scholarly journals Flow of Room Air Leads to Rapid Changes in Mucociliary Transport in the Tracheal Epithelium

2020 ◽  
Author(s):  
Susyn Joan Kelly ◽  
Paul Martinsen ◽  
Stanislav Tatkov
Keyword(s):  
Body Temperature ◽  
Beat Frequency ◽  
Tracheal Epithelium ◽  
Mucociliary Transport ◽  
Negative Effects ◽  
Initial State ◽  
Upper Airways ◽  
Lower Airways ◽  
Humidified Air

Abstract BACKGROUND: Inspired air is heated and humidified in the nose before it reaches lower airways. This mechanism is bypassed during tracheostomy, directly exposing the lower airways to colder and drier air from the environment, which is known to have negative effects on mucociliary transport; however, little is known about how quickly mucociliary transport deteriorates. The purpose of this study was to determine the short-term effect of flowing room air on mucociliary transport in the trachea. In an ovine perfused in vitro tracheal model (N=7) the epithelium was exposed to 25 L/min of flow, heated to lamb body temperature (38 °C) and fully saturated with water vapor as the control, followed by room air (22 °C and 50% relative humidity) for a short duration, until mucociliary transport had visually stopped. Mucus transport velocity (MTV) and cilia beat frequency (CBF), as well as the area of the surface with beating cilia, were continuously measured with video-microscopy.RESULTS: Exposing the tracheal epithelium to air heated to body temperature and fully humidified resulted in stable MTV 9.5 ± 1.1 mm/min and CBF 13.4 ± 0.6 Hz. When exposed to the flow of room air, MTV slowed down to 0.1 ± 0.1 mm/min in 2.0 ± 0.4 seconds followed by a decrease in CBF to 6.7 ± 1.9 Hz, after 2.3 ± 0.8 second. Both MTV and CBF recovered to their initial state when heated and humidified air-flow was re-introduced. CONCLUSIONS: This study demonstrates mucociliary transport can deteriorate within seconds of exposing the tracheal epithelium to flowing room air. The reduction in MTV precedes slowing of CBF. Their relationship is non-linear and a minimum CBF of approximately 6 Hz is required for MTV > 0. Clinically these findings indicate a potential rapid detrimental effect of breathing with non-humidified air via bypassed upper airways.

scholarly journals Rapid changes in mucociliary transport in the tracheal epithelium caused by unconditioned room air or nebulized hypertonic saline and mannitol are not determined by frequency of beating cilia

2021 ◽  
Author(s):  
Susyn Joan Kelly ◽  
Paul Martinsen ◽  
Stanislav Tatkov
Keyword(s):  
Body Temperature ◽  
Hypertonic Saline ◽  
Beat Frequency ◽  
Tracheal Epithelium ◽  
Mucociliary Transport ◽  
Short Term ◽  
Initial State ◽  
Upper Airways ◽  
Subsequent Increase ◽  
Humidified Air

Abstract BACKGROUND: Inspired air is heated and humidified in the nose before it reaches lower airways. This mechanism is bypassed during tracheostomy, directly exposing the airways to colder and drier air from the environment, known to negatively affect mucociliary transport; however, little is known about how quickly mucociliary transport deteriorates. This study determines the short-term effect of flowing room air and nebulized hypertonic saline and mannitol on mucociliary transport in the trachea. In an ovine perfused in vitro tracheal model (N=9) the epithelium was exposed to 25 L/min of flow, heated to lamb body temperature (38°C) and fully saturated with water vapor as the control, followed by either room air (22°C and 50% relative humidity) or nebulized solutions of NaCl 7% and mannitol 20% up to 1 min for a short duration, until mucociliary transport had visually changed. Mucus transport velocity (MTV) and cilia beat frequency (CBF) were continuously measured with video-microscopy. RESULTS: Exposing the tracheal epithelium to air heated to body temperature and fully humidified had stable MTV 9.5±1.1mm/min and CBF 13.4±0.6Hz. When exposed to flow of room air, MTV slowed down to 0.1±0.1mm/min in 2.0±0.4seconds followed by a decrease in CBF to 6.7±1.9Hz, after 2.3±0.8 second. Both MTV and CBF recovered to their initial state when heated and humidified air- flow was re-introduced. Exposing the tracheal epithelium to nebulized hypertonic saline and nebulized mannitol for 1 min increased MTV without a subsequent increase in CBF.CONCLUSIONS: This study demonstrates mucociliary transport can deteriorate within seconds of exposing the tracheal epithelium to flowing room air and increase rapidly when exposed to nebulized hypertonic solutions. The reduction in MTV precedes slowing of CBF with room air and MTV increases without a subsequent increase in CBF during the nebulization. Their relationship is non-linear and a minimum CBF of approximately 6Hz is required for MTV>0, while MTV can reach 10.9mm/min without CBF increasing. Clinically these findings indicate a potential rapid detrimental effect of breathing with non-humidified air via bypassed upper airways and the short-term effects of nebulized osmotic agents that increase MTV.

