Pathogenic mechanisms underlying the clinical symptoms of allergic rhinitis

This paper reviews our previous studies on an objective evaluation of nasal symptoms, a quantitative determination of biochemical mediators, and inflammatory cells in nasal secretions of atopic patients after nasal allergen challenge (NAC) and during natural allergen exposure. The use of the microsuction technique has proved to be a useful and reliable nasal sampling method permitting quantitative analysis of important mediators in nasal secretions. This has provided accurate data on the activity of some important inflammatory cells such as mast cells, basophils, and eosinophils in allergic rhinitis. Our studies demonstrate that a significant increase in the concentrations of histamine, tryptase, and LTC4 in nasal secretions occurs within seconds or minutes after NAC, and this is accompanied by itching, sneezing, rhinorrhea, and nasal obstruction. The infiltration and activation of eosinophils are found to be the predominant condition during the late-phase reaction (LPR), which is mainly characterized by unilateral and/or bilateral nasal obstruction with little sneezing and rhinorrhea. The latter condition is found to be very much similar to the pathophysiology of patients with ongoing allergic rhinitis. In conclusion, our studies demonstrate that patients with ongoing allergic rhinitis seem to be in a continuous late phase state of eosinophilia and increased mediator release, a condition that can explain priming and nonspecific hyperreactivity of the nasal mucous membrane.     

Immunoglobulins in nasal secretions of patients with allergic rhinitis and chronic rhinosinusitis

Allergic rhinitis and chronic rhinosinusitis are the most frequently encountered inflammatory reactions of the sinonasal mucosa. Nasal-associated lymphoid tissue has been suggested as an inductive site for humoral and cellular immune responses in the upper respiratory tract. Immunoglobulins are important elements in human adaptive immune responses and deficiencies of serum immunoglobulins may be associated with recurrent or refractory infections. However, the local humoral immune response to offending antigens in the nasal environment has not been well elucidated. To determine the levels of IgA and IgG subclasses antibodies in the nasal secretions of patients with allergic rhinitis and chronic rhinosinusitis, 25 patients with allergic rhinitis and 20 with chronic rhinosinusitis were included and their nasal secretions were collected to measure the levels of secretary IgA (sIgA), total IgA (tIgA), and IgG subclasses antibodies. There was a significant elevation of IgG₃ in the nasal secretions of patients with chronic rhinosinusitis. No difference was noted in the levels of sIgA, tIgA, IgG₁, IgG₂ and IgG₄ among the three groups. The local defense mechanism of nose reacts to microorganisms and pathogenic antigens by inducing the adaptive humoral immune response to increase the amount of immunoglobulins, with IgG₃ being the major up-regulated antibody.     

Die (ausschließlich) lokale IgE-Produktion in der Nasenschleimhaut

Background

IgE production at the site of the nasal mucosa without systemic allergic sensitization in skin tests or in serum represents so-called “local allergic rhinitis (LAR)” as a subgroup of patients with symptoms of allergic rhinitis (AR). Formerly, in case of negative allergological test results, seasonal (intermittent) or perennial (persistent) allergic symptoms have been diagnosed as “non-allergic rhinitis” (NAR). However, there is evidence for specific Th2 cytokine, tryptase, and ECP (eosinophil catonic protein) production in the nasal secretion after allergen exposure in these patients without systemic sensitization.

Diagnosis

Taking this into account, we recommend performing an allergen-specific nasal challenge and measuring the (local) nasal IgE-levels in addition to standard allergy tests in clinical routine in this subgroup of patients. These tests should be perfomed while or shortly after allergen exposure. In addition, an update of the allergy testing should be performed after a time interval since it has been demonstrated that patients formerly diagnosed with NAR may develop LAR or AR, or patients with LAR may develop AR in the future.

Treatment

The pharmacological therapeutic options in LAR are in line with the treatment of AR. If and to what extent this subgroup of AR patients benefit from allergen-specific immunotherapy (SIT) is currently being evaluated in clinical trials.     

