Lung rejection
Effect of inhaled fluticasone propionate on BAL TGF-β1 and bFGF concentrations in clinically stable lung transplant recipients

https://doi.org/10.1016/S1053-2498(03)00199-2Get rights and content

Abstract

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)–β1 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-β1 and bFGF concentrations.

Results

In LTRs before treatment, BAL TGF-β1 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-β1 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 (FEV1) and BAL TGF-β1 concentration in the FP group (r = −0.53, p = 0.04), and between FEV1 and BAL TGF-β1 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-β1 or bFGF concentrations.

Conclusions

Bronchoalveolar fluid TGF-β1 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-β1 or bFGF production in BAL fluid.

Section snippets

Study design

A double-blind, randomized, placebo-controlled, and parallel-group study was conducted. Patients received either 750 μg inhaled FP or inhaled placebo twice a day for 3 months, in addition to conventional immunosuppression. The standardized immunosuppression consisted of cyclosporine (to achieve a trough blood concentration of 250–300 μg/liter by enzyme-multiplied immunoassay technique [Syya, CA]); azathioprine (1–2 mg/kg, maintaining white blood cells >5 × 109/liter); and prednisolone, tapering

Subject demography and clinical characteristics

We recruited 28 single LTRs (15 in FP group, 13 in placebo group) who underwent transplantation between April 1997 and May 1999 and who were at an average of 145 ± 70 days after transplantation. All patients had bronchoscopy and lung function measurements on 2 occasions. We found no significant difference in age (p = 0.17), FEV1 (p = 0.80), and best FEV1% after transplantation (p = 0.27) between FP and placebo groups (Table 1). However the sex distribution (10 women in the FP group vs 3 women

Discussion

In this double-blind, randomized, placebo-controlled study, we evaluated the effects of high-dose, inhaled FP on BAL TGF-β1 and bFGF concentrations in clinically stable LTRs during a 3-month period of treatment. Inhaled FP added to the conventional immunosuppressant regimen had little effect on the concentrations of bFGF in BAL fluid from the studied subjects. Bronchoalveolar lavage fluid TGF-β1 concentrations were significantly greater before treatment in the single LTRs than in controls, and

Acknowledgements

The authors thank Christopher Ward for assistance in the administration of this study.

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    Grant support from the National Health and Medical Research Council of Australia and Glaxo Welcome R&D.

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