scholarly journals Rapid changes in mucociliary transport in the tracheal epithelium caused by unconditioned room air or nebulized hypertonic saline and mannitol are not determined by frequency of beating cilia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Susyn Joan Kelly ◽  
Paul Martinsen ◽  
Stanislav Tatkov
Keyword(s):  
Body Temperature ◽  
Hypertonic Saline ◽  
Beat Frequency ◽  
Tracheal Epithelium ◽  
Mucociliary Transport ◽  
Short Term ◽  
Initial State ◽  
Upper Airways ◽  
Subsequent Increase ◽  
Humidified Air

Abstract Background Inspired air is heated and humidified in the nose before it reaches lower airways. This mechanism is bypassed during tracheostomy, directly exposing the airways to colder and drier air from the environment, known to negatively affect mucociliary transport; however, little is known about how quickly mucociliary transport deteriorates. This study determines the short-term effect of flowing room air and nebulized hypertonic saline and mannitol on mucociliary transport in the trachea. In an ovine perfused in vitro tracheal model (N = 9) the epithelium was exposed to 25 L/min of flow, heated to lamb body temperature (38 °C) and fully saturated with water vapor as the control, followed by either room air (22 °C and 50% relative humidity) or nebulized solutions of NaCl 7% and mannitol 20% up to 1 min for a short duration, until mucociliary transport had visually changed. Mucus transport velocity (MTV) and cilia beat frequency (CBF) were continuously measured with video-microscopy. Results Exposing the tracheal epithelium to air heated to body temperature and fully humidified had stable MTV 9.5 ± 1.1 mm/min and CBF 13.4 ± 0.6 Hz. When exposed to flow of room air, MTV slowed down to 0.1 ± 0.1 mm/min in 2.0 ± 0.4 s followed by a decrease in CBF to 6.7 ± 1.9 Hz, after 2.3 ± 0.8 s. Both MTV and CBF recovered to their initial state when heated and humidified air-flow was re-introduced. Exposing the tracheal epithelium to nebulized hypertonic saline and nebulized mannitol for 1 min increased MTV without a subsequent increase in CBF. Conclusions This study demonstrates mucociliary transport can deteriorate within seconds of exposing the tracheal epithelium to flowing room air and increase rapidly when exposed to nebulized hypertonic solutions. The reduction in MTV precedes slowing of CBF with room air and MTV increases without a subsequent increase in CBF during the nebulization. Their relationship is non-linear and a minimum CBF of approximately 6 Hz is required for MTV > 0, while MTV can reach 10.9 mm/min without CBF increasing. Clinically these findings indicate a potential rapid detrimental effect of breathing with non-humidified air via bypassed upper airways and the short-term effects of nebulized osmotic agents that increase MTV.

scholarly journals Variability in tracheal mucociliary transport is not controlled by beating cilia in lambs in vivo during ventilation with humidified and non-humidified air

2021 ◽  
Author(s):  
Susyn Joan Kelly ◽  
Vojta Brodecky ◽  
Elizabeth M. Skuza ◽  
Philip Berger ◽  
Stanislav Tatkov
Keyword(s):  
Body Temperature ◽  
Surface Temperature ◽  
Beat Frequency ◽  
Mucosal Surface ◽  
Mucociliary Transport ◽  
Mechanically Ventilated ◽  
Inhaled Particles ◽  
Different Temperatures ◽  
Humidified Air

