Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study.

Abstract

In a double-blind, parallel-group study, we examined the effect of short-term treatment with inhaled fluticasone propionate (FP) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms. We administered FP (250 microg twice daily) or matched placebo for 6 wk. Methacholine challenge was performed before treatment, after 3 wk, and at the end of treatment. Each patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy before and after treatment. Eight patients in the placebo group and nine patients in the FP group completed the study. Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP (p < 0.05). When we compared the FP group with the placebo group, we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 (ICAM-1) and MAC-1 (p < 0.04 and p < 0.03, respectively). Moreover, we saw that the tryptase level in BAL decreased (p < 0.001), whereas the eosinophil cationic protein (ECP) level did not change significantly. Additionally, the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group (p < 0.02 and p < 0.01, respectively). Additionally, in the FP group, we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group (p < 0.05). In conclusion, our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens. Moreover, short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma.

TBX21 : A functional variant predicts improvement in asthma with the use of inhaled corticosteroids

“…The glutamine 33 carriers randomized to corticosteroids demonstrated substantial improvement in their PC 20 over time, with an average value at the end of the study in the normal range for nonasthmatics. These findings are consistent with both known association of corticosteroid usage with improvement in PC 20 (21,22) and the known biology of TBX21 (10). Moreover, the pharmacogenetic association reported represents a true geneby-environment interaction, in that the change noted in subjects possessing both the genetic variant of interest and treatment of interest was considerably greater than that represented by genetic variation, treatment effect, or the combination of these effects alone (Figs.…”

“…Use of inhaled corticosteroids improves airway inf lammation, hyperresponsiveness, obstruction, and clinical symptoms in asthma (21,22,30). Improvement in PC 20 in the CAMP corticosteroid arm has been documented (13) and is ref lected in our results (Table 1 and Fig.…”

Regulation of stem cell factor expression in inflammation and asthma

“…These findings of the mast cell signature confirmed previous data from the literature in glucocorticoid-treated asthmatics (Bradding et al 1994, Koshino et al 1996, Djukanovic et al 1997, Olivieri et al 1997.…”

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

“…These changes that include goblet cell hyperplasia (GCH), smooth muscle hypertrophy/hyperplasia, airway wall thickening and increased deposition of extracellular matrix proteins are present even in patients with mild asthma [2] and early in the disease process [3,4]. Most [5][6][7][8][9], but not all [10,11], biopsy studies show a limited effect of ICS on remodelling of asthmatic airways, possibly attributable to an effect on growth factor expression [8] or on the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 [9]. Comparison of these studies is hampered by differences in the steroids used, dosing regimen or treatment duration.…”