Clinical effectiveness of house dust mite immunotherapy in mono- versus poly-sensitised patients with allergic rhinitis: a systematic review and meta-analysis.

Selecting an appropriate allergen-specific immunotherapy (AIT) regimen for polysensitised allergic rhinitis (AR) patients is challenging for clinicians. Although previous studies showed comparable effectiveness of single-allergen AIT with house dust mite (HDM) extract between monosensitised and polysensitised AR patients, there is no systematic review and meta-analysis demonstrating the comparable effectiveness of HDM AIT. In this meta-analysis, we analysed nine studies to compare the clinical effectiveness of HDM AIT. The primary outcome was nasal symptom score and secondary outcomes were medication and quality of life scores. The changes in nasal symptom score after HDM AIT did not significantly differ between monosensitised and polysensitised patients. The clinical effectiveness of HDM AIT regarding medication and quality of life score was not significantly different between monosensitised and polysensitised patients). In conclusion, single-allergen AIT with HDM extract showed comparable clinical effectiveness between polysensitised and monosensitised patients with AR.

Type III interferons are critical host factors that determine susceptibility to Influenza A viral infection in allergic nasal mucosa.

BACKGROUND: Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon (IFN)-related immune responses, but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown. OBJECTIVES: To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify whether higher loads of influenza A virus (IAV) in allergic nasal mucosa could be controlled with IFN treatment. METHODS: Influenza A virus mRNA, viral titres and IFN expression were compared in IAV-infected normal human nasal epithelial (NHNE, N = 10) and allergic rhinitis nasal epithelial (ARNE, N = 10) cells. We used in vivo model of allergic rhinitis (BALB/c mice, N = 10) and human nasal mucosa from healthy volunteers (N = 72) and allergic rhinitis patients (N = 29) to assess the induction of IFNs after IAV infection. RESULTS: Influenza A virus mRNA levels and viral titres were significantly higher in ARNE compared with NHNE cells. IFN-ß and IFN-λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN-λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN-λs mRNA level was also significantly lower in the nasal mucosa of AR patients, and we found that recombinant IFN-λ treatment attenuated viral mRNA levels and viral titres in IAV-infected ARNE cells. In vivoAR mouse exhibited higher viral load after IAV infection, but intranasal inoculation of IFN-λ completely decreased IAV protein expression and viral titre in nasal mucosa of IAV-infected AR mouse. CONCLUSION: Higher susceptibility of the allergic nasal mucosa to IAV may depend on impairment of type III IFN induction, and type III IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.

Resveratrol prevents development of eosinophilic rhinosinusitis with nasal polyps in a mouse model.

BACKGROUND: Since the recent establishment of a murine model of eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), both the development of new drugs for treatment or prevention of eosinophilic CRSwNP and elucidation of their pathogenesis have been feasible. We investigated the therapeutic effects of resveratrol on CRSwNP and its mechanism of action using a murine model. METHODS: After induction of eosinophilic CRSwNP, the therapeutic effects of resveratrol were tested and compared with those of triamcinolone acetonide. Histopathologic changes were evaluated using hematoxylin and eosin for overall inflammation, Sirius red for eosinophils, and Masson's trichrome stain for collagen. The expression levels of the interleukin (IL)-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were assessed by quantitative real-time PCR. Cyclooxygense-2 and 5-lipoxygense levels were evaluated by immunohistochemical staining and Western blot analysis. RESULTS: The degree of eosinophilic infiltration and subepithelial fibrosis was significantly decreased by administration of high-dose resveratrol, the potency of which was similar to that of triamcinolone acetonide. The expression levels of the IL-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were significantly decreased by administration of low- or high-dose resveratrol. The production of 5-lipoxygenase was strongly inhibited by high-dose resveratrol. CONCLUSIONS: Resveratrol may be useful for the prevention of eosinophilic CRSwNP. A key mechanism of its action is believed to be its anti-inflammatory effect, particularly on eosinophils, by inhibiting the lipoxygenase pathway.

Anti-tumor necrosis factor-alpha treatment reduces allergic responses in an allergic rhinitis mouse model.

