Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and nasal polyposis

OBJECTIVE: To compare concentrations of interleukin-5 (IL-5), immunoglobulin E (IgE), eosinophilic cationic protein (ECP), and soluble intercellular adhesion molecule-1 (sICAM-1) in nasal secretion and serum of patients with chronic nonallergic sinusitis, allergic rhinitis, and nonallergic nasal polyposis to obtain information about the pathogenesis of these diseases. METHODS: Nasal secretion and serum were analyzed by routine enzyme-linked immunosorbent assay techniques. Nineteen patients with chronic nonallergic sinusitis, 24 patients with seasonal allergic rhinitis, and 18 patients with nonallergic nasal polyposis were included in the study. Eight healthy, nonallergic probands served as control subjects. RESULTS: Significantly elevated concentrations of IL-5 (5-fold, P < .05) and IgE (15-fold, P < .01) were detected in nasal secretion of patients with allergic rhinitis (IL-5, 51.8 +/- 13.2 pg/mL; IgE, 41.9 +/- 20.9 kU/L) or nonallergic nasal polyposis (IL-5, 57.9 +/- 36.9 pg(mL; IgE, 40.5 +/- 20.2 kU/L) compared with controls (IL-5, 10.6 +/- 7.8 pg/mL; IgE, 2.8 +/- 0.5 kU/L) or with patients with chronic nonallergic sinusitis (IL-5, 16.5 +/- 13.2 pg/mL; IgE, 5.4 +/- 3.1 kU/L). There were no significant differences between patients with allergic rhinitis and those with nonallergic nasal polyposis. Concentrations of ECP were significantly elevated (sixfold, P < .01) in patients with allergic rhinitis (297.8 ng/mL +/- 173.1) compared with controls (52.4 +/- 28.0 ng/mL) or patients with chronic nonallergic sinusitis (44.8 +/- 40.1 ng/mL), whereas twofold higher concentrations (not significant) of ECP were observed in patients with nonallergic nasal polyposis (107.1 +/- 26.6 ng/mL). Significantly elevated concentrations of sICAM-1 in nasal secretion (threefold, P < .05) were detected only in patients with chronic nonallergic sinusitis (79.4 +/- 45.6 ng/mL). The elevated sICAM-1 nasal secretion values in this group correlated significantly (P < .05) to the serum values. CONCLUSIONS: Equally elevated concentrations of IL-5 and IgE in patients with allergic rhinitis and nonallergic nasal polyposis implicated similar pathogenic processes in both diseases. Whereas the pathogenesis of allergic rhinitis is IgE-specific, the pathogenesis of nasal polyps is not as clear. IL-5 was suggested to play a pivotal role in tissue eosinophilia, which was confirmed by data in the present study. Elevated concentrations of ECP were suggested to result from tissue eosinophilia--a characteristic of both diseases. Elevated concentrations of sICAM-1 in patients with chronic nonallergic sinusitis pointed to its key role in the recruitment of neutrophils into the inflamed tissue, whereas an important role in eosinophil recruitment was ruled out.     

Activated and Non-activated Eosinophils in Patients with Chronic Rhinosinusitis

Nasal polyps develop out of an oedematous swelling of the mucous membrane, which is probably a localized mediator-dependent reaction of the mucous membrane in the lamina propria. Among other things, eosinophil cationic protein (ECP) is released from activated eosinophils. In previous studies, ECP was considered as measuring the degree of allergic dermatological illnesses and therapy was given accordingly. A group of 54 patients with massive polyposis requiring functional endoscopic sinus surgery was examined. After surgery they were treated with local and systemic cortisone. Polypous tissue samples were collected and counted for the number and ratio of activated and non-activated eosinophils, and the serum titre of ECP was measured simultaneously using a fluoroimmunoassay (test kit, Kabi Pharmacia, Sweden). The aim of the study was to evaluate the activity of the disease and to gain hints for a specific therapy. The presence of these eosinophils was demonstrated by immunohistochemical methods, using EG antibodies against non-activated and EG antibodies against activated (i.e. secreted form of ECP) eosinophils. Depending on the duration of treatment with systemic and local corticosteroids, there was a considerable decrease in activated eosinophils and the level of serum ECP. Consequently, cortisone can be applied in the treatment of eosinophilic nasal polyps. As the number of activated eosinophils in the tissue is an indicator for the activity of the chronic inflammation it can be deduced from our study that local and/or systemic cortisone application successfully stops the growth of eosinophilic nasal polyps. The number and ratio of activated and non-activated eosinophils seem to be reliable indicators for the activity of chronic polyposis.     

