Mucociliary Clearance Velocity Research Articles

Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model

Mucus clearance, a primary innate defense mechanism of airways, is defective in patients with cystic fibrosis (CF) and CF animals. In previous work, the combination of a low dose of the cholinergic agonist, carbachol with forskolin or a β adrenergic agonist, isoproterenol synergistically increased mucociliary clearance velocity (MCCV) in ferret tracheas. Importantly, the present study shows that synergistic MCCV can also be produced in CF ferrets, with increases ~ 55% of WT. Synergistic MCCV was also produced in pigs. The combined agonists increased MCCV by increasing surface fluid via multiple mechanisms: increased fluid secretion from submucosal glands, increased anion secretion across surface epithelia and decreased Na+ absorption. To avoid bronchoconstriction, the cAMP agonist was applied 30 min before carbachol. This approach to increasing mucus clearance warrants testing for safety and efficacy in humans as a potential therapeutic for muco-obstructive diseases.

Blocking ATP-releasing channels prevents high extracellular ATP levels and airway hyperreactivity in an asthmatic mouse model

Allergic asthma is a chronic airway inflammatory response to different triggers like inhaled allergens. Excessive ATP in fluids from patients with asthma is considered an inflammatory signal and an important autocrine/paracrine modulator of airway physiology. Here, we investigated the deleterious effect of increased extracellular ATP (eATP) concentration on the mucociliary clearance (MCC) effectiveness and determined the role of ATP releasing channels during airway inflammation in an ovalbumin (OVA)-sensitized mouse model. Our allergic mouse model exhibited high levels of eATP measured in the tracheal fluid with a luciferin-luciferase assay and reduced MCC velocity determined by microspheres tracking in the trachea ex vivo. Addition of ATP had a dual effect on MCC, where lower ATP concentration (µM) increased microspheres velocity, whereas higher concentration (mM) transiently stopped microspheres movement. Also, an augmented ethidium bromide uptake by the allergic tracheal airway epithelium suggests an increase in ATP release channel functionality during inflammatory conditions. The use of carbenoxolone, a nonspecific inhibitor of connexin and pannexin1 channels reduced the eATP concentration in the allergic mouse tracheal fluid and dye uptake by the airway epithelium, providing evidence that these ATP release channels are facilitating the net flux of ATP to the lumen during airway inflammation. However, only the specific inhibition of pannexin1 with 10Panx peptide significantly reduced eATP in bronchoalveolar lavage and decreased airway hyperresponsiveness in OVA-allergic mouse model. These data provide evidence that blocking eATP may be a pharmacological alternative to be explored in rescue therapy during episodes of airflow restriction in patients with asthma.

Mucociliary Clearance of Different Respiratory Conditions: A Clinical Study.

Introduction Mucociliary clearance (MCC) is the first line of defense of the pulmonary system. Mucociliary clearance impairment may lead to increased risk of respiratory infections, lung injury, pulmonary repair problems, chronic dysfunctions and progression of respiratory diseases. Objective To characterize the MCC of active and passive smokers and individuals with chronic obstructive pulmonary disease (COPD) and compare the MCC behaviors between men and women of different age groups. Methods Patients with COPD (current smokers and ex-smokers) and apparently healthy individuals (current smokers, passive smokers and nonsmokers) were evaluated. All of the subjects underwent lung function and MCC evaluation (saccharin transport test [STT]). Smokers (with or without COPD) were questioned about the smoking history. Results A total of 418 individuals aged 16 to 82 years old, of both genders, were evaluated. The STT values of active and passive smokers were statistically higher than those of the control group ( p < 0.01). Men of the control group had lower values of STT than active smokers (9.7 ± 7.1 and 15.4 ± 10.1 minute, respectively, p < 0.01). In addition, higher MCC velocity was observed in women that are current smokers (11.7 ± 6.8 minute) compared with men (15.4 ± 10.1 minute) in this group ( p = 0.01). Among the younger age groups (< 50 years old), only passive smokers presented higher STT in relation to the control group. Conclusion Passive and active smoking are factors that influence negatively the MCC, and passive smokers may present losses of this mechanism at a younger age. Additionally, male smokers present worse MCC than male nonsmokers.

