Using an E-Health Application for Post-operative Monitoring After Inguinal Hernia Repair: A Feasibility Study.

BACKGROUND: E-Health care is already well established in some (non-) surgical specialties and is considered as a means of improving patient-centred care. Considering the demand of remote health care changes, especially in the COVID-19 pandemic, it is essential to investigate the feasibility of e-Health care within one of the most performed surgery procedures: inguinal hernia repair. METHODS: A total of 60 patients used the e-Health application in this study compliant. Primary objectives were to investigate the accuracy of the "deviating post-operative course" alerting by the e-Health application. Secondary objectives included patient perspective and e-Health costs analysis. RESULTS: Forty-four patients reported no deviation in the post-operative course using the e-Health application of which 93.2% (n = 41) was in concordance with the findings during standard follow-up. Within 16 patients reporting a deviating post-operative course, a true complication was found in 25% (n = 4). Based on in-hospital costs, a hypothetical e-Health follow-up scenario was more expensive (€59.5 per patient) than current standard follow-up care (€28.2 per patient). Usage of the e-Health application showed a high perceived overall patient satisfaction: 4.2 (on a Likert-scale of 1-5). CONCLUSION: An e-Health application is a promising tool for identifying patients who require in-person or phone follow-up assessment. Patients' perspectives surveys revealed high potential and willingness of using this application. A hypothetical e-Health follow-up scenario showed to be more expensive compared to current standard follow-up. If the identified (dis)advantages can be improved, e-Health follow-up care appears to be promising in terms of safety and feasibility. Future studies can leverage on this study and further investigate the use of e-Health within the field of general surgery.

Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?

BACKGROUND: Neuroinflammation in utero may contribute to brain injury resulting in life-long neurological disabilities. The pivotal role of the efferent cholinergic anti-inflammatory pathway (CAP) in controlling inflammation, e.g., by inhibiting the HMGB1 release, via the macrophages' α7 nicotinic acetylcholine receptor (α7nAChR) has been described in adults, but its importance in the fetus is unknown. Moreover, it is unknown whether CAP may also exert anti-inflammatory effects on the brain via the anatomically predominant afferent component of the vagus nerve. METHODS: We measured microglial activation in the ovine fetal brain near term 24 h after the umbilical cord occlusions mimicking human labor versus controls (no occlusions) by quantifying HMGB1 nucleus-to-cytosol translocation in the Iba1+ and α7nAChR+ microglia. Based on multiple clinical studies in adults and our own work in fetal autonomic nervous system, we gauged the degree of CAP activity in vivo using heart rate variability measure RMSSD that reflects fluctuations in vagus nerve activity. RESULTS: RMSSD correlated to corresponding plasma IL-1ß levels at R = 0.57 (p = 0.02, n = 17) and to white matter microglia cell counts at R = -0.89 (p = 0.03). The insult increased the HMGB1 translocation in α7nAChR+ microglia in a brain region-dependent manner (p < 0.001). In parallel, RMSSD at 1 h post insult correlated with cytosolic HMGB1 of thalamic microglia (R = -0.94, p = 0.005), and RMSSD at pH nadir correlated with microglial α7nAChR in the white matter (R = 0.83, p = 0.04). Overall, higher RMSSD values correlated with lower HMGB1 translocation and higher α7nAChR intensity per area in a brain region-specific manner. CONCLUSIONS: Afferent fetal CAP may translate increased vagal cholinergic signaling into suppression of cerebral inflammation in response to near-term hypoxic acidemia as might occur during labor. Our findings suggest a new control mechanism of fetal neuroinflammation via the vagus nerve, providing novel possibilities for its non-invasive monitoring in utero and for targeted treatment.

Lung-derived mediators induce cytokine production in downstream organs via an NF-κB-dependent mechanism.

In the setting of acute lung injury, levels of circulating inflammatory mediators have been correlated with adverse outcomes. Previous studies have demonstrated that injured, mechanically ventilated lungs represent the origin of the host inflammatory response; however, mechanisms which perpetuate systemic inflammation remain uncharacterized. We hypothesized that lung-derived mediators generated by mechanical ventilation (MV) are amplified by peripheral organs in a "feed forward" mechanism of systemic inflammation. Herein, lung-derived mediators were collected from 129X1/SVJ mice after 2 hours of MV while connected to the isolated perfused mouse lung model setup. Exposure of liver endothelial cells to lung-derived mediators resulted in a significant increase in G-CSF, IL-6, CXCL-1, CXCL-2, and MCP-1 production compared to noncirculated control perfusate media (P < 0.05). Furthermore, inhibition of the NF-κB pathway significantly mitigated this response. Changes in gene transcription were confirmed using qPCR for IL-6, CXCL-1, and CXCL-2. Additionally, liver tissue obtained from mice subjected to 2 hours of in vivo MV demonstrated significant increases in hepatic gene transcription of IL-6, CXCL-1, and CXCL-2 compared to nonventilated controls. Collectively, this data demonstrates that lung-derived mediators, generated in the setting of MV, are amplified by downstream organs in a feed forward mechanism of systemic inflammation.