BACKGROUND: Tumor necrosis factor (TNF)-α is a principal mediator of the acute inflammatory response, including allergic rhinitis. TNF-α inhibitors are widely used for the treatment of inflammatory conditions such as rheumatoid arthritis and inflammatory bowel diseases; however, the effects of TNF-α inhibitors on allergic rhinitis are not well established. We aimed to investigate the effects of infliximab, a TNF-α inhibitor, on allergic rhinitis in a mouse model. METHODS: BALB/c mice were sensitized with ovalbumin (OVA) and alum, and challenged intranasally with OVA. The TNF-α inhibitor, infliximab was administered intraperitoneally, and multiple parameters of allergic responses were evaluated to determine the effects of infliximab. RESULTS: Infliximab reduced allergic symptoms and eosinophilic infiltration into the nasal mucosa. It also suppressed total and OVA-specific IgE levels, and inhibited local Th2 cytokine transcription in the nasal mucosa and systemic Th2 cytokine production by splenocytes. Furthermore, the expression of E-selectin, neither intercellular adhesion molecule 1 (ICAM-1) nor vascular cell adhesion molecule 1 (VCAM-1), in the nasal mucosa was suppressed in the infliximab-treated group when compared to the nontreated group. CONCLUSION: This study shows that the TNF-α inhibitor infliximab induces anti-allergic effects by decreasing local and systemic Th2 cytokine (IL-4) production, total and OVA-specific IgE levels, adhesion molecule (E-selectin) expression, and eosinophil infiltration into the nasal mucosa in an allergic rhinitis model. Therefore, infliximab should be considered as a potential agent in treating allergic rhinitis.

Characteristics and risk factors of mucosal cysts in the paranasal sinuses.

BACKGROUND: Though mucosal cysts in the paranasal sinuses (PSMCs) are common findings on radiographic images, the nature of PSMCs and risk factors for the development of PSMCs have not yet been determined. The aim of this study was to evaluate the characteristics of PSMCs using brain magnetic resonance (MR) imaging. METHODOLOGY/PRINCIPAL: A total of 6831 subjects who underwent health checkup including brain MR imaging were included in this study. The characteristics of PSMCs, including their location, number and size, as well as the presence of obstruction of the sinus ostium and sinusitis, were analysed using brain MR images. Structured questionnaires and medical records were reviewed to evaluate the smoking status and comorbid medical conditions. RESULTS: The overall prevalence of PSMCs was 7.4% and was significantly higher in females than in males. PSMCs were most commonly found in the maxillary sinus, most of which were located unilaterally as a solitary cyst. Large cysts were associated with obstruction of the sinus ostium and subsequent sinusitis. Smoking was a single important risk factor for developing PSMCs. No significant associations were found between symptoms (nasal/respiratory) and the presence of PSMCs. CONCLUSIONS: The prevalence of PSMCs was 7.4% and decreased with age. Large cysts may lead to obstruction of the sinus and subsequent sinusitis. Smoking was an important risk factor for PSMCs, and the total amount of smoking correlated with cyst size. Most subjects were asymptomatic, and specific treatment was not performed.

Class III beta-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Recent researches revealed that class III beta-tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in head and neck squamous cell carcinoma (HNSCC) is not defined yet. We analyzed the significance of TUBB3 expression along with p53 and ERCC1 in locally advanced HNSCC patients receiving cisplatin-based induction chemotherapy. MATERIALS AND METHODS: Retrospective review of medical records at Seoul National University Hospital between 1998 and 2007 was carried out. Immunohistochemical stain of TUBB3, p53, and ERCC1 was done in paraffin-embedded tumor tissue. We assessed response to treatment, progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Eighty-five patients with oropharyngeal, hypopharyngeal, and laryngeal cancers received induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (n = 55), or 5-FU, cisplatin, and docetaxel (Taxotere) (n = 30). Eighty-three received definitive treatment after induction chemotherapy, where 62 received radiotherapy and 21 received surgery. TUBB3-positive patients showed lower response rate than TUBB3-negative patients (69% versus 88%, P = 0.039). Shorter median PFS was observed in TUBB3-positive group (12 versus 47 months, P = 0.001). Shorter median OS was observed in TUBB-positive group not reaching statistical significance (30 versus 59 months, P = 0.072). TUBB3 status significantly influenced CSS (35 months versus not reached, P = 0.017). Positive p53 status was related to poorer OS and CSS. ERCC1 showed no influence on chemotherapy response, PFS, OS, and CSS. CONCLUSION: TUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.

Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSNP) and asthma are inflammatory lesions of the respiratory epithelium. This study was conducted to evaluate predictive factors of bronchial hyperresponsiveness (BHR) in patients with CRSNP. METHODS: BHR was evaluated using a methacholine bronchoprovocation test (MBPT) in 122 consecutive patients newly diagnosed with CRSNP at Seoul National University Hospital from January 2004 to June 2006. The following parameters were analyzed and compared between the BHR and non-BHR groups: symptoms, atopic status, current smoking, disease severity of CRSNP based on the Lund-Mackay scoring system of sinus CT, and counts of eosinophils in the serum and nasal tissues. RESULTS: Thirty-five percent of the patients were found to have BHR, and BHR was found to occur more frequently in patients that were currently suffering from sneezing (P = 0.007). In addition, the mean eosinophil counts of the serum and nasal tissues were higher in the BHR group than in the non-BHR group (P = 0.001 for the serum, P = 0.045 for the nasal tissues), and the eosinophil counts of the serum correlated to those of the nasal tissues (r = 0.334, P = 0.013). The disease severity, as determined by the Lund-Mackay scoring system, was not different between the two groups (P > 0.05). The best cutoff serum eosinophil count for predicting BHR in CRSNP patients was determined to be 300 cells/microl (sensitivity 70%, specificity 70%). CONCLUSION: Taken together, these results indicate that moderate to severe sneezing and a serum eosinophil count > or = 300 cells/microl may be predictive factors for BHR in patients with CRSNP.

Effects of phenylephrine on ciliary beat in human nasal respiratory epithelium: quantitative measurement by video-computerized analysis.

The in vitro effects of phenylephrine solution on ciliary beat frequency (CBF) in terms of different concentrations and exposure times were investigated using a video-computerized analysis technique. Nasal epithelial cells were taken from inferior turbinate of 10 volunteers by scraping the nasal mucosa with a cytology brush. CBF was measured in five different concentrations including 0.125%, 0.25%, 0.5%, 1%, and 2.5%. Each specimen was incubated in different solution for 6 days and CBF was measured at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, and 6 days. CBF decreased significantly after 12-hour incubation in 0.125% phenylephrine solution and after 8-hour incubation in 0.25% phenylephrine solution, both clinically used concentrations. There were significant decreases in CBF after incubation in 0.5% phenylephrine for 2 hours, in 1% for 1 hour, and in 2.5% for 30 minutes (P < 0.05, repeated measure analysis of variance [ANOVA]). CBF of the nasal respiratory ciliated cells significantly decreased with increasing concentrations of phenylephrine solution and with increasing incubation times at the same concentration (P < 0.05, repeated measure ANOVA). The results of this study suggest that phenylephrine may inhibit ciliary beat in vitro by its pharmacological effect at lower concentrations than clinically used ones.

Effects of alpha-toxin of Staphylococcus aureus on the ciliary activity and ultrastructure of human nasal ciliated epithelial cells.