Role of local immunoglobulin E production in the pathophysiology of noninvasive fungal sinusitis

OBJECTIVES/HYPOTHESIS: Immunoglobulin (Ig)E-mediated hypersensitivity to fungi has been postulated to explain allergic fungal sinusitis (AFS). Not all patients suspected to have AFS demonstrate systemic evidence of allergy. Locally produced IgE might explain those patients with no systemic evidence of allergy but clinical features of AFS. The aim was to determine whether fungal-specific IgE could be demonstrated in sinus mucin in patients with eosinophilic mucin rhino-sinusitis. STUDY DESIGN: A prospective study was undertaken in a tertiary rhinology practice in Adelaide, South Australia. METHODS:: Eighty-six consecutive patients with nasal polyposis and thick, colored macroscopically "fungal-like" sinus mucin at time of surgery for chronic sinusitis were entered in the study. The sinus mucin was liquefied and underwent testing for fungal-specific IgE (Pharmacia UniCAP) and fungal culture. Serum fungal-specific and total IgE, eosinophil count, C-reactive protein (CRP), and eosinophilic cationic protein (ECP) were measured. RESULTS: Fifty-six (65%) patients were fungal culture positive, and 37% had a detectable fungal-specific IgE in sinus mucin. Data were available to classify 81 patients: AFS = 24 (30%), AFS-like = 6 (7%), nonallergic eosinophilic fungal sinusitis = 32 (40%), nonallergic, nonfungal eosinophilic sinusitis = 19 (23%). Patients with AFS were significantly more likely to have fungal-specific IgE in sinus mucin (17/24, 71%, P =.02). In all fungal culture-positive patients, positive mucin fungal-specific IgE was significantly associated with systemic fungal allergy (P =.005), but a raised total serum IgE was not. Six (19%) of the 32 patients with positive fungal cultures but negative serum fungal-specific IgE had a positive mucin fungal-specific IgE, suggesting that they may be reclassified as AFS. The mean ECP and total IgE were raised most significantly in the AFS subgroup. CONCLUSIONS: This is the first study to show that fungal-specific IgE may be demonstrated in sinus mucin. It was significantly associated with systemic fungal allergy and may play a role in a minority of fungal sinusitis patients in the absence of systemic fungal allergy.     

白细胞介素-5与嗜酸性粒细胞阳离子蛋白在鼻息肉发病中的意义及相互关系

目的：探讨白细胞介素—5(IL—5)及嗜酸性粒细胞阳离子蛋白(ECP)在鼻息肉发病中的作用及相互关系。方法：采用pharmacia CAP荧光免疫系统和ELISA双抗体夹心法对30例鼻息肉患者(鼻息肉组)和8例鼻中隔偏曲或阻塞性睡眠呼吸暂停综合征(OSAS)患者(对照组)分别进行血清中ECP及组织匀浆中ECP、IL—5的检测。结果：鼻息肉组匀浆中IL—5的水平明显高于对照组，其差异有显著性意义(P＜0．05)；鼻息肉组血清与匀浆中的ECP含量明显高于对照组，其差异亦有显著性意义(P＜0．05)。鼻息肉组匀浆中IL—5与血清中ECP水平呈明显正相关(r＝0．598，P＜0．05)；与匀浆中的ECP水平也呈正相关(r＝0．451，P＜0．05)。结论：ECP是嗜酸性粒细胞活化的标志，也是导致鼻腔炎症发生的重要因子；IL—5在鼻息肉组织中高表达，并与血清和组织中ECP水平密切相关，共同促进鼻腔炎症过程的不断加重。     

A study on the concentration of eosinophil cationic protein in chronic sinusitis]

The relationship between eosinophil and chronic sinusitis was investigated by measuring the concentration of eosinophil cationic protein (ECP). In addition to the blood, a cytological brush was inserted into middle meatus to scrape the nasal membrane, and the concentration of ECP in the collected specimen was measured. There was a moderate degree of correlation between the blood eosinophil count and the ECP concentration in the blood (r = 0.543, p < 0.01). On the other hand, there was high degree of correlation between the number of EG2-positive cells and ECP of the nasal membrane in the middle meatus (r = 0.805, p < 0.001), reflecting the amount of ECP in the nasal mucous membrane. The ECP in 10 control group subjects and 14 patients with severe chronic sinusitis and nasal polyps was significantly lower than that in 14 patients with severe chronic sinusitis and asthma (p < 0.01). The ECP concentration of the nasal membrane in the middle meatus was significantly lower in patients showing a good postoperative course compared with patients showing a poor postoperative course following Endoscopic Sinus Surgery (p < 0.01). These findings suggest that eosinophils are closely related to the pathology and clinical course of chronic sinusitis, and that the ECP concentration of the nasal membrane in the middle meatus reflects the pathology of chronic sinusitis. The ECP concentration thus has potential as a prognostic indicator for chronic sinusitis.     