Mucociliary transport in the respiratory epithelium depends on beating of cilia to move a mucus layer containing trapped inhaled particles towards the mouth. Little is known about the relationship between cilia beat frequency (CBF) and mucus transport velocity (MTV) in vivo under normal physiological conditions and when inspired air is dry or not fully humidified. This study was designed to use video-microscopy to simultaneously measure CBF and MTV in the tracheal epithelium through an implanted optical window in mechanically ventilated lambs. The inspired air in 6 animals was heated to body temperature and fully saturated with water for 4 hours as a baseline. In another series of experiments, 5 lambs were ventilated with air at different temperatures and humidities while the mucosal surface temperature was also monitored with infrared macro-imaging. In the baseline experiments during ventilation with fully humidified air at body temperature CBF remained fairly constant, mean 13.9±1.6Hz but MTV varied considerably between 0.1 and 26.1mm/min with mean 11.0±3.9mm/min, resulting in a maximum mucus displacement of 34.2µm/cilia beat. Fully humidified air at body temperature prevented fluctuations in the surface temperature during breathing indicating a thermodynamic balance in the airways. When lambs were ventilated with dryer air, the mucosal surface temperature and MTV dropped without a significant change in CBF. When inspired air was dry, mainly latent heat (92%) was transferred to air in the trachea, reducing the surface temperature by 5°C. Reduced humidity of the inspired air lowered the surface temperature and reduced MTV in the epithelium during ventilation.

Mucociliary interaction in vitro: effects of physiological and inflammatory stimuli

1990 ◽  
Vol 68 (4) ◽  
pp. 1421-1426 ◽  
Author(s):  
Z. V. Seybold ◽  
A. T. Mariassy ◽  
D. Stroh ◽  
C. S. Kim ◽  
H. Gazeroglu ◽  
...  
Keyword(s):  
Liquid Velocity ◽  
Beat Frequency ◽  
Platelet Activating Factor ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Base Line ◽  
Mucociliary Transport ◽  
Epithelial Surface ◽  
Surface Liquid

Mucociliary transport in the airways is governed by the interaction between ciliary activity and the depth and rheological properties of the liquids (mucus) covering the epithelial surface. A change in one of these parameters may not predict the direction and magnitude of a concomitant change in mucociliary transport. We therefore determined the effects of physiological (neurotransmitters) and pathological (inflammatory mediators) stimuli on ciliary beat frequency (CBF), surface liquid velocity (SLV), surface liquid depth (SLD), and viscoelasticity of mucus in pieces of sheep trachea (n = 5 for each treatment) mounted in a chamber such that the submucosal side was bathed with Krebs-Henseleit perfusate (KH) and the luminal side was exposed to conditioned air. SLV, SLD, and CBF were measured with a microscope provided with an electronic micrometer and strobe light. Apparent viscosity and shear elastic modulus were measured with a microcapillary method using mucus collected at the downstream end of the preparation. Control CBF, SLV, and SLD were 11.6 +/- 0.4 (SE) Hz, 91 +/- 8 micron/s, and 33 +/- 5 microns, respectively, at base line and did not change during KH perfusion for 100 min. Perfusion with both acetylcholine and epinephrine (10(-5) to 10(-3) M) produced concentration-dependent increases in mean CBF (maximum increases at 10(-3) M of 16 and 9%, P less than 0.05), whereas only acetylcholine increased mean SLV (+56% at 10(-3) M, P less than 0.05). Perfusion with platelet-activating factor (10(-7) to 10(-5) M) decreased both mean CBF and SLV in a dose-dependent fashion (-6 and -63% at 10(-5) M, P less than 0.05), whereas antigen perfusion (1:60 dilution) increased mean CBF (+10%, P less than 0.05) but decreased SLV (-47%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Combination therapy with cystic fibrosis transmembrane conductance regulator modulators augment the airway functional microanatomy

2016 ◽  
Vol 310 (10) ◽  
pp. L928-L939 ◽  
Author(s):  
Susan E. Birket ◽  
Kengyeh K. Chu ◽  
Grace H. Houser ◽  
Linbo Liu ◽  
Courtney M. Fernandez ◽  
...  
Keyword(s):  
Ion Transport ◽  
Functional Imaging ◽  
Clinical Benefit ◽  
Effective Viscosity ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Clinical Results ◽  
Mucociliary Transport ◽  
Sweat Chloride

