Lysosomal proteases and protease inhibitors in nasal allergy and non-atopic sinusitis

Patterns of protease activity and levels of protease inhibitors were analyzed in both nasal secretions and tissue extracts from patients with nasal allergy and non-atopic sinusitis to investigate the role of proteases in the inflammatory reaction. Protease activity was measured using specific methyl-coumaryl-7-amide substrates. The pattern of protease activity in the nasal secretions of chronic sinusitis patients was similar to that in neutrophil lysate and quite different from that in plasma. Both gluthatione activation testing and inhibition testing using synthetic inhibitors revealed that the majority of proteases in both secretions and tissues are lysosomal thiol proteases such as cathepsins B and L. Neutrophilic elastase is also a major protease in nasal secretions. In acute sinusitis, both protease activity and inhibitor levels were very high, suggesting an interaction between proteases and inhibitors. Cathepsin B and B-like thiol proteases appear to play a key role in prolonging chronic inflammation against the healing process, due to their resistance to plasma inhibitors and the shortage of thiol protease inhibitors. Protease activity in the secretions of nasal allergy patients was very weak, and the reaction between proteases and inhibitors appeared to be weak.     

TNF-alpha and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion

OBJECTIVE: Vascular endothelial growth factor (VEGF) promotes angiogenesis and is associated with the invasion and metastasis of malignant tumors. It enhances vascular permeability and is expressed in inflammatory nasal as well as middle-ear mucosa. As the mechanism of VEGF induction during chronic inflammation, such as chronic paranasal sinusitis (CPS) remains to be clarified, we studied the factors regulating the production of VEGF in cultured human nasal fibroblasts and discussed the role of VEGF in the pathogenesis of CPS. METHODS: We used ELISA to quantify VEGF levels in paranasal sinus effusions, nasal secretions, and serum from patients with CPS. In addition, we cultured human nasal fibroblasts isolated from nasal polyps of CPS patients and studied the effects of hypoxia, TNF-alpha, and endotoxin on their production of VEGF using ELISA and PCR. RESULTS: The VEGF concentration was significantly higher in paranasal sinus effusions than in nasal secretions and serum. Nasal fibroblasts produced high levels of VEGF, when cultured under hypoxic condition and this production was remarkably enhanced in the presence of TNF-alpha or endotoxin. CONCLUSION: VEGF is locally produced in paranasal sinuses as well as nasal mucosa and its production is increased in patients with CPS. Hypoxia is associated with the production of VEGF by nasal fibroblasts and TNF-alpha and endotoxin may act synergistically to enhance VEGF production in paranasal sinuses under hypoxic condition.     

A protease inhibitor from human allergic nasal secretions

Protease and antiprotease activities were estimated in nasal secretions from patients with chronic sinusitis and nasal allergy, using [3H]-casein as substrate. In the purulent nasal secretions, strong protease activity was measured, but there was less activity in the allergic nasal secretions. In contrast, trypsin inhibitory activity in allergic nasal secretions was much higher than in nasal secretions from the patients with chronic sinusitis. A protease inhibitor was partially isolated from nasal secretions of the nasal allergic patients by Sephadex G-150 gel chromatography and characterized. This protease inhibitor has an apparent molecular weight of 10,000 D, determined by SDS-polyacrylamidegel electrophoresis. It depresses the activities of bovine pancreatic trypsin, bovine pancreatic chymotrypsin and proteases in nasal purulent secretions, whereas it does not inhibit porcine pancreatic elastase, papain, or human plasmin.     

变应性鼻炎鼻分泌物中上皮细胞集落和嗜酸粒细胞的检测

为了观察变应性鼻炎（allesgicrhinitis，AR）患者鼻分泌物中的上皮细胞集落和嗜酸粒细胞，对20例AR患者（AR组）和15例鼻窦炎患者（感染组）鼻分泌物中细胞成分进行了电镜观察，发现AR组鼻分泌物中有大量上皮细胞集落，其特征是数个至数十个上皮细胞成片状脱落，上皮细胞集落的数量和嗜酸粒细胞的数量、嗜酸粒细胞阳离子蛋白（eosinophiliccationicprotein，ECP）的含量呈正相关。感染组中上皮细胞集落和嗜酸粒细胞极少，ECP含量甚微。结果提示嗜酸粒细胞的ECP可能导致AR患者的鼻粘膜上皮呈片状脱落，对上皮结构造成损害。     

