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.     

Asthma outcomes after endoscopic sinus surgery in aspirin-tolerant versus aspirin-induced asthmatic patients

BACKGROUND: Certain diseases affect both upper and lower airways. Aspirin-induced asthma (AIA) is a clinical entity characterized by asthma, nasal polyposis, and aspirin intolerance. To understand the response of the lower airway to surgical treatment of the sinuses, we examined asthma outcomes in AIA compared with a second group of aspirin-tolerant asthmatic (ATA) patients to establish if there were any differences between the two groups after endoscopic sinus surgery (ESS). METHODS: A retrospective record review was performed of 91 asthmatic subjects with chronic rhinosinusitis. Forty-one subjects had AIA and 50 subjects had ATA. Subjective and objective asthma outcome parameters were used to compare between the two groups at three time points: immediately before ESS and 6 and 12 months after ESS. RESULTS: Preoperatively, AIA patients had significantly higher asthma severity (p<0.0001) and lower forced expiratory volume in 1 second values (p=0.04). At 12 months after ESS, a statistically significant difference between the two groups with better results in AIA patients was seen in asthma severity improvement (p=0.010) and in the decrease of ICS doses (p<0.0001), without significant differences between the two groups in other asthma outcome parameters. CONCLUSION: AIA patients usually present with more severe asthma. The asthmatic complaints of AIA and ATA patients continue to improve significantly over 6 and 12 month after ESS. Although ESS helped both groups of patients, AIA had statistically significant better results compared with ATA patients in asthma severity scores and decreased need for ICS.     

Nasal polyposis, bronchial asthma and analgesic intolerance

A retrospective case-control study was conducted in 1042 arbitrarily selected bronchial asthma patients (197 patients with AIA and 845 controls with normal analgesic tolerance). Two thirds of all AIA patients reported one or more diseases in the region of the upper airways. Quite different from the control group, highly significant coincidence of AIA with nasal polyposis (42.6%), paranasal sinus diseases (39%), and chronic rhinitis (42,1%) was recorded in the AIA patients. AIA was characterized by stronger inclination to recurrence of nasal polyps and more frequent negative impact of polypectomy upon the course of asthma. The classical triad of "intrinsic asthma - nasal polyps - analgesic intolerance" was established in 39% of the AIA patients. The pathogenetic factors causing the association of asthma with polyps and the even more strongly association of AIA with polyps are still unknown. The presumed pathogenetic relationship between chronic hyperplastic alterations in the upper airways and the phenomenon of AIA might be caused by disorders in phospholid metabolism (liberation of arachidonic acid, lipoxygenase products, radical mechanisms).     

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.     

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。     

Sinonasal Outcomes After Endoscopic Sinus Surgery in Asthmatic Patients With Nasal Polyps: A Difference Between Aspirin‐Tolerant and Aspirin‐Induced Asthma?

Objectives/Hypothesis: Aspirin‐sensitivity, asthma, and nasal polyposis (NP) comprise the clinical entity of Samter's triad. The aim of this study is to report the sinonasal outcomes of endoscopic sinus surgery (ESS) in treating NP in asthmatic patients, comparing aspirin‐induced asthmatic (AIA) patients with aspirin‐tolerant asthmatics (ATA). Study Design: Retrospective chart review. Methods: The records of 66 patients with NP and asthma were retrospectively reviewed. Forty‐one AIA patients were compared with 25 ATA patients. For each patient, a Lund‐Mackay computed tomography (CT) score of the preoperative scans and the available postoperative CT scans in a period of 18 months were calculated and used as primary endpoint. Sinonasal improvement assessed by patients and reported with a symptoms scale was used as the secondary endpoint for the comparison immediately before surgery and 6 months and 12 months following ESS. Results: Preoperative CT scores in AIA patients compared with ATA patients were significantly higher 19 (standard deviation, 4.82) vs. 14 (standard deviation, 6.8), respectively (P = .006). This difference was sustained for the available postoperative CT scans (P < .0001). During the period of 18 months follow‐up, 63.4% of AIA patients vs. 96% of ATA patients had CT improvement with a statistically significant difference between the two groups (P = .003). At 6 months following ESS, 63.4% of AIA patients vs. 56% of ATA patients had symptomatic improvement. At 12 months, 68.3% of AIA patients vs. 60% of ATA patients had symptomatic improvement, with no significant difference between the two groups. Conclusion: AIA patients had more extensive sinonasal disease than ATA patients. Both groups showed statistically significant improvement in sinonasal outcomes after ESS. The difference between the two groups was statistically significant for patients' CT improvement with worse CT scores being seen in AIA patients.     

