The FAM13A Long Isoform Regulates Cilia Movement and Co-ordination in Airway Mucociliary Transport.

SNPs in the FAM13A locus are amongst the most commonly reported risk alleles associated with chronic obstructive pulmonary disease (COPD) and other respiratory diseases, however the physiological role of FAM13A is unclear. In humans, two major protein isoforms are expressed at the FAM13A locus: 'long' and 'short', but their functions remain unknown, partly due to a lack of isoform conservation in mice. We performed in-depth characterisation of organotypic primary human airway epithelial cell subsets and show that multiciliated cells predominantly express the FAM13A long isoform containing a putative N-terminal Rho GTPase activating protein (RhoGAP) domain. Using purified proteins, we directly demonstrate RhoGAP activity of this domain. In Xenopus laevis, which conserve the long isoform, Fam13a-deficiency impaired cilia-dependent embryo motility. In human primary epithelial cells, long isoform deficiency did not affect multiciliogenesis but reduced cilia co-ordination in mucociliary transport assays. This is the first demonstration that FAM13A isoforms are differentially expressed within the airway epithelium, with implications for the assessment and interpretation of SNP effects on FAM13A expression levels. We also show that the long FAM13A isoform co-ordinates cilia-driven movement, suggesting that FAM13A risk alleles may affect susceptibility to respiratory diseases through deficiencies in mucociliary clearance. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Evaluation of Nasal Mucociliary Clearance Time in Patients with Schizophrenia.

Nasal mucociliary clearance time (NMCT) is prolonged in patients with olfactory disorders. It is essential to differentially diagnose conductive and neural olfactory disorders. Here, we used the mucociliary clearance test to investigate a disease associated with neural olfactory disorders, i.e. schizophrenia. Data on age, gender, and duration of disease were collected. The study involved 56 schizophrenia patients and 56 healthy controls. There was no significant difference between the groups regarding age and gender (p = 0.459 and p = 0.768 respectively). Mean NMCT of patients with schizophrenia was 13.82 ± 3.22 min and mean NMCT of healthy controls was 10.15 ± 2.94 min. There was significant difference between the groups regarding NMCT (p < 0.001). In the patient group, there was a significant positive correlation between duration of disease, age, and NMCT (Pearson r = 0.286, p = 0.032, and Pearson r = 0.522, p < 0.001 respectively). This study has shown a prolonged NMCT in patients with schizophrenia compared to the healthy control group.

Acute Effect of E-Cigarette Inhalation on Mucociliary Clearance in E-Cigarette Users.

Background: Recent studies show e-cigarette (EC) users have increased rates of chronic bronchitic symptoms that may be associated with depressed mucociliary clearance (MCC). Little is known about the acute or chronic effects of EC inhalation on in vivo MCC. Methods: In vivo MCC was measured in young adult vapers (n = 5 males, mean age = 21) after controlled inhalation of a radiolabeled (Tc99m sulfur colloid) aerosol. Whole-lung clearance of radiolabeled deposited particles was measured over a 90-minute period for baseline MCC and associated with controlled periodic vaping over the first 60 minutes of MCC measurements. The vaping challenge was administered from a fourth generation box mod EC containing unflavored e-liquid (65% propylene glycol/35% vegetable glycerin, 3 mg/mL freebase nicotine). The challenge was administered at the start of each 10-minute interval of MCC measurements and consisted of 1 puff every 30 seconds for 5 minutes (i.e., 10 puffs for each 10-minute period for a total of 60 puffs during the initial 60 minutes of MCC measurements). Results: Compared with baseline, peripheral lung average clearance (%) over the 90 minutes of MCC measures was enhanced, associated with EC challenge, 12 (±6) versus 24 (±6), respectively (p < 0.05 by Wilcoxon signed-rank test). Conclusions: Acute enhancement of in vivo MCC during EC challenge is contrary to recent studies showing nicotine-associated slowing of ciliary beat and mucus transport at higher nicotine levels than those used here. However, our findings are consistent with an acute increase in fluid volume and mucin secretion to the bronchial airway surface that is likely short lived. Research reported in this publication was supported by the National Institutes of Health R01HL139369 and registered with ClinicalTrials.gov (NCT03700892).

