Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis.

BACKGROUND: Enhancing chloride (Cl- ) secretion in sinus epithelia represents a novel therapeutic approach to chronic rhinosinusitis (CRS). Herbal dry extract BNO 1011 enhances mucociliary clearance (MCC) via upregulation of Cl- secretion in sinonasal cultures in vitro and murine epithelium in vivo. The objective of this study is to evaluate whether the BNO 1011 improves MCC and clinical parameters in a rabbit model of CRS. METHODS: After the development of CRS in 30 New Zealand white rabbits, animals were randomly assigned to receive oral placebo (n = 10), BNO 1011 (low dose [LD], 25 mg/kg/daily) (n = 10), or BNO1011 (high dose [HD], 125 mg/kg/daily) (n = 10) for 4 weeks. Outcomes included sinus opacification (Kerschner's rabbit sinus CT grade), maxillary epithelial Cl- secretion (sinus potential difference [PD] assay), airway surface liquid (ASL) depth using micro-optical coherence tomography (µOCT), and submucosal gland density (SMD) on histopathology. Outcome parameters were analyzed by 2 blinded investigators. RESULTS: BNO 1011 significantly cleared sinus opacification (HD = 1.21 ± 0.63, LD = 1.26 ± 0.37,) compared to placebo (4.02 ± 0.92) (p = 0.009). BNO 1011 resulted in markedly greater mean sinus PD polarization (HD = -12.23 ± 1.4 mV, LD = -12.0 ± 3.0 mV) when compared to rabbits treated with placebo (-4.1 ± 1.1 mV) (p = 0.03). ASL depth was significantly improved when treated with HD (4.08 ± 0.06 µm) and LD (4.05 ± 0.06 µm) compared to placebo (3.5 ± 0.05 µm) (post hoc analysis, p < 0.0001). Histologically, epithelial thickness (HD = 10.0 ± 0.7 µm; LD = 13.7 ± 0.9 µm; placebo = 21.1 ± 2.3 µm; p < 0.005), subepithelial thickness (HD = 63.1 ± 6.6 µm; LD = 103.2 ± 6.7 µm; placebo = 113.3 ± 6.0 µm; p < 0.001), and SMD (HD = 22.2 ± 2.9%; LD = 31.8 ± 1.1%; placebo = 43.8 ± 1.7%; p < 0.0001) were noticeably better with the HD. CONCLUSION: Herbal dry extract BNO 1011 improves radiographic, histologic, and MCC parameters in a rabbit model of CRS.

Hypertonic Saline Versus Isotonic Saline Nasal Irrigation: Systematic Review and Meta-analysis.

Background Saline nasal lavage is one of the treatments of sinonasal diseases. Evidence from basic research favors hypertonic saline (HS) over isotonic saline (IS) for mucociliary clearance, but evidence from clinical studies is controversial. Conversely, HS may carry greater side effects. Objective To compare the effects of HS and IS nasal irrigation in treating sinonasal diseases. Methods Systematic search with Ovid MEDLINE, Scopus, PubMed, Google Scholar, and Manual additional sources was conducted. Randomized controlled trials comparing HS with IS nasal irrigation in treating any sinonasal diseases, including rhinitis and rhinosinusitis, were included. Data were pooled for meta-analyses. Outcomes were symptom scores, sinonasal outcome test (SNOT), and adverse events. Heterogeneity was explored by subgroup analyses. Results Nine studies (740 patients) were included. HS nasal irrigation brought greater benefits over IS in symptom reduction (standardized mean difference (SMD) -0.58; 95% confidence interval [CI]: -0.76, -0.40); however, no difference was shown in SNOT-20 improvement (mean difference 1.81; 95% CI: -0.68, 4.30). In subgroup analyses, effects favoring HS on symptoms were larger in 4 subgroups. These were (1) patients with rhinitis (SMD -1.09; 95% CI: -1.42, -0.76) compared with rhinosinusitis (SMD -0.37; 95% CI: -0.58, -0.15), P < .01; (2) patients under the age of 18 years (SMD -1.22; 95% CI: -1.53, -0.91) compared with patients over the age of 18 years (SMD -0.26; 95% CI: -0.49, -0.04), P < .01; (3) saline irrigation using high volume (SMD -0.89; 95% CI: -1.18, -0.60) compared with low volume (SMD -0.39; 95% CI: -0.62, -0.16), P < .01; and (4) saline irrigation with hypertonicity of <3% (SMD -1.09; 95% CI: -1.42, -0.76) and hypertonicity of 3%-5% (SMD -1.20; 95% CI: -1.61, -0.78) compared with hypertonicity of >5% (SMD 0.20; 95% CI: -0.15, 0.55), P < .01. Buffered saline and operative status did not have impact. HS brought greater minor adverse effects. No major adverse effects were reported. Conclusion HS improves symptoms over IS nasal irrigation in treating sinonasal diseases. There is no difference in disease-specific quality of life. However, HS brings greater minor side effects than IS.

