Mucociliary Clearance Rate Research Articles

Airway Pressure Gradient May Decrease the Beating Amplitude of Cilia

Motile cilia reside on the surface of the epithelial layer of the lungs and facilitates the clearance of mucus in the airways. Bordering the epithelial layer and surrounding cilia is the periciliary liquid (PCL) that lubricates the epithelial layer. In the present work, we propose a novel approach to study how changes in biomechanics affect the physiological functioning of cilia in healthy subjects and in patients with CF, COPD and primary ciliary dyskinesia (PCD). In particular, we investigate the response of cilia to different local pressure gradient during gaseous exchange. We hypothesize that the airway pressure gradient that occur during inhalation and exhalation may displace mucus and PCL and exert pressure on cilia. Therefore, cilia must be able to withstand the forces created by the airway pressure gradient, otherwise the magnitude of its efficient strokes and its rate of mucociliary clearance would decrease. We develop a computational model of the airways to quantify the effect of airway pressure gradient on cilia dynamics. In the model, cilia are represented as elastic solids, PCL and mucus is represented as fluids with different densities and viscosities. The simulation results show that in diseases such as PCD, where there exist changes in ciliary structure, the airway pressure gradient may affect the effective stroke of cilia and decrease the rate of mucociliary clearance. Simulation results predict that the average stress experienced by cilia varies exponential with the number of cilia shed from CF and COPD airways.

In vitro safety and performance evaluation of a seawater solution enriched with copper, hyaluronic acid, and eucalyptus for nasal lavage.

BackgroundThe common cold is a viral infectious disease with symptoms such as runny nose, sore throat, and mainly, nasal congestion. State-of-the-art therapeutic approaches focus on alleviating the symptoms of this disease by non-invasive and simple-to-use methods. Nasal irrigation is one of the most accepted approaches to ease nasal congestion which, if left untreated, has a negative impact on the quality of life of patients.PurposeIn this study, the safety and efficacy of a novel hypertonic seawater solution for nasal lavage enriched with hyaluronic acids, eucalyptus oil, copper, and manganese salts (Stérimar Stop & Protect Cold and Flu; SSPCF) have been investigated in vitro.MethodsAn in vitro 3D reconstituted human nasal epithelium tissue model, MucilAir™, has been used in this study to investigate the safety of SSPCF on nasal epithelium by measuring transepithelial electrical resistance (TEER), lactate dehydrogenase (LDH), and interleukin-8 (IL-8) secretion. The efficacy of SSPCF was measured by mucociliary clearance (MCC), ATP release, Alcian blue and aquaporin (AQP3) stainings.ResultsSSPCF treatment respected nasal epithelium tissue integrity and enhanced barrier function without inducing a cytotoxic response. Secreted LDH and IL-8 levels were similar to untreated controls. MCC rate was increased 2.5-fold and ATP release decreased 87% upon SSPCF treatment, indicating improved decongestion activity. SSPCF treatment after hypotonic stress helped recover cellular organization, as shown by Alcian blue and AQP3 staining assays.ConclusionSSPCF appears as a safe and effective nasal irrigation formula that may alleviate the symptoms associated with common cold such as nasal congestion.

Mice with a Deletion of Rsph1 Exhibit a Low Level of Mucociliary Clearance and Develop a Primary Ciliary Dyskinesia Phenotype.

Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disease caused by mutations in over 40 different genes. Individuals with PCD caused by mutations in RSPH1 (radial spoke head 1 homolog) have been reported to have a milder phenotype than other individuals with PCD, as evidenced by a lower incidence of neonatal respiratory distress, higher nasal nitric oxide concentrations, and better lung function. To better understand genotype-phenotype relationships in PCD, we have characterized a mutant mouse model with a deletion of Rsph1. Approximately 50% of cilia from Rsph1-/- cells appeared normal by transmission EM, whereas the remaining cilia revealed a range of defects, primarily transpositions or a missing central pair. Ciliary beat frequency in Rsph1-/- cells was significantly lower than in control cells (20.2 ± 0.8 vs. 25.0 ± 0.9 Hz), and the cilia exhibited an aberrant rotational waveform. Young Rsph1-/- animals demonstrated a low rate of mucociliary clearance in the nasopharynx that was reduced to zero by about 1 month of age. Rsph1-/- animals accumulated mucus in the nasal cavity but had a lower bacterial burden than animals with a deletion of dynein axonemal intermediate chain 1 (Dnaic1-/-). Thus, Rsph1-/- mice display a PCD phenotype similar to but less severe than that observed in Dnaic1-/- mice, similar to what has been observed in humans. The results suggest that some individuals with PCD may not have a complete loss of mucociliary clearance and further suggest that early diagnosis and intervention may be important to maintain this low amount of clearance.

