Effect of budesonide transnasal nebulization in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: There is little evidence on the efficacy of glucocorticoid transnasal nebulization therapy in patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We sought to evaluate the immunologic and remodeling effects of budesonide transnasal nebulization in patients with eosinophilic CRSwNP. METHODS: Sixty patients with eosinophilic CRSwNP were randomized to receive budesonide or placebo treatment for 14 days by means of transnasal nebulization in a double-blind manner. Endoscopic polyp size scores (maximum = 6 points, Kennedy score) and visual analog scale scores for nasal symptoms were assessed before and after treatment. Similarly, polyp samples were evaluated for inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) by using an immunoassay; collagen by using histochemistry; eosinophils by using hematoxylin and eosin stain; and T-cell subsets by using flow cytometry. RESULTS: Budesonide transnasal nebulization significantly reduced polyp size compared with placebo (mean difference between groups, -0.73 units; 95% CI, -1.15 to -0.32 units; P = .002) and improved symptoms. Polyp IL-5 and eotaxin expression decreased significantly, whereas TGF-ß and IL-10 expression increased. Expression of IFN-γ and IL-17 was not altered. Budesonide transnasal nebulization consistently reduced eosinophil infiltration and TH2 cell frequency and increased natural regulatory T-cell and type 1 regulatory T-cell frequencies. Indices of remodeling, including albumin, MMP-2, MMP-7, MMP-8, and MMP-9, were significantly decreased, whereas collagen deposition and TIMP-1, TIMP-2, and TIMP-4 levels were significantly increased. Budesonide transnasal nebulization did not suppress the hypothalamic-pituitary-adrenal axis or cause any serious side effects. CONCLUSION: Short-term budesonide transnasal nebulization is an effective and safe treatment option in patients with eosinophilic CRSwNP, achieving clinical improvement by regulating remodeling, cytokine expression, and T-cell subset distribution.

Upregulation of interleukin-35 subunits in regulatory T cells in a murine model of allergic rhinitis.

OBJECTIVE: Regulatory T (Treg) cells play a critical role in the pathophysiology of allergic rhinitis (AR). We investigated the regulatory roles of interleukin (IL)-35, an immunosuppressive cytokine expressed by CD4(+)CD25(+)Foxp3(+) Treg cells, in a murine model of AR. METHODS: The expression of IL-35 subunits (Ebi3, encoded by Ebi3, and IL-12p35, encoded by IL12a) and IL-35 receptor chains (IL12rb and IL6st) in nasal mucosa and in spleen-derived Treg cells from ovalbumin (OVA)-sensitized AR was analyzed by immunohistochemistry and quantitative real-time RT-PCR techniques. RESULTS: IL-35 subunit secretion was associated with local OVA sensitization in this murine model of AR. Ebi3 and IL-12p35, as well as CD3, were expressed differentially in the same regions of nasal mucosa of both AR and control animals. Ebi3 mRNA levels were significantly downregulated in the nasal mucosa of AR mice compared with control mice. Similarly, Ebi3 and IL12a mRNA levels were significantly upregulated in CD4(+)CD25(+) Treg cells and, correspondingly, downregulated in CD4(+)CD25(-) T effector (Teff) cells. IL6st mRNA levels were also significantly downregulated in CD4(+)CD25(-) Teff cells. CONCLUSIONS: Decreased Ebi3 may have a crucial regulatory effect on the nasal mucosa in AR. The increased IL-35 subunit expression in CD4(+)CD25(+) Treg cells may contribute to regulating the pathogenesis of AR.

The expression of epithelial intercellular junctional proteins in the sinonasal tissue of subjects with chronic rhinosinusitis: a histopathologic study.

