Role of CD23 Activated ERK Signaling Pathway in the Pathogenesis of Eosinophilic Chronic Sinusitis with Nasal Polyps.

Objective: In the context of the rising prevalence of eosinophilic chronic sinusitis accompanied by nasal polyps, this study aims toinvestigate the role of CD23 in the pathogenesis of eosinophilic chronic sinusitis with nasal polyps. Methods: The cross-sectional study was conducted, 75 patients with chronic sinusitis and nasal polyps treated in our hospital from January 2019 to May 2021 were selected, including 40 cases of eosinophilic patients with the average age of 29.92 years and 35 cases of non-eosinophilic patients with the average age of 30.05 years and 30 patients with the average age of 30.14 years who underwent skull base benign tumor resection in our hospital were selected as the control group, the expression of CD23 in polyp tissue was detected by immunohistochemistry, and the expression of CD23, p-ERK and CCL20 in polyp tissue were detected by Western blot. Specifically, tissue samples were processed and subjected to staining using specific antibodies targeting CD23. The stained sections were then visualized under a microscope to determine the expression levels of CD23. CD23, p-ERK, and CCL20 expressions in polyp tissue were evaluated via Western blot. Total protein was extracted, separated on a gel, transferred to a membrane, and probed with specific antibodies. Chemiluminescence allowed visualization and quantification of protein expressions. Results: Immunohistochemistry showed that CD23 expression was high in the eosinophilic group but low in the non-eosinophilic and control groups. The relative expression levels of CD23 protein, p-ERK protein, and CCL20 protein in polyp tissue s of the eosinophilic group were (0.892 ± 0.092), (0.733 ± 0.101) and (0.813 ± 0.106), respectively, which were significantly higher than those in non-eosinophilic group and control group (P < .05). The relative expression levels of CD23 protein, p-ERK protein, and CCL20 protein in the non-eosinophilic group were (0.461 ± 0.087), 0.412 ± 0.096) and (0.424 ± 0.098), which were significantly higher than those in the control group (P < .05). The relative expression level of CD23 protein in the eosinophilic group was positively correlated with the relative expression levels of p-ERK protein and CCL20 protein (P < .05). The Lund-Kennedy score in the eosinophilic group was (6.10 ± 1.01), which was significantly higher than that in the non-eosinophilic group (P < .05). The relative expression level of CD23 protein in the eosinophilic group was positively correlated with Lund-Kennedy score (P < .05). Conclusion: Eosinophilic chronic sinusitis with nasal polyp mucosal tissue CD23 expression is up-regulated, which is positively correlated with the ERK signaling pathway and disease severity. This study provides valuable insights into potential therapeutic targets that could be explored to develop future treatment modalities. The potential clinical significance of the study is to reveal the important role of CD23 in the pathogenesis of chronic sinusitis with nasal polyps. The upward adjustment of CD23 is positively related to the severity of the disease, which provides valuable guidance for future treatment strategies. This discovery may provide new ways for the development of CD23 treatment methods, so as to better control the progress of the disease of eosinophilic chronic sinusitis with nasal polyps. Further research can explore the molecular mechanism of CD23 regulation, further verify the feasibility of CD23 as the treatment target, and evaluate the potential value of CD23 as a prognostic logo.

Topical Vitamin D May Modulate Human Sinonasal Mucosal Responses to House Dust Mite Antigen.