Effects of High Frequency Chest Wall Oscillation (HFCWO) on Clinical Symptoms in COPD.

Background: Mucociliary clearance plays a critical role in pulmonary host defense. Abnormal mucociliary clearance contributes to the pathogenesis of pulmonary disorders, including COPD. In bronchiectasis, treatments targeting mucus obstruction in the airways include the use of high frequency chest wall oscillation (HFCWO) therapy. This prospective outcome based study was designed to investigate the changes in symptoms and quality of life (QOL) to measure the effect of adjunctive HFCWO therapy to standard of care therapy for patients with COPD. Research Question: When HFCWO is indicated and used as intended, will the quality of life for those patients with COPD improve and sustain improvement. Study Design and Methods: We conducted a prospective, openl-label, observational study in COPD patients without concomitant bronchiectasis. Participants had assessments of QOL at baseline (day 0) and then at 30 and 90 days after initiation of HFCWO therapy. The St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) was employed and longitudinally followed at each timepoint. Paired t-tests were used to compare means between each time points adjusted for multiple comparisons. A linear mixed model for the analysis of longitudinal data was then constructed to determine the simultaneous contribution of race, gender, ethnicity, time, and selected interactions in the primary outcome of change in SGRQ-C across 0, 30, and 90 days. Results: The cohort of patients (n=102) demonstrated a significant reduction in the SGRQ-C at 30 and sustained at 90 days compared to baseline. In addition, two component scores of the SGRQ-C questionnaire ("Symptoms" and Impacts") were significantly reduced at 30 and 90 days. Interpretation: This prospective, observational study demonstrates statistically significant and clinically favorable responses to HFCWO as an adjunctive therapy for patients with a primary diagnosis of COPD without concomitant bronchiectasis. Results of this study inform the design of additional additional studies of HFCWO to prove efficacy inCOPD patients.

Postnasal Drip.

Postnasal drip (PND) is a common symptom encountered when evaluating subjects with sinonasal disease; it may be present without sinonasal disease or as a symptom of laryngopharyngeal reflux. It is postulated that PND stems from dysfunction of normal mucus clearance mechanisms; however, there is no definitive evidence elucidating an exact pathophysiology. Compounding the uncertainties surrounding PND is the lack of an objective assessment tool. Instead, treating physicians must rely on subjective complaints and investigators utilize validated patient-reported outcome instruments, such as the Sino-Nasal Outcome Test, to determine treatment efficacy. This review seeks to discuss the current understanding of PND and evidence regarding effective treatment strategies.

Impact of particulate air pollution on airway injury and epithelial plasticity; underlying mechanisms.

Air pollution plays an important role in the mortality and morbidity of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Particulate matter (PM) is a significant fraction of air pollutants, and studies have demonstrated that it can cause airway inflammation and injury. The airway epithelium forms the first barrier of defense against inhaled toxicants, such as PM. Airway epithelial cells clear airways from inhaled irritants and orchestrate the inflammatory response of airways to these irritants by secreting various lipid mediators, growth factors, chemokines, and cytokines. Studies suggest that PM plays an important role in the pathogenesis of chronic airway diseases by impairing mucociliary function, deteriorating epithelial barrier integrity, and inducing the production of inflammatory mediators while modulating the proliferation and death of airway epithelial cells. Furthermore, PM can modulate epithelial plasticity and airway remodeling, which play central roles in asthma and COPD. This review focuses on the effects of PM on airway injury and epithelial plasticity, and the underlying mechanisms involving mucociliary activity, epithelial barrier function, airway inflammation, epithelial-mesenchymal transition, mesenchymal-epithelial transition, and airway remodeling.

