Eosinophil markers in seasonal allergic rhinitis

Background The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon.
Methods Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. ( n =26), 0.2 mg o.d. ( n =25), or placebo (n = 12). Six healthy persons served as controls.
Results During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001 – P<0.05). Significant differences were seen between the steroid grotips and the placebo group for all parameters (P<0.001–F<0.05). Higher eosinophil count (P<0.05), serum EPO (F<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001).
Conclusions Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.     

Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid

BACKGROUND: Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils. OBJECTIVE: We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression. METHODS: Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 microgram/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season. RESULTS: Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season. CONCLUSION: Expression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.     

Nasal histamine challenge in nonallergic and allergic subjects evaluated by acoustic rhinometry

Nasal patency shows spontaneous variations but is influenced by a number of factors like exercise and allergic conditions. Nasal histamine challenge has been used to define nasal hypersensitivity. We have applied acoustic rhinometry as a new objective method to study the spontaneous variations of the nasal mucosa and its response to histamine challenge in 12 nonallergic subjects and 12 subjects with nasal allergy to pollen, but out of the pollen season. Measurements of the minimum cross-sectional area and the volume of the nasal cavities were done every 15 min for 6 h. More pronounced spontaneous variations, defined by the coefficient of variation of the measurements, were encountered in the allergic than in the nonallergic subjects, especially with regard to the minimum cross-sectional areas in the nasal cavities (P < 0.02). Allergic subjects showed increased sensitivity to histamine, as compared with nonallergic subjects, during low-concentration (0.1%) challenge (P < 0.05) and a prolonged effect of histamine challenge (P = 0.01). Antihistamine (cetirizine) had a significant effect on the histamine-induced symptoms and decrease of nasal dimensions during histamine challenge, but no significant effect on pollen-induced changes. In the allergic group, the decrease in minimum area during allergen provocation correlated with the level of specific IgE (r = 0.81; P = 0.0015).     

Changes in airway inflammation following nasal allergic challenge in patients with seasonal rhinitis

BACKGROUND: Seasonal allergic rhinitis could predispose to the development of chronic bronchial inflammation as observed in asthma. However, direct links between nasal inflammation, bronchial inflammation and airway responsiveness in patients with seasonal allergic rhinitis and without asthma are not fully understood. The aim of this study was to analyse the changes induced by allergic nasal challenge outside the pollen season in airway responsiveness and bronchial inflammation of patients with seasonal allergic rhinitis. METHODS: Nine patients were evaluated after either grass pollens or placebo nasal challenge in a randomized cross-over double-blinded trial. Nasal parameters were recorded hourly and airway responsiveness was assessed by methacholine challenge. Cytological examinations and cytokine measurements were performed in nasal lavage and induced sputum. Eosinophil activation was investigated by eosinophil-cationic protein expression and secretion. RESULTS: Airway responsiveness was increased after allergic nasal challenge. Total eosinophils and eosinophils expressing eosinophil-cationic protein were increased in induced sputum after allergic nasal challenge. Both eosinophil number and eosinophil-cationic protein concentration in induced sputum were correlated to methacholine responsiveness. CONCLUSIONS: These results suggest that eosinophils participate to the bronchial inflammation in patients with seasonal allergic rhinitis following allergic nasal challenge outside the pollen season and might explain changes in airway responsiveness.     

Efficacy and onset of action of fluticasone propionate aqueous nasal spray on nasal symptoms, eosinophil count, and mediator release after nasal allergen challenge in patients with seasonal allergic rhinitis

We studied the effect and onset of action of fluticasone propionate aqueous nasal spray (FPANS) on mediator release and eosinophil accumulation in nasal secretions and on nasal symptoms of patients with seasonal allergic rhinitis after nasal allergen challenge (NAC). At the end of the pollen season, 28 patients were randomized in a double-blind and crossover design to receive 7 days' treatment with FPANS (200 μg, once daily) and matching placebo. NACs were performed before and at 6 h and 1. 2. 3. and 7 days during treatment with FPANS or placebo. Nasal secretions were collected for a quantitative determination of mediators and eosinophil count before and 5 min after each challenge. Nasal symptoms were assessed by scales grading the severity of symptoms at the same time. Results showed that for mediator concentrations there was a significant decrease of leukotriene C4 (P<0.001) at 7 days after the first administration of FPANS as compared to placebo. Two days after FPANS. both eosinophil counts and eosinophil cationic protein (ECP) concentrations were lower than those of placebo (eosinophils; f=0.032; ECP; F=0.038). The onset became even more important at day 7 (eosinophils; P=0.001; ECP; P=0.009) during the FPANS treatment period. For the subjective nasal symptoms, a significant reduction of symptom scores for nasal obstruction occurred also at day 3 (F=0.017) and for sneezing at day 7 (f=0.003). There was not yet any significant improvement of the objective nasal airway resistance after the different NACs during the study period. In conclusion, this study demonstrated that topical fluticasone propionate is effective in the treatment of mucosal inflammation induced by NAC. For optimal control of nasal symptoms induced by repeated maximal allergen challenges, a treatment period of more than 1 week is required.     