BACKGROUND: Respiratory epithelium is a key defense against inhaled pathogens. Vitamin D3 (VD) has been suggested to modulate airway inflammation; however, its effect on innate airway defenses, the physical barrier, mucociliary apparatus, and cytokine release remains unclear. OBJECTIVE: To investigate the outcomes of VD application prior to challenge in an in vitro model of human sinonasal epithelium, through assessment of epithelial transepithelial resistance (TER), cilia beat frequency (CBF), and interleukin (IL)-6 release, and secondarily to determine whether topical VD is beneficial to patients with inflammatory sinonasal pathology. METHODS: Primary human sinonasal epithelial cells from patients with eosinophilic chronic rhinosinusitis (eCRS) and healthy controls were cultured in air-liquid interface (ALI). Well-differentiated cultures from each patient were pretreated for 24 hours with 4 different VD doses. Toxicity was quantified at 24 hours in unchallenged ALI by lactate dehydrogenase (LDH) assay. Innate responses were assessed by measuring TER and CBF before and up to 24 hours after house dust mite Dermatophagoides pteronyssinus challenge. IL-6 release was evaluated 24-hour postchallenge. RESULTS: Fifteen patients (53 ± 13.5 years, 60% females, 53% eCRS) representing 120 ALI wells were assessed. VD (0, 25, 50, 150 IU/mL) released less LDH than vehicle, indicating noncytotoxicity (0.15 ± 0.02; 0.15 ± 0.00; 0.14 ± 0.02; 0.11 ± 0.01 vs 0.17 ± 0.03, P = .004). VD increased TER for eCRS wells at 5 minutes (50 IU/mL: Δ6.76 ± 3.93 vs Δ3.87 ± 2.46, P = .04) and 24 hours (50 IU/mL: Δ0.88 ± 0.49 vs Δ0.40 ± 0.42, P = .02; 150 IU/mL: Δ1.06 ± 0.58 vs Δ0.47 ± 0.46, P = .01). CBF increased at 1 hour for eCRS wells (50 IU/mL: Δ0.62 ± 0.14 vs Δ0.41 ± 0.13, P = .001; 150 IU/ml: Δ0.60 ± 0.13 vs Δ0.38 ± 0.11, P < .001). IL-6 release was similar between normal and eCRS wells. CONCLUSION: Topical VD supplementation in eCRS patients may be beneficial for innate epithelial defenses. VD is noncytotoxic and does not adversely affect the physical barrier, mucociliary apparatus, or IL-6 release. Further studies should clarify its potential as a therapeutic agent.

Ethno-medicinal study of Artemisia ordosica Krasch. (traditional Chinese/Mongolian medicine) extracts for the treatment of allergic rhinitis and nasosinusitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

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.

New case of concha bullosa from Bronze Age Iberia (Granada, Spain).

OBJECTIVE: This study aims to expand knowledge of Concha bullosa in a prehistoric population. MATERIALS: The skull of an adult female from the Bronze Age archeological site ofCastellón Alto (Granada, Spain), dated between 1900 and 1600 BCE. METHODS: The diagnosis of middle turbinateconcha bullosa was based on macroscopic, radiographic, and computed tomography studies. RESULTS: This is one of the oldest findings ofconcha bullosa in Europe. Despite the possible obstruction of the osteomeatal complex by the concha bullosa in this individual, no signs of sinusitis were observed in maxillary sinuses. CONCLUSIONS: The maxillary sinuses of this female showed no signs of sinusitis related to theconcha bullosa. SIGNIFICANCE: This study provides new evidence on the chronological limits of this condition. The particular funeral rites of these populations have preserved the majority of skeletons at this site in an excellent condition. LIMITATIONS: The identification ofconcha bullosa continues to be rare in ancient populations, in part due to the poor preservation of nasal bones in archeological collections. Suggestions for further research: Detailed study of the nasal cavity of adequately preserved individuals can be expected to identify further cases of concha bullosa in ancient populations.

Anti-inflammatory effect of bee venom in an allergic chronic rhinosinusitis mouse model.

Bee venom (BV) has long been used as anti-inflammatory agent in traditional oriental medicine; however, the effect of BV on chronic rhinosinusitis (CRS) is not commonly studied. The aim of the present study was to determine the anti-inflammatory effect of BV on an allergic CRS mouse model. An allergic CRS mouse model was established following the administration of ovalbumin with Staphylococcus aureus enterotoxin B (SEB) into the nose. A total of 0.5 or 5 ng/ml of BV were intranasally applied 3 times a week for 8 weeks. Histopathological alterations were observed using hematoxylin and eosin, and Periodic acid Schiff staining. The levels of inflammatory cell infiltration, interleukin (IL)­4, IL­10 and interferon (INF)­Î³ in nasal lavage fluid (NLF) were measured. Nuclear factor (NF)­κB and activator protein (AP)­1 expressions were also determined by immunohistochemical staining. The group treated with BV had significantly decreased inflammatory cell infiltration and PAS­positive cells. The levels of INF­Î³, and neutrophil and eosinophil counts in NLF were significantly decreased, and the SEB­induced NF­κB and AP­1 expressions in mouse nasal mucosa were significantly suppressed by 0.5 and 5 ng/ml BV. Thus, BV exerted significant anti­inflammatory effects in an allergic CRS mouse model and may have potential value for the treatment of CRS.