OBJECTIVE: To evaluate the expression of five epithelial intercellular junctional proteins in the sinonasal tissue of subjects with chronic rhinosinusitis (CRS). METHODS: Forty-one samples of nasal polyp tissue of CRS patients with nasal polyps (wNP), 20 ethmoid sinus mucosa of CRS patients without nasal polyps (sNP) and 19 nasal mucosa of controls were collected and assessed for the expression of zonulae occludens (ZO-1), claudin-1, E-cadherin and desmoglein-1 and -2 (DSG1, DSG2) using immunohistochemical staining. Interleukin (IL)-5, IL-6 and IL-8 concentrations in the tissues were also measured using ELISA. RESULTS: The expression of ZO-1, claudin-1, DSG1 and DSG2 in the CRSwNP patient group and the expression of claudin-1, DSG1 and DSG2 of the CRSsNP patient group was significantly lower compared to that of the control group. Furthermore, the expression of DSG1 in the CRSwNP patient group was also significantly lower than in the CRSsNP patient group. In contrast, the expression of E-cadherin in the CRSwNP and the CRSsNP patient groups was significantly greater compared to the controls. The assessment of associations between the expression of the intercellular junctional proteins and cytokines demonstrated negative correlations between IL-5 and claudin-1, IL-6 and claudin-1, IL-6 and DSG2, IL-8 and DSG1, and IL-8 and DSG2. In contrast, a positive correlation was found between IL-8 and E-cadherin. CONCLUSIONS: Differences in the expression of epithelial intercellular junctional proteins may play an important role in the pathogenesis of CRS.

Clinical characteristics and expression of thymic stromal lymphopoetin in eosinophilic and non-eosinophilic chronic rhinosinusitis.

OBJECTIVE: To evaluate the differences in clinical features and expression of cytokine thymic stromal lymphopoetin (TSLP) and its receptors in patients with eosinophilic and non-eosinophilic chronic rhinosinusitis (ECRS and NECRS). METHOD: 36 ECRS patients and 50 NECRS patients were evaluated for symptoms, nasal sinus computed tomography scanning, nasal endoscopy, skin prick test (SPT) positivity, and total IgE. Expression of TSLP and receptors in ethmoid sinus mucosa from the ECRS and NECRS groups were investigated by using immunohistochemical staining. RESULTS: ECRS patients demonstrated significantly higher scores of cough and hyposmia. 66.7% of ECRS patients also demonstrated nasal polyps, compared to 50% of NECRS patients, with significantly higher polyp endoscopy scores. 80.6% of ECRS patients demonstrated SPT positivity, compared to 14% of NECRS patients. The overall expression of TSLP, TSLP receptors and IL-7R was significantly greater in eosinophils in the mucosa of ECRS patients than in NECRS patients. The expression of TSLP and receptors in SPT-positive ECRS patients was significantly greater than in SPT-negative patients, with a significant correlation noted between the expression of TSLP and nasal polyp scores. CONCLUSION: The clinical manifestations of ECRS are likely to be influenced by atopic status of an individual and TSLP-mediated eosinophil infiltration of the rhinosinusoidal mucosa.

Regulation of ciliary beat frequency by the nitric oxide signaling pathway in mouse nasal and tracheal epithelial cells.

OBJECTIVES: Our purpose was to investigate the role of the nitric oxide (NO) signaling pathway in the regulation of ciliary beat frequency (CBF) in mouse nasal and tracheal epithelial cells. METHODS: We studied the effects of the NO donor l-arginine (L-Arg) and specific inhibitors of the NO signaling pathway on CBF of both nasal and tracheal epithelial cells by using high-speed digital microscopy. We also examined eNOS, sGC ß, PKG I and acetylated α tubulin expression in native mouse nasal and tracheal epithelium using immunohistochemical methods. RESULTS: L-Arg significantly increased CBF of cultured nasal and tracheal epithelial cells, and the effects were blocked by pretreatment with N(G)-nitro-l-arginine methyl ester (L-NAME), a NOS inhibitor, with LY-83583, a sGC inhibitor, or with KT-5823, a PKG inhibitor. Positive immunostaining for NO signaling molecules including eNOS, sGC ß and PKG I was observed in either nasal or tracheal ciliated epithelium. CONCLUSION: NO plays a role in regulating CBF of mouse respiratory epithelial cells via a eNOS-NO-sGC ß-cGMP-PKG I pathway.

