Study on eosinophil cationic protein (ECP) and arylsulfatase B in nasal secretions and sera from patients with nasal allergy

Recently four tissue toxic proteins namely major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) were found in eosinophilic leucocytes. Although the characteristics of these proteins concerning tissue damage in the local site of type I allergic reaction have been investigated mainly in lower respiratory tract, the actual clinico-pathological roles of these proteins in nasal allergy are not clarified. Contrary, eosinophils also have histaminase, arylsulfatase, phospholipase D, which are considered to act on a negative feedback mechanism in allergic reaction through inactivation of chemical mediators. Therefore, estimation of ECP and simultaneously arylsulfatase B in nasal secretion and the sera from patients with nasal allergy may clarify the dynamics of clinico-pathological state, especially in the late phase of allergic reaction in each patients. ECP concentrations in the nasal secretions from 22 patients and in the sera from 12 patients with nasal allergy were measured by RIA method. The activities of arylsulfatase B in the nasal secretions and the sera were also estimated in the same specimens as ECP by measuring its hydrolytic activity using p-nitro cathecol sulfate as a substrate. The results obtained were as follows; 1) There was a significant correlation between ECP concentrations in the nasal secretions and the severities of clinical symptoms, especially the degree of nasal obstruction. ECP concentrations also significantly correlated to the score of eosinophilic leucocytes in the nasal smears. 2) The serum ECP concentrations significantly correlated to the number of eosinophilic leucocytes in the peripheral blood, and also showed slight tendency of correlation to the severity of clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Electrophoretic evaluation of nasal discharge in patients with allergic rhinitis and vasomotor rhinitis

BACKGROUND: Allergic rhinitis and vasomotor rhinitis are two common diseases that have similar symptoms and physical findings. This study was designed to assess the efficacy of electrophoretic analysis of nasal discharge for the differential diagnosis of allergic rhinitis and vasomotor rhinitis. METHODS: Two different groups of patients with allergic rhinitis (n = 18) and with vasomotor rhinitis (n = 18) diagnosed by current methods and 10 healthy subjects as a control group were included in this study. Component analyses of proteins in nasal wash were made by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS: The mean levels of total protein, 66-kDa proteins and 26-kDa proteins (277.2 +/- 9 microg/mL, 114.5 +/- 9 microg/mL, and 67.0 +/- 4 microg/mL, respectively), in nasal washing samples of patients with allergic rhinitis were found to be higher than in the samples, (222.0 +/- 6 microg/mL, 65.6 +/- 6 microg/mL, and 42.9 +/- 4 microg/mL respectively) obtained from patients with vasomotor rhinitis. The control group showed the lowest rate of these proteins (167.8 +/- 7 microg/mL 34.3 +/- 3 microg/mL, and 25.0 +/- 3 microg/mL, respectively). The differences between mean levels of these proteins in all groups were statistically significant (p < 0.05). CONCLUSIONS: These findings indicate that electrophoretic analysis of nasal discharge can be used for the diagnosis of allergic rhinitis and vasomotor rhinitis. However, further studies are needed to standardize the technique of nasal wash and to determine the range of proteins in nasal secretions that will confirm the diagnosis.     

鼻息肉组织嗜酸粒细胞中水通道蛋白-1和抗凋亡基因Bcl-2 mRNA的表达及意义

OBJECTIVE: To study the significance of aquaporin-1 (AQP-1) expression in the eosinophils of nasal polyps. The expression and location of AQP-1 mRNA and apoptosis associated gene Bcl-2 mRNA in nasal polyps were explored. METHODS: Sixteen nasal polyp samples were collected from 11 women and 5 men aged 20-65 years during routine endonasal surgery. Nasal mucosa specimens from the inferior turbinates of 10 patients with allergic rhinitis (7 women and 3 men, aged 16-58 years), collected during septoplasty, were used as controls. The expression of AQP-1 mRNA and Bcl-2 mRNA was detected in serial adjacent sections by in situ hybridization and eosinophils were examined by stain MGG. RESULTS: AQP-1 mRNA expression was found in all 16 nasal polyps and in 4 of 10 inferior turbinate tissues, the mean expression rates were (93.16 +/- 13.25)% and (19.54 +/- 4.98)%, respectively. All 16 nasal polyps and 10 control nasal tissues expressed Bcl-2 mRNA, by the average rates of (84.74 +/- 12.10)% and (16.45 +/- 3.12)%, respectively. The expression of AQP-1 mRNA was positively correlated with Bcl-2 mRNA expression in nasal polyps (r = 0.875, P < 0.01). CONCLUSIONS: AQP-1 contributes to the survival of eosinophils in nasal polyps by keeping the permeation balance of eosinophils.     

