Mucociliary Transport Velocity Research Articles

Tacrolimus impairs airway mucociliary clearance of rats

ObjectivesTacrolimus (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. MethodsSixty 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. ResultsThere 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). ConclusionsTAC impairs airway mucociliary clearance of rats.

Nasal polyps show decreased mucociliary transport despite vigorous ciliary beating

ObjectiveMucociliary transport function in the airway mucosa is essential for maintaining a clean mucosal surface. This function is impaired in upper and lower airway diseases. Nasal polyps are a noticeable pathological feature that develop in some of the patients with chronic rhinosinusitis. Like ordinary nasal mucosae, nasal polyps have a ciliated pseudostratified epithelium with vigorous ciliary beating. We measured ex vivo Mucociliary Transport Velocity (MCTV) and Ciliary Beat Frequency (CBF) and explored the expressions of Planar Cell Polarity (PCP) proteins in nasal polyps in comparison with turbinate mucosae. MethodsInferior turbinates and nasal polyps were surgically collected from patients with chronic rhinosinusitis. Ex vivo MCTV and CBF were measured using a high-speed digital imaging system. Expressions of PCP proteins were explored by fluorescence immunohistochemistry and quantitative RT-PCR. ResultsThe MCTV of nasal polyps was significantly lower than that of the turbinates (7.43 ± 2.01 vs. 14.56 ± 2.09 μm/s; p = 0.0361), whereas CBF did not differ between the two tissues. The MCTV vector was pointed to the posteroinferior direction in all turbinates with an average inclination angle of 41.0 degrees. Immunohistochemical expressions of Dishevelled-1, Dishevelled-3, Frizzled3, Frizzled6, Prickle2 and Vangl2 were lower in the nasal polyps than in the turbinates. Confocal laser scanning microscopy showed that Frizzled3 was localized along the cell junction on the apical surface. The expression levels of mRNAs for Dishevelled-1, Dishevelled-3 and Frizzled3 in the nasal polyps were also decreased in comparison with the turbinates. ConclusionThese results indicate that muco ciliary transport in nasal polyps is impaired although vigorous ciliary beating is maintained, and that the impairment may be caused by a decrease in Dishevelled/Frizzled proteins and resultant PCP disarrangement. Level of evidenceLevel 3.

Basiliximab Does Not Impair Airway Mucociliary Clearance of Rats.

Previous studies have shown that immunosuppressive drugs impair the airway mucociliary clearance of rats. However, considering the high specificity of basiliximab (BSX) and the absence of studies reporting its side effects, our aim was to investigate whether BSX, associated or not with triple therapy, impairs the mucociliary system. Forty rats were divided into 4 groups: Control, BSX, Triple, and BSX + Triple. After 15days of treatment, animals were euthanized and the ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), neutral and acid mucin production, Muc5ac and Muc5b gene expression, inflammatory cell number, and interleukin (IL)-6 concentration were analyzed. CBF and MCTV were lower in Triple and BSX + Triple groups (p < 0.05). Neutral mucin percentage was higher in Triple group (p < 0.05), and acid mucin percentage was higher in Triple and BSX + Triple groups (p < 0.05). The Muc5ac and Muc5b gene expression was higher in Triple and BSX + Triple groups (p < 0.05). Animals from Triple and BSX + Triple groups presented fewer mononuclear cells (p < 0.05). The number of polymorphonuclear cells was higher in the Triple group (p < 0.05). In the analysis of inflammatory cells in the blood, there was a decrease in lymphocytes and an increase in neutrophils in the Triple and BSX + Triple groups (p < 0.05). The concentration of IL-6 significantly increased in the animals of the Triple and BSX + Triple groups (p < 0.05). BSX did not change the mucociliary apparatus of rats.

A quantitative interspecies comparison of the respiratory mucociliary clearance mechanism

