Altered Sinonasal Ciliary Dynamics in Chronic Rhinosinusitis

2006 ◽  
Vol 20 (3) ◽  
pp. 325-329 ◽  
Author(s):  
Bei Chen ◽  
Jeffrey Shaari ◽  
Steven Eau Claire ◽  
James N. Palmer ◽  
Alexander G. Chiu ◽  
...  

Background Although multiple etiologies contribute to the development of rhinosinusitis, a common pathophysiological sequelae is ineffective sinonasal mucociliary clearance, resulting in stasis of sinonasal secretions, with subsequent infection, and persistent inflammation. The respiratory cilia beat continually at a basal rate, while during times of stress, such as exercise or infection, ciliary beat frequency (CBF) increases, accelerating mucus clearance. Previous investigations have led to conflicting results with some authors reporting decreased CBF while others have found normal values of CBF in patients with chronic rhinosinusitis (CRS). Additionally, these studies have only analyzed basal CBF. The goal of this study was to compare the basal as well as the stimulated sinonasal CBF in patients with CRS versus controls. Methods A dual temperature controlled perfusion chamber, differential interference contrast microscopy, and high-speed digital video were used to analyze both basal and adenosine triphosphate (100 μM)–stimulated CBF in human sinonasal mucosal explants. Results Although no difference in basal CBF was detected between control and CRS patients, a marked difference in stimulated CBF was noted. Exogenously applied adenosine triphosphate resulted in a 50–70% increase of CBF in control tissue with a minimally observed CBF increase in explants from CRS patients. Conclusion Dynamic regulation of respiratory ciliary activity is critical for the respiratory epithelium to adapt to varying environmental situations. Thus, diminished or absent adaptation could predispose the sinonasal cavity to accumulation of inhaled infectious and noxious particulate matter resulting in infection/inflammation. Our findings suggest that CRS patients have decreased sinonasal ciliary adaptation to environmental stimuli.

2011 ◽  
Vol 49 (4) ◽  
pp. 407-412
Author(s):  
J.U. Sommer ◽  
B.A. Stuck ◽  
C. Heiser ◽  
S.S. Kassner ◽  
K. Hormann ◽  
...  

Background: In recent years, the positive effect of topically applied estriol nose ointment in the adjuvant therapy of Morbus-Rendu-Osler (HHT) has been proven. Due to the induced metaplasia, a complete destruction of the ciliated cells may be expected. However, data regarding the ciliary function of HHT patients with and without the use of topical estriol application are currently lacking. Methodology/principal: Ciliated samples were obtained by gently brushing the inferior nasal turbinate of 19 healthy volunteers and 15 patients with known HHT (8 of them regularly using 0.1% estriol nose ointment for 2 years (HHTwE) and 7 of them not using the ointment in the last 12 months (HHTwoE)). Analysis was done with an inverted phase contrast microscope connected to a high-speed digital camera. Recorded parameters were the visual integrity (VI) of the ciliary beat and its frequency (CBF) in Hz. Results: The VI index of all samples showed an undisrupted, even beating pattern with a difference between the three groups. The mean CBF in all HHT patients was reduced compared to the control group`s mean CBF. Within the HHT group itself, the mean CBF was reduced in the HHTwE group compared to the HHTwoE group. Conclusions: The ciliary beat frequency of HHT patients is impaired compared to the control group and even more so if the HHT patients topically apply estriol more than 6 months. An undisrupted beating pattern is found in the HHTwE group despite the fact that estrogens induce a transformation of the ciliated columnar into a keratinizing squamous epithelium. This data may justify the adjuvant application of estriol as a nose ointment in the treatment of epistaxis in HHT patients without the fear of damage to the nose`s mucus clearance.


Author(s):  
С.И. Алексеенко ◽  
А.В. Скальный ◽  
С.А. Карпищенко ◽  
С.А. Артюшкин ◽  
С.В. Барашкова ◽  
...  