Quantitative Assessment of Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging Using the Change in Penetration Index.

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study compared the use of change in penetration index (PI) with conventional whole lung clearance in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (1) healthy nonsmoking controls (n = 9), (2) smoking controls who were current smokers with normal lung function (n = 10), and (3) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volume at 1 second (FEV1) for the three groups was 109 (±18), 94 (±5), and 78 (±12), respectively. Following inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Total lung clearance and tracheobronchial clearance (TBC; normalized to 24-hour clearance) were calculated. A novel parameter, the normalized change in PI (NOCHIP), was also evaluated. PI is the ratio of counts between outer and inner lung zones normalized to lung volume. Results: More aerosol was deposited in central airways in COPD compared to nonsmoking controls, using 24-hour clearance measurements (p < 0.001). Smoking controls had intermediate values. The optimal endpoint for MCC assessment was chosen to be 3 hours, when intersubject variability was minimal, while preserving a measure of early clearance. There was no statistical difference between the three groups in mean total lung clearance, or TBC, at 3 hours. NOCHIP at 3 hours was reduced significantly, compared to nonsmoking controls, in both smoking controls (p = 0.007) and COPD (p < 0.0001). It also correlated with FEV1 (p = 0.003). A higher proportion of smoking control subjects had NOCHIP values in the nonsmoking control range than in the COPD group. Conclusions: NOCHIP was a more sensitive measure of MCC than whole lung clearance and TBC in mild-to-moderate COPD.

The effect of erdosteine on airway defence mechanisms and inflammatory cytokines in the settings of allergic inflammation

IntroductionMucoactive agent, erdosteine, besides mucolytic activity, is characterized by many other pharmacodynamic properties which could be beneficial in the management of inflammatory conditions. BackgroundUsing guinea pig experimental model of allergic inflammation, we evaluated the ability of erdosteine to modulate airway defence mechanisms and inflammation after 10 days (10 mg/kg/day) administration. MethodsIn vivo changes in specific airway resistance and amplitude of tracheal contraction were estimated to evaluate the bronchodilatory effect. The sensitivity of chemically induced cough reflex was estimated via in vivo method. The ciliary beat frequency assessed on brushed tracheal cells was used as an indicator of the mucociliary clearance rate. The concentrations of the inflammatory cytokines IL-4, IL-5, IL-13 and IL-10 were measured in BALF using multiplex detecting method. ResultsOur data show that 10 days erdosteine administration resulted in bronchodilation and stimulation of ciliary beat frequency. Erdosteine did not affect the parameters of chemically induced cough reflex. Erdosteine demonstrated the modest decline in inflammatory cytokines IL-5, IL-13 and an increase in the concentration of IL-10, which is a potent regulator of inflammatory responses and plays a critical role in controlling allergic airway inflammation. ConclusionIn summary, we can state, that erdosteine is multi-action drug and it seems to have many beneficial and complementary effect in the management of chronic inflammatory airway diseases complicated by viscous mucus.

Mucociliary Clearance in Mice Measured by Tracking Trans-tracheal Fluorescence of Nasally Aerosolized Beads

Mucociliary clearance (MCC) is the first line of defense in clearing airways. In genetically engineered mice, each component of this system (ciliary beat, mucus, airway surface hydration) can be studied separately to determine its contribution to MCC. Because MCC is difficult to measure in mice, MCC measurements are often omitted from these studies. We report a simple method to measure MCC in mice involving nasal inhalation of aerosolized fluorescent beads and trans-tracheal bead tracking. This method has a number of advantages over existing methods: (1) a small volume of liquid is deposited thus minimally disturbing the airway surface; (2) bead behavior on airways can be visualized; (3) useful for adult or neonatal mice; (4) the equipment is relatively inexpensive and easily obtainable. The type of anesthetic had no significant effect on the rate of MCC, but overloading the airways with beads significantly decreased MCC. In addition, the rate of bead transport was not different in alive (3.11 mm/min) vs recently euthanized mice (3.10 mm/min). A 5-min aerosolization of beads in a solution containing UTP significantly increased the rate of MCC, demonstrating that our method would be of value in testing the role of various pharmacological agents on MCC.

