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Effect of oral prednisolone on the bronchoprotective effect of formoterol in patients with persistent asthma

¹ Dept of Pulmonology, Leijenburg Hospital, The Hague and ² Leiden University Medical Centre, Leiden, the Netherlands

CORRESPONDENCE: D.C. Grootendorst, Dept of Pulmonology, Leijenburg Hospital, P.O. Box 40551, NL-2504 LN The Hague, The Netherlands. Fax: 31 703592150

Keywords: bronchial hyperresponsiveness, bronchoprotection, corticosteroids, long-acting ß₂-agonists, severe asthma, tolerance

Received: March 14, 2000
Accepted October 18, 2000

This work was supported by a grant from Astra Pharmaceutica, (Zoetermeer, the Netherlands).

Tolerance to the bronchoprotective effects by long-acting ß₂-agonists (LAB) in patients with asthma is not prevented by inhaled corticosteroids (ICS). This study examined whether oral prednisolone can restore the bronchoprotective effects of formoterol in 24 patients with persistent asthma already treated with ICS (at least 800 µg budesonide·day^–1 or equivalent) and LAB, using a parallel-group design.

During a 2-week run-in period and during the study, patients used formoterol 12 µg twice daily by Turbuhaler^®, instead of their own LAB. At baseline and at the end of 7-days treatment with oral placebo or prednisolone (30 mg·day^–1), provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC₂₀ histamine) was measured on two separate days after randomized single-dose inhalation of placebo (postP) or formoterol (postF). In addition, PC₂₀postF was measured 24 h after starting oral treatment. The protective effect by formoterol at baseline and during treatment was calculated as the difference between the logs of PC₂₀postP and PC₂₀postF.

The mean±sem in doubling dose (DD) bronchoprotective effect at baseline was 0.8±0.4 DD in the placebo group and 1.0±0.4 DD in the prednisolone group. At the end of the treatment period, the protective effect changed to 1.0±0.5 DD and 0.8±0.6 DD in the placebo and prednisolone treated groups, respectively. This change was not different between the groups (p>0.4).

In conclusion, the bronchoprotective effect by formoterol is not influenced by 1 week prednisolone treatment in patients with asthma who are using regular inhaled corticosteroids and long-acting ß₂-agonists. These findings indicate that tolerance to long-acting ß₂-agonists cannot be restored by oral steroid therapy.

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