Chest

Chest

Volume 110, Issue 1, July 1996, Pages 35-41
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Clinical Investigations: Asthma
Is Delayed Introduction of Inhaled Corticosteroids Harmful in Patients With Obstructive Airways Disease (Asthma and COPD)?

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Background

The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma. It is yet unknown what is the best time to start inhaled corticosteroid therapy and especially whether delayed introduction is harmful.

Phase 1

In a previous study in patients with asthma and COPD, we found that 2.5 years of treatment with a β2-agonist plus inhaled corticosteroid (BA+CS) was more effective in improving the FEV1 and the provocative concentration of histamine causing a 20% reduction in FEV1 (PC20) than treatment with a β2-agonist plus anticholinergic (BA+AC) or placebo (BA+PL).

Phase 2

We extended this study with 6 months to investigate whether delayed introduction of inhaled CS therapy (800 pg beclomethasone dipropionate) in the groups previously not treated with inhaled CS (BA±AC) could also improve FEV1 and PC20 to the same degree. A distinction was made between patients with predominantly asthma (high baseline reversibility, ΔFEV1 ≥9% of predicted), and predominantly COPD (low baseline reversibility, AFEV1 <9% of predicted).

Results

Improvement of FEV1 percent predicted by inhaled CS was comparable both in the asthmatics between phase 1 (13.8% predicted) and phase 2 (8.5% predicted; p=0.13) as well as in the patients with COPD (2.5% and 1.5% predicted, respectively). PC20, however, increased significantly more in the asthmatics in phase 1 (1.77 doubling concentration [DC]) than in phase 2 (0.79 DC; p=0.03). Improvement of PC20 in the patients with COPD was not significantly higher in phase 1 (0.74 DC) than in phase 2 (0.00 DC; p=0.19).

Conclusions

Our study indicates that although delayed introduction of inhaled CS in asthmatics leads to similar improvements in FEV1, improvements in PC20 are significantly less. These findings in patients with longer-existing asthma concur with other findings in newly detected asthma. We suggest that institution of inhaled CS therapy should not be postponed in asthmatics with documented airways obstruction and reversibility.

Section snippets

MATERIALS AND METHODS

The current investigation is an extension of a 2.5-year multicenter study.7 Patients aged 18 to 60 years with mild to moderately severe obstructive airways disease (asthma and COPD) were selected from 6 university outpatient clinics if they met the following 2 criteria: (1) a concentration of histamine causing a 20% decrease in FEV1 (PC20) of 8 mg/mL or less24,20; and (2) baseline FEV1 more than 1.2 L and 1.64 to 4.5 residual standard deviations (RSD) below the predicted value, or the FEV1

RESULTS

Of the 274 patients randomised in phase 1, 101 patients were withdrawn before the end of the study. The withdrawal rate was significantly larger in the BA+PL and BA+AC groups (44 and 45 patients, respectively) than in the original BA+CS group (12; p<0.0001). Seventy percent of this withdrawal was related to an increase in pulmonary symptoms.7 Of the remaining 94 patients not treated with ICS in phase 1 (47 in both the BA+AC and BA+PL group), 76 agreed to continue in phase 2. Baseline

DISCUSSION

This study suggests that a delay in the introduction of ICS therapy in patients with obstructive airways disease and marked reversibility may blunt their beneficial effect. When ICS therapy was instituted after 2.5 years of therapy with inhaled bronchodilators only, FEV1 in asthmatics and in COPD patients improved to a similar degree as in the group that received this treatment 2.5 years earlier. Improvement of airways hyperresponsiveness, however, was smaller after delayed institution, the

APPENDIX

The Dutch Chronic Nonspecific Lung Disease (CNSLD) Study Group consists of a steering committee (K.F. Kerrebijn, Ph.H. Quanjer, and H.J. Sluiter†), of members from the departments of pulmonology of the University Hospital of Amsterdam (E.M. Pouw, D.F.M.E. Schoonbrood, C.M. Roos, H.M. Jansen), Groningen (P.L.P. Brand, H.A.M. Kerstjens, A. de Gooijer, D.S. Postma, Th.W. van der Mark, H.J. Sluiter, † G.H. Koeter), Leiden (P.M. de Jong, P.J. Sterk, A.M.J. Wever, J.H. Dijkman), Nijmegen (P.N.R.

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    This study was supported by a grant from the Netherlands' Health Research Promotion Program (SGO). We acknowledge the support from three pharmaceutical companies who supplied the study medication in identical mete red-dose inhalers: Astra Pharmaceuticals, Boehringer Ingelheim, and Glaxo.

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    Copyright © 1996 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.