Low- and high-dose fluticasone propionate in asthma; effects during and after treatment

Abstract

The dose dependency of the effects of inhaled corticosteroids on markers of asthmatic airway inflammation have not been well studied. There is a need to study the dose/response effects on this inflammation.In order to determine the dose/response effects of fluticasone propionate (FP), 24 asthmatic subjects were randomized to low-(100 mg . day -1 ) or high-dose (1,000 mg . day -1 ) FP for six weeks followed by placebo for 3 weeks.During treatment, the median increase in forced expiratory volume in one second (FEV1) was 12% in the high-dose group (p<0.05) and 10% in the low-dose group (p<0.05) (p>0.05 between groups); the median decrease in the percentage of sputum eosinophils was 93% in the high-dose group (p<0.05) and 46% in the low-dose group (p<0.05) (p>0.05 between groups). Symptoms, salbutamol use, morning peak flow, provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophil cationic protein concentration and tryptase activity improved significantly in both groups (p<0.05), but only the improvement in salbutamol use was greater in the highdose group (p<0.05). During the run-out, the improvements in FEV1 and PC20 were rapidly reversed in both groups, but the improvements in peak flow and tryptase activity persisted; the improvement in sputum eosinophil concentration persisted only in the high-dose group (p<0.05).It was concluded that dose/response effects for FP are not easily demonstrable because low-dose FP is quite effective. For most outcomes, the effects of high-and lowdose FP are relatively short-lived after treatment is stopped. This finding raises questions about the extent to which inhaled corticosteroids are disease-modifying in asthma. Eur Respir J 2000; 15: 11±18.

Starting inhaled corticosteroids in asthma: when, how high, and how long

“…After cessation of the active treatment, improvements in FEV1 and PC20 quickly reversed in both groups, but the improvements in peak flow and tryptase persisted for at least 3 weeks. The current authors agree with GERSHMAN et al [4] that the dose response effects were difficult to demonstrate because low dose FP was quite effective.…”

“…GERSHMAN et al [4] report a study in which patients with asthma received treatment with a low (100 mg . day -1 ) or a high dose (1,000 mg .…”

“…There were no differences between groups in the common outcome parameters such as symptoms, lung function and b-agonist use for the relief of symptoms. The study of GERSHMAN et al [4] shows again that there is no hard evidence to advise clinicians to treat all their newly detected steroid naive patients with asthma with an initial high dose of inhaled corticosteroids. Only a few of these patients, and presumably merely the patients with severe asthma, will benefit from an initial high dose of inhaled corticosteroids.…”

Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

“…To date, the dose-dependent effect of ICS on airway eosinophilia has mainly been assessed on induced sputum samples. These studies also indicate that ICS are effective, from low doses onwards, at reducing eosinophil number, and that the dose-response curve is relatively flat [17][18][19][20]. To what extent this is paralleled by changes in mucosal eosinophil number has not been fully established in humans.…”

Bronchial hyperresponsiveness to methacholine/AMP and the bronchodilator response in asthmatic children

“…The low-dose inhaled corticosteroids administered to most of the subjects requiring controller therapy are reported to have short-lived (within 1 week) effects on methacholine and AMP reactivity after treatment is stopped [22,23]. Conversely, the time course of changes in BDR following inhaled corticosteroid withdrawal has not been studied.…”