Bio-Inspired Magnetically Responsive Silicone Cilia: Fabrication Strategy and Interaction with Biological Mucus.

Cilia are biological structures essential to drive the mobility of secretions and maintain the proper function of the respiratory airways. However, this motile self-cleaning process is significantly compromised in the presence of silicone tracheal prosthesis, leading to biofilm growth and impeding effective treatment. To address this challenge and enhance the performance of these devices, we propose the fabrication of magnetic silicone cilia, with the prospect of their integration onto silicone prostheses. The present study presents a fabrication method based on magnetic self-assembly and assesses the interaction behavior of the cilia array with biological mucus. This protocol allows for the customization of cilia dimensions across a wide range of aspect ratios (from 6 to 85) and array densities (from 10 to 80 cilia/mm2) by adjusting the fabrication parameters, offering flexibility for adjustments according to their required characteristics. Furthermore, we evaluated the suitability of different cilia arrays for biomedical applications by analyzing their interaction with bullfrog mucus, simulating the airways environment. Our findings demonstrate that the fabricated cilia are mechanically resistant to the viscous fluid and still exhibit controlled movement under the influence of an external moving magnet. A correlation between cilia dimensions and mucus wettability profile suggests a potential role in facilitating mucus depuration, paving the way for further advancements aimed at enhancing the performance of silicone prostheses in clinical settings.

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study.

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age. While no significant differences in MCC endpoints were associated with HS discontinuation, significant improvement in whole and peripheral lung MCC was observed after discontinuing DA. These results suggest that pwCF on ETI with mild lung disease do not experience a subclinical deterioration in MCC that could later impact health outcomes after discontinuing HS, and in fact may benefit from improved MCC after stopping DA treatment.

Effect of turbinate surgery on mucociliary clearance. A systematic review and metanalysis / Efecto de la cirugía turbinal en el aclaramiento mucociliar. Revisión sistemática y metaanálisis

Despite the fact that turbinate surgery provides satisfactory results regarding nasal obstruction, most of these procedures are destructive, to some extent, for the respiratory epithelium. There are valid hypotheses suggesting either that turbinate surgery may improve mucociliary clearance (MCC) by improving rhinitis, as well hypotheses suggesting that these surgeries may impair it by damaging the nasal ciliated epithelia. This systematic review is designed with the objective of exploring the effect of turbinate surgery on MCC. Pubmed (Medline), the Cochrane Library, EMBASE, SciELO were analyzed. Four authors members of the YO-IFOS rhinology study group independently analyzed the articles. Extracted variables encompassed: sample size, age, indication for surgery, surgical technique, method used to measure mucociliary clearance, mucociliary transport time before and after surgery, and main outcome. 15 studies with a total population of 1936 participants (1618 patients excluding healthy controls) met the inclusion criteria. 9 studies could be combined in a metanalysis, wich revealed a non-statistically significant decrease of 3.86 min in MCTT after turbinate surgery (p = 0.06). The subgroup analysis of the 5 cohorts who underwent microdebrider turbinoplasty reached statistical significance under a random effect model, revealing a 7.02 min decrease in MCTT (p < 0.001). The laser turbinoplasty subgroup, composed of 4 cohorts, also reached significance, although the difference was lower than that for microdebrider turbinoplasty, 1.01 min (p < 0.001). This systematic review and meta-analysis suggests that turbinate surgery does not compromise mucociliary clearance. The available evidence also suggests that turbinate surgery with mucosa sparing techniques improves MCC, while with aggressive techniques it increases or remains the same. ... . (AU)

