Mucociliary Transport Function Research Articles

Effects of Thickening Agents on the Mucociliary Transport Function: Comparison by the Type of Thickening Agents and the Viscosity of Thickened Water.

Thickening agents effectively prevent liquid aspiration, but their impact on the ease of discharging aspirated liquids from the trachea remains unclear due to alterations in the physical properties of liquids. This study clarifies the effects of thickening agents, comprising various raw materials, on mucociliary transport function, focusing on the viscosities of thickened waters. The subjects were 23 healthy adults. Five types of saccharin solution were prepared: a solution without a thickening agent, a starch-based nectar-like solution, a starch-based honey-like solution, a xanthan-gum-based nectar-like solution, and a xanthan-gum-based honey-like solution. Using these five types of saccharin solutions randomly, each subject underwent five trials of the saccharine dye test to evaluate the mucociliary transport function of the respiratory tract. The saccharin time was defined as the time from the placement of the saccharin solution on the nasal vestibule of the subject to when the subject reported that they became aware of the sweetness. The saccharin transit times for all samples of thickened water were longer compared to those of water without a thickening agent (p < 0.01). A comparison between thickened water samples with different viscosities showed that the saccharin transit time was longer when thickened water samples with high viscosity were prepared using the same thickening agent (p < 0.01). This suggests that while thickening reduces aspiration, the use of thickening agents may increase the difficulty in discharging aspirated fluids from the trachea.

Bronchial Asthma and Mucociliary Clearance - A Bidirectional Relationship

Abstract: The integrity of the airway epithelium plays an important role in the defence against pathogens and various immunogenic stimuli from the external environment. Properly functioning mucociliary clearance is an indispensable part of the respiratory system defence and it relies on adequate viscoelastic properties of mucus, as well as the intact function of a significant number of healthy ciliated cells. The movement of the cilia can be affected by many endogenous and exogenous factors. Complex mucociliary clearance dysfunction can be seen as a part of the respiratory system inflammation. Bronchial asthma is one of the most common inflammatory diseases of the respiratory system. It is characterised by structural and functional changes in the airways. The last decades of bronchial asthma research point to asthmatic inflammation as the cause of airway remodelling with subsequent impairment of mucociliary transport function. Changes in the respiratory epithelium in patients with bronchial asthma include hypertrophy of secretory cells, overproduction of mucus, increase in mucus viscosity, decline of ciliated cells, decrease of ciliary beat frequency, and more. Cytokines of T2-high type of asthmatic inflammation, such as interleukin IL-13 and IL-4, have been shown to contribute to these changes in the airway epithelium significantly. There is strong evidence of cytokine-induced overexpression of important transcription factors, which results in hyper- and metaplasia of secretory cells and also transdifferentiation of ciliary cells. Impaired mucociliary clearance increases the risk of airway infection and contributes to the worsening of bronchial asthma control.

Mucociliary clearance augmenting drugs block SARS-CoV-2 replication in human airway epithelial cells.

The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve the barrier function of the airway epithelium and reduce viral replication and, ultimately, COVID-19 outcomes. We tested five agents known to increase MCT through distinct mechanisms for activity against SARS-CoV-2 infection using a model of human respiratory epithelial cells terminally differentiated in an air/liquid interphase. Three of the five mucoactive compounds tested showed significant inhibitory activity against SARS-CoV-2 replication. An archetype mucoactive agent, ARINA-1, blocked viral replication and therefore epithelial cell injury; thus, it was further studied using biochemical, genetic, and biophysical methods to ascertain the mechanism of action via the improvement of MCT. ARINA-1 antiviral activity was dependent on enhancing the MCT cellular response, since terminal differentiation, intact ciliary expression, and motion were required for ARINA-1-mediated anti-SARS-CoV2 protection. Ultimately, we showed that the improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment.

Targeting ATP12A, a Nongastric Proton Pump α Subunit, for Idiopathic Pulmonary Fibrosis Treatment.

