Mucus Transport Research Articles

Effects of furosemide, exercise, and atropine on tracheal mucus transport rate in horses

SUMMARY Effects of furosemide, exercise, and atropine on tracheal mucus transport rate (tmtr) in horses were investigated. Atropine (0.02 mg/kg of body weight) administered iv or by aerosolization significantly (P < 0.05) decreased tmtr at 60, but not at 30 minutes after its administration in standing horses. Furosemide (1.0 mg/kg, iv) did not have any significant effect on tmtr when measured at 2 or 4 hours after its administration in standing horses. Exercise alone or furosemide (1.0 mg/kg, iv) administration followed 4 hours later by exercise did not alter tmtr, compared with values for standing control or exercised horses administered saline solution. Atropine (0.02 mg/kg, iv) administered after exercise significantly (P < 0.05) decreased tmtr, compared with values for no exercise standing controls, for exercise after administration of saline solution, and for furosemide and exercise.

Ultrastructure and mucociliary transport of bronchial respiratory epithelium in intubated patients.

The objective of this study was to investigate whether reduced bronchial mucus transport velocity (BTV) is associated with a loss of cilia or ultrastructural abnormalities of cilia in intubated patients. The patients were studied prospectively in a convenience sample trial. The study took place in a university hospital. 29 orally intubated patients in a surgical ICU. BTV was measured with radiolabeled microspheres in the right and left primary bronchus. Following these measurements, biopsy samples were taken from the bronchi for scanning (SEM) and transmission (TEM) electron-microscopic investigations. SEM: Patients with normal or slight impaired BTV (group 1, n = 14: BTV: 8.5 mm/min (3.8-11.5); median with range) showed more cilia on the luminal surface than patients with markedly depressed BTV (p < 0.05) (group 2, n = 15: BTV: 0 (0-2.1)). The difference was statistically significant. The BTV values correlated moderately with the number of cilia on the luminal surface (r = 0.46; p = 0.02). TEM: In group 1, 6.5% (3.9-14.9) of cilia were abnormal (median with range) vs 9.3% (4.9-13.7) in group 2; these differences were not statistically significant. Neither was there any significant correlation between BTV and the frequency of abnormal cilia. Impaired mucociliary transport in intubated patients is associated with a loss of cilia rather than ultrastructural abnormalities of cilia, which are less relevant.

The Ciliary Transportability of Sputum is Slow on the Mucus-depleted Bovine Trachea

Mucus retention in the lungs is a feature of several chest diseases. It is unclear to what extent suboptimal mucus transportability is responsible for the poor clearance of lung secretions. We describe a new model, the mucus-depleted bovine trachea, for measurement of the ciliary transportability of respiratory mucus. Mucus depletion was demonstrated microscopically and functionally, and it was accomplished by simple physical means without impairing ciliary action. Control mucus from the tracheas of humans and animals was transported rapidly on this system. However, sputum from 54 patients with bronchiectasis was transported slowly, at a mean of 15% of the rate of control mucus. There was no correlation between sputum transportability and either purulence or the presence of Pseudomonas aeruginosa. This work suggests that there is a serious defect in the ciliary transportability of sputum that is unrelated to the presence of infection. The model should allow in vitro assessment of agents designed to aid mucociliary clearance.

The ciliary transportability of sputum is slow on the mucus-depleted bovine trachea.

Mucus retention in the lungs is a feature of several chest diseases. It is unclear to what extent suboptimal mucus transportability is responsible for the poor clearance of lung secretions. We described a new model, the mucus-depleted bovine trachea, for measurement of the ciliary transportability of respiratory mucus. Mucus depletion was demonstrated microscopically and functionally, and it was accomplished by simple physical means without impairing ciliary action. Control mucus from the tracheas of humans and animals was transported rapidly on this system. However, sputum from 54 patients with bronchiectasis was transported slowly, at a mean of 15% of the rate of control mucus. There was no correlation between sputum transportability and either purulence or the presence of Pseudomonas aeruginosa. This work suggests that there is a serious defect in the ciliary transportability of sputum that is unrelated to the presence of infection. The model should allow in vitro assessment of agents designed to aid mucociliary clearance.

Effect of methacholine on mucociliary transport in bovine trachea in vitro

Abstract A method is described to evaluate pharmacologic influence on bovine tracheal mucus transport in vitro. In this model, cholinergic agonist methacholine stimulated transport velocity. Methacholine at concentration of 10−6M increased velocity by 13.6%, whereas 10−5M increased velocity by 26%. Stimulation was inhibited by atropine.