A pesar de que la cirugía turbinal tiene efectos positivos en la ventilación nasal, gran parte de estos procedimientos son agresivos con el epitelio respiratorio. Existen hipótesis que sugieren que la cirugía turbinal puede mejorar el aclaramiento mucociliar (AMC) al mejorar la rinitis, así como alterarlo al lesional el epitelio nasal. Esta revisión se diseña con el objetivo de explorar el efecto de la cirugía turbinal en el AMC. Se revisó Pubmed (Medline), the Cochrane Library, EMBASE, SciELO. 4 autores miembros de YO-IFOS grupo de estudio en rinología, analizaron de manera independiente los artículos. Las variables analizadas fueron tamaño muestral, edad, indicación quirúrgica, técnica quirúrgica, método de medición de AMC, AMC antes y después de la cirugía y resultado principal. Se incluyeron 15 estudios con 1936 participantes (1618 excluyendo controles sanos). 9 estudios fueron combinados en un metanálisis que demostró una diferencia no estadísticamente significativa de -3,86 minutos en AMC tras cirugía (p = 0,06). El análisis por subgrupos de las 5 cohortes sometidas a turbinoplastia con microdebridador si fueron estadísticamente significativas con una diferencia de -7,02 minutos (p < 0,001). El grupo sometido a laser (4 cohortes) también obtuvo diferencia estadística, aunque menor, -1,01 minutos (p < 0,001). Esta revision y metaanálisis sugiere que la cirugía turbinal no afecta al aclaramiento mucociliar. La evidencia disponible también sugiere que las técnicas menos agresivas con la mucosa mejoran el AMC, mientras que las agresivas podrían aumentarlo o no modificarlo. Este efecto beneficioso se observa desde el 1º al 3º mes postquirúrgico. Sin embargo, para poder obtener adecuadas conclusiones, debe existir un método estandarizado para medir el AMC, así como un método para describir adecuadamente la extensión quirúrgica. (AU)

Dual-color live imaging unveils stepwise organization of multiple basal body arrays by cytoskeletons.

For mucociliary clearance of pathogens, tracheal multiciliated epithelial cells (MCCs) organize coordinated beating of cilia, which originate from basal bodies (BBs) with basal feet (BFs) on one side. To clarify the self-organizing mechanism of coordinated intracellular BB-arrays composed of a well-ordered BB-alignment and unidirectional BB-orientation, determined by the direction of BB to BF, we generated double transgenic mice with GFP-centrin2-labeled BBs and mRuby3-Cep128-labeled BFs for long-term, high-resolution, dual-color live-cell imaging in primary-cultured tracheal MCCs. At early timepoints of MCC differentiation, BB-orientation and BB-local alignment antecedently coordinated in an apical microtubule-dependent manner. Later during MCC differentiation, fluctuations in BB-orientation were restricted, and locally aligned BB-arrays were further coordinated to align across the entire cell (BB-global alignment), mainly in an apical intermediate-sized filament-lattice-dependent manner. Thus, the high coordination of the BB-array was established for efficient mucociliary clearance as the primary defense against pathogen infection, identifying apical cytoskeletons as potential therapeutic targets.

Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models.

Airway epithelium, the first defense barrier of the respiratory system, facilitates mucociliary clearance against inflammatory stimuli, such as pathogens and particulates inhaled into the airway and lung. Inhaled particulate matter 2.5 (PM2.5) can penetrate the alveolar region of the lung, and it can develop and exacerbate respiratory diseases. Although the pathophysiological effects of PM2.5 in the respiratory system are well known, its impact on mucociliary clearance of airway epithelium has yet to be clearly defined. In this study, we used two different 3D in vitro airway models, namely the EpiAirway-full-thickness (FT) model and a normal human bronchial epithelial cell (NHBE)-based air-liquid interface (ALI) system, to investigate the effect of diesel exhaust particles (DEPs) belonging to PM2.5 on mucociliary clearance. RNA-sequencing (RNA-Seq) analyses of EpiAirway-FT exposed to DEPs indicated that DEP-induced differentially expressed genes (DEGs) are related to ciliary and microtubule function and inflammatory-related pathways. The exposure to DEPs significantly decreased the number of ciliated cells and shortened ciliary length. It reduced the expression of cilium-related genes such as acetylated α-tubulin, ARL13B, DNAH5, and DNAL1 in the NHBEs cultured in the ALI system. Furthermore, DEPs significantly increased the expression of MUC5AC, whereas they decreased the expression of epithelial junction proteins, namely, ZO1, Occludin, and E-cadherin. Impairment of mucociliary clearance by DEPs significantly improved the release of epithelial-derived inflammatory and fibrotic mediators such as IL-1ß, IL-6, IL-8, GM-CSF, MMP-1, VEGF, and S100A9. Taken together, it can be speculated that DEPs can cause ciliary dysfunction, hyperplasia of goblet cells, and the disruption of the epithelial barrier, resulting in the hyperproduction of lung injury mediators. Our data strongly suggest that PM2.5 exposure is directly associated with ciliary and epithelial barrier dysfunction and may exacerbate lung injury.