Collectively coordinated ciliary activity propels the airway mucus, which lines the luminal surface of the vertebrate respiratory system, in cranial direction. Our contemporary understanding on how the quantitative characteristics of the metachronal wave field determines the resulting mucociliary transport is still limited, partly due to the sparse availability of quantitative observational data. We employed high-speed video reflection microscopy to image and quantitatively characterize the metachronal wave field as well as the mucociliary transport in excised bovine, porcine, ovine, lapine, turkey and ostrich samples. Image processing techniques were used to determine the ciliary beating frequency (CBF), the velocity and wavelength of the metachronal wave and the mucociliary transport velocity. The transport direction was found to strongly correlate with the mean wave propagation direction in all six species. The CBF yielded similar values (10–15 Hz) for all six species. Birds were found to exhibit higher transport speeds (130–260 upmum/s) than mammals (20–80 upmum/s). While the average transport direction significantly deviates from the tracheal long axis in mammals, no significant deviation was found in birds. The metachronal waves were found to propagate at about 4–8 times the speed of mucociliary transport in mammals, whereas in birds they propagate at about the transport speed. The mucociliary transport in birds is fast and roughly follows the TLA, whereas the transport is slower and proceeds along a left-handed spiral in mammals. The longer wavelengths and the lower ratio between the metachronal wave speed and the mucociliary transport speed provide evidence that the mucociliary clearance mechanism operates differently in birds than in mammals.

Effects of BNO 1016 on ciliary transport velocity and cell culture surface liquid height of sinonasal epithelial cultures

BackgroundBNO 1016 is an ethanolic extract of a mixture of five herbs that has been sold in different formulations for decades in the European market and more recently, in the United States market as an over-the-counter treatment for rhinosinusitis. Previous studies indicated activation of chloride secretion and increase in ciliary beat frequency by BNO 1016 but the functional consequences on mucociliary transport velocity and airway surface liquid homeostasis are unknown. This study intends to examine the effects of BNO 1016 on these properties in vitro.ResultsHuman sinonasal epithelial cells were grown at an air-liquid interface, with addition of BNO 1016 basolaterally in each experiment. Polystyrene fluorescent microspheres were added to the apical surface of the culture, and distance traveled across the surface of the culture over a fixed time period was measured using live imaging. BNO 1016 concentrations of 50 μg/ml and 500 μg/ml were tested. Basolateral application of compound resulted in a non-dose-dependent increase in culture surface liquid height compared to controls at 30 min, and this effect persisted through the one-hour duration of the experiment (p < 0.01). Basolateral application of BNO 1016 also resulted in a non-dose-dependent increase in microsphere transport velocity at 45 and 60 min following compound application (p < 0.01).ConclusionsBasolateral application of BNO 1016 at a concentration mimicking post-ingestion serum levels appears to elicit increases in cell culture surface liquid height and mucociliary clearance, as assessed by microsphere transport velocity. These properties can potentially be leveraged for therapeutic efficacy in diseases affecting mucus production and mucociliary transport.

Particle coating alters mucociliary transit in excised rat trachea: A synchrotron X-ray imaging study

We have previously developed non-invasive in vivo mucociliary transport (MCT) monitoring methods using synchrotron phase contrast X-ray imaging (PCXI) to evaluate potential therapies for cystic fibrosis (CF). However, previous in vivo measurements of MCT velocity using this method were lower than those from alternate methods. We hypothesise this was due to the surface chemistry of the uncoated particles. We investigated the effect of particle surface coating on MCT marker performance by measuring the velocity of uncoated, positively-charged (aminated; NH2), and negatively-charged (carboxylated; COOH) particles. The effect of aerosolised hypertonic saline (HS) was also investigated, as previous in vivo measurements showed HS significantly increased MCT rate. PCXI experiments were performed using an ex vivo rat tracheal imaging setup. Prior to aerosol delivery there was little movement of the uncoated particles, whilst the NH2 and COOH particles moved with MCT rates similar to those previously reported. After application of HS the uncoated and COOH particle velocity increased and NH2 decreased. This experiment validated the use of COOH particles as MCT marker particles over the uncoated and NH2 coated particles. Our results suggest that future experiments measuring MCT using synchrotron PCXI should use COOH coated marker particles for more accurate MCT quantification.

Inflammation Increases the Opening State of Channels in the Epithelium, Releasing High Levels of ATP that Resulted in a Decrease on Mucociliary Transport Velocity in the Airways