Surface properties of respiratory secretions: Relationship with mucus transport

Surface properties of respiratory secretions: Relationship with mucus transport

Dose-dependent in vitro effect of recombinant human DNase on rheological and transport properties of cystic fibrosis respiratory mucus

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis (CF) respiratory mucus, to improve pulmonary function and to reduce the risk of respiratory tract infectious exacerbations, but its effect on mucus transportability has not so far been investigated. The dose-dependent effect of rhDNase was analysed in vitro on mucus transport rate (tr) by ciliary activity and by simulated cough (cough transport (ct)), as well as on mucus viscosity and surface properties. Purulent CF sputa (n = 15) were incubated for 30 min at 37 degrees C with either rhDNase at three different concentrations (final concentrations 0.2, 2 or 20 micrograms.ml-1 of mucus) or placebo. No significant dose-dependent effect of rhDNase on the mucociliary transport rate was observed when the samples wer statistically analysed together. However, in the larger group of mucus samples (n = 11) with a low initial mucociliary transport rate, the latter was improved at each rhDNase concentration (tr0.2 = 0.69, tr2 = 0.88 and tr20 = 0.87) as compared to placebo (trp = 0.58). In the smaller group of mucus samples (n = 4) with high initial transport rate, a decrease in mucociliary transport rate was observed, particularly at the highest concentration rhDNase assayed, i.e. 20 micrograms.ml-1 of mucus (tr20 = 0.58) as compared to placebo (trp = 0.86). The mucus cough transport was increased by rhDNase (ct0.2 = 25 mm, ct2 = 27.5 mm and ct20 = 31 mm) as compared to placebo (ctp = 23.5 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Guaifenesin on Nasal Mucociliary Clearance and Ciliary Beat Frequency in Healthy Volunteers

Mucociliary clearance is an important host defense function of the upper respiratory tract that requires the coordinated beating of cilia and results in the transport of mucus to the oropharynx. Guaifenesin is a commonly prescribed drug that is reported to improve the clearance of respiratory secretions. We hypothesized that guaifenesin increases nasal mucociliary clearance related to increases in ciliary beat frequency (CBF) and that a direct relationship exists between nasal CBF and nasal mucociliary clearance. Double-blind placebo-controlled crossover study. Ten healthy volunteers with a previous history of sinus disease. Subjects received guaifenesin or placebo on days 1 to 7 or days 14 to 21. In vivo saccharine transit time (STT) was measured by noting the time in minutes required for the subject to taste a saccharin particle placed on the inferior turbinate of the naris. The CBF was determined by video microscopy on ten separate groups of beating ciliated nasal mucosal cells obtained by brushing immediately after each STT determination. We found that there was no significant change between the guaifenesin-or placebo-treated groups from baseline values of STT (p = 0.94) or CBF (p = 0.46). Regression analysis demonstrated no relationship between STT and CBF for repeated measures within subjects (mean r2 = 0.18; mean p = 0.66) and between STT and CBF when all paired measurements were combined across subjects (r2 = 0.47; p = 0.46). We conclude that guaifenesin exerts no measurable effect on in vivo nasal mucociliary clearance or ex vivo nasal ciliary motility in healthy volunteers with previous sinus disease. In addition, there appears to be no relationship between nasal STT measured in vivo and CBF measured ex vivo. The lack of correlation is most likely due to variations in CBF related to sampling artifacts introduced by the nasal brushing process.

Species differences in the physical and transport properties of airway secretions.

The clearance of airway secretions is vital in protecting the mammalian lung from pollution and infection. Diverse animal models have been used to study lung diseases associated with impaired secretion clearance. The extrapolation of data from animal models to humans is based on the assumption that there are structural and functional similarities in the airway epithelium and secretions. This manuscript reviews regulation of mucus secretion as well as the physical and transport properties of respiratory mucus. As tracheal size increases, the rigidity of airway secretions decreases, and rigidity is inversely correlated with mucociliary transportability. These differences are placed in the context of previously reported species and regional differences in transepithelial potential difference and the tracheobronchial epithelial cell population. Tracheal mucus transport velocity varies with the species studied and has been shown to positively correlate with tracheal surface area. A progressive increase in the rate of mucus transport from the small to the large airways has also been reported. The reduction in mucus rigidity from small to large airways could be one of the mechanisms responsible for velocity gradients, which facilitate mucociliary transport. Because airway dimensions, rather than anatomic level of the airway, may better predict epithelial secretory response, studies to assess the physiologic responses in human airways require the use of an animal model with a similar-sized airway.