Tacrolimus impairs airway mucociliary clearance of rats.

OBJECTIVES: Tacrolimus (TAC) is the most widely used immunosuppressive agent after lung transplantation. Considering that the ciliary beat frequency (CBF) mainly depends on the cytoplasmic calcium concentration and that TAC can affect this due to its binding with the intracellular immunophilin FKBP12, we hypothesized that TAC could also impair the airway mucociliary clearance of rats. METHODS: Sixty rats were divided into two groups (n = 30 each): Control = water; TAC = tacrolimus. After 7, 15 or 30 days of treatment, ten animals from each group were euthanized and the following parameters were studied: mucus transportability, CBF, mucociliary transport velocity (MCTV), and neutral and acid mucus production. RESULTS: There was a significant decrease in CBF (Control vs TAC: 7 days, p = 0.008; 15 days, p = 0.007; 30 days, p = 0.001) and MCTV (Control vs TAC: 7 days, p = 0.004; 15 days, p < 0.001; 30 days, p < 0.001) in all immunosuppressed animals. TAC therapy also caused an increase in acid mucus production at all treatment times (Control vs TAC: 7 days, p = 0.001; 15 days, p = 0.043; 30 days, p = 0.001). CONCLUSIONS: TAC impairs airway mucociliary clearance of rats.

Effect of elexacaftor/tezacaftor/ivacaftor on mucus and mucociliary clearance in cystic fibrosis.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (E/T/I) is highly effective clinically for those with at least one F508del-CFTR allele. The effects of E/T/I on mucociliary clearance (MCC) and sputum properties are unknown. We, therefore, sought to characterize the effects of E/T/I on in vivo MCC and sputum characteristics hypothesized to impact mucus transport. METHODS: Forty-four participants ≥12 years of age were enrolled into this prospective, observational trial prior to initiation of E/T/I and had baseline measurement of MCC and characterization of induced sputum and exhaled breath condensate (EBC) samples. Study procedures were repeated after 1 month of E/T/I treatment. RESULTS: Average age was 27.7 years with baseline forced expiratory volume in 1 second (FEV1) of 78.2 % predicted. 52 % of subjects had previously been treated with a 2-drug CFTR modulator combination. The average whole lung MCC rate measured over 60 min (WLAveClr60) significantly improved from baseline to post-E/T/I (14.8 vs. 22.8 %; p = 0.0002), as did other MCC indices. Sputum% solids also improved (modeled mean 3.4 vs. 2.2 %; p<0.0001), whereas non-significant reductions in sputum macrorheology (G', G") were observed. No meaningful changes in exhaled breath condensate endpoints (sialic acid:urea ratio, pH) were observed. CONCLUSIONS: E/T/I improved the hydration of respiratory secretions (% solids) and markedly accelerated MCC. These data confirm the link between CFTR function, mucus solid content, and MCC and help to define the utility of MCC and mucus-related bioassays in future efforts to restore CFTR function in all people with CF.

Effect of turbinate surgery on mucociliary clearance. A systematic review and metanalysis.