E-选择素在鼻息肉中的分泌与表达

目的:检测黏附分子E选择素在鼻息肉中的分泌水平与表达部位,借以探讨其与鼻息肉可能的病理机制的相关性。方法:采用酶联免疫吸附测定法检测25例鼻息肉(鼻息肉组)组织匀浆中E选择素水平,以9例鼻中隔手术患者之代偿肥大的下鼻甲后端黏膜作为对照(对照组);同时对上述标本进行苏木精伊红染色及E选择素免疫组织化学染色,观察其表达情况。结果:鼻息肉组大量嗜酸粒细胞浸润。E选择素浓度为(42.58±13.52)μg/L,对照组为(11.35±3.17)μg/L,差异有统计学意义(P<0.01)。E选择素主要表达于血管内皮、腺体上皮、间质和浸润炎症细胞上。鼻息肉组腺体上皮阳性表达率为92.0%,对照组为55.6%,差异有统计学意义(P<0.05)。鼻息肉组在血管内皮上阳性表达率为84.0%,对照组为44.4%;鼻息肉组在间质及浸润炎症细胞阳性表达率为92.0%,对照组为33.3%,差异均有统计学意义。Spearman相关性分析E选择素在血管内皮上的表达和在间质及浸润炎症细胞上的表达呈正相关(r=0.544,P<0.01)。结论:高表达的E选择素可能通过参与嗜酸粒细胞等炎症细胞的浸润、活化、增殖,从而在鼻息肉的形成过程中起重要作用。     

Cytolysis of eosinophils in nasal secretions

It is still unknown how eosinophils degranulate in nasal mucus. Currently, cytolysis is being reevaluated as the mode of degranulation of eosinophils in allergic nasal mucosa. To examine whether eosinophils migrating to the nasal mucus degranulate by cytolysis, we sampled nasal mucus from 9 patients with nasal allergy and observed it under electron and light microscopes. Both intact and necrotic eosinophils were observed in the nasal mucus. Although the total eosinophil count in the nasal mucus was not correlated with the frequency of sneezes, there was a significant correlation (p = .0025) between the rate of eosinophil lysis and the frequency of sneezes. Whereas extracellular release of eosinophil peroxidase was not detected from the eosinophils with intact cell membranes, large quantities of eosinophil peroxidase were found outside the eosinophils with injured cell membranes. We concluded that eosinophils migrating to the nasal mucus degranulate mainly by cytolysis, and that granular proteins released from the necrotic eosinophils into the nasal mucus are one of the important factors causing hypersensitivity in the nasal mucosa.     

