Concentrations of chemical mediators in nasal secretions after nasal allergen challenges in atopic patients

By using a microsuction technique, a quantitative determination of chemical mediators in nasal secretions was performed in 18 hay-fever patients and in a control group of 10 healthy volunteers. The authors then compared these quantitative data for mediators with objective nasal findings counting the number of sneezes, passive anterior rhinomanometry (PAR) and nasal inspiratory peak flow. A sampling protocol was designed with a follow-up of 3 days after nasal allergen challenge (NAC) in order to investigate both early and late allergic reactions. Median baseline concentrations of five major mediators were obtained: histamine, 19 ng/g; leukotriene C4 (LTC4), 5.7 ng/g. tryptase, 0; prostaglandin D2 (PGD2), 477 pg/g; eosinophil cationic protein (ECP), 105 ng/g. Significant increases in histamine (214 ng/g) , LTC4 (20 ng/g) and tryptase (28 μU/g) were found, but a significant decrease occurred in ECP (47 ng/g) and PGD (226 pg/g) immediately after NAC in the patients studied. Most ECP concentrations (94%) increased slowly 1 h after NAC and reached a significantly higher level 24 h later. In evaluating nasal symptoms, sneezes were present in a high percentage of cases (76%) during the early phase but were uncommon during the late phase (29%). Total nasal obstruction occurred in 94% during the early phase. In contrast, unilateral nasal obstruction presented in 82% during the late phase, whereas total nasal obstruction was present only in 41%. The most common type of late phase nasal obstruction shown by PAR was alternating nasal obstruction.     

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.     

The study of chemical mediators in the patients with allergic rhinitis 2). Histamine, leukotriene and kinins in the nasal secretion during dual phase response

In order to clarify the details of a late phase response (LPR) in allergic rhinitis, serial changes of nasal symptoms and concentration of chemical mediators (histamine, leukotriene (LT) C4 and kinins) in nasal lavage fluid were investigated after the nasal antigen challenge in ten patients with perennial allergic rhinitis with a positive intradermal skin reaction to mite extract. Samples were collected periodically for 8 hours following the challenge. Nasal airway resistance (NAR) and clinical symptoms were also recorded serially. Three out of ten patients showed only early phase response (EPR) and the other seven patients showed both early and late phase response after the challenge. The chief nasal symptom in LPR was nasal obstruction. In EPR, concentrations of chemical mediators in the nasal lavage fluid always increased. In dual (early and late) phase responders, increases of chemical mediators in nasal lavage fluids were notable during both early and late phase responses. In EPR, there was a significant correlation between severity of sneezing attack and concentration of histamine. In LPR, increase of LTC4 level was significantly correlated with the increase of NAR. RAST score and daily nasal symptoms tended to be higher and more sever in dual phase responders compared with early phase responders. We suggest that the amounts of released chemical mediators during allergic reaction denoted the LPR in allergic rhinitis patients.     

Late Phase Response in Nasal Mucosa Closely Correlated with Immediate Phase Reaction and Hyperreactivity to Histamine

It has been suggested that the onset of the late phase response (LPR) and hyperreactivity to non-specific stimuli occurs in the lower airway. However, its relationship in the nose has not yet been studied. This study was designed to examine the mechanism of LPR and the relationship between LPR and hyperreactivity. A total of 25 Japanese cedar pollinosis patients participated in this study. On the first visit, the frequency of sneezes, weight of nasal discharge, and the nasal airway resistance (NAR) were time-dependently measured without antigen challenge. The histamine reactivity was observed after 12 h. The same protocol was used during the second to fourth visits. The frequency of sneezes, weight of nasal discharge, and NAR were measured continuously for 12 h after antigen challenge, and nasal reactivity to histamine was observed. The percent change of NAR during immediate phase response (IR) and during LPR showed a significant correlation. The frequency of sneezes and weight of nasal discharge induced by histamine were both significantly higher in the positive than in the negative LPR group. These results suggest that the chemical mediators and inflammatory cells inducing nasal swelling during IR cause, directly or indirectly, nasal swelling during LPR, and induce hyperreactivity to histamine.     

