Glucocorticoid‐induced attenuation of mucosal exudation of fibrinogen and bradykinins in seasonal allergic rhinitis

The effect of fluticasone on the airway inflammatory response to organic dust. A. Ek, L. Palmberg, K. Larsson. #ERS Journals Ltd 2004. ABSTRACT: Exposure to organic dust in a swine house causes acute airway inflammation and increased bronchial responsiveness to methacholine in healthy subjects. The aim of this study was to investigate whether an inhaled glucocorticoid, fluticasone propionate, alters the acute airway responses induced by exposure in a swine barn.In 15 healthy subjects, analysis of nasal lavage fluids, serum samples and bronchial methacholine responsiveness were performed before and after exposure to organic dust in a swine house for 3 h. Seven subjects received fluticasone propionate (500 mg b.i.d. by inhalation and 100 mg intranasally once daily) and eight subjects received placebo during the 2 weeks prior to exposure.Post-exposure plasma interleukin (IL)-6 levels and body temperature were significantly lower in the fluticasone group than in the placebo group. Intranasally administered fluticasone propionate significantly attenuated the plasma protein (assessed as albumin concentrations) leakage and IL-8 and tumour necrosis factor-a response induced by exposure. Fluticasone propionate inhalation exerted no influence on the increased bronchial responsiveness to methacholine induced by exposure.In conclusion, glucocorticoid treatment attenuated the inflammatory response to inhaled organic dust without influencing the increased bronchial responsiveness to methacholine.

Section: Discussionsupporting

confidence: 89%

The effect of fluticasone on the airway inflammatory response to organic dust

Palmberg²

2004

“…The present study demonstrated an increased baseline exudation of plasma during the season and confirmed the graded exudation of plasma that occurs acutely in response to nasal challenges with histamine or allergen. When the nasal airway received a direct, topical treatment with glucocorticosteroids, the baseline exudation in allergic rhinitis was effectively inhibited [8]. In contrast, orally inhaled budesonide did not attenuate the nasal plasma exudation response in the present study.…”

Section: Discussioncontrasting

confidence: 69%

“…We have examined nasal symptoms, indices of exudative and eosinophilic nasal inflammation, blood eosinophils, bronchial symptoms, and bronchial response to methacholine. All the selected variables may be abnormal in both allergic asthma and allergic rhinitis, and most of them show glucocorticosteroid sensitivity [1,8,9].…”

mentioning

confidence: 99%

Effects of orally inhaled budesonide in seasonal allergic rhinitis

Greiff¹,

Andersson²,

Svensson³

et al. 1998

It has previously been demonstrated that topical nasal treatment with glucocorticosteroids has significant effects on the bronchial airways. Less is known about effects on nasal disease by topical bronchial treatment with these drugs. The present study examined effects on nasal allergic disease of inhaled budesonide (avoiding nasal deposition of the drug). Patients with seasonal allergic rhinitis, but without asthma, were thus given inhalations of budesonide (600 microg b.i.d.) or placebo. The aim of the design was to allow the study of eosinophilic airway disease in a part of the airway other than the directly treated locus. Moderate to high birch pollen levels were recorded during the study season, and nasal symptoms were significantly increased in both treatment groups, although they were milder in patients receiving budesonide than in the placebo group (p<0.05). Nasal brush eosinophils and nasal lavage fluid levels of eosinophil cationic protein as well as blood eosinophils were increased during the season (p<0.05), but these increases were prevented by the inhaled budesonide. Nasal lavage fluid levels of alpha2-macroglobulin were particularly elevated in the placebo group but did not differ between patients receiving placebo and budesonide. Budesonide prevented the seasonal development of increased bronchoconstrictor responses to methacholine challenge (p<0.05). In conclusion, budesonide reduced the seasonal eosinophilia both in the circulation and in the nose along with an attenuation of seasonal nasal symptoms. Hence, at a daily dose of 600 microg b.i.d., known to cause no, or minimal, adverse effects, inhaled budesonide produces clinically significant anti-inflammatory effects in the entire airways, including the nasal mucosa, which is not exposed topically to the drug. We suggest that nasal and systemic anti-eosinophil actions are produced at commonly employed dose levels of orally inhaled budesonide.

“…By determination of a large plasma protein (fibrinogen) and a plasma-derived mediator (bradykinin) in nasal lavage fluid. SVENSSON et al [79] have demon-strated topical steroid-mediated inhibition of plasma ex-udation and, hence, inhibition of its derived peptides in seasonal allergic rhinitis. Interestingly, steroids are not universally effective.…”

Section: Antiexudative Effects Of Drugsmentioning

confidence: 99%

Plasma-derived proteins in airway defence, disease and repair of epithelial injury

Persson

Erjefält²,

Greiff³

et al. 1998

123

One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.