Mediators released from LPS-challenged lungs induce inflammatory responses in liver vascular endothelial cells and neutrophilic leukocytes.

The systemic inflammatory response plays an important role in the progression of acute lung injury (ALI) to multiple organ dysfunction syndrome (MODS). However, the role of lung-derived inflammatory mediators in induction of the inflammatory response in remote organs is poorly understood. To address the above, we investigated the effects of lung inflammation on induction of inflammatory response(s) in the liver in vitro. Inflammation in mouse lungs was induced by intranasal administration of lipopolysaccharide (LPS; 1 mg/ml) followed by mechanical ventilation using the isolated perfused mouse lung method to obtain and characterize lung perfusate from the pulmonary circulation. LPS administration to mouse lungs resulted in an increased release of inflammation-relevant cytokines and chemokines into the perfusate (Luminex assay) compared with the saline-controls. Subsequently, primary mouse liver vascular endothelial cells (LVEC) or mouse polymorphonuclear leukocytes (PMN) in vitro were stimulated with the perfusate obtained from saline- or LPS-challenged lungs and assessed for various inflammation-relevant end points. The obtained results indicate that stimulation of LVEC with perfusate obtained from LPS-challenged lungs results in 1) reactive oxygen species (ROS) production; 2) activation of NF-kappaB; and 3) expression of E-selectin, ICAM-1, and VCAM-1 and a subsequent increase in PMN rolling and adhesion to LVEC. In addition, perfusate from LPS-challenged lung induced activation of PMN with respect to increased ROS production and upregulation of cell surface levels of adhesion molecules MAC-1 and VLA-4. Heat-inactivation of the perfusate obtained from LPS-challenged lungs was very effective in suppressing increased proadhesive phenotype (i.e., E-selectin and ICAM-1 expression) in LVEC, whereas targeted inhibition (immunoneutralization) of TNF-alpha and/or IL-6 in LPS-lung perfusate had no effect. Taken together, these findings indicate that multiple proinflammatory mediators (proteinaceous in nature) released from inflamed lungs act synergistically to induce systemic activation of circulating PMN and promote inflammatory responses in liver vascular endothelial cells.

Quantifying lung morphology with respiratory-gated micro-CT in a murine model of emphysema.

Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography.

Lung morphology and function in human subjects can be monitored with computed tomography (CT). Because many human respiratory diseases are routinely modeled in rodents, a means of monitoring the changes in the structure and function of the rodent lung is desired. High-resolution images of the rodent lung can be attained with specialized micro-CT equipment, which provides a means of monitoring rodent models of lung disease noninvasively with a clinically relevant method. Previous studies have shown respiratory-gated images of intubated and respirated mice. Although the image quality and resolution are sufficient in these studies to make quantitative measurements, these measurements of lung structure will depend on the settings of the ventilator and not on the respiratory mechanics of the individual animals. In addition, intubation and ventilation can have unnatural effects on the respiratory dynamics of the animal, because the airway pressure, tidal volume, and respiratory rate are selected by the operator. In these experiments, important information about the symptoms of the respiratory disease being studied may be missed because the respiration is forced to conform to the ventilator settings. In this study, we implement a method of respiratory-gated micro-CT for use with anesthetized free-breathing rodents. From the micro-CT images, quantitative analysis of the structure of the lungs of healthy unconscious mice was performed to obtain airway diameters, lung and airway volumes, and CT densities at end expiration and during inspiration. Because the animals were free breathing, we were able to calculate tidal volume (0.09 +/- 0.03 ml) and functional residual capacity (0.16 +/- 0.03 ml).

Rat liver and lung mitochondria do not incorporate radioactivity from glycerol-3-phosphate or CDP-choline into glycero-3-phosphocholine.