Eotaxin基因和趋化因子受体3在变应性鼻炎大鼠模型鼻腔黏膜和骨髓中的表达及意义

目的：探讨Eotaxin（嗜酸粒细胞趋化因子）基因和趋化因子受体3（CCR3）在变应性鼻炎（AR）大鼠模型鼻腔黏膜和骨髓中的表达及其意义。方法：采用6～8周龄雄性SD大鼠20只,随机分成实验组（AR组）和对照组,每组10只,以卵清蛋白致敏激发制成AR模型,瑞特染色计数骨髓涂片和外周血涂片中白细胞比例,免疫组织化学技术检测骨髓中CCR3的表达;制备大鼠鼻腔黏膜组织病理标本,苏木精-伊红染色,原位分子杂交方法检测鼻腔黏膜中Eotaxin mRNA的表达,免疫组织化学技术检测Eotaxin在鼻腔黏膜中的表达。结果：AR组骨髓涂片中嗜酸粒细胞比例显著高于对照组（P〈0．01）,AR组外周血涂片中嗜酸粒细胞比例显著高于对照组（P〈0．01）;与对照组比较,AR组大鼠鼻腔黏膜中Eotaxin阳性细胞数与EotaxinmRNA表达明显增强（P〈0．01）,且二者呈正相关性（r=0．804,P〈0．01）。AR组Eotaxin的表达与鼻腔黏膜嗜酸粒细胞的数量呈显著正相关（r=0．795,P〈0．01）。AR组骨髓涂片中CCR3阳性细胞比例显著高于对照组（P〈0．01）,AR组骨髓涂片中CCR3阳性细胞比例和外周血嗜酸粒细胞比例呈显著正相关（r=0．736,P〈0．05）。结论：AR组中Eotaxin和CCR3表达增强,为嗜酸粒细胞从骨髓快速募集到鼻腔黏膜提供了可能。     

ELISA for determination of immunoreactive free elastase and elastase in complex with alpha 1-antitrypsin in nasal secretions with sinusitis

Sensitive double antibody sandwich ELISA methods was developed in order to quantify immunoreactive neutrophil elastase (NE) levels in nasal secretions with chronic sinusitis (CS). Microwell plate as a solid phase was coated with anti-NE antibody. Two different horseradish peroxidase (HRP) labelled antibodies used as the second antibody were anti-NE-HRP for measuring total (free + complexed) NE level and anti-alpha 1-antitrypsin (AT)-HRP for complexed NE level. Mean value of total NE was 31.0 +/- 20.7 micrograms/ml in nasal secretions from adult patients with CS, and the percentage of complexed NE in total NE was 33.7 +/- 21.4%. This sandwich ELISA is a useful method for measuring both total and complexed NE levels in nasal secretions.     

变应性鼻炎鼻分泌物嗜酸性粒细胞与肺功能相关性研究

目的 研究单纯性变应性鼻炎(AR)患者发作及稳定期鼻分泌物嗜酸性粒细胞(Eos)含量与肺功能的相关性。 方法 选取成年单纯性AR患者102例为AR组,53名健康体检者为对照组,应用肺功能仪及鼻分泌物涂片检测AR组发作期、稳定期及对照组各项肺功能指标和鼻分泌物Eos计数。 结果 对照组及AR患者发作期、稳定期检测的鼻腔分泌物Eos计数及肺功能指标PEF、MEF₇₅、FEV₁均存在差异,差异有统计学意义(P<0.001);AR患者发作期、稳定期鼻分泌物Eos计数与自身PEF,FEV₁,MEF₇₅具有相关性,其中与FEV₁呈显著相关(r=-0.53,P<0.001)。 结论 AR患者鼻腔分泌物Eos计数与肺功能关系密切,大部分AR患者存在着不同程度的基础肺功能损害,且随着气道变态反应加重,肺功能下降明显。     

白细胞介素-5及嗜酸性粒细胞在鼻息肉中的相关性研究

目的探讨白细胞介素-5(IL-5)在鼻息肉中的表达及其在鼻息肉形成与发展中的作用。方法采用双抗体夹心酶联免疫吸附测定法检测31例鼻息肉患者、11例慢性鼻窦炎患者及6例正常人组织匀浆中IL-5含量;对15例鼻息肉、11例慢性鼻窦炎及6例正常人进行HE切片染色,以观察组织中嗜酸性粒细胞的数量。结果①鼻息肉、慢性鼻窦炎及正常对照组IL-5含量(pg／mg)分别为23．44±6．68,16．41±3．09,12．86±4．17,鼻息肉组织IL-5含量高于慢性鼻窦炎及正常对照组(P<0．01)。②鼻息肉、慢性鼻窦炎及正常对照组的苏木精伊红染色嗜酸性粒细胞数分别为7．42±2．33,1.30±0．59,1．07±0．70,鼻息肉组嗜酸性粒细胞数高于慢性鼻窦炎和正常对照组(P<0．05)。结论鼻息肉是以嗜酸性粒细胞浸润为特征的疾病过程,对嗜酸性粒细胞有活化作用的IL-5对鼻息肉的形成起着一定的作用。     

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.     

