Effect of endosinusal treatment on cellular markers in mild and moderate asthmatics

OBJECTIVE: To determine the efficacy of topical endosinusal treatment in terms of reduction in activation of inflammatory cells and asthma/rhinosinusitis symptoms in patients with asthma and chronic rhinosinusitis (CRS). MATERIAL AND METHODS: Eighteen mild-to-moderate asthmatics with CRS were subjected to antral sinoscopy and endosinusal treatment with 2 mg of dexamethasone and 40 mg of gentamicin per maxillary sinus for 7 days. Sinus lavage and serum samples were taken before and after the treatment and bacteriological swabs from the sinuses were taken at the time of inclusion in the study. Subjective scores for CRS symptoms and forced expiratory volume in 1 s (FEV1) were tested at inclusion and after 30 days. Levels of eosinophil cationic protein (ECP), tryptase and myeloperoxidase (MPO) were analyzed in serum and sinus fluid before and after the treatment. RESULTS: ECP and tryptase levels were significantly reduced in both serum and sinus fluid, but serum MPO did not show significant changes after the treatment. MPO in sinus lavage was reduced only in moderate asthmatics. Subjective scores for CRS and FEV1 were significantly improved for the whole group. ECP, usually used as a parameter for asthma staging, was mostly affected at the systemic level, whilst tryptase was more markedly reduced at the local level. CONCLUSION: The topical endosinusal treatment used in this clinical study significantly reduced activation of eosinophils and mastocytes, improved FEV1 and reduced symptoms of CRS in mild-to-moderate asthmatics.     

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.     

Th2 immunological inflammation in allergic fungal sinusitis, nonallergic eosinophilic fungal sinusitis, and chronic rhinosinusitis

BACKGROUND: Noninvasive fungal sinusitis is a heterogenous group of conditions including allergic fungal sinusitis (AFS) and nonallergic eosinophilic fungal sinusitis (NEFS). Th2-mediated cascades have been postulated to be the major inflammatory response in patients with AFS although other mechanisms also may be involved. The detailed mucosal Th2 cytological status of NEFS still has not been studied in great depth. METHODS: Using a meticulous patient selection algorithm over a 2-year period, infundibular mucosal tissue from patients with AFS, NEFS, chronic rhinosinusitis (CRS), and normal controls was studied (n = 59). Immunohistochemistry for mast cells, eosinophils, and immunoglobulin E (IgE) cells was performed and cell counts per unit area were measured. RESULTS: Mast cell, eosinophil, and IgE+ cell numbers were significantly raised in patients with AFS, NEFS, and CRS when compared with controls. There was no significant difference between cell numbers in patients with AFS and NEFS. CONCLUSION: Patients with AFS exhibit a classic Th2 inflammatory response in nasal mucosal tissue with NEFS and CRS patients showing evidence of a similar Th2 cascade, including the presence of IgE+ cells.     

Effect of nasal antifungal therapy on nasal cell activation markers in chronic rhinosinusitis

OBJECTIVE: To examine the effect of nasal antifungal treatment on eosinophil cationic protein (ECP) and tryptase levels in samples of nasal lavage fluid from patients with chronic rhinosinusitis and nasal polyps. DESIGN: Prospective double-blind placebo-controlled clinical trial. SETTING: Tertiary surgical center. PATIENTS: Subjects with severe chronic rhinosinusitis and nasal polyps. Of 120 screened patients, 76 were eligible. Six patients withdrew because of minor adverse events, and 10 dropped out for other reasons. In total, 60 patients completed the study according to the study protocol. INTERVENTIONS: Nasal treatment with amphotericin B or saline control for 8 weeks. MAIN OUTCOME MEASURES: Nasal lavages were performed before and after treatment. Fungal elements were assessed by culture and with different polymerase chain reaction assays. Levels of ECP and tryptase were determined by fluorescent enzyme immunoassay. RESULTS: No correlation between cell activation markers and fungus detection was observed before treatment (all P>.20). Nasal amphotericin B treatment had no effect on levels of ECP (P = .17) or tryptase (P = .09) in nasal lavage samples. Moreover, successful fungus eradication, defined as fungus detection before but not after treatment, did not influence nasal ECP or tryptase levels (all P>.40). CONCLUSION: Neither topical amphotericin B therapy nor fungal state before and after treatment had any significant influence on activation markers of nasal inflammatory cells in chronic rhinosinusitis.     

