Tan K S, McFarlane L C, Lipworth B J
Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom.
Am J Respir Crit Care Med. 1997 Apr;155(4):1273-7. doi: 10.1164/ajrccm.155.4.9105066.
Female sex-steroid hormones may play an important influence in asthma. The aim of this study was to compare airway reactivity to adenosine monophosphate (AMP) in female asthmatics with natural menstrual cycles and those taking the oral combined contraceptive pill (OCP). Eighteen asthmatic subjects were evaluated. Nine subjects, mean (SEM) age, 24 (6) years, FEV1 93% (10) predicted, with natural cycles (group 1) were compared with nine subjects, age 24 (6) years, FEV1 93% (9) predicted taking the OCP (group 2). Group 1 subjects were evaluated at the follicular (visit 1) and luteal (visit 2) phases; group 2 subjects were evaluated during the week off OCP (visit 1) and at the end of the OCP cycle (visit 2). At each visit, serum progesterone and estradiol were measured. Airway reactivity to AMP was evaluated and expressed as PC20 (FEV1; mg/ml). Morning and evening peak expiratory flow rates (PEFR) were monitored throughout the study. In group 1, there was a significant increase in serum progesterone (nmol/l) and estradiol (pmol/l). (Visit 1 vs. 2): 2.5 vs. 13.5 (95% CI 2.1 to 19.9; p = 0.02) and 152.3 vs. 358.1 (95% CI 113.0 to 298.5; p < 0.001), respectively. In group 2, however, there was no increase between visit 1 vs. 2 in hormones: 0.9 vs. 1.0 and 75.7 vs. 21.8 for progesterone and estradiol, respectively. There was a significant increase in airway reactivity in group 1 during the luteal phase. Geometric mean PC20 (mg/ml) was 18.8 and 4.7 at visit 1 and 2, respectively: a 4.0-fold difference (95% CI 1.25 to 13.03; p = 0.03) amounting to two doubling doses. In contrast, there was no change in PC20 in group 2. Geometric mean PC20 was 23.5 and 21.4: a 1.06-fold difference (95% CI 0.41 to 2.78; p = 0.83). In group 1, morning and evening PEFR (l/min) were significantly different at both visits: at visit 1 (A.M. PEFR vs. P.M. PEFR) 403 vs. 430 (95% CI 5 to 50; p < 0.001) and visit 2, 415 vs. 439 (95% CI 1 to 46; p < 0.001). In group 2, there was no significant difference in diurnal PEFR variability at both visits; 411 vs. 417 at visit 1 and 413 vs. 427 at visit 2. In conclusion, asthmatic patients receiving the OCP had attenuated cyclical change in airway reactivity as well as reduced diurnal PEFR variability, which was associated with suppression of the normal luteal phase rise in sex-hormones.
女性甾体激素可能在哮喘中发挥重要影响。本研究的目的是比较处于自然月经周期的女性哮喘患者与服用口服复方避孕药(OCP)的女性哮喘患者对单磷酸腺苷(AMP)的气道反应性。对18名哮喘受试者进行了评估。将9名平均(标准误)年龄为24(6)岁、FEV1为预测值的93%(10)、处于自然月经周期的受试者(第1组)与9名年龄为24(6)岁、FEV1为预测值的93%(9)、服用OCP的受试者(第2组)进行比较。第1组受试者在卵泡期(第1次访视)和黄体期(第2次访视)接受评估;第2组受试者在停用OCP的那周(第1次访视)和OCP周期结束时(第2次访视)接受评估。每次访视时,均测量血清孕酮和雌二醇。评估对AMP的气道反应性,并以PC20(FEV1;mg/ml)表示。在整个研究过程中监测早晚的呼气峰值流速(PEFR)。在第1组中,血清孕酮(nmol/l)和雌二醇(pmol/l)有显著升高。(第1次访视与第2次访视):分别为2.5对13.5(95%可信区间2.1至19.9;p = 0.02)和152.3对358.1(95%可信区间113.0至298.5;p < 0.001)。然而,在第2组中,第1次访视与第2次访视之间激素水平没有升高:孕酮和雌二醇分别为0.9对1.0和75.7对21.8。第1组在黄体期气道反应性有显著增加。第1次和第2次访视时几何平均PC20(mg/ml)分别为18.8和4.7:相差4.0倍(95%可信区间1.25至13.03;p = 0.03),相当于两个加倍剂量。相比之下,第2组的PC20没有变化。几何平均PC20为23.5和21.4:相差1.06倍(95%可信区间0.41至2.78;p = 0.83)。在第1组中,两次访视时早晚的PEFR(l/min)均有显著差异:第1次访视时(上午PEFR对下午PEFR)为403对430(95%可信区间5至50;p < 0.001)以及第2次访视时为415对439(95%可信区间1至46;p < 0.001)。在第2组中,两次访视时昼夜PEFR变异性均无显著差异;第1次访视时为411对417,第2次访视时为413对427。总之,服用OCP的哮喘患者气道反应性的周期性变化减弱,昼夜PEFR变异性降低,这与抑制正常黄体期性激素升高有关。