A Double-blind Study on the Effect of Inhaled Corticosteroids on Plasma Protein Exudation in Asthma

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: 88%

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

Palmberg²

2004

“…In line with this, the reduction of the amount of FN in the airway wall by FP in the present study can be attributed both to an effect on plasma leakage and on fibroblast function. Treatment with inhaled FP significantly reduced plasma protein leakage in human airways [26]. It has also been shown in vitro that dexamethasone dose-dependently inhibited FN synthesis by rat lung fibroblasts [27].…”

Section: Discussionmentioning

confidence: 99%

Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

Vanacker¹,

Palmans²,

Pauwels³

et al. 2002

To examine whether fluticasone propionate (FP) dose-dependently inhibits inflammatory as well as structural changes, Brown Norway rats were sensitised to ovalbumin (OA) on day 0 and 7. From day 14-28, rats were exposed to aerosolised OA (1%) or phosphate buffered saline every 2 days. Thirty minutes before each allergen exposure, animals were pre-treated with aerosolised placebo or FP (0.1, 1 or 10 mg) or prednisolone 3 mg?kg -1 i.p.At day 29, 0.1 mg FP had no measurable effect, either on inflammatory or structural changes, such as goblet cell hyperplasia and airway wall thickening. The allergeninduced increase in eosinophilic inflammation in bronchoalveolar lavage fluid and in the airway mucosa, as well as increased fibronectin deposition, were inhibited by treatment with FP from a dose of 1 mg onwards. Inhibition of goblet cell hyperplasia and thickening of the airway wall required 10 mg inhaled FP. At this dose, systemic effects were observed. However, for a comparable degree of systemic activity, prednisolone was far less effective at preventing airway changes.The dose of inhaled fluticasone propionate required to inhibit allergen-induced structural alterations was higher than to prevent eosinophil influx, and caused systemic side-effects. However, for a similar systemic activity, prednisolone was ineffective in preventing airway remodelling.

“…In addition to serving as the source of nutrients to the bronchial wall [73], the airway circulation has important roles in heat and water exchange [74,75], airway hyperreactivity [7,14,17,76], and possibly the regulation of airway calibre in the lung periphery [10][11][12][13][77][78][79][80]. Furthermore, the airway circulation functions as the conduit for inflammatory cell recruitment [81,82], and participates in the clearance of locally released, biologically active substances [83,84] and inhaled materials transported from the surface to the deeper tissue [85].…”

Section: The Airway Vasculature In Patients With Asthmamentioning

confidence: 99%

“…In patients with asthma, inhaled corticosteroid therapy has been shown to suppress the increased microvascular permeability and plasma leakage into the airway lumen, as determined by measuring concentrations of high molecular weight proteins (e.g. a 2 -macroglobulin) in induced sputum [121,196] and bronchoalveolar lavage fluid [14,197]. Because increased microvascular permeability has a role in asthma-associated airflow obstruction, the anti-permeability actions of corticosteroids may be of therapeutic value.…”

Section: Inhibition Of Oedema Formationmentioning

confidence: 99%

“…The major structural and functional changes related to the airway circulation include the proliferation of blood vessels (angiogenesis) [2][3][4], increased blood flow [5,6], increased microvascular permeability [7,8], and oedema formation in the airway wall [9]. These vascular components seem to have significant clinical implications because of their correlations to asthma severity, including airflow limitation [10][11][12][13] and bronchial hyperresponsiveness [7,11,[14][15][16][17][18]. Recent advances in the understanding of the cellular mechanisms responsible for these vascular abnormalities may ultimately lead to new therapeutic approaches for the treatment of asthma.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma

Horváth

Wanner²

2006

Inhaled corticosteroids suppress airway inflammation and components of airway remodelling in bronchial asthma. In the tracheobronchial (airway) vasculature, these include the inhibition of inflammatory hyperperfusion, microvascular hyperpermeability, mucosal oedema formation, and the formation of new blood vessels (angiogenesis).Corticosteroids are now known to exert their effects on the airway vasculature through genomic and nongenomic mechanisms. Genomic actions involve the regulation of target genes, and suppress most of the vascular elements of inflammation and angiogenesis in the airway. In contrast, nongenomic actions are mediated by rapid cellular mechanisms, and induce transient vasoconstriction in the airway, thereby reversing inflammatory hyperperfusion.The vascular actions of corticosteroids contribute to controlling clinical symptoms of asthma primarily by influencing airway calibre in the lung periphery and airway hyperreactivity.In this review article, recent advances into the understanding of cellular mechanisms and the clinical implications of the interaction of inhaled corticosteroids and the airway vasculature in asthma are reviewed.