The proposed formation of glycero-3-phosphocholine (GPC) from glycerol-3-phosphate (GP) and CDP-choline catalysed by the enzyme GPC-synthetase has been examined in liver and lung subcellular fractions. Previous observations on the incorporation of radioactive GP into the GPC-spot on paper chromatograms have been interpreted as evidence for the GPC-dependent synthesis of phosphatidylcholine. Although we could reproduce this incorporation of GP, we could not detect any incorporation of radioactive CDP-choline into the GPC-spot using the same paper chromatographic system. TLC separation of the substrate and products showed no detectable formation of GPC with either radioactive substrate. These results strongly suggest that the previously reported formation of GPC in liver and lung was due to an inaccurate identification of the true radioactive products. We demonstrate that the major radioactive product formed in liver mitochondria is glucose. A small amount of radioactive glycerol was also detected. Lung mitochondria incorporate radioactive GP into glycerol and into another unidentified compound or compounds. It is concluded that the occurrence of the GPC dependent formation of phosphatidylcholine is unlikely.

Dissociation of surfactant protein B from canine surfactant large aggregates during formation of small surfactant aggregates by in vitro surface area cycling.

Pulmonary surfactant isolated by lavage can be separated into large aggregates (LA) and small aggregates (SA). Pulse labeling experiments have shown that the LA subtype is the precursor of the SA subtype. Conversion of LA to SA can be demonstrated in vitro using the technique of surface area cycling. The precise mechanisms of surfactant subtype conversion remain unknown. We have previously reported a decline in surfactant-associated protein B (SP-B) during in vitro subtype conversion of canine surfactant. This led to the hypothesis that SP-B may be degraded by a serine protease 'convertase' during cycling. The current studies used a quantitative slot-blot assay to investigate the fates of SP-A and SP-B during in vitro cycling. These studies confirmed some SP-A is present in SA, but SP-B is confirmed to LA. Conversion leads to an apparent loss of SP-B during cycling. However, SP-B can be recovered from the walls of polypropylene and Teflon tubes by washing with chloroform:methanol. Recovered SP-B migrated on non-reducing tricine gels as a single band with an apparent molecular weight of 17 kDa, corresponding to intact SP-B dimer. Reconstitution studies demonstrated that the recovered SP-B retained its surface active properties as determined on a pulsating bubble surfactometer. We conclude in vitro surface area cycling of canine LA results in the dissociation of SP-B from surfactant lipids resulting in an apparent decline in SP-B levels.

The role of lipids in pulmonary surfactant.

Pulmonary surfactant is composed of approx. 90% lipids and 10% protein. This review article focusses on the lipid components of surfactant. The first sections will describe the lipid composition of mammalian surfactant and the techniques that have been utilized to study the involvement of these lipids in reducing the surface tension at an air-liquid interface, the main function of pulmonary surfactant. Subsequently, the roles of specific lipids in surfactant will be discussed. For the two main surfactant phospholipids, phosphatidylcholine and phosphatidylglycerol, specific contributions to the overall surface tension reducing properties of surfactant have been indicated. In contrast, the role of the minor phospholipid components and the neutral lipid fraction of surfactant is less clear and requires further study. Recent technical advances, such as fluorescent microscopic techniques, hold great potential for expanding our knowledge of how surfactant lipids, including some of the minor components, function. Interesting information regarding surfactant lipids has also been obtained in studies evaluating the surfactant system in non-mammalian species. In certain non-mammalian species (and at least one marsupial), surfactant lipid composition, most notably disaturated phosphatidylcholine and cholesterol, changes drastically under different conditions such as an alteration in body temperature. The impact of these changes on surfactant function provide insight into the function of these lipids, not only in non-mammalian lungs but also in the surfactant from mammalian species.

Examination of the potential role of the glycerophosphorylcholine (GPC) pathway in the biosynthesis of phosphatidylcholine by liver and lung.

The potential involvement of the glycerophosphorylcholine (GPC) pathway for the synthesis of phosphatidylcholine (PC) has been examined in rat liver and lung and in a human line, the A549 cell which possesses characteristics representative of mature alveolar type II epithelial cells. Although mitochondrial and microsomal fractions from the above sources readily incorporated radioactive glycerophosphate into lipids, the only incorporation observed with radioactive GPC was a small variable labelling with the mitochondrial and microsomal fractions from rat lung. Even with these fractions, no radioactivity from GPC was incorporated into PC or lysoPC. Attempts to increase the incorporation of GPC into lipids by manipulating the incubation conditions were unsuccessful. It was concluded that the occurrence of the GPC pathway in liver and lung is unlikely.