Quantitative cytology of nasal secretions under various conditions

Quantitative cytology was performed in nasal secretions of normal control (NC), seasonal allergic rhinitis in season (SAR), perennial allergic rhinitis (PAR), chronic sinusitis with mucoid secretion (MS), and chronic sinusitis with mucopurulent secretion (MPS). The majority of inflammatory cells were neutrophils in NC, MS, and MPS; the majority were eosinophils in SAR and PAR. The concomitant appearance of inflammatory cells in nasal secretions was found, i.e., there were significant correlations between neutrophil and eosinophil counts in MPS, and between eosionophil and basophil counts in SAR. The eosinophil/neutrophil ratio was more than 0.1 in SAR and PAR, but the ratio was less than 0.1 in all NC, all MPS, and in 93% of MS; this indicates that 0.1 in eosinophil/neutrophil ratio is the critical value between allergic and nonallergic nasal diseases.     

A technique for quantitative cytology of nasal secretions

Summary To quantitatively analyze cellular elements in mucopurulent nasal secretions from patients with chronic paranasal sinusitis, we studied five mucus-liquefying agents — dithiothreitol (DTT), ethylenediaminetetraacetic acid tetrasodium salt, propylene glycol, serratio peptidase and urea — with Hanks' balanced salt solution used as a control. Agents were compared for the number of cells, the mucus-liquefying effect and the staining characteristic of cells in cytocentrifuge-prepared smears. The results indicated that the treatment of nasal secretions with 10 mM DTT provides more clear and detailed cytological preparations for quantitative cytology of nasal secretions.     

Immunohistochemical detection of serous cells in nasal mucosa with monoclonal antibody against a component in human nasal secretion.

Secreting mechanisms of secretory cells in nasal mucosa and the changes of nasal secretions in chronic inflammatory sinusitis have been studied by the biochemical and histochemical methods. These methods could not clarify the changes of quality and quantity of nasal secretions and secretory cells. In order to obtain the specific marker for the secretions in different cells, we have produced monoclonal antibodies against a component in human nasal discharge. One antibody was selected for further characterization, because it stained submucosal serous cells specifically. This antibody stained the components of serous cells with molecular weight of 14 kD specifically, and was sensitive to periodate oxidation treatment. This antibody will be useful for detecting the subpopulation in secretory cells of human nasal mucosa, and may be serve as a biochemical probe for secretory activity of particular secretory cell types.     

Secretory IgA and serum type IgA in nasal secretion and antibody activity against the M protein

We studied IgA immunoglobulins in nasal secretions in order to clarify mucosal immunity of the nasal cavity and paranasal sinuses during chronic nasal infection. Secretory IgA and serum type IgA of 165 samples of nasal secretions were analyzed quantitatively by use of electroimmunodiffusion techniques, and the specific antibody activity of secretory IgA against the M protein of Streptococcus pyogenes was investigated by use of enzyme-linked immunosorbent assay. Results show that although the secretory IgA content in nasal secretions was elevated in chronic sinusitis, its specific antibody activity against the M protein was lower than that in normal subjects. This evidence suggests that nonspecific secretory IgA antibodies are predominantly produced in chronic sinusitis, and that mucosal immunity preventing the adherence of bacteria is impaired in the diseased mucosa.     

慢性鼻-鼻窦炎鼻息肉与正常鼻黏膜差异蛋白质的检测及其意义

目的采用蛋白质组学技术筛选慢性鼻-鼻窦炎、鼻息肉和正常鼻黏膜组织之间差异表达的蛋白质,初步鉴定出慢性鼻-鼻窦炎和鼻息肉的候选蛋白质标记物。方法应用固相pH4~7胶条行双向凝胶电泳,胶体考马斯亮蓝染色后,扫描2-DE胶,应用PDquest图像分析软件比较慢性鼻-鼻窦炎、鼻息肉和正常鼻黏膜组织2-DE图谱,得到三组之间差异表达的蛋白质点。经MALDI-TOF-MS鉴定后获得这些差异表达蛋白质的肽质量指纹图谱,用Mascot软件查询NCBInr和SWISS-PROT数据库,得出被测蛋白质的鉴定结果。结果所获双向凝胶电泳图谱分辨率高、重复性好。测得鼻息肉、慢性鼻-鼻窦炎及正常鼻黏膜组织的蛋白质平均斑点数分别为1020±40、1112±10和1008±25;平均匹配率分别为(93±2)%、(95±1)%和(90±3)%。三组之间共计有13个明显差异表达的蛋白质点。初步筛选出角蛋白8和阿朴脂蛋白AI作为鼻息肉的候选标志物,以及PLUNC蛋白、超氧化物歧化酶、自然杀伤细胞促进因子B、垂体腺苷酸环化酶激活肽为慢性鼻-鼻窦炎的候选标志物。结论用蛋白质组学技术能高通量筛选慢性鼻-鼻窦炎、鼻息肉和正常鼻黏膜间存在的差异表达蛋白质,这将为慢性鼻-鼻窦炎、鼻息肉分类、分型分期和预后判断标准寻找新的客观参考指标。     