Effects of topical budesonide and levocabastine on nasal symptoms and plasma exudation responses in seasonal allergic rhinitis

This study compares the effects of two topical nasal treatments for allergic rhinitis, budesonide and levocabastine, on symptom development during seasonal pollen exposure. Additionally, the protective effects of drug treatments on allergen-challenge-induced responses (symptoms and microvascular exudation of plasma) are examined late into the pollen season. Forty-four patients with seasonal allergic rhinitis to birch pollen participated in this single-blind, randomized, and placebo-controlled study. Topical nasal treatment with either levocabastine (200 p.g b.i.d.: n = 16), budesonide (200 μg b.i.d.; n = 16), or placebo (n= 12) was instituted before the start of the pollen season and continued for 5 weeks until the end of the birch pollen season. The participants kept diaries for scores of nasal and ocular symptoms. Nasal allergen challenges with increasing doses of a birch pollen extract (10², 10³ and lC SQ-U) were carried out both before, when patients were asymptomatic and without treatment, and late into the pollen season. A nasal lavage followed each challenge, and the lavage fluid levels of albumin were measured as an index of the acute inflammatory response of the allergic mucosa. The birch pollen season was rather mild, producing only small increases in nasal symptoms. Budesonide treatment reduced the total nasal symptoms compared to placebo (P<0.01) and to levocabastine (P<0.05), while levocabastine treatment did not differ significantly from placebo. Ocular symptoms and use of rescue medication did not differ between placebo and the active treatments. At the end of the pollen season, both treatments reduced allergen-challenge-induced nasal symptoms compared to placebo (P<0.01). Only budesonide reduced allergen-challenge- induced increments of albumin levels in postchallenge nasal lavage fluids (P<0.05, in comparison with placebo). The results suggest that budesonide reduces both seasonal and allergen-challenge-induced nasal symptoms, while levocabastine is effective against allergen-challenge-induced symptoms also during the season. In addition, the topical steroid treatment, but not the antihistamine, inhibits the inflammatory exudation evoked by allergen challenge in patients with active seasonal disease.     

Retrospective study on fluticasone propionate aqueous nasal spray efficacy in patients with allergic rhinitis: evaluation of clinical and laboratory parameters

BACKGROUND: In allergic rhinitis, allergenic stimulation causes the release of various mediators that induce symptoms and the development of chronic inflammation, which, in turn, is caused by cells involved in the late phase of inflammation, such as eosinophils. The eosinophils also cause damage at the mucosal level through the secretion of eosinophil cationic protein and other preformed factors contained in their granules. The objective was to verify the efficacy of fluticasone propionate aqueous nasal spray in patients with allergic rhinitis; in a retrospective study, we have evaluated mediators of inflammation, making correlations with the clinical symptoms score during and outside the pollen season. METHODS: Forty patients with allergic rhinitis and 15 normal controls were included in our study. Eosinophil cationic protein, eosinophil chemotactic activity, and blood and nasal lavage eosinophil count were evaluated as laboratory parameters. RESULTS: We found a significant increase in nasal lavage levels of eosinophil cationic protein in allergic patients, and this was strictly correlated with the clinical symptoms score. No differences were found in the eosinophil count of allergic patients and in the serum eosinophil cationic protein of patients sensitized to seasonal allergens in comparison with normal subjects. By contrast, an increase in serum eosinophil cationic protein level was found in patients sensitized to perennial allergens. After topical administration of fluticasone propionate aqueous nasal spray, a reduction in nasal lavage eosinophil cationic protein secretion was obtained with a reduction of eosinophil chemotactic activity at the local level. This reduction correlated with an improvement of clinical symptoms. CONCLUSIONS: The clinical improvement and reduction in nasal lavage eosinophil cationic protein and eosinophil chemotactic activity after administration of fluticasone propionate aqueous nasal spray further confirms the role of this treatment in allergic rhinitis.     