Idiopathic pulmonary fibrosis (IPF) is a pathological condition of unknown etiology that results from injury to the lung and an ensuing fibrotic response that leads to the thickening of the alveolar walls and obliteration of the alveolar space. The pathogenesis is not clear, and there are currently no effective therapies for IPF. Small airway disease and mucus accumulation are prominent features in IPF lungs, similar to cystic fibrosis lung disease. The ATP12A gene encodes the α-subunit of the nongastric H+, K+-ATPase, which functions to acidify the airway surface fluid and impairs mucociliary transport function in patients with cystic fibrosis. It is hypothesized that the ATP12A protein may play a role in the pathogenesis of IPF. The authors' studies demonstrate that ATP12A protein is overexpressed in distal small airways from the lungs of patients with IPF compared with normal human lungs. In addition, overexpression of the ATP12A protein in mouse lungs worsened bleomycin induced experimental pulmonary fibrosis. This was prevented by a potassium competitive proton pump blocker, vonoprazan. These data support the concept that the ATP12A protein plays an important role in the pathogenesis of lung fibrosis. Inhibition of the ATP12A protein has potential as a novel therapeutic strategy in IPF treatment.

Expression of T-Type Voltage-Gated Calcium Channel in the Cilia of Human Nasal Epithelial Cells

Introduction: The mucociliary transport function of the airway epithelium is largely dependent on ciliary beating. The control signal of ciliary beating is thought to be intracellular Ca2+. We herein investigated the expression of T-type voltage-gated calcium channel (VGCC), a generator of intracellular Ca2+ oscillation, in the human nasal mucosa. Methods: The inferior turbinate was collected from patients with chronic hypertrophic rhinitis. The expression of T-type VGCC α1 subunits was examined by immunohistochemistry, transmission immunoelectron microscopy, Western blot, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Participation of T-type VGCC in the ciliary beat regulation was examined by pharmacological inhibition tests using specific blockers of T-type VGCC in ex vivo measurements of the ciliary beat frequency (CBF) and ATP release and in intracellular Ca2+ imaging of isolated ciliated cells. Results: Immunohistochemical staining showed the expressions of T-type VGCC α1 subunits, Cav3.1 and Cav3.3, on the surface of the epithelial cells. At the ultrastructural level, immunoreactivity for Cav3.1 was localized on the surface of the cilia, and that for Cav3.3 was localized in the cilia and at the base of the cilia. The existence of Cav3.1 and Cav3.3 was confirmed at the protein level by Western blot and at the transcriptional level by real-time RT-PCR. Specific blockers of T-type VGCC, mibefradil and NNC 55-0396, significantly inhibited CBF. These blockers also inhibited a CBF increase induced by 8-bromo-cAMP/8-bromo-cGMP and significantly lowered the intracellular Ca2+ level of isolated ciliated cells in a time-dependent manner. On the other hand, the ATP release from the nasal mucosa was not changed by mibefradil or NNC 55-0396. Conclusion: These results indicate that T-type VGCC α1 subunits, Cav3.1 and Cav3.3, exist at the cilia of the nasal epithelial cells and participate in the regulation of ciliary beating and that these channels act downstream of cAMP/cGMP.

Topical therapy drugs containing silver in acute adenoiditis sinusitis in children