Mixed nasal mucus as a model for sinus mucin gene expression studies

OBJECTIVE/HYPOTHESIS: It is necessary to obtain sinus mucus from the paranasal sinus cavities to study mucin gene expression occurring in the sinuses during chronic sinusitis. This requires an invasive procedure to access the sinus cavity. There are embryological as well as histological similarities between nasal and sinus epithelia; therefore, we postulated that the mucin expression in the secreted nasal and sinus mucins might be similar. Nasal mucus, which can be obtained easily, could then replace sinus mucus in these studies. STUDY DESIGN: Sinus and nasal mucus from six patients with chronic sinusitis were analyzed in this study. METHODS: High-molecular-weight glycoproteins (mucins) were isolated and purified by sequential density gradient centrifugation in caesium chloride (CsCl). Enzyme-linked immunosorbent assay was performed to identify the antigenic identity of these mucins. RESULTS: The MUC2, MUC5AC, and MUC5B mucin genes were all expressed in the nasal and sinus mucus secretions. Antigenic studies showed an inverse relationship between MUC2 and MUC5AC expression in nasal and sinus mucus secretions. The MUC5B gene was the major mucin gene expressed in sinus mucus but not in nasal mucus. Expression of MUC2 was significantly higher in sinus mucus. Expression of MUC5AC was different between nasal and sinus mucus. CONCLUSIONS: Individual mucin expression in sinus and nasal mucus was markedly different. From this preliminary study, we conclude that nasal mucus is not a suitable substitute for sinus mucus in sinus mucin gene studies and that different pathological processes are taking place in nasal and sinus tissue in chronic sinusitis.     

Pulmonary aspiration of nasal secretions in patients with chronic sinusitis and asthma

BACKGROUND: The role of silent aspiration of nasal secretions in the pathogenesis of asthma has often been questioned. OBJECTIVE: To investigate the presence of pulmonary aspiration of nasal secretions during sleep in patients with chronic sinusitis and asthma and in healthy controls. DESIGN: Prospective, controlled trial. SUBJECTS: The study included 13 patients with chronic sinusitis and asthma and 12 healthy controls. The diagnoses were based on history, physical examination findings, radiologic assessments, and pulmonary function test results. INTERVENTIONS: A radioactive tracer was prepared by diluting 10 mCi of technetium 99m-labeled macroaggregated albumin in 10 mL of physiologic saline. At 10 PM, just before the patients went to sleep, the solution was sprayed into their nostrils. The subjects were examined with a gamma camera to obtain views of the thorax at 8 AM the following morning. The average counts of the lungs and background and the actual lung counts (average lung count minus average background count) were determined. RESULTS: The average counts of the lungs were significantly greater than the average counts of the background in both the sinusitis-asthma group (P =.001) and the control group (P =.002). The difference in the actual counts of the lungs was not significant between the 2 groups (P =.79). CONCLUSIONS: The nasal secretions were aspirated into the lungs both in patients with sinusitis and asthma and in healthy adults during sleep, and the relative amounts that were aspirated did not differ significantly between the 2 groups (P =.79). The amount of the aspirated material alone is probably not responsible for the pathogenesis of asthma in patients with chronic sinusitis.     

Retention fluids of chronic sinusitis induce neutrophil adherence to microvascular endothelial cells.