Несмотря на указания на роль цинка в функции реснитчатого эпителия, данные относительно влияния коррекции обмена цинка на цилиарную функцию у пациентов с хроническим риносинуситом отсутствуют. Целью настоящего исследования явилась оценка эффективности хирургического лечения, активности мукоцилиарного аппарата, а также местной воспалительной реакции слизистой оболочки носа в послеоперационном периоде у детей с хроническим риносинуситом на фоне применения цинка. Методы. Обследовано 192 ребенка с хроническим риносинуситом, в лечении которых применялась эндоскопическая риносинусохирургия. Из них 131 ребенок в послеоперационном периоде получал стандартные назначения, тогда как 61 ребенок дополнительно получал цинк в суточной дозе 10 мг в течение 90 дней. Оценка концентрации цинка в сыворотке крови осуществлялась методом ИСП-МС. Для определения функции цилий использована видеоцитоморфометрия. Определение эффективности лечения осуществлялось с использованием опросника SNOT-20, а также шкал Лунд-Кеннеди и Лунд-Маккей. Результаты. Проведение эндоскопической операции приводило к достоверному снижению значений шкал SNOT-20, Лунд-Кеннеди и Лунд-Маккей у пациентов вне зависимости от приема цинка. В то же время, пациенты, принимавшие цинк, характеризовались достоверно меньшим риском ревизионной хирургии. Цинк также оказывал значительное влияние на функционирование реснитчатого эпителия. В частности, к 12-му месяцу наблюдения количество клеток с подвижными цилиями, частота биения цилий, длина цилий и выживаемость клеток у пациентов, принимавших цинк, превышала соответствующие показатели в контрольной группе. Повышение уровня цинка в организме также сопровождалось многократным снижением количества инфильтрирующих слизистую оболочку нейтрофилов и лимфоцитов. Заключение. Предполагается, что цинк ускоряет репаративные процессы в слизистой оболочке носа и обладает противовоспалительным действием. Despite the presence of certain indications of the role of zinc in ciliated epithelium functioning, data on the potential effect of Zn supplementation in ciliary function in patients with chronic rhinosinusitis are absent. The aim of this study was to evaluate the efficiency of surgical treatment, ciliary activity, as well as local inflammation of nasal mucosa in children with chronic rhinosinusitis undergoing functional endoscopic surgery. Methods. 192 pediatric patients with chronic rhinosinusitis were examined. 131 patients received standard postoperative prescriptions, whereas 61 children received 10 mg Zn daily for 90 days. Serum Zn concentrations were measured by inductively coupled plasma mass spectrometry. Ciliary function was evaluated by video cytomorphometry. Surgery efficiency was assessed with a SNOT-20 questionnaire, as well as with Lund-Kennedy and Lund-Mackay scales. Results. Functional endoscopic sinus surgery resulted in a significant decrease in total SNOT-20, Lund-Kennedy, and Lund-Mackay scores independent of Zn supplementation. At the same time, Zn supplemented patients had a significantly lower risk of revision surgery. Zn also had a significant impact on ciliary function. Specifically, up to the 12th mo postoperatively, Zn supplementation resulted in higher number of cells with motile cilia, ciliary beat frequency, ciliary length, and cell viability as compared to controls. Increased Zn status was also associated with a manyfold decrease in mucosal neutrophil and lymphocyte infiltration. Conclusions. It is proposed that Zn enhances reparative processes in nasal mucosa and possesses anti-inflammatory activity.


2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
S. Alekseenko ◽  
S. Karpischenko ◽  
S. Artyushkin ◽  
S. Barashkova ◽  
I. Anikin

Background: The objective of the study is evaluation of ciliary function and mucosal cytology after endoscopic sinus surgery in children with chronic rhinosinusitis (CRS). Methodology: A total of 132 children with CRS who underwent endoscopic sinus surgery, as well as 15 healthy controls were involved in the study. In this follow-up study patients were examined preoperatively, as well as 3, 6, 9, and 12 months after endoscopic sinus surgery. Assessment of ciliary function and sinonasal mucosal cytology was performed using high-speed videomicroscopy. Lund-Kennedy, Lund-Mackay, and sinonasal outcome test 20 (SNOT20) scores were also evaluated. Results: Total SNOT-20, Lund-Mackay, and Lund-Kennedy values significantly decreased after sinus surgery. In contrast, ciliary function and mucosal cytology only tended to improve after 6 months. 9 months after surgery the number of ciliated cells, ciliary beat frequency, cell viability, and ciliary length were significantly higher than preoperatively. The most significant improvement of ciliary function and cell height was observed 12 months after operation, whereas epithelial dystrophy and neutrophil infiltration were significantly reduced. Conclusions: Substantial improvement was observed only in a year after surgery, whereas 0 to 3 months after the surgery ciliary function was severely impaired thus predisposing to recurrent sinusitis or other complications.


2014 ◽  
Vol 129 (S1) ◽  
pp. S45-S50 ◽  
Author(s):  
J H Kim ◽  
J Rimmer ◽  
N Mrad ◽  
S Ahmadzada ◽  
R J Harvey

AbstractObjective:This study investigated the effect of Betadine on ciliated human respiratory epithelial cells.Methods:Epithelial cells from human sinonasal mucosa were cultured at the air–liquid interface. The cultures were tested with Hanks' balanced salt solution containing 10 mM HEPES (control), 100 µM ATP (positive control), 5 per cent Betadine or 10 per cent Betadine (clinical dose). Ciliary beat frequency was analysed using a high-speed camera on a computer imaging system.Results:Undiluted 10 per cent Betadine (n = 6) decreased the proportion of actively beating cilia over 1 minute (p < 0.01). Ciliary beat frequency decreased from 11.15 ± 4.64 Hz to no detectable activity. The result was similar with 5 per cent Betadine (n = 7), with no significant difference compared with the 10 per cent solution findings.Conclusion:Betadine, at either 5 and 10 per cent, was ciliotoxic. Caution should be applied to the use of topical Betadine solution on the respiratory mucosal surface.


