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Notes: Background Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms.Objective We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 μg given once daily, administered in mono-therapy or combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season.Methods One hundred patients aged 12–50 years (mean±SD 31.8±9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 μg once daily (n=20) or with FPANS 200 μg once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 μg once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage.Results All treatments showed significant differences (P〈0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P〈0.001) and nasal congestion daily (P〈0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P〈0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P〈0.001) and for nasal congestion on daily (P〈0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P〈0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P〈0.001) compared with PLA. Besides, there were significant differences (P〈0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK.Conclusion The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.

Notes: Background: The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU).Methods: Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine.Results: For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P 〈 0.0001; A vs. B2, P 〈 0.0001; A vs. C1, P 〈 0.0001; A vs. C2, P 〈 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P 〈 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P 〈 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients.Conclusion:  Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.

Notes: Background: Topical corticosteroids are beneficial in the treatment of allergic respiratory disorders; they exert effects on a number of cells involved in allergic inflammatory reactions. On the other hand, major histocompatibility complex (MHC)-unrestricted cytotoxicity (i.e., natural killer [NK] cell activity) may play a role in the inflammatory allergic reaction. The objective was to gain insight into the mechanisms of the therapeutic effects of fluticasone propionate (FP), an inhaled corticosteroid used in asthma and rhinitis therapy. Therefore, we evaluated the NK and lymphokine-activated killer (LAK) activity of effector cells in vitro treated or not with FP. Methods: Evaluations were made on peripheral blood mononuclear cells (PBMNCs), obtained from healthy volunteers (n=10) and from asthmatic atopic subjects (n=10) with allergy to Parietaria. Results: Asthmatic patients had significantly increased NK activity (P=0.0008), and interleukin (IL)-2- (P=0.0005) and interferon (IFN)-α-induced LAK activities (P=0.0005). In both groups, FP 10−7 M significantly reduced NK activity (P〈0.0001), IL-2-induced LAK activity (P〈0.0001), and IFN-α-induced LAK activity (P〈0.0001). Similar results were obtained
with FP 10−8 M. Conclusions: Since MHC-unrestricted cytotoxicity has been implicated in the development of allergen-induced eosinophilic airway inflammation, inhibition of NK and LAK activity by FP may contribute to the steroid therapeutic effect in asthma.