Rubin Bruce K
Department of Pediatrics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1081, USA.
Respir Care. 2007 Jul;52(7):859-65.
In health, the airways are lined by a layer of protective mucus gel that sits atop a watery periciliary fluid. Mucus is an adhesive, viscoelastic gel, the biophysical properties of which are largely determined by entanglements of long polymeric gel-forming mucins, MUC5AC and MUC5B. This layer entraps and clears bacteria and inhibits bacterial growth and biofilm formation. It also protects the airway from inhaled irritants and from fluid loss. In diseases such as cystic fibrosis there is almost no mucin (and thus no mucus) in the airway; secretions consist of inflammatory-cell derived DNA and filamentous actin polymers, which is similar to pus. Retention of this airway pus leads to ongoing inflammation and airway damage. Mucoactive medications include expectorants, mucolytics, and mucokinetic drugs. Expectorants are meant to increase the volume of airway water or secretion in order to increase the effectiveness of cough. Although expectorants, such as guaifenesin (eg, Robatussin or Mucinex), are sold over the counter, there is no evidence that they are effective for the therapy of any form of lung disease, and when administered in combination with a cough suppressant such as dextromethorphan (the "DM" in some medication names) there is a potential risk of increased airway obstruction. Hyperosmolar saline and mannitol powder are now being used as expectorants in cystic fibrosis. Mucolytics that depolymerize mucin, such as N-acetylcysteine, have no proven benefit and carry a risk of epithelial damage when administered via aerosol. DNA-active medications such as dornase alfa (Pulmozyme) and potentially actin-depolymerizing drugs such as thymosin beta(4) may be of value in helping to break down airway pus. Mucokinetic agents can increase the effectiveness of cough, either by increasing expiratory cough airflow or by unsticking highly adhesive secretions from the airway walls. Aerosol surfactant is one of the most promising of this class of medications.
在健康状态下,气道内衬有一层保护性黏液凝胶,其位于水样的纤毛周围液之上。黏液是一种具有黏性的黏弹性凝胶,其生物物理特性在很大程度上由长链聚合凝胶形成黏蛋白MUC5AC和MUC5B的缠结所决定。这一层黏液能捕获并清除细菌,抑制细菌生长和生物膜形成。它还能保护气道免受吸入性刺激物的侵害,并防止液体流失。在诸如囊性纤维化等疾病中,气道中几乎没有黏蛋白(因此也没有黏液);分泌物由炎症细胞衍生的DNA和丝状肌动蛋白聚合物组成,类似于脓液。气道内这种脓液的潴留会导致持续的炎症和气道损伤。黏液活性药物包括祛痰剂、黏液溶解剂和促黏液排出药物。祛痰剂旨在增加气道内的水分或分泌物量,以提高咳嗽的效果。尽管祛痰剂,如愈创甘油醚(如罗必塔斯或沐舒坦)可在柜台购买,但没有证据表明它们对任何形式的肺部疾病治疗有效,并且当与止咳药如右美沙芬(某些药物名称中的“DM”)联合使用时,存在气道阻塞加重的潜在风险。高渗盐水和甘露醇粉目前在囊性纤维化中用作祛痰剂。使黏蛋白解聚的黏液溶解剂,如N-乙酰半胱氨酸,没有已证实的益处,通过气雾剂给药时存在上皮损伤的风险。DNA活性药物如重组人脱氧核糖核酸酶(普米克令舒)和潜在的肌动蛋白解聚药物如胸腺素β4可能有助于分解气道脓液。促黏液排出剂可以通过增加呼气咳嗽气流或使高度黏附的分泌物从气道壁上松解来提高咳嗽的效果。气雾剂表面活性剂是这类药物中最有前景的药物之一。