Does Heating up Saline for Nasal Irrigation Improve Mucociliary Function in Chronic Rhinosinusitis?

Background Mucociliary function is affected by temperature. Exposure to cold air may impair ciliary beat frequency. While saline nasal irrigation improves in ciliary beat activity, there is no evidence supporting the use of heated saline irrigation in treating patients with chronic rhinosinusitis. Objective To compare the effects of heated saline to room-temperature saline nasal irrigation on mucociliary clearance in chronic rhinosinusitis patients. Methods Adult patients with chronic rhinosinusitis were randomized into two groups receiving either heated saline or room-temperature saline nasal irrigation. Healthy subjects were included as control. Saccharin transit time was measured before and after nasal irrigation. Nasal patency was assessed by peak nasal inspiratory flow, anterior rhinomanometry, acoustic rhinometry, nasal obstruction score, and breathe-comfort score. Any adverse events were reported. Results Twenty-three patients with chronic rhinosinusitis and nine healthy subjects were enrolled. Saccharin transit time was decreased after nasal irrigation in both heated saline subgroup (baseline 12.3 ± 4.5 min vs. postirrigation 8.4 ± 4.9 min, p = 0.05) and room-temperature subgroup (baseline 12.8 ± 5.0 min vs. postirrigation 8.9 ± 4.2 min, p = 0.01). The saccharin transit time improvement was not different between heated saline (3.8 ± 6.2 min) and room-temperature saline (3.8 ± 4.0 min), p = 0.13. Postheated saline irrigation saccharin transit time of chronic rhinosinusitis patients (8.4 ± 4.9 min) was not different to healthy subjects (9.2 ± 3.7 min), p = 0.69. Nasal patency was not different between groups. There was no adverse event reported. Conclusion Nasal saline irrigation is beneficial to patients with chronic rhinosinusitis on mucociliary improvement. Warming saline is not necessary and adds no additional benefit to room-temperature saline irrigation.

Therapeutic effect of hyaluronic acid in reducing nasal mucosa recovery time after septoplasty.

Mucociliary clearance represents a host defense mechanism of airways that can be compromised by various pathologic conditions, such as nasal septal deviation. Although septoplasty can resolve obstruction, it impairs mucociliary clearance in the immediate postoperative period. Clinical studies have demonstrated how hyaluronic acid can interfere with this function. Our study aims to provide evidence of a therapeutic effect of hyaluronic acid on nasal mucosa recovery after septoplasy. Sixty-five patients underwent septoplasty. On postoperative day 1, patients were randomized to a control arm that was treated with mupirocin ointment or an experimental arm that received additional treatment with sodium hyaluronate solution. Pre- and postoperatively, anterior rhinoscopy was performed to analyze mucosal status, and mucociliary clearance was measured by using the saccharin transit time (STT) method. The t test was used for independent groups. During the preoperative evaluation, we observed a significant difference in STT between the convex and concave side in both groups. Fifteen days after surgery, we observed a significant difference preoperatively to postoperatively for both the convex and the concave side (p < 0.02 and p < 0.008, respectively). One month after surgery, we observed a reduction of STT when comparing preoperative control group values and, after 1 month, postoperative values in both sides (p < 0.015 and p < 0.005, convex and concave side, respectively). Our results show a significant reduction of the STT for both nasal sides as soon as 15 days after septoplasty in patients randomized to additional treatment. Our experience provides further evidence for the therapeutic effect of hyaluronic acid in accelerating nasal mucosa recovery after septoplasty.

Nasal rinsing with an atomized spray improves mucociliary clearance and clinical symptoms during peak grass pollen season.