A systematic review of randomized controlled trials with herbal medicine on chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common disease with evidence to show that its incidence and prevalence are increasing. Medicinal plants are commonly used to treat CRS. This systematic review aimed to assess the effectiveness and safety of herbal preparations for treatment of the patients with CRS. Cochran, Embase, ISI, PubMed, and Scopus databases were searched until August 1, 2016. Only randomized controlled trials were included. Four randomized controlled trials were included in this systematic review. Various medicinal plants were studied in each article. Inclusion and exclusion criteria, and outcome measures varied among different articles. The results of this trials showed that this special medicinal plants may be effective in the treatment of CRS. No serious reactions were reported during the administration of herbal remedies in the 4 studies. However, trials with a well-designed approach are needed to study the actual safety and efficacy of herbs in the treatment of CRS.

Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism.

RATIONALE: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). METHODS: Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. RESULTS: Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. CONCLUSIONS: VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

Nasal nitric oxide in unilateral sinus disease.

Unilateral sinus disease (USD) can sometimes be difficult to accurately diagnose before surgery. The application of nasal nitric oxide (nNO) for USD diagnosis and its surgical outcome in USD has not been reported in the literature. We prospectively enrolled sixty-six USD patients who underwent endoscopic sinus surgery for fungal rhinosinusitis (n = 19), chronic rhinosinusitis (CRS) without nasal polyps (n = 13), CRS with nasal polyps (n = 12) and sinonasal mass lesions (n = 22). nNO levels were measured preoperatively and at three and six months postoperatively. Correlations between nNO levels and potential clinical parameters, type of disease, disease severity, and disease-related quality of life (QOL) were assessed. Unlike bilateral CRS, in USD, nNO levels did not correlate with disease severity or postoperative QOL improvements. Except for fungus group, there were no differences in nNO levels between lesion and non-lesion sides in all the other groups. nNO levels on both sides were significantly elevated six months postoperatively in all groups. Fungal rhinosinusitis patients had the lowest preoperative nNO levels, and a cutoff of 239.3 ppb had the best sensitivity (79.0%) and specificity (87.2%) for preoperative diagnosis. While preoperative nNO levels cannot serve as an alternative marker for disease severity of USD, they were lower in fungal rhinosinusitis patients than in other USD patients and may be useful for more accurate diagnosis prior to surgery.

Prevalence of Sinusitis Detected by Magnetic Resonance Imaging in Subjects with Dementia or Alzheimer's Disease.

BACKGROUND: It has been reported that periodontitis is associated with Alzheimer's disease. However, the association between paranasal sinusitis and Alzheimer's disease has not been studied, although olfactory dysfunction frequently precedes the progress of dementia or Alzheimer's disease. METHODS: We studied 783 patients (283 men, 500 women; mean age 77.0 ± 7.9 years) who visited the Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, and 2139 control subjects who participated in a population-based study conducted by the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA) in Japan. Sinusitis was evaluated using magnetic resonance imaging (MRI) according to the Lund-Mackay scoring system. A sinusitis score of ≥ 4 was classified as positive and a score of ≤ 3 was classified as negative. RESULTS: The prevalence of positive sinusitis was 6.3% in patients with a mini-mental state examination (MMSE) score of < 24 (n = 507), and 5.7% in patients with Alzheimer's disease (n = 280). The rate of positive sinusitis was7.2% in the control group. The prevalence of sinusitis was not significantly different between normal controls and patients with dementia or Alzheimer's disease after adjustments for age and sex. The rate of positive sinusitis was higher in male than in female subjects in both groups. CONCLUSION: The prevalence of sinusitis in patients with Alzheimer's disease or dementia was not higher than in the general population.

Vitamin D decreases the secretion of eotaxin and RANTES in nasal polyp fibroblasts derived from Taiwanese patients with chronic rhinosinusitis with nasal polyps.