Adipose-derived mesenchymal stem cells in collagen-hyaluronic acid gel composite scaffolds for vocal fold regeneration.

OBJECTIVES: We sought to characterize the changes in the extracellular matrix (ECM) of the lamina propria following the implantation of autologous adipose-derived mesenchymal stem cells (ADSCs) in composite scaffolds in a rabbit vocal fold wound model. METHODS: The ADSCs were co-cultured with collagen or hyaluronic acid gel. Each vocal fold was injured by localized resection and injected with ADSC complexes, ADSCs, or scaffolds or left untreated. From 15 days to 12 months, the vocal fold shape and the characteristics of the ECM components were analyzed. RESULTS: With implantation of the ADSC complexes, the collagen content was significantly increased and had a disorderly distribution at 3 months. Subsequently, it began to decrease and reached close to normal by 12 months. The hyaluronic acid content was increased at 40 days, but it was reduced to normal levels and was limited to the superficial and middle layers of the lamina propria over the following 12 months. Fibronectin continued to be scattered in the lamina propria, at peak levels at 40 days, and then decreased over the following 12 months to reach near-normal levels. At 12 months, the vocal folds had a normal surface. CONCLUSIONS: ADSC complexes can play a facilitatory role in vocal fold regeneration, regulating the generation and orderly distribution of ECM.

Decreased expression of EBI3 and Foxp3 in CD4+CD25+ regulatory T cells in murine experimental allergic rhinitis.

BACKGROUND: Epstein-Barr virus-induced gene 3 (EBI3) is a widely expressed interleukin-12-related protein that plays a critical role in the regulation of effector T cells and inflammatory responses. METHODS: Allergic rhinitis (AR) was induced in mice by both intraperitoneal injection and intranasal administration of ovalbumin. By using immunohistochemical techniques, we investigated EBI3 expression in mouse spleens. The expressions of EBI3 and forkhead transcription factor 3 (Foxp3) in CD4+CD25+ regulatory T (T(reg)) cells isolated from spleens were assessed by flow cytometry. RNA extraction and RT-PCR were used to measure EBI3 and Foxp3 mRNA expression. RESULTS: EBI3 and Foxp3 were expressed mainly in the white pulp of the spleens. Flow cytometry analysis showed that EBI3 and Foxp3 coexpressed in mouse CD4+CD25+ T(reg) cells. Furthermore, RT-PCR and flow cytometry analysis showed that expression of both Foxp3 and EBI3 was reduced in CD4+CD25+ T(reg) cells in an AR mouse model compared with controls, but there was no difference in the frequency of CD4+CD25+ T(reg) cells. CONCLUSIONS: The deficiency in CD4+CD25+ T(reg) cell suppressive activity in AR is associated with the molecular mediators EBI3 and Foxp3.

Characteristics of experimental recurrent laryngeal nerve surgical injury in dogs.

OBJECTIVES: We characterized various recurrent laryngeal nerve (RLN) injuries in dogs. METHODS: Sixteen dogs were classified as having complete injuries (transection) or incomplete injuries (ligation, half-section, and crush). The characteristics of nerve injuries were evaluated by endoscopic examination, laryngeal electromyography (LEMG), and histopathologic examination at 0 to 12 months after the injury. RESULTS: After the RLN injury, the average muscle fiber diameter and the average muscle bundle diameter of the affected muscles were decreased, and the average number of muscular cell nuclei per square inch increased. Fibrillation potentials were found 1 to 3 months after injury, and reinnervation potentials appeared 3 to 6 months after incomplete injury. For nerve transection and ligation, there was no reaction with LEMG instantly after injury involving vocal fold fixation. Vocal fold motion did not improve in members of the complete injury group, whereas all of the vocal folds in the members of the nerve ligation subgroup had limited activity in the later period. Various forms of vocal fold mobility were observed after injury in the half-section subgroup. Animals in the crush subgroup had normal EMG signals combined with abnormal LEMG signals with lower amplitudes after injury. Vocal fold fixation was not observed in this subgroup. CONCLUSIONS: We found the causes of nerve injury, in order of decreasing severity, to be transection, ligation, half-section, and crush.