ATP is one of the chemical signals locally released by the airway epithelium associated with an autocrine/paracrine mechanism to control basal ciliary beat frequency (CBF). A recent study has reported that ATP has a dual effect on CBF, since ATP (μM) increases CBF, but high levels of ATP (mM) significantly decreases CBF in cultures of mouse tracheal epithelial cell. This nucleotide can be released by different mechanisms that include hemichannels of connexins (Cx43) and pannexins (Panx1), and more recently the Calhm1 channel. In several cell types it has recently reported that in pathophysiological conditions, connexins and pannexins channels could modify their opening state. Furthermore, high levels of ATP have been measured in the bronchoalveolar fluid of asthmatic patients and ovoalbumin‐induced asthmatic mouse model (OVA). The asthmatic patients also have infiltration of inflammatory cells in the pulmonary epithelium, reduced CBF and mucociliary transport effectiveness. Mucociliary transport is the first defense mechanism in the airways, where particles are trapped in the mucus and removed by the ciliary beating to the pharynx. We proposed the following objective: Determine the relation between levels of ATP of an asthmatic OVA mouse model, the opening state of the channels that control the release of this nucleotide and the effectiveness of mucociliary transport in the airways. The protocols used in this study were approved, by the ethics committee of the university that follow international guidelines for animal care. We measured extracellular ([ATP]e) with a luminometric assay and evaluated the infiltration of inflammatory cells in the lung parenchyma by histochemistry (H&amp;E). The ethidium bromide (5μM) capture was recorded with a camera mounted on an Olympus upright microscope. The microspheres (6μm) velocity on the surface of the trachea epithelium was registered with a videomicroscopy system and analyzed with the ImageJ program. We observed greater infiltration of inflammatory cells in the pulmonary parenchyma of the asthmatic mouse, compared with the control mouse. Also, we established that high levels of ATP were present in asthmatic mice trachea lavage compared to control animals. The microspheres velocity was diminished in OVA mouse model compare to control mice and addition of 1mM of ATP in control or asthmatic mice transiently stopped the microspheres movement. Furthermore, we observed a significant increase in the percentage of ethidium bromide capture by the epithelium of asthmatic mice compare to controls. These results demonstrated that in an inflammatory condition, channels involved in the ATP release increased their opening state in the airways epithelium. This effect could be associated to high levels of ATP measured in asthma, condition that resulted in a deleterious effect on mucociliary transport effectiveness.Support or Funding InformationCONICYT 21160416, LL.A. Millennium Institute on Immunology and Immunotherapy (P09/016‐F) MV.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Endoscopic detection of fast mucociliary pathways in endoscopic sinus surgery: a marker for local mucociliary function

IntroductionThe mucociliary transport velocity is heterogenous showing areas of slow and fast pathways. The aim of this study was to assess fast mucociliary pathways (FMP) in the maxillary sinus in chronic rhinosinusitis.Patients and MethodsEndoscopic recording of mucociliary clearance (MCC) and FMP was performed on the posterior wall of the maxillary sinus in 22 chronic rhinosinusitis patients subjected to endoscopic sinus surgery and 12 normal volunteers undergoing septal or turbinate surgery. MCC was assessed intraoperatively using methylene blue over 20 min. MCC was designated as complete, incomplete, or absent. For all patients and controls, the preoperative and postoperative sinonasal outcome scores (SNOT 20) were determined, and the transnasal and transmaxillary saccharin test, and preoperative computed tomography radiological staging were performed.ResultsFMP were more frequent in the controls (75%) than the patients (40%), with no statistical significance. Delay, direction, site, and duration of FMP were not statistically different in both groups. Six patients with no FMP (absent MMC in five and partial in one) had extremely prolonged transmaxillary saccharin times, with no postoperative improvement. Otherwise, SNOT 20, transnasal, and transmaxillary saccharin times improved significantly in the patients. Controls showed a significant improvement in the SNOT 20 and transmaxillary sacchrin time. FMP correlated significantly with MCC (r=0.636; P<0.01), transnasal (r=−0.7, P<0.05), and transmaxillary (r=−0.553; P<0.05) saccharin times. In a discriminant model, the only predictive variables of FMP detection were MCC (positive) and transnasal saccharin time (negative) with total correction classification (91.2%). This study describes the different characteristics of FMP. Our results suggest that FMP can be used as a marker of local MCC.

The Effects of Electronic Cigarette (ECIG)-Generated Aerosol and Conventional Cigarette Smoke on the Mucociliary Transport Velocity (MTV) Using the Bullfrog (R. catesbiana) Palate Paradigm.