Effect of the temperature of nasal lavages on mucociliary clearance: a randomised controlled trial.

The respiratory epithelium is mainly constituted by caliciform (produces mucus, responsible of keeping moisture and trapping particles) and ciliated cells (transports mucus into the pharynx, by the movement of multiple cilia). For centuries, nasal lavages have been used for different rhinosinusal conditions. Some studies suggest not only a direct effect on the mobilisation of secretions, but also an improvement in mucociliary clearance rates. To our knowledge, the impact of temperature in nasal lavages has been scarcely studied. We used the saccharin test-applying it in the inferior turbinate and timing the detection of its taste-, to estimate mucociliary clearance rates before and after nasal lavages with saline solution at room (20°C) or body (37°C) temperatures. 78 healthy subjects were studied, with a mean saccharin test time of 13.88min. Then, a nasal lavage was performed, half with 20°C saline and the other with 37°C. In both, times improved from baseline (from 13.66 to 11.59 and 14.06 to 9.4min, respectively) with p values < 0.05. Nasal lavages with saline solution improve mucociliary clearance as measured by saccharin test. Temperature seems to matter, which should be taken into account when indicating nasal lavages to our patients.

Cigarette smoke promotes HIV infection of primary bronchial epithelium and additively suppresses CFTR function

Recurrent lung infections are a common cause of morbidity and mortality in people living with HIV and this is exacerbated in smokers even when administered combination antiretroviral therapy (cART). The incidence of pneumonia is increased with smoking and treatment interruption and is directly dependent on viral load in patients when adjusted for CD4 counts. CFTR dysfunction plays an important role in aberrant airway innate immunity as it is pivotal in regulating mucociliary clearance (MCC) rates and other antibacterial mechanisms of the airway. In our earlier work, we have demonstrated that bronchial epithelium expresses canonical HIV receptors CD4, CCR5 and CXCR4 and can be infected with HIV. HIV Tat suppresses CFTR mRNA and function via TGF-β signaling. In the present study, we demonstrate that cigarette smoke (CS) potentiates HIV infection of bronchial epithelial cells by upregulating CD4 and CCR5 expression. HIV and CS individually and additively suppress CFTR biogenesis and function, possibly explaining the increased incidence of lung infections in HIV patients and its exacerbation in HIV smokers.

Effect of inhaled and oral n-acetylcysteine on airway defense mechanism

Abstract Aim: N-acetylcysteine is the prototype of mucolytic agents. The aim of this study was to evaluate the acute and chronic effect of inhaled and oral N-acetylcysteine on airway reactivity, cough reflex and ciliary beat frequency and parameters of mentioned defense mechanisms were assessed in physiological conditions. Methods: An experiment was performed using healthy guinea pigs treated with inhaled (0.6 M; 5min) and oral N-acetylcysteine (20 mg/kg), administrated either acutely as a single dose or chronically during 7 days. The cough reflex and specific airway resistance were assessed by in vivo method, using a double chamber plethysmograph box. The ciliary beat frequency was evaluated in in vitro conditions on tracheal brushed samples using light microscope coupled to high speed video camera. Results: Inhaled and oral N-acetylcysteine, either administrated as a single dose or during 7 days, have shown a tendency to decrease sensitivity of the cough reflex and increase the airway reactivity. Acute administration of inhaled and oral N-acetylcysteine had no statistically relevant effect on the ciliary beat frequency, whereas chronic administration of both inhaled and oral N-acetylcysteine led to a marked reduction in the ciliary beat frequency. Conclusion: Chronic administration of oral and inhaled N-acetylcysteine had a negative impact on the ciliary beat frequency, which represents one of the key factors determining the rate of mucociliary clearance. Thus, administration of N-acetylcysteine is less likely to increase the expulsion of mucus by ciliary movement. In addition, the observed tendency of inhaled and oral N-acetylcysteine to increase the airway reactivity may limit its use in conditions with severe airflow obstruction.