Despite the fact that turbinate surgery provides satisfactory results regarding nasal obstruction, most of these procedures are destructive, to some extent, for the respiratory epithelium. There are valid hypotheses suggesting either that turbinate surgery may improve mucociliary clearance (MCC) by improving rhinitis, as well hypotheses suggesting that these surgeries may impair it by damaging the nasal ciliated epithelia. This systematic review is designed with the objective of exploring the effect of turbinate surgery on MCC. Pubmed (Medline), the Cochrane Library, EMBASE, SciELO were analyzed. Four authors members of the YO-IFOS rhinology study group independently analyzed the articles. Extracted variables encompassed: sample size, age, indication for surgery, surgical technique, method used to measure mucociliary clearance, mucociliary transport time before and after surgery, and main outcome. 15 studies with a total population of 1936 participants (1618 patients excluding healthy controls) met the inclusion criteria. 9 studies could be combined in a metanalysis, wich revealed a non-statistically significant decrease of 3.86 min in MCTT after turbinate surgery (p = 0.06). The subgroup analysis of the 5 cohorts who underwent microdebrider turbinoplasty reached statistical significance under a random effect model, revealing a 7.02 min decrease in MCTT (p < 0.001). The laser turbinoplasty subgroup, composed of 4 cohorts, also reached significance, although the difference was lower than that for microdebrider turbinoplasty, 1.01 min (p < 0.001). This systematic review and meta-analysis suggests that turbinate surgery does not compromise mucociliary clearance. The available evidence also suggests that turbinate surgery with mucosa sparing techniques improves MCC, while with aggressive techniques it increases or remains the same. This beneficial effect is evident since the first to third month after surgery. However, for solid conclusions, a standard way to measure MCTT should be stablished, as well as a method to appropriately describe the extension of the surgery.

Effects of THE PEEP-ZEEP Maneuver in Adults Receiving Mechanical Ventilation: A Systematic Review with Meta-Analysis.

INTRODUCTION: It is important to clarify the secretion clearance and lung-related effects of the PEEP-ZEEP maneuver in adults undergoing mechanical ventilation (MV). There is no published comprehensive meta-analysis of the effects of PEEP-ZEEP in adults receiving MV. OBJECTIVES: The aim of this study was to analyze published randomized controlled trials, investigating the effects of the PEEP-ZEEP maneuver in adults undergoing mechanical ventilation. METHODS: We searched Embase, PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from the date of inception of the databases until 6 May 2023. Quality assessment was using the Cochrane Systematic Assessment Handbook. The GRADE system was used to grade the quality of the evidence. RESULTS: A total of 12 trials were included, and the results of the meta-analysis showed that PEEP-ZEEP was not superior to bag squeezing for the removal of bronchial secretions. One study showed a significant increase in the amount of secretion retrieved with the PEEP-ZEEP when compared with tracheal suctioning. Additionally, PEEP-ZEEP was more effective than bag squeezing at improving oxygen saturation. However, one trial showed that bag squeezing was better at improving dynamic compliance. No other differences were found between PEEP-ZEEP and other techniques, except for one study showing more frequent changes in diastolic blood pressure with PEEP-ZEEP compared with ventilator hyperinflation. CONCLUSION: PEEP-ZEEP was not superior to bag squeezing in removing bronchial secretions. However, it improves oxygen saturation when compared to bag squeezing, and no adverse effects on patients' respiratory systems have yet been observed.

Human airway tuft cells influence the mucociliary clearance through cholinergic signalling.