Expression of the Foxp3 gene in spleen mononuclear cells of a mouse model with allergic rhinitis.

OBJECTIVE: There is growing speculation that the impairment in regulatory-T-cell (Treg)-mediated dominant tolerance may play an important role in the pathogenesis of allergic rhinitis (AR). The aim of this study was to investigate whether the changes in the forkhead transcription factor 3 (Foxp3) gene expression may aggravate nasal mucosal inflammation in allergic mice, and whether or not these features result from the loss of Tregs. METHODS: AR was induced by both intraperitoneal injection and intranasal administration of ovalbumin in BALB/c mice, while the control mice were treated with saline. A comparison of the frequency of CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells of the AR and control mice was made by flow cytometry. Spleen mononuclear cells were used for RNA extraction and RT-PCR was used to measure Foxp3 mRNA expression. RESULTS: The expression of the Foxp3 gene was significantly reduced in spleen mononuclear cells in AR mice compared with the control. Moreover, a significant decrease in the percentage of CD4+CD25+Foxp3+ Tregs was exhibited in peripheral blood mononuclear cells of AR mice compared with the control mice. CONCLUSION: The insufficiency of Tregs and the Foxp3 gene may contribute to the development of AR in mice.

[A histopathological study: chronic rhinosinusitis in adolescents versus adults].

OBJECTIVE: To conduct a histopathology study of adolescents with chronic rhinosinusitis (CRS) to compare the sinus mucosa with adult CRS and to explore their different pathological characteristics and lesion patterns. METHODS: Twenty cases of adolescents (median age: 14 years; range: 11-16 years) and 16 cases of adult CRS (median age: 36 years; range: 21-56 years) were performed functional endoscopy operation despite conventional medical therapy, histopathology of uncinate process mucosa were analyzed for inflammatory cell and morphologic studies. Archival tissue from adolescents and adults with CRS were stained with HE, AB-PAS (alcian blue-periodic acid-schiff) as well as Van Gieson. Statistical analysis t-test was performed using SPSS. RESULTS: Adolescents CRS sinus mucosa, as compared with adult CRS control, had a higher density of submucosal lymphocytes (t = 2.09, P = 0.04), higher density of submucosal plasma cell (t = 2.46, P = 0.02), lower density of submucosal eosinophils (t = -3.72, P = 0.01), thinner basement membranes and more intact epithelium (t = -2.50, P = 0.02 and t = 5.63, P = 0.00 respectively) and fewer submucosal mucous glands (t = -2.13, P = 0.04). There were significant differences between two groups. CONCLUSION: Lymphocytes were the predominant inflammatory cell type in the sinus mucosa of adolescents with CRS. But it has less eosinophilic inflammation, more plasma cell infiltration, basement membrane thickening, and mucus gland hyperplasia in characteristic adult CRS. Differences between adolescents and adult CRS suggest differing pathogenic mechanisms or progression in the inflammatory response with a protracted disease.

Associations among air pollutants, grass pollens, and daily number of grass pollen allergen-positive patients: a longitudinal study from 2012 to 2016.