Histamine induces nasal obstruction via calcitonin gene-related peptide in sensitized guinea pigs

The purpose of this study was to characterize the late phase nasal obstruction that is induced by a nasal histamine challenge in sensitized guinea pigs. The volume of the nasal cavity was measured using an acoustic rhinometer. A nasal histamine challenge to unsensitized animals induced nasal obstruction at 30 minutes after the challenge while a challenge to sensitized animals induced nasal obstruction not only at 30 minutes but also at 4-6 hours. Histamine (measured by high-performance liquid chromatography), cysteinyl leukotriene (enzyme-linked immunosorbent assay (ELISA)), prostaglandin D2 (ELISA), eosinophils and basophilic cells of sensitized guinea pigs were not changed in the late phase after histamine challenge. Administration of pyrilamine, a histamine H1 receptor antagonist, and calcitonin gene-related peptide (CGRP) (8-37), a CGRP-1 receptor antagonist, significantly improved histamine-induced nasal obstruction at 30 minutes and in the late phase, respectively. These results suggest that a nasal histamine challenge induces nasal obstruction not only immediately through the histamine H1 receptors but also in a late phase via CGRP.     

Comparison of antigen-induced leukotriene and histamine release from nasal scrapings in allergic rhinitis

BACKGROUND: In the early phase response of allergic rhinitis, the nasal mucosa produces important mediators including histamine and leukotrienes. OBJECTIVE: To investigate the relationship between antigen-induced leukotriene release and histamine secretion in nasal scrapings. METHODS: Using nasal mucosal scrapings from patients sensitized to only house dust mite, we studied the time course of antigen-induced leukotriene release and its relationship to histamine release. RESULTS: Cumulative peptydyl leukotriene (LT) production from nasal scrapings increased from 10 min to approximately 90 min following exposure to mite antigen. The rate of LT release was small (<5 pg/10 min) until 10 min following antigen exposure, increased to approximately 250 to 350 pg LT/10 min from 10 to 45 min post exposure, was reduced to <100 pg/10 min by 60 to 150 min, and by 180 min LT production was negligible. By contrast, histamine secretion began 30 sec after antigen exposure and was complete within approximately 10 min. Net antigen-induced LT secretion strongly correlated (R=0.72) with net antigen induced histamine secretion with a ratio of 1:8.7. In addition, net LT/ng histamine and total LT secretion correlated well with antigen-specific IgE in serum, and with the patients' symptoms. CONCLUSION: There is a close relationship between amounts of histamine and LT secretion from antigen challenged nasal mucosa, although the time course of LT release is delayed. In the early phase response, LT are likely to be generated from mucosal mast cells, and thus, mast cell activation will provide an important therapeutic target.     

The roles of histamine, leukotriene C4 and bradykinin on nasal vascular permeability in experimental nasal allergy of guinea pigs.

The releases of histamine, leukotriene C4 (LTC4) and bradykinin into the nasal cavity were measured following nasal antigenic challenge in ovalbumin (OA) sensitized guinea pigs, or following nasal stimulation with one of these chemical mediators in OA-non-sensitized animals. In sensitized animals, increased vascular permeability of nasal mucosa was recognized immediately after antigenic stimulation and lasted for 90 minutes. The release of histamine into the nasal lavage fluid was observed only immediately after the antigenic stimulation. The releases of LTC4 and kinins into the nasal lavage fluid were augmented not only immediately after the antigenic challenge, but also 60 to 90 minutes after the stimulation. Nasal stimulation with one of these chemical mediators also increased nasal vascular permeability, but lasted for less than 40 minutes. These results suggest that the antigen-induced release of these chemical mediators might play some important roles in early increase of nasal vascular permeability, and that the increase of LTC4 and kinin levels might be involved in the prolonged nasal vascular permeability after nasal allergic response.     