Capsaicin significantly reduces sinonasal polyps

Some reports indicate that topical nasal treatment with capsaicin, which is usually effective in reducing symptoms of vasomotor rhinitis, may also reduce symptoms in patients with nasal polyps. The aim of this study was to investigate the effect of topical capsaicin treatment in severe sinonasal polyposis. Nine non-allergic, non-asthmatic patients with diffuse eosinophilic nasal polyposis were subjected to topical capsaicin treatment: for 3 consecutive days 0.5 ml 30 micromol/l capsaicin solution and on days 4 and 5 100 micromol/l capsaicin solution was sprayed into each nostril. Coronary computed tomography (CT) images were made shortly before treatment. Baseline nasal lavages and a questionnaire containing subjective symptoms and nasal endosocpy were taken just prior to the first application. Nasal lavages were performed prior to and after the last treatment and over 4 weeks, endoscopy and subjective scores at each weekly visit, and correspondent CT scans 4 weeks after the treatment. CT images were analysed by computer, calculating the nose sinuses air volume (NSAV) from the surface of aerated parts of nasal and sinus cavities for each slice per patient prior to and after treatment. Statistical analysis was performed comparing NSAV, subjective scores, endoscopy scores and eosinophil cationic protein (ECP) levels in nasal lavages prior to and after treatment. Topical treatment with capsaicin significantly increased NSAV and very significantly improved subjective and endoscopy scores, but did not significantly alter ECP levels in nasal lavages.     

Histopathologic characteristics of chronic sinusitis with bronchial asthma

CONCLUSION: These findings suggest that patients with both sinusitis and asthma present the histopathologic characteristic of a marked chronic inflammatory reaction, and that eosinophil infiltration may play a significant role in this marked inflammation of the sinus mucosa. OBJECTIVE: Chronic sinusitis and bronchial asthma are known to be closely related. However, the appearance of the mucosa in chronic sinusitis patients with asthma is somewhat different from that in patients without asthma. MATERIAL AND METHODS. We compared the sinus mucosal histopathologies of asthmatic patients with those of non-asthmatic patients. Fifty-three sinusitis patients with a diagnosis of asthma and 54 sinusitis patients without asthma, who served as controls, were enrolled in the study. All of these patients underwent endoscopic sinus surgery. The following seven light microscopic findings were compared in the asthmatic and non-asthmatic groups: the thickness of the basement membrane, goblet cell hyperplasia, subepithelial edema, submucous gland formation, eosinophil infiltration, lymphocyte infiltration and polymorphonuclear leukocyte infiltration. In addition, we explored a possible link between asthma and sinusitis by comparing the following factors in asthmatic and non-asthmatic patients: the presence of allergy, the degree of preoperative polyposis and the extent of preoperative disease as scored by means of ostiomeatal unit CT findings. RESULTS: No statistically significant differences were found between the two groups in terms of the presence of allergy, the degree of preoperative polyposis or the extent of preoperative disease. Basement membrane thickening, goblet cell hyperplasia and eosinophil infiltration were more prominent in the asthmatic compared to the non-asthmatic group (p <0.05).     

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.     

