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 microg bid by Diskus) for 4 weeks in 24 steroid naive patients with mild persistent asthma, symptomatic and with a sputum eosinophilia >or=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 (Delta) in FEV1 after treatment with FP negatively correlated with the Delta in sputum eosinophils, while the Delta in MMP-9 values positively correlated with Delta 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.
Vignola
A M
AM
Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy.
Riccobono
L
L
Profita
M
M
Foresi
A
A
Di Giorgi
R
R
Guerrera
D
D
Gjomarkaj
M
M
Di Blasi
P
P
Paggiaro
P L
PL
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D015536:Down-Regulation; D004802:Eosinophilia / Q000188:drug therapy; D004804:Eosinophils / Q000276:immunology / Q000502:physiology; D005260:Female; D000068298:Fluticasone; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016896:Treatment Outcome
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D000068298:Fluticasone; D020780:Matrix Metalloproteinase 9