BACKGROUND: Grass pollen is the most prevalent sensitizing aeroallergen to cause respiratory allergies in northern China. Air pollutants have a substantial effect on respiratory health and some pollens. This study aimed to investigate relationships among airborne grass pollen, air pollutants and allergic diseases, in order to determine their effects on patients with grass pollen allergies in Beijing, China, during the period from 2013 to 2016. METHODS: Data regarding autumnal grass pollens and air pollutants measured in Beijing from 2012 to 2016 were obtained from local governmental agencies. Patient data regarding specific immunoglobulin E (IgE) analyses from 2013 to 2016 were obtained from the Department of Allergy in Beijing Tongren Hospital. Spearman's rank correlation analysis was used to assess associations between the daily number of grass pollen allergen-positive patients and the following parameters: 3 clinically-relevant grass pollen genera (Artemisia, Humulus, and Chenopodium) and inhalable pollutants. RESULTS: Correlation analysis indicated that the daily number of grass pollen-positive patients was significantly associated with the peak period of grass pollens, as well as pollutants SO2 and NOx. Moreover, concentrations of air pollutants (eg, ozone, oxides of nitrogen [NOx ], and SO2 ) were consistently and significantly associated with concentrations of grass pollens; particulate matter 2.5 µm in diameter was negatively associated with Artemisia and Chenopodium pollens. CONCLUSION: Grass pollens exhibited substantial impact on allergic disease morbidity. Air pollutants impacted allergic disease and grass pollen. Thus, public health and clinical approaches to anticipate and reduce allergic disease morbidity from pollen and pollutants are needed.

Changes in gene expression in chronic allergy mouse model exposed to natural environmental PM2.5-rich ambient air pollution.

Particulate matter (PM) air pollution has been associated with an increase in the incidence of chronic allergic diseases; however, the mechanisms underlying the effect of exposure to natural ambient air pollution in chronic allergic diseases have not been fully elucidated. In the present study, we aimed to investigate the cellular responses induced by exposure to natural ambient air pollution, employing a mouse model of chronic allergy. The results indicated that exposure to ambient air pollution significantly increased the number of eosinophils in the nasal mucosa. The modulation of gene expression profile identified a set of regulated genes, and the Triggering Receptor Expressed on Myeloid cells1(TREM1) signaling canonical pathway was increased after exposure to ambient air pollution. In vitro, PM2.5 increased Nucleotide-binding oligomerization domain-containing protein 1 (Nod1) and nuclear factor (NF)-κB signaling pathway activation in A549 and HEK293 cell cultures. These results suggest a novel mechanism by which, PM2.5 in ambient air pollution may stimulate the innate immune system through the PM2.5-Nod1-NF-κB axis in chronic allergic disease.

Evaluating bone remodeling by measuring Hounsfield units in a rabbit model of rhinosinusitis: is it superior to measuring bone thickness?

BACKGROUND: The traditional method of evaluating bone remodeling in chronic rhinosinusitis is to measure bone thickness. The objective of this study was to determine the feasibility of measuring the computed tomography (CT) value in Hounsfield units (HU) as an method and explore whether it is superior to measuring bone thickness. METHODS: The study was a prospective animal trial. Twenty normal rabbits were included in the control group, and 60 rabbit models were inoculated with Staphylococcus aureus to induce rhinosinusitis. The rabbit models were divided into 3 groups according to the time of infection. All animals were euthanized after the CT exam. The samples were scored based on mucus and bone changes. The rabbits were divided into negative and positive groups according to whether bone remodeling was observed. We obtained diagnostic threshold values by measuring the bone thickness and HU of each rabbit's maxillary sinus and compared the values obtained using the 2 methods by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: The AUC for the measured bone thickness was 0.838, the diagnostic threshold was 1.165 mm. The AUC for the measured HU value was 0.937, the diagnostic threshold was 904.5. The correlation coefficients were r1 = 0.645 for the measured bone thickness and r2 = 0.797 for the HU measurement (r2 > r1 ; p < 0.01). CONCLUSION: Evaluating bone remodeling is feasible by measuring either the bone wall thickness or the CT value. However, using CT to evaluate the sinus bones in rabbits with rhinosinusitis appears to be a more valuable option.

A model to predict the incidence of allergic rhinitis based on meteorological factors.

