Airway Blood Flow Changes and Airway Obstruction Following Lung Injury

edema so severe in fire victims who had sustained smoke inhalation injury that foam was coming out of their mouths. These investigators had to place the patients on a ventilator with positive end expiratory pressure to reduce the edema. To study this phenomenon in greater detail, we developed a model of inhalation injury in sheep (Traber et al., 1985, 1986). As was the case in humans, the sheep produced foam from their airway about 8h after smoke inhalation (Herndon et al., 1984). As we began to study this phenomenon, we discovered that the foam coming from the patient’s mouth was not pulmonary edema but an exudate from the airway. This material flowed into the airway at a very rapid rate and contained neutrophils, mucus, and free epithelial cells (Herndon et al., 1984). The exudate contained protein in concentrations to suggest that its formation was associated with an increase in vascular permeability (Barrow et al., 1990). We discovered that with smoke inhalation there was also sloughing of the airway epithelium (Abdi et al., 1990a). In this case the columnar epithelial cells were free in the exudative material. Airway hyperemia and edema have been used to diagnose inhalation injury (Pruitt et al., 1990). It was found that there was an almost 20-fold increase in bronchial blood flow within 30min of smoke inhalation (Abdi et al., 1990b), and that this increase in airway blood flow was sustained for several days (Stothert et al., 1990). Thus the exudative materials were formed as a result of increases in microvascular pressure, permeability, and surface area perfused in the bronchial circulation. Perhaps the most serious problem that developed as a result of the formation of the exudate was that the material clotted to form airway casts (Herndon et al., 1984; Pruitt et al., 1970). These casts can totally obstruct the airway (Barrow et al., 1990; Pruitt et al., 1970). Cast formation following inhalation injury has been reported (Nakae et al., 2001; Pietak & Delahaye, 1976; Pruitt et al., 1970). Perhaps more importantly, it is reported with other disease entities of the airway as well (Costello et al., 2002; Seear et al., 1997; Kuyper et al., 2003). In consideration of the moribund nature of these casts, stratagems were developed to prevent the formation of casts and to aggressively remove them. We tested the use of nebulized heparin in our model and found that it was effective in reducing lung injury (Brown et al., 1988; Kimura et al., 1988). This has led to clinical use of nebulized heparin in the treatment of burned patients with inhalation injury (Desai et al., 1998). In addition, considering that this airway injury might play an important role in the parenchymal damage, we determined the role of the bronchial circulation in the pulmonary injury (Abdi et al., 1991; Sakurai et al., 1998). We discovered that limiting the bronchial circulation markedly reduced the parenchymal damage seen with smoke inhalation. This work was later confirmed by the Hale’s group (Efimova et al., 2001; Hales et al., 1989). More recently we have taken another look at this airway phenomenon as a result of the recent NIH sponsored multicenter study relating increased ventilatory pressures and volumes to lung injury (Authors, 2000). Our Pathology group developed a technique for quantitating the degree of airway obstruction in the sheep (Cox et al., 2003). Using this technique, in a model of burn and inhalation injury, they were able to determine that by 24h post injury, the bronchi were obstructed by 34 ± 12% (mean ± SD), bronchioles by 6.4 ± 3.9% and terminal bronchi by 0.1 ± 1.9%. As time post injury SHORT REVIEW