Safety and benefits of inhaled hypertonic saline following airway challenges with endotoxin and allergen in asthmatics

ABSTRACTObjective: To determine whether induced sputum (IS) with hypertonic saline inhalation is safe to use in asthmatics within 24 hours of two commonly used airway challenges, namely endotoxin and dust mite allergen, and to assess whether IS can enhance mucociliary clearance (MCC) rates in asthmatics. Methods: IS (three 7-minute inhalation periods of 3%, 4%, and 5% hypertonic saline) was employed before (N = 29) and within 24 hours of inhaled challenges with endotoxin (N = 13) and dust mite allergen (N = 12) in a cohort of mild to moderate asthmatics. Safety was assessed by lung function (Forced Expiratory Volume in 1 second; FEV1) and MCC was measured using a radiolabeled gamma scintigraphy method (Tcm99 sulfur colloid). IS was performed pre and post MCC. Results: No significant lung function decrement was observed before or after inhaled challenges with endotoxin or dust mite allergen. IS significantly enhanced MCC rates before and after inhaled endotoxin challenge. Conclusion: Based on a small cohort, IS is safe to use in mild to moderate asthmatics before and within 24 hours of inhaled challenges with endotoxin and dust mite allergen. Furthermore, IS has beneficial effects on host defense function in asthmatics by enhancing MCC rates.

Mucociliary Function: Its Variations with Disease

ABSTRACT Introduction This study compares the nasal mucociliary clearance time of patients with chronic sinusitis (pre- and postoperatively) and smokers, with controls, attending the ear, nose, and throat outpatient department at Southern Railway Headquarters Hospital, Perambur, Chennai. Materials and methods Saccharin granule was used to study mucociliary clearance as it is safe, easy, fast, and reliable. A total of 32 patients in each group were studied. In chronic rhinosinusitis patients, the test was done preoperatively and 4 weeks postoperatively. Results The average mucociliary clearance time pre- and post-operatively in chronic rhinosinusitis patients was 29.54 ± 28.68 and 12.17 ± 5.84 respectively. Cigarette smokers had a longer mucociliary clearance time (27.63 ± 21.11) compared with beedi smokers (24.04 ± 24.93). Controls had the fastest mucociliary clearance rate of 9.67 ± 4.62 among the study subjects. Conclusion Surgery for chronic rhinosinusitis improves both the overall symptoms of chronic rhinosinusitis and the protective functions of the nose and paranasal sinuses. Smokers had an impaired clearance rate compared with normals. As age advances, the mucociliary clearance rate becomes slower. How to cite this article Vamanshankar H, Kumar SC, Preetham AP, Feshan M. Mucociliary Function: Its Variations with Disease. Clin Rhinol An Int J 2016;9(2):68-73.

Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Development of a CFD Model.

The objective of this study was to develop a computational fluid dynamics (CFD) model to predict the deposition, dissolution, clearance, and absorption of pharmaceutical particles in the human nasal cavity. A three-dimensional nasal cavity geometry was converted to a surface-based model, providing an anatomically-accurate domain for the simulations. Particle deposition data from a commercial nasal spray product was mapped onto the surface model, and a mucus velocity field was calculated and validated with in vivo nasal clearance rates. A submodel for the dissolution of deposited particles was developed and validated based on comparisons to existing in vitro data for multiple pharmaceutical products. A parametric study was then performed to assess sensitivity of epithelial drug uptake to model conditions and assumptions. The particle displacement distance (depth) in the mucus layer had a modest effect on overall drug absorption, while the mucociliary clearance rate was found to be primarily responsible for drug uptake over the timescale of nasal clearance for the corticosteroid mometasone furoate (MF). The model revealed that drug deposition in the nasal vestibule (NV) could slowly be transported into the main passage (MP) and then absorbed through connection of the liquid layer in the NV and MP regions. As a result, high intersubject variability in cumulative uptake was predicted, depending on the length of time the NV dose was left undisturbed without blowing or wiping the nose. This study has developed, for the first time, a complete CFD model of nasal aerosol delivery from the point of spray formation through absorption at the respiratory epithelial surface. For the development and assessment of nasal aerosol products, this CFD-based in silico model provides a new option to complement existing in vitro nasal cast studies of deposition and in vivo imaging experiments of clearance.