Nasal polyposis: from cytokines to growth

Nasal polyposis (NP) is a chronic inflammatory condition that is mostly characterized by an infiltration of eosinophils. How this eosinophilic inflammation leads to polyp formation remains largely unclear. In order to identify the most important factors in polyp growth, first we report the histologic features of two early stage manifestations of eosinophilic nasal polyps compared to their surrounding normal mucosa and mature polyps from the same patients. Histomorphologic analysis of these early stage manifestations of NP showed the presence of eosinophils, forming a subepithelial cap over a pseudocyst area that was filled with albumin. In mature NP, a large pseudocyst area containing albumin was surrounded by subepithelial eosinophilia. Second, in an approach to quantify and to study possible relations between eosinophilic inflammation and changes in extracellular tissue components we measured interleukin-5 (IL-5), eotaxin, eosinophil cationic protein (ECP), leukotrienes (LTC4/D4/E4), transforming growth factor-beta 1 (TGF-beta 1), fibronectin, hyaluronic acid, and albumin in nasal tissue homogenates of 31 subjects. Nasal polyp samples (n = 16) were obtained during routine endonasal sinus surgery, whereas control non-polyp samples (n = 15) from subjects with (6) and without (9) allergic rhinitis were obtained from the inferior turbinate during septum surgery. In the group of polyp patients 11 received no treatment, whereas 5 were treated with oral glucocorticoids (GCS) within 4 weeks before surgery. IL-5 was measurable in 8 of 11 untreated NP, whereas IL-5 could not be detected in all 15 controls nor in 4 of 5 oral corticoid-treated polyps. The comparison between the untreated polyp group and controls showed significantly higher concentrations of IL-5, eotaxin, ECP, and albumin in polyp supernatants, whereas TGF-beta 1 was significantly lower. In the oral GCS-treated group, ECP and albumin were significantly reduced compared to untreated nasal polyps. The same tendency, but not reaching significance, was seen for eotaxin and fibronectin, while no difference was found for LTC4/D4/E4 and hyaluronic acid between the groups. Our observations suggest a deposition of albumin (and possibly other plasma proteins) and extracellular matrix proteins, which may be regulated by the subepithelial eosinophilic inflammation, as a possible pathogenic principle of polyp formation and growth. IL-5 and eotaxin are found to be key factors for eosinophilic accumulation and activation in NP. Oral corticoid treatment may lead to the shrinkage of NP by downregulation of the eosinophilic inflammation and reduction of the extravasation and deposition of albumin in NP.     

Humoral mucosal immunity in allergic rhinitis

BACKGROUND: Mucosa-immunologic aspects are gaining an increasing awareness in the pathophysiology of type I allergies. Humoral mucosal immune responses are dominated by secretory IgA, but there is evidence for a relevant role of IgG in nasal mucosa-associated lymphoid tissue. OBJECTIVE: was to measure allergen-specific immunoglobulins (IgA and IgG) in nasal secretions as an expression of a humoral mucosal immune response in allergic rhinitis. For tissue eosinophilia we studied nasal Eosinophilic Cationic Protein (ECP) and for mast cell activation nasal tryptase. METHODS: Nasal secretions of 40 patients suffering from allergic rhinitis were analyzed for allergen-specific IgA, IgG, and IgE, and for ECP and tryptase. Patients were highly sensitized against the major allergens of house dust mites, timothy, and birch pollen. 43 non-atopic individuals served as controls. In order to study possible effects of the actual pollen season on the studied parameter we secondly compared patients allergic to seasonal allergens co- (n = 28) and extra-seasonally (n = 41). In order to determine a possible influence of allergen-specific IgA in eosinophilic degranulation we additionally studied 5 patients after nasal allergen challenge. RESULTS: In allergic rhinitis we found significantly increased levels of allergen-specific immunoglobulins of all studied subclasses and allergens in nasal secretions. Comparison of nasal ECP and tryptase showed significantly increased concentrations in allergic individuals as well. Co-seasonally we found elevated allergen-specific IgE, ECP, and tryptase but lower concentrations of allergen-specific IgA and IgG. There was no association between late phase eosinophilia and IgA concentrations after local allergen challenge. CONCLUSIONS: The occurrence of allergen-specific immunoglobulins in nasal secretions is interpreted as a local humoral mucosal immune response. The physiologic role of local allergen-specific immunoglobulins is not clear to date. Involvement in degranulation of eosinophils or mast cells, like suggested before, seems unlikely.     