Recently approved therapies that modulate CFTR function have shown significant clinical benefit, but recent investigations regarding their molecular mechanism when used in combination have not been consistent with clinical results. We employed micro-optical coherence tomography as a novel means to assess the mechanism of action of CFTR modulators, focusing on the effects on mucociliary clearance. Primary human airway monolayers from patients with a G551D mutation responded to ivacaftor treatment with increased ion transport, airway surface liquid depth, ciliary beat frequency, and mucociliary transport rate, in addition to decreased effective viscosity of the mucus layer, a unique mechanism established by our findings. These endpoints are consistent with the benefit observed in G551D patients treated with ivacaftor, and identify a novel mechanism involving mucus viscosity. In monolayers derived from F508del patients, the situation is more complicated, compounded by disparate effects on CFTR expression and function. However, by combining ion transport measurements with functional imaging, we establish a crucial link between in vitro data and clinical benefit, a finding not explained by ion transport studies alone. We establish that F508del cells exhibit increased mucociliary transport and decreased mucus effective viscosity, but only when ivacaftor is added to the regimen. We further show that improvement in the functional microanatomy in vitro corresponds with lung function benefit observed in the clinical trials, whereas ion transport in vitro corresponds to changes in sweat chloride. Functional imaging reveals insights into clinical efficacy and CFTR biology that significantly impact our understanding of novel therapies.

Adenosine A3 receptor-mediated potentiation of mucociliary transport and epithelial ciliary motility

2002 ◽  
Vol 282 (3) ◽  
pp. L556-L562 ◽  
Author(s):  
Manako Taira ◽  
Jun Tamaoki ◽  
Kazuyuki Nishimura ◽  
Junko Nakata ◽  
Mitsuko Kondo ◽  
...  
Keyword(s):  
Mucociliary Clearance ◽  
Beat Frequency ◽  
Blue Dye ◽  
Dependent Manner ◽  
Mucociliary Transport ◽  
Concentration Dependent Manner ◽  
Maximal Increase ◽  
Ciliary Motility

To examine the effect of adenosine A3 receptor stimulation on airway mucociliary clearance, we measured transport of Evans blue dye in rabbit trachea in vivo and ciliary motility of epithelium by the photoelectric method in vitro. Mucociliary transport was enhanced dose dependently by the selective A3 agonist N 6-(3-iodobenzyl)-5′- N-methylcarbamoyladenosine (IB-MECA) and to a lesser extent by the less-selective N 6-2-(4-amino-3-iodophenyl)ethyladenosine, whereas the A1 agonist N-cyclopentyladenosine (CPA) and the A2 agonist CGS-21680 had no effect. The effect of IB-MECA was abolished by pretreatment with the selective A3 antagonist MRS-1220 but not by the A1 antagonist 1,3-dipropyly-8-cyclopentylxanthine or the A2 antagonist 3,7-dimethyl-l-propargylxanthine. Epithelial ciliary beat frequency was increased by IB-MECA in a concentration-dependent manner, the maximal increase being 33%, and this effect was inhibited by MRS-1220. The IB-MECA-induced ciliary stimulation was not altered by the Rp diastereomer of cAMP but was greatly inhibited by Ca2+-free medium containing BAPTA-AM. Incubation with IB-MECA increased intracellular Ca2+ contents. Therefore, A3 agonist enhances airway mucociliary clearance probably through Ca2+-mediated stimulation of ciliary motility of airway epithelium.

scholarly journals Epithelial Cell Culture from Human Adenoids: A Functional Study Model for Ciliated and Secretory Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia González ◽  
Marisol Espinosa ◽  
María Trinidad Sánchez ◽  
Karla Droguett ◽  
Mariana Ríos ◽  
...  
Keyword(s):  
Experimental Model ◽  
Defense Mechanism ◽  
Beat Frequency ◽  
Ciliated Cell ◽  
Functional Study ◽  
Secretory Cells ◽  
Ciliary Activity ◽  
Control Mechanisms ◽  
Mucociliary Transport

Background. Mucociliary transport (MCT) is a defense mechanism of the airway. To study the underlying mechanisms of MCT, we have both developed an experimental model of cultures, from human adenoid tissue of ciliated and secretory cells, and characterized the response to local chemical signals that control ciliary activity and the secretion of respiratory mucinsin vitro.Materials and Methods. In ciliated cell cultures, ciliary beat frequency (CBF) and intracellular Ca2+levels were measured in response to ATP, UTP, and adenosine. In secretory cultures, mucin synthesis and secretion were identified by using immunodetection. Mucin content was taken from conditioned medium and analyzed in the presence or absence of UTP.Results. Enriched ciliated cell monolayers and secretory cells were obtained. Ciliated cells showed a basal CBF of 10.7 Hz that increased significantly after exposure to ATP, UTP, or adenosine. Mature secretory cells showed active secretion of granules containing different glycoproteins, including MUC5AC.Conclusion. Culture of ciliated and secretory cells grown from adenoid epithelium is a reproducible and feasible experimental model, in which it is possible to observe ciliary and secretory activities, with a potential use as a model to understand mucociliary transport control mechanisms.