The article presents the results of Russian authors’ research aimed at studying the clinical efficacy of topical drugs containing silver in treating acute serous adenoiditis and sinusitis in children. The authors noted the efficacy and safety of the drug (silver proteinate and polyvinyl-N-pyrrolidone) in the complex treatment of inflammatory diseases of the nose and paranasal sinuses in children. Clinical observation was carried out – comparison of two groups of 30 patients aged from 5 to 14 years, average age 6 years 3 months, the groups included: 17 boys (56.7%) and 13 girls (43.3%), all children had adenoid vegetations of the 1st-2nd degree. To assess the clinical efficacy of the drug, a control group of children with similar pathology was recruited, comparable in age and sex (14 boys and 16 girls). The main group received the drug Sialor and irrigation therapy. The control group received local antibacterial drugs and decongestants according to age. At the beginning of treatment normal values of mucociliary transport were not observed in any patient (0%) of the main and control groups. Disorder of the 1st degree mucociliary transport function was determined in 6 children (20%) of the main group and 7 children (23.3%) of the control group, 2nd degree – in 21 children (70%) of the main group and 19 children (63.3%) of the control group, 3rd degree – in 3 (10%) patients of the main group and 4 children (13.4%) of the control group. In 7 days from the beginning of treatment normal values of MCT were observed in 28 patients (93.3%) of the main group and 9 patients (30%) of the control group, the disorder of MCT function of the 1st degree had 3 patients (9%) of the main and control groups, the 2nd degree was not in the main group and was revealed in 18 patients (60%) of the control group, no disorder of MCT function of the 3rd degree was revealed (neither in the main nor control groups). The average time of MCT was: before treatment – 49 minutes (main group) and 47 minutes (control group), the 3rd day of treatment – 28 minutes (main group) and 36 minutes (control group). On the 7th day of the drug intake – 14 minutes (main group) and 21 minutes (control group). Thus, normalization of MCT time was noted only in patients of the main group. On the 7th day of treatment with Sialor in the main group of children under examination, nasal mucosa edema, nasal excretion and adenoid tissue size decreased, mucociliary transport parameters normalized, nasal breathing improved. Sialor has a pronounced anti-inflammatory and anti-edema effect, is well tolerated by patients and can be recommended for inclusion in standard treatment protocols of patients with diseases of the nasal cavity, paranasal sinuses.

Evaluation of Cilia Function in Rat Trachea Reconstructed Using Collagen Sponge Scaffold Seeded with Adipose Tissue-Derived Stem Cells.

The tracheal lumen is essential for conducting air to the lung alveoli and for voice production. However, patients with severe tracheal stenosis and malignant tumors invading the trachea often require tracheal resection. Recently, various reported tissue engineering methods for tracheal reconstruction show that regeneration of ciliated epithelium in the reconstructed areas, as well as preservation of the luminal structure is possible. However, only few studies report on the mucociliary transport function in reconstructed tracheae. We investigated mucociliary transport function within rat tracheal epithelium, reorganized after autologous adipose tissue-derived stem cell (ASC) transplantation. Rat ASCs were expanded in culture, and then seeded in a collagen sponge, which was physically supported with a polypropylene framework. The ASC-seeded collagen sponge was transplanted into the rat tracheal defect. We then examined the motility and transport function of cilia generated in the transplanted area using ciliary beat frequency (CBF) and microsphere movement analyses. Our data suggested that autologous ASC transplantation promoted ciliogenesis, consistent with previous reports. The CBF analysis revealed that motility of the cilia generated in the ASC group was comparable to that observed in the normal rat tracheal epithelium. Transport function in the ASC group was higher than that in the control group. These data suggested that autologous ASC transplantation increased ciliated cells in the reconstructed area without significantly disrupting cilia motility, thereby promoting transport function regeneration. Autologous ASC transplantation is expected to be beneficial in morphological and functional regeneration of tracheal epithelium. Anat Rec, 303:471-477, 2020. © 2019 American Association for Anatomy.