Background: While ECIGs are under scrutiny concerning safety, particularly in reference to the physiological impact that aerosolized ECIG liquid (E-liquid) may have on respiratory tissues, others believe that ECIGs are a “Harm Reduction” alternative to conventional cigarettes. Previous studies investigating ciliated respiratory epithelium indicate that smoking shortens cilia length, reduces cilia beat frequency and disrupts respiratory epithelium, which most likely contributes to the inhibition of mucocilliary clearance. Monitoring mucous clearance of respiratory tissues exposed to ECIG-generated aerosol or conventional cigarette smoke, as indexed by mucous transport velocity (MTV), is one way to gauge the impact aerosol and smoke have on the respiratory tract. Therefore, we designed an experiment to test the effect of ECIG-generated aerosol and smoke on MTV using the frog palate paradigm.Methods: Peristaltic pumps transport ECIG-generated aerosol and conventional cigarette smoke into custom-made chambers containing excised bullfrog palates. MTVs were determined before exposure, immediately after exposure and approximately 1 day following exposure. MTVs were also determined (at the same time points) for palates exposed to air (control). Surface and cross sectional SEM images of palates from all three groups were obtained to support MTV data.Results: The results indicate that ECIG-generated aerosol has a modest inhibitory effect (p < 0.05) on MTV 1 day post-exposure (0.09 ± 0.01) compared to control MTV (0.16 ± 0.03 mm/s). In contrast, smoke completely inhibits MTV from 0.14 ± 0.03 mm/s immediately before exposure to 0.00 mm/sec immediately after exposure and the MTV is unable to recover 1 day later. SEM images of control palates and palates exposed to ECIG-generated aerosol both show cilia throughout their epithelial surface, while some areas of palates exposed to smoke are completely devoid of cilia. Additionally, the epithelial thickness of aerosol-exposed palates appears thicker than control palates while smoke-exposed palates appear to be thinner due to epithelial disruption.Conclusions: These results indicate that ECIG-generated aerosol has only a modest effect on mucocilary clearance of bullfrog palates and aerosol sedimentation accounts for epithelial thickening. In accordance with the primary literature, conventional cigarette smoke dramatically inhibits mucociliary clearance and is, in part, due to decreased number of cilia and disruption of the smoke-exposed epithelium.

In vitro studies of a distillate of rectified essential oils on sinonasal components of mucociliary clearance.

Herbal remedies predate written history and continue to be used frequently for many common ailments. The essential oil mixture standardized is a phytopharmaceutical with a distillate of a mixture of rectified essential oils of eucalyptus, sweet orange, myrtle, and lemon as active ingredients used to treat respiratory diseases such as bronchitis and rhinosinusitis. We evaluated the pharmacologic effects of a distillate of rectified essential oils standardized on primary human upper respiratory epithelial cultures specifically addressing electrolyte transport, cilia beat frequency (CBF), airway surface liquid (ASL) hydration, and mucus transport velocity. Well-differentiated primary human sinonasal epithelial cultures grown at an air-liquid interface were treated on the apical or basolateral surface with varying concentrations of a distillate of rectified essential oils standardized. Changes in CBF were determined using the Sissons-Ammons Video Analysis system while changes in chloride flux were determined using the fluorescent dye 6-methoxy-N-(3-sulfopropyl)quinolinium. ASL hydration was quantified using Texas red dextran and mucociliary transport velocity was measured using fluorescent microspheres and time lapse photography. When applied to the basolateral surface, a distillate of rectified essential oils standardized activated chloride efflux and ciliary beat in a dose-dependent fashion, increasing ASL height and accelerating mucociliary transport velocity. The ancillary apical application of a distillate of rectified essential oils standardized had minimal effects on the CBF. Basolateral application of a distillate of rectified essential oils standardized stimulates both chloride efflux and cilia beat frequency resulting in a synergistic effect dramatically augmenting mucociliary transport velocity. These in vitro data support the clinical efficacy of this phytopharmaceutical in respiratory inflammatory disorders.

Assessment of technetium-99m labeled macroaggregated albumin rhinoscintigraphy for the measurement of nasal mucociliary transport rate: intratest, interobserver, and intraobserver reproducibility.

Objectives. The measurement of mucociliary transport velocity by rhinoscintigraphy with Tc-99m-macroaggregated albumin (99mTc-MAA) is reliable measure of mucociliary clearance. The aim of this study is to assess the intratest, interobserver, and intraobserver reproducibility of nasal mucociliary transport rate (NMTR) measurement. Materials and Methods. Twenty-two subjects were evaluated to determine intratest reproducibility and a group of 35 subjects was examined to determine inter- and intraobserver reproducibility. Rhinoscintigraphy with 99mTc-MAA was used to measure NMTR in all study subjects. Paired NMTR measurements were compared using a range of statistical methodologies. Intraclass correlation coefficients (ICC) and repeatability coefficients and Bland-Altman plots were applied to assess the degree of intratest, interobserver, and intraobserver variation. Results. Statistical analysis of test and retest experiments demonstrated the statistical equivalence of intratest NMTR measurements, interobserver NMTR measurements, and intraobserver NMTR measurements. The intratest ICC, interobserver ICC, and intraobserver ICC were 0.96, 0.83, and 0.91, respectively, indicating that intratest and intraobserver reproducibility are excellent and interobserver reproducibility is good. Conclusions. Rhinoscintigraphy using 99mTc-MAA results in highly reproducible measurement of NMTR. The use of radionuclide imaging in measuring NMTR results in excellent intratest and intraobserver reproducibility and good interobserver reliability.