Objective assessments of allergic and nonallergic rhinitis in young children

Background:  Allergic and nonallergic rhinitis are common childhood disorders.
Objective:  To study nasal eosinophilia and nasal airway patency in young children with allergic and nonallergic rhinitis to assess the pathology behind such diagnoses.
Methods:  We investigated 255 children at six years of age from the Copenhagen Prospective Study on Asthma in Childhood birth cohort assessing rhinitis history, specific immunoglobulin E relevant to rhinitis symptoms, nasal eosinophilia and nasal airway patency by acoustic rhinometry before and after decongestion. Associations were studied in a multivariate graphical model corrected for gender, height and nasal steroid usage.
Results:  Allergic rhinitis was significantly and directly associated with irreversible nasal airway obstruction (reduced decongested nasal airway patency) ( P  =   0.004), whereas nonallergic rhinitis was not. Both allergic rhinitis ( P  =   0.000) and nonallergic rhinitis ( P  =   0.014) were directly and significantly associated with nasal eosinophilia, but this association was stronger for allergic rhinitis.
Conclusion:  Allergic rhinitis and nonallergic rhinitis are of different pathologies as suggested from their different associations not only to allergy but importantly also to irreversible nasal airway obstruction and eosinophilic inflammation. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling of the nasal mucosa in children at the age of 6 years. Nonallergic rhinitis exhibited no change in the nasal airway patency, but some nasal mucosal eosinophilia albeit less than children with allergic rhinitis.     

Effects of topical corticosteroid and combined mediator blockade on domiciliary and laboratory measurements of nasal function in seasonal allergic rhinitis.

BACKGROUND: Both domiciliary and laboratory measures of nasal function have been used to evaluate treatment response in allergic airways disease; however, these measures have not been compared. OBJECTIVE: To determine the relationship of domiciliary measures (daily symptoms, peak inspiratory nasal flow, and nasal oral index) and laboratory measures (rhinomanometry, acoustic rhinometry) in assessing treatment response with topical steroids and specific inflammatory mediator blockage. METHODS: Twenty-one patients with seasonal allergic rhinitis and asthma were enrolled into a single-blind, placebo-controlled, crossover study comparing 2 weeks of 1) 400 microg inhaled plus 200 microg intranasal budesonide once daily and 2) 10 mg montelukast plus 10 mg cetirizine once daily. Before each treatment, patients received 7 to 10 days of placebo period. Laboratory measurements were made of nasal resistance by posterior rhinomanometry, and nasal volume between 0 and 5 cm by acoustic rhinometry after both placebo and active treatment periods. Daily domiciliary recordings were made of allergic rhinitis nasal symptoms scores and peak nasal and oral inspiratory flow rate (enabling the calculation of a nasal/oral index) throughout the study. RESULTS: There were significant (P < 0.05) improvements for all allergic rhinitis symptoms with both therapies, after factoring for pollen count. Spearman's rank correlation for comparison among nasal symptoms and the objective responses were: nasal inspiratory flow rate (R = -0.50, P = 0.02); nasal/oral index (R = -0.55 P = 0.01); rhinomanometry (R = 0.24, P = 0.30); and acoustic rhinometry (R = -0.21, P = 0.36). CONCLUSIONS: Both treatments were effective in managing allergic rhinitis symptoms, and patients' symptoms were more closely associated with domiciliary measurements of nasal flow than laboratory measurements of nasal function.     

Effects of monotherapy with intra-nasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis

BACKGROUND: The combination of a leukotriene receptor antagonist with an antihistamine may have beneficial effects in seasonal allergic rhinitis (SAR). OBJECTIVE: To determine how combined oral mediator blockade compares to monotherapy with intranasal corticosteroid in the treatment of SAR. METHODS: Twenty-two patients with seasonal allergic rhinitis were enrolled in a placebo controlled crossover study comparing 2 weeks therapy of either (a) 200 microg intranasal mometasone furoate (MF) once daily or (b) 10 mg oral montelukast plus 10 mg oral cetirizine once daily (MON/CZ), with a 7-10 day placebo period prior to each treatment period. Domiciliary measures of symptoms and nasal flow were recorded daily. Measurements of posterior rhinomanometry, acoustic rhinometry and nasal nitric oxide were made after all treatment and placebo periods. RESULTS: There were significant (P < 0.05) improvements in domiciliary peak nasal flow (l/min) with both MF (133 (3.8)) and MON/CZ (124 (3.8)) compared to pooled placebo (110 (4.0). Both treatments also showed significant improvement in terms of nasal blockage (units) (PL: 1.1(0.1), MF: 0.5 (0.1), MON/CZ 0.7 (0.1); and total nasal symptoms (units) (PL: 3.5 (0.3), MF 1.6 (0.3), MON/CZ 1.7 (0.3)), although there was no significant difference between the two active treatments. There were no significant differences between placebo and treatment for rhinomanometry, acoustic rhinometry or nitric oxide. CONCLUSIONS: Both intranasal mometasone furoate as monotherapy and oral cetirizine plus montelukast as cotherapy were equally effective for objective and subjective measures of treatment response in SAR. Domiciliary measurements of symptoms and peak flow were more sensitive than laboratory measurements of rhinomanometry, acoustic rhinometry and nasal nitric oxide.     

Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response

Background: Patients with idiopathic rhinitis (IR) are considered to be nonallergic because they have a negative skin prick test (SPT) and allergen specific‐IgE in serum. The concept of localized mucosal allergy in the absence of atopy has recently been proposed. The immunological mechanisms involved in seasonal IR have not been sufficiently studied. We examined nasal mucosa inflammation, the presence of nasal specific‐IgE and the response to nasal allergen provocation test (NAPT) in patients with seasonal IR who presented symptoms only in spring. Methods: We evaluated 32 patients with seasonal IR and 35 with persistent allergic rhinitis to pollen (PAR‐P) and compared these with healthy controls and persons with PAR to house dust mite during the pollen season, as well as by NAPT out‐of‐season with grass and Olea europea. We measured the nasal leukocyte–lymphocyte phenotype (CD45, CD33, CD16, CD3, CD4 and CD8), eosinophil‐cationic‐protein, and total and specific‐IgE to grass and olive pollen in serum and nasal lavage and performed NAPT. Results: In the IR group, 62.5% had a positive NAPT (IR‐PosNAPT), 20/32 to grass, with four of these having a positive NAPT to olive pollen as well. IR‐PosNAPT patients showed a similar nasal leukocyte–lymphocyte profile to the PAR‐P patients and different to controls. We detected nasal specific‐IgE in 35% of IR‐PosNAPT patients. Conclusions: These results support the hypothesis that a subgroup of patients with IR have seasonal symptoms with evidence of a nasal allergic immune reaction in the absence of a positive SPT or serum specific IgE.     

Low levels of CC16 in nasal fluid of children with birch pollen-induced rhinitis

BACKGROUND: Clara cell protein 16 (CC16; secretoglobin 1A1) is an anti-inflammatory protein mainly expressed in the epithelial cells in the airways. OBJECTIVE: To compare the levels of CC16 in nasal lavage (NAL) from children with intermittent allergic rhinitis and healthy controls and to study the effect of a local steroid. METHODS: Thirty schoolchildren with birch pollen allergy and 30 healthy controls from the same schools were included in the study. The NAL fluid was collected before the season, during the birch pollen season and, for the patients, after 1 week of treatment with a local steroid. Symptom scores were obtained on every occasion. CC16 and eosinophil cationic protein (ECP) were analyzed with enzyme-linked immunosorbent assay. RESULTS: The nasal fluid levels of CC16 were significantly lower in patients than in controls, before and during pollen season. Before the season, the median CC16 concentrations were 9.1 (range 1.1-117) microg/l in patients and 25.7 (6.1-110.2) microg/l in controls. During the season, the median CC16 concentrations in nasal fluid were 12.9 (2.3-89.7) microg/l in the allergic children and 22.0 (9.5-90.1) microg/l in the healthy controls (P = 0.0005). Symptom scores, nasal fluid eosinophils and ECP were higher in patients during the season. Treatment with a local steroid did not change the CC16 levels. CONCLUSIONS: Nasal fluid CC16 levels were lower in children with birch pollen-induced allergic rhinitis than in healthy controls both before and during the pollen season. We speculate that reduction in anti-inflammatory activity by CC16 may contribute to the pathogenesis of allergic rhinitis.     