Relações entre atividade física, tabagismo, transportabilidade mucociliar nasal e função pulmonar

***Relationships between physical activity, smoking, nasal mucociliary transportability and pulmonary function***AIMS: To compare smokers and non-smokers, physically active and insufficiently active, on mucociliary transportability and lung function.METHODS: Cross-sectional study. The volunteers were interviewed to obtain personal data, information on smoking habits and level of physical activity. Then, they were evaluated for anthropometric data, nasal mucociliary transport (by saccharin transit time test) and lung function (by measuring forced expiratory volume in the first second and forced vital capacity). Analysis of variance was used for investigation between the groups and analysis of covariance (adjusted for confounding factors) to investigate cofactors on the transit time of saccharin. The significance level of 5% and the 95% confidence interval were adopted.RESULTS: A total of 139 individuals were selected and assigned to four groups, according to the smoking habits and the level of physical activity: 45 smokers who were not physically active; 25 physically active smokers; 31 non-smokers who were not physically active; and 38 physically active non-smokers. The mean age and body mass index did not present statistically significant differences between the four groups. In the saccharin transit time test, physically active non-smokers presented a time of 8.73 minutes, while in the insufficiently active, the time was 13.0 minutes (p=0.0409). Physically active smokers presented lower values of forced expiratory volume in the first second compared to those who were not physically active (z score in relation to predicted values -1.01 and -0.55, respectively; p=0.0207).CONCLUSIONS: In this sample of healthy adults of both sexes, the practice of physical activity was beneficial for nasal mucociliary transportability, but only in individuals who never smoked. On the other hand, physically active smokers presented lower values of lung function when compared to insufficiently active smokers, suggesting that physical exercises may cause additional lung function impairment if the individual does not change the smoking habit.

Rhinophototherapy in persistent allergic rhinitis

Previous published results have revealed that Rhinolight® intranasal phototherapy is safe and effective in intermittent allergic rhinitis. The present objective was to assess whether phototherapy is also safe and effective in persistent allergic rhinitis. Thirty-four patients with persistent allergic rhinitis were randomized into two groups; twenty-five subjects completed the study. The Rhinolight® group was treated with a combination of UV-B, UV-A, and high-intensity visible light, while the placebo group received low-intensity visible white light intranasal phototherapy on a total of 13 occasions in 6weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak flow, quantitative smell threshold, mucociliary transport function, and ICAM-1 expression of the epithelial cells. All nasal symptom scores and nasal inspiratory peak flow measurements improved significantly in the Rhinolight® group relative to the placebo group and this finding persisted after 4weeks of follow-up. The smell and mucociliary functions did not change significantly in either group. The number of ICAM-1 positive cells decreased non-significantly in the Rhinolight® group. No severe side-effects were reported during the treatment period. These results suggest that Rhinolight® treatment is safe and effective in persistent allergic rhinitis.

Changes in Intramaxillary Sinus Pressure following Antrostomy, Draining Tubes, and YAMIK Procedures in 25 Patients Treated for Chronic Paranasal Sinusitis

When conservative therapies are not effective in treating sinus infections, alternate steps can be taken to improve paranasal cavity ventilation. These measures may include surgical procedures such as intranasal endoscopic or maxillary sinus fenestration, and other procedures such as placement of a maxillary sinus tube or a YAMIK sinus catheter. We conducted a prospective study of 25 patients to investigate the effects on the nasal mucosa of improved ventilation between the nasal and paranasal cavities. We accomplished this by comparing (1) the results of simultaneously measured nasal cavity and intramaxillary sinus pressures before and after widening of ventilation openings, (2) changes in mucociliary transport function as measured by the saccharin test, and (3) changes in nasal airway resistance. Just as multiple transit routes between the nasal cavity and maxillary sinus give rise to greater fluctuations in intramaxillary sinus pressure, and just as rapid breathing gives rise to even greater pressure fluctuations than does quiet breathing, we believe that both intranasal cavity airflow velocity and the number of ventilation openings present have an effect on the state of ventilation between the nasal cavity and maxillary sinus. We also suggest that the establishment of maxillary sinus ventilation openings improves mucociliary clearance.

Effect of macrolide antibiotics on ciliary motility in rabbit airway epithelium in-vitro.