Eosinophils are important inflammatory cells involved in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Vitamin D and its derivatives, in addition to their classic role as regulators of electrolytes homeostasis, have modulatory effects in immunological and inflammatory responses. Such properties suggest that vitamin D might also play a role in inflammatory airway diseases such as CRSwNP. In this study, we investigated the effect of vitamin D derivatives (calcitriol and tacalcitol) on the secretion of eotaxin and Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES), the two major eosinophil chemoattractants, in fibroblasts derived from the polyps of Taiwanese CRSwNP patients. Patients diagnosed with eosinophilic CRSwNP but without malignancies or asthma and undergoing elective endoscopic sinus surgery were recruited. Three primary fibroblast cultures were established using the polyp specimens obtained from these patients. The third to eighth passages of the fibroblasts were used for in vitro studies. Nasal polyp-derived fibroblasts were stimulated with IL-1ß (10 ng/mL) for 24 hours, followed by replacement with media alone or with calcitriol or tacalcitol (10 µM) and incubation for another 24 hours. After the treatments, the levels of secreted eotaxin and RANTES were evaluated by ELISA assays. The results showed that IL-1ß could substantially stimulate the secretion of eotaxin (p < 0.01) and RANTES (p < 0.01) in nasal polyp-derived fibroblasts. More importantly, this stimulatory effect was significantly suppressed by adding calcitriol (p ≤ 0.002 for eotaxin and p ≤ 0.008 for RANTES) or tacalcitol (p ≤ 0.009 for eotaxin and p ≤ 0.02 for RANTES). Therefore, the inhibitory effect of vitamin D derivatives on eotaxin and RANTES secretion might shed light not only on the disease mechanism, but also on the potential use of vitamin D in pharmacotherapy of Taiwanese patients with CRSwNP.

Nasal congestion in infants and children: a literature review on efficacy and safety of non-pharmacological treatments.

The most common causes of nasal obstruction and runny nose in infants and children are infections, mainly of viral origin, or allergies. In neonates and infants viral upper respiratory tract infections (URTI) are frequently observed during episodes of nasal obstruction. Saline irrigation of the nose is believed to alleviate URTI symptoms by helping to eliminate excess mucus, to reduce congestion and by contributing to improve breathing. Objective of the study was to review the efficacy and safety of non-pharmacological options for the treatment of nasal congestion and its sequelae, in infants and children, with a special focus on hypertonic and isotonic solutions and other medical devices, including nasal aspirators. Available data indicate that nasal symptoms in children with allergic rhinitis or acute sinusitis significantly improved following nasal saline irrigation. The use of medical devices is less documented. Nasal aspiration with a medical device, associated with an isotonic saline solution, during viral rhinitis, has been shown to lower the risk of developing acute otitis media and rhinosinusitis, in comparison with a group treated with physiological saline solution alone. Safety and tolerability have been evaluated and no serious adverse events have been reported. Literature data highlighted the good tolerability. The use of isotonic and hypertonic saline solutions to relief nasal congestion in infants and children is widespread; it is a safe and valuable therapeutic support, and can reduce the use of medications (antihistamines, decongestant, antibiotics, corticosteroids) during the treatment of URTIs.

Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis.

BACKGROUND: Cigarette smoke (CS) plays a role in the exacerbation of chronic rhinosinusitis (CRS); however, the mechanism for this is unknown. We hypothesize that CS impairs human sinonasal epithelial cell (HSNEC) conversion of 25(OH)D3 (25VD3) to 1,25-dihydroxyvitamin D3 (1,25VD3) and, furthermore, that supplementation with 1,25VD3 will reverse smoke-induced inflammatory responses by HSNECs. OBJECTIVE: We sought to determine the effect of CS on vitamin D3 (VD3) levels, conversion, and regulation of CS-induced inflammation in control subjects and patients with CRS. METHODS: Blood and sinus tissue explants were collected at the time of surgery from control subjects, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic sinusitis with nasal polyps (CRSwNP). Expression of VD3 metabolizing enzymes were measured by using RT-PCR. Primary HSNECs were cultured from tissue explants. 25VD3 with and without cigarette smoke extract (CSE) was used to examine conversion of 25VD3 to 1,25VD3, as well as HSNEC production of proinflammatory cytokines. RESULTS: CS exposure was associated with reduced circulating and sinonasal 25VD3 levels in all groups compared with those seen in CS-naive, disease-matched counterparts. CS exposure decreased expression of CYP27B1 and was especially pronounced in patients with CRSwNP. CSE impairs control HSNEC conversion of 25VD3. HSNECs from patients with CRSwNP also demonstrate an intrinsic reduction in conversion of 25VD3 to 1,25VD3. Exogenous 1,25VD3 reduces CSE-induced cytokine production by HSNECs. CONCLUSIONS: Exposure to CS is associated with reduced 25VD3 levels and an impaired ability of HSNECs to convert 25VD3 to 1,25VD3. Addition of 1,25VD3 reduces the proinflammatory effects of CS on HSNECs. Impaired VD3 conversion by CS exposure represents a novel mechanism through which CS induces its proinflammatory effects.