Fungal-specific humoral response in eosinophilic mucus chronic rhinosinusitis

OBJECTIVES/HYPOTHESIS: An immunoglobulin (Ig)E-mediated allergic pathogenesis is presumed in allergic fungal sinusitis (AFS), yet extensive polyps and eosinophilic mucus (EM) in the paranasal sinuses may also occur in the absence of allergy. Although a noninvasive fungal pathogenesis is presumed in all chronic rhinosinusitis with EM (EMCRS), fungal-specific nonallergic immune responses have not been thoroughly investigated. We tested the hypothesis that there is a fungal-specific humoral response in EMCRS and that it is not confined to IgE. STUDY DESIGN: EMCRS patients were prospectively stratified into subgroups based on the presence or absence of fungi within EM and of fungal-specific systemic IgE. There were 12 AFS, 5 AFS-like, 8 nonallergic fungal eosinophilic sinusitis (NAFES), and 5 nonallergic, nonfungal eosinophilic sinusitis (NANFES) patients. METHODS: Alternaria alternata and Aspergillus fumigatus-specific serum IgE, IgG, IgM, and IgA was measured by enzyme-linked immunosorbent assay and compared with strictly defined healthy and disease-control groups. RESULTS: Fungal-specific IgG (Alternaria alternata P = .0002; Aspergillus fumigatus P = .004), and IgA levels (Alternaria alternata P = .0016; Aspergillus fumigatus P = .002) were higher in EMCRS compared with healthy volunteers but not with disease controls. Fungal-specific IgG3 levels were significantly elevated in all the EMCRS subgroups compared with controls for either fungal antigen (P < .0001). Importantly, fungal-specific IgE levels were not significantly different between fungal-allergic EMCRS and disease controls. CONCLUSIONS: Fungal-specific immunity characterized by serum IgG3 and not IgE, distinguished the EMCRS subgroups from control groups regardless of the presence of fungus within EM or of systemic fungal allergy. Fungal-specific IgE responses in fungal-allergic EMCRS were no different to those in fungal-allergic controls, thus challenging the presumption of a unique pathogenic role of fungal allergy in "allergic fungal sinusitis."     

Study of allergic fungal sinusitis in 40 surgical cases of chronic paranasal sinusitis

Allergic fungal sinusitis is chronic and paranasal, related to fungal allergy. Many papers on allergic fungal sinusitis have been reported in the United State, and the incidence is 5% to 10% among patients with chronic paranasal sinusitis. Although cases of allergic fungal sinusitis have been reported in Japan, the incidence is unclear. We studied allergic fungal sinusitis in 40 consecutive patients--26 men and 14 women--undergoing endoscopic sinus surgery at Keiyukai Sapporo Hospital December 2000 to July 2001. We checked for allergic rhinitis and asthma, a history of surgery for nasal polyps and chronic sinusitis, the presence of nasal polyps, grading of sinusitis via computed tomography, nonspecific IgE and allergen-specific IgE for fungi in serum, eosinophilia in nasal smears, paranasal eosinophilic mucin, and histology and fungal culture of paranasal sinus mucus. None had typical allergic fungal sinusitis, but 1 had eosinophilic paranasal mucin, high IgE, and false-positive IgE for fungi. We studied clinical data and histology of fungi and paranasal mucosa in 9 cases with fungal maxillary sinusitis, but none had allergy or eosinophilic mucin. This suggested that few patients with allergic fungal sinusitis exist among those with chronic paranasal sinusitis.     