OBJECTIVE: The in vitro effects of staphylococcal alpha-toxin on ciliary activity were investigated at different concentrations and exposure times. STUDY DESIGN: Ciliated epithelial cells of the sphenoid sinus were taken from patients operated on for pituitary tumors. Video-computerized analysis technique and transmission electron microscopy were used to analyze the effects of the toxin on ciliary activity. METHODS: Ciliary beat frequency (CBF) was measured in four different concentrations of alpha-toxin including 0.1, 1, 10, and 50 microg/mL. CBF was measured at 2, 4, 6, 12, 24, and 48 hours after administration of the toxin. To observe reversibility of the reduced ciliary activity, after 24-hour incubation in the media containing 10 microg/mL of alpha-toxin, the media were replaced with alpha-toxin-free media. The tissues were also processed for transmission electron microscopy to observe ultrastructural changes of the epithelial cells. RESULTS: CBF increased significantly at 2-hour incubation and then decreased significantly after 12-hour incubation in 10 microg/mL of alpha-toxin (P< .05, repeated-measures ANOVA). The transmission electron microscopic findings showed mitochondrial swelling and a slight protrusion of the plasma membrane of the cilia. In toxin-free media, loss of ciliary activity was not recovered. CONCLUSIONS: CBF increased at first, but with increasing incubation time ciliary movements decreased gradually and stopped eventually. This loss of CBF may be an irreversible change associated with ultrastructural changes in the mitochondria and the plasma membrane of the cilia.

Regulation of mucociliary motility by nitric oxide and expression of nitric oxide synthase in the human sinus epithelial cells.

OBJECTIVES: This study was performed to investigate the changes in ciliary beat frequency (CBF) after treatment with Larginine in the human sinus mucosa and to determine the distribution of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in the healthy sinus mucosa. STUDY DESIGN/METHODS: CBF was measured in the sphenoid sinus mucosa of 12 patients who underwent trans-septal trans-sphenoidal hypophysectomy for the treatment of pituitary gland tumor. CBF was measured over 24 hours in Dulbecco's modified Eagle's medium (DMEM) after treatment with L-arginine, its inactive spatial isomer D-arginine, or an NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). DMEM without treatment with these materials was used as a control. Other pieces of the mucosa were exposed to L-NAME and its inactive spatial isomer D-NAME after preincubation with L-arginine. The specimens were immunohistochemically stained for iNOS and eNOS. RESULTS: CBF increased 24 hours after treatment with L-arginine as compared with control groups. CBF increased in proportion to the increasing concentrations of L-arginine. There was no significant change after treatment with D-arginine or L-NAME. CBF increased after treatment with L-arginine at 30 minutes and maintained for 24 hours. L-NAME inhibited the increase in CBF by L-arginine, but D-NAME showed no such effect. Immunoreactivity to both iNOS and eNOS was frequently observed in the ciliated epithelial cells and was stronger to eNOS than to iNOS. CONCLUSIONS: From the results of this study it is suggested that nitric oxide (NO) produced by iNOS and eNOS using L-arginine may increase CBF in the healthy sinus mucosa and that NO may have a regulatory function in ciliary motility in the human sinus mucosa.

Changes of nasal function after temperature-controlled radiofrequency tissue volume reduction for the turbinate.

OBJECTIVES: Temperature-controlled and temperature-monitored radiofrequency tissue volume reduction (RFTVR) for the turbinate is a new treatment modality for nasal obstruction secondary to turbinate hypertrophy. We compared the nasal functions after the treatment ofRFTVR and laser vaporizing turbinoplasty (LVT) using subjective symptom scores and objective tests. STUDY DESIGN: Prospective, randomized clinical trial. METHODS: Twenty-four patients with nasal obstruction secondary to inferior turbinate hypertrophy were prospectively evaluated from March 1999 to October 1999 at Seoul National University Hospital (Seoul, Korea). Sixteen patients were treated with RFTVR, and eight patients with LVT. The preoperative and postoperative nasal functions were investigated by visual analogue scale of symptoms, butanol threshold test, saccharine test, acoustic rhinometry, rhinomanometry, and ciliary beat frequency. RESULTS: At 8 weeks postoperatively, the severity and the frequency of nasal obstruction improved subjectively in 81.3% and 93.8% of RFTVR group and in 87.5% and 87.5% of LVT group, respectively. Significant improvement of nasal symptoms began from 2 to 3 days after the operation in the RFTVR group, whereas there was significant improvement of nasal symptoms at 8 weeks after operation in the LVT group. However, objective nasal functions including nasal volume and total nasal resistance were significantly improved at 8 weeks after surgery in both groups. Among patients reporting symptoms of hyposmia, 55.6% of RFTVR group and 63.6% of LVT group showed improved olfaction. Saccharin transit time and ciliary beat frequency were preserved after RFTVR CONCLUSION: RFTVR for the turbinate may be useful as an alternative approach for the treatment of chronic turbinate hypertrophy.