BACKGROUND: Airway tuft cells, formerly called brush cells have long been described only morphologically in human airways. More recent RNAseq studies described a chemosensory cell population, which includes tuft cells, by a distinct gene transcription signature. Yet, until which level in the tracheobronchial tree in native human airway epithelium tuft cells occur and if they function as regulators of innate immunity, e.g., by regulating mucociliary clearance, remained largely elusive. METHODS: We performed immunohistochemistry, RT-PCR and immunoblotting analyses for various tuft cell markers to confirm the presence of this cell type in human tracheal samples. Immunohistochemistry was conducted to study the distribution of tuft cells along the intrapulmonary airways in humans. We assessed the influence of bitter substances and the taste transduction pathway on mucociliary clearance in mouse and human tracheal samples by measuring particle transport speed. RESULTS: Tuft cells identified by the expression of their well-established marker POU class 2 homeobox 3 (POU2F3) were present from the trachea to the bronchioles. We identified choline acetyltransferase in POU2F3 expressing cells as well as the transient receptor potential melastatin 5 (TRPM5) channel in a small population of tracheal epithelial cells with morphological appearance of tuft cells. Application of bitter substances, such as denatonium, led to an increase in mucociliary clearance in human tracheal preparations. This was dependent on activation of the TRPM5 channel and involved cholinergic and nitric oxide signalling, indicating a functional role for human tuft cells in the regulation of mucociliary clearance. CONCLUSIONS: We were able to detect tuft cells in the tracheobronchial tree down to the level of the bronchioles. Moreover, taste transduction and cholinergic signalling occur in the same cells and regulate mucociliary clearance. Thus, tuft cells are potentially involved in the regulation of innate immunity in human airways.

Effect of Functional Endoscopic Sinus Surgery on Functional and Symptomatic Outcomes in Patients with Chronic Rhinosinusitis: A Cross Sectional Study.

Chronic Rhinosinusitis (CRS) is a common condition causing significant symptoms to those affected, cause burden to the healthcare consumption and productivity loss (Fokkens et al. in Rhinol J 58:82-111, 2020). Chronic Rhinosinusitis is diagnosed clinically on the basis of characteristic symptoms with inflammation of the mucosa of the nose and paranasal sinuses of at least 12 consecutive weeks duration (Fokkens et al. in A summary for otorhinolaryngologists Rhinology 50:1-12, 2012). Functional Endoscopic Sinus Surgery is a minimally invasive procedure recommended for chronic Rhinosinusitis. Patients are not routinely assessed specifically for functional and symptomatic improvement after surgery. Previous studies assessed either subjective or objective outcome of surgery (Elwany et al. in Eur Arch Otorhinolaryngol 255:511-514, 1998; Sino-nasal Outcome Test (SNOT-22): A predictor of post-surgical improvement in patients with chronic sinusitis - PMC, 2022. The present study assessed pre and post operative comparison of nasal mucociliary clearance, nasal patency and Sino-nasal outcome score and evaluated both subjective and objective outcomes of functional endoscopic sinus surgery simultaneously. To assess the effect of functional and symptomatic outcomes after Functional Endoscopic Sinus Surgery in patients with Chronic Rhinosinusitis visiting a tertiary care centre in South India. The present study was a hospital based cross-sectional study conducted in the Department of Otorhinolaryngology, in a tertiary care centre in South India, between February 2021 and May 2022. After obtaining informed consent all the patients fulfilling inclusion and exclusion criteria in the given time period were selected as the study population via consecutive sampling method. Detailed history, clinical examination and Diagnostic nasal endoscopy, Computed Tomography (CT) paranasal sinuses were done in all cases. Pre operative Saccharine transit time (STT), Peak nasal inspiratory flow rate (PNIFR) and Sino nasal outcome test (SNOT) 22 score were measured. All cases underwent Functional Endoscopic Sinus Surgery (FESS). Patients were followed up at 1st, 3rd and 6th month for functional and symptomatic outcomes. Data were analysed statistically using Friedman's ANOVA test. A total of 40 patients between the age of 20 and 60 with Chronic Rhinosinusitis with /without nasal polyposis were analysed. Incidence was found to be more common in middle aged group (37.5%). Among the study group 52.5% were females and 47.5% were males 55% was diagnosed as Chronic Rhinosinusitis with nasal polyp (CRSwNP) type and 45% as without nasal polyp (CRSsNP) type. On comparing the variation of Saccharine transit time, Peak nasal inspiratory flow rate and SNOT 22 score with post operative results done at, 1st, 3rd and 6th months using Friedman's ANOVA test showed statistically significant results (P value < 0.05). According to our study there is significant improvement in functional and symptomatic outcomes after Functional Endoscopic sinus surgery and restoration of mucociliary function in Chronic Rhinosinusitis patients. Thus, FESS is an excellent choice for treatment of CRS.