Effects of alveolar surfactant aggregates on T-lymphocyte proliferation.

The effects of alveolar large aggregate (LA) and small aggregate (SA) surfactant subfractions isolated from healthy adult rats on mitogen-stimulated proliferative responses of human peripheral blood mononuclear cells (PBMC) was examined. Various concentrations of total surfactant suppressed proliferation of stimulated lymphocytes by up to 95% of mitogen-stimulated cells alone. LA subfractions of total surfactant had no effect on proliferation, whereas SA significantly enhanced the lymphocyte proliferation at lower concentrations (7.8 microg/ml) compared to mitogen-stimulated cells alone. Higher concentrations of SA (62.5 microg/ml) inhibited lymphocyte proliferation. This concentration-dependent effect of SA on proliferation of PBMC was also present when cells were stimulated with various lectins including anti-CD3, concanavalin A and phytohemagglutinin. Analysis of the supernatant of mitogen-stimulated cell cultures treated with inhibitory concentrations of SA showed decreased amounts of interleukin (IL)-2, compared to cells alone, which could be reversed by adding exogenous IL-2 to the cell cultures with the SA. These results suggest that alveolar surfactant subfractions have distinct functions within the alveoli, both biophysically and with respect to their effects on the host's immunomodulatory responses.

Can viral load, semi-quantitatively evaluated, of human papillomavirus predict cytological or histological outcome in women with atypical squamous or glandular cells of undetermined significance cytology?

OBJECTIVE: 1) To assess the regression to normal cytology in women with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) and absence or clearance of human papillomavirus (HPV) infection; 2) To evaluate the association between viral load, semi-quantitatively evaluated, and cytological or histological outcome. MATERIAL AND METHODS: In this cohort study HPV test and biopsy was taken in 148 women with ASCUS/AGUS cytology. After 12-18 months a HPV test and cervical smear were repeated in 121 women. RESULTS: Absence or clearance of HPV showed significantly more regression to normal cytology than persistent or newly acquired infected women, odds ratio 27 (95% confidence interval; 7-103). The viral load of the HPV test at enrollment was not correlated with the follow-up cytological outcome (Spearman correlation coefficient 0.2, p = 0.2). A marked association between viral load and histological outcome at enrollment was shown (Spearman correlation coefficient 0.43, p < 0.0001). CONCLUSION: Absence or clearance of HPV can predict regression to normal cytology. Viral load at enrollment cannot predict cytological regression. There was a marked association between viral load and the underlying CIN at enrollment. However, there was large overlapping of viral loads among the grades of CIN. Therefore, viral load is not a useful parameter to predict high-grade lesions in women with ASCUS/AGUS cytology.

Analysis of the performance of pathologists in the grading of bladder tumors.

Fifty-seven transurethrally resected bladder tumors were analyzed to determine whether different pathologists, using the World Health Organization grading system, graded the same bladder tumor differently (interindividual consistency) and whether the same pathologist graded a bladder tumor differently at different times (intraindividual consistency). Disturbingly high inter- and intraindividual inconsistency in the grading of bladder tumors was found. All pathologists showed essentially the same degree of intraindividual inconsistency: In almost 50 per cent of cases the tumor was graded differently at different times by the same pathologist. The inconsistencies might invalidate the usefulness of bladder tumor grading in clinical decision-making.

Morphometric grading of bladder tumors in comparison with histologic grading by pathologists.

The authors describe the results of the grading of bladder tumors using morphometry and then compare these with results of histologic grading of the same tumors by different pathologists. Nuclear sizes of cells obtained from superficial and deep cell layers of each carcinoma and from giant cells were measured in 27 cases in which histologic tumor grading by different pathologists was unequivocal. In cells from all three areas, nuclear area increased with higher tumor grade. However, tumors of grades I and II showed significant differences in the size only of the large cells. It is concluded that morphometry is a valuable tool in the objective grading of bladder tumors, with the exception of carcinoma in situ lining the bladder lumen.

Exogenous surfactant therapy in thirty-eight hour lung graft preservation for transplantation.