慢性鼻窦炎鼻息肉中转录因子NKX2-1调控嗜酸性炎症反应的作用

目的 研究新型转录因子NKX2-1在慢性鼻窦炎伴鼻息肉发病中调控嗜酸性免疫炎症反应的作用。 方法 功能性鼻内镜手术获取鼻息肉及非变应性单纯鼻中隔偏曲患者鼻甲标本,通过酶联免疫、免疫组化及蛋白印迹检测细胞因子IL-5、IFN-γ、IL-17A,转录因子NKX2-1及趋化因子CCL17在患者中的表达。 结果 鼻息肉患者中IL-5阳性表达率为24%,并伴有IL-4、IgE等炎症介质及酸性粒细胞浸润升高特征;40%鼻息肉患者关键细胞因子阴性表达并伴有IL-1β、IL-8等非嗜酸性炎症升高特征。单纯IL-5+鼻息肉患者NKX2-1表达低于非变应性单纯鼻中隔偏曲患者,单纯IL-5+鼻息肉患者中趋化因子CCL17高于非变应性单纯鼻中隔偏曲患者,且与趋化嗜酸性粒细胞相关。 结论 新型转录因子NKX2-1在不同内在型鼻息肉患者中具有表达差异,其在单纯IL-5+鼻息肉患者中表达下降且有负性调控嗜酸性炎症反应作用。     

Expression of ecalectin, a novel eosinophil chemoattractant, in nasal polyps

CONCLUSION: Ecalectin, which is produced in the mucosa of nasal polyps, seems to play an important role in the accumulation and activation of eosinophils in nasal polyps, regardless of the presence or absence of atopic predisposition. OBJECTIVE: Ecalectin is a recently discovered eosinophil chemoattractant which elongs to the galectin family. We investigated the expression of ecalectin in nasal polyp tissues associated with various nasal and paranasal diseases in order to clarify the pathogenesis of eosinophilia in nasal polyposis. MATERIAL AND METHODS: Nasal polyps were taken from 56 patients diagnosed as having chronic sinusitis with nasal polyposis. The surgically resected polyps and nasal turbinates were immunohistochemically stained using antibodies against EG2, human mast cell tryptase, CD3 and ecalectin. RESULTS: The number of EG2- and ecalectin-positive cells was significantly higher in nasal polyps than control turbinates. Ecalectin-positive cells were observed in the subepithelial layer, where many EG2-positive cells were present. The number of ecalectin-positive cells correlated significantly with the number of EG2-positive cells in nasal polyps. Many ecalectin mRNA-positive cells were also observed in nasal polyps with an accumulation of EG2-positive cells.     

The pathogenesis of nasal polyposis by immunoglobulin E and interleukin-5 is completed by transforming growth factor-beta1

OBJECTIVES/HYPOTHESIS: Nasal polyps are benign mucosal protrusions into the nasal cavity of multifactorial origin and are characterized by chronic mucosal inflammation. The suggested multifactorial pathological mechanisms comprise several factors including cytokines and immunoglobulin E (IgE). The study was designed to examine the suggested roles of IgE, interleukin-5 (IL-5), and transforming growth factor-beta1 (TGF-beta1) in the pathogenesis of nasal polyposis. METHODS: Nasal polyps (n = 34) and healthy nasal mucosa samples (n = 9) were taken during routine endonasal surgeries. Immunoglobulin E (n = 13), IL-5 (n = 22), and TGF-beta1 (n = 27) concentrations were measured with enzyme-linked immunosorbent assay technique in homogenized polyp tissue and in control mucosa. Atopic and nonatopic groups were selected and compared. Histomorphological examination and immunohistochemical analysis to detect IL-5 and TGF-beta1 were performed in five specimens. RESULTS: The level of tissue-bound IgE was significantly higher in polyps compared with control specimens and in atopic compared with nonatopic polyps, but between nonatopic polyps and control specimens the difference was not significant. However, significant correlation was found between tissue and serum IgE in the complete polyp (P =.001) and atopic polyps group (P =.05). Tissue IL-5 concentration was significantly higher in polyps compared with control specimens, in which it was below the limit (15 pg/mL), and there was no difference between atopic and nonatopic polyps. In atopic polyps there was significant correlation between tissue IgE and IL-5. Transforming growth factor-beta1 concentration proved to be significantly higher in control mucosa than in polyps, with no difference between atopic and nonatopic polyps. Immunohistochemical analysis revealed numerous IL-5-positive eosinophil cells and TGF-beta1 positivity in the lamina propria of polyp samples, but none in control specimens. CONCLUSIONS: High tissue TGF-beta1 quantity in healthy nasal mucosa without its active form on the cell surface and its low quantity in polyps may reflect its essential role in the inhibitory mechanisms of nasal polyposis. Interleukin-5 plays a key role in the eosinophil recruitment and activation, and both atopic and nonatopic pathways might activate this process. The main sources of IL-5 and TGF-beta1 are the eosinophils and macrophages. Immediate hypersensitivity, besides other mechanisms, might be related to atopic polyps, but the involvement of other, local allergic mechanisms in IgE production of nonatopic polyp tissue cannot be excluded.     