Glandular Proteome Identifies Antiprotease Cystatin C as a Critical Modulator of Airway Hydration and Clearance.

Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel lead to viscous secretions from submucosal glands that cannot be properly hydrated and cleared by beating cilia in cystic fibrosis (CF) airways. The mechanisms by which CFTR, and the predominant epithelial sodium channel (ENaC), control the hydration and clearance of glandular secretions remain unclear. We used a proteomics approach to characterize the proteins contained in CF and non-CF submucosal gland fluid droplets and found that differentially regulated proteases (cathepsin S and H) and their antiprotease (cystatin C) influenced the equilibration of fluid on the airway surface and tracheal mucociliary clearance (MCC). Contrary to prevailing models of airway hydration and clearance, cystatin C, or raising the airway surface liquid (ASL) pH, inhibited cathepsin-dependent ENaC-mediated fluid absorption and raised the height of ASL, and yet decreased MCC velocity. Importantly, coupling of both CFTR and ENaC activities were required for effective MCC and for effective ASL height equilibration after volume challenge. Cystatin C-inhibitable cathepsins controlled initial phases of ENaC-mediated fluid absorption, whereas CFTR activity was required to prevent ASL dehydration. Interestingly, CF airway epithelia absorbed fluid more slowly owing to reduced cysteine protease activity in the ASL but became abnormally dehydrated with time. Our findings demonstrate that, after volume challenge, pH-dependent protease-mediated coupling of CFTR and ENaC activities are required for rapid fluid equilibration at the airway surface and for effective MCC. These findings provide new insights into how glandular fluid secretions may be equilibrated at the airway surface and how this process may be impaired in CF.

Comparison of nasal mucociliary clearance in adenoid hypertrophy with or without otitis media with effusion

ObjectiveTo investigate pre- and postoperative mucociliary clearance in patients with adenoid hypertrophy or combined with otitis media with effusion. MethodsPatients were divided into two groups: Group 1—patients with adenoid hypertrophy (AH), and Group 2—patients with AH and otitis media with effusion (AHOME). In all patients, AH size was recorded, and the Andersen saccharin and methylene blue tests were conducted before and 1 month after surgery to obtain mucociliary clearance time (MCT). Nasal cavity length was measured intraoperatively to establish mucociliary clearance velocity (MCV). Patients with allergic rhinitis, active infection, and history of nasal or ear surgery were excluded. ResultsThis study included 64 patients with a mean age of 8.34±2.98 years (range: 3–18 years). Pre- and postoperative MCT were 14.60±4.83 and 9.48±2.63min in Group 1 and 16.03±4.31 and 12.12±3.78min in Group 2, respectively. Pre- and postoperative MCV were 0.77±0.30 and 1.16±0.42mm/min in Group 1 and 0.67±0.16 and 0.89±0.28mm/min in Group 2, respectively. MCT and MCV were significantly improved postoperatively in both groups (p<0.001). In addition, the postoperative MCT and MCV of Group 1 were significantly better than those of Group 2 (p<0.001). Exposure to cigarette smoking and adenoid size had negative correlations with mucociliary clearance. ConclusionsOtitis media was associated with impaired mucociliary clearance and further studies should be performed to demonstrate the causes of this deficiency.