2001 ◽  
Vol 280 (6) ◽  
pp. C1485-C1497 ◽  
Author(s):  
Diane M. Morse ◽  
Jennifer L. Smullen ◽  
C. William Davis

The purinergic regulation of ciliary activity was studied using small, continuously superfused explants of human nasal epithelium. The P2Y2 purinoceptor (P2Y2-R) was identified as the major purinoceptor regulating ciliary beat frequency (CBF); UTP (EC50 = 4.7 μM), ATP, and adenosine-5′- O-(3-thiotriphosphate) elicited similar maximal responses, approximately twofold over baseline. ATP, however, elicited a post-peak sustained plateau in CBF (1.83 ± 0.1-fold), whereas the post-peak CBF response to UTP declined over 15 min to a low-level plateau (1.36 ± 0.16-fold). UDP also stimulated ciliary beating, probably via P2Y6-R, with a maximal effect approximately one-half that elicited by P2Y2-R stimulation. Not indicated were P2Y1-R-, P2Y4-R-, or P2Y11-R-mediated effects. A2B-receptor agonists elicited sustained responses in CBF approximately equal to those from UTP/ATP [5′-( N-ethylcarboxamido)adenosine, EC50 = 0.09 μM; adenosine, EC50 = 0.7 μM]. Surprisingly, ADP elicited a sustained stimulation in CBF. The ADP effect and the post-peak sustained portion of the ATP response in CBF were inhibited by the A2-R antagonist 8-( p-sulfophenyl)theophylline. Hence, ATP affects ciliary activity through P2Y2-R and, after an apparent ectohydrolysis to adenosine, through A2BAR.


2017 ◽  
Author(s):  
Csaba Verasztó ◽  
Nobuo Ueda ◽  
Luis A. Bezares-Calderón ◽  
Aurora Panzera ◽  
Elizabeth A. Williams ◽  
...  

AbstractCiliated surfaces harbouring synchronously beating cilia can generate fluid flow or drive locomotion. In ciliary swimmers, ciliary beating, arrests, and changes in beat frequency are often coordinated across extended or discontinuous surfaces. To understand how such coordination is achieved, we studied the ciliated larvae of Platynereis dumerilii, a marine annelid. Platynereis larvae have segmental multiciliated cells that regularly display spontaneous coordinated ciliary arrests. We used whole-body connectomics, activity imaging, transgenesis, and neuron ablation to characterize the ciliomotor circuitry. We identified cholinergic, serotonergic, and catecholaminergic ciliomotor neurons. The synchronous rhythmic activation of cholinergic cells drives the coordinated arrests of all cilia. The serotonergic cells are active when cilia are beating. Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency. Based on their connectivity and alternating activity, the catecholaminergic cells may generate the rhythm. The ciliomotor circuitry thus constitutes a stop-and-go pacemaker system for the whole-body coordination of ciliary locomotion.


2019 ◽  
Vol 57 (4) ◽  
pp. 237-244 ◽  
Author(s):  
Sylvain Blanchon ◽  
Marie Legendre ◽  
Mathieu Bottier ◽  
Aline Tamalet ◽  
Guy Montantin ◽  
...  

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.MethodsWe prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).ResultsSixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.ConclusionQuantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.


1995 ◽  
Vol 113 (5) ◽  
pp. 582-588 ◽  
Author(s):  
Rodney J. Schlosser ◽  
Judith M. Czaja ◽  
Thomas V. McCaffrey

Substance P is a neuropeptide released by afferent neurons in the respiratory tract during inflammatory reactions. It produces effects on blood vessels, bronchial smooth muscle, nasal glands, and respiratory cilia. We studied the in vitro effect of substance P on the ciliary beat frequency of human adenoid explants and its mechanism of action. Substance P was added to cultured adenoid at concentrations of 10−10, 10−8, 10−6, and 10−4 mol/L. Ciliary beat frequency was determined with phase-contrast microscopy and microphotometry. Substance P increased ciliary beat frequency a maximum of 11.9% ± 3.8% ( p < 0.01). Diclofenac (10−6 mol/L) significantly blocked the ciliostimulatory effects of SP ( p < 0.022), indicating that prostaglandin synthesis is an intermediate step in the action of substance P on ciliary beat frequency. The L-arginine analogs, NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, inhibit nitric oxide synthesis from L-arginine. L-Arginine analogs (10−4 to 10−2 mol/L) inhibited the effect of substance P ( p < 0.02 at the higher concentration). This inhibition was reversed by adding L-arginine, demonstrating that nitric oxide production is a required step in substance P-induced ciliostimulation. Substance P stimulates ciliary activity in human nasal mucosa as a result of secondary production and release of endogenous prostaglandins and nitric oxide. It is likely that inflammatory disease processes that stimulate release of substance P and subsequent prostaglandin and nitric oxide production modify mucociliary transport. Pharmacologic modification of substance P and its second messengers may eventually permit regulation of this important defense mechanism and control of neurogenic inflammation.


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