Pattern of inflammation and impact of Staphylococcus aureus enterotoxins in nasal polyps from southern China

BACKGROUND: This study analyzes the impact of Staphylococcus aureus enterotoxins (SAEs) and the inflammatory pattern in polyps from China. METHODS: Nasal tissue was obtained from 27 consecutive bilateral nasal polyps and 15 control patients and assayed for eotaxin, interleukin-5, soluble interleukin-2 receptor, transforming growth factor (TGF) beta, myeloperoxidase, eosinophil cationic protein, total IgE, and specific IgE to SAEs. Activated eosinophils were stained using EG2 antibodies in polyps from Chinese and comparative white patients. RESULTS: The number of EG2+ eosinophils was significantly lower in polyps from Chinese patients versus white patients. Chinese polyps showed significantly increased IgE and soluble interleukin-2 receptor versus control samples, whereas TGF-beta1 was significantly decreased. Ten of 27 samples in the polyp group versus 0 of 15 controls contained SAE-IgE (p < 0.01). TGF-beta1 was significantly down-regulated in SAE+ samples versus SAE- samples (p = 0.04). CONCLUSION: Nasal polyps from China are characterized by B- and T-cell activation, a minor eosinophilic inflammation compared with polyps from white subjects, and a decrease in TGF-beta1 in comparison with control inferior turbinate tissue. One-third of patients with polyps showed an IgE response to SAEs.     

Clinical factors influencing the eosinophil infiltration of nasal polyps

AIMS AND METHODS: Our study, based on a retrospective chart analysis, was aimed 1) to describe the varying degree of eosinophil infiltration in a series of 263 adult patients operated on diffuse and bilateral nasal polyposis (NPS) after failure of medical treatment, in 15 cystic fibrosis patients with bilateral nasal polyps, and in 31 patients with chronic sinusitis without polyps (18 bilateral, 13 unilateral) 2) to search for clinical factors that might influence the degree of eosinophil infiltration. Eosinophil infiltration was expressed semi-quantativity as a percentage of inflammatory cells. RESULTS: Our study confirms that eosinophil infiltration is a striking feature of nasal polyposis. All patients with chronic sinusitis showed less than 10% eosinophils (mean +/- SEM = 2 +/- 2%) whereas 88% of patients with NPS showed more than 10% eosinophils (50 +/- 2%). Cystic fibrosis lied in between with 40% of patients showing more than 10% eosinophils. In idiopathic bilateral NPS the number of eosinophils was increased in patients with asthma (58 +/- 3%) and even more in Widal's triad (75 +/- 4%). Atopic patients did not have more eosinophils (52 +/- 5%). Patients treated with systemic steroids within two months before surgery showed decreased eosinophil infiltration (22 +/- 3% vs 50 +/- 2 for treated versus untreated) whereas patients treated with topical steroids did not (47 +/- 2%). CONCLUSIONS: Thus, a link might exist between clinical presentation and eosinophil infiltration. Chronic sinusitis and nasal polyps are probably not the same disease. Eosinophils appear as a link between nasal polyps, asthma and aspirin intolerance. Atopic status does not modify eosinophil infiltration of nasal polyps. Systemic steroids appear significantly more effective to reduce the eosinophil infiltrate than topical steroids in our selected group of operated patients.     

Eosinophilic cationic protein as a marker of nasal inflammation in patients with cystic fibrosis.

OBJECTIVES: Evaluation was made of eosinophilic cationic protein (ECP) in nasal secretion for measuring the degree of nasal inflammation and monitoring response to therapy in cystic fibrosis (CF) patients with chronic rhinosinusitis. Symptoms and findings in regard to ECP levels before and after treatment were described. STUDY DESIGN: Study was prospective, with 21 CF patients aged 4 to 19 years; 20 healthy volunteers served as controls. Collection of nasal secretion by a sponge was performed, and blood samples were obtained for serum. Cystic fibrosis (CF) patients were classified according to nasal symptoms and findings. METHODS: ECP was measured by fluoroimmunoassay. Age, sex, nasal symptoms, and endoscopic and histological findings were obtained, and examinations were conducted before and after treatment; recurrences were recorded. RESULTS: In CF patients with chronic nasal inflammation, increased nasal levels of ECP were detected when compared with asymptomatic CF patients or healthy nonatopic subjects. ECP concentrations were strongly related to the extent of nasal disease; patients with nasal polyps had higher levels than those without. Checked at 1 and 4 months after treatment, ECP levels declined with regression of symptoms, and in patients with exacerbation of nasal disease, ECP levels rose. CONCLUSIONS: According to our study, there is a relationship between levels of ECP in nasal secretions and the degrees of nasal inflammation. In addition, the measurement of ECP could be useful in monitoring nasal disease in CF patients.     

