Nasal Mucociliary Clearance Research Articles

The effect of the nasal cycle on mucociliary clearance

The nasal cycle is a well-recognised physiological phenomenon where each side of the nose alternates through phases of congestion and decongestion. Although many physiological properties of the nose alternate with the nasal cycle whether this has any effect on the nasal mucociliary clearance is less clear. As the nose is a potential site for the administration of pharmaceuticals, it is essential that any factors that could affect clearance (and hence absorption) are identified. This study set out to investigate if mucociliary clearance rates differed between the clear and obstructed airway at a morning peak of the nasal cycle in five healthy volunteers with normal nasal anatomy using a dual-radioisotope labelling procedure that allows both sides of the nose to be assessed simultaneously. The clearance of the radiopharmaceutical formulations from the nasal cavity was monitored using gamma scintigraphy and decay-adjusted 50%-clearance times were calculated for each nostril. The ratios of clearance times from the patent nostril when compared to the obstructed nostril were statistically significant (two-tailed t-test; P = 0.039), the mean ratio being 2.5 : 1 (SEM +/- 0.5). It can be concluded that the nasal cycle has a marked effect on the mucociliary clearance patterns of the nose. This may have both theoretical and practical implications for the nasal delivery of drugs.

Nasal mucociliary clearance in healthy children in a tropical country

Introduction: Nasal mucociliary clearance is an important physiological function of nasal cavity that helps in protecting the lower respiratory tract from undesirable organic and inorganic matter including the micro organisms. The study was designed to establish normal mucociliary clearance time in healthy children in a tropical environment. Material and methods: The study was carried out in 100 randomly selected normal school children aged 4–15 years using saccharin method. The diseases that are known to affect the nasal mucociliary clearance were excluded. The study variables were age and sex. Results: Mean nasal mucociliary clearance time was 5.7±2.59 min with no significant difference between males and females. The clearance time was found to be impaired in groups A and B including children of 4–7 and 8–11 years of age respectively. Conclusion: Nasal mucociliary clearance is impaired in children of either sex between 4 and 11 years probably due to subclinical adenoiditis. However clearance returns to normal level at the time of puberty, which coincides with adenoids involution.

Scintigraphic evaluation in rabbits of nasal drug delivery systems based on carbopol 971p ® and carboxymethylcellulose

The residence time of apomorphine mucoadhesive preparations incorporating 99mTc labeled colloidal albumin in rabbit nasal cavity was evaluated by gamma scintigraphy. This technique was used to compare the nasal clearance of preparations based either on Carbopol 971P ® or lactose (control), each with and without apomorphine, or carboxymethylcellulose with apomorphine. The planar 1-min images showed an excipient-dependent progressive migration of radioactivity with time from the nasal cavity to the stomach and intestine. Thirty minutes post insufflation, the percentages of the formulations cleared from the nasal cavity were 47% for lactose, 26% for lactose/apomorphine, 10% for Carbopol 971P ®, and 3% for both Carbopol 971P ®/apomorphine and carboxymethylcellulose/apomorphine. Three hours post insufflation, the percentages of the formulations cleared from the nasal cavity were 70% for lactose, 58% for lactose/apomorphine, 24% for Carbopol 971P ®, 12% for Carbopol 971P ®/apomorphine, and 27% for carboxymethylcellulose/apomorphine. Apomorphine inhibited nasal mucociliary clearance since migration of the radioactivity administered with apomorphine containing preparations was in all cases slower than that of the corresponding powder without apomorphine. The peak plasma concentration of apomorphine was attained while all the formulations were still within the nasal cavity. The use of mucoadhesive polymers such as Carbopol 971P ® or carboxymethylcellulose in nasal dosage forms increases their residence time within the nasal cavity and provides the opportunity for sustained nasal drug delivery.

Rhinoscintigraphy: a simple radioisotope technique to study the mucociliary system.