Rheological determinants of mucociliary transport in the nose of the rat

The present work was designed to investigate whether the rheological determinants for nasal mucociliary transport are the same in the intact preparation (in situ), as they are when the mucus is added exogenously to the isolated, mucus-depleted frog palate (in vitro). We evaluated the association between estimators of mucociliary transport in both conditions and rheological parameters using multiple regression techniques. Two kinds of rats were used: (a) specific pathogen free (SPF) rats, representing the normal condition of respiratory epithelium; (b) non-SPF rats (NSPF), which have a chronic inflammatory process in the airways. In situ mucociliary clearance (MCC) was determined by measuring the displacement of charcoal particles placed in the nasal septum. In vitro mucociliary transport (MCT) of rat nasal mucus was measured using the isolated frog palate preparation. Mucus rheologic properties were determined by magnetic microrheometry, in oscillatory deformations performed at 1, 10 and 100 radians/sec. No differences were detected between SPF and NSPF rats in terms of rheological parameters. A decreased MCC was found in NSPF in comparison with the SPF group, but no differences were observed between groups in terms of MCT, as could be predicted by rheological data. When all animals were pooled, in situ transport was significantly associated with the viscosity/elasticity ratio, whereas in vitro transport was dependent on the total mechanical impedance of the mucus sample. In conclusion, in situ mucus transport is influenced by other rheological parameters than those associated with in vitro transportability.

Physical and Functional Properties of Airway Secretions in Cystic Fibrosis – Therapeutic Approaches

The airway secretions which line the respiratory tract form a biphasic layer composed of an aqueous 'sol' layer and a more superficial 'gel' layer. In the sol layer, also described as the 'periciliary' layer or 'airway surface fluid', the cilia beat and relax. The lubricant sol layer enables the gel mucus present at the tips of the cilia to be transported by the ciliary beating of the ciliated cells. Due to difficulties with sampling, little is known about the physical and biochemical properties of the sol layer. The gel layer is composed of high molecular weight glycoproteins (mucins) linked with proteins and lipids. They form a gel network with a high water content (95%) and rheologic and physical properties (viscoelasticity, adhesivity) adapted in normal conditions to protect the airway mucosa, particularly through mucociliary transport. The adhesive properties of mucus, which are influenced by its lipid composition and degree of hydration, are very important in controlling the efficacy of mucus transport through ciliary activity and coughing. An intermediate viscosity and elasticity is required for optimal mucociliary transport. In obstructive airway diseases, either of genetic origin, such as cystic fibrosis (CF), or acquired (acute or chronic bronchitis), and particularly during inflammatory and infectious episodes, mucus dehydration is associated with an increase in secreted or transudated molecules and with marked augmentation of DNA content. These abnormalities contribute to the increased viscosity and adhesivity of the airway secretions and are responsible for their abnormally low transport rate by ciliary activity and for inefficient cough clearance. In view of these alterations in the physical and functional properties of CF airway secretions, pharmacologic approaches should aim to rehydrate the mucus and to restore normal mucociliary or cough transport by stimulating chloride ion secretion (i.e. using UTP or ATP associated with amiloride in order to block sodium ion and water reabsorption). During acute episodes of infection, recombinant human DNase (rhDNase) may rapidly prevent mucus stasis by improving its rheologic properties. Lubrication of the mucus at the sol phase interface by 'surfactant' therapy may also represent a very promising therapeutic perspective to reduce the hyperviscosity and hyperadhesivity of airway secretions.

Mucus secretion and transport

Mucus secretion and transport

Regional Mucus Transport Following Unproductive Cough and Forced Expiration Technique in Patients With Airways Obstruction

It has previously been shown that unproductive coughing in both healthy subjects and patients with airways obstruction is not effective in clearing lung secretions. This study investigates the regional mucus transport in a group of subjects with airways obstruction who failed to expectorate following instructed cough and forced expiration technique. Fourteen patients (mean +/- SEM age: 68 +/- 2 years) with airways obstruction (mean +/- SEM percent predicted. FEV1: 54 +/- 5; daily wet weight sputum: 9.1 +/- 2.0 g) took part in the study which was a randomized, three-way crossover within-patient design. Each patient underwent three treatment maneuvers: control, cough (30 coughs over a 10-min period), and forced expiration (30 forced expirations over a 10-min period). An objective radioaerosol technique was used to monitor regional mucus movement within the lungs of the patients. The lungs were divided arbitrarily into four regions of interest: tracheal, inner, intermediate, and outer. Peak expiratory flow rate during cough and forced expiration was measured at the mouth. There was no correlation between the radioaerosol clearance from all regions and (1) mean peak flow during cough and forced expiration, and (2) mean 24-h sputum production prior to the study day. There were no differences in regional radioaerosol clearance between cough and forced expiration. However, both cough and forced expiration resulted in significant clearance compared with control for all regions with the exception of the forced expiration in the outer region. To our knowledge, this study is the first to demonstrate that unproductive cough and forced expiration result in movement of secretions proximally from all regions of the lung in patients with airways obstruction.