BACKGROUND: Nasal rinsing with an atomizer spray was found to be effective in the treatment of allergic rhinitis. Two parameters express the nasal functions: (1) mucociliary clearance (MCC), and (2) the pH and its stability. MCC is the main factor that defines the time of pollen transition on the nasal mucosa and, therefore, the amount of the allergen glycoprotein elution. OBJECTIVE: We hypothesized that the nasal wash efficacy could be due to the reduction of contact time of the grass pollen on the nasal mucosa (improving MCC). METHODS: Forty patients with seasonal grass pollen oculorhinitis were randomized in two groups: 20 received three times daily nasal rinsing with hypertonic solution buffered to pH 6.1, before and during the peak pollen season in 2015 (active group), and another 20 patients were allocated to the control group and received no nasal treatment. The daily symptoms score and the use of oral antihistamines when required were evaluated during the grass pollen peak season. All the patients completed the study. RESULTS: In comparison with the control group, in the active group, a significant decrease of both nasal symptoms (p = 0.01) and consumption of antihistamines (p = 0.035) was found. Furthermore, the MCC was significantly worse (p = 0.011) only in the control group. CONCLUSION: The nasal treatment maintained the efficiency of the MCC in the patients in the active group, who showed a significant reduction of symptoms and medication score. The MCC decreased the transit time of the pollen on the nasal mucosa, which favored an elution of the allergenic proteins.

Pharmacological strategies to reduce exacerbation risk in COPD: a narrative review.

Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge. Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype. Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype. Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting ß2-agonist (LABA). For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype. Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents. For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered. In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.

Sinupret activates CFTR and TMEM16A-dependent transepithelial chloride transport and improves indicators of mucociliary clearance.

INTRODUCTION: We have previously demonstrated that Sinupret, an established treatment prescribed widely in Europe for respiratory ailments including rhinosinusitis, promotes transepithelial chloride (Cl-) secretion in vitro and in vivo. The present study was designed to evaluate other indicators of mucociliary clearance (MCC) including ciliary beat frequency (CBF) and airway surface liquid (ASL) depth, but also investigate the mechanisms that underlie activity of this bioflavonoid. METHODS: Primary murine nasal septal epithelial (MNSE) [wild type (WT) and transgenic CFTR(-/-)], human sinonasal epithelial (HSNE), WT CFTR-expressing CFBE and TMEM16A-expressing HEK cultures were utilized for the present experiments. CBF and ASL depth measurements were performed. Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers, Fura-2 intracellular calcium [Ca(2+)]i imaging, cAMP signaling, regulatory domain (R-D) phosphorylation of CFTR, and excised inside out and whole cell patch clamp analysis. RESULTS: Sinupret-mediated Cl- secretion [ΔISC(µA/cm(2))] was pronounced in WT MNSE (20.7+/-0.9 vs. 5.6+/-0.9(control), p<0.05), CFTR(-/-) MNSE (10.1+/-1.0 vs. 0.9+/-0.3(control), p<0.05) and HSNE (20.7+/-0.3 vs. 6.4+/-0.9(control), p<0.05). The formulation activated Ca(2+) signaling and TMEM16A channels, but also increased CFTR channel open probability (Po) without stimulating PKA-dependent pathways responsible for phosphorylation of the CFTR R-domain and resultant Cl- secretion. Sinupret also enhanced CBF and ASL depth. CONCLUSION: Sinupret stimulates CBF, promotes transepithelial Cl- secretion, and increases ASL depth in a manner likely to enhance MCC. Our findings suggest that direct stimulation of CFTR, together with activation of Ca(2+)-dependent TMEM16A secretion account for the majority of anion transport attributable to Sinupret. These studies provide further rationale for using robust Cl- secretagogue based therapies as an emerging treatment modality for common respiratory diseases of MCC including acute and chronic bronchitis and CRS.

In vitro studies of a distillate of rectified essential oils on sinonasal components of mucociliary clearance.

BACKGROUND: Herbal remedies predate written history and continue to be used frequently for many common ailments. The essential oil mixture standardized is a phytopharmaceutical with a distillate of a mixture of rectified essential oils of eucalyptus, sweet orange, myrtle, and lemon as active ingredients used to treat respiratory diseases such as bronchitis and rhinosinusitis. We evaluated the pharmacologic effects of a distillate of rectified essential oils standardized on primary human upper respiratory epithelial cultures specifically addressing electrolyte transport, cilia beat frequency (CBF), airway surface liquid (ASL) hydration, and mucus transport velocity. METHODS: Well-differentiated primary human sinonasal epithelial cultures grown at an air-liquid interface were treated on the apical or basolateral surface with varying concentrations of a distillate of rectified essential oils standardized. Changes in CBF were determined using the Sissons-Ammons Video Analysis system while changes in chloride flux were determined using the fluorescent dye 6-methoxy-N-(3-sulfopropyl)quinolinium. ASL hydration was quantified using Texas red dextran and mucociliary transport velocity was measured using fluorescent microspheres and time lapse photography. RESULTS: When applied to the basolateral surface, a distillate of rectified essential oils standardized activated chloride efflux and ciliary beat in a dose-dependent fashion, increasing ASL height and accelerating mucociliary transport velocity. The ancillary apical application of a distillate of rectified essential oils standardized had minimal effects on the CBF. CONCLUSION: Basolateral application of a distillate of rectified essential oils standardized stimulates both chloride efflux and cilia beat frequency resulting in a synergistic effect dramatically augmenting mucociliary transport velocity. These in vitro data support the clinical efficacy of this phytopharmaceutical in respiratory inflammatory disorders.