Effect of Pseudomonas aeruginosa rhamnolipids on mucociliary transport and ciliary beating

1992 ◽  
Vol 72 (6) ◽  
pp. 2271-2277 ◽  
Author(s):  
R. C. Read ◽  
P. Roberts ◽  
N. Munro ◽  
A. Rutman ◽  
A. Hastie ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Guinea Pig ◽  
Beat Frequency ◽  
Membrane Damage ◽  
Dependent Manner ◽  
Mucociliary Transport ◽  
Tracheal Mucosa ◽  
Ciliary Beating

Pseudomonas aeruginosa rhamnolipid causes ciliostasis and cell membrane damage to rabbit tissue, is a secretagogue in cats, and inhibits epithelial ion transport in sheep tissue. It could therefore perturb mucociliary clearance. We have investigated the effect of rhamnolipid on mucociliary transport in the anesthetized guinea pig and guinea pig and human respiratory epithelium in vitro. Application of rhamnolipid to the guinea pig tracheal mucosa reduced tracheal mucus velocity (TMV) in vivo in a dose-dependent manner: a 10-microgram bolus caused cessation of TMV without recovery; a 5-micrograms bolus reduced TMV over a period of 2 h by 22.6% (P = 0.037); a 2.5-microgram bolus caused no overall changes in TMV. The ultrastructure of guinea pig tracheal epithelium exposed to 10 micrograms of rhamnolipid in vivo was normal. Application of 1,000 micrograms/ml rhamnolipid had no effect on the ciliary beat frequency (CBF) of guinea pig tracheal rings in vitro after 30 min, but 250 micrograms/ml stopped ciliary beating after 3 h. Treatment with 100 micrograms/ml rhamnolipid caused immediate slowing of the CBF (P less than 0.01) of human nasal brushings (n = 7), which was maintained for 4 h. Mono- and dirhamnolipid had equivalent effects. The CBF of human nasal turbinate organ culture was also slowed by 100 micrograms/ml rhamnolipid, but only after 4 h (CBF test, 9.87 +/- 0.41 Hz; control, 11.48 +/- 0.27 Hz; P less than 0.05, n = 6), and there was subsequent recovery by 14 h.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Continuous mucociliary transport by primary human airway epithelial cells in vitro

2015 ◽  
Vol 309 (2) ◽  
pp. L99-L108 ◽  
Author(s):  
Patrick R. Sears ◽  
Wei-Ning Yin ◽  
Lawrence E. Ostrowski
Keyword(s):  
Epithelial Cells ◽  
Beat Frequency ◽  
Multicomponent System ◽  
Airway Epithelial Cells ◽  
Mucociliary Transport ◽  
Airway Epithelial ◽  
Innate Defense ◽  
Human Airway ◽  
Human Airway Epithelial Cells

Mucociliary clearance (MCC) is an important innate defense mechanism that continuously removes inhaled pathogens and particulates from the airways. Normal MCC is essential for maintaining a healthy respiratory system, and impaired MCC is a feature of many airway diseases, including both genetic (cystic fibrosis, primary ciliary dyskinesia) and acquired (chronic obstructive pulmonary disease, bronchiectasis) disorders. Research into the fundamental processes controlling MCC, therefore, has direct clinical application, but has been limited in part due to the difficulty of studying this complex multicomponent system in vitro. In this study, we have characterized a novel method that allows human airway epithelial cells to differentiate into a mucociliary epithelium that transports mucus in a continuous circular track. The mucociliary transport device allows the measurement and manipulation of all features of mucociliary transport in a controlled in vitro system. In this initial study, the effect of ciliary beat frequency and mucus concentration on the speed of mucociliary transport was investigated.

Sign in / Sign up

Export Citation Format

Share Document