慢性鼻窦炎手术前后ECP、EGF、IL-6的水平变化及临床意义

目的 探究慢性鼻窦炎(CRS)鼻息肉患者鼻内镜手术(ESS)前后患者鼻腔分泌物中嗜酸性粒细胞阳离子蛋白(ECP)、表皮生长因子(EGF)、白细胞介素-6(IL-6)的变化,分析它们在术腔创伤愈合中的意义。 方法 选取行ESS的163例CRS鼻息肉患者作为研究对象,另选同期健康体检者50例作为对照组。所有患者术前及术后1、6、12周行鼻内镜检查并采集鼻腔分泌物,采用酶联免疫荧光分析技术检测鼻腔分泌物中ECP、EGF、IL-6的浓度。 结果 与对照组相比,术前ECP、EGF、IL-6含量显著升高(P<0.05)。术后1周ECP、EGF、IL-6含量显著低于对照组、术前(P<0.05)。术后6周ECP、EGF、IL-6含量显著高于对照组、术前、术后1周(P<0.05)。术后12周ECP、EGF、IL-6含量显著低于术前及术后6周(P<0.05),显著高于术后1周(P<0.05),与术前相比差异无统计学意义(P>0.05)。线性回归分析结果表明,术前ECP、EGF、IL-6含量影响术后6周和术后12周患者术腔创伤愈合情况(P<0.05)。 结论 CRS鼻息肉患者术前ECP、EEG、IL-6含量显著升高,且在术后创伤愈合过程中的动态变化与术后上皮修复过程可能有相关性,术前ECP、EEG、IL-6含量是影响鼻黏膜术后上皮修复的指标。     

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

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

Evidence of mast cell activity in the middle ears of children with otitis media with effusion

OBJECTIVES: This is the first study to report the presence of tryptase, a reflection of mast cell activity, in chronic middle ear effusion of patients whose atopic status was characterized. DESIGN AND METHODS: Mediator activity of mast cells and eosinophils was measured prospectively from effusion of 33 randomly selected patients and 5 control subjects with chronic otitis media with effusion (OME). Atopy was determined by enzyme-linked immunosorbent assay. Middle ear biopsies from a second group of 8 OME patients and 4 controls were fixed in plastic and stained immunohistochemically for mast cells. RESULTS: Sixty-one percent of patients had extensive activation of mast cells in their middle ears. Among those with elevated tryptase in their effusion, 95.6% were atopic and 94.7% also had elevated levels of effusion eosinophilic cationic protein (ECP). Tryptase levels were elevated only in the effusion of atopic patients, as compared with 5 controls (P < .01). Mast cells were present in 6 of 8 OME ears and absent in all 4 normal ears. CONCLUSION: Mast cells and its mediator tryptase, both indicators of a Th2-driven immune response, are present in a majority of ears that have chronic effusion. These findings support the hypothesis that middle ear mucosa is capable of an allergic response and that the inflammation within the middle ear of most OME patients is allergic in nature.     

鼻息肉中总IgE与嗜酸粒细胞浸润的相关性研究

目的:探讨总IgE及嗜酸粒细胞(EOS)在鼻息肉中的表达及其相关关系,以分析其在鼻息肉发病中的作用。方法:采用免疫组织化学SP法检测38例鼻息肉、15例中鼻甲黏膜组织中总IgE阳性细胞表达;采用Chromotrope2R染色法检测EOS浸润情况。结果:①鼻息肉组织中总IgE及EOS水平均明显高于中鼻甲黏膜组织,均P<0.01;②鼻息肉组织中总IgE与EOS呈明显正相关关系(r=0.843,P<0.01)。结论:EOS浸润在鼻息肉的形成和发展中起重要作用,IgE介导的Ⅰ型变态反应对鼻息肉中EOS浸润发挥一定作用。     

Activated eosinophils in nasal polyps: a comparison of asthmatic and non‐asthmatic patients

