Clara cell protein as a marker of Clara cell damage and bronchoalveolar blood barrier permeability.
(9/1773)
The 16 kDa Clara cell protein (CC16), an abundant component of airway secretions, has recently been proposed in humans as a pulmonary marker measurable not only in bronchoalveolar lavage fluid (BALF) but also in serum. The aim of the present study was to investigate the changes and determinants of CC16 concentrations in these fluids in normal rats and rats with lung injury. Female Sprague-Dawley rats were given a single i.p. injection of arachis oil (n=20) or chemicals in arachis oil (n=10) that mainly damage Clara cells (4-ipomeanol (IPO) 8 mg x kg(-1) and methylcyclopentadienyl manganese tricarbonyl (MMT) 5 mg x kg(-1)) or endothelial cells (alpha-naphthylthiourea (ANTU) 5 mg x kg(-1)). CC16 concentration (mean+/-sD in microg x L(-1)), measured by a sensitive latex immunoassay, was significantly reduced in BALF of all treated groups (IPO 380+/-100; MMT 730+/-200; ANTU 1,070+/-200; controls 1,700+/-470). The same pattern of decrease was observed in the labelling of Clara cells with an anti-CC16 antiserum as well as in the CC16 messenger ribonucleic acid levels assessed by Northern enzyme-linked immunosorbent assay. In serum, by contrast, CC16 was significantly increased in all treated groups (IPO 31+/-7; MMT 22+/-12; ANTU 52+/-24; controls 15+/-6). This rise of CC16 in serum was associated with an elevation of albumin in BALF which is an index of increased bronchoalveolar/blood barrier permeability. In conclusion, lung injury induces a decrease of the 16 kDa Clara cell protein in bronchoalveolar lavage fluid owing to a reduced production by damaged Clara cells, and an increase in serum protein levels resulting from its enhanced leakage across the bronchoalveolar/blood barrier. This study provides new insights into the understanding of the changes of lung secretory proteins in bronchoalveolar lavage fluid and serum. (+info)
Secretory leukocyte proteinase inhibitor is preferentially increased in patients with acute respiratory distress syndrome.
(10/1773)
Inappropriate release of proteases from inflammatory and stromal cells can lead to destruction of the lung parenchyma. Antiproteinases such as alpha-1-proteinase inhibitor (alpha1-Pi), secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (elafin) control excess production of human neutrophil elastase. In the present study, the concentrations of alpha1-Pi, SLPI and elafin found in bronchoalveolar lavage (BAL) fluid from control subjects, patients at risk of developing acute respiratory distress syndrome (ARDS) and patients with established ARDS were determined. Levels of all three inhibitors were raised in patients compared with normal subjects. SLPI was increased in the group of patients who were at risk of ARDS and went on to develop the condition, compared with the "at-risk" group who did not progress to ARDS (p=0.0083). Alpha1-Pi and elafin levels were similar in these two populations. In patients with established ARDS, both alpha1-Pi and SLPI levels were significantly increased, compared to patients at risk of ARDS who did (p=0.0089) or did not (p=0.0003) progress to ARDS. The finding of increased antiproteinases shortly before the development of acute respiratory distress syndrome provide further evidence for enhanced inflammation prior to clinical disease. (+info)
Volumetric capnography in patients with acute lung injury: effects of positive end-expiratory pressure.
(11/1773)
The aim of the study was to analyse the effects of positive end-expiratory pressure (PEEP) on volumetric capnography and respiratory system mechanics in mechanically ventilated patients. Eight normal subjects (control group), nine patients with moderate acute lung injury (ALI group) and eight patients with acute respiratory distress syndrome (ARDS group) were studied. Respiratory system mechanics, alveolar ejection volume as a fraction of tidal volume (VAE/VT), phase III slopes of expired CO2 beyond VAE and Bohr's dead space (VD/VT(Bohr)) at different levels of PEEP were measured. No differences in respiratory system resistances were found between the ALI and ARDS groups. VD/VT(Bohr) and expired CO2 slope beyond VAE were higher in ALI patients (0.52+/-0.01 and 13.9+/-0.7 mmHg x L(-1), respectively) compared with control patients (0.46+/-0.01 and 7.7+/-0.4 mmHg x L(-1), p<0.01, respectively) and in ARDS patients (0.61+/-0.02 and 24.9+/-1.6 mmHg x L(-1), p<0.01, respectively) compared with ALI patients. VAE/VT differed similarly (0.6+/-0.01 in control group, 0.43+/-0.01 in ALI group and 0.31+/-0.01 in ARDS group, p<0.01). PEEP had no effect on VAE/VT, expired CO2 slope beyond VAE and VD/VT(Bohr) in any group. A significant correlation (p<0.01) was found between VAE/VT and expired CO2 slope beyond VAE and lung injury score at zero PEEP. Indices of volumetric capnography are affected by the severity of the lung injury, but are unmodified by the application of positive end-expiratory pressure. (+info)
Effects of exogenous surfactant on acute lung injury induced by intratracheal instillation of infant formula or human breast milk in rabbits.