Correlation of mucociliary clearance and symptomatology before and after adenoidectomy in children

ObjectiveThe goal of this study is to better understand the role of adenoid hypertrophy and its impact on mucociliary clearance as it relates to the symptoms of chronic sinusitis in children. More specifically, the goal is to better understand which symptoms of chronic rhinosinusitis might be most likely to improve in children undergoing an adenoidectomy. MethodsWe conducted this study on 35 healthy children (>3 and <18 years of age), either male or female, who underwent adenotonsillectomy or adenoidectomy (with or without tympanostomy tube insertion). Eighteen patients completed pre- and postoperative surveys, with 10 also completing the Andersen's saccharine test (AST). The nasal mucociliary clearance will be evaluated with the AST, in which a saccharin particle (1.5mm diameter) is carefully placed on the floor of the nasal cavity approximately 1cm behind the anterior end of the inferior turbinate. The time taken by the subjects from placement of particle to the perception of the sweet taste will be taken as mucociliary clearance time (MCT). The length of the nasal cavity is measured intraoperatively as the distance between the upper medial incisor and the inferior edge of the soft palate. From these two values nasal mucociliary clearance velocity (MCV) (cm/min) can be calculated and assessed. This study took place at an academic institution. ResultsSymptomatic improvement was seen in all categories, as measured by the mean score improvement postoperatively. The greatest improvements were seen in nasal obstruction (mean=2.67 points±.59) on the symptom survey, and emotional distress (mean=2.56±.47) on the SN5 survey. Quality of life improved by a mean=2.61±.49. Both MCT and MCV improved postoperatively (mean 3.64min±.84 and mean 1.96cm/min±.90, respectively). ConclusionsWe believe this study has the potential to provide otolaryngologists across the country with a benchmark to communicate the specific symptomatic benefits from adenoidectomy.

Mucociliary clearance. Results in smokers, nonsmokers and patients with with respiratory tract diseases

Using the modified radiographic teflon particle method the tracheal mucociliary clearance velocity (TCV) was found to be 13.5 +/- 4.5 mm/min in 36 normal probands. In 18 "normal" smokers there was a statistically slightly significant diminution when compared with 18 age-matched non-smokers (12.1 +/- 5.7 vs 15.0 +/- 4.2 mm/min; P less than 0.1). Some smokers with values below 7 mm/min could be "potential chronic bronchitis". Acute exposure to cigarette smoke led to a decrease of TCV from 19 to 8 in healthy smokers, and from 20 to 5 mm/min in nonsmokers. Whereas TCV was equally diminished to values between 0 and 5 mm/min in chronic bronchitis (n = 42), bronchial carcinoma (n = 8) and advanced bronchial asthma (n = 8), patients with bronchiectasis (n = 8) showed marked negative tracheal clearance of up to -25 mm/min.

Evaluation of the Effects of Nasal Septal Deviation and its Surgery on Nasal Mucociliary Clearance in Both Nasal Cavities

In this study the effects of nasal septal deviation (NSD) and its surgery on nasal mucociliary clearance velocity (NMCV) in both nasal cavities were evaluated. This study included 20 patients with NSD and 20 healthy subjects as a control group who had no complaint related to the nose. NMCV was measured with rhinoscintigraphy using technetium-99m-macroaggregated albumin (Tc-99m-MAA). Before the septal surgery, the NMCV of concave (10.24 +/- 3.96 mm/minute) and convex sides (10.78 +/- 3.53 mm/minute) of the patients were significantly lower than the control group (17.94 +/- 2.89 mm/minute). There is no statistically significant difference between the NMCV of the concave and convex sides. After septal surgery, the NMCVs of the concave (16.34 _ 4.40 mm/minute) and convex sides (17.21 +/- 3.43 mm/minute) were not significantly different from control groups (17.94 +/- 2.89 mm/minute). Postoperative NMCVs of the concave and convex sides was significantly better than preoperative NMCVs. The results of this study showed that NSD significantly impaired NMCVs in both sides and that septoplasty significantly improved NMCVs in both sides.

