Cataldi M, Sblendorio V, Leo A, Piazza O
Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University of Naples, Via Pansini 5, 80131 Napoli, Italy.
Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University of Naples, Via Pansini 5, 80131 Napoli, Italy.
Pulm Pharmacol Ther. 2014 Aug;28(2):98-108. doi: 10.1016/j.pupt.2013.11.002. Epub 2013 Nov 16.
Biofilms are a key factor in the development of both acute and chronic airway infections. Their relevance is well established in ventilator associated pneumonia, one of the most severe complications in critically ill patients, and in cystic fibrosis, the most common lethal genetic disease in Caucasians. Accumulating evidence suggests that biofilms could have also a role in chronic obstructive pulmonary disease and their involvement in bronchiectasis has been proposed as well. When they grow in biofilms, microorganisms become multidrug-resistant. Therefore the treatment of biofilm-dependent airway infections is problematic. Indeed, it still largely based on measures aiming to prevent the formation of biofilms or remove them once that they are formed. Here we review recent evidence suggesting that the mucokinetic drug ambroxol has specific anti-biofilm properties. We also discuss how additional pharmacological properties of this drug could be beneficial in biofilm-dependent airway infections. Specifically, we review the evidence showing that: 1-ambroxol exerts anti-inflammatory effects by inhibiting at multiple levels the activity of neutrophils, and 2-it improves mucociliary clearance by interfering with the activity of airway epithelium ion channels and transporters including sodium/bicarbonate and sodium/potassium/chloride cotransporters, cystic fibrosis transmembrane conductance regulator and aquaporins. As a whole, the data that we review here suggest that ambroxol could be helpful in biofilm-dependent airway infections. However, considering the limited clinical evidence available up to date, further clinical studies are required to support the use of ambroxol in these diseases.
生物膜是急性和慢性气道感染发展的关键因素。其相关性在呼吸机相关性肺炎（危重症患者最严重的并发症之一）以及囊性纤维化（白种人中最常见的致命性遗传病）中已得到充分证实。越来越多的证据表明，生物膜在慢性阻塞性肺疾病中也可能起作用，并且有人提出其与支气管扩张有关。当微生物以生物膜形式生长时，它们会产生多重耐药性。因此，治疗依赖生物膜的气道感染存在问题。实际上，目前治疗仍主要基于旨在防止生物膜形成或在其形成后将其清除的措施。在此，我们综述了近期的证据，表明黏液促动药物氨溴索具有特定的抗生物膜特性。我们还讨论了该药物的其他药理特性如何有益于依赖生物膜的气道感染。具体而言，我们综述了以下证据：1. 氨溴索通过在多个层面抑制中性粒细胞的活性发挥抗炎作用；2. 它通过干扰气道上皮离子通道和转运体（包括钠/碳酸氢根和钠/钾/氯共转运体、囊性纤维化跨膜传导调节因子和水通道蛋白）的活性来改善黏液纤毛清除功能。总体而言，我们在此综述的数据表明氨溴索可能有助于治疗依赖生物膜的气道感染。然而，鉴于目前可用的临床证据有限，需要进一步的临床研究来支持在这些疾病中使用氨溴索。