Generation of clusters of free eosinophil granules (Cfegs) in seasonal allergic rhinitis

Generation of clusters of free eosinophil granules (Cfegs), through lysis of eosinophils, has recently been proposed as a major paradigm for ultimate activation of airway mucosal eosinophils. In the present study involving patients with seasonal allergic rhinitis, we have investigated whether generation of Cfegs in the nasal mucosa is a feature of allergic rhinitis. Nasal mucosal biopsies were obtained before and late in a birch-pollen season, and were subjected to histochemical staining of eosinophil peroxidase. In biopsies obtained before the pollen season, a few, intact eosinophils were observed, and Cfegs were scarce. In biopsies taken during the pollen season, the numbers of eosinophils were increased about 10-fold (P<0.05) and the Cfegs about 25-fold (P<0.05). We conclude that generation of Cfegs is a significant feature of seasonal allergic rhinitis and that this process represents the ultimate activation of mucosal eosinophils in this disease.     

Budesonide powder administration for the treatment of grass-pollen-induced allergic rhinitis

The new dry-powder inhaler system, Turbuhaler®, has proved to be equivalent to metered-dose inhalers when used in the nose, and the objective of this study was to investigate the efficacy, dose-response effects, and safety of budesonide powder given in the morning during the grass pollen season to patients with grass-pollen-induced allergic rhinitis. Of 190 randomized patients, 186 were treated and 180 completed this double-blind study, which comprised a 4-week treatment period, preceded by a 1-week run-in period. The patients were randomized to three parallel treatment groups: budesonide 400 μg, budesonide 200 μg, or placebo once in the morning. Assessment of efficacy, by comparing changes in mean scores of nasal symptoms from run-in to treatment, showed a statistically significant effect for all symptoms with active treatments, as compared with placebo. The mean reduction of symptom severity was more pronounced in the 400-μg group than in the 200-μg group, and this difference was statistically significant for runny nose (P<0.02) and combined nasal symptoms (P<0.02). Nasal peak-inspiratory flow improved significantly in both budesonide-treated groups, as compared with placebo (P<0.01 and P<0.01). During the treatment period, patients on active treatment showed, on average, a reduction of all nasal symptoms, whereas the placebo-treated patients, on average, showed an increase of nasal symptoms. Approximately 40% in the high-dose group felt total control of rhinitis symptoms, as compared with 26% in the low-dose group. There was no difference between budesonide- and placebo-treated groups in side-effects. Budesonide delivered from a Turbuhaler once daily in the morning is effective, and better symptom control is achieved by 400 μg than 200 μg in the treatment of seasonal allergic rhinitis. However, the low dose may be sufficient in patients with mild symptoms. Budesonide from a Turbuhaler may be preferable to pressurized-dose aerosols and aqueous pump sprays because it does not contain carrier gas, preservatives, or lubricants.     

Oxygen radical production by blood eosinophils is reduced during birch pollen season in allergic patients

Background The eosinophil granulocyte takes part in allergic inflammatory diseases, like asthma and rhinitis. The aim of this study was to investigate the oxidative metabolism of the blood eosinophils and neutrophils from birch pollen allergic patients, during and after exposure to their allergen. Methods Thirteen birch pollen allergic patients, with seasonal symptoms of rhinitis, with or without asthma, were followed. The cells were purified using a percoll gradient and the MACS system. The eosinophil purity in all samples was >95%. The oxidative metabolism of both the PMN and the eosinophils was measured by means of a chemiluminescenee (CL) assay, with luminol or lucigenin as the amplifier, and using PMA (16nM) as the activator. Results In relative terms, the lucigenin CL by the eosinophils was 5-10-foId higher than that of the PMN, P= 0.002. The eosinophils of the birch pollen allergic patients produced less oxygen radicals during the season, compared to the reference group, measured both with luminol CL and lucigenin CL, P=0.01 and P= 0.02 respectively. Out of season, there was no difference. There was also no difference, during either period, between patients and references in PMN CL. Separating the eosinophils into hypodense and normodense fractions, showed a decreased oxidative metabolism by the hydrodense eosinophils. Conclusion We conclude that the eosinophils of birch pollen allergic patients have reduced production of oxygen radicals when the patients are exposed to their allergen, which could depend on higher amounts of hypodense eosinophils in the blood during season.     