Evaluation of Nasal Mucociliary Clearance as an Indicator of Nasal Function in Obsessive-Compulsive Patients: A Cross-Sectional Study.

This clinical study aimed to compare the mucociliary clearance time in patients with OCD, a disease associated with neural olfactory disorders, with a healthy control group. The mucociliary clearance time of fifty-one patients with OCD and fifty-two healthy patients (control group) was compared. The saccharin nasal mucociliary clearance test (NMCT) was applied and recorded the sociodemographic data of all participants. The NMCT was longer in OCD patients than healthy controls. There was no statistically significant difference in sociodemographic data between the groups. Our results show that olfactory transmission pathways may be affected in OCD patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03972-2.

Glutathione and bicarbonate nanoparticles improve mucociliary transport in cystic fibrosis epithelia.

INTRODUCTION: Cystic fibrosis (CF) airway disease is characterized by thick mucus and impaired mucociliary transport (MCT). Loss of functional cystic fibrosis transmembrane receptor (CFTR) leads to acidification and oxidation of airway surface mucus. Replacing bicarbonate (HCO3 - ) topically fails due to rapid reabsorption and neutralization, while the scavenging antioxidant, glutathione sulfhydryl (GSH), is also rapidly degraded. The objective of this study is to investigate GSH/NaHCO3 nanoparticles as novel strategy for CF airway disease. METHODS: GSH/NaHCO3 poly (lactic-co-glycolic acid) nanoparticles were tested on primary CF (F508del/F508del) epithelial cultures to evaluate dose-release curves, surface pH, toxicity, and MCT indices using micro-optical coherence tomography. In vivo tests were performed in three rabbits to assess safety and toxicity. After 1 week of daily injections, histopathology, computed tomography (CT), and blood chemistries were performed and compared to three controls. Fluorescent nanoparticles were injected into a rabbit with maxillary sinusitis and explants visualized with confocal microscopy. RESULTS: Sustained release of GSH and HCO3 - with no cellular toxicity was observed over 2 weeks. Apical surface pH gradually increased from 6.54 ± 0.13 (baseline) to 7.07 ± 0.10 (24 h) (p < 0.001) and 6.87 ± 0.05 at 14 days (p < 0.001). MCT, ciliary beat frequency, and periciliary liquid were significantly increased. When injected into the maxillary sinuses of rabbits, there were no changes to histology, CT, or blood chemistries. Nanoparticles penetrated rabbit sinusitis mucus on confocal microscopy. CONCLUSION: Findings suggest that GSH/NaHCO3 - nanoparticles are a promising treatment option for viscous mucus in CF and other respiratory diseases of mucus obstruction such as chronic rhinosinusitis.

Computational fluid dynamics modeling of aerosol particle transport through lung airway mucosa.

Delivery of aerosols to the lung can treat various lung diseases. However, the conducting airways are coated by a protective mucus layer with complex properties that make this form of delivery difficult. Mucus is a non-Newtonian fluid and is cleared from the lungs over time by ciliated cells. Further, its gel-like structure hinders the diffusion of particles through it. Any aerosolized treatment of lung diseases must penetrate the mucosal barrier. Using computational fluid dynamics, a model of the airway mucus and periciliary layer was constructed to simulate the transport of impacted aerosol particles. The model predicts the dosage fraction of particles of a certain size that penetrate the mucus and reach the underlying tissue, as well as the distance downstream of the dosage site where tissue concentration is maximized. Reactions that may occur in the mucus are also considered, with simulated data for the interaction of a model virus and an antibody.