Thorax 1998;53:753-761 ( September )

Fluticasone propionate induced alterations to lung function and the immunopathology of asthma over time

John L Faul,^a Colm T Leonard,^a Conor M Burke,^a Vincent J Tormey,^b Leonard W Poulter^b

^a Department of Respiratory Medicine, James Connolly Memorial Hospital, Dublin, Ireland, ^b Department of Clinical Immunology, Royal Free Hospital School of Medicine, London NW3 2PF, UK

Correspondence to: Professor L W Poulter.

Received 27 May 1997; Returned to authors 7 August 1997; Revised version received 23 March 1998; Accepted for publication 12 May 1998

BACKGROUNDInhaled corticosteroids are the most widely used treatment for asthma, a disease characterised by both functional and immunopathological abnormalities. This study investigated the relative effects of inhaled corticosteroids on these two features of asthma over time.
METHODSA randomised, double blind, placebo controlled, parallel group study with inhaled fluticasone propionate, (FP 2 mg daily) was conducted in 27 patients with asthma. Following baseline analysis, the study tested the effects of short term (two weeks) and longer term (eight weeks) treatment. At each time point (0, 2, and 8 weeks) lung function tests were performed and endobronchial biopsy specimens obtained to determine the distribution and number of lymphocyte, macrophage and eosinophil subsets using immunohistological analysis. Twenty three patients completed the study, 11 on FP and 12 placebo.
RESULTSFEV₁, FEV₁, FEF_25-75, and FEV₁/FVC all improved after two weeks of FP treatment. This improvement was maintained but not increased after eight weeks. PC₂₀FEV₁ showed a trend to increase but was not significantly improved at eight weeks. No significant changes were seen in the placebo group. The numbers of T cells, macrophages, and eosinophils in the bronchial wall were reduced by two weeks of treatment with FP but were unaltered by placebo. The improvement offered by FP continued over the eight week period. Reductions in CD4:CD8 ratio and numbers of activated (EG2+) eosinophils were only significant after eight weeks of treatment.
CONCLUSIONSThese results reveal that FP influences both functional and immunopathological parameters of asthma. Temporal relationships suggest that these are parallel but not necessarily interrelated effects. While short term treatment is effective in "normalising" the functional abnormalities in asthma, the impact of FP on bronchial inflammation appears to be progressive, taking up to eight weeks and more.

Keywords: asthma; steroids; physiology; immunopathology; kinetics

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© 1998 by Thorax
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