This was a radioisotope study of nasal mucociliary clearance of total and subtotal nasal obstruction. Rhinoscintigraphy was performed by insufflating 1.85 MBq (69 mCi) Tc-99m MAA in 20 patients. Six cases were regarded as the control group, because the presence of small spurs does not affect nasal patency. The remaining 14 patients had various rhinopathic conditions. Two regions of interest were selected, one in the nasal cavity and one in the pharynx. Mucociliary transport speed was calculated. This parameter appeared to be a sensitive index for the assessment of the degree of mucociliary alteration. It showed that polyposis impairs mucociliary transport most severely, thus confirming the results of other published studies. Rhinoscintigraphy proved to be a reliable, easily reproducible, and harmless method, so it may be used for follow-up examinations in patients who have had surgery of the nose and paranasal sinuses, and for drug therapy of rhinopathic conditions.

Nasal Mucociliary Clearance and Nasal and Oral pH in Patients with Insulin-Dependent Diabetes

We studied 32 patients with insulin-dependent diabetes mellitus to determine how their rate of mucociliary clearance and their levels of nasal and oral pH compared with those of 10 nondiabetic controls and how these rhinologic measurements varied within different subsets of diabetic patients. Although we found very few statistically significant differences in all our comparisons, we did find that nasal mucociliary clearance and oral pH levels in the diabetic patients were significantly different from those of healthy subjects.

정상성인에서 방사선동위원소 추적자를 이용하여 측정한 고장성 식염수(Hypertonic Saline)가 비강의 점액섬모청소능(Mucociliary Clearance)에 미치는 영향

Background and Objectives: Nasal irrigation has been used usually in the treatment of patients with acute and chronic sinusitis and has also been utilized in the postoperative care of functional endoscopic sinus surgery patients. Nasal irrigation aids in the clearance of secretion, infective debris and intranasal crust which may lead to adhesion. Solutions used for nasal irrigation should not allow any impairment on the mucociliary system which contributes to the defense mechanism of the respiratory tract. For many decades, rhinologists have used normal saline as an ideal solution for mucociliary system. Recently, there are some reports that nasal irrigation with hypertonic (3%) saline is more effective on sinusitis and postoperative care of sinus surgery than irrigation with normal saline. But those were based on data using saccharine, which is a soluble tracer. And there is no report using insoluble tracer which reflects transport ability of gel layer of the mucous blanket. Therefore we performed this test in order to evaluate the effect of hypertonic saline on nasal mucociliary clearance in normal adults. Materials and Method: We studied 20 normal adults who did not have nasal diseases, aged from 17 to 24 years old, using human albumin tagged with radioisotope (Tc 99m). Nasal flow test was done with Glatzel mirror and open side was chosen. Control measurement was done before spray of normal saline and hypertonic (3%) saline. Also, the effects of normal saline and hypertonic saline on mucociliary clearance were measured after spray. Results: After spray of normal saline, mucociliary clearance increased to 4.96±2.33 mm/min, whereas in the control group was 4.60±1.85 mm/min. However, there were no statistical differences between the normal saline group and the control group (p=0.5288). But mucociliary clearance of hypertonic saline group increased to 5.96±2.50 mm/min, whereas in the control group was 4.92 ±2.34 mm/min and there were significant differences between hypertonic saline group and the control group (p=0.0142). Conclusion: The results of this study suggest that hypertonic (3%) saline irrigation has the effect of improving nasal mucociliary clearance. Also the results suggest that hypertonic saline affects the gel layer. Further rheologic studies should be made in order to know the mechanism of effect of hypertonic saline on mucociliary clearance. (J Clinical Otolaryngol 1999;10:61-65)

The effect of antiallergic intranasal formulations on ciliary beat frequency of human nasal epithelium in vitro.