Relationship between nasal hyperreactivity, mediators and eosinophils in patients with perennial allergic rhinitis and controls

Background In perennial allergic rhinitis, patients are almost daily exposed to aeroallergens. This ongoing allergic reaction results in increased sensitivity to allergens and non-specific stimuli. It is generally known that inflammatory cells and mediators are involved in the pathogenesis of the allergic reaction. Objectives To study the relationship between nasal hyperreactivity and nasal inflammation during natural allergen exposure. Methods In 48 patients with perennial allergic rhinitis and in 11 volunteers a nasal brush, a nasal lavage and a histamine challenge were performed. Nasal inflammation was estimated by the number of eosinophils, levels of albumin, tryptase, prostaglandin D₂ (PGD₂), eosinophil cationic protein (ECP) and leukotriene C₄/D₄/E₄ (LTC₄/D₄/E₄). Results In contrast to PGD₂ and tryptase, eosinophils (1.9 vs 0%, P = 0.0023), LTC₄/ D₄/E₄ (17.51 vs 1.43pg/mL, P= 0.0001) and albumin (8.61 vs 2.37mg/mL, P= 0.0008) were significantly increased in rhinitis patients as compared with controls. Patients also showed increased responses to nasal histamine challenge assessed using a composite symptom score (21.5 vs 4 points, P=0.0001). The nasal response to histamine was weakly correlated with the total number of eosinophils in the cytospin (correlation coefficient r=0.38, P= 0.009). Conclusion Nasal hyperreactivity is correlated with the percentage of eosinophils in patients with perennial rhinitis. The patients' mediator profiles suggest that eosinophils are important in the ongoing allergic reaction and nasal hyperreactivity.     

Non-specific airway hyperresponsiveness in mono-sensitive Sicilian patients with allergic rhinitis. Its relationship to total serum IgE levels and blood eosinophils during and out of the pollen season

Background Initial attempts to evaluate the association between allergic rhinitis and nonspecific bronchial responsiveness has produced conflicting results. In fact, some studies showed a strong correlation and other failed to find an association. However, little is known about the effect of natural specific allergen exposure on the bronchial reactivity of mono-sensitive patients with rhinitis in the southern Mediterranean area, in relation to skin reactivity to allergens, total serum IgE levels and blood eosinophiis. Objectives The significance of the association between allergic rhinitis, and abnormal airway responsiveness with regard to the pathogenesis of asthma is unclear. For this reason, we have studied non-specific bronchiai hyperreactivity. in patients with seasonal allergic rhinitis, with reference to the responsible allergen. The aim of the study was to correlate the responsiveness to bronchoprovocation with methacholine in subjects a with allergic rhinitis during and out of the pollen season with total serum IgE and blood eosinophils. Methods Fourty-nine non-smoking patients with clinical diagnosis of allergic rhinitis and mono-sensitive skinprick tests to pollen allergens were enrolled in the study. Twenty patients suffered from seasonal rhinitis to Parietaria pollen. 15 patients to Gramineae pollen and 14 patients to Olea pollen. In all patients lung function measurements (assessed as response to methacholine). tolal serum IgE and blood eosinophii counts were measured during and out of the pollen season. Results During pollen season. 16 out of 49 rhinitis patients demonstrated values of bronchial responsiveness measured as response to inhaled metbacholine in the asthmatic range whereas out of the pollen season only eight patients were in the asthmatic range. By analysing the results with reference to the responsible allergen, during the pollen season 5 out of 16 patients were Parietaria -sensitive and out of the pollen season seven out of eight patients. Finally, in Parietaria -sensitive rhinitis bronchial responsiveness signifi-cantly correlated, during and out of the pollen season, with total serum IgE and with blood eosinophil counts. Conclusions Our results are consistent with the hypothesis that Parietaria is more important than Olea and Gramineae as a risk for developing non- specific bronchial hyperresponsiveness. On the whole, present observations provide further evidence that there is an interrelationship of allergen kind, total serum IgE. eosinophil and bronchial hyperressponsiveness suggesting that they may play a role in the development of bronchial asthma in rhinitis patients.     

