Vignola A Maurizio
Institute of Respiratory Disease, University of Palermo and IBIM, CNR, Italy.
Drugs. 2003;63 Suppl 2:35-51. doi: 10.2165/00003495-200363002-00004.
Chronic inflammation and smooth muscle dysfunction are consistent features of asthma, and are responsible for disease progression and airway remodelling. The development of chronic airway inflammation depends upon the recruitment and activation of inflammatory cells and the subsequent release of inflammatory mediators, including cytokines. Cellular and histological evaluation of drugs with anti-inflammatory activity, such as inhaled corticosteroids (ICSs), is achieved by analysing samples of lung tissue or biological fluids, obtained by techniques such as bronchial biopsy, bronchoalveolar lavage and sputum induction. These provide valuable information on the inflammatory processes occurring in the lung, although not all are equal in value. The beneficial effects of ICSs in asthma treatment are a consequence of their potent and broad anti-inflammatory properties. Furthermore, there have been promising results indicating that ICSs can reverse some of the structural changes that contribute to airway remodelling. Long-acting beta2-agonists (LABAs) added to ICSs provide greater clinical efficacy than ICSs alone, suggesting the possibility of complementary activity on the pathophysiological mechanisms of asthma: inflammation and smooth muscle dysfunction. Leukotrienes play a part in the pathogenesis of asthma. Leukotriene receptor antagonists (LTRAs) directly inhibit bronchoconstriction and may have some anti-inflammatory effects, although the extent to which inhibiting one set of inflammatory mediators attenuates the inflammatory response is questionable. In concert with their effect on a broad variety of inflammatory mediators and cells, treatment with ICSs (including ICSs and LABAs) results in superior control of the pathophysiology of asthma and superior clinical efficacy as assessed by the greater improvements in pulmonary function and overall control of asthma compared with LTRAs.
慢性炎症和平滑肌功能障碍是哮喘的常见特征，与疾病进展和气道重塑有关。慢性气道炎症的发展取决于炎症细胞的募集和激活以及随后炎症介质（包括细胞因子）的释放。对具有抗炎活性的药物（如吸入性糖皮质激素）进行细胞和组织学评估，是通过分析肺组织样本或生物体液来实现的，这些样本通过支气管活检、支气管肺泡灌洗和痰液诱导等技术获取。这些方法能提供有关肺部炎症过程的宝贵信息，尽管其价值不尽相同。吸入性糖皮质激素在哮喘治疗中的有益作用源于其强大而广泛的抗炎特性。此外，有一些令人鼓舞的结果表明，吸入性糖皮质激素可以逆转一些导致气道重塑的结构变化。在吸入性糖皮质激素基础上加用长效β2受体激动剂比单用吸入性糖皮质激素具有更高的临床疗效，这提示两者在哮喘病理生理机制（炎症和平滑肌功能障碍）上可能具有互补作用。白三烯在哮喘发病机制中起作用。白三烯受体拮抗剂可直接抑制支气管收缩，可能具有一定的抗炎作用，尽管抑制一组炎症介质对减轻炎症反应的程度尚存在疑问。与它们对多种炎症介质和细胞的作用一致，吸入性糖皮质激素（包括吸入性糖皮质激素和长效β2受体激动剂联合使用）治疗可更好地控制哮喘病理生理过程，与白三烯受体拮抗剂相比，在肺功能改善和哮喘总体控制方面有更大提升，从而具有更高的临床疗效。