Meteorological factors have been shown to affect the physiology, distribution, and amounts of inhaled allergens. The aim of this study was to develop a model to predict the trends for onset of allergic rhinitis (AR) patients. A total of 10,914 consecutive AR outpatients were assessed for the number of daily patient visits over a period of 4 years. Meteorological data were used to assess the relationship between meteorological factors and AR incidence by time-series data and regression analysis. Predictive models for incidence of AR were established in pollen-, dust mite- and mould-sensitive groups of patients, and the predictive performances of meteorological factors on the incidence of AR were estimated using root mean squared errors (RMSEs). The incidence of pollen-, dust mites- and mould-sensitive AR patients was significantly correlated with minimum temperature, vapour pressure, and sea-level pressure, respectively. The correlation between comprehensive meteorological parametric (CMP) and incidence of AR was higher than the correlation between the individual meteorological parameters and AR incidence. CMP had higher performance than individual meteorological parameters for predicting the incidence of AR patients. These findings suggest that the incidence of pollen-, dust mites- and mould-sensitive AR can be predicted employing models based on prevailing meteorological conditions.

Computed tomography and histopathological evaluation of osteitis in rabbit models with rhinosinusitis.

CONCLUSIONS: There is clear correspondence between HU and histopathological evaluation of osteitis. It is feasible to evaluate bone remodeling in rabbit models with rhinosinusitis by measuring the HU. OBJECTIVE: The objective of this study was to determine whether the HUs of rabbit CRS models can be used to objectively evaluate the degree of osteitis. METHODS: Sixty rabbit models were inoculated with staphylococcus aureus. The rabbits were divided into three groups. Each group was divided into a medication administration team and a control team. The HU of the bone in each image was measured. All of the animals were executed after the CT exam. The samples for the mucous and bone changes using light microscope observation were scored. These scores and the HU measurements were compared to the actual bone remodeling over time to examine whether we could evaluate bone remodeling by measuring the HU. RESULTS: The average HU scores in Groups A, B, and C were significantly higher than those of normal rabbits (p < .05). The mucous and bone scores increased as the experimental period lengthened (p = .042, 0.002). HU correlated with the mucous and bone scores in rabbit models with rhinosinusitis (coefficient r = .830, 0.641, 0.586, p = .000).

Anatomical and computed tomographic analysis of the interaction between the uncinate process and the agger nasi cell.

CONCLUSIONS: The agger nasi cell, together with the postosuperior portion of the uncinate process, was the key that unlocked the frontal recess. OBJECTIVES: To investigate the anatomical interaction between the upper portion of the uncinate process and the agger nasi cell. MATERIALS AND METHODS: Twenty-one skeletal skulls (42 sides) were studied by spiral computed tomography (CT) and endoscopy, and one cadaver head (2 sides) was studied by collodion-embedded sectioning in the coronal plane. RESULTS: The endoscopic view of the entrance of the middle meatus showed the middle part of the uncinate process and the middle part of the middle turbinate fused together as the axilla of the middle meatus. The middle portion of the uncinate process attached to the frontal process of the maxilla in all of the skeletal nasal cavities, as well as the lacrimal bone in 33 sides of the skeletal nasal cavities. On CT scans, the agger nasi cell was present in 38 sides of the skeletal nasal cavities. The agger nasi cell was medially, superiorly and inferiorly bounded by the uncinate process. The superior portion of the uncinate extended into the frontal recess and may insert into the lamina papyracea (33%), skull base (10%), middle turbinate, and a combination of these (57%).

Intranasal application of Epstein-Barr virus/lipoplex to abrogate eosinophillia in murine model of allergic rhinitis.