变应性鼻炎引起嗅觉障碍的临床分析

目的分析变应性鼻炎引起嗅觉障碍的发病机制。方法选取216例变应性鼻炎患者作为实验对象,同时选取99例健康志愿者作为对照组。采用嗅棒气味嗅觉测试方法测定两组患者的嗅觉功能;采用酶联免疫吸附法检测鼻腔分泌物中嗜酸性粒细胞阳离子蛋白（eosinophil ationicprotein,ECP）及类胰蛋白酶的含量;应用鼻压计测定鼻气道阻力。结果变应性鼻炎患者鼻气道阻力与对照组比较差异无统计学意义（P〉0．05）;变应性鼻炎组患者嗅觉功能,鼻腔分泌物ECP和鼻腔分泌物类胰蛋白酶与对照组比较,差异具有统计学意义（P〈0．05）。结论嗜酸性粒细胞和肥大细胞的活性增加可能导致了变应性鼻炎患者的嗅觉障碍,而鼻腔阻塞可能不是引起变应性鼻炎患者嗅觉障碍的主要原因。     

免疫治疗对变应性鼻炎患者鼻分泌物中螨变应原特异性IgG1和IgG4抗体水平的影响

目的检测变应性鼻炎患者和健康人群鼻分泌物中螨变应原特异性IgG1和IgG4抗体水平，以了解变应原特异性IgG亚型抗体在人群鼻分泌物中的分布和免疫治疗对抗体浓度的影响。方法利用负压吸引法收集健康人群、变应性鼻炎未治疗组和免疫治疗组患者的鼻分泌物，采用间接非竞争生物素一链亲和素酶联免疫法检测鼻分泌物中粗制螨变应原、螨纯化变应原Der f Ⅰ和Der f Ⅱ各变应原特异性IgG1和IgG4亚型抗体浓度。结果变应性鼻炎患者鼻分泌物中螨粗制变应原特异性IgG1和IgG4抗体浓度均高于健康人(Z=-3．623、-3．061，P均＜0．01)；免疫治疗组患者IgG1和IgG4抗体浓度均高于非治疗组(Z=-2．453、-3．408，P均＜0．01)。免疫治疗组变应性鼻炎患者鼻分泌物中螨纯化变应原DerfI特异性Igc,4抗体水平较健康人群增高(Z=-3．518，P＜0．01)；而免疫治疗组DerfⅡ特异性IgG1和IgG4抗体水平均高于健康人(Z=-2．366、-2．936，P均＜0．01)和未治疗组(Z：-2．366、-2．937，P均＜0．01)。IgG1和IgG4亚群抗体中，螨粗制抗原、Der f Ⅰ和Der f Ⅱ特异性抗体水平相互间具有相关性；三类变应原特异性IgG1和IgG4抗体间存在相关性；免疫治疗组患者鼻分泌物中螨粗制变应原IgG1和IgC4抗体与血清中特异性IgE抗体间具有相关性。结论健康人群和变应性鼻炎患者均具有对其环境变应原产生特异性IgG1和IgG4抗体的能力，而变应性鼻炎患者具有更高的反应性，能产生高于健康人的特异性IgG亚型抗体，而变应原特异性免疫治疗能显著增加鼻分泌物中IgG1和IgC4抗体的水平。鼻分泌物中IgG1和IgG4抗体的增加可能是免疫治疗有效的机制之一。     

Nasal histamine reactivity; relationships to skin-test responses, allergen provocation and symptom severity in patients with long-continuing allergic rhinitis

It has been reported that skin-test reactivity and rhinitis symptom severity weaken in the course of time. A corresponding weakening might also be seen in non-specific nasal hyper-reactivity, but the relationships of these responses are poorly understood. Our aim was to measure nasal responsiveness to histamine in a series of patients with long-continuing allergic rhinitis and to compare these measurements with skin test responses, allergen provocation and changes in severity of allergic rhinitis symptoms. A total of 73 patients in whom allergic rhinitis had been verified over 20 years earlier were re-interviewed and re-investigated. Skin prick tests with common allergens were performed and the presence of nasal allergy was confirmed by allergen provocation. Non-specific nasal hyper-reactivity was determined with nasal histamine challenge using four concentrations of histamine phosphate. The response was registered by counting sneezes, recording changes in nasal discharge and mucosal swelling and measuring nasal airway resistance. Sneezing and discharge scores showed that milder non-specific nasal hyper-reactivity was associated with lack of reactivity in skin prick tests and nasal allergen challenge. No association was observed between allergy test results and changes in nasal airway resistance during the histamine provocation. In most patients the symptoms of rhinitis had become milder or disappeared during the follow-up, but the results of the histamine challenge showed no relationship with the changes in symptom severity. In patients with allergic rhinitis, reactivity to histamine is associated with a concomitant change in skin and nasal mucosal reactivity to allergens.     