Objectives: There is a recognized clinical association between nasal polyps and asthma. Nasal polyps and the airways of asthmatic patients demonstrate marked eosinophilia suggesting that this inflammatory cell may have a key role to play in both conditions. The objective of this study was to determine whether nasal polyps from patients with asthma had a greater density of activated eosinophils than patients with no associated respiratory disease. Design: Archived specimens were retrieved from patients who had undergone nasal polyp surgery and their case notes reviewed. Activated eosinophils were identified using immunohistochemistry for a monoclonal antibody to secreted eosinophil cationic protein (EG2). Setting: Teaching hospital otolaryngology unit. Participants: Consecutive patients who had undergone nasal polyp surgery in 1994 were recruited. The diagnosis of asthma was based on a documented physician diagnosis and appropriate drug treatment. Twenty‐four asthmatic and 35 non‐asthmatic patients were studied. Main outcome measures: Eosinophil density was measured using a standardized counting technique. Results: Asthmatic patients were significantly more likely to have had previous polyp surgery (chi‐square test: P < 0.05). Areas of intense eosinophilia were identified in all samples. There was a significant greater degree of activated eosinophilia in the asthmatic patients (t‐test: P < 0.05). Conclusions: We have demonstrated a higher number of previous operations in asthmatic patients, and also a greater degree of activated eosinophilia in asthmatic polyps compared with non‐asthmatics. This would suggest that eosinophil activity has a role to play in the pathogenesis of nasal polyps.     

Molecular and cellular staging for the severity of chronic rhinosinusitis

OBJECTIVES: To correlate objective and subjective clinical parameters with molecular, cellular, and histologic markers and to acknowledge the importance of these basic science parameters in a severity classification system for chronic rhinosinusitis (CRS). STUDY DESIGN: Retrospective analysis of prospectively collected data of consecutive patients undergoing endoscopic sinus surgery for CRS in an academic institution. METHODS: The preoperative computed tomography (CT) scans of all patients with CRS scheduled for surgery were graded according to Lund and Mackay. The patients completed a Sino-Nasal Outcome Test (SNOT)-20 questionnaire and had a preoperative nasal endoscopy performed, which was graded by assigning an endoscopy score according to Lanza and Kennedy. Subjects had a medical questionnaire regarding presence of aspirin sensitivity, allergic rhinitis, asthma, and medication usage. Subjects also underwent pulmonary function testing and had skin tests for allergies. At the time of surgery, blood was drawn to determine the level of peripheral eosinophilia and the degree of polymorphisms of the leukotriene C4 synthase gene. Sinus mucosal and polyp tissue was examined pathologically for the number of eosinophils per high-powered filed (HPF) and was stained for EG2 to determine the portion of activated eosinophils. Leukotriene C4 levels (pg/g of tissue) were determined using a sensitive competitive enzyme immunoassay. Endoscopy and SNOT-20 scores were reevaluated 1 year after surgery. Data were analyzed for disease-severity correlation to recommend a severity classification system for CRS that incorporates the contribution of clinical, molecular, cellular, and histologic parameters. RESULTS: The presence of polyps resulted in higher preoperative CT scores and higher preoperative and postoperative symptom scores. Average preoperative CT scores were significantly higher in asthmatics and allergy patients and correlated with endoscopy scores. Patients with more than five eosinophils/HPF of sinus tissue had higher frequency of polyps and asthma and higher CT and endoscopy scores than patients without sinus tissue eosinophilia (less than or equal to 5 cells/HPF sinus tissue). The subgroup of patients with eosinophilic nasal polyps (eosinophilic hyperplastic rhinosinusitis) had more severe disease by CT and endoscopy than the subgroup of patients with nasal polyps (hyperplastic rhinosinusitis) but without eosinophilia. Similarly, patients without polyps but with tissue eosinophilia had more severe disease than patients without polyps and without eosinophilia. Leukotriene C4 levels were elevated in all patient groups. Symptom scores did not correlate with any of the parameters. CONCLUSION: We suggest the following severity classification system for CRS: 1) eosinophilic chronic hyperplastic rhinosinusitis (ECHRS): patients with polyps and sinus tissue eosinophilia; 2) noneosinophilic chronic hyperplastic rhinosinusitis (NECHRS): patients with polyps but without sinus tissue eosinophilia; 3) eosinophilic chronic rhinosinusitis (ECRS): patients without polyps but with sinus tissue eosinophilia; 4) noneosinophilic chronic rhinosinusitis (NECRS): patients without polyps and without sinus tissue eosinophilia.     

