Airway obstruction, and in the most extreme case, airway closure, may be effected by two distinct but related processes: constriction of airway smooth muscle and narrowing of the lumen due to liquid. In addition to narrowing of the lumen, contraction of airway smooth muscle produces epithelial projections which invade the luminal space. These epithelial ridges form interstices that are a locus for collection of liquid. Together these two processes represent the primary pathobiology of acute obstructive airway diseases. These process may act in concert to amplify the obstructive response that would result from the individual effect each. Although much is known about the role of smooth muscle in airway constriction, little is known about the airway liquid lining. In particular, the state of hydration of the normal airway, the interfacial tension between luminal air and liquid, that factors that regulate liquid layer thickness, regulate liquid mobility or predispose the airway to closure are not known. These questions bear on asthma as well as neonatal and adult respiratory distress syndrome. Furthermore, the airway liquid layer serves both to protect the epithelium from direct contact with airborne irritants a to provide a mechanism for clearance from the lung. The factors that determine the thickness and mobility of this liquid layer provide critical questions for which only minimal understanding exists. We propose to use theoretical methods, physical models and animal models to study airway luminal liquid and the consequences of its collection and movement. We will develop theoretical models predicting the sites of airway liquid collection and factors driving airway liquid movement. We will test these theories in physical models. We will also induce various forms of bronchoconstriction in animals, and image the airways using low-temperature scanning electron microscopy (LTSEM) to determine the amount and locus of liquid collection. The animals experiments will provide vigorous test of our theoretical constructs.
| Yager, D; Martins, M A; Feldman, H et al. (1996) Acute histamine-induced flux of airway liquid: role of neuropeptides. J Appl Physiol 80:1285-95 |
| Yager, D; Kamm, R D; Drazen, J M (1995) Airway wall liquid. Sources and role as an amplifier of bronchoconstriction. Chest 107:105S-110S |
| Yager, D; Cloutier, T; Feldman, H et al. (1994) Airway surface liquid thickness as a function of lung volume in small airways of the guinea pig. J Appl Physiol 77:2333-40 |
| Otis Jr, D R; Ingenito, E P; Kamm, R D et al. (1994) Dynamic surface tension of surfactant TA: experiments and theory. J Appl Physiol 77:2681-8 |
| Espinosa, F F; Shapiro, A H; Fredberg, J J et al. (1993) Spreading of exogenous surfactant in an airway. J Appl Physiol 75:2028-39 |
| Otis Jr, D R; Johnson, M; Pedley, T J et al. (1993) Role of pulmonary surfactant in airway closure: a computational study. J Appl Physiol 75:1323-33 |
| McCray Jr, P B; Bettencourt, J D; Bastacky, J (1992) Secretion of lung fluid by the developing fetal rat alveolar epithelium in organ culture. Am J Respir Cell Mol Biol 6:609-16 |
