Harrison T W, Wisniewski A, Honour J, Tattersfield A E
Division of Respiratory Medicine, Nottingham City Hospital, Nottingham NG5 1PB, UK.
Thorax. 2001 Mar;56(3):186-91. doi: 10.1136/thorax.56.3.186.
The potential for long term adverse effects from inhaled corticosteroids relates to their systemic absorption, usually assessed from proxy markers in short term studies. When fluticasone propionate and budesonide have been compared in this way the results have been inconsistent. To determine whether this is because of the subjects studied or the sensitivity of the systemic marker used, we have compared the effects of fluticasone propionate and budesonide in healthy and asthmatic subjects and investigated the effect of treatment on three systemic markers.
Forty six healthy subjects were randomised to receive inhaled fluticasone propionate 1500 microg/day (via an Accuhaler), budesonide 1600 microg/day (via a Turbuhaler), or placebo; 31 subjects with moderately severe asthma were randomised to receive the same doses of fluticasone propionate or budesonide but not placebo. Systemic effects in healthy and asthmatic subjects were compared after 7 days. Treatment was continued for another 21 days in the subjects with asthma when systemic effects and asthma control were assessed.
At baseline healthy subjects had higher urinary levels of total cortisol metabolites (TCM) than subjects with asthma. After 7 days of treatment with fluticasone propionate urinary TCM levels in the healthy subjects were significantly lower than in the subjects with asthma (mean difference between groups 1663 microg/day, 95% CI 328 to 2938). This was not the case with budesonide, however, where urinary TCM levels in the healthy subjects remained above those in the asthmatic subjects (mean difference between groups 1210 microg/day, 95% CI -484 to 2904). Urinary TCM levels were considerably more sensitive to the effects of inhaled corticosteroids than morning serum cortisol or osteocalcin concentrations. Only budesonide reduced the serum level of osteocalcin.
When given by dry powder inhaler for 7 days, fluticasone propionate 1500 microg/day has a greater effect on the hypothalamic-pituitary-adrenal axis in healthy subjects than in subjects with asthma, but this is not the case for budesonide 1600 microg/day. These findings, together with the differences in sensitivity between systemic markers, explain many of the discrepancies in the literature.
吸入性糖皮质激素的长期不良反应可能性与其全身吸收有关，通常在短期研究中通过替代指标进行评估。当以这种方式比较丙酸氟替卡松和布地奈德时，结果并不一致。为了确定这是由于所研究的受试者还是所使用的全身指标的敏感性所致，我们比较了丙酸氟替卡松和布地奈德对健康受试者和哮喘患者的影响，并研究了治疗对三种全身指标的作用。
46名健康受试者被随机分为接受每日吸入1500微克丙酸氟替卡松（通过准纳器）、每日吸入1600微克布地奈德（通过都保）或安慰剂；31名中度至重度哮喘患者被随机分为接受相同剂量的丙酸氟替卡松或布地奈德，但不接受安慰剂。7天后比较健康受试者和哮喘患者的全身效应。哮喘患者继续治疗21天，评估全身效应和哮喘控制情况。
基线时，健康受试者尿中总皮质醇代谢物（TCM）水平高于哮喘患者。用丙酸氟替卡松治疗7天后，健康受试者尿中TCM水平显著低于哮喘患者（组间平均差异为1663微克/天，95%可信区间为328至2938）。然而，布地奈德并非如此，健康受试者尿中TCM水平仍高于哮喘患者（组间平均差异为1210微克/天，95%可信区间为-484至2904）。尿中TCM水平对吸入性糖皮质激素的作用比早晨血清皮质醇或骨钙素浓度更为敏感。只有布地奈德降低了骨钙素的血清水平。
当通过干粉吸入器给药7天时，每日1500微克丙酸氟替卡松对健康受试者下丘脑-垂体-肾上腺轴的影响大于哮喘患者，但每日1600微克布地奈德并非如此。这些发现，连同全身指标之间敏感性的差异，解释了文献中的许多差异。