We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro. Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect. The rank order potency of macrolide was roxithromycin > erythromycin >> clarithromycin. The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin. Roxithromycin increased intracellular cAMP concentrations. These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract.

Effect of erythromycin on mucociliary transport and clinical symptoms in patients with sinobronchial syndrome

The effect of erythromycin (EM) on mucociliary transport function assessed by saccharin test and clinical symptoms were studied in 19 patients with sinobronchial syndrome (SBS). Before treatment with EM, the mean nasal clearance time (NCT) of SBS patients was 51.9 +/- 40.5 (SD) min, which was significantly (p < 0.01) longer than that of control subjects (12.4 +/- 5.3 min). After 4-week treatment with oral EM (600 mg/day), NCT of SBS patients significantly (p < 0.01) improved (29.2 +/- 34.2 min). In 11 of 19 SBS patients, bacteria from sputum culture disappeared after EM therapy. Frequency of cough and volume of sputum were significantly (p < 0.05) decreased by EM therapy. Nasal symptoms (such as nasal obstruction and rhinorrhea) were also significantly (p < 0.05) improved by EM therapy. These findings suggested that disorder of mucociliary transport function was present in patients with SBS, and EM therapy improved this function. EM clinically improved not only the lower airway symptoms, but also the nasal symptoms.

Rotation Frequency of Human Bronchial and Nasal Epithelial Spheroids as an Indicator of Mucociliary Function

Background: We evaluated a new in vitro model for mucociliary transport function. Spheroids of human respiratory epithelium show beating cilia at their surface. When cultured in their own mucus, spheroids can rotate along their axis due to coordinated ciliary beating. Objective and Methods: To assess whether this setup yields meaningful results we measured rotation frequency (RF) of human bronchial or nasal epithelial spheroids under different temperatures and concentrations of isoproterenol. Isoproterenol was administered either as caged compound releasing active isoproterenol after illumination with UV light, or through a permeable membrane in a two-chamber system. Results: Under stable conditions, RF remained constant over 200 min. Between 27 and 35°C, there was a temperature-dependent increase: RF₂₇_°_C = 0.27 ± 0.08 s^–1, and RF₃₇_°_C = 0.43 ± 0.10 s^–1 (means ± SEM). Isoproterenol (10^–5, 10^–4 and 10^–3 mmol/l) induced concentration-dependent increases in RF (9, 20 and 25%, respectively; medians) if applied in the two-chamber system. The experiments with caged isoproterenol did not yield conclusive results, probably because the byproducts from photolysis negatively affected ciliary function. The transport velocity at the surface of bronchial and nasal spheroids was estimated to be 2.96 and 3.62 mm/min (medians), respectively, which is in the same range as mucus transport velocity measured in vivo in humans. Conclusions: This setup can be used to study mucociliary transport function under controlled conditions in vitro, in particular as RF is likely to reflect not only ciliary beat frequency, but also the coordination of ciliary beating and the properties of the mucus.

Effect of Nitric Oxide and Peroxynitrite on Mucociliary Transport Function of Experimental Otitis Media

To determine the role of nitric oxide (NO) and peroxynitrite on mucociliary activity in experimental otitis media with effusion (OME). Twenty guinea pigs were divided into 1 control and 3 experimental groups; lipopolysaccharide (LPS), N(G)-nitro-L-arginine methyl ester (L-NAME), and uric acid (UA) groups. Ten ears were used in each group. OME was induced by transtympanic injection of LPS in experimental groups. Twenty-four hours after the transtympanic injection, dye transfer time (DTT) was measured and the temporal bone was taken for histopathologic examination. Expression of peroxynitrite was determined by immunohistochemical stain for 3-nitrotyrosine (3-NT). Dye transfer time was significantly delayed in LPS group compared to control group; by contrast it was significantly reduced in L-NAME or UA treated groups (P < 0.01). Histopathologic examination showed reduced inflammation and mucosal thickening in the treatment groups when compared to LPS group. These findings, however, were not statistically significant. Immunoreactivity to 3-NT was intense in LPS group and decreased in the treatment groups (P < 0.05). It is suggested that LPS induced mucociliary dysfunction in the middle ear by NO and peroxynitrite-mediated pathways.