Nasal cytological assessment after crenotherapy in the treatment of chronic rhinosinusitis in the elderly.

Chronic rhinosinusitis (CRS) determines irreversible alterations of the nasal mucosa with consequent impairment of ciliary movements and, therefore, mucociliary clearance (MCC). People of all ages can be affected by CRS but the elderly are subjects at the highest risk. CRS in the elderly with an age-related physiological impairment of nasal respiratory function, often accompanied by other chronic diseases, requires additional therapies to be added to the numerous daily medications. Since the currently available therapies for CRS include the use of drugs that can have adverse effects and contraindications, crenotherapy could represent a therapeutic option. Indeed, because the adverse effects and contraindications of crenotherapy are scarce, it can be safely used in elderly patients with comorbidities. The aim of this study is to evaluate the nasal cytological assessment after crenotherapy in elderly subjects with CRS. Two groups, comprising a total of 84 elderly subjects with CRS, were treated with crenotherapy with sodium chloride sulphate hyperthermal water rich in mineral salts (group I, n=49) and saline solution (group II n=35). Cytological assessment for both groups took place at baseline (T0) and 1 month after treatment (T30). At T30 the nasal cytological assessment showed statistically significant improvements in the ciliary motility and in the count of neutrophils and spores in group I, but not in group II. Conversely, there were no significant differences in the count of eosinophils, mast cells, bacteria and biofilm in either group. Our data for the first time focused on the role of crenotherapy in the improvement of cytological assessment of CRS in the elderly.

Evaluation of bacterial adherence and biofilm arrangements as new targets in treatment of chronic rhinosinusitis.

Several promising candidate drugs that target bacterial adherence and biofilm formation are being developed. Such hopeful drugs cannot be studied in chronic rhinosinusitis (CRS) without the evaluation of such virulence criteria in different forms of the disease with and without nasal polyposis (CRSwNP and CRSsNP). The aim of this study was to evaluate bacterial adherence, response to antibiotics and degree of accumulation of bacterial biofilms as new targets of treatment in CRSwNP and CRSsNP. Twenty CRS patients and 10 normal subjects with airway obstructing concha bullosa were prospectively enrolled in the present study. Scanning electron microscopy and cultures were performed on paranasal sinus tissue samples. Bacterial adherence tests using the tissue culture plate method were measured quantitatively. Strongly adherent bacteria were identified significantly in 6/9 (77%) cases of CRSsNP in comparison to 1/7 (14%) cases of CRSwNP. Strongly adherent bacteria that were sensitive to ciprofloxacin, vancomycin, and impenim were identified in 75% of the cultured coagulase positive staphylococci. A significant difference (P = 0.007) in the degree of accumulation of bacterial biofilms existed between the two groups. In CRSsNP, a more advanced stage of bacterial biofilms with strong bacterial adherence was observed which make them attractive targets for new drugs. In CRSwNP, lower stage bacterial biofilms with low bacterial adhesion were identified, which may help explain the low bacterial virulence in an environment of suboptimal, organizational arrangements.

Effects of sulfurous, salty, bromic, iodic thermal water nasal irrigations in nonallergic chronic rhinosinusitis: a prospective, randomized, double-blind, clinical, and cytological study.