鼻息肉组织中抗金黄色葡萄球菌肠毒素IgE的检测及超抗原学说分析

目的寻找鼻息肉组织中金黄色葡萄球菌(简称金葡菌)肠毒素发挥超抗原作用的证据,为鼻息肉发病的超抗原假说提供佐证。方法在42例主要由不伴哮喘的鼻息肉、慢性鼻-鼻窦炎患者和对照组构成的人群中,运用UniCAP系统检测鼻黏膜组织中抗金葡菌肠毒素(staphylococcusaureusenterotoxins,SE)A和B的特异性IgE(SIgE)、总IgE、嗜酸粒细胞阳离子蛋白(eosinophiliccationicprotein,ECP);以及外周血中总IgE和抗SEA和SEB的SIgE(仅在8例中)。同时对中鼻道分泌物进行需氧菌培养。结果在所有组织样本中(42例)和部分(8例)患者的血清样本中,没有明确证据支持抗SEA和SEB的SIgE存在。组织中的总IgE(以每2mg组织蛋白中的含量表示)范围为4·59~70·21kIU,平均(x-±s,17·85±14·31)kIU;血清中总IgE为7·44~344·00kIU/L,平均(88·65±80·03)kIU/L。金葡菌培养阳性3例(鼻息肉1例,单纯鼻-鼻窦炎2例)。在鼻息肉组、慢性鼻-鼻窦炎组和对照组之间,SIgE的荧光值、总IgE、ECP值差异均无统计学意义(P值均>0·05)。结论在不伴持续性哮喘的鼻息肉患者中,没有发现金葡菌超抗原作用的证据,提示对超抗原假说仍需要大量的临床调查和研究来论证。     

Clinical significance of eosinophilic cationic protein levels in nasal secretions of patients with nasal polyposis

Nasal polyps are characterized by eosinophilic infiltration, and frequently coexist with asthma, aspirin intolerance and allergy. Eosinophilic cationic protein (ECP) is a specific eosinophil granule protein released upon activation of eosinophils. We investigated the ECP levels in nasal secretions of patients with nasal polyposis (NP) in order to correlate them with disease severity and associated diseases and to compare ECP levels between patients with and without recurrence of NP after surgical treatment. A total of 78 patients who had surgery for NP were followed up for a minimum of 18 months. The presence of asthma, allergies or aspirin intolerance was noted. Nasal secretions were obtained 1 day before the surgery and during the follow-up period after surgery. Immunoassays were used to quantify ECP in nasal secretions and serum and interleukin (IL)-5 in nasal secretions. ECP levels in nasal secretions were higher in patients with asthma or aspirin intolerance than in patients without asthma or aspirin intolerance, while no significant differences were found between allergic and non-allergic patients. ECP levels in nasal secretions correlated significantly with IL-5 levels in nasal secretions, the degree of tissue eosinophilia and computed tomographic (CT) scores. In total, 30 patients (38%) developed recurrent NP during the follow-up period. Preoperative ECP and IL-5 levels in nasal secretions were significantly higher in patients with recurrence compared to patients without recurrence. During the follow-up period, patients without recurrence demonstrated a significant reduction in the ECP levels in nasal secretions, whereas there was no significant reduction in the ECP levels of patients with recurrence. The results of this study provide evidence that ECP levels in nasal secretions of patients with NP correlate with the presence of asthma or aspirin intolerance and severity of NP determined by CT scores.     