The manifestation of proliferating cell nuclear antigen in adenoid cystic carcinoma.

OBJECTIVE: This study was conducted to evaluate the prognostic value of immunostaining with a genetically engineered monoclonal antibody (PC10) to proliferating cell nuclear antigen in patients with adenoid cystic carcinoma (ACC). DESIGN: Formalin-fixed, paraffin-embedded tissue blocks from patients with ACC were stained with PC10, and an index (percentage of positively staining cells per tumor cells) was calculated. The patients' clinical course was compared with the PC10 index. Follow-up ranged from 12 to 177 months (mean, 64 months). SETTING: Patient selection and immunohistochemical studies were done at Seoul (Korea) National University Hospital. PATIENTS: Twenty-eight cases of ACC were retrieved from our files between January 1979 and December 1992. MAIN OUTCOME MEASURE: All of the cases expressed the PC10 antibody. The PC10 index ranged from 1.0% to 44% (mean, 14.5%). We divided the 28 cases into two groups: group 1 (PC10 index, less than 15%) and group 2 (PC10 index, greater than 15%). RESULTS: The PC10 index (groups 1 and 2) did not correlate with established pathologic grades, tumor staging, local recurrences, or survival rates. However, those with higher PC10 indexes (group 2) exhibited significantly increased distant metastases compared with those with lower indexes (group 1). CONCLUSION: We conclude that the proliferating cell nuclear antigen in ACC may be used as an indicator in the prediction of distant metastasis.

Effects of mucokinetic drugs on rheological properties of reconstituted human nasal mucus.

OBJECTIVE: To investigate the effects of mucokinetic drugs on the rheological properties of human nasal mucus in patients with chronic sinusitis. DESIGN: We reconstituted human nasal mucus obtained from 74 patients with chronic sinusitis and determined the effects of 4 mucokinetic drugs, including acetylcysteine, deoxynuclease I, 2% sodium bicarbonate, and a combination product containing tyloxapol (Alevaire), on rheological properties of reconstituted human nasal mucus (RHNM). We used 5% RHNM dissolved in phosphate-buffered solution as the optimal buffer and concentration of RHNM for the study because it showed a viscoelastic response similar to that of freshly collected nasal mucus from patients with chronic sinusitis. METHODS: Four experiments were performed to determine the influence of each drug on dynamic viscosity and elasticity of 5% RHNM. Distilled water was used as a control. RESULTS: Acetylcysteine and deoxynuclease I significantly decreased both dynamic viscosity and elastic modulus, while distilled water had no effect on rheological properties of 5% RHNM in vitro. Alevaire significantly reduced both dynamic viscosity and elastic modulus. Sodium bicarbonate significantly reduced elastic modulus but not dynamic viscosity. Reduction of elastic modulus by Alevaire was significantly greater than that by sodium bicarbonate, while there was no difference in reduction of dynamic viscosity between them. CONCLUSION: Our results indicate that RHNM may be useful for studying the topical effects of various drugs on nasal mucus from patients with chronic sinusitis.

Adenoid cystic carcinoma of the head and neck.

Adenoid cystic carcinoma of the head and neck is relatively rare and is characterized by slow evolution, multiple recurrences, protracted clinical course, and late distant metastasis. This article presents its peculiar clinical course, response to therapy, and long-term treatment results by analyzing 67 cases treated from 1979 to 1991 at the Seoul (Korea) National University Hospital. The most common primary site was the parotid gland in the major salivary glands and the nose and paranasal sinuses in the minor salivary glands. The local control rate was 71.1% at 5 years and 44.3% at 8 years. Late-occurring distant metastases did not allow a plateau in survival curves, even after 8 years. Our study also revealed that surgery combined with postoperative radiotherapy could yield better local control.