The adherence of circulating leukocytes to the vascular endothelium is a critical step in the emigration of leukocytes through blood vessel walls to inflammatory lesions. The influence of nasal secretions on the adherence of neutrophils to the vascular endothelium was investigated using monolayers of human mucosal microvascular endothelial cells derived from the inferior turbinate. Preincubation of vascular endothelial cells with retention fluids from the maxillary sinus of the patients with chronic sinusitis showed increased neutrophil adherence. Recombinant IL-1 beta was also tested and found to induce adherence of neutrophils to human mucosal microvascular endothelial cells. However, no adhesive effect was observed with the nasal secretions of nasal allergy. An enzyme-linked immunosorbent assay detected considerable amounts of IL-1 beta in the chronic sinusitis retention fluids, while the amounts of IL-1 alpha and TNF-alpha were very low. The increased adhesion of the neutrophils by the retention fluids of chronic sinusitis was also neutralized by the incubation with anti-IL-1 beta antibody in a dose dependent manner. These findings suggest that IL-1 beta in the paranasal secretion of chronic sinusitis induces the adherence of neutrophils to vascular endothelium and subsequent infiltration of neutrophils in the paranasal sinuses, thus contributing to the persistence of chronic sinusitis.     

Monoclonal antibody-detectable carbohydrate epitopes of human nasal secretions are differentially expressed in tissue and diseases

To study the differential carbohydrate expression of airway secretions, we have produced a series of monoclonal antibodies that recognize human nasal secretory cell products. Mice were immunized with purified nasal secretion from patients with chronic sinusitis (CS) and hybridomas were selected by ELISA and immunohistochemical staining of the maxillary sinus mucosa from patients with CS. Eighteen antibodies were obtained. Antibody HCS 18 reacted with epithelial goblet cells, antibody HCS 4, 5, 6, and 16 stained submucosal gland cells, and antibody HCS 13 and 15 reacted with epithelial goblet cells, submucosal gland cells, and endothelial cells of vessels. The other eleven antibodies recognized epithelial goblet cells and submucosal gland cells. Cross-reactivity of these antibodies with secretory cells in other organs and in other species was determined and the different staining pattern was observed between upper and lower airway tissue, suggesting that secretory products from upper and lower airways may be different. Reactivity of the antibodies with nasal secretory cells was also examined in patients with perennial allergic rhinitis (AR) and normal subjects. Antibody HCS 18 weakly reacted with nasal glands in the tissue from CS and AR patients, but minimally reacted with gland cells in normal tissue. Antibody HCS 1 and 7 partially lost their reactivity with nasal epithelium of inferior turbinate from normal subjects and AR patients. These antibodies may be useful to study nasal secretions.     

阿奇霉素对慢性鼻-鼻窦炎患者术腔黏膜中NF-kBp65IL-8表达的影响

目的 观察阿奇霉素对慢性鼻-鼻窦炎患者术腔黏膜中NF-kBp65、IL-8表达的影响,探讨阿奇霉素治疗术腔慢性炎症的机制。方法 将45例慢性鼻-鼻窦炎术后2周的患者随机分成阿奇霉素组、头孢菌素组和对照组进行随访治疗,所有患者均应用布地奈德喷鼻、生理盐水冲洗术腔,阿奇霉素组加用阿奇霉素500mg口服,每日1次;头孢菌素组加用头孢菌素500mg口服,每日1次;对照组继续同前治疗,连续3周后,取术腔病变黏膜作为实验标本,应用免疫组织化学PV-6000二步法检测各组治疗前后及三组间术腔黏膜上皮细胞、炎性细胞中NF-kBp65和IL-8表达的情况,计数阳性细胞数。结果 慢性鼻-鼻窦炎患者术腔黏膜呈慢性炎症表现,NF-kBp65主要表达在术腔黏膜的黏膜上皮细胞、炎性细胞的胞浆和部分胞核。IL-8主要表达在黏膜的上皮细胞、炎性细胞的胞浆。三组治疗后NF-kBp65和IL-8在上皮细胞和炎性细胞中的表达均较治疗前减少(P<0.05);阿奇霉素组治疗后术腔黏膜上皮细胞和炎性细胞中NF-kBp65、IL-8的表达均较头孢菌素组、对照组明显减少(P<0.05);头孢菌素组与对照组治疗后上皮细胞和炎性细胞中NF-kBp65、IL-8的表达无明显差别(P>0.05)。结论 阿奇霉素联合应用布地奈德抑制慢性鼻-鼻窦炎患者术腔黏膜上皮细胞、炎性细胞中NF-kBp65、IL-8的表达,较单独应用布地奈德明显,可能是阿奇霉素治疗慢性炎症的机制之一,对慢性鼻-鼻窦炎患者术腔黏膜慢性炎症的转归具有促进作用。     