Immunosuppression Effects on Airway Mucociliary Clearance: Comparison Between Two Triple Therapies

Tacrolimus and mycophenolate have now become the most widely used combination for maintenance immunosuppressive regimens after lung transplantation in comparison with cyclosporine and azathioprine. However, limited information is available with respect to their effects on cells, other than those from the immunologic compartment. We hypothesized that different triple therapies could have different effects on airway mucociliary clearance, playing an important role in respiratory infections observed after lung transplantation. Ninety rats were assigned to three groups (n = 30 each): control = vehicle, therapy 1 = tacrolimus + mycophenolate + prednisone, and therapy 2 = cyclosporine + azathioprine + prednisone. After 7, 15, or 30 days of treatment by gavage, the animals were killed and the following parameters were studied: mucus transportability, ciliary beating frequency, mucociliary transport velocity, and neutral and acid mucus production. There was a significant decrease in ciliary beating frequency, mucociliary transport velocity, and neutral mucus production in all immunosuppressed animals; indeed, both therapies, mainly therapy 1, caused an increase in acid mucus production for as long as 15 days of treatment. Both triple therapies impaired airway mucociliary clearance of rats, but therapy 1 had a more deleterious effect. These data suggest that these undesirable effects can contribute to the high incidence of respiratory infections observed in patients undergoing lung transplantation.

Tacrolimus Causes Airway Mucociliary Clearance Impairment

Purpose According to ISHLT Registry, the vast majority of lung transplant patients receive a tacrolimus-based maintenance immunosuppressant therapy. However, its side effects on respiratory tract are not very well studied. We hypothesized that tacrolimus could impair airway mucociliary clearance. Methods and Materials Twenty Wistar rats were assigned into two groups: Control (n=10): saline solution; and TAC (n=10): tacrolimus (1 mg/kg/day). After 15 days of therapy by gavage, animals were killed and in situ mucociliary transport velocity (MCTV) and ciliary beating frequency (CBF) were measured by microscopic direct view of airway ciliated epithelium. Mucus production by goblet cells was quantified in periodic acid Schiff and alcian blue stained slides of the tracheobronchial tissue. This study was support by Sao Paulo Research Foundation - Fapesp. Results There was a significant decrease in MCTV (1.77±0.50 and 0.73±0.34 mm/min, Control and TAC, respectively, p Conclusions Our study showed that TAC plays an important role on the impairment of the mucociliary clearance either by decreasing CBF and MCTV or by increasing mucus production. This impairment can be related with the high level of respiratory infection observed during the first 30 days after lung transplantation and must receive good attention from clinicians.

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.

Effects of Prednisone on Mucociliary Clearance in a Murine Model

All transplant patients are at increased risk of developing pulmonary infections, a significant cause of morbidity and mortality. Immunosuppressants increase the incidence of lung infection by acting not only directly on the inflammatory cells, but also on the native immune system. Experimental studies have shown corticosteroid therapy, which is used in most immunosuppressive protocols after transplantation, to suppress mucus production by inhibiting calceiform. The objective of this study was to evaluate the effects of prednisone on mucociliary clearance. A total of 120 male Wistar rats were distributed into 4 groups. Animals in P1, P2, and P3 groups received daily doses of prednisone (0.625, 1.25, and 2.5 mg/kg/d), and hosts in the Sal group underwent gavage with saline solution (2.5 mL/d). After 7, 15, and 30 days, treatment, animals were killed. We assessed ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), and mucus transportability (MT). There was no significant difference for CBF regarding dose (P = .089) or treatment duration (P = .175). MCTV values of 0.60 ± 0.14 in group P1, 0.59 ± 0.13 in group P2, 0.51 ± 0.19 in group P3, and 0.61 ± 0.08 Group Sal, showed P3 to significantly differ from P1 (P = .048) and Sal (P = .007) groups. Regardless of the prednisone dose, all groups displayed impaired MT compared with the Sal group: P1 (P = .02); P2 (P = .02) P3 (P = .03). There was no interaction between the therapy and the treatment time for CBF (P = .10), MCTV (P = .71), and MT (P = .64). Prednisone reduced the transportability of mucus even when administered at low doses; however, this change was not sufficient to alter the mucociliary clearance. Only high doses of prednisone impaired mucociliary clearance.