A double-blind randomized controlled trial of normal saline, lactated Ringer's, and hypertonic saline nasal irrigation solution after endoscopic sinus surgery.

BACKGROUND: Nasal douching is commonly performed after endoscopic sinus surgery (ESS). There is a lack of studies comparing the clinical effect of various douching solutions after ESS. This study investigated the clinical effects of normal saline, lactated Ringer's, and hypertonic saline nasal douching solutions after ESS. METHODS: Adult patients (41.8 ± 12.9 years) undergoing bilateral ESS for chronic rhinosinusitis at a single tertiary referral center were blindly randomized to one of the three study solutions and reviewed on postoperative weeks 1, 3, and 6. The 20-item Sino-Nasal Outcome Test (SNOT-20) scores, visual analog scale (VAS) symptom scores, digital video capture of the sinus cavities, and mucociliary clearance (MCC) times were performed at each visit. The mucosa appearances were scored by a second investigator, blinded to the douching solution. RESULTS: Seventy-four patients were recruited. All groups showed an improvement with treatment in SNOT-20 scores and VAS scores, as well as endoscopic evaluation of mucosa appearance over time. There was no improvement of MCC during the treatment period. Irrigation with lactated Ringer's solution resulted in better symptom scores in SNOT-20 (p < 0.05) and VAS (p < 0.05), compared with irrigation with normal saline or hypertonic saline solutions. Patients receiving hypertonic saline solutions had less polypoidal mucosa at week 6. CONCLUSION: Douching with lactated Ringer's solution after ESS results in better improvement in sinonasal symptoms, compared with normal saline or hypertonic saline solutions.

Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.

BACKGROUND: Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis. OBJECTIVES: To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: 13 June 2013.We also conducted a PubMed search on 26 February 2013 for relevant published articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently assessed trials for inclusion, analysed risk of bias and extracted data. MAIN RESULTS: Searches identified 23 trials; nine trials (255 participants) are included, of these seven trials are more than 10 years old. Three trials of nebulized thiol derivatives were identified (one compared 20% N-acetylcysteine to 2% N-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Six trials of oral thiol derivatives were identified. Three trials compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and placebo; one compared carbocysteine to ambroxol; and one compared low and high-dose N-acetylcysteine. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. AUTHORS' CONCLUSIONS: We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.

Comparison of buffered and nonbuffered nasal saline irrigations in treating allergic rhinitis.

OBJECTIVES/HYPOTHESIS: We aimed to study the effect of alkalinity of isotonic nasal saline irrigation on nasal symptoms, mucociliary clearance, nasal patency, and patient's preference in patients with allergic rhinitis (AR). STUDY DESIGN: A double-blind, randomized, three-arm crossover study. METHODS: Patients with AR were enrolled. Three kinds of isotonic nasal saline irrigations: nonbuffered (pH 6.2-6.4), buffered with mild alkalinity (pH 7.2-7.4), and buffered with alkalinity (pH 8.2-8.4) were given one at a time, in different orders. Patients rinsed their nose with 240 ml of one solution twice daily for 10 days and then swapped to the others. The washout period was at least 5 days. Primary outcomes were nasal symptoms, mucociliary clearance time, and nasal patency. Outcomes were compared between baseline and posttreatment and also between various kinds of solution. Secondary outcomes were patients' preference and adverse events. RESULTS: Thirty-six subjects entered the study, and there were no dropouts. Overall nasal symptom was significantly improved from baseline (P = 0.03) only by buffered solution with mild alkalinity. Sneezing was significantly improved from baseline (P = 0.04) only by buffered solution with alkalinity. No other significant improvements were achieved by any solution. When comparing between the three nasal irrigations, there were no differences in all parameters. The patients significantly preferred the buffered solution with mild alkalinity (P = 0.02). CONCLUSIONS: Buffered isotonic saline with some degree of alkalinity may improve nasal symptoms. Isotonic saline irrigations, regardless of alkalinity, may not improve mucociliary function and nasal patency. Buffered isotonic saline with mild alkalinity is the most preferred.

