Effect of inhaled fluticasone propionate on BAL TGF-beta(1) and bFGF concentrations in clinically stable lung transplant recipients.
BACKGROUND
Inhaled fluticasone propionate (FP) therapy decreases inflammation and sub-basement membrane thickness in asthmatic airways. Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTRs) involves progressive airway fibrosis and obliteration. Therefore, augmented immunosuppression may be of some benefit in treating BOS. In this study, we examined the effect of 3 months of treatment with high-dose inhaled FP on the concentrations of 2 fibrogenic factors, transforming growth factor (TGF)-beta(1) and beta fibrogenic growth factor (bFGF) in bronchoalveolar lavage (BAL) fluid from clinically stable LTRs.


METHODS
We conducted a randomized, double-blind, placebo-controlled, parallel group study with inhaled FP (750 microg, twice/day for 3 months) in 28 LTRs (15 FP and 13 placebo). We recruited 23 healthy controls. We performed spirometry, bronchoscopy, and bronchoalveolar lavage procedures before treatment and after 3 months of treatment. We used commercially available enzyme-linked immunosorbent assay kits to measure BAL fluid TGF-beta(1) and bFGF concentrations.


RESULTS
In LTRs before treatment, BAL TGF-beta(1) concentrations (but not bFGF concentrations), total cell counts, and neutrophil percentage increased compared with controls (p < 0.05). We found no significant differences between FP and placebo groups at baseline measurements. After treatment, BAL TGF-beta(1) concentrations significantly increased in the FP group (p = 0.03), but we found no difference between FP and placebo groups; BAL bFGF concentrations increased during treatment in both groups compared with controls (p < 0.05), but not significantly within either patient group (p > 0.05). We found a reverse correlation between forced expiratory volume in 1 second (FEV(1)) and BAL TGF-beta(1) concentration in the FP group (r = -0.53, p = 0.04), and between FEV(1) and BAL TGF-beta(1) concentration in the placebo group (r = -0.74, p = 0.004). Multivariable analysis indicated no significant independent effects of inhaled FP in either BAL TGF-beta(1) or bFGF concentrations.


CONCLUSIONS
Bronchoalveolar fluid TGF-beta(1) concentrations increased in LTRs after transplantation and may correlate with the decrease in lung function. Inhaled FP added to conventional immunosuppression had no effect on TGF-beta(1) or bFGF production in BAL fluid.
Zheng
L
L
Department of Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Australia.
Walters
E H
EH
Wang
N
N
Whitford
H
H
Orsida
B
B
Levvey
B
B
Bailey
Michael
M
Williams
T J
TJ
Snell
G I
GI
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001989:Bronchiolitis Obliterans / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005346:Fibroblast Growth Factors / Q000187:drug effects* / Q000378:metabolism; D000068298:Fluticasone; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D016212:Transforming Growth Factor beta / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005346:Fibroblast Growth Factors; D000068298:Fluticasone