In vitro transport of carbon in the trachea of veal calves

Carbon transport was studied in vitro in preparations of trachea and bronchus from veal calves. The mean velocity varied from 4.2 mm/min in the main bronchi to 6.3 mm/min in the ventral trachea. In some locations no transport was observed. Stereomicroscopic evaluation of Alcian blue-phloxine stained mucosal surfaces revealed differences in the appearance of the mucus layer between locations with and without mucus transport. It is concluded that quality and integrity of the mucus layer play an important role in mucus transport.

Mucus transport mechanisms in relation to the effect of high frequency chest compression (HFCC) on mucus clearance.

High frequency chest compression (HFCC) appears promising as a form of chest physiotherapy. Studies published by several clinical centers support its efficacy, and further clinical data are expected to become available.

Mucous gel transport in a simulated cough machine: effects of longitudinal grooves representing spacings between arrays of cilia.

Under some conditions, such as inhalation injury, an array of longitudinal channels without cilia may be formed on the epithelial surface, affecting mucus transport in the lung during coughing. Moreover, in certain cases of the diseased state of the lung, immotile cilia remain embedded in the serous fluid and may form channels in the direction of air motion during coughing, providing a resistance-free pathway for serous layer fluid and assist in mucus clearance. To understand this phenomenon, we have conducted experiments with mucous gel simulants (MGS) in a simulated cough machine (SCM) using soap solution as a serous layer simulant (SLS). The channel structure of the airway surface was modeled by introducing bottom plates with longitudinal grooves about 10 cm long having different depths, widths and number of grooves. It was shown that mucous gel transport increases as the cross-sectional area occupied by channel grooves increases. The effects of sinusoidal constriction and mucous gel filance were also investigated in this model system. It was found that mucous gel transport increases in the constricted case (minimum gap, 3 mm, and maximum gap, 9 mm) in comparison with that in the parallel case (constriction gap of 9 mm). The effect of increasing the mucous gel filance was to decrease the transport,, as reported in previous studies.

Mucociliary Transport in ICU Patients

The objectives of this study were to determine the bronchial mucus transport velocities in ventilated ICU patients and to study the possible role of impaired mucus transport in the development of retention of secretion and pneumonia. The patients were studied prospectively in a convenience sample trial. The study took place at a university hospital. Thirty-two ventilated patients in a surgical ICU were included in the study. The study was approved by the Ethics Committee of the University of Ulm. Bronchial mucus transport velocity (BTV) was measured with a small volume of technetium 99m-labeled albumin microspheres within the first 3 days of mechanical ventilation. The radiolabeled bolus was deposited at the distal end of the right and left main bronchus via flexible bronchoscopy. The movement of the microspheres toward the trachea was visualized and recorded using a scintillation camera. After determination of BTV, the patients were examined daily for 4 days to record pulmonary complications (defined as retention of secretion and nosocomial pneumonia). The median BTV in the right primary bronchus was 0.8 mm/min and in the left it was 1.4 mm/min. In nine patients both radioactive drops remained at the application site. In 14 patients, a total of 19 pulmonary complications occurred (10 times retention of secretion, 9 times pneumonia). Patients with pulmonary complications had statistically significant lower BTV compared with patients without pulmonary complications; in the left bronchus 0 (0 to 6.5) mm/min (median with range) vs 3.5 (0 to 10.5) mm/min (p < 0.01) and in the right bronchus 0 (0 to 3.0) mm/min vs 4.7 (0 to 11.7) mm/min (p < 0.01). Ventilated patients in the ICU frequently have impaired mucus transport, which is associated with the development of retention of secretion and pneumonia.

Mucolytic treatment with N-acetylcysteine L-lysinate metered dose inhaler in dogs: airway epithelial function changes.