The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures.

BACKGROUND: Herbal remedies predate written history and continue to be used more frequently than conventional pharmaceutical medications. The novel dry extract BNO 1011 is based on a combination of five herbs that is used to treat acute and chronic rhinosinusitis. We evaluated the pharmacologic effects of the novel dry extract BNO 1011 on human respiratory epithelial cultures specifically addressing electrolyte transport and cilia beat frequency (CBF). METHODS: Well-differentiated human bronchial epithelial cultures grown at an air-liquid interface were treated on the apical or basolateral surface with varying concentrations of dry extract BNO 1011. Changes in transepithelial sodium and chloride transport were determined in Ussing chambers under voltage-clamped conditions. Changes in CBF were determined using the Sissons-Ammons Video Analysis system (Ammons Engineering, Mt. Morris, MI). RESULTS: When applied to the apical surface, dry extract BNO 1011 activated forskolin-stimulated chloride secretion and ciliary beat in a dose-dependent fashion. Basolateral application of dry extract BNO 1011 did not alter the measured physiological properties. CONCLUSION: Apical application of dry extract BNO 1011 stimulates both chloride secretion and CBF and therefore may augment mucociliary clearance.

Effect of myrtol standardized and other substances on the respiratory tract: ciliary beat frequency and mucociliary clearance as parameters.

INTRODUCTION: Myrtol standardized is a phytomedicine obtained by distillation, consisting of many constituents. In vitro and in vivo, the major monterpenes, d-limonene, 1,8-cineole, and alpha-pinene, are used as biological marker substances. Myrtol standardized has secretolytic, secretomotor, and mucolytic effects in addition to anti-inflammatory and antioxidative actions. The aim of the study was to investigate the effects of different concentrations of Myrtol standardized on in vivo mucociliary clearance in mice and the ciliary beat frequency (CBF) in rat tracheal rings. METHODS: Data regarding the effects of 1,8-cineole and N-acetylcysteine (NAC) were compared. Salbutamol was used as a positive control. CBF was measured using rat tracheal explants and a high-speed video camera linked to a microscope with specific software equipment. Mucociliary clearance was determined using the microdialysis technique, which measured the acceleration of a fluorescent sample in the trachea in vivo. RESULTS: Myrtol standardized accelerated both CBF and mucociliary transport in a concentration-dependent manner. Significant effects were seen at a concentration of 0.01% Myrtol regarding CBF (P<0.01) and 17.1 mg/kg body weight regarding mucociliary clearance experiments (P<0.05) according to doses relevant to humans. The 1,8-cineole dosage relative to humans only accelerated the mucociliary clearance in vivo without having an effect on the CBF. Extremely high doses of Myrtol were not able to additionally increase the CBF effect in comparison to salbutamol. Compared to NAC, also used in a dosage relative to humans, Myrtol standardized showed a tendency to be more effective. CONCLUSION: In summary, the present data suggest that Myrtol standardized is a pharmacologically important drug which, when used at a dose relative to humans, shows positive effects on both measured parameters, CBF and mucociliary clearance, in vivo.

Effect of silymarin and harpagoside on inflammation reaction of BEAS-2B cells, on ciliary beat frequency (CBF) of trachea explants and on mucociliary clearance (MCC).

Silymarin and harpagoside are derived from drugs which are used for their protective effects against hepatotoxicity and inflammatory processes. Both are now investigated with respect to the respiratory tract. They were able to reduce the release of the inflammatory cytokine RANTES (regulated on activation, normal T cells expressed and secreted) from BEAS-2B cells in a concentration-dependent manner when stimulated by a cytokine mix (10 ng/mL of TNF- α and IFN- γ). This effect was not due to a possible toxic effect (control experiments using LDH release as a marker). Silymarin but not harpagoside was able to increase ciliary beat frequency. Effects were comparable to positive controls (isoprenaline and salbutamol). Silymarin also increases mucociliary clearance. In conclusion, silymarin should be further investigated for its clinical use in distinct respiratory diseases.

Surfactant protein D modulates pulmonary clearance of pollen starch granules.