The effects on mucociliary clearance of prednisone associated with bronchial section

OBJECTIVE:Infections have been and remain the major cause of morbidity and mortality after lung transplantation. Because mucociliary clearance plays an important role in human defense mechanisms, the influence of drugs on the mucociliary epithelium of patients undergoing lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy on mucociliary clearance.METHODS:A total of 120 rats were assigned to 4 groups according to surgical procedure or drug therapy: prednisone therapy (1.25 mg/kg/day); bronchial section and anastomosis + prednisone therapy (1.25 mg/kg/day); bronchial section + saline solution (2 ml/day); and saline solution (2 ml/day). After 7, 15, or 30 days, the animals were sacrificed, and the lungs were removed from the thoracic cavity. The in situ mucociliary transport velocity, ciliary beat frequency and in vitro mucus transportability were evaluated.RESULTS:Animals undergoing bronchial section surgery and anastomosis had a significant decrease in the ciliary beat frequency and mucociliary transport velocity 7 and 15 days after surgery (p<0.001). These parameters were normalized 30 days after the surgical procedure. Prednisone improved mucous transportability in the animals undergoing bronchial section and anastomosis at 15 and 30 days (p<0.05).CONCLUSION:Bronchial section and anastomosis decrease mucociliary clearance in the early postoperative period. Prednisone therapy improves mucus transportability in animals undergoing bronchial section and anastomosis.

Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model

OBJECTIVE:To study the effects of mycophenolate sodium on mucociliary clearance.INTRODUCTION:Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied.METHODS:Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured.RESULTS:The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001).DISCUSSION:These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.

The influence of Flutter ®VRP1 components on mucus transport of patients with bronchiectasis

The Flutter(®)VRP1 combines high frequency oscillation and positive expiratory pressure (PEP). To separately evaluate the effect of the Flutter(®)VRP1 components (high frequency oscillation and PEP) on mucus transportability in patients with bronchiectasis. Eighteen patients with bronchiectasis received sessions with the Flutter(®)VRP1 or PEP for 30 min daily in a randomized, crossover study. The treatment duration was four weeks with one of the therapies, one week of a "wash-out" period and followed by four more weeks with the other treatment. Weekly secretion samples were collected and evaluated for mucociliary relative transport velocity (RTV), displacement in a simulated cough machine (SCM) and contact angle measurement (CAM). For the proposed comparisons, a linear regression model was used with mixed effects with a significance level of 5%. The Flutter(®)VRP1 treatment resulted in greater displacement in SCM and lower CAM when comparing results from the first (9.6 ± 3.4 cm and 29.4 ± 5.7°, respectively) and fourth weeks of treatment (12.44 ± 10.5 cm and 23.28 ± 6.2°, respectively; p < 0.05). There was no significant difference in the RTV between the treatment weeks for either the Flutter(®)VRP1 or PEP. The use of the Flutter(®)VRP1 for four weeks is capable of altering the respiratory secretion transport properties, and this alteration is related to the high frequency oscillation component.

The effects of calcitonin nasal preparations and their excipients on mucociliary clearance in an ex-vivo frog palate test.

The topical tolerability of the commercial preparation of 1-7 Asu-eel and salmon calcitonin with 2% ammonium glycyrrhyzinate and 0.01% benzalkonium chloride, respectively, and of their excipients mixture in solution with increasing concentrations of ammonium glycyrrhyzinate and benzalkonium chloride, respectively, were assessed by investigating their effects on the mucociliary transport velocity in the ex-vivo frog palate preparation. This preparation provides an integrated biological model readily usable in the laboratory which closely resembles human nasal mucociliary clearance mechanism and can be used for rapid testing and toxicity of agents proposed for topical administration in the upper and lower airways. Frog-Ringer control, 1-7 Asu-eel and salmon calcitonin commercial spray preparations and the excipients plus 2% ammonium glycyrrhyzinate and plus 0.01% benzalkonium chloride did not modify significantly the mucociliary transport velocity, confirming their very good tolerability on ciliated epithelium. Higher concentrations of ammonium glycyrrhyzinate (10 and 20%) caused significant slowing, on average -32 and -55%, respectively. Higher concentrations of benzalkonium chloride (0.05 and 0.1%) also caused significant slowing, on average, -43.5 and -87%, respectively.