Expression and clinical significance of PLUNC protein in nasal polyp and chronic sinusitis tissue

We conducted a study to validate the expression of PLUNC (palate, lung, and nasal epithelial clone) protein in nasal polyp and chronic sinusitis tissue by immunohistochemistry. We also explored the relationship between the intensity of positive immunohistochemical staining for PLUNC protein and postoperative therapeutic efficacy. Our study population consisted of 34 patients with nasal polyps and 30 with chronic sinusitis who had undergone surgical treatment, along with 18 healthy controls who did not undergo surgery. All samples were stained according to the streptavidin-peroxidase immunohistochemical method to examine PLUNC protein expression. The surgical patients were evaluated for clinical therapeutic efficacy 6 months postoperatively. The association between efficacy and the intensity of PLUNC protein positivity was examined by the Spearman rank correlation analysis. Intensity was rated as either +++(>50% positive cells), ++ (26 to 50% positive cells),+ (≤25% positive cells), or -(no positive cells). We found that the most common levels of PLUNC positivity were + in the patients with nasal polyps, +++ in the patients with chronic sinusitis, and ++ in the controls (p< 0.01). Analysis of the Spearman rank correlation indicated that the intensity of PLUNC protein expression was significantly correlated with postoperative therapeutic efficacy (p< 0.001). We conclude that PLUNC protein is an essential factor in the innate defense mechanism of the nasal mucosa. The immunohistochemical staining of PLUNC protein could have clinical benefit in terms of predicting therapeutic efficacy and outcomes in patients with nasal polyps or chronic sinusitis.     

Role of local immunoglobulin E specific for Alternaria alternata in the pathogenesis of nasal polyposis

OBJECTIVE/HYPOTHESIS: The role of fungal pathogens in the etiology of nasal polyposis remains unclear. The aim of this study was to determine whether there was a correlation between the presence of Alternaria-specific immunoglobulin (Ig)E antibodies, eosinophilic inflammation, and the development of nasal polyps. STUDY DESIGN: Prospective study. METHODS: Serum and nasal tissue homogenates from 21 patients with manifestations of chronic sinusitis with nasal polyps were compared with specimens from 13 chronic sinusitis patients without polyps and 8 healthy controls. The Phadia ImmunoCAP and enzyme-linked immunosorbent assay were used to quantify levels of total IgE and Alternaria-specific (IgE, IgG, and IgA) antibodies. Eosinophil cationic protein (ECP) and tryptase levels were measured in tissue homogenates, whereas the inflammatory response was evaluated using tissue eosinophil counts in tissue samples. RESULTS: Serum analysis revealed no difference in the levels of total IgE and Alternaria-specific IgE, IgG, and IgA antibodies between the study groups. In contrast, the levels of Alternaria-specific IgE in tissue with polyps were significantly higher than in nonpolyp tissue. Increases in total tissue IgE paralleled increased levels of Alternaria-specific IgG and IgA antibodies in chronic sinusitis with nasal polyps as compared with control groups. A positive correlation was found between Alternaria-specific IgE and ECP in tissue. Increased mean levels of ECP corresponded to increased eosinophil counts in the group of patients with polyps. CONCLUSIONS: Alternaria-specific IgE and eosinophilic inflammation in nasal tissue correlates with the incidence of nasal polyps irrespective of specific IgE antibodies in serum. Together, the correlation between the local immune responses and the eosinophilic inflammation in nasal polyps suggests a possible role of Alternaria in the pathogenesis of nasal polyposis.     

儿童鼻窦炎鼻息肉治疗分析

目的探讨儿童鼻窦炎鼻息肉患者的治疗方式与疗效。方法对175例(288侧)儿童鼻窦炎鼻息肉患者的临床资料进行分析。年龄5～17岁,男女比例124:51。其中合并鼻中隔偏曲68例(38.86%),合并鼻窦囊肿16例(9.14%),合并腺样体肥大17例(9.71%)。鼻窦炎并发眶内并发症4例,并发面部蜂窝织炎1例,并发球后视神经炎2例。有哮喘病史者21例(12%),伴有变应性鼻炎症状者62例(35.43%)。173例行鼻内镜手术治疗及系统的术后6～12个月复查随访。结果治愈103例(58.86%),好转54例(30.86%),总有效率89.71%,无效18例(10.29%)。结论儿童鼻窦炎鼻息肉经系统保守治疗无效,应采用手术疗法,手术方式应根据患者的年龄、病变范围及合并症情况综合考虑,以改善鼻腔鼻窦通气引流功能为目的。术中应建立宽敞的术腔入路以利于术后换药及避免术腔粘连。     