The nasal mucociliary clearance is an important defense mechanism of the upper respiratory tract. It is known to be influenced by many pharmacologic substances. We investigated the effects of three topical intranasal antiallergic formulations containing disodium cromoglycate (DNCG), dimethindene maleate (DMM), and azelastine-HCL (AZL) on nasal ciliary beat frequency (CBF) in vitro. Nasal ciliated cells were harvested from 16 healthy volunteers. Cells were diluted 1:10 in culture medium and incubated with a placebo formulation (PLAC), containing 0.022% benzalkonium chloride, which was part of all formulations, a registered 2% formulation of DNCG, a 0.1% formulation of DMM, and a registered 0.1% formulation of AZL. After an incubation period of 20 min, CBF was registered by a photoelectric measurement device. Under control conditions (CONTROL), CBF was 11.4 +/- 1.3 Hz. PLAC reduced CBF to 9.7 +/- 2.3 Hz (NS). DNCG reduced CBF to 9.7 +/- 2 Hz (NS). DMM reduced CBF to 7.2 +/- 1.7 Hz (P < or = 0.05 vs CONTROL, NS vs PLAC), and AZL reduced CBF to 0.9 +/- 1.8 Hz (P < or = 0.001 vs CONTROL, P < or = 0.001 vs DNCG, P < or = 0.001 vs PLAC). In conclusion, a possible influence of antiallergic intranasal formulations on nasal ciliary function has to be considered in clinical application.

Effect of arginine on mucociliary function in primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetic disease characterised by defective motility of cilia and abnormally low nasal nitric oxide (NO)1 which has a key role in host defence and in up-regulation of ciliary motility in vitro.2 Inhibitors of NO synthesis decrease ciliary beating in airway epithelium.3 We investigated whether arginine, a precursor of NO synthesis,3 could increase nasal NO and improve ciliary beat frequency and nasal mucociliary clearance in patients with and without PCD.

Effects of luteinising-hormone-releasing hormone on nervous-system tumours

in CBF in patients and controls (r=0·76, p<0·05, and r=0·63, p<0·05, respectively). L-arginine decreased nasal mucociliary clearance time in patients with and without PCD (figure), and the maximum increases in NO and nasal mucociliary clearance time correlated significantly for the two groups (r=0·72, p<0·05 and r=0·71, p<0·02). Studies of human airway cilia have shown ciliary-beatfrequency stimulation by cyclic guanosine monophosphate and endogenous prostaglandin E2. NO increases concentrations of cyclic guanosine monophosphate and leads to the release of prostaglandin E2. Therefore, arginine, by the increasing NO in ciliated epithelial cells, may modulate the ciliary activity through a rise in cyclic guanosine monophosphate and prostaglandin E2 or via other as yet unknown mechanisms, leading to faster more coordinated ciliary beating and improved mucociliary clearance. Measurement of nasal NO may help to diagnose PCD. Our findings suggest that arginine may have a therapeutic role in PCD.

Subjective and objective assessments in patients with seasonal allergic rhinitis: Effects of therapy with mometasone furoate nasal spray

Background: Efficacy of topical nasal steroid therapy for allergic rhinitis is usually evaluated by patient and clinician assessments of subjective symptom changes in diaries and at clinical interviews. Objective: We sought to complement the subjective measures with objective measures of nasal cytology, biochemistry, and function. Methods: In this double-blind, randomized study patients with seasonal allergic rhinitis (SAR) 12 years of age or older received 200 μg mometasone furoate nasal spray ( n = 80) or placebo spray ( n = 41) once daily for 2 weeks. Subjective assessments by clinician and patient comprised symptom/sign scores and overall therapeutic response evaluations. Objective measures included nasal cytology, nasal biochemistry, nasal airway resistance (NAR), mucociliary clearance, and olfactory functions. Results: Mometasone furoate produced a significantly greater decrease than placebo in subjective measures of SAR for total symptom score (–46% vs –30%, p < 0.05), total nasal score (–47% vs –30%, p < 0.024), individual nasal symptom scores, and overall therapeutic response. The objective measures of eosinophil, basophil, and neutrophil counts and mucociliary clearance were significantly better in mometasone furoate– than in placebo-treated patients. Similarly, within-treatment statistically significant improvements were produced by mometasone furoate but not by placebo sprays for levels of eosinophilic cationic protein, tryptase and albumin, NAR, and odor identification. Significant positive correlations were found between NAR and nasal stuffiness and between eosinophils, basophils, and neutrophils and both eosinophilic cationic protein and albumin. Conclusion: Subjective measures of SAR were significantly improved in the mometasone furoate group by comparison with placebo-treated patients. Objective assessments supported the subjective findings because within-treatment measures were frequently significantly improved after mometasone furoate treatment but not after placebo treatment. (J Allergy Clin Immunol 1998;102:39-49.)