Expression of MCP-4 by TLR ligand-stimulated nasal polyp fibroblasts

CONCLUSION: These results indicate that nasal polyp fibroblasts contribute to innate immunity and eosinophilic inflammation such as nasal polyposis. OBJECTIVE: It is generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play an essential role in the pathogenesis of nasal polyposis. Nasal polyposis is characterized by chronic eosinophilic inflammation. The mechanisms that cause the predominance of eosinophilic infiltration in nasal polyposis have yet to be clarified. There is growing evidence that fibroblasts could be a major source of Th2 chemokines. Because the nasal and paranasal mucosae are the first respiratory tissues that environmental agents encounter, those tissues are exposed to injurious agents, including microorganisms and their breakdown products. We investigated whether nasal polyp fibroblasts produce a C-C chemokine, MCP-4, when stimulated with the breakdown products of microorganisms and a Th2 cytokine (interleukin (IL)-4). MATERIALS AND METHODS: Fibroblast lines were established from nasal polyp tissues. The expression of MCP-4 mRNA was evaluated by real-time RT-PCR. The amount of MCP-4 in the supernatants was measured by ELISA. RESULTS: TLR2, 3, 4 and 5 ligands, but not TLR7/8 or 9 ligands, induced small amounts of MCP-4. TLR2, 3, 4 and 5 ligands synergized with IL-4 to induce the production of MCP-4.     

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.     

The role of anti-IgE immunoglobulin therapy in nasal polyposis: a pilot study

BACKGROUND: Although the etiology of nasal polyposis (NP) remains unknown, emerging evidence showing elevated local IgE levels and eosinophilic infiltration suggests an allergic etiology. Given this evidence, this pilot study examined whether anti-IgE therapy is efficacious in the treatment of NP. METHODS: Data were retrospectively collected on two groups of patients with atopic asthma and NP who underwent endoscopic sinus surgery (ESS), including a control group (n=4) and an anti-IgE treatment group (n=4), who received the anti-IgE agent, omalizumab, postoperatively. Both groups were evaluated by sinus computed tomography (CT) and nasal endoscopic examination, and comparisons were made between the groups with respect to differences in the recurrence of NP after ESS. RESULTS: Collectively, the subjects showed a direct relationship between NP severity and pretreatment total serum IgE levels. Preoperatively, there were no differences between the groups with regard to their total serum IgE levels, sinus CT scores, and endoscopically determined NP scores. Relative to corresponding preoperative values, there was no significant improvement in the sinus CT scores in either treatment group postoperatively. In contrast, relative to preoperative values, the nasal polyp scores significantly improved in the anti-IgE group, whereas the control group showed no significant improvement. CONCLUSION: This pilot study provides new evidence establishing that (1) endoscopic NP severity directly correlates to total serum IgE levels and (2) inclusion of anti-IgE therapy in the postpolypectomy management of atopic asthmatic individuals may reduce the severity of NP recurrence.     

The human leukocyte antigen G molecule (HLA-G) expression in patients with nasal polyposis

IntroductionSinonasal polyposis (NP) is a chronic inflammatory pathology of the nasal/paranasal cavities which affects from 1%-4% of the population. Although polyps seem to be a manifestation of chronic inflammation in both allergic and non-allergic subjects, the pathogenesis of nasal polyposis remains unknown. HLA-G molecules are a kind of no classic class I antigen with anti-inflammatory and tolerogenic properties. Little attention has been paid to the role of HLA-G chronic inflammatory disorders.ObjectiveThe aim of this study is to investigate the expression of HLA-G in the NP.Materials and methodsProspective study involving samples of patients presenting with nasal polyposis that were subjected to the immunohistochemistry technique. After a skin prick test, all patients were divided into atopic and nonatopic groups and classified as asthmatic or non-asthmatic.ResultsImmunohistochemical staining demonstrated a higher expression of the HLA-G molecule in samples from nonatopic than in those from atopic patients, and was significantly lower in the non-asthmatic patients.ConclusionThese results indicate that HLA-G may play an important role in the pathology of nasal polyposis. Considering the anti-inflammatory properties of HLA-G, this study suggests that it could reduce susceptibility to atopy and asthma.     