Hypertonic saline decreases ciliary movement in human nasal epithelium in vitro.

Various saline solution formulae are frequently used in patients with rhinosinusitis. Osmolarity affects ciliary beat frequency (CBF); however, little is known about the effects of saline solutions on ciliary activity of nasal epithelial cells. The aim of this study was to assess whether CBF of normal turbinate mucosa is affected by hypertonic, isotonic, or hypotonic saline solution in vitro and whether histologic changes are associated with the alteration of ciliary movement. We assessed variations of CBF after exposure to 0.06%, 0.12%, 0.9%, 3.0%, or 7.0% saline solutions and histologic changes were examined by transmission electron microscopy. Isotonic and hypotonic solutions produced no ciliary slowing; however, ciliostasis was observed within a few minutes in 3.0% or 7.0% solution. The histologic changes demonstrated that the ciliary slowing might be attributed to epithelial damage by fluid transport toward the surrounding medium. In conclusion, hypertonic saline solutions decrease CBF and disrupt nasal epithelial cells in vitro.

Cytokine gene expression in nasal polyps.

Nasal polyps are the most common mass lesion of the nasal cavity. Various pathogenetic mechanisms have been proposed. However, the cause is still largely unknown, and treatment methods have not been changed for several hundred years. In order to investigate the role of cytokines in the pathogenesis of nasal polyps, expression of cytokine messenger RNAs (mRNAs) in nasal polyps was investigated. We performed reverse transcriptase-polymerase chain reaction and Southern blot to examine gene expression of the cytokines interleukin (IL)-1 beta, IL-6, IL-8, transforming growth factor (TGF)-beta, IL-4, IL-5, and interferon (IFN)-gamma and compared the results with the gene expressions of these cytokines in normal nasal mucosa. Nasal polyp tissues were obtained from 14 patients undergoing polypectomy for nasal obstruction. Among them, 4 patients suffered from associated perennial allergic rhinitis. The mRNAs of IL-4 and IL-5 (Th2 cytokines) as well as IFN-gamma (Th1 cytokine) were expressed in all of the nasal polyps obtained from the 14 patients, irrespective of the presence or absence of allergy, while 2, 0, and 4 of 6 normal turbinate mucosae expressed IL-4, IL-5, and IFN-gamma mRNAs, respectively. The mRNAs of IL-1 beta, IL-6, IL-8, and TGF-beta were expressed in 6, 1, 2, and 3 of 6 normal turbinate mucosae, respectively, while the mRNAs of these cytokines were expressed in all of the 14 polyp tissues except IL-6 mRNA, which was expressed in 13 nasal polyp tissues. There were no differences in the mean density ratios of each cytokine band on Southern blot between polyp tissues with allergy and those without allergy. These results suggest that many cytokines are produced in nasal polyps, that they may play important roles in the pathogenesis of nasal polyps, and that allergy per se may not play a fundamental role in the pathogenesis of nasal polyps.

Increase in expression of IL-4 and IL-5 mRNA in the nasal mucosa of patients with perennial allergic rhinitis during natural allergen exposure.

To understand the role of cytokines in allergic nasal disease in humans, we designed this study to investigate the expression of cytokine mRNA in the nasal mucosa of 10 control subjects and 10 patients with perennial allergic rhinitis using a reverse transcription-polymerase chain reaction (RT-PCR) for IL-4, IL-5 (Th2 cytokines), and IFN-gamma (Th1 cytokine). Both IL-4 and IL-5 mRNAs were expressed in a significantly larger number of patients with allergic rhinitis than in control subjects. When the levels of expression of cytokines and beta-actin mRNA were quantitated, the mean density ratios (cytokine/beta-actin) for IL-4 and IL-5 were higher in patients with allergic rhinitis than in control subjects. In contrast, there were no differences in the number of subjects who showed expression of IFN-gamma mRNA, or in mean density ratios for IFN-gamma between the two groups. This study suggests that both IL-4 and IL-5 mRNAs are expressed almost universally in the nasal mucosa of patients with perennial allergic rhinitis during natural allergen exposure and also that Th2-type cytokines play a crucial role in the development of allergic nasal diseases in vivo.

