in the 102 patients (p = 0.72 and p = 0.28, respectively), between the non-suppurative chronic otitis media patients (without cholesteatoma) and chronic otitis media with cholesteatoma patients (p > 0.05), or between the study and control groups (p > 0.05). The present study, with a larger sample size compared to previously published literature, supports the conclusion that unilateral nasal obstruction is unlikely to lead to chronic otitis media on the same side. The results also suggest that nasal functions do not contribute to the development of cholesteatoma.

The effect of inferior turbinate surgery on ciliated epithelium: A randomized, blinded study.

The aim of this study was to evaluate statistically the effects of radiofrequency ablation, diode laser, and microdebrider-assisted inferior turbinoplasty techniques on ciliated epithelium and mucociliary function. Prospective randomized study. A total of 66 consecutively randomized adult patients with enlarged inferior turbinates underwent either a radiofrequency ablation, diode laser, or microdebrider-assisted inferior turbinoplasty procedure. Assessments were conducted prior to surgery and 3 months subsequent to the surgery. The effect on ciliated epithelium was evaluated using a score based on the blinded grading of the preoperative and postoperative scanning electron microscopy images of mucosal samples. The effect on mucociliary function, in turn, was evaluated using saccharin transit time measurement. The score of the number of cilia increased statistically significantly in the radiofrequency ablation (P = .03) and microdebrider-assisted inferior turbinoplasty (P = .04) groups, but not in the diode laser group. The score of the squamous metaplasia increased statistically significantly in the diode laser group (P = .002), but not in the other two groups. There were no significant changes found between the preoperative and postoperative saccharin transit time values in any of the treatment groups. Radiofrequency ablation and microdebrider-assisted inferior turbinoplasty are more mucosal preserving techniques than the diode laser, which was found to increase the amount of squamous metaplasia at the 3-month follow-up. The number of cilia seemed to even increase after radiofrequency ablation and microdebrider-assisted inferior turbinoplasty procedures, but not after diode laser. Nevertheless, the mucociliary transport was equally preserved in all three groups. 1b Laryngoscope, 129:18-24, 2019.