Prechallenge antibodies moderate disease expression in adults experimentally exposed to rhinovirus strain hanks.

This double-blind study determined the influence of serum neutralizing antibody titers on the rate of infection and magnitude of disease expression after experimental exposure of adult volunteers to rhinovirus strain Hanks (RV-H). A total of 133 healthy volunteers were tested for antibody status, cloistered for a 6-day period, and challenged with RV-H at the end of the first cloister day. On these days, response to viral challenge is assessed with symptom diaries and physical examinations. The low-titer infected group was significantly different from the intermediate-titer infected and the uninfected groups in terms of postchallenge nasal and throat symptoms, expelled secretion weights, nasal mucociliary clearance rates, and frequency of negative middle ear pressures. A similar trend held for the infected high-titer vs. low-titer group comparisons. These data show that high homotypic serum neutralizing antibody titers are associated with protection from infection and lessened signs and symptoms following experimental RV-H exposure.

정상 성인에서 방사성동위원소 추적자를 이용한 비강점액청소능에 관한연구

정상 성인에서 방사성동위원소 추적자를 이용한 비강점액청소능에 관한연구

Nasal mucociliary clearance of chronic sinusitis in relation to rheological properties of nasal mucus.

The role of the viscosity (eta') and elasticity (G') of nasal mucus in nasal mucociliary clearance (MCC) in chronic sinusitis (CS) was studied. The nasal mucus was collected from 17 patients with CS, and both eta' and G' were determined by an oscillating sphere magnetic rheometer. Following the nasal mucus collection, nasal MCC was measured by a radioisotope method in the patients and 22 normal subjects. Nasal MCC in the patients was significantly reduced compared with that in the normal subjects (p < .05). No significant correlation was noted between nasal MCC and eta', or between nasal MCC and G'. The results suggest that factors other than eta' and G' of nasal mucus may control nasal MCC in CS.

The Effect of Smoking on Nasal Mucociliary Clearance

The Effect of Smoking on Nasal Mucociliary Clearance

The effect of smoking on nasal mucociliary clearance

The effect of smoking on nasal mucociliary clearance

Prechallenge antibodies: moderators of infection rate, signs, and symptoms in adults experimentally challenged with rhinovirus type 39.

This study determined the influence of serum neutralizing antibody titers on infection rate, symptom manifestations, and provoked signs and pathophysiologies in adults experimentally exposed to rhinovirus type 39 (RV-39). Antibody status was determined for 151 healthy volunteers who were then cloistered in a hotel for 6 days. At the end of the first cloister day, the volunteers were challenged with RV-39 in a median tissue culture infective dose of 100. On each of the 6 days, a nasal examination was performed, symptoms were scored, and objective tests of nasal mucociliary function, nasal airway patency, secretion production, and middle ear pressures were completed. Both subjects and investigators were blinded to the prechallenge serum homotypic antibody titers of the subjects. Four subjects presented with a wild virus and were excluded from the analysis. Of the 147 included subjects, prechallenge serum antibody titers to RV-39 were low (under 2) in 56 subjects, intermediate (2 to 8) in 51 subjects, and high (above 16) in 40 subjects. The high-titer group was significantly different from the low-titer group with respect to viral shedding, symptom load, subjective extent of illness, and secretion production, as well as in the frequency of subjects with abnormal nasal mucociliary clearance and positive middle ear pressures. The study results document that for experimental RV-39 exposure, high levels of homotypic serum neutralizing antibody titers are associated with protection from infection and a lessened degree of disease expression, but not with a reduction of otologic complications.

