Systemic bioactivity profiles of intranasal triamcinolone and mometasone in patients with perennial allergic rhinitis

Systemic bioactivity profiles of intranasal triamcinolone and mometasone in patients with perennial allergic rhinitis

j ALLERGYCLIN IMMUNOL VOLUME 111, NUMBER 2 Aspergillus, Fusarium, Penicillium, before and after 2 months of fluconazole treatment in dose 100 rag/day...

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j ALLERGYCLIN IMMUNOL VOLUME 111, NUMBER 2

Aspergillus, Fusarium, Penicillium, before and after 2 months of fluconazole treatment in dose 100 rag/day, was performed. RESULTS: 29 (50.9%) patients with CS had fungi in the material sinuses: Candidu, 24 (82.8%); Aspergillus niger, 3 (10.4%); Alternaria, 1 (3.4%); Penicillium, 1 (3.4%). PMC were observed more often in women (55.2%), but NMC in men (67.0%). In both groups the additional symptoms as bronchial asthma (27.6% vs 32.1%) and atopic dermatitis (17.2% vs 10.7%) in the similar percentage occurred. In NMC more often occurred other organs (75.0% vs 10.3%). IgG against fungi was increased in 100.0% PMC and in 75.0% NMC. In majority the improvement was observed after fluconazole treatment. The liver parameters were normal, but decreased IgG against fungi. CONCLUSIONS: (1) The fungi play an important role in pathogenesis of CS. (2) In half of patients with CS it was possible to obtain PMC, but 87.7% had increased IgG against them, which suggests the necessity of further investigations and to look at the organs with mycoses. (3) Fluconazole medication in dose 100 mg/day was efficacious and safe.

Funding: Self-funded

fJ~A Comparative In Viva Bioactivity of Modern Hi-Antihistamines in j , , r Atapic Asthma C. E. Bates, D. K. C. Lee, G. P. Currie, B. J. Lipworth; Asthma and Allergy Research Group, Dundee, UNITED KINGDOM. BACKGROUND: Modern Hi-antihistamines differ in their in vitro binding affinity, but their comparative in vivo bioactivity in asthmatic airways is unknown. We have therefore compared clinically recommended doses of three Hi-antihistamines on airway hyperresponsiveness (AHR) to adenosine monophosphate (AMP) challenge (the primary outcome variable). METHODS: 16 mild to moderate atopic asthmatic patients (all positive to house dust mite on skin prick testing) were randomized in a doubleblind, placebo-controlled, cross-over fashion to receive single doses of desloratadine (DES) 5 mg, fexofenadine hydrochloride (FEX) 180 mg, levocetirizine dihydrochloride (LEV) 5 mg or placebo (PL), with AMP challenge performed 12 hours after dosing. RESULTS: All Hi-antihistamines demonstrated significantly greater (p < 0.05) geometric mean (+ SEM) AMP PC20 (mg/ml) compared to PL (86 _+ 29); DES (189 • 54), FEX (176 +_ 57), and LEV (163 • 48). Pre-challenge FEF25_75 (% predicted) but not FEV I was significantly higher (p < 0.05) for all Ht-antihistamines compared to PL (53 -+ 4); DES (62 _+ 4), FEX (62 • 4), and LEV (59 _+3). There were no significant differences in either AMP PC:0 or lung function between the H~-antihistamines. CONCLUSION: Single doses of Hi-antihistamines improved AHR and small airways caliber to a similar degree. Data for in vitro binding affinity do not therefore translate into commensurate differences in in vivo bioactivity at clinically recommended doses.

Funding: University of Dundee

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Systemic Bioactivity Profiles of Intranasal Triamcinolone and Mametasone in Patients with Perennial Allergic Rhinitis

F. Robb, D. K. C. Lee, E. J. Sims, G. P. Currie, L. C. McFarlane, B. J. Lipworth; Asthma and Allergy Research Group, Dundee, UNITED KINGDOM. RATIONALE: The absolute bioavailability from single-dose pharmacokinetics in healthy subjects is higher with triamcinolone acetonide (TA) than mometasone furoate (MF). Having previously shown that once daily TA 220 /.tg or MF 200 /.tg given for 5 days had no detectable systemic

Abstracts

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bioactivity in patients with seasonal allergic rhinitis, we undertook this study to assess patients with perennial allergic rhinitis (PAR) given intranasal glucocorticosteroids over a longer period of 3 weeks. OBJECTIVE: To evaluate whether differences in single-dose bioavailability are translated into systemic pharmacodynamic effects during chronic dosing with usual recommended doses of TA and MF in PAR. METHODS: 27 patients with PAR were randomized to receive 3 weeks in crossover fashion of either TA 220 ~tg or MF 200 ktg once daily in the morning, with a 2 week placebo period prior to each randomized treatment. Measurements were made at baseline after each placebo period and after each randomized treatment, comprising overnight 10-hour urinary cortisol corrected for creatinine (OUCC) excretion (primary outcome), 8 am plasma cortisol and 8 am serum osteocalcin. RESULTS: There were no differences between baseline placebo values prior to TA or ME There were also no differences for any outcome measures comparing randomized treatments to respective placebo baseline values or comparing TA to ME For OUCC compared to placebo, the geometric mean fold suppression (95% CI) was 1.02 (0.78-1.33) for TA (2% decrease), 1.07 (0.80-1.42) for MF (7% decrease), and 1.05 (0.79-1.39) for TA versus MF (5% decrease). CONCLUSION: Neither TA nor MF at usual recommended doses had detectable systemic bioactivity. Thus, differences in pharmacokinetic bioavailability do not predict pharmacodynamic systemic bioactivity after chronic dosing in patients with PAR.

Funding: Asthma and Allergy Research Group

6 Aspirin (ASA) Hypersensitivity as a Risk Factor Responsible for the Development of Severe Asthma in Outpatients

M. Kupczyk, I. Kuprys, E Kuna, E G6rski; Department of Medicine Medical University of Lodz, Division of Pneumonology and Allergy, Lodz, POLAND. Although the occurrence of bronchial asthma is still increasing the possible factors responsible for asthma severity have not been completely determined. The aim of this retrospective study was to evaluate the incidence of severe asthma and its determinants in outpatients. Aspirin (ASA) intolerance, HDM allergy, male sex, age over 65 years and asthma duration over l0 years were investigated as the potential risk factors. 598 women and 408 men, with average age 44,59 (SD _+ 16,45) randomly chosen from asthmatics followed up at the Outpatient Clinic were included. On the basis of medical documentation data about patients' history was gathered. The screening spirometry and skin prick tests were performed. ASA hypersensitivity must have been confirmed by inhaled challenge. Intermittent asthma was diagnosed in 35,4%, chronic mild in 33,4%, moderate in 23,8% and severe in 7,45% of studied patients. 95 cases of ASA intolerance were found. 30,7% patients with severe asthma suffered from ASA intolerance (OR=5,44). Logistic regression revealed that ASA hypersensitivity was the strongest risk factor responsible for the development of severe asthma (~=5,79, p < 0,00001). 789 patients were atopic. HDM allergy was a significant risk factor for the development of severe asthma in atopic patients group (OR=5,65). 341 patients were suffering from asthma for at least l0 years which was a significant risk factor (OR=3,64). The data from our study show that aspirin hypersensitivity is the strongest risk factor responsible for the development of severe asthma in outpatients. HDM allergy and asthma duration over l0 years are also significant risk factors.

Funding: Self-funded