Distribution of rantes and interleukin-5 in allergic nasal mucosa and nasal polyps.

Eosinophil-chemoattracting cytokines are thought to be important in the pathogenesis of allergic inflammation. However, little is known about the presence and significance of RANTES in nasal allergy and nasal polyps, two well-known rhinologic disorders characterized by eosinophil infiltration in the tissue. In order to evaluate the role of RANTES in eosinophil infiltration in vivo, the tissue distributions of RANTES and interleukin-5 (IL-5) and their correlation with eosinophil infiltration were investigated. Nasal mucosa specimens were obtained from 9 allergic and 12 control subjects, and nasal polyps from 6 allergic and 9 nonallergic subjects. All the subjects were divided into 4 groups: normal mucosa, allergic mucosa, nonallergic polyps, and allergic polyps. To identify the cellular localizations of RANTES and IL-5, we used specific immunohistochemical staining. We also investigated the differences in cytokine expression among the 4 groups, and the correlation between cytokine expression and eosinophil infiltration in the tissue. RANTES was expressed in the epithelium, endothelium, and some submucosal cells, while IL-5 was confined to the cells in the submucosa. Expression of both RANTES and IL-5 significantly increased in allergic mucosa and nasal polyps compared to normal mucosa; however, there was no significant difference in their expression between allergic and nonallergic polyps. Both cytokines had a significant correlation between their expression and either total or activated eosinophil numbers. The results of this study suggest that RANTES, as well as IL-5, plays a role in eosinophil recruitment in allergic nasal mucosa and nasal polyps in vivo.

Effects of clarithromycin on rheological properties of nasal mucus in patients with chronic sinusitis.

Macrolide antibiotics have a variety of actions along with antimicrobial action. To determine the effects of oral administration of clarithromycin (CAM) on rheological properties, we measured the spinability, dynamic viscoelasticity, and solid composition of human nasal mucus from 18 patients with chronic sinusitis before and after administration of CAM for 4 weeks. After administration of CAM, the spinability and percent solid composition of nasal mucus increased from 26.5 +/- 12.2 mm to 40.2 +/- 18.7 mm and 7.86% +/- 3.47% to 13.90% +/- 3.67% (p < .05), respectively, whereas the ratio of the viscosity to the elasticity (eta'/G') of nasal mucus after the administration of CAM decreased in all of the mucus samples. These results suggest that treatment with CAM may modulate the rheological properties of nasal mucus in patients with chronic sinusitis.

Ciliary beat frequency in cultured human nasal epithelial cells.

This study aimed to determine the characteristics of ciliogenesis and the ciliary beat frequency (CBF) of cultured human nasal epithelial cells by means of an in vitro air-liquid interface (ALI) culture system. On the 14th, 21st, and 27th days of ALI culture, CBFs of cultured cells were measured with a video computerized analysis system, and the epithelial cell-collagen matrix complex was examined by scanning and transmission electron microscopy. Using a CBF distribution map, we calculated the proportion of ciliary beating area (CBA) on the cultured cells. On the 14th day, ciliated cells could be easily distinguished from other cells on scanning electron microscopy by their elongated cilia. Between the 14th and 27th days, the number of mature cilia increased, and after 27 days of air exposure, the cilia of each cell pointed to one direction. From the beginning of air-exposure culture until the 7th day, the number of secretory cells increased; however, from the 7th day to the 27th day, it decreased, and the number of ciliated cells increased. Total CBAs increased from the 7th day to the 21st day. The proportions of actively beating cells and the mean CBFs of beating cells among cultured epithelial cells increased with culture time. On the 21st day, the mean CBF of the cultured cells was similar to that of nasal ciliated cells in biopsy specimens (10.9 +/- 0.5 Hz versus 11.4 +/- 1.3 Hz), but until the 27th day, the CBF of cultured cells increased significantly (13.9 +/- 0.8 Hz). It is suggested that there may be some difference in CBF between nasal epithelial cells submitted to biopsy and nasal epithelial cells cultured by the ALI culture system.