Intranasal mucociliary clearance of putative bioadhesive polymer gels

Abstract Rapid clearance of a drug away from the site of absorption is one factor that limits the bioavailability of compounds administered nasally. The effects of putative bioadhesive polymers including methylcellulose, sodium carboxymethylcellulose, hydroxypropyl-methylcellulose, chitosan glutamate, Carbopol 934P, polyethylene oxide 600K and Pluronic F127 on slowing nasal mucociliary clearance were investigated using a rat model. The clearance of these polymer gels from the nasal cavity was measured by following the removal of fluorescently labeled microspheres incorporated into the formulation. Due to the increased residence times of the gel formulations in the nasal cavity, the clearance rate of each polymer gel was slower than the clearance rate of a control microsphere suspension. The clearance rate constants were in the range of 7–57% of the control clearance constants. Methylcellulose gel (3%) resulted in the most prolonged nasal clearance whereas Carbopol 934P aqueous gel (0.2%) had the most rapid clearance. A Carbopol 934P gel with propylene glycol and glycerol formal as cosolvents was prepared to investigate the effect of an in situ gelling system on nasal clearance. The initial clearance of this cosolvent gel was not significantly different than the suspension, yet the total mass recovered was significantly lower than the control. The clearance of a 3% methylcellulose gel formulation from a damaged nasal mucosa was also investigated in order to obtain further information about the characteristics of nasal mucociliary clearance. Results showed that from 4 h through the 7th day following the initial damage, although the initial clearance rate constants were slightly higher, the time for 90% of the observed particle clearance was significantly extended and the total masses recovered were significantly lower than those obtained from a non-damaged mucosa.

15. Nasal mucociliary clearance measured by 99Tcm-HSA

15. Nasal mucociliary clearance measured by 99Tcm-HSA

Ciliary disorientation alone as a cause of primary ciliary dyskinesia syndrome.

Ciliary disorientation has been proposed as a variant of primary ciliary dyskinesia (PCD); cilia have normal ultrastructure and normal or near normal ciliary beat frequency (CBF) but lack efficacy because their beat direction is disorientated. We have identified 11 patients, including two siblings, with the clinical features of PCD, who satisfy these criteria. A chest radiograph, pulmonary function tests, nasal mucociliary clearance (NMCC), CBF, ciliary ultrastructure, and orientation were assessed in each subject. One patient had biopsies taken from the nose and both main bronchi. Eight patients had a computed tomography scan (CT) of the thorax; the clinical features were compatible with PCD. Cilia ultrastructure was normal and NMCC was absent in all cases. Mean CBF was normal (11.6-14.9 Hz) in five cases and slow in six (range 8.4-9.7 Hz). Ciliary beat pattern was stiff in seven cases, six of which had slow CBF. The cilia were disorientated when measured by both the central pair (range, 21.8 degrees - 26.4 degrees) and basal feet (range, 20.6 degrees - 28.9 degrees) compared with 16 normal controls (range, 11.0 degrees - 15.5 degrees and 12.3 degrees - 17.6 degrees, respectively). Two siblings had the clinical features of PCD and ciliary disorientation alone on repeated biopsies taken 10 yr apart. Orientation of cilia from the nose and bronchus was similar. Two cases had unchanged ciliary disorientation after 3 mo of treatment with antibiotics and topical corticosteroids. We concluded that ciliary disorientation alone can lead to the clinical syndrome of PCD.

Work related impairment of nasal function in Swedish woodwork teachers.

To study the relation between exposure and nasal function in woodwork teachers. 39 selected woodwork teachers employed full time and 32 control subjects (other school personnel) were examined at the beginning and at the end of a working week with symptom rating, nose and throat inspection, rhinomanometry, nasal mucociliary clearance test, and a smell identification test. During one working day of the same week climate, dust and terpene concentrations were measured in all 39 schools. The ventilation rate was highest in rooms with mechanical ventilation. Range of total dust (personally sampled) was 0.12-1.18 mg/m3, respirable dust 0.02-0.21 mg/m3, and terpenes (area sampled) 0.02-6.8 mg/m3. In contrast to the control subjects, the woodwork teachers had more nasal symptoms on the Thursday afternoon than on the Monday morning, especially those working in rooms without mechanical ventilation. Their mucociliary clearance worsened during the week (mean increase 4 min, P < 0.001). A small impairment of olfactory function was also found, but their rhinomanometric values did not change significantly. Nasal symptoms correlated weakly with the percentage of respirable dust in the total dust. Otherwise there were no significant dose-effect relations between measured dust or terpene concentrations and nasal tests. The woodwork teachers had mainly reversible nasal complaints, impaired nasal mucociliary clearance and olfactory function related to the work environment, with dust concentrations below the Swedish threshold limit value of 2 mg/m3.