Polosa R, Renaud L, Cacciola R, Prosperini G, Crimi N, Djukanovic R
Istituto Malattie Apparato Respiratorio, University of Catania, Italy.
Eur Respir J. 1998 Sep;12(3):551-6. doi: 10.1183/09031936.98.12030551.
Hyperresponsiveness of the airways to various spasmogenic stimuli is a characteristic feature of bronchial asthma. However, the association between the different stimuli to which asthmatic airways are hyperresponsive and airways inflammation is not completely understood. We have investigated the relationship between airway inflammation and airway hyperresponsiveness in asthma, as assessed by bronchoprovocation tests to methacholine and bradykinin, two well defined bronchoconstrictor agonists. Sputum induction by hypertonic saline and methacholine and bradykinin challenges were performed in 14 nonsmoking subjects with mild-to-moderate asthma. Airway responsiveness to either agonist did not correlate with sputum neutrophils, lymphocytes, and macrophages. Whilst the absolute number of eosinophilia failed to be significantly related to methacholine responsiveness (r=-0.47; p=0.09), it correlated markedly and significantly with provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (r=0.72; p<0.01). When expressed as % of total cell counts, sputum eosinophils correlated with both types of responsiveness (r=-056; p=0.04 and r=-0.76, p<0.001, respectively). Although the concentration of eosinophil cationic protein (ECP) in the sputum correlated with the absolute numbers of eosinophils (r=0.62; p<0.02), no correlation was found between ECP levels and the airway responsiveness to any of the agonists tested. In subjects with mild-to-moderate asthma, airway responsiveness to bradykinin is more strongly associated with the magnitude of eosinophilic inflammation in the airways than methacholine. This finding underlines the selectivity of diverse agonists in assessing airway hyperresponsiveness and cellular inflammation in asthma.
气道对各种致痉刺激的高反应性是支气管哮喘的一个特征。然而,哮喘气道对其产生高反应的不同刺激与气道炎症之间的关联尚未完全明确。我们通过对乙酰甲胆碱和缓激肽这两种明确的支气管收缩激动剂进行支气管激发试验,研究了哮喘患者气道炎症与气道高反应性之间的关系。对14名轻度至中度哮喘的非吸烟受试者进行了高渗盐水诱导痰液以及乙酰甲胆碱和缓激肽激发试验。气道对任何一种激动剂的反应性与痰液中的中性粒细胞、淋巴细胞和巨噬细胞均无相关性。虽然嗜酸性粒细胞的绝对数量与乙酰甲胆碱反应性无显著相关性(r = -0.47;p = 0.09),但它与导致一秒用力呼气量下降20%的乙酰甲胆碱激发浓度显著相关(r = 0.72;p < 0.01)。当以占总细胞计数的百分比表示时,痰液嗜酸性粒细胞与两种反应性均相关(分别为r = -0.56;p = 0.04和r = -0.76,p < 0.001)。尽管痰液中嗜酸性粒细胞阳离子蛋白(ECP)的浓度与嗜酸性粒细胞的绝对数量相关(r = 0.62;p < 0.02),但未发现ECP水平与气道对任何一种受试激动剂的反应性之间存在相关性。在轻度至中度哮喘患者中,气道对缓激肽的反应性比乙酰甲胆碱更强烈地与气道嗜酸性炎症程度相关。这一发现强调了不同激动剂在评估哮喘气道高反应性和细胞炎症方面的选择性。