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

Abstract

Tolerance to the bronchoprotective effects by long-acting b 2 -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 mg 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 mg twice daily by Turbuhaler1, 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 singledose 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 (pw0.4).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 b 2 -agonists. These findings indicate that tolerance to long-acting b 2 -agonists cannot be restored by oral steroid therapy.

Formoterol Thrice Weekly Does Not Result in the Development of Tolerance to Bronchoprotection

“…The development of a downward trend of PC 20 in our daily formoterol data may have significance with longer treatment duration, a larger sample size or both; a trend toward the loss of bronchoprotection following administration of 12 µg formoterol twice a day for seven days has been previously documented (9). We did not consider concomitant administration or inconsistent administration of inhaled corticosteroid to be a contributing factor in the difference between our results and others' because inhaled corticosteroid administration does not prevent the development of tolerance (10), and oral prednisolone does not reverse established tolerance (11).…”

Scientific rationale for inhaled combination therapy with long-acting β2-agonists and corticosteroids

“…However, this may be because the ICS does not reach b 2 -receptors in airway smooth muscle. However, even oral corticosteroids fail to protect against the loss of bronchoprotective effect of formoterol [66]. However, it remains to be determined whether ICS would protect against the loss of protection against mastcell activating constrictor stimuli, such as AMP or allergen, or against the desensitization of plasma exudation effects.…”

Rosiglitazone reverses salbutamol‐induced β2‐adrenoceptor tolerance in airway smooth muscle

“…The same result was obtained by Hall et al . (1993) in human airway smooth muscle cells chronically exposed to isoprenaline, and there is evidence indicating that tolerance to β 2 ‐adrenoceptor agonists cannot be restored by systemic steroid therapy in asthma patients (Grootendorst et al ., 2001). On the other hand, 1 h incubation of human lung slices with dexamethasone prevented β 2 ‐adrenoceptor desensitization (Cooper and Panettieri, 2008).…”