慢性鼻窦炎鼻息肉与变应性因素相关性的探讨

目的 探讨变应性因素在慢性鼻窦炎鼻息肉发病中的作用。方法回顾性分析1882例慢性鼻窦炎鼻息肉患者术前鼻腔分泌物涂片嗜酸粒细胞及变应原皮肤试验检查结果，并将其变应性症状和体征出现的比例与临床分型分期加以比较。结果①1882例慢性鼻窦炎鼻息肉患者中60．4％(1137例)的患者伴有不同程度的变应性症状和体征，25．3％(477例)的患者合并变应性鼻炎，2．1％(39例)的患者合并支气管哮喘；②在Ⅰ型(708例)和Ⅱ型(823例)各分期的患者中，合并变应性鼻炎及支气管哮喘的发生率和嗜酸粒细胞、皮肤变应原试验阳性率以及变应性鼻炎临床症状出现的百分率分别由低到高出现，Ⅱ型3期各项比例最高；③42．2％(795例)的患者变应原皮肤试验阳性，其中94．3％对常年性变应原呈阳性反应；④26．3％(495例)的患者伴有变应性鼻炎的临床症状，其中99．8％(494／495例)为常年性发作；⑤有前期手术史的病例占38．9％(732例)，其中合并变应性鼻炎者占有前期手术史例数的38．3％(280例)，占合并变应性鼻炎患者的58．7％(477例)。结论变应性因素特别是常年性变应性鼻炎与慢性鼻窦炎鼻息肉的病变程度和病变范围有关。同时变应性鼻炎也促进了疾病的复发。     

Vascular endothelial growth factor and children featuring nasal polyps

BACKGROUND: The aim of this study is to explore the expression of vascular endothelial growth factor within nasal polyps, and the implication of such expression as regards the development of nasal polyps amongst children. MATERIAL AND METHODS: Sixty children suffering from chronic rhinosinusitis were enrolled in this study. Amongst them, 30 patients featured rhinosinusitis with associated nasal polyps. A biopsy specimen was taken from the stalk or the base of the nasal polyp for nasal-polyp sufferers, and the ethmoid sinus for study participants who featured no nasal polyps. The primary lesions biopsied were immunohistochemically stained with a specific endothelial-cell marker and also stained for the presence of vascular endothelial growth factor. The specific level of vascular endothelial growth factor and the mean number of blood vessels present in a visual microscopic (biopsied-specimen) field were calculated under light microscopy (x400). RESULTS: The number of vascular endothelial growth factor-expressing cells for the nasal-polyp group and for the sinusitis group was, respectively, 20.8+/-4.0 and 11.5+/-3.4 per visual field. Correspondingly, the mean intra-polyp blood-vessel density for the nasal-polyp group and that for the control group was, respectively, 10.5+/-2.6 and 5.0+/-1.9 per visual field. The mean intra-polyp blood-vessel density and the number of vascular endothelial growth factor-expressing cells proved to be significantly greater amongst individuals from the nasal-polyp group than was the case for their analogs from the sinusitis group (P<0.01, for both). The presence of vascular endothelial growth factor was found to be distributed predominantly within the vascular endothelium and the mast cells of polyp tissue. In addition, the level of vascular endothelial growth-factor expression and the mean blood-vessel count per field correlated significantly for nasal-polyp tissue (P<0.001). Furthermore, the relative size of nasal polyps correlated significantly with the number of (intra-polyp) vascular endothelial-cell growth factor-expressing cells and the mean blood-vessel density (P<0.05, for both). CONCLUSION: The level of expression of vascular endothelial-cell growth factor (VEGF) and the mean blood-vessel density were shown to be significantly greater within nasal polyps than within corresponding sinusitis mucosa. Clinically, the expression of both of these parameters correlated well with the relative size of nasal polyps. Vascular endothelial growth factor participates in the formation of nasal polyps amongst children suffering from chronic rhinosinusitis (CRS).