Nasal Histamine Reactivity; Relationships to Skin-test Responses,Allergen Provocation and Symptom Severity in Patients with Long-continuing Allergic Rhinitis

It has been reported that skin-test reactivity and rhinitis symptom severity weaken in the course of time. A corresponding weakening might also be seen in non-specific nasal hyper-reactivity, but the relationships of these responses are poorly understood. Our aim was to measure nasal responsiveness to histamine in a series of patients with long-continuing allergic rhinitis and to compare these measurements with skin test responses, allergen provocation and changes in severity of allergic rhinitis symptoms. A total of 73 patients in whom allergic rhinitis had been verified over 20 years earlier were re-interviewed and re-investigated. Skin prick tests with common allergens were performed and the presence of nasal allergy was confirmed by allergen provocation. Non-specific nasal hyper-reactivity was determined with nasal histamine challenge using four concentrations of histamine phosphate. The response was registered by counting sneezes, recording changes in nasal discharge and mucosal swelling and measuring nasal airway resistance. Sneezing and discharge scores showed that milder non-specific nasal hyper-reactivity was associated with lack of reactivity in skin prick tests and nasal allergen challenge. No association was observed between allergy test results and changes in nasal airway resistance during the histamine provocation. In most patients the symptoms of rhinitis had become milder or disappeared during the follow-up, but the results of the histamine challenge showed no relationship with the changes in symptom severity. In patients with allergic rhinitis, reactivity to histamine is associated with a concomitant change in skin and nasal mucosal reactivity to allergens.     

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.     

变应性鼻炎鼻黏膜上皮细胞免疫活性研究进展

鼻黏膜上皮细胞构成的物理和化学屏障是呼吸道接触外源性微生物、变应原和环境污染物等的第一道防线。除理化屏障功能,上皮细胞在变应性鼻炎发病机制中的免疫调控作用受到越来越多的重视。上皮细胞对天然免疫和获得性免疫均具有重要的免疫调控功能,这种免疫调控功能的实现依赖于功能性细胞因子的表达及上皮细胞与下游免疫细胞的相互信息传递。现就鼻黏膜上皮细胞与变应原及其他免疫细胞之间的信息传递做一简要梳理。     

慢性鼻窦炎鼻息肉与变应性因素相关性的探讨

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

An in vitro model for measuring tryptase release from nasal mucosa in response to allergen challenge

A simple in vitro nasal mucosal culture model has been developed to measure release of the mast cell specific enzyme tryptase in response to allergen challenge. Patients who were undergoing inferior turbinectomy were skin-tested for commonly inhaled allergens. The mucosa from the inferior turbinates was kept viable using Minimal Essential Medium. Tryptase release into the medium was measured using the Pharmacia Riact Assay. There was a significant increase in tryptase release in response to allergen challenge from the mucosa harvested from skin-test positive patients. Mucosa from skin-test negative patients failed to demonstrate an increase in tryptase release. This could prove to be a useful research model for the study of nasal type I hypersensitivity and drugs that affect it.     

Changes in the nasal mucosal microvascular with allergic rhinitis]

The nasal mucosal microvascular of 37 patients with allergic rhinitis had been studied by nasal mucosal microcirculation microscope. It was found that the nasal mucosal microvascular diameter was wider after the nasal challenge test than before, but both after and before the nasal challenge test, the nasal mucosal microvascular diameter in patients with allergic rhinitis was narrower than in normal persons. The number of the microvascular in patients was also less than that in normal persons. The results indicate that the nasal mucosal microvascular with allergic rhinitis are characterized by dilated capacitance vessels and exchange vessels and constricted resistance vessels after nasal allergen challenge.     