Nasal allergy and leukotriene. 2. Kinetics of peptide leukotrienes and inflammatory cells in nasal lavage fluid after antigen challenge

The purpose of this study is to clarify the role of peptide leukotrienes (LTs) on the onset of characteristic hyperreactive nasal symptoms of nasal allergy by observing the time course of the correlation among degrees of nasal symptoms, and by observing the amount of chemical mediators and the number of inflammatory cells in the nasal lavage fluid after nasal antigen challenge in subjects with Japanese cedar pollinosis during off season. Sneezing was terminated within 10 minutes and nasal discharge within 2 hours. However, time course change of the percent increase of nasal airway resistance showed dual response consisting of immediate and late phase responses. The peak of the former was seen at 30 minutes and the latter was at 7 hours after provocation. The significant increase of eosinophils in the nasal lavage fluid was observed during both the immediate and the late phase responses, but during the late phase response, the increase was more prominent. Basophilic cells definitely increased during the late phase response. The amount of LTs in the nasal lavage fluid increased significantly during both the immediate and the late phase responses. In contrast, the level of histamine increased significantly only during the immediate phase response. Considering that LTs, especially LTD4, has potent and persistent effect on causing swelling of nasal mucosa, LTs may play important role in causing nasal obstruction during both the immediate and the late phase responses after antigen challenge. On the other hand, the role of histamine may be confined to cause the hyperreactive nasal symptoms during the immediate phase response.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

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.     

Clinical symptoms and mediators in the allergic early and late phase reaction

BACKGROUND: This examination focused on the allergic early and late phase reaction via nasal symptom scores, acoustic rhinometry, and the determination of mediators possibly involved in late phase eosinophilia. We examined nasal secretions for IL-5; the chemokines IL-8, MCP-1, and Eotaxin; the adhesion molecule sVCAM-1, and the leukotriene LTC4 for their suggested impacts on tissue eosinophilia. METHODS: 13 patients suffering from seasonal allergic rhinitis were challenged intranasally out of the natural pollen season by their specific allergen. In a time window of 8 h following the provocation, patients completed symptom questionnaires, and underwent acoustic rhinometry. Nasal secretions were gained by the cotton wool method over a time period of 8 h. Nasal secretions were analyzed for the above mentioned mediators. RESULTS: Individual evaluation of the acoustic rhinometry measurements revealed an early phase reaction in 100 % of the cases and a late phase reaction in 92 %. The need to sneeze and a runny nose were the strongest symptoms during the allergic early and late phase reaction. A typical late phase kinetic was observed for IL-5, MCP-1, Eotaxin, sVCAM-1, and LTC4. IL-8 was characteristic for early phase reaction but increased in late phase as well. CONCLUSIONS: The need to sneeze, a runny nose, and the overall quality of life were most apt to evaluate the allergic early and late phase reaction. Highly significant correlations between nasal obstruction and acoustic rhinometry measurements indicate a high sensitivity of visual analogue scales in the representation of minimal changes in nasal symptom scores during the allergic reaction. Our data point to a relevant role of the TH2 cytokine IL-5; of the chemokines IL-8, MCP-1, and Eotaxin; of the adhesion molecule sVCAM-1, and of the leukotriene LTC4 for the allergic late phase eosinophilia.     

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.     

Arachidonic acid metabolites during nasal challenge

In order to assess the role of arachidonic acid metabolites in the early reaction to antigen, we challenged six allergic individuals with and without premedication with aspirin and recorded their clinical response, as indicated by number of sneezes, and measured the levels of inflammatory mediators. The early reaction to antigen was associated with increases in the levels of histamine, N-alpha-tosyl-L-arginine methyl esterase (TAME-esterase) activity, prostaglandin (PG) D2, leukotriene C4, PGE, and thromboxane. Aspirin significantly inhibited the increases in the cyclooxygenase metabolites PGE, PGD2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane but did not affect the amount of sneezing or the levels of histamine, TAME-esterase activity, or leukotrienes. The pattern of the metabolites and their response to pretreatment with aspirin parallel the response of purified human lung mast cells, supporting the notion that the early phase of allergic rhinitis is a mast cell-dominated event.     

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.     

Assessment of early- and late-phase nasal obstruction in atopic patients after nasal allergen challenge*

In order to study the types of nasal obstruction in allergic rhinitis, nasal allergen challenge was performed in 18 atopic patients, compared with a control group consisting of 10 healthy volunteers. Passive anterior rhinomanometry was used as an objective evaluation of nasal airway resistance. A 100% increase of nasal airway resistance was considered to be a positive reaction. In the control group, no obvious nasal obstruction was recorded after nasal phosphate buffered saline challenge. In the patient group, nasal obstruction occurred only after challenge in 94% during the early phase and in 82% during the late phase. During the late-phase four major types of nasal obstruction were found, i.e. no nasal obstruction; onesided nasal obstruction only; bilateral nasal obstruction; and alternating nasal obstruction. Of the four types, the alternating type was the most common (47%) type, especially during the late-phase.     