Mucociliary Transport Function and Damage of Ciliated Epithelium

The influence of epithelial damage on mucociliary transport was studied in relation to the amount of mucus. The mucosal epithelium of mucus-depleted frog palate was dissected and mounted on a plastic plate. Mechanical damages were created on the frog mucosa by pressing a different thickness of boards (2, 3, 5, and 8 mm). Two different amounts of frog mucus (7.9 microL [small amount of mucus (S-mucus]]) and 51.0 microL [large amount of mucus [L-mucus]]) were acpplied on the frog mucosa witih and without mucosal damage. There was no difference in mucociliary transport rate (MTR) on undamaged frog mucosa between S-mucus and L-mucus. However, on the damaged mucosa, MTR of S-miucus was significantly decreased compared with that of L-mucus. Moreover, capability of mucus transportation across the mucosal damage was significantly lower in S-mucus than in L-mnucus. Results indicate that the larger the mucus amount becomes, the more the mucus travels the damaged epithelium. Moreover, MTR of L-mucus was decreased with increasing the degree of epithelial damage. This study indicates that the degree of loss of cilia is an important factor of mucociliarn deceleration.

YM-40461, a potent surfactant secretagogue, improves mucociliary clearance in SO2-exposed guinea pigs.

The effects of the new pulmonary surfactant secretagogue YM-40461, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl) urea, on tracheal mucociliary transport (MCT) were assessed using guinea pigs with acute bronchitis. Acute bronchitis was induced by SO2 gas exposure (400 ppm for 3 h). MCT velocity was measured by means of the dye gelatin technique. YM-40461 at doses of 1-10 mg/kg, p.o. induced recovery of MCT function, with an ED50 value of 2.4 mg/kg. Maximal recovery (78.0+/-12.5%) was observed 2 h in the animals treated with 10 mg/kg of YM-40461. Ambroxol and bromhexine showed less effect on the MCT dysfunction than YM-40461. An artificial surfactant (Surfacten) also aided recovery. YM-40461 at a dose of 10 mg/kg, p.o. significantly improved surfactant production without affecting mucus secretion. These results show that YM-40461 ameliorates MCT dysfunction caused by SO2 exposure by activation of pulmonary surfactant secretion.

A New, Simple Method for Measuring Mucociliary Clearance in Guinea-pigs

Airway mucociliary transport (MCT), which continuously removes inhaled particles and cellular debris from deep in the lung, is impaired in a number of diseases such as bronchitis and asthma. In order to determine the effects of candidate drugs on MCT function in the airway, a new in situ method to measure MCT function was established. MCT function is represented by the distance a gelatin solution containing Evans blue as a marker moves after injection into the trachea. The basal rate of dye transport in non-treated guinea-pigs was 4.4±0.2 mm/min. Theβ2-adrenoceptor agonist salbutamol (2, 6, 10, 20 mg/kg, po), dose-dependently accelerated the basal MCT rate. However, its effect was completely inhibited by pretreatment with the non-selectiveβ-adrenoceptor antagonist, propranolol (1 mg/kg, iv). MCT function in guinea-pigs was significantly attenuated to 2.6±0.3 mm/min by SO2gas exposure. Salbutamol failed to prevent MCT dysfunction in SO2-exposed animals at doses previously shown to accelerate basal MCT rate. This simple method is useful for estimating MCT function in several airway disease models and for examining new drugs designed to improve MCT function in airway diseases.

