Glucocorticosteroids and rhinitis

Background: Intranasal application of glucocorticoids is an efficacious treatment of allergic rhinitis and some cases of nonallergic rhinitis. However, no data on binding of glucocorticoids to nasal tissue are available. Pronounced binding of the compound to the target tissue is favorable as it might serve as a local deposit delivering the glucocorticoid to specific receptors and it slows down the efflux of the compound into systemic circulation. Methods: Human nasal tissue was incubated with fluticasone propionate, budesonide, flunisolide and beclomethasone-17-monopropionate. Kinetics of binding and redistribution of the tissue-bound fraction into human plasma was monitored. Results: Binding of glucocorticoids to human nasal tissue was fast and highest for the lipophilic fluticasone propionate, followed by beclomethasone-17-monopropionate. Also, highest concentrations of these lipophilic glucocorticoids remained in nasal tissue after equilibration of drug-saturated tissue with plasma. Conclusions: Lipophilic compounds exhibit a high tissue binding and retention which is an important property of topically applied glucocorticoids. It is the basis for prolonged action and low concentration of the compound in systemic circulation.

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“…by decreasing mucosal edema and inhibition of inflammatory mediators. The effects on the hypothalamic pituitary-adrenal axis are minimal [1]. …”

Section: Introductionmentioning

confidence: 99%

Binding of Glucocorticoids to Human Nasal Tissue in vitro

Esmailpour

Högger²,

Rohdewald³

2000

Int Arch Allergy Immunol

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“…Topically delivered inhaled and intranasal corticosteroids are widely recognized as effective anti-inflammatory treatment for both conditions (5,6). They work by altering gene transcription to increase or decrease a plethora of cytokines, inflammatory mediators and enzymes, and adhesion molecules (7).…”

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confidence: 99%

Antiasthmatic Effects of Mediator Blockade versus Topical Corticosteroids in Allergic Rhinitis and Asthma

Wilson

Orr

Sims

et al. 2000

Am J Respir Crit Care Med

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To compare the antiasthmatic efficacy of inflammatory mediator blockade versus topical corticosteroid therapy in patients with seasonal allergic rhinitis (SAR) and asthma, 14 patients were enrolled into a single-blind, double-dummy, placebo-controlled crossover study comparing 2 wk therapy of ( 1 ) 400 g orally inhaled budesonide plus 200 g intranasal budesonide (BUD) or ( 2 ) 10 mg oral montelukast plus 10 mg oral cetirizine (ML ϩ CZ). Before each treatment period, patients received 7 to 10 d placebo washout. All treatments were given once daily in the morning. Throughout the study, patients recorded the following domiciliary measures: peak expiratory flow (PEF), rescue inhaler requirement, asthma symptoms, and daily activity score. Laboratory measurements were made at trough of adenosine monophosphate (AMP) bronchial challenge and exhaled nitric oxide (NO). Compared with pooled placebo (PL), there were significant (p Ͻ 0.05) improvements in all domiciliary measures with both treatments (mean PEF [L/min] PL: 463; BUD: 478; ML ϩ CZ: 483). For geometric mean AMP PC 20 (mg/ml), there was an improvement (p Ͻ 0.05), compared with PL (47), for ML ϩ CZ (133) but not for BUD (51); whereas for NO (ppb) there was significant suppression with BUD (7.6) but not ML ϩ CZ (11.5) compared with PL (13.6). In conclusion, both combined mediator blockade and combined topical corticosteroids are equally effective antiasthma therapy in patients with asthma and SAR.Asthma and allergic rhinitis are common conditions, occurring with increasing prevalence, and frequently coexisting (1). Both conditions occur in patients with underlying atopy and have a common etiology and pathophysiology. Untreated rhinitis can result in increased lower respiratory tract inflammation (2) due to a variety of possible mechanisms (3). There is good evidence to show that treating the upper airway inflammation in seasonal allergic rhinitis with intranasal corticosteroids alone has beneficial effect on lower airway inflammation in terms of an improvement in bronchial hyperreactivity (4).Topically delivered inhaled and intranasal corticosteroids are widely recognized as effective anti-inflammatory treatment for both conditions (5, 6). They work by altering gene transcription to increase or decrease a plethora of cytokines, inflammatory mediators and enzymes, and adhesion molecules (7). Histamine and cysteinyl leukotrienes are important inflammatory mediators in the pathogenesis of asthma and allergic rhinitis. With the introduction of leukotriene receptor antagonists it is now possible to selectively block the effects of both of these mediators. This may have a theoretical advantage over corticosteroid therapy as a result of a better adverse effect profile as well as the preference for taking tablets rather than inhalers and nasal sprays.The anti-inflammatory properties of leukotriene receptor antagonists have been shown to exhibit beneficial effects on asthma disease control (8). Antihistamines have been considered to be effective in the management of asthma ...

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“…The fact that in the literature several studies have been reported is not ignored [3, 4, 7, 8, 9, 10], but it is difficult to compare them, since different challenge protocols were adopted or different intervals between challenge and rechallenge were used. The results of the present study should be valuable both in reviewing the previous studies and in designing new ones.…”

Section: Introductionmentioning

confidence: 99%

Allergen-Specific Nasal Challenge: Response Kinetics of Clinical and Inflammatory Events to Rechallenge

Ciprandi

Ricca

Landi

et al. 1998

Int Arch Allergy Immunol

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Allergen-specific nasal challenge is a valid and reliable tool for studying the pathophysiological mechanisms involved in allergic inflammation. Nasal challenge induces an immediate clinical response in allergic subjects and a concomitant appearance of an inflammatory infiltrate. The mucosal inflammation may persist up to 48–72 h after allergen exposure. If the subjects are rechallenged within this period the response is more pronounced: the so-defined priming effect. The aim of the study was to evaluate the effects of the nasal rechallenge, performed at different time intervals: 3 days, 1, 2 and 4 weeks after the first challenge. Forty allergic subjects underwent two nasal challenges: at baseline and after the periods mentioned above (10/group). Symptoms and inflammatory cells (eosinophils and neutrophils recovered by nasal brushing) were assessed. The 3-day-interval group showed a hyperreactive response (priming effect), the 1- and 4-week-interval groups showed a response similar to baseline, and the 2-week-interval group showed a hyporeactive response (‘tolerogenic effect’). The last phenomenon may be due to a possible immunologic response similar to that achievable during local specific immunotherapy. The present results further elucidate the kinetics of allergen-driven inflammatory events and highlight the importance of the time period chosen for rechallenge. The latter fact may be of primary importance in clinical trials involving specific challenge.

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Glucocorticosteroids and rhinitis

Cited by 90 publications

References 130 publications

Binding of Glucocorticoids to Human Nasal Tissue in vitro

Binding of Glucocorticoids to Human Nasal Tissue in vitro

Antiasthmatic Effects of Mediator Blockade versus Topical Corticosteroids in Allergic Rhinitis and Asthma

Allergen-Specific Nasal Challenge: Response Kinetics of Clinical and Inflammatory Events to Rechallenge

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