Serum eosinophil granule proteins predict asthma risk in allergic rhinitis

Background: Allergic rhinitis is a common disease, in which some patients will deteriorate or develop asthma. It is important to characterize these patients, thereby offering the possibility for prevention. This study evaluated eosinophil parameters as potential indicators of deteriorating allergic airway disease. Methods: The subjects of the study included all patients who suffered seasonal allergic rhinitis and had participated in a study 6 years earlier, in which blood eosinophils, serum eosinophil cationic protein (ECP) serum eosinophil peroxidase (EPO), nasal lavage ECP and nasal lavage EPO levels were measured. Patients in the present study were interviewed on occurrence of rhinitis symptoms during the last season, rhinitis outside season, asthma‐like symptoms and asthma diagnosis, and were skin‐prick tested for common aeroallergens. Eosinophil parameters from the study 6 years earlier were then tested for the ability to predict occurrence of new allergies, worsening of rhinitis and occurrence of asthma. Results: Forty‐four patients participated in the study. In four patients seasonal rhinitis symptoms had deteriorated, 10 had experienced perennial rhinitis symptoms, 14 reported asthma‐like symptoms and seven had been diagnosed with asthma. Thirteen had developed additional sensitization. Patients developing asthma‐like symptoms compared with patients with no such symptoms had significantly higher serum ECP (16.7 μg/l vs 8.2 μg/l; P ≤ 0.01) and serum EPO (17.9 μg/l vs 8.8 μg/l; P ≤ 0.05). Results were similar, considering patients diagnosed with asthma. Blood eosinophils and nasal lavage parameters were not related to development of asthma and asthma‐like symptoms. No eosinophil parameter was related to deterioration of rhinitis or additional sensitization. Conclusion: Serum ECP and EPO in patients with seasonal rhinitis demonstrated a high predictive ability for later development of asthma.     

Evaluation of eicosanoids in nasal lavage as biomarkers of inflammation in patients with allergic rhinitis

Introduction

Cysteinyl leukotrienes (cys-LTs), 8-isoprostane and prostaglandin E2 (PGE₂) constitute fundamental mediators in allergic inflammation; therefore we wanted to determine the utility of PGE₂, 8-isoprostane and cys-LT levels in nasal lavage as biomarkers of allergic inflammation.

Material and methods

Twenty-one patients with allergic rhinitis (AR) were included on the basis of a positive history of AR symptoms and positive results of skin prick tests to grass pollen allergens. The main exclusion criteria were: uncontrolled asthma, nasal polyps, respiratory infection, tuberculosis, neoplastic and autoimmune diseases, current smoking and immunotherapy. Both outside the pollen season and at the height of the pollen season, total nasal symptom score (TNS-4) was evaluated and the levels of cys-LTs, 8-isoprostane and PGE₂ were measured in nasal lavage fluid (NALF).

Results

Natural allergen stimulation resulted in a significant increase of TNS-4 (p < 0.001) and nasal eosinophilia (p < 0.001). The concentration of PGE₂ dominated in the NALF outside the pollen season and decreased significantly at the height of natural exposure (p < 0.01). In contrast, lower baseline concentrations of cys-LTs and 8-isoprostane increased significantly upon allergen stimulation (p < 0.05). There was a significant correlation between mean concentration of PGE₂ and eosinophil number in NALF (r = 0.67, p = 0.0439).

Conclusions

The NALF concentrations of cys-LTs and 8-isoprostane change simultaneously with TNS-4 and nasal eosinophilia. However, due to the lack of any significant correlation, their utility as markers of allergic rhinitis should be warily considered. The decrease of PGE₂ concentration in NALF which correlated with nasal eosinophilia may participate in escalation of allergic inflammation and needs further evaluation.     

Comparison of the effects of desloratadine 5-mg daily and placebo on nasal airflow and seasonal allergic rhinitis symptoms induced by grass pollen exposure

BACKGROUND: Nasal congestion is a chronic symptom of seasonal allergic rhinitis (SAR) that is often difficult to treat with antihistamines. Desloratadine, a new, potent, H1-receptor antagonist has been shown to decrease nasal congestion in clinical trials and to maintain nasal airflow in response to grass pollen exposure. We compared the effects of desloratadine 5 mg and placebo on nasal airflow, nasal secretion weights and SAR symptoms, including nasal congestion, in patients exposed to grass pollen in an environmental exposure unit. METHODS: Forty-six grass pollen allergic SAR patients received desloratadine or placebo for 7 days, followed by a 10-day washout, and then crossed over to the other treatment for 7 days. A 6-h allergen exposure was performed at the end of each treatment period. RESULTS: Desloratadine was significantly superior to placebo in maintaining nasal airflow (P 相似文献