(12/1773)
BACKGROUND: An animal experimental model of acute lung injury after intratracheal instillation of acidified milk products has been recently demonstrated. Exogenous administration of surfactant has proved to be successful treatment for acute lung injury induced by many causes including acid aspiration. The authors conducted this study to investigate whether exogenous surfactant can reduce the magnitude of lung damage induced in rabbits by acidified milk products. METHODS: The lung injury was induced by intratracheal instillation of acidified human breast milk or acidified infant formula (0.8 ml/kg, pH 1.8). Thirty minutes after the insult, some animals were treated with intratracheal surfactant 100 or 200 mg/kg. Lung compliance and alveolar-to-arterial oxygen gradient were recorded during ventilation. After 4 or 12 h, the lungs were excised to determine physiologic and histologic lung damage. Albumin, interleukin-8, and eicosanoids in bronchoalveolar lavage fluid and superoxide production by neutrophils were measured. RESULTS: The acidified milk products increased A-aD(O2)(550+/-52 and 156+/-28 mmHg; mean+/-SD at 4 h in saline solution and infant formula groups, respectively), lung wet-to-dry weight ratio (6.6+/-0.5 and 5.6 +/- 0.2), %neutrophils in bronchoalveolar lavage fluid (84+/-4% and 8+/-20%), and decreased compliance (0.76+/-0.09 and 1.90+/-0.11 ml/cm H2O). Surfactant improved these variables in a dose-dependent manner (A-aDO2 = 363+/-50 and 237+/-55 mmHg in 100-mg/kg and 200-mg/kg surfactant groups). Surfactant attenuated extensive histologic changes caused by the milk products. Superoxide production was less in rabbits receiving surfactant than in those not receiving it. CONCLUSION: Exogenous surfactant improved physiologic, histologic, and biochemical lung injury induced by acidified milk products in a dose-dependent manner. The effectiveness of surfactant may be caused, in part, by inhibition of neutrophils' sequestration and activation. These data indicate that intratracheal instillation of surfactant may be a promising therapeutic modality in acute lung injury resulting from aspiration of acidified milk products. (+info)
Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS).
(13/1773)
The goals of this study were to determine whether the Fas-dependent apoptosis pathway is active in the lungs of patients with the acute respiratory distress syndrome (ARDS), and whether this pathway can contribute to lung epithelial injury. We found that soluble Fas ligand (sFasL) is present in bronchoalveolar lavage (BAL) fluid of patients before and after the onset of ARDS. The BAL concentration of sFasL at the onset of ARDS was significantly higher in patients who died. BAL from patients with ARDS induced apoptosis of distal lung epithelial cells, which express Fas, and this effect was inhibited by blocking the Fas/FasL system using three different strategies: anti-FasL mAb, anti-Fas mAb, and a Fas-Ig fusion protein. In contrast, BAL from patients at risk for ARDS had no effect on distal lung epithelial cell apoptosis. These data indicate that sFasL is released in the airspaces of patients with acute lung injury and suggest that activation of the Fas/FasL system contributes to the severe epithelial damage that occurs in ARDS. These data provide the first evidence that FasL can be released as a biologically active, death-inducing mediator capable of inducing apoptosis of cells of the distal pulmonary epithelium during acute lung injury. (+info)
Vaporized perfluorocarbon improves oxygenation and pulmonary function in an ovine model of acute respiratory distress syndrome.
(14/1773)
BACKGROUND: Perfluorocarbon liquids are being used experimentally and in clinical trials for the treatment of acute lung injury. Their resemblance to inhaled anesthetic agents suggests the possibility of application by vaporization. The authors' aim was to develop the technical means for perfluorocarbon vaporization and to investigate its effects on gas exchange and lung function in an ovine model of oleic acid-induced lung injury. METHODS: Two vaporizers were calibrated for perfluorohexane and connected sequentially in the inspiratory limb of a conventional anesthetic machine. Twenty sheep were ventilated in a volume controlled mode at an inspired oxygen fraction of 1.0. Lung injury was induced by intravenous injection of 0.1 ml oleic acid per kilogram body weight. Ten sheep were treated with vaporized perfluorohexane for 30 min and followed for 2 h; 10 sheep served as controls. Measurements of blood gases and respiratory and hemodynamic parameters were obtained at regular intervals. RESULTS: Vaporization of perfluorohexane significantly increased arterial oxygen tension 30 min after the end of treatment (P < 0.01). At 2 h after treatment the oxygen tension was 376+/-182 mmHg (mean +/- SD). Peak inspiratory pressures (P < 0.01) and compliance (P < 0.01) were significantly reduced from the end of the treatment interval onward. CONCLUSION: Vaporization is a new application technique for perfluorocarbon that significantly improved oxygenation and pulmonary function in oleic acid-induced lung injury. (+info)
Aerosolized endotoxin is immediately bound by pulmonary surfactant protein D in vivo.
(15/1773)
Collectins are carbohydrate binding proteins that are implicated in innate host defense. The lung collectins, surfactant proteins A and D (SP-A and SP-D), bind a variety of pathogens in vitro and influence phagocytosis by alveolar macrophages. In this report we show that SP-D binds endotoxin (lipopolysaccharide, LPS) in vivo in a rat model of acute respiratory distress syndrome (ARDS). Intratracheal aerosolization of LPS in rats resulted in the typical features of human ARDS. Total amounts of SP-D, as well as the carbohydrate binding properties of SP-D were measured in lung lavage as a function of time. The amount of SP-D did not change during 24 h. Interestingly, SP-D in lung lavage isolated from rats during the first 2 h after LPS treatment, was not able to bind to carbohydrate. Further analysis revealed that the carbohydrate binding sites of SP-D were occupied by LPS, suggesting that SP-D is an LPS scavenging molecule in vivo. Electron microscopic analysis indicated that, 1 h after LPS aerosolization, aggregates of SP-D with LPS were found in lysosomal structures in alveolar macrophages. We conclude that the lung collectin SP-D binds inhaled endotoxin in vivo, which may help to protect the lung from endotoxin-induced disease. (+info)
Combining partial liquid ventilation and prone position in experimental acute lung injury.
(16/1773)
BACKGROUND: Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI. METHODS: ALI was induced in 20 medium-sized pigs (29.2+/-2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position. RESULTS: In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone. CONCLUSIONS: The authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium-sized pigs. (+info)