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Effect of Inhaled Fluticasone Propionate on BAL TGF-ß1; and bFGF Concentrations in Clinically Stable Lung Transplant Recipients

journal contribution
posted on 2023-05-16, 15:25 authored by Zheng, L, Eugene WaltersEugene Walters, Wang, N, Whitford, H, Orsida, B, Levvey, B, Bailey, M, Williams, TJ, Snell, GI
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)-β 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 μg, 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-β 1 and bFGF concentrations. Results In LTRs before treatment, BAL TGF-β 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-β 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-β 1 concentration in the FP group (r = -0.53, p = 0.04), and between FEV 1 and BAL TGF-β 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-β 1 or bFGF concentrations. Conclusions Bronchoalveolar fluid TGF-β 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-β 1 or bFGF production in BAL fluid.

History

Publication title

Journal of Heart and Lung Transplantation

Volume

23

Issue

4

Pagination

446-455

ISSN

1053-2498

Department/School

Tasmanian School of Medicine

Publisher

ELSEVIER SCIENCE INC

Place of publication

New York, USA

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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