Recent advances in the immunopathogenesis of severe asthma

Regulatory T Cells, a Viable Target Against Airway Allergic Inflammatory Responses in Asthma

“…These pathophysiological changes result in alterations in the composition and structural organization of molecular and cellular components that constitute the airway. As a consequence, the asthmatic patients manifest the presence of airway narrowing and edema, AHR, and mucus hypersecretion, which is relevant to the poor clinical outcomes in asthmatic patients (93).…”

Epithelial regeneration in vivo in pathogenesis of severe asthma

“…Much is to be learned from the expert updates on severe asthma by Al Heialy et al 1 Evidently, bronchial epithelium takes center stage in development of asthma severity. 1 In their inclusive discussion of airway epithelium, Al Heialy et al 1 inserted the following unreferenced sentence: ''Microvascular-epithelial exudation of plasma proteins provides a neutrophil-rich, fibrin-fibronectin net cover over the denuded patches.'' This sentence is almost a verbatim excerpt from recent discussions on plasma exudation focusing on in vivo and ''bedside'' data on asthma.…”

“…Whereas epithelial culture data 1 hardly illustrate ''microvascular-epithelial'' events, the cited in vivo work, in association with the aforementioned sentence, concerns data demonstrating scattered deposition of fibrin in pulmonary parenchyma. 1 However, this event is unrelated to the ''fibrin-fibronectin net cover.'' 2,3 The fibrin-fibronectin net cover is strictly localized to the surface of a denuded epithelial basement membrane (BM).…”

“…4 Thus, the role of plasma exudation in first-line airways' antimicrobial defense has been overlooked, 3,4 and plasma exudation has been unduly interpreted as a sign of epithelial barrier defect. 1 Sputum in patients with severe asthma contains hundreds of Creola bodies, 5 likely reflecting numerous patches of epithelial loss creating hot spots of epithelial regeneration. 2 Experimental in vivo studies indicate that epithelial regeneration alone evokes not only increased plasma exudation and neutrophilia but also eosinophil cytolysis, local hypersecretion as well as smooth muscle and reticular BM remodeling.…”

Reply

“…We appreciate the interest by Persson 1 in our review, and we believe that his correspondence is a valuable addition to understanding the features of epithelial remodeling that we have discussed in our published report. 2 It is with great interest that we read Persson's letter, in which he raised an important aspect of the role of plasma exudation of the airway epithelium to enlighten readers regarding the importance of plasma-derived fibrin-fibronectin gel cover to support epithelial regeneration and reestablish epithelial integrity. 1 Plasma exudation of the airway mucosa is an often underestimated physiologic phenomenon in both health and disease.…”