Visualization of drug translocation in the nasal cavity and pharmacokinetic analysis on nasal drug absorption using positron emission tomography in the rat

We performed positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) to evaluate the pharmacokinetics of nasal drug absorption in the rat. The dosing solution of [18F]FDG was varied in volume (ranging from 5 to 25μl) and viscosity (using 0% to 3% concentrations of hydroxypropylcellulose). We modeled the pharmacokinetic parameters regarding the nasal cavity and pharynx using mass balance equations, and evaluated the values that were obtained by fitting concentration–time profiles using WinNonlin® software. The regional nasal permeability was also estimated using the active surface area derived from the PET images. The translocation of [18F]FDG from the nasal cavity was visualized using PET. Analysis of the PET imaging data revealed that the pharmacokinetic parameters were independent of the dosing solution volume; however, the viscosity increased the absorption rate constant and decreased the mucociliary clearance rate constant. Nasal permeability was initially higher but subsequently decreased until the end of the study, indicating regional differences in permeability in the nasal cavity. We concluded that the visualization of drug translocation in the nasal cavity in the rat using PET enables quantitative analysis of nasal drug absorption, thereby facilitating the development of nasal formulations for human use.

The Effect of Stimulatory Compounds on Baseline and Impaired Mucociliary Clearance in the Guinea Pig

Mucociliary clearance (MCC) is an important mechanism for clearing the lung of foreign matter and is impaired in diseases such as COPD. Smoking reduces MCC in humans and may contribute to the disease, whereas agents such as β2-adrenergic agonists, hypertonic saline and mannitol are known to increase MCC rate. We have developed a model which can be used to identify compounds with potential to increase or rectify defective MCC. Methods Guinea pigs were exposed to air or tobacco smoke (TS) for 4 days and 24hrs after the last exposure the trachea was exposed and fluorescent beads applied via a small cut near the carina. After a set time, the distance traveled by the beads was visualised and measured. Isotonic saline, hypertonic saline (7%), mannitol (16%) or Formoterol (1.7µg/kg) were dosed i.n. 1hr prior to bead administration. All data are given as mean±SD. Results Administration of mannitol increased (+62%, p<0.001) MCC rate compared to air-exposed controls (5.44±0.93 vs 3.36±0.65mm/min). Hypertonic saline had no effect (3.91±0.96 vs 3.36±0.65mm/min). Formoterol, at a known bronchodilator dose, also reproducibly increased (+65%) MCC rate (5.56±1.69 vs 3.34±1.17mm/min). Exposure to TS caused a marked decrease (-36%) in MCC rate (3.88±1.03 vs 2.49±0.72mm/min, p<0.001). The TS-induced reduction in MCC rate was reproducible over 5 separate studies. Formoterol significantly increased MCC rate (+60%) in the TS-exposed animals (3.71±0.54 vs 2.49±0.72mm/min, p<0.05) to within air exposed, vehicle control group levels. This model demonstrates that MCC rate can be reproducibly measured in the guinea pig trachea. The baseline rate can be enhanced by Formoterol and mannitol, impaired by TS-exposure and subsequently restored to baseline rate by Formoterol. Funded by Argenta

Nasal mucociliary clearance in obstructive sleep apnea syndrome patients.

The main objective of this study was to investigate the correlation between the level of mucociliary dysfunction and severity of obstructive sleep apnea syndrome (OSAS). The effect of smoking in OSAS patients on mucociliary dysfunction was also assessed. It is a descriptive study that compares variables between groups (univariate analysis). In this clinical trial 122 patients with varying degrees of OSAS and 49 healthy volunteers were included (n = 171). Patients were divided into three groups as having mild, moderate, and severe OSAS, according to their apnea hypopnea index (AHI) values. (AHI values are typically categorized as 5-15/hr, mild OSAS; 15-30/hr, moderate OSAS; and >30/hr, severe OSAS.) The control group was comprised of healthy subjects. Each group was divided into smoking and nonsmoking subgroups. The mucociliary rates of the subjects were measured using the saccharin test. Statistical analysis was performed with the GraphPad Prism Version 3 pocket program. Mild and moderate OSAS groups showed similar results with control group (p = 0.869), but severe OSAS patients showed a statistically significant difference with control group (Kruskal-Wallis [KW] = 32.28; p = 0.0032 and p < 0.05). Although in the moderate OSAS group the mucociliary clearance rates showed a tendency to decrease, this decrease was not significant (p = 0.453). A statistically significant difference was observed between smokers and nonsmokers in terms of mucociliary clearance times in all groups (KW = 18.24; p = 0.001). The nasal mucociliary system is significantly deteriorated in severe OSAS patients and they should be meticulously observed to prevent sinonasal infections. Measures to enhance mucociliary activity in these patients should be taken. Smoking, a well-known inhibitor of mucociliary activity, also has a negative impact on the mucociliary function of OSAS patients and quitting smoking would be of benefit for these patients.