特异性鼻粘膜激发试验中鼻气道的反应性

目的：探讨对特异性鼻粘膜激试验（ＳＮＰＴ）阳性的评价方法。方法：对３０例常年性变应性鼻炎患者（鼻炎组）和１４例正常成年人（对照组）进行ＳＮＰＴ，观察鼻部症状及鼻气道阻力变化。结果：激发后，鼻炎组在多数患者在０．５￣３．０ｍｉｎ内出现鼻痒、喷嚏、流清滋等症状。连续喷嚏５个以上者占８３．３％，与对照组（２１．４％）之间有显著性差异（Ｐ〈０．０１）；鼻腔总阻力和激发侧鼻阻力增加比例，两组间有明显差异，而     

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.     

Factors contributing to nasal allergic late phase eosinophilia

OBJECTIVE: This study focused on factors contributing to eosinophilia after intranasal allergen challenge. METHODS: Nasal secretions of 13 allergic individuals were gained over a period of 8 hours after nasal allergen challenge. Early and late phase reactions were determined by acoustic rhinometry and changes of volume and total protein in nasal secretions. Eosinophilia was demonstrated by nasal eosinophilic cationic protein. Interleukin (IL)-5; the chemokines IL-8, monocyte chemotactic protein (MCP)-1 and MCP-3, and eotaxin; soluble vascular cell adhesion molecule 1 (sVCAM-1); and the leukotriene C4 (LTC4) were analyzed by enzyme-linked immunosorbent assay for their suggested impacts on tissue eosinophilia. RESULTS: By means of rhinometry, we observed in 69% an alternating type of late phase response, followed by a bilateral (15%) or unilateral (8%) type. A biphasic kinetic could be demonstrated by changes in nasal volume and total protein of nasal secretions, reflecting the early and late phase responses. A typical late phase kinetic was observed for IL-5, MCP-1, eotaxin, sVCAM-1, and LTC4. Interleukin 8 was characteristic for early phase reaction but increased in late phase as well. We could not detect any MCP-3 in our samples. CONCLUSIONS: Our data point to a relevant role of the T(H)2 cytokine IL-5; of the chemokines IL-8, MCP-1, and eotaxin; of the adhesion molecule sVCAM-1; and of the leukotriene LTC4 for the allergic late phase eosinophilia.     

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。     

Dual symptomatic and exudative nasal responses are not characteristics of perennial allergic rhinitis.

Acute and late phase (dual) symptomatic responses after allergen challenge commonly occur in allergic asthma. The aim of the present study was to explore the occurrence of allergen challenge-induced biphasic responses in patients with chronic perennial allergic rhinitis living in an area with high house dust mite (HDM) exposure. Fifteen patients with perennial rhinitis and evident allergy to HDM participated. Nasal challenges with HDM and sham were performed on separate days in a crossover design. Nasal symptoms, forced expiratory volume in 1 s (FEV1) and orally exhaled nitric oxide were recorded every hour for up to 8 h after each challenge. Alpha2-macroglobulin and eosinophil cationic protein (ECP) were analysed in hourly nasal lavages, and nasal histamine provocations were carried out after 8 h. HDM, but not sham, caused an immediate increase in nasal symptoms which gradually abated over the 8-h period. No reoccurrence of nasal late phase symptoms was seen. HDM, but not sham, induced an early increase in alpha2-macroglobulin and ECP levels: both indices remained elevated for up to 3 h after challenge. HDM challenge evoked hyper-responsiveness to histamine expressed as increased nasal symptoms (p < 0.05; HDM vs sham). No differences in exhaled nitric oxide or FEV1 were demonstrated at any one time point between the HDM- and sham-challenged days. It is concluded that nasal symptomatic and exudative late phase responses may not be a general feature, even in subjects with perennial rhinitis challenged with high, symptom-provoking, doses of HDM allergen.