Roxythromycin Stimulates the Mucociliary Activity of the Eustachian Tube and Modulates Neutrophil Activity in the Healthy Guinea Pig

Low-dosage, long-term erythromycin chemotherapy is useful in the treatment of chronic airway inflammatory diseases such as chronic sinusitis. The exact working mechanism of macrolides behind the clinical effectiveness still remains unclear. However, some have been considered including anti-inflammatory effect, effects on airway secretory functions, and steroid sparing effects. Otitis media with effusion (OME) is a chronic inflammatory disease in the tubotympanum. The epithelium of the tubotympanum is a modified respiratory epithelium. Therefore, macrolides might be effective in the treatment of patients with chronic OME. It was recently demonstrated that macrolides such as roxythromycin (RXM), enhance the ciliary activity in vitro. However, such ciliostimulatory effects found in an in vitro system are not always applicable to the mucociliary system in situ. The mucociliary system in situ might behave differently when in contact with RXM, and might deteriorate following oral administration of RXM. The present study aimed at investigating the in vivo effect of RXM on the mucociliary system in the tubotympanum and neutrophil activities of the guinea pig. The healthy guinea pigs were treated with oral administration of 5 or 50 mg/kg/day of RXM for 14 successive days, and the ciliary activity and the mucociliary clearance time of the tubotympanum was determined 24 h after the final administration. The ciliary activity in the Eustachian tube was significantly increased by oral administration of either dosage of RXM for 14 successive days. In addition, the mucociliary clearance velocity was accelerated by oral administration of such dosages of RXM. Therefore, the present data clearly demonstrate that RXM is a pharmacological agent with ciliostimulation and concurrent acceleration ability of the mucociliary clearance in the Eustachian tube. Oral administration of 5 as well as 50 mg/kg/day of RXM for 14 successive days did not significantly affect the phagocytosis activity of neutrophils but significantly increased the superoxide production of neutrophils. Since the effusions are considered to be the result of inflammatory events in the tubotympanum, the increased superoxide production activity of neutrophils confirmed in our study should result in an increased killing activity of infectious pathogens, thereby leading to control of the disease chronicity. In conclusion, our study argues in favor of the clinical usefulness of RXM in the treatment of OME.

Mucociliary function and nasal resistance evaluation before and after adenoidectomy

Thirty-four children with clinically and radiologically confirmed adenoid hypertrophy underwent otoscopy, impedance tests, active anterior rhinomanometry and nasal mucociliary clearance evaluation before and 6 months after adenoidectomy. Mucociliary clearance velocity increased significantly while binasal resistances decreased after surgery. The authors conclude that mucociliary evaluation and objective measurements of nasal resistances should be added to impedance tests as indicators to adenoidectomy.

Adenoid hypertrophy and nasal mucociliary clearance in children. A morphological and functional study.

The authors have studied nasal mucociliary function and adenoid surface characteristics in a group of 86 children, aged between 4 and 10 years, divided in two groups according to the presence or absence of clinical, instrumental and röntgenographic signs of nasal obstruction due to hypertrophied adenoids. Each group was divided into 3 age-related subgroups (group I: 4-5 years; group II: 6-7 years; group III: 8-10 years). A population of normal adults was chosen both for functional and ultrastructural characteristics. Nasal mucociliary clearance velocity values were evaluated by means of the saccharine method and the surface characteristics of the adenoid tissue by means of scanning electron microscopy. The data obtained show that the nasal mucociliary function is generally reduced in children but, while in the group with poorly developed adenoids an early and progressive improvement can be observed, the children with severely hypertrophied adenoids show an impaired function up to 10 years, without age-related improvements. At almost 10 years, children with poorly developed adenoids reach normal adult clearance values. These functional data can be related to the surface characteristics of adenoid tissue. In fact, while poorly developed adenoids are characterized by a compact layer of ciliated cells, severely hypertrophied adenoids are characterized by a metaplasic epithelium, with almost complete loss of cilia. Such findings, which are probably due to the inflammatory events frequently complicating adenoid hypertrophy, could explain, together with the obstructive effects, the impairment of the nasal mucociliary clearance in childhood.