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Korzh Oleksiy, Kharkov, Ukraine

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  1. INFLUENCE OF SALMETEROL/FLUTICASONE PROPIONATE COMBINATION ON VASCULARITY OF THE BRONCHIAL MUCOSA IN PATIENTS WITH ASTHMA Korzh Oleksiy, Kharkov, Ukraine

  2. Airway remodeling overview

  3. Glucocorticoids (GCS) - Primary anti-inflammatory Therapy for asthma and related disorders. transrepression. negative modulation of gene transcription by GCS via non genomic mechanisms. Transrepression is due at least in part to direct, physical interactions between monomeric GR and transcription factors Trans repression

  4. The aim of this study was to examine the effect of inhaled salmeterol/fluticasone propionate combination on airway vascularity in bronchial biopsy specimens taken from asthmatic patients.

  5. Comparison of percent vascularity of bronchial biopsies from asthmatic subjects and controls

  6. Comparison of vessel numbers in bronchial biopsies from asthmatic subjects and controls

  7. Effect of Salmeterol/Fluticasone propionate combination on basement membrane thickness µm p = 0.23 p < 0.01 25 20 15 10 5 Before After 6 weeks Before After 6 weeks Salmeterol/Fluticasone propionat combination Placebo

  8. Correlation between the change in percent vascularity and change in collagen III thickness in treated patients D % vascularity R=0,78 P<0,01 Change in collagen III thickness

  9. Basement membrane thickening P Jeffery, in: Asthma, Academic Press 1998

  10. Effect of glucocorticoids (GCS) on other components of airway remodelling • Current data suggests that GCS have little or no effect on • Expression or activation of Epidermal Growth Factor receptors • (Puddicombe et al., FASEB J., 2000) • Release of ECM proteins from asthmatic airway smooth muscle • (Johnson et al., Am. J. Respir. Crit. Care Med, 2000). • TGFb secretion and effects • Furthermore in the laboratory in in vitro settings: • The inhibitory effects of GCS are mitogen specific, with GPCRinhibited more than receptor tyrosine kinases (RTKs) • GCS may paradoxically increase the proliferation of airway smooth muscle and fibroblasts.

  11. CONCLUSIONS: • These findings suggest that treatment of asthma with inhaled salmeterol/fluticasone propionate combination reduced airway wall vascularity during airway remodelling.