Changes of Alpha1-Antitrypsin Levels in Allergen-induced Nasal Inflammation

Objectives

Alpha1-antitrypsin (AAT) is the main inhibitor of human neutrophil elastase, and plays a role in counteracting the tissue damage caused by elastase in local inflammatory conditions. The study evaluated the involvement of AAT in nasal allergic inflammation.

Methods

Forty subjects with mono-sensitization to Dermatophagoides pteronyssinus (Dpt) were enrolled. Twenty allergic rhinitis patients frequently complained of nasal symptoms such as rhinorrhea, stuffiness, sneezing, and showed positive responses to the nasal provocation test (NPT) with Dpt (Group I). The other 20 asymptomatic patients showed sensitization to Dpt but negative NPT (Group II). The levels of AAT, eosinophil cationic protein (ECP), and Dpt-specific IgA antibodies were measured in the nasal lavage fluids (NLFs), collected at baseline, 10 minutes, 30 minutes, 3 hours, and 6 hours after the NPT. Nasal mucosa AAT expression was evaluated with immunohistochemical staining from Group I and Group II.

Results

At baseline, only the Dpt-specific IgA level was significantly increased in the NLFs of Group I compared with Group II, while ECP and AAT levels were not significantly different between two groups. After Dpt provocation, AAT, ECP, and Dpt-specific IgA levels were significantly increased in the NLFs of Group I during the early and late responses. The protein expression level of AAT was mostly found in the infiltrating inflammatory cells of the nasal mucosa, which was significantly increased in Group I compared to Group II.

Conclusion

The increment of AAT showed a close relationship with the activation of eosinophils induced by allergen-specific IgA in the NLFs of patients with allergic rhinitis after allergen stimulation. These findings implicate AAT in allergen-induced nasal inflammation.     

Immunoglobulins and inflammatory cytokines in nasal secretions in humoral immunodeficiencies

OBJECTIVE: Chronic respiratory tract infections are a common problem in patients with severe humoral immunodeficiency despite intravenous immunoglobulin therapy (IVIG), often presenting as rhinosinusitis. METHODS: Because it is unclear whether IVIG is a good substitute at the mucosal surface, we analyzed immunoglobulin levels and inflammatory cytokines (ECP, IL-8, and TNF-alpha) in nasal secretions of 13 patients with common variable immunodeficiency (CVID) and in 10 patients with IgA deficiency. RESULTS: In patients with CVID, median IgG and IgM levels did not differ significantly from controls, whereas inflammatory cytokines were markedly elevated, reflecting persistent inflammation at the mucosal site. In contrast, patients with IgA deficiency showed significantly raised IgG and IgM levels, whereas ECP and TNF-alpha were only slightly increased. CONCLUSION: Low levels of SIgA might be compensated locally at the mucosal site by high levels of IgM and IgG. Our findings implicate that adequate IVIG is not sufficient to prevent chronic inflammation of the sinuses in patients with severe humoral immunodeficiency.     

Local and systemic immunotherapy in nasal allergy

Two assays have been done to evaluate the effect of immunotherapy in nasal allergy. First, a trial of nasal immunotherapy and second, the study of mediator release after vaccines. Local immunotherapy, applied directly, triggers different response mechanisms. Specific nasal immunotherapy started before seasonal or perennial symptoms peak, has been done by increasing the doses of allergen three times a week during a 3-month period and a manutention period of a weekly nasal puff of the same allergen. Symptom scores and drug consumption have been registered. The results have been compared with the scores obtained in the same patients over the same period of the same year before immunotherapy. In perennial rhinitis blockage, rhinorrea, sneezing and itching scores all decreased. In seasonal rhinitis, a similar score decrease was obtained for blockage, rhinorrea, sneezing and itching. Pharmacological scores also decreased. These data point to a short-term effect of nasal immunotherapy. Tryptase release has been evaluated in nasal washings after nasal challenge with a Parietaria (Pellitory wall) extract before and after specific systemic immunotherapy, in order to evaluate changes in mast cells reactivity. Eight patients were studied, all allergic to Parietaria. Nasal provocation tests have been done before the season with increasing doses of 10, 100 and 1000 PNU and tryptase assayed in nasal washings at 10, 20 and 30 min after provocation. Immunotherapy decreased tryptase release after nasal challenge. The data point to the effect of systemic specific immunotherapy on mast cell reactivity.     

