轻度哮喘患者短期内每日1次糠酸氟替卡松对乙酰甲胆碱诱导的支气管收缩的影响
2019/10/17
摘要
背景：吸入糖皮质激素（ICS）可降低气道炎症和气道高反应性（AHR）。以往的研究一般都是在中高剂量激素治疗几周或几个月后，研究ICS对乙酰甲胆碱诱导的AHR的影响。
目的：观察每日1次糠酸氟替卡松（FF）100μg对乙酰甲胆碱诱导的AHR及气道炎症的短期影响。
方法：对11例轻度哮喘患者进行随机、双盲交叉研究。为期7天的每天一次FF（100μg）或相同剂量的安慰剂Ellipta®吸入器吸入，并伴有2周的药物洗脱期。在第1次、第3次和第7次给药之前和之后24小时进行乙酰甲胆碱激发。首次和第7天测量呼出的部分一氧化氮（FeNO）。
结果：FF显著（p=0.0009-0.0078）增加乙酰甲胆碱PD20（激发剂量导致1 s用力呼气量下降20%）。第1次、第3次和第7次给药后的剂量倍增（95%CI）分别为1.23（0.60-1.86）、1.17（0.68-1.67）和1.44（0.93-1.94）。FF治疗后7天，FENO（几何平均值，95%CI）从最初的37.9 ppb（23.7-60.5）降至22.9 ppb（14.8-35.5）。安慰剂不影响乙酰甲胆碱PD20或FeNO。
结论：单剂量FF 100μg可降低24小时内的乙酰甲胆碱AHR，但随着每天持续使用超过7天，AHR并没有明显改善。每天给药一周后AHR的降低与第7天FeNO的显著减少相一致。与过去的假设相反，ICS FF似乎能迅速将降低乙酰甲胆碱诱发的AHR。
Short-term effect of once-daily fluticasone furoate on methacholine-induced bronchoconstriction in mild asthmatics.
Okonkwo CS, Davis BE, Blais CM, Cockcroft DW.
Abstract
BACKGROUND: Inhaled corticosteroids (ICS) decrease airway inflammation and airway hyperresponsiveness (AHR). Previous studies have generally investigated the effect of ICS on methacholine-induced AHR following weeks or months of medium to high dose treatment.
PURPOSE: The short-term effects of once-daily fluticasone furoate (FF) 100 mcg on methacholine-induced AHR and airway inflammation were examined over the course of one week.
METHODS: Eleven mild asthmatics completed this randomized, double-blind crossover study. Once-daily FF (100 mcg) and identical appearing placebo Ellipta® inhalers were given for 7 days with a 2-week washout. Methacholine challenges were performed before and 24 h after the first, third and seventh doses. Fractional exhaled nitric oxide (FeNO) was measured initially and at 7 days.
RESULTS: FF significantly (p = 0.0009-0.0078) increased methacholine PD20 (provocative dose causing 20% fall in forced expiratory volume in 1 s) at all times. Doubling dose shifts (95% CI) were 1.23 (0.60-1.86), 1.17 (0.68-1.67) and 1.44 (0.93-1.94) after the first, third and seventh dose respectively. FeNO (geometric mean, 95% CI) decreased significantly (p = 0.0049) following FF treatment from 37.9 ppb (23.7-60.5) initially to 22.9 ppb (14.8-35.5) at 7 days. Placebo did not affect methacholine PD20 or FeNO.
CONCLUSION: Single-dose FF 100 mcg decreased methacholine AHR at 24 h without significant further improvement with continued daily use over 7 days. The inhibition in AHR after one week of daily dosing coincided with a significant decrease in FeNO at 7 days. Contrary to past assumptions, the ICS FF appears to rapidly reduce AHR to methacholine.
背景：吸入糖皮质激素（ICS）可降低气道炎症和气道高反应性（AHR）。以往的研究一般都是在中高剂量激素治疗几周或几个月后，研究ICS对乙酰甲胆碱诱导的AHR的影响。
目的：观察每日1次糠酸氟替卡松（FF）100μg对乙酰甲胆碱诱导的AHR及气道炎症的短期影响。
方法：对11例轻度哮喘患者进行随机、双盲交叉研究。为期7天的每天一次FF（100μg）或相同剂量的安慰剂Ellipta®吸入器吸入，并伴有2周的药物洗脱期。在第1次、第3次和第7次给药之前和之后24小时进行乙酰甲胆碱激发。首次和第7天测量呼出的部分一氧化氮（FeNO）。
结果：FF显著（p=0.0009-0.0078）增加乙酰甲胆碱PD20（激发剂量导致1 s用力呼气量下降20%）。第1次、第3次和第7次给药后的剂量倍增（95%CI）分别为1.23（0.60-1.86）、1.17（0.68-1.67）和1.44（0.93-1.94）。FF治疗后7天，FENO（几何平均值，95%CI）从最初的37.9 ppb（23.7-60.5）降至22.9 ppb（14.8-35.5）。安慰剂不影响乙酰甲胆碱PD20或FeNO。
结论：单剂量FF 100μg可降低24小时内的乙酰甲胆碱AHR，但随着每天持续使用超过7天，AHR并没有明显改善。每天给药一周后AHR的降低与第7天FeNO的显著减少相一致。与过去的假设相反，ICS FF似乎能迅速将降低乙酰甲胆碱诱发的AHR。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Respir Med. 2019 Sep;156:53-57. doi: 10.1016/j.rmed.2019.08.007.)
(Respir Med. 2019 Sep;156:53-57. doi: 10.1016/j.rmed.2019.08.007.)
Short-term effect of once-daily fluticasone furoate on methacholine-induced bronchoconstriction in mild asthmatics.
Okonkwo CS, Davis BE, Blais CM, Cockcroft DW.
Abstract
BACKGROUND: Inhaled corticosteroids (ICS) decrease airway inflammation and airway hyperresponsiveness (AHR). Previous studies have generally investigated the effect of ICS on methacholine-induced AHR following weeks or months of medium to high dose treatment.
PURPOSE: The short-term effects of once-daily fluticasone furoate (FF) 100 mcg on methacholine-induced AHR and airway inflammation were examined over the course of one week.
METHODS: Eleven mild asthmatics completed this randomized, double-blind crossover study. Once-daily FF (100 mcg) and identical appearing placebo Ellipta® inhalers were given for 7 days with a 2-week washout. Methacholine challenges were performed before and 24 h after the first, third and seventh doses. Fractional exhaled nitric oxide (FeNO) was measured initially and at 7 days.
RESULTS: FF significantly (p = 0.0009-0.0078) increased methacholine PD20 (provocative dose causing 20% fall in forced expiratory volume in 1 s) at all times. Doubling dose shifts (95% CI) were 1.23 (0.60-1.86), 1.17 (0.68-1.67) and 1.44 (0.93-1.94) after the first, third and seventh dose respectively. FeNO (geometric mean, 95% CI) decreased significantly (p = 0.0049) following FF treatment from 37.9 ppb (23.7-60.5) initially to 22.9 ppb (14.8-35.5) at 7 days. Placebo did not affect methacholine PD20 or FeNO.
CONCLUSION: Single-dose FF 100 mcg decreased methacholine AHR at 24 h without significant further improvement with continued daily use over 7 days. The inhibition in AHR after one week of daily dosing coincided with a significant decrease in FeNO at 7 days. Contrary to past assumptions, the ICS FF appears to rapidly reduce AHR to methacholine.
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