Plasma exudation and asthma

Abstract

Several pieces of evidence support the view that exudation of plasma into the airway wall and into the airway lumen occurs in asthma. Vascular leakage of plasma results from inflammatory mediator-induced separation of endothelial cells in postcapillary venules belonging to the tracheobronchial circulation. Whereas proposed mediators of asthma induce reversible leakage, several antiasthma drugs exhibit antileakage effects in animals and humans. Potential consequences of plasma exudation are many. Mucosal/submucosal edema might contribute to airway hyperresponsiveness. Plasma exudate in the airway lumen in asthma may contribute to sloughing of epithelium, impairment of mucociliary transport, narrowing of small airways, and mucus plug formation. Exuded plasma may cause airway inflammation and constriction because of its content of powerful mediators, and chemoattractant factors and plasma proteins may condition the inflammatory cells abundant in asthmatic airways to release mediators in response to stimuli that otherwise would be innocuous to the cells. It is concluded that inflammatory stimulus-induced increase in macromolecular permeability of the tracheobronchial microvasculature and mucosa may be a significant pathogenetic mechanism in asthma and that the postcapillary venular endothelium and airway epithelium that regulate leakage of plasma are important effector cells in this disease.

Contribution of Plasma‐Derived Molecules to Mucosal Immune Defence, Disease and Repair in the Airways

“…The steroidinduced inhibition of exudation occurred without concomitant reduction of sputum levels of secretory indices [32]. The poor anti-secretory effect of glucocorticosteroids adds to a long list of significant differences between airway secretory and exudative processes, and supports the notion that the (plasma-) exudative response may reflect airway inflammation better than other physiological end-organ responses in the airways [33].…”

“…Thus, ample evidence of plasma exudation, as a characteristic of asthma and rhinitis, has accumulated during several decades (confirming early historical hints of 'plasma, serum, and fibrinoplastic substances' in the lumen of these inflamed airways) [3,4,32]. In the nose, almost any plasma protein occurring in lavage fluids may be a good index of the exudation [5] but, as delineated below, in the bronchi this may not be so.…”

“…Nasal and endobronchial challenge experiments have demonstrated that the allergic human airway mucosa responds to allergen, within a few minutes, with luminal entry of bulk plasma (including a 2 -macroglobulin and fibrinogen) [18,20,32]. Allergen challenge in subjects with allergic asthma produces both immediate and late-phase plasma exudative responses [19,20,51].…”

Role of endogenous nitric oxide in airway microvascular leakage induced by inflammatory mediators

“…Airway plasma leakage is due to endothelial contraction and the resulting enlargement of the gaps in postcapillary venules, as supported by ultrastructural, pathological, and pharmacological studies [1,4]. Thus, NO may be directly involved in the process of airway plasma leakage via endothelial contraction at the leaky site.…”

“…Microvascular leakage of protein-rich plasma is thought to be one of the inflammatory events in airway diseases, such as bronchial asthma [1]. A variety of inflammatory mediators, including histamine, leukotrienes (LTs) and tachykinins, released from inflammatory cells and sensory nerves, are known to cause airway microvascular leakage [2], which may produce airway hyperresponsiveness to nonspecific stimuli via oedema formation in airway mucosa [3].…”