Eosinophils and mast cells: a comparison of nasal mucosa histology and cytology to markers in nasal discharge in patients with chronic sino-nasal diseases

Allergic rhinitis (AR), nasal polyps (NP) as well as chronic rhinosinusitis (CRS) are all known to be associated with eosinophilic infiltration and elevated numbers of mast cells (MC) within the mucosa. Both cell types and their markers eosinophilic cationic protein (ECP) and tryptase are utilized in the diagnosis and management of chronic sino-nasal diseases. Mucosal cytology samples were gathered by cytobrush, histological samples were obtained from the inferior turbinate. In both sample sets, the number of eosinophils and MC was determined. Their corresponding markers ECP and tryptase were quantified from nasal discharge. Patients were grouped with reference to their main diagnosis: AR (n = 34), NP (n = 25), CRS (n = 27) and controls (n = 34). Eosinophil counts from cytobrush and ECP levels were significantly elevated in NP compared to all other groups—31- and 13-fold over control, respectively. However, histologic review did not reveal any difference in eosinophil count among groups. Tryptase was significantly elevated threefold in AR versus CRS and controls. No correlation to cytological and histological MC counts could be found. ECP levels in nasal discharge as well as eosinophil counts can provide useful information with regard to the diagnosis. Likewise, tryptase concentrations can do. The presented data show that the measurement of markers in nasal discharge is superior in differentiating among diagnosis groups. Given that the collection of nasal secretions is more comfortable for patients than the more invasive techniques, we recommend first line ECP and tryptase testing performed on nasal secretions.     

Nasal polyps in eosinophilic granulomatosis with polyangiitis: Structured histopathology and CD105 expression

PurposeDistinguishing the prodromal nasal polyposis of eosinophilic granulomatosis with polyangiitis (EGPA) from chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenge for rhinologists and rheumatologists. It has recently been reported that angiogenesis and CD105 expressed on vascular endothelial cells could have a role in the pathogenesis and development of nasal polyps.This exploratory study examined the structured histopathology of nasal polyps in patients with EGPA and CRSwNP, comparing CD105 expression in their nasal tissue with that of a control group with no chronic sinonasal inflammation.MethodsA structured histopathological study was performed on surgical specimens of nasal tissue from 32 adults (13 with EGPA, 14 with CRSwNP, 5 controls), considering CD105 as a marker to determine microvessel density (MVD).ResultsThe mean eosinophil count was higher in EGPA patients with tissue inflammation (p = .002), and in CRSwNP patients with sub-epithelial edema (p = .009). Neutrophil infiltration was significantly associated with severe tissue inflammation in EGPA patients (p = .04), but with the absence of fibrosis in CRSwNP patients (p = .04). In the EGPA group, CD105-MVD correlated with tissue eosinophil count (p = .05). Mean CD105-MVD was significantly higher in EGPA patients with mucosal ulceration (p = .004). In the CRSwNP group, a CD105-MVD correlated positively and significantly with tissue eosinophil count (p = .01).ConclusionAlongside the known abundance of eosinophils, other cells might contribute to inflammatory processes. Neutrophils may amplify inflammation, eosinophil recruitment and tissue damage. CD105 expression in CRSwNP and EGPA nasal polyps supports the hypothesized involvement of angiogenesis in the pathogenesis and development of nasal polyps.     

Regulation of immunoglobulin secretion by plasma cells infiltrating nasal polyps

OBJECTIVE/HYPOTHESIS: To learn more about the role of plasma cells infiltrating nasal polyps in the pathogenesis of nasal polyposis, we examined their function by analyzing immunoglobulin (Ig) production and the factors implicated in the secretion. STUDY DESIGN: A series of 19 consecutive nasal polyp tissue samples and, as a control, peripheral blood samples from the same patients, were studied by histopathological and immunological examination. METHODS: Hematoxylin-eosin and immunohistochemical staining was carried out to identify plasma cells infiltrating nasal polyps. Nasal polyp mononuclear cells (NPMNCs) were purified from nasal polyp tissue samples, and Ig-secreting cells were identified in cytospin preparations stained with fluorescein isothiocyanate-conjugated antibodies against IgA, IgG, IgM, and IgE. Purified NPMNCs were cultured in basal conditions and after the addition of several stimuli. Ig secreted into the culture supernatants was evaluated by an enzyme-linked immunosorbent assay. RESULTS: Plasma cells accounted for an important fraction of the inflammatory infiltrate. The main Ig isotype synthesized by these cells was IgA, whereas little IgE was detected. In vitro cultures demonstrated that the plasma cells actively secreted Ig for a short period. When cytokine dependence was analyzed, interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) were shown to be partially responsible for the Ig production. Dependence on CD95-mediated apoptosis was not observed. CONCLUSIONS: Nasal polyp-infiltrating plasma cells are mainly IgA-secreting cells, the latter property being related to the mucosal immune system. The IgA production is partly dependent on IL-10 and TNF-alpha. The absence of IgE-secreting cells in most of the samples suggests that a type I hypersensitivity reaction is not essential for the development of nasal polyp.