Wallin Annika, Sue-Chu Malcolm, Bjermer Leif, Ward Jonathan, Sandström Thomas, Lindberg Anne, Lundbäck Bo, Djukanović Ratko, Holgate Stephen, Wilson Susan
Department of Respiratory Medicine and Allergy, University Hospital, Umeå.
J Allergy Clin Immunol. 2003 Jul;112(1):72-8. doi: 10.1067/mai.2003.1518.
The clinical benefit of combining long-acting beta(2)-agonists with inhaled corticosteroids rather than doubling the dose of corticosteroid has been well-documented. However, there are concerns that this might result in a masking of underlying airway inflammation.
The aim of this study was to test the hypothesis that the addition of the long-acting beta(2)-agonist salmeterol (SALM) to a low dose of the inhaled corticosteroid fluticasone propionate (FP) has a steroid-sparing effect and does not result in a worsening of bronchial inflammation compared to doubling the dose of inhaled corticosteroid.
Fifty-six asthmatic subjects, previously not well-controlled on inhaled corticosteroids, were randomized to receive 3 months of treatment with inhaled FP 500 microg twice a day (FP 1000) or FP 200 microg twice a day plus SALM 50 microg twice a day (FP 400 + SALM). Fluticasone propionate 200 microg twice a day served as the control (FP400). Bronchial mucosal biopsy specimens, bronchial washings (BW), and bronchoalveolar lavage were obtained before and after treatment. The primary end points for the study were submucosal mast cell and eosinophil counts.
There was a significant improvement in FEV(1) in the FP400 + SALM group compared to both the FP400 and FP1000 groups. This was accompanied by a significant improvement in peak expiratory flow in the FP400 + SALM group in both the morning and evening compared to the FP1000 group. There were no significant between treatment differences in the change in the number of submucosal mast cells or eosinophils. However, in the FP400 + SALM group there was a significant decrease in submucosal mast cells after 12 weeks of treatment. The addition of SALM to FP was not associated with any increases in airway inflammation in the biopsy specimens, bronchoalveolar lavage, or bronchial washings.
These findings confirm that addition of SALM to FP has clinical benefits but does not mask or exacerbate airway inflammation and suggest that long-acting beta(2)-adrenoceptor agonists might influence mast cell numbers.
长效β2受体激动剂与吸入性糖皮质激素联合使用，而非单纯加倍糖皮质激素剂量，其临床益处已有充分记录。然而，有人担心这可能会掩盖潜在的气道炎症。
本研究旨在验证以下假设：与加倍吸入性糖皮质激素剂量相比，在低剂量吸入性糖皮质激素丙酸氟替卡松（FP）中添加长效β2受体激动剂沙美特罗（SALM）具有糖皮质激素节省效应，且不会导致支气管炎症恶化。
56名此前吸入糖皮质激素治疗效果不佳的哮喘患者被随机分为两组，分别接受为期3个月的治疗：一组每天两次吸入500微克FP（FP 1000）；另一组每天两次吸入200微克FP加每天两次吸入50微克SALM（FP 400 + SALM）。每天两次吸入200微克丙酸氟替卡松作为对照组（FP400）。在治疗前后获取支气管黏膜活检标本、支气管灌洗（BW）和支气管肺泡灌洗样本。该研究的主要终点是黏膜下肥大细胞和嗜酸性粒细胞计数。
与FP400组和FP1000组相比，FP400 + SALM组的第一秒用力呼气容积（FEV1）有显著改善。与FP1000组相比，FP400 + SALM组早晚的呼气峰值流速也有显著改善。治疗组间黏膜下肥大细胞或嗜酸性粒细胞数量变化无显著差异。然而，在FP400 + SALM组中，治疗12周后黏膜下肥大细胞数量显著减少。在活检标本、支气管肺泡灌洗或支气管灌洗中，FP添加SALM与气道炎症增加无关。
这些发现证实，FP添加SALM具有临床益处，但不会掩盖或加重气道炎症，并表明长效β2肾上腺素能受体激动剂可能会影响肥大细胞数量。