Pollen starch granules (PSGs) are allergen particles that get into contact with pulmonary surfactant and phagocytes in the terminal airways. In this study, the effects of surfactant protein D (SP-D) on the interaction of PSGs with phagocytes and on the pulmonary clearance of PSGs were determined. Fluorescently labeled PSGs were incubated in vitro with murine lung macrophages or dendritic cells (DCs) ± recombinant rat SP-D (rrSP-D). In addition, the effect of SP-D on uptake of PSGs by lung macrophages and DCs was studied in vivo. Furthermore, PSGs were instilled in Balb/c mice and the effects of SP-D on total lung clearance were assessed by optical imaging. SP-D treatment increased the number of PSG-positive macrophages and DCs in vitro. Furthermore, SP-D accelerated uptake/binding by alveolar macrophages and reduced the number of PSG-positive tissue macrophages and DCs at 24 hours. However, SP-D did not affect total lung clearance of PSGs and it did not enhance the T-cell proliferation induced by PSG-positive DCs. In conclusion, SP-D increased PSG-positive cells in vitro and accelerated PSG binding/uptake in vivo. The observed effects were limited to cellular clearance mechanisms and did not affect the total clearance of PSGs from the lung.

Impact of thymol in thyme extracts on their antispasmodic action and ciliary clearance.

Thyme is a herb with broncholytic und secretomotoric effects. Its activity on beta (2) receptors as a possible mechanism of action was demonstrated. Major components are thymol and carvacrol which are claimed to be responsible for its effects and, therefore, used for standardization in the German pharmacopoeia (0.03 % phenols calculated as thymol). Our aim was to investigate the impact of thymol by using thyme extracts with either normal or extremely low thymol concentrations (< 0.005 % or > 0.038 %). The antispasmodic effect on smooth muscles of the trachea and the ileum and the effect on ciliary activity (respiratory clearance) were investigated. In addition, pure thymol and carvacrol were investigated separately and in spiking experiments. Thymol and carvacrol had a concentration-dependent antispasmodic effect in the rat trachea either being stimulated by acetylcholine, K (+) or Ba (++). The same result was observed with respect to the increase of mucociliary transport in mice. Extracts with very low thymol contents are effective in all models used except acetylcholine-induced rat ileum contraction. When thyme extracts with normal thymol contents or with very low thymol contents were compared, the extract with normal thymol contents was more effective, both as a relaxant (rat ileum) and as an antispasmodic compound (rat trachea contraction induced by either acetylcholine, Ba (++) or K (+)) and in ciliary transport experiments. Thyme extracts with very low thymol contents (practically free of volatile oil) were equally effective with respect to endothelin effects. When an extract with very low thymol contents is spiked with increasing concentrations of thymol, a concentration-dependent increase concerning the antispasmodic effect (Ba (++)-induced trachea contraction) is observed. In conclusion, the data show that in various models of antispasmodic effect (ileum and trachea) and by measuring ciliary activity, thymol (and carvacrol) is (are) active, although other not identified components of thyme extract appear to be very important as well, since extracts with very low thymol contents are active. On the basis of these results the standardization on thymol alone appears not to be justified.

The effect of myrtol standardized on human nasal ciliary beat frequency and mucociliary transport time.

BACKGROUND: This study was designed to observe the effects of myrtol standardized (Gelomyrtol forte), a secretomucolytic phytomedicine, on both ciliary beat frequency (CBF) in vitro and mucociliary transport time (MTT) in vivo. METHODS: Changes in cultured human nasal CBF in response to immediate treatment with 75, 150, or 300 ng/mL of myrtol standardized and prolonged treatment (12 or 24 hours) with 300 ng/mL of myrtol standardized were quantified by using high-speed digital microscopy. In addition, MTT before and after oral application of myrtol standardized (three times a day, 900 mg/day, 10 days) was determined using the saccharine test, and the effects of this treatment regime on nasal patency was measured by acoustic rhinometry and active anterior rhinomanometry in 22 patients with nonallergic chronic rhinitis. Another 10 patients without medication, who had the same examinations twice with a 10-day interval, were involved as controls. RESULTS: Neither immediate nor prolonged treatment with myrtol standardized produced a distinguishable change in CBF. Meanwhile, only in patients with treatment, MTT, as well as a unilateral minimum cross-sectional area, the volume of 0-5 cm inside the nasal cavity, the unilateral nasal resistance at 75 Pa and total symptom visual analog score were significantly improved after treatment. CONCLUSION: Based on these results we propose that a 10-day treatment with an herbal medicine, myrtol standardized, improves nasal mucociliary clearance as well as nasal patency in patients with chronic rhinitis. However, it has no impact on ex vivo CBF.