N-acetylcysteine L-lysinate Nacystelyn (L-NAC) is a newly synthesized mucolytic agent, of which the action in vivo has not been well defined. In six healthy mongrel dogs, the rheological properties of mucus, its mucociliary and cough clearability, and the transepithelial potential difference (PD) of the tracheobronchial epithelium were evaluated after placebo and L-NAC metered dose inhaler (MDI) aerosols. The principal index of mucus rigidity, log G*, decreased at all airway sites with L-NAC administration, i.e. the mucus became less rigid and more deformable (the overall change in G* was 0.29 log units, i.e. ca. twofold decrease). The viscoelasticity-derived mucus transportability parameters, mucociliary (MCI) and cough (CCI) clearability indices, increased with L-NAC MDI, particularly CCI, which predicts the effect of mucus rheology on cough clearability. PD increased significantly with L-NAC administration at all measurement sites, which appears to be a novel effect for a direct acting mucolytic agent. Tracheal mucus linear velocity (TMV) increased after L-NAC compared with placebo, as did the normalized frog palate transport rate (NFPTR). The increase in NFPTR was greater than that predicted from the mucus rheological properties alone, suggesting that L-NAC still resident in the collected mucus stimulated the frog palate cilia. The index of mucus flux, the collection rate in mg.min-1, was higher with L-NAC compared with placebo. From our results, we conclude that L-NAC shows potential benefit in terms of improving mucus rheological properties and clearability. It may act, in part, by stimulating the fresh secretion of mucus of lower viscoelasticity. The stimulation of mucociliary clearance could be related to ion flux changes, as indicated by the increase in PD.

Distearoyl phosphatidylglycerol liposomes improve surface and transport properties of CF mucus

We have previously shown that a decreased level of phosphatidylglycerol in cystic fibrosis (CF) respiratory mucus is partly responsible for its marked adhesiveness and stickiness, which impair mucus transport, and that distearoyl phosphatidylglycerol (DSPG) was the most efficient form of phosphatidylglycerol in the enhancement of respiratory mucus clearance. The aim of our study was to analyse the effect of distearoyl phosphatidylglycerol liposomes on the transport by cough and cilia of cystic fibrosis respiratory mucus. The surface and transport properties of mucus were measured: 1) on native cystic fibrosis mucus; 2) on cystic fibrosis mucus complemented with DSPG liposomes at a non-cytotoxic concentration; and 3) on cystic fibrosis mucus complemented with water. The work of adhesion of cystic fibrosis mucus was significantly decreased by DSPG liposomes, but not by water. For mucociliary transport, the cystic fibrosis mucus was transported at a higher rate with DSPG liposomes and water compared to native cystic fibrosis mucus. The cough clearance of cystic fibrosis respiratory mucus was significantly improved in the presence of DSPG and water, but the effect was more pronounced with DSPG liposomes than with water. We conclude that the use of DSPG liposomes as a lubricating agent proves to be an interesting therapeutic approach for improving the cough and mucociliary transport in cystic fibrosis patients.

Bronchial mucus transport in chronic smokers and nonsmokers during general anesthesia

Study Objective: To compare bronchial mucus transport velocity in smokers and nonsmokers. Design: Prospective consecutive-sample trial. Setting: University hospital. Patients: 12 smokers and 22 nonsmokers undergoing major abdominal or thoracic surgery with postoperative mechanical ventilation. Interventions: After the end of the operation, bronchial mucus transport velocity was measured with a small volume (0.05 to 0.08 ml) of technetium 99-m labeled albumin microspheres with an activity of 1.5 MBq. The radiolabeled bolus was deposited on the dorsal mucosal surface at the distal end of the right and left main bronchus via flexible bronchoscopy. The movement of the microspheres toward the trachea was visualized and recorded using a scintillation camera. Quantitative evaluation was based on the pathtime diagram. After determination of bronchial mucus transport velocity, patients were examined daily over 4 days to record pulmonary complications (retention of secretion and nosocomial pneumonia). Measurements and Main Results: Smokers were comparable to nonsmokers with respect to age, preoperative lung function tests, body temperature, duration of mechanical ventilation, dose of anesthetics, and intraoperative blood loss. Smokers had a significantly slower bronchial mucus transport velocity compared with nonsmokers: in the left bronchus, 1.3 mm/min (0 to 9.6 mm/min) (median with range) versus 9.7 mm/min (3.7 to 15.3 mm/min) ( p < 0.001); in the right bronchus, 2.5 mm/min (0 to 16.0 mm/min) versus 8.3 mm/min (5.5 to 15.3 mm/min) ( p < 0.01). Pulmonary complications occurred in 4 smokers and 1 nonsmoker. Conclusions: When measured during general anesthesia, smokers have a slower bronchial mucus transport than nonsmokers. This may be related to postoperative pulmonary complications in smokers.