BACKGROUND: Currently anti-inflammatory therapy with steroids for allergic rhinitis need long-term repeated administration, although it is effective. Gene therapy is being suggested to substitute it. The aim of this study was to investigate nonviral vector mediated exogenous gene expression in COS-7 cells in vitro and the effect of intranasal mouse interleukin (mIL)-12 transgene expression on allergen induced eosinophil infiltration of nasal mucosa in a murine model of allergic rhinitis. METHODS: In vitro COS-7 cells were infected with Epstein-Barr virus (EBV)/lipoplex. The expression of IL-12 p70 in cell culture supernatant was examined by enzyme-linked immunosorbent assay (ELISA). In mice with ovalbumin (OVA) induced allergic rhinitis, EBV/lipoplex was administered by nasal drops before OVA challenge once a day from day 1 to day 10. The expression of IL-12 mRNA and protein, the change of eosinophil count in nasal mucosa and serum total IgE were measured 24 hours after the last challenge. RESULTS: EBV/lipoplex could effectively transfect COS-7 cells. The expression of IL-12 p70 in cell culture supernatant was significantly more than in blank control. IL-12 via EBV plasmid vector transduction could be overexpressed in vivo. In pGEG.mIL-12 treated models, the nasal mucosa revealed a high level of widespread mIL-12 transduction by immunohistochemistry and in situ hybridization. Histological evaluation revealed marked suppression of eosinophil infiltration in nasal mucosa. The eosinophil count in allergic rhinitis group [(26.5 +/- 9.8)/high-power field (HPF)] was significantly increased over control group [(0.40 +/- 0.52)/HPF] (F = 56.94, P < 0.01), while the count in IL-12 gene therapy group [(4.60 +/- 2.63)/HPF] was significantly less than that of allergic group (F = 56.9, P < 0.01). Serum total IgE between in gene therapy mice [(88.83 +/- 6.71) ng/ml] and allergic rhinitis mice [(103.1 +/- 5.7) ng/ml] showed a significant difference (F = 1216, P < 0.05). CONCLUSIONS: Nonviral EBV plasmid vector, pGEG.mIL-12 was able to overexpress exogenous gene both in vitro and in murine nasal mucosa in vivo. IL-12 overexpression via EBV/lipoplex could stem allergen induced eosinophil infiltration in nasal mucosa in murine models of allergic rhinitis, which may suggest a new cytokine immunogenetic therapy for allergic rhinitis.

[Histopathologic study of the ethmoid bone in chronic sinusitis].

OBJECTIVE: To investigate the histopathologic study of the ethmoid bone in chronic sinusitis (CRS) and the role of bone pathology in the pathogenesis of CRS. METHODS: Specimens of mucosa of ethmoid sinus with bone were collected during operation from 40 patients with CRS, 25 males and 15 females, aged 44.8, and specimens of mucosa of ethmoid sinus were collected from 16 patients with other otorhinolaryngologic diseases, 9 males and 7 females, aged 40.9 during operation. The specimens underwent HE, tartrate-resistant acid phosphatase, alkaline phosphatase, and Van Gieson staining so as to obtain the scores of nasal mucosa inflammation, pathology of mucoperiosteum and bone, and activity of bone remodeling. RESULTS: The average score of mucosal inflammation of the CRS group was 2.30 +/- 0.88, significantly higher than that of the control group (1.38 +/- 0.81, P = 0.004). The score of mucoperiosteum and bone pathology of the CRS group was 1.65 +/- 0.84, significantly higher than that of the control group (1.00 +/- 0.73, P = 0.004). The score of bone remodeling activity of the CRS group was 2.15 +/- 0.74, significantly higher than that of the control group (1.56 +/- 0.63, P = 0.007). In the CRS patients, the score of mucosal inflammation was not significantly correlated with the mucoperiosteum and bone pathology (R = 0.047, P = 0.772), and the activity of bone remodeling (R = 0.021, P = 0.897). CONCLUSION: The ethmoid bone of CRS patients shows marked fibrosis, bone remodeling, structure of woven bone, and pathologic changes similar to those of chronic osteomyelitis, especially bone absorption, new bone formation, etc.