Expression of RANTES by IL-1 beta and TNF-alpha stimulated nasal polyp fibroblasts

OBJECTIVE: Accumulation of eosinophils (Eo) is one of the most characteristic feature of nasal polyps. However, the question remains why eosinophils accumulate into the nasal polyp tissue. RANTES (regulated upon activation, normal T cell expressed and presumably secreted) is a recently described chemokine that is said to play a role in the recruitment of eosinophils into inflammatory tissue sites. Fibroblasts are a rich source of cytokines and inflammatory mediators. The objective of this study was to demonstrated the expression of the chemokine RANTES in nasal polyp fibroblasts after stimulation with proinflammatory cytokines like TNF-alpha and IL-1 beta. METHODS: Fibroblast lines were established from human nasal polyp biopsy tissues taken from patients with chronic sinusitis who had no other associated diseases. Cultured nasal polyp fibroblasts were stimulated with TNF-alpha or IL-1 beta at various doses (0.1, 1.0, 1 ng/ml) or for various times (l, 6, 12, 24, 48, 72 h). To detect the RANTES gene expression, RT-PCR was performed. The resulting supernatants were assayed with ELISA for the level of RANTES. RESULTS: We demonstrated that TNF-alpha and IL-1 beta induced the gene expression and protein production of RANTES in nasal polyp fibroblasts. This responsiveness to TNF-alpha and IL-1 beta was time and dose-dependent. CONCLUSION: These findings suggest that nasal polypfibroblasts may also play an important role in the recruitment of Eo through the production of RANTES.     

Presence of platelet-activating factor in nasal polyps and eosinophils

Platelet-activating factor (PAF) has been reported to play a role in allergy and inflammatory reactions but its role in the pathogenesis of nasal polyps remains unclear. In this study, we examined both PAF and peptide leukotrienes (peptLTs) in individual preparations from nasal polyps. The amounts of PAF were much greater than those of peptLTs in all preparations. Nasal polyps were divided into two groups according to the severity of eosinophil infiltration: a severe group (eosinophil count > or = 50/mm2) and a mild group (eosinophil count < 50/mm2). The amounts of PAF in the nasal polyps were significantly higher in the severe group than in the mild group (p < 0.01). PAF activity correlated with tissue eosinophilia and polyps obtained from patients with aspirin-sensitive asthma contained relatively large amounts of PAF, with enriched infiltration of eosinophils.     

The effect of nasal polyp epithelial cells on eosinophil activation

OBJECTIVES/HYPOTHESIS: Eosinophil infiltration into an inflammatory site is a characteristic histological finding in patients with chronic rhinosinusitis and nasal polyps. Most of the eosinophils in chronic rhinosinusitis are activated in the nasal cavity, but the exact activation mechanism of eosinophils is unknown. The study was designed to investigate the effect of human nasal epithelial cells on the activation of eosinophils. STUDY DESIGN: Peripheral blood eosinophils were isolated from healthy volunteers and incubated in human nasal polyp epithelial cell conditioned media (HPECM). Superoxide production and eosinophil-derived neurotoxin were measured to determine eosinophils activation. HPECMs were assayed by ELISAs for interleukin-8 (IL-8), granulocyte-macrophage colony stimulating factor (GM-CSF), eotaxin, and regulated on activation normal T expressed and secreted (RANTES). To identify the chemical mediators involved in the activation of eosinophils. RESULTS: HPECM (n = 7) contained 31.48 ng/mL interleukin-8, 533.43 pg/mL GM-CSF, 5.90 pg/mL eotaxin, and 11.06 pg/mL RANTES. Eosinophils were activated by HPECM and inhibited only by anti-GM-CSF antibody, not by the other chemical mediators. CONCLUSION: The results suggest that eosinophils in nasal secretions are activated by GM-CSF, which is produced by nasal epithelial cells.     

