A455E is a common mutation causing cystic fibrosis in the Netherlands. Although several mutations are known to be associated with less severe pancreatic disease, our findings demonstrate a correlation between the A455E mutation and mild pulmonary disease. Because mortality in this disease depends primarily on the progression of pulmonary disease, patients with the A455E mutation have a better prognosis than patients who are homozygous for the delta F508 mutation.
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.
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