Influence of allergy in patients with nasal polyposis after endoscopic sinus surgery

CONCLUSION: Allergy does not modify the symptoms and steroid consumption (oral and local) of nasal polyposis (NP) patients after functional endoscopic sinus surgery (FESS). OBJECTIVES: To assess the role of allergy in the evolution after FESS of patients presenting with the diagnosis of NP. PATIENTS AND METHODS: This was a prospective study of 63 consecutive patients with NP (57% males, mean age 45.8 years), who were analyzed to detect whether the results of a surgical treatment of NP were influenced by the presence of positive allergic tests (Phadiatop). Three nasal criteria were scored: nasal obstruction, posterior rhinorrhea, and the loss of smell. The frequency of asthma was evaluated. Medical treatment of NP after FESS consisted of washing of the nasal cavities, steroid spray, and oral steroid administration. The amount of consumption of steroids (prednisolone and beclomethasone) was studied. RESULTS: Decrease of all nasal symptoms was not statistically different in the two groups of patients with and without allergy. Cumulative consumption of prednisolone and beclomethasone after surgery was similar in the two groups.     

Effects of Sinus Surgery on Asthma in Aspirin Triad Patients

The aspirin triad (nasal polyposis, asthma and sensitivity to aspirin) is a well-recognized clinical entity, also known as aspirin-induced asthma (AIA). The sinusitis associated with AIA is often difficult to treat and aggravates the asthmatic symptoms. In order to evaluate the surgical treatment of sinusitis in AIA, 22 patients who underwent sinus surgery were studied. Twenty patients (90.9%) got any relief of their asthma symptoms from sinus surgery. Postoperative pulmonary function test 1 year after surgery showed statistically significant improvement over the preoperative one. Three of 5 patients (60%) who used systemic steroids were able to eliminate or reduce their dosages. Also, 8 of 17 patients (47.1%) who were using inhaled topical steroids reduced their dosages and statistical analysis showed a significant difference in the doses of topical steroid used before and after surgery. Subjective evaluation of 20 patients (90.9%) indicated that the sinus surgery was effective for their asthma condition; showing from mild to marked improvement. For AIA patients aggravated by sinus disease, we recommend sinus surgery to improve the quality of life.     

Effects of sinus surgery on asthma in aspirin triad patients.

The aspirin triad (nasal polyposis, asthma and sensitivity to aspirin) is a well-recognized clinical entity, also known as aspirin-induced asthma (AIA). The sinusitis associated with AIA is often difficult to treat and aggravates the asthmatic symptoms. In order to evaluate the surgical treatment of sinusitis in AIA, 22 patients who underwent sinus surgery were studied. Twenty patients (90.9%) got any relief of their asthma symptoms from sinus surgery. Postoperative pulmonary function test 1 year after surgery showed statistically significant improvement over the preoperative one. Three of 5 patients (60%) who used systemic steroids were able to eliminate or reduce their dosages. Also, 8 of 17 patients (47.1%) who were using inhaled topical steroids reduced their dosages and statistical analysis showed a significant difference in the doses of topical steroid used before and after surgery. Subjective evaluation of 20 patients (90.9%) indicated that the sinus surgery was effective for their asthma condition; showing from mild to marked improvement. For AIA patients aggravated by sinus disease, we recommend sinus surgery to improve the quality of life.     

Expression of MCP-4 by TLR ligand-stimulated nasal polyp fibroblasts

Conclusion. These results indicate that nasal polyp fibroblasts contribute to innate immunity and eosinophilic inflammation such as nasal polyposis. Objective. It is generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play an essential role in the pathogenesis of nasal polyposis. Nasal polyposis is characterized by chronic eosinophilic inflammation. The mechanisms that cause the predominance of eosinophilic infiltration in nasal polyposis have yet to be clarified. There is growing evidence that fibroblasts could be a major source of Th2 chemokines. Because the nasal and paranasal mucosae are the first respiratory tissues that environmental agents encounter, those tissues are exposed to injurious agents, including microorganisms and their breakdown products. We investigated whether nasal polyp fibroblasts produce a C-C chemokine, MCP-4, when stimulated with the breakdown products of microorganisms and a Th2 cytokine (interleukin (IL)-4). Materials and methods. Fibroblast lines were established from nasal polyp tissues. The expression of MCP-4 mRNA was evaluated by real-time RT-PCR. The amount of MCP-4 in the supernatants was measured by ELISA. Results. TLR2, 3, 4 and 5 ligands, but not TLR7/8 or 9 ligands, induced small amounts of MCP-4. TLR2, 3, 4 and 5 ligands synergized with IL-4 to induce the production of MCP-4.     

Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis

Objective

Monitoring of fractional concentrations of exhaled nitric oxide (FeNO) has become a reliable marker of inflammation in human nose and paranasal sinuses. However, it is still unknown to what extent nasal NO levels contribute to the pathology of chronic rhinosinusitis (CRS). In the present study, we aimed to examine FeNO levels and the underlying mechanism of NO production and metabolism in patients with eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS.

Methods

Thirty-three untreated ECRS patients, 16 non-ECRS patients, and 38 normal subjects were enrolled in this cross-sectional study of FeNO levels. Oral and nasal FeNO levels were measured before treatment using an electrochemical NO analyzer (NObreath^®) with a nose adaptor. The mRNA expression of three nitric oxide synthase (NOS) isoforms, interleukin-5 (IL-5), and transforming growth factor-beta (TGF-β) in the ethmoid sinus mucosa and nasal polyps were analyzed by real-time PCR. Immunohistological localization of inducible NOS (iNOS) and nitrotyrosine (NT), a marker for oxidized NO metabolites, was also examined.

Results

ECRS patients showed significantly higher oral FeNO levels compared to non-ECRS patients and normal subjects (mean values, 47.6, 13.5, and 15.3 ppb, respectively). Nasal FeNO levels of the non-ECRS patients (30.5 ppb) were significantly lower than those of the ECRS patients (53.9 ppb) and normal subjects (45.5 ppb). Positive correlations existed between the blood eosinophil percentage and FeNO levels in ECRS patients. Histologically, ECRS patients showed higher eosinophil accumulation in the ethmoid mucosa than non-ECRS patients (103.1 vs. 16.3 cells/HPF). Real-time PCR analysis showed significant upregulation of iNOS and IL-5 mRNA expression in the ethmoid mucosa of the ECRS patients compared to those of non-ECRS patients. Positive iNOS immunoreactivity was observed in ciliated epithelial cells, submucosal glands and associated inflammatory cells in both groups. NT immunoreactivity was detected in the epithelium and around inflammatory cells. Intense NT staining was co-localized with eosinophil accumulation and ECRS patients showed significantly higher rates of NT-positive cells than non-ECRS patients.

Conclusion

A combination of oral and nasal FeNO measurement is a valid marker for the classification and definition of different CRS subtypes in Japan. Higher levels of oral and nasal FeNO in ECRS patients may reflect the persistence of eosinophilic inflammation in sinus mucosa with concomitant iNOS upregulation and accompanying deposition of oxidized NO metabolites.     

Eicosanoid metabolism and eosinophilic inflammation in nasal polyp patients with immune response to Staphylococcus aureus enterotoxins

BACKGROUND: Staphylococcus aureus-derived enterotoxins (SEs) have been implicated in the pathogenesis of airway inflammatory diseases, especially nasal polyposis. However, the exact role of these molecules in the regulation of eicosanoid synthesis in this pathology remains unexplored. We studied the possible impact of SE-induced immune responses on the eicosanoid production in nasal polyp (NP) patients. METHODS: Tissue sample homogenates from NP patients, with (NP-SEs[+]) and without detectable IgE-antibodies to SEs (NP-SEs[-]; ImmunoCap system), were assayed for IL-5, myeloperoxidase, leukotriene CJD4/E4 (LTC4/D4/E4), LTB4, lipoxin A4, total IgE, and eosinophil cationic protein. RESULTS: Inflammatory makers, eicosanoids, and total IgE were significantly increased in NP-SEs(+) compared with NP-SEs(-) tissues, with the exception of myeloperoxidase, which was similar in both groups. Eicosanoid concentrations correlated to IL-5 and eosinophil cationic protein; however, only cys-leukotriene levels correlated with IgE-antibodies to SEs, independently of allergy and asthma. CONCLUSION: Eicosanoid synthesis is up-regulated in polyp tissue of patients with immune response to SEs and seems to be related to the inflammatory reaction induced by these enterotoxins.     