Exhaled and nasal nitric oxide in patients with Japanese cedar pollinosis and effects of nasal steroids

INTRODUCTION: Nitric oxide (NO) is produced by the action of NO synthase (NOS) using L-arginine as a substrate in various cells and found in air exhaled by humans. Previous studies suggest that almost all exhaled NO is derived from the upper airways and increases in patients with untreated asthma and allergic rhinitis. Exhaled NO is inhibited by treatment with inhalation of steroids that may be caused by inhibition of inducible nitric oxide synthase (iNOS). The purpose of this study is to determine whether exhaled and nasal NO increases in patients with Japanese cedar pollinosis compared with nonallergic healthy subjects, and whether it is affected by treatment with nasal steroids. Furthermore, we investigated its relation to nasal function and allergic rhinitis. SUBJECTS AND METHODS: 10 patients with Japanese cedar pollinosis and 5 healthy normal subjects were tested. All subjects had no history of respiratory infection for at least 2 weeks and did not smoke. Exhaled NO was collected in a sampling bag from oral and nasal breathing, and nasal NO was sampled directly from the nasal cavity. Both were measured by a chemiluminescence NO analyzer, ML9841, at a detection limit of 1 part per billion (ppb). Subjects used nasal steroids for 2 weeks and were measured similarly afterwards. RESULTS: NO concentrations in nasal air and air exhaled from the nose in patients with Japanese cedar pollinosis (277.9 +/- 59.5 ppb, 34.4 +/- 3.9 ppb, n = 10) were higher than the normal subjects (153.3 +/- 30.6 ppb, 19.9 +/- 3.4 ppb, n = 5) (p < 0.05). NO exhaled from the mouth was not significantly different between patients (20.5 +/- 4.9 ppb) and normal subjects (23.7 +/- 2.6 ppb). In patients with Japanese cedar pollinosis, the concentration of nasal NO and nasal exhaled NO were significantly decreased after treatment with nasal steroids (144.0 +/- 21.0 ppb, 26.1 +/- 3.0 ppb) (p < 0.01, p < 0.05), but there was no change in oral exhaled NO (17.2 +/- 3.3 ppb). In normal subjects, oral (22.5 +/- 5.3 ppb), nasal exhaled NO (19.1 +/- 2.3 ppb), and nasal NO (151.2 +/- 24.8 ppb) were not changed. CONCLUSION: In patients with Japanese cedar pollinosis, nasal NO was increased and decreased by nasal steroids. These results suggest that increased nasal NO in patients with allergic rhinitis is produced by induction of iNOS and that nasal NO produces the symptoms of nasal obstruction and rhinorrhea.     

Reduced nasal resistance after simple tonsillectomy in patients with obstructive sleep apnea

BACKGROUND: The aim of this study was to investigate the effects of simple tonsillectomy on nasal resistance in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Conventional tonsillectomy was performed in 20 patients who were refractory to treatment with continuous positive airway pressure. The subjects consisted of 17 men and 3 women (mean age, 32.9 +/-6.3 years). The effects of tonsillectomy were evaluated with preoperative and postoperative polysomnography and nasal resistance. RESULTS: After tonsillectomy, nasal resistance decreased significantly from 0.39+/-0.30 Pa/cm(3) per second to 0.27 +/-0.16 Pa/cm(3) per second (p < 0.05). Simultaneously, the apnea-hypopnea index decreased significantly from 55.7 +/-22.5 to 21.2 +/-14.2 (p < 0.05). There was no significant correlation between tonsillar weight and percentage of change in bilateral nasal resistance (p > 0.05). CONCLUSION: The reduction in nasal resistance induced by simple tonsillectomy could play an important role in improving OSAS, as does nasal surgery or adenotomy.     

Sildenafil and nasal obstruction

OBJECTIVE: Sildenafil (Viagra; Pfizer), a phosphodiesterase inhibitor, promotes penile erection through increased intracellular cyclic guanine monophosphate (a second messenger) in response to nitric oxide (a first messenger) release following sexual stimulation. Nitric oxide is involved in nasal vasodilation, secretion, and mucociliary clearance. The aim of this study was to assess the effect of sildenafil on nasal patency. DESIGN: Pilot study. SETTING: Teaching hospital. METHODS: Nasal patency was assessed by a visual analogue score and by measurement of the peak nasal inspiratory flow (PNIF) in five subjects before and after administration of sildenafil. MAIN OUTCOME MEASURES: Visual analogue score and PNIF. RESULTS: There was a significant increase in the subjective sensation of nasal obstruction (p = .003; -9.6 +/- 2.7, -15.4 to -3.7 [mean +/- SEM, 95% CI) and a significant reduction of PNIF (p < .001; 70.7 +/- 13.2, 43.1 to 98.3). CONCLUSIONS: This pilot study suggests that nasal patency may be reduced following the administration of sildenafil. The role of phosphodiesterase inhibitors in nasal physiology merits further investigation.     