变应性因素对慢性鼻-鼻窦炎影响的研究

目的:探讨变应性因素与慢性鼻-鼻窦炎(CRS)疾病严重程度之间的相关性以及其对CRS的病情发展和转归的影响.方法:101例CRS患者进行变应性因素血清相关指标检测:血清总IgE浓度、血清特异性变应原IgE半定量检测、血清嗜酸粒细胞阳离子蛋白(ECP)浓度及病史询问、Lund-Mackay CT系统评分.结果:CRS组血清总IgE浓度及血清ECP浓度均高于正常对照组(P＜0.01);CRS组血清总IgE浓度增高发生率及血清ECP浓度增高发生率随着临床分型的加重而显著增加,并且在有既往相关手术史的患者中较无相关手术史患者中亦有显著增高(P＜0.05);血清总IgE浓度及血清ECP浓度增高患者的平均Lund-Mackay CT评分较浓度正常患者CT评分有显著性增高.CRS组血清特异性变应原IgE半定量检测阳性率为67.32%,强阳性率27.72%;各分型之间特异性变应原强阳性率差异有统计学意义(P＜0.05);有既往相关手术史的患者变应原强阳性率较无手术史患者的强阳性率显著性增高(P＜0.05);变应原强阳性患者CT评分较阴性患者CT评分有显著性增高(P＜0.05).结论:变应性因素对CRS的病变程度有一定负面作用,是影响疾病严重度及手术预后的不良因素.     

Perennial rhinitis: an analysis of skin testing, serum IgE, and blood and smear eosinophilia in 201 patients

Allergen skin testing, eosinophil counting in blood and nasal smear and serum IgE determination were performed in patients with simple perennial rhinitis, and in patients with rhinitis and asthma. The results were compared with those obtained in normal controls. As a positive skin test was demonstrated in 40% of patients with simple rhinitis and in 88% of patients with rhinitis and asthma, skin testing is considered relevant in all patients with perennial rhinitis. While blood eosinophil count and serum IgE level were elevated in a fair proportion of asthmatic patients, only a few subjects with simple perennial rhinitis had an elevated level, and the diagnostic values of these tests is questionable. On the other hand, examination of a nasal smear for eosinophils could usually separate the patients from the controls. The study emphasizes the importance of making a distinction between simple perennial rhinitis and perennial rhinitis associated with other symptoms and diseases.     

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.     

Association of Otitis Media With Effusion and Allergy as Demonstrated by Intradermal Skin Testing and Eosinophil Cationic Protein Levels in Both Middle Ear Effusions and Mucosal Biopsies

This study was performed to ascertain the role of allergy, as defined by skin testing and histochemical markers, in the pathogenesis of otitis media with effusion (OME). A historical perspective of allergy as it relates to OME is presented. The study included 89 patients: 48 with persistent effusion but no recent acute infection, 25 with purulent OME complicated by a superimposed infection, and 16 control subjects. All 89 patients had persistent effusion for more than 2 months and subsequently required the placement of tympanostomy tubes. Allergy was defined using the radioallergosorbent test (RAST), serum immunoglobulin E (IgE) levels, and skin tests. Allergies were present in 97% of the patients with nonacute OME. The relationship between allergy and OME was corroborated clinically in 89% of patients and was also substantiated by elevated levels of effusion eosinophil cationic protein (ECP) in 87.5% of OME patients. Histologically, polyclonal antibody staining for ECP demonstrated the presence of eosinophils in middle ear mucosal biopsy specimens. This study confirms that OME is a sign of allergic inflammation in the middle ear that is associated with an increase in eosinophils and a concomitant release of ECP into the effusion in individuals with allergy demonstrated by skin testing.     

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.