Pathogenesis of airway inflammation in bronchial asthma

Bronchial asthma is a chronic disorder characterized by airway inflammation, reversible airway obstruction, and airway hyperresponsiveness. Eosinophils are believed to play important roles in the pathogenesis of asthma through the release of inflammatory mediators. In refractory eosinophilic asthma, anti-IL-5 mAb reduces exacerbations and steroid dose, indicating roles of eosinophils and IL-5 in the development of severe eosinophilic asthma. Even in the absence of IL-5, it is likely that the “Th2 network”, including a cascade of vascular cell adhesion molecule-1/CC chemokines/GM-CSF, can sufficiently maintain eosinophilic infiltration and degranulation. Cysteinyl leukotrienes can also directly provoke eosinophilic infiltration and activation in the airways of asthma. Therefore, various mechanisms would be involved in the eosinophilic airway inflammation of asthma.In the pathogenesis of severe asthma, not only eosinophils but also mast cells or neutrophils play important roles. Mast cells are much infiltrated to smooth muscle in severe asthma and induce airway remodeling by release of inflammatory mediators such as amphiregulin. Treatment with anti-IgE Ab, which neutralizes circulating IgE and suppresses mast cell functions, reduces asthma exacerbations in severe asthmatic patients. Furthermore, infiltration of neutrophils in the airway is also increased in severe asthma. IL-8 plays an important role in the accumulation of neutrophils and is indeed upregulated in severe asthma. In the absence of chemoattractant for eosinophils, neutrophils stimulated by IL-8 augment the trans-basement membrane migration of eosinophils, suggesting that IL-8-stimulated neutrophils could lead eosinophils to accumulate in the airways of asthma. In view of these mechanisms, an effective strategy for controlling asthma, especially severe asthma, should be considered.     

NARES: a risk factor for obstructive sleep apnea?

BACKGROUND: Nonallergic rhinitis with eosinophilia syndrome (NARES) constitutes a rare nasal condition characterized by a chronic, eosinophilic inflammation. Patients' major complaints constitute nasal congestion and rhinorrhea. Obstructive sleep apnea syndrome (OSAS) is a potentially life-threatening condition characterized by recurrent episodes of obstruction of the upper airways resulting in oxygen desaturation. Nasal congestion constitutes one predisposing factor for OSAS. OBJECTIVE: The purpose was to study whether NARES constitutes a risk factor for OSAS. METHODS: The study included 26 patients presenting typical symptoms of sleep apnea. Ten patients were diagnosed to suffer from NARES (mean age 56.8 +/- 12.5, body mass index [BMI] 29.3 kg/m(2) +/- 2.8; 9 men:1 woman) and were compared with 16 age- and BMI-matched individuals (mean age 58.8 +/- 11.6, BMI 29.7 kg/m(2) +/- 3.8, 16 men) without any nasal inflammation, such as allergic rhinitis, sinusitis, nasal polyposis, or vasomotor rhinitis. All patients were tested by polysomnography for an OSAS. RESULTS: Patients suffering from NARES revealed significantly (P <.01) impaired polysomnographic parameters (hypopnea index, apnea-hypopnea index, mean and minimal oxygen saturation) compared with patients without any nasal inflammation. CONCLUSIONS: Our data point to NARES as a risk factor for the induction or augmentation of OSAS. NARES patients suffered from severe OSAS, whereas nondiseased individuals suffered only from moderate OSAS, according to the criteria of the American Academy of Sleep Medicine. Our data support results of others, suggesting chronic nasal inflammation to cause OSAS. Mechanisms for our observations are not fully understood yet. Nasal obstruction or neuronal reflexes might be involved.     

Interleukin-17A expression in patients presenting with nasal polyposis

Sinonasal polyposis (SNP) is a chronic inflammatory pathology of the nasal/paranasal cavities which affects from 1%-4% of the population. Although polyps seem to be a manifestation of chronic inflammation of nasal/paranasal sinus mucosa in both allergic and non-allergic subjects, the pathogenesis of nasal polyposis remains unknown. Interleukin-17A (IL-17A) is a key inflammatory cytokine in many disorders. Little attention has been paid to the role of IL-17A in chronic inflammatory disorders.ObjectiveTo investigate the expression of IL-17A in the SNP and verify if this expression is a marker of good or bad prognosis.MethodProspective study with 25 patients presenting with SNP were subjected to the immunohistochemistry technique. After a skin prick test, all patients were divided into atopic and nonatopic groups, and asthmatic or non-asthmatic.ResultsThe IL-17A expression was observed in both atopic and nonatopic patients. The numbers of IL-17A positive cells were greater in nasal polyps of atopic patients than nonatopic (p = 0.0128).ConclusionThese results indicate that IL-17A may play an important role in the pathology of SNP. Considering the inflammatory properties of IL-17A, this study suggests that it could increase susceptibility to atopy and asthma.