気管支ぜん息と気道過敏性の発症機序 薬理学的展開 気道分泌こう進と粘液線毛輸送障害

Mucociliary transport function can be determined by ciliary motility of airway epithelial cells, the amount and physicochemical properties of airway surface fluid, and the airway integrity. Mucus glycoprotein is released from submucosal glands and goblet cells in response to a variety of stimuli and, on other hand, water is secreted by airway epithelial cells through the movement of electrolytes. Marked airway goblet cell hyperplasia has been found in patients who died of severe asthma, indicating that goblet cell hypersecretion may play a significant role in the formation of mucus plugs in the respiratory tract. Goblet cell secretion is regulated by autonomic nerves and various chemical mediators associated with asthma. Antigen challenge causes an increase in mucus discharge from goblet cells in ovalbumin-sensitized animals, and this effect can be greatly inhibited by an histamine H2-receptor antagonist. Similarly, histamine released by antigen challenge stimulates airway epithelial Cl secretion and, hence, water secretion toward the airway lumen. There is ample evidence that mucociliary clearance is impaired in patients with asthma, which results in deterioration of airflow limitation. The precise mechanism for this impairment remains uncertain, but bronchospasm and the increased mucus secretion induced by peptide leukotrienes may be involved.

Effect of Chlorpheniramine on Airway Physiology and Symptoms during Natural Pollen Exposure

Previous studies have documented the changes in airway physiology which accompany natural pollen exposure. This study was designed to determine the effect of chlorpheniramine (8 mg b.i.d.) on seasonal changes in airway physiology and symptoms. Pollen counts, eustachian tube (ET) function, nasal resistance, mucociliary transport, and nasal symptoms were assessed weekly before, during, and after ragweed pollen season in 15 chlorpheniramine-treated and 15 placebo-treated allergic rhinitis (AR) subjects in a double-blind protocol and in 10 untreated control (non-AR) subjects. In placebo-treated AR subjects, the degree of congestion, rhinorrhea, sneezing, ET dysfunction, and nasal obstruction closely tracked pollen counts. However, symptoms, ET obstruction, and nasal obstruction persisted well beyond the temporal peak in pollen counts. There were no changes in mucociliary transport or pulmonary function during pollen exposure. Compared to placebo, chlorpheniramine-treated subjects manifested significantly less (p &lt; .05) seasonal sneezing and rhinorrhea, but similar degrees of nasal congestion, ET dysfunction, and nasal obstruction. Pollen-related changes in nasal physiology and symptoms were not detected in the non-AR subjects. These data document that chlorpheniramine significantly attenuated the seasonal increases in rhinorrhea and sneezing, but did not lessen the concommitant physiologic alterations or the increase in nasal congestion.

Effect of azelastine on sulphur dioxide induced impairment of ciliary motility in airway epithelium.

The effect of azelastine on airway mucociliary transport function was studied by measuring ciliary motility of human bronchial epithelium in vitro with a photoelectric method. Bronchial epithelial cells were obtained by fibreoptic bronchoscopy, mounted in a Rose chamber, and perfused with Krebs-Henseleit solution. The preparations were placed on a microscope stage equipped with an illuminator, and the variations of light intensity caused by ciliary beating were detected by a photometer. The addition of azelastine to the perfusate increased ciliary beat frequency (CBF) in a dose dependent manner without ciliary discoordination. The mean (SE) maximal increase from the baseline value and the concentration required to produce a half maximal effect were 27.0 (4.2)% and 9.2 x 10(-6) mol/l, respectively. Exposure of the cells to the perfusate containing 3 ppm sulphur dioxide rapidly decreased CBF by 59.2 (5.0)%, and was accompanied by a reduction in intracellular cyclic AMP levels from 38.1 (4.3) to 10.1 (2.4) pmol/mg protein. This effect was prevented by pretreatment of cells with azelastine in a dose dependent manner. Azelastine not only stimulates ciliary motility of airway epithelium and hence mucociliary transport function, but may also protect against sulphur dioxide induced ciliary dysfunction, probably by inhibiting intracellular cyclic AMP loss.