Flonase
Modulation of the constitutive or cytokine-induced bronchial epithelial cell functions in vitro by fluticasone propionate.

Sabatini F, Silvestri M, Sale R, Serpero L, Raynal ME, Di Blasi P, Rossi GA.

Pulmonary Diseases Unit, G. Gaslini Institute, Largo G. Gaslini 5, 16147, Genoa, Italy.

When exposed to proinflammatory mediators, human bronchial epithelial cells (HBECs) upregulate the 'constitutive' adhesion molecule expression and cytokine/chemokine release. We tested whether and to what extent the inhibitory effect of fluticasone propionate on HBECs could involve the 'constitutive' and 'cytokine-induced' proinflammatory functions. Stimulation of the HBECs with interleukin (IL)-4 plus tumour necrosis factor (TNF)-alpha was more effective in upregulating intercellular adhesion molecule (ICAM)-1 ( approximately 2.2-fold increase) than vascular adhesion molecule (VCAM)-1 ( approximately 1.6-fold increase) expression (P<0.05) and in increasing the release of 'regulated on activation normal T cell expressed' (RANTES, 5.7-fold increase) than of IL-8 (3.5-fold increase) and granulocyte macrophage-colony stimulating factor (GM-CSF, 2.8-fold increase), (P<0.01). Fluticasone propionate, at the two concentrations tested (10 and 100 nM), was more effective in inhibiting the 'IL-4 plus TNF-alpha-induced' ICAM-1 expression than VCAM-1 expression (P<0.05) and in downregulating RANTES than IL-8 or GM-CSF secretion (P<0.05). The degree of inhibition demonstrated by fluticasone propionate appeared to be related to the degree of cell activation. In addition, for both adhesion molecules, the effect of fluticasone propionate at both concentrations tested appeared to be related to a complete inhibition of 'IL-4 plus TNF-alpha-induced' expression with no involvement of the 'constitutive' expression. Slightly different results were observed for cytokine/chemokine release. Indeed, evaluating RANTES, a complete inhibition of the 'IL-4 plus TNF-alpha-induced' release with a partial inhibition also of the 'constitutive' release at both concentrations of the drug tested was found, whereas for GM-CSF and IL-8, only a partial inhibition of the 'IL-4 plus TNF-alpha-induced' release in the presence of fluticasone propionate 10 and 100 nM. Thus, HBECs can constitutively or upon activation express adhesion molecules and secrete proinflammatory proteins at various levels and the different ability of fluticasone propionate to modulate the HBEC functions appears to be mostly related to the different inhibition of the various 'IL-4 plus TNF-alpha-induced' responses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14556981&dopt=Abstract fluticasone Flonase



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The effects of one-week fluticasone propionate inhalation therapy for Tc-99m DTPA radioaerosol distribution in asthma of children: a preliminary report.

Chen AC, Tsai FJ, Tsai JJ, Lin CC, Lee CC, Kao A.

Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan.

This study evaluated the effects of fluticasone propionate inhalation therapy for the distribution pattern of Tc-99m DTPA radioaerosols in 10 children with asthma. The homogeneous degree of depositing Tc-99m DTPA radioaerosol was evaluated using a modified standard score system over the bilateral lungs. The baseline scores were calculated from Tc-99m DTPA radioaerosol inhalation lung scintigraphy before inhalation therapy (100 microg fluticasone propionate two times daily for one week), and the scores were recalculated after inhalation therapy to evaluate the effects of one-week of fluticasone propionate inhalation therapy for Tc-99m DTPA radioaerosol distribution patterns. After one week of fluticasone propionate inhalation therapy, the scores were decreased in all of the 10 children, which may mean that the bronchial constriction degree due to asthma is decreased. In addition, there was a significantly statistical difference in the scores before and after one-week fluticasone propionate inhalation therapy (p < 0.05). In conclusion, one-week fluticasone propionate inhalation therapy could significantly improve the bronchial constriction due to asthma in children based on the evidence of Tc-99m DTPA radioaerosol inhalation lung scintigraphic findings.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14565688&dopt=Abstract fluticasone Flonase



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Prevalence of esophageal candidiasis among patients treated with inhaled fluticasone propionate.

Kanda N, Yasuba H, Takahashi T, Mizuhara Y, Yamazaki S, Imada Y, Izumi Y, Kobayashi Y, Yamashita K, Kita H, Tamada T, Chiba T.

Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

OBJECTIVES: Development of oropharyngeal candidiasis is a frequently reported adverse effect of inhaled corticosteroid use, but the prevalence of esophageal candidiasis is unknown. The aim of this study was to estimate the prevalence of esophageal candidiasis among patients treated with an inhaled corticosteroid, fluticasone propionate. METHODS: Upper GI endoscopy was performed on 49 patients treated with inhaled fluticasone propionate to examine the prevalence of esophageal candidiasis. Of the patients, 36 had bronchial asthma and 13 had chronic obstructive pulmonary disease. To compare the prevalence with control patients, upper GI endoscopy was performed on 700 consecutive patients without malignancy or immunosuppression. RESULTS: The prevalence of esophageal candidiasis was 37% among patients treated with inhaled fluticasone propionate, whereas only 0.3% of the control patients had the infection. The prevalence was especially high among patients with diabetes mellitus or those who were treated with a high dose of inhaled fluticasone propionate. Moreover, a reduction in the daily dose of inhaled fluticasone propionate eliminated the infection in four of five patients. CONCLUSIONS: Esophageal candidiasis is a common complication of inhaled corticosteroid use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14572559&dopt=Abstract fluticasone Flonase



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Differential prescribing of inhaled corticosteroids in New Zealand general practice.

Hall J, Penrose A, Tomlin A, Reid J.

Royal New Zealand College of General Practitioners Research Unit, Department of General Practice, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. jhall gp.otago.ac.nz

AIM: To determine how inhaled budesonide, beclomethasone and fluticasone are prescribed by general practitioners in New Zealand. METHODS: Retrospective study of computerised clinical records from 42 general practices in New Zealand for the period 1 July 1997 to 30 June 1998. The study population comprised 174 929 consulting patients, of whom 9878 patients were prescribed budesonide, fluticasone, or beclomethasone with full dosing instructions. RESULTS: The mean daily prescribed dose was higher for patients receiving inhaled budesonide (886 microg) than beclomethasone (547 microg), a difference of 339 microg (95% CI 311 microg to 367 microg), and fluticasone (508 microg), a difference of 378 microg (95% CI 344-412). The difference between mean daily prescribed doses of beclomethasone and fluticasone was 39 microg (95% CI 15-63). The overall difference was consistent across age groups and with different types of inhalation device. Evidence of systematic prescribing of higher doses of budesonide to patients with more severe asthma was not found. Patients prescribed fluticasone were more likely to have been prescribed oral steroids in the preceding year. CONCLUSIONS: Conclusions about the relative potencies of inhaled corticosteroids cannot be made with the data presented. However, data presented show that inhaled corticosteroids have not been prescribed in line with their reported relative potencies. This study provides benchmark data for the prescribing of inhaled steroids in New Zealand general practice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14581985&dopt=Abstract fluticasone Flonase