Nasal eosinophilia as a marker for allergic rhinitis: a controlled study of 50 patients

Eosinophils are the principal effector cells involved in the pathogenesis of allergic inflammation. We conducted a study to investigate the validity of the nasal smear examination for detecting eosinophilia in patients with allergic rhinitis. Our study group was made up of 50 patients with allergic rhinitis and 50 age- and sex-matched controls without allergic rhinitis. Smears were obtained from nasal secretions in both groups and then fixed, stained, and studied under light microscopy. Statistical analysis revealed that the odds ratio for eosinophilia positivity in nasal smears in the rhinitis group was 25.61 with a 95% confidence interval of 8 to 78. The sensitivity, specificity, positive predictive value, and negative predictive value of this test were 74, 90, 88, and 77%, respectively. We conclude that the nasal eosinophilia test is highly specific and moderately sensitive in diagnosing allergic rhinitis, and that it therefore can be used as an easy, noninvasive, and inexpensive procedure for screening patients and for conducting epidemiologic studies of this disorder.     

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

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

变应性鼻炎患者血清嗜酸粒细胞阳离子蛋白在特异性免疫治疗中的变化

目的:通过观察变应性鼻炎患者接受特异性免疫治疗前后血清嗜酸粒细胞阳离子蛋白(ECP)的变化,评价免疫治疗的效果,探讨其治疗机制.方法:52例变应性鼻炎患者随机分为治疗组32例和对照组20例,治疗组用舌下含服变应原特异性免疫治疗,对照组给予布地奈德喷鼻,在治疗前后抽静脉血查ECP.结果:治疗组和对照组治疗前血清ECP分别为(26.2±5.9)μg/L和(27.4±6.3)μg/L,差异无统计学意义(P>0.05);治疗后血清ECP分别为(18.3±3.4)μg/L和(23.2±3.7)μg/L,差异有统计学意义(P<0.01).两组治疗后与治疗前相比,血清ECP差异均有统计学意义(治疗组P<0.01,对照组P<0.05).结论:特异性免疫治疗能有效降低患者血清ECP,其可能的免疫机制是有效地抑制了嗜酸粒细胞在鼻腔的聚集与活化,降低其释放ECP的能力,起到治疗作用.     

Signals through CD40 play a critical role in the pathophysiology of Schistosoma mansoni egg antigen--induced allergic rhinitis in mice

BACKGROUND: Interaction between CD40 and CD40L is thought to regulate immune responses in several allergic diseases. However, little is known about its in vivo role in the pathophysiology of allergic rhinitis. We sought to determine whether the lack of signals through CD40 affects the pathophysiology of allergic rhinitis using a murine model. METHODS: Wild type (WT) and CD40-deficient BALB/c (CD40-/-) mice were sensitized intranasally to Schistosoma mansoni egg antigen (SEA). After repeated sensitization, histamine responsiveness, serum antibody titer including immunoglobulin E (IgE), nasal eosinophilia, and cytokine production by nasal mononuclear cells were determined in each group. RESULTS: Intranasal sensitization with SEA in WT mice elicited a strong Th2 response including SEA-specific IgE production, nasal eosinophilia, and interleukin (IL)-4, and IL-5 production by nasal mononuclear cells after antigen challenge. Production of SEA-specific IgE and IgG1 was abolished in SEA-sensitized CD40-/- mice. These mice showed impaired nasal eosinophilia and displayed markedly reduced histamine-induced nasal hyperresponsiveness as compared with WT mice. Furthermore, reduced production of IL-4 and IL-5 by nasal mononuclear cells was seen in CD40-/- mice. CONCLUSION: These results show that signals through CD40 play a critical role in not only IgE production but also pathophysiology of allergic rhinitis such as nasal hyperresponsiveness and nasal eosinophilia.     

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.