Quantitative imaging of airway liquid absorption in cystic fibrosis.

New measures are needed to rapidly assess emerging treatments for cystic fibrosis (CF) lung disease. Using an imaging approach, we evaluated the absorptive clearance of the radiolabeled small molecule probe diethylene triamine penta-acetic acid (DTPA) as an in vivo indicator of changes in airway liquid absorption. DTPA absorption and mucociliary clearance rates were measured in 21 patients with CF (12 adults and nine children) and nine adult controls using nuclear imaging. The effect of hypertonic saline on DTPA absorption was also studied. In addition, in vitro studies were conducted to identify the determinants of transepithelial DTPA absorption. CF patients had significantly increased rates of DTPA absorption compared with control subjects but had similar mucociliary clearance rates. Treatment with hypertonic saline resulted in a decrease in DTPA absorption and an increase in mucociliary clearance in 11 out of 11 adult CF patients compared with treatment with isotonic saline. In vitro studies revealed that ∼ 50% of DTPA absorption can be attributed to transepithelial fluid transport. Apically applied mucus impedes liquid and DTPA absorption. However, mucus effects become negligible in the presence of an osmotic stimulus. Functional imaging of DTPA absorption provides a quantifiable marker of immediate response to treatments that promote airway surface liquid hydration.

Effect of Clenbuterol on Tracheal Mucociliary Transport in Horses Undergoing Simulated Long‐Distance Transportation

Pneumonia is observed in horses after long-distance transportation in association with confinement of head position leading to reduction in tracheal mucociliary clearance rate (TMCR). Clenbuterol, a beta-2 agonist shown to increase TMCR in the horse, will ameliorate the effects of a fixed elevated head position on large airway contamination and inflammation in a model of long-distance transportation model. Six adult horses. A cross-over designed prospective study. Horses were maintained with a fixed elevated head position for 48 hours to simulate long-distance transport, and treated with clenbuterol (0.8 μg/kg PO q12h) or a placebo starting 12 hours before simulated transportation. TMCR was measured using a charcoal clearance technique. Data were collected at baseline and 48 hours, and included TMCR, tracheal wash cytology and quantitative culture, rectal temperature, CBC, fibrinogen, and serum TNFα, IL-10, and IL-2 levels. There was a 18-21 day washout between study arms, and data were analyzed using regression analysis and Wilcoxon rank-sum tests. Tracheal mucociliary clearance rate was significantly decreased after transportation in both treatment (P = .002) and placebo (P = .03) groups. There was a significant effect of treatment on TMCR, with the treatment group showing half the reduction in TMCR compared with the placebo group (P = .002). Other significant differences between before- and after-transportation samples occurred for serum fibrinogen, peripheral eosinophil count, quantitative culture, tracheal bacteria, and degenerate neutrophils, though no treatment effect was found. Treatment with clenbuterol modestly attenuates the deleterious effects of this long-distance transportation model on tracheal mucociliary clearance.

The Impact of Unilateral Concha Bullosa on Mucociliary Activity: An Assessment by Rhinoscintigraphy