OBJECTIVES: Nasal irrigations are mentioned among the adjunctive measures for treating several sinonasal conditions. Hyperchromatic supranuclear stria (HSS) in the ciliated cells (CCs) has recently been suggested as a potential cytological marker of the anatomofunctional integrity of nasal mucosa. The aim of this study was to compare the effects of nasal irrigations with sulfurous, salty, bromic, iodic (SSBI) thermal water or isotonic sodium chloride solution (ISCS) in patients with nonallergic chronic rhinosinusitis, considering the endoscopic, functional, microbiological, and cytological evidence (including the ratio of HSS-positive CCs to total CCs [the HSS+ rate]). METHODS: In a prospective, randomized, double-blind setting, 80 patients were recruited for nasal irrigations with SSBI water or ISCS for 1 month. RESULTS: An endoscopically assessed significant clinical improvement was seen after both SSBI thermal water and ISCS irrigations. Before treatment, Staphylococcus aureus was isolated in 5 patients in the SSBI thermal water group and 4 in the ISCS group. After the nasal irrigations, there was no sign of the bacteria in either group. Only the SSBI water irrigations significantly reduced total nasal resistance, as determined by rhinomanometry. Mild nasal irritation (6 cases) and episodes of extremely limited epistaxis (5 cases) were only reported after SSBI thermal water irrigations. Neither type of nasal irrigation significantly increased the mean HSS+ rate at cytological control after 1 month. CONCLUSIONS: Both types of nasal irrigation improved the endoscopic and microbiological features of patients with nonallergic chronic rhinosinusitis, whereas only SSBI irrigations significantly reduced total nasal resistance. Further investigations are needed based on longer treatments and follow-up periods to establish whether the HSS+ rate is useful for monitoring clinical improvements in chronic rhinosinusitis treated with nasal irrigations.

The microbiology and the efficacy of antibiotic-based medical treatment of chronic rhinosinusitis in Singapore.

BACKGROUND: Medical therapy including appropriate antibiotic treatment is advocated for the management of chronic rhinosinusitis (CRS), with sinus surgery reserved for treatment failures. This study investigates the microbiology of CRS and their response to culture-directed antibiotic treatment. METHODS: Sinus aspirates of mucopus from 172 consecutive CRS patients, with (n=89) and without (n=83) previous antibiotic treatment, were obtained for bacterial culture at their first visit. Medical treatment which included initial empirical and subsequent culture-directed antibiotics was instituted. Endoscopic sinus surgery (FESS) was performed for patients with persistent CRS and/or complications of CRS. A follow-up of 12 months was scheduled for all patients. RESULTS: One hundred and twenty (69.8%) patients were treated successfully by with antibiotic-based medical therapy. Thirty-eight patients (22.1%) did not respond to medical treatment and eventually underwent FESS. The incidence of CRS with nasal polyps (CRSwNP) was higher in FESS group (n=13, 34.2%) than patients with medical treatment only (n=9, 6.7%). Staphylococcus aureus was the most common pathogen (n=43, 25%) and amongst patients with no prior antibiotic treatment, the incidence was higher in patients with CRSwNP (n=8, 53 %) than CRS without NP (CRSwoNP) (n=20, 27%). The rate of sensitivity of the cultured microbes to amoxicillin with clavulanate and cephalosporins was 78% and 70%, respectively. CONCLUSION: The microbiology of CRS in Singapore is described. Staphylococcus aureus appears to be the most common bacterial isolates in both CRS with and without nasal polyps. Medical treatment with CRS using culture-directed antibiotics is effective in the majority of patients, especially in patients without nasal polyps.

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.

[Pharmacology of Sinupret. Recent results on the rational for the Sinupret compound]. / Pharmakologische Effekte von Sinupret. Neue Erkenntnisse zur Rationalen für die Zusammensetzung von Sinupret.

The herbal medicinal product Sinupret has been successfully used for the treatment of sinusitis for 70 years. In Germany the product is established as a standard in the therapy of sinusitis. The most recent pharmacodynamic findings resulted from close scientific cooperation with Pontus Stierna and co-workers from the Karolinska Institute in Stockholm: Mice were infected intranasally with Streptococcus pneumoniae to induce bacterial rhinosinusitis. Animals were randomized to treatment with ampicillin, dexamethasone, Sinupret, or sham treatment. All groups receiving active treatment showed a reduction in bacterial growth after 4 days and a significant reduction of bacterial growth after 8 days. Similar results were observed regarding histopathology. Initial findings in a sinusitis model in the New Zealand White rabbit confirmed the results observed in the aforementioned studies in mice. Understanding of the pharmacological profile of Sinupret supports the knowledge about the clinical efficacy of this herbal medicinal product.