NARES: a model of inflammation caused by activated eosinophils?

Twenty patients were selected on the basis of perennial rhinitis, the absence of allergy and with an eosinophil count higher than 20% of total leucocytes in nasal secretions (NARES). Nasal endoscopy with biopsies from the middle turbinate and sinus CT were performed. Biopsies were processed for histological examination and for immunofluorescence. The clinical progress during treatment was scrutinized. An acute congestive aspect of the nasal mucosa was noted in 4 cases, and micropolyposis in 9 cases. Sinus CT showed opacity of the ethmoidal cells in 87% of cases (maxillary sinuses: 75%; frontal sinus: 46%; sphenoidal sinus: 31%). An eosinophilic infiltrate of the nasal mucosa was constituted in 9 cases: In 6 cases, the cells expressed the Fc epsilon RII receptor, recognized by the monoclonal antibody Bb10. Anti-H1 drugs usually failed to result in a clinical improvement and local eosinophilia was not changed. Local corticoids were more effective but not sufficient in some cases, so that oral corticotherapy was needed. Ethmoidectomy was performed in three cases. NARES seems to evolve in three stages: (1) migration of eosinophils from the vessels to the secretions; (2) retention of eosinophils in the mucosa which might be linked to activation of unknown origin; (3) nasal polyposis. Numerous interactions between irritation of the epithelium, release of substance P, and eosinophils, lead to the hypothesis of a neurogenic origin of NARES.     

鼻内镜手术前后鼻腔分泌液中血小板源性生长因子和肿瘤坏死因子α及透明质酸的变化

目的探讨鼻内镜手术前后鼻腔分泌液中血小板源性生长因子(platelet delived growth factor，PDGF)、肿瘤坏死因子α(tumour necrosis factor-α，TNF-α)、透明质酸(hyaluronic acid，HA)的变化，研究鼻黏膜愈合情况的预测因素。方法用酶联免疫吸附试验(enzyme-linked immunosorbert assay，ELISA)对22例行鼻内镜手术的鼻-鼻窦炎鼻息肉患者术前、术后第1、4、8、12周鼻腔分泌液中PDGF、TNF-α、HA的含量进行测定，同时测定22例健康者鼻腔分泌液中3种因子的含量作为对照，观察术后第1、4、8、12周术腔愈合情况，并与患者的性别、年龄、体重、分型分期、术前3种因子的含量之间进行Logistic回归分析。结果①鼻-鼻窦炎鼻息肉患者术前鼻腔分泌液中3种因子的含量为：PDGF在正常范围内，TNF-α高于对照组(P=0．034)，HA明显比对照组低(P=0．003)。3种因子的含量均在术后升高，第1周达高峰(与对照组相比，PDGF、TNF-α、HA的P值依次为0．000、0．020、0．038)，而后逐渐下降，PDGF第12周降至正常(与对照组相比，P=0．087)，TNF-α第8周降至正常(与对照组相比，P=0．104)，12周又出现了升高(与对照组相比，P=0．002)，HA第4周降至正常(与对照组相比，P=0．304)。②术后第1、4、8、12周术腔愈合良好者分别占0、4．5％(1／22)、36．4％(8／22)、81．8％(18／22)，鼻黏膜愈合情况与年龄、术前PDGF含量有关，年龄越小，PDGF含量越低，愈合越好。结论在鼻黏膜的创伤愈合过程中，PDGF、TNF-α、HA具有不同的变化规律，年龄和术前PDGF含量是预测鼻黏膜愈合情况的参考指标。