Effects of low doses of inhaled fluticasone propionate on inflammation and remodelling in persistent-mild asthma

In asthma a dysregulation of eosinophil apoptosis and an imbalance of metalloproteinase-
9 (MMP-9) and tissue inhibitor metalloproteinase-1 (TIMP-1) play
an important role in airway inflammation and remodelling. We evaluated the
effects of a low dose of inhaled fluticasone proprionate (FP) (100 lg bid by
Diskus) for 4 weeks in 24 steroid naive patients with mild persistent asthma,
symptomatic and with a sputum eosinophilia ?3% on clinical outcomes and
inflammatory markers such as the induced sputum eosinophils, the induced
sputum apoptotic eosinophils, the levels of MMP-9 and TIMP-1 and their molar
ratio in the induced sputum supernatants. After FP treatment forced expiratory
volume (FEV1) and FEV1/forced vital capacity values, PEF (L/min), sputum
apoptotic eosinophils, and MMP-9/TIMP-1 molar ratio in sputum supernatants
of asthmatic subjects were significantly increased in comparison with baseline,
while sputum eosinophils significantly decreased. Change (D) in FEV1 after
treatment with FP negatively correlated with the D in sputum eosinophils, while
the D in MMP-9 values positively correlated with D in TIMP-1 values. This
study shows that the clinical improvement achieved by the use of low doses of
FP in asthmatics is related, at least in part, to the resolution of eosinophilic
inflammation and the downregulation of remodelling markers.