In this study, we aimed to compare the differences of nasal mucociliary clearance rate (NMCR) by rhinoscintigraphic examination between the nasal cavities of patients with unilateral concha bullosa (CB). The study group consisted of 43 patients (18 men and 25 women), with unilateral CB ranging in age from 20 to 58 years (mean age, 33.5 ± 9.51 years). The nasal mucociliary clearance was described as the velocity (mm/min) of nasal mucociliary transport of the technetium 99m-macroaggragated albumin droplet. Rhinoscintigraphy was performed on each nasal cavity with 2-day intervals in the patients. The mucociliary clearance rates obtained in the unaffected side were accepted as control values. The average values for mucociliary clearance rate were 2.29 ± 0.42 mm/min in the CB side of the nasal cavity, and 3.19 ± 0.52 mm/min in the other side of the nasal cavity. Mucociliary transport took a longer time in the CB side of the nasal cavity than in the other side of the nasal cavity, which was found to be statistically significant (p < 0.001). Our study showed that unilateral CB might impair NMCR in the ipsilateral side of the nasal cavity. Thus surgical intervention to reduce the middle concha volume may result in a better mucociliary clearance with possibly a less chance of development of chronic sinus diseases and nasal pathologies. Obviously, it is of utmost importance that new studies be planned with larger patient series to better understand nasal mucociliary transport mechanism and CB relationships.

Comparison of two different adenoidectomy techniques with special emphasize on postoperative nasal mucociliary clearance rates: Coblation technique vs. cold curettage

ObjectiveTo compare the cold curettage and coblation techniques for pediatric adenoidectomy by means of intraoperative blood loss, operation time, and pre- and postoperative nasal mucociliary clearance rates. MethodsThe study included 60 consecutive patients undergoing adenoidectomy operation upon the diagnosis of adenoid hypertrophy ranging in age 4–8 years (mean age: 5.82±1.25 years). Two groups consist of 30 patients. The two different adenoidectomy techniques were compared by means of intraoperative blood loss, operation duration, preoperative and postoperative nasal mucociliary clearance rate (NMCR) values. The nasal mucociliary clearance was described as the velocity (mm/min) of nasal mucociliary transport of the 99mTc-MAA droplet. Rhinoscintigraphy was performed on right nasal cavity before and after the surgery in all the patients. ResultsThe average NMCR of the curettage adenoidectomy and coblation adenoidectomy groups before surgery was 1.33±0.20mm/min and 1.35±0.19mm/min, respectively. There was no statistically significant difference between the two groups before surgery (p=0.615). In the six weeks of the post-operative period, the average NMCR of the curettage adenoidectomy and coblation adenoidectomy groups were 1.80±0.21mm/min and 2.06±0.31mm/min, respectively. The NMCR differences of preoperative and postoperative periods in coblation adenoidectomy group were higher than curettage adenoidectomy group (p<0.001). Mean operative time was 20.5±5.5min for coblation adenoidectomy group (n: 30), and 13.5±5.2min for curettage adenoidectomy group (n: 30). Mean intraoperative blood loss was 5.25±3.5ml for coblation adenoidectomy group, and 21.55±8.2ml for curettage adenoidectomy group. The difference between mean intraoperative blood loss and operative time of two groups were statistically significant (p<0.05). ConclusionThe coblation technique provides a less bleeding surgical bed but a longer operation time when compared to curettage technique. Also the better NMCR values that we have found with coblation adenoidectomy may be translated to a more rapid recovery of ciliary function of the surface mucosa.

Adenosine increases nasal mucociliary clearance rate in mice through A2A and A2B adenosine receptors

Mucociliary clearance (MCC) is an important mechanism of host defense in the upper and lower respiratory tract. Impaired MCC plays a critical role in the development and perpetuation of chronic rhinosinusitis (CRS). The aim of this investigation was to determine the influence of adenosine on nasal MCC, and to determine the receptors mediating this physiology in vivo. Prospective study using an animal model. Nasal MCC was measured by whole-nose scintigraphic acquisition in vivo. The effects of both endogenous and exogenous adenosine were investigated in wild-type and adenosine receptor knockout (A(2A)(-/-), A(2B)(-/-), A(2A)(-/-)A(2B)(-/-), and A(1)(-/- )A(3)(-/-)) mice. Exogenous adenosine aerosol robustly enhanced nasal MCC. The augmentation of MCC by adenosine was abolished in mice lacking both A(2A) and A(2B) receptors, but remained robust in mice lacking either A(2A) or A(2B) . Likewise, basal nasal MCC was reduced in mice lacking both the A(2A) and A(2B) receptors, but was statistically identical among wild-type mice and mice lacking either A(2A) or A(2B) . These findings indicate that activation of both G(s) -coupled adenosine receptors can accelerate nasal MCC. Targeting these receptors may represent a novel therapeutic approach for enhancing MCC in CRS.