Previous work in our laboratory has documented alterations in surfactant composition and function after prolonged lung graft storage and transplantation in dogs (Am Rev Respir Dis 1993;148:208-15). To determine whether exogenous surfactant therapy was beneficial, we pretreated 13 canine double lung blocks with prostacyclin, flushed them with 4 degrees C modified Euro-Collins solution, and stored them at 4 degrees C for 37 to 38 hours. After left lung transplantation and immediately before reperfusion, eight dogs were administered 50 mg of bovine lung lipid extract surfactant per kilogram (50 mg/ml) directly into the left main bronchus and five served as nontreated control animals. Blood gases, peak inspired pressures, and individual pulmonary artery blood flows were measured every 30 minutes during 6 hours of reperfusion. The native right and transplanted left lungs were then lavaged and surfactant large and small aggregates and protein yields were analyzed. All nontreated animals had physiologic evidence of severe ischemia-reperfusion lung injury during reperfusion. Three of eight dogs treated with bovine lung lipid extract surfactant had near normal lung function at 6 hours of reperfusion, as reflected by maintenance of an oxygen tension/inspired oxygen fraction ratio of more than 400 mm Hg and a normal carbon dioxide tension. Five of eight dogs did not respond to surfactant therapy and had decreases in gas exchange identical to those of the control animals. Blood flow through the left pulmonary artery was maintained in the three animals that responded to exogenous surfactant, whereas flow significantly decreased to the left lung in all other animals, reflecting the patterns of gas exchange. In addition, the ratio of poorly functioning small surfactant aggregates to the well-functioning large aggregates isolated from lung lavage after 6 hours of reperfusion was decreased in surfactant-treated animals, especially in those exhibiting a beneficial physiologic response to surfactant therapy. We conclude that therapy with bovine lung lipid extract surfactant can result in excellent preservation of lung grafts after prolonged storage and transplantation, but that the results are not consistent. Further investigations are required to determine the factors responsible for the differential response to surfactant therapy.

Mitigation of injury in canine lung grafts by exogenous surfactant therapy.

BACKGROUND: Exogenous surfactant therapy of lung donors improves the preservation of normal canine grafts. The current study was designed to determine whether exogenous surfactant can mitigate the damage in lung grafts induced by mechanical ventilation before procurement. METHODS AND RESULTS: Five donor dogs were subjected to 8 hours of mechanical ventilation (tidal volume 45 ml/kg). This produced a significant decrease in oxygen tension (p = 0.007) and significant increases in bronchoscopic lavage fluid neutrophil count (p = 0.05), protein concentration (p = 0.002), and the ratio of poorly functioning small surfactant aggregates to superiorly functioning large aggregates (p = 0.02). Five other animals given instilled bovine lipid extract surfactant and undergoing mechanical ventilation in the same manner demonstrated no significant change in oxygen tension values, lavage fluid protein concentration, or the ratio of small to large aggregates. All 10 lung grafts were then stored for 17 hours at 4 degrees C. Left lungs were transplanted and reperfused for 6 hours. After 6 hours of reperfusion the ratio of oxygen tension to inspired oxygen fraction was 307 +/- 63 mm Hg in lung grafts administered surfactant versus 73 +/- 14 mm Hg in untreated grafts (p = 0.007). Furthermore, peak inspired pressure was significantly (p < 0.05) lower in treated animals from 90 to 360 minutes of reperfusion. Analysis of lavage fluid of transplanted grafts after reperfusion revealed small to large aggregate ratios of 0.17 +/- 0.04 and 0.77 +/- 0.17 in treated versus untreated grafts, respectively (p = 0.009). CONCLUSIONS: Instillation of surfactant before mechanical ventilation reduced protein leak, maintained a low surfactant small to large aggregate ratio, and prevented a decrease of oxygen tension in donor animals. After transplantation, surfactant-treated grafts had superior oxygen tension values and a higher proportion of superiorly functioning surfactant aggregate forms in the air space than untreated grafts. Exogenous surfactant therapy can protect lung grafts from ventilation-induced injury and may offer a promising means to expand the donor pool.

Quantitative morphometry of squamous cell hyperplasia of the larynx.

The histopathological diagnosis of squamous cell hyperplasia of the larynx is very subjective. Since morphometry is highly reproducible, this method was applied to routine processed slides of 45 such lesions to assess objectively the epithelial characteristics. In each case measurements of nuclei of 50 cells in the basal, intermediate, and superficial cell layers were carried out. The data were analysed statistically. The findings suggest that quantitative morphometry may be helpful for the histopathological classification of squamous cell hyperplasia of the laryngeal mucosa.

Effects of ventilation on the surfactant system in sepsis-induced lung injury.

The present study examined the effects of mechanical ventilation, with or without positive end-expiratory pressure (PEEP), on the alveolar surfactant system in an animal model of sepsis-induced lung injury. Septic animals ventilated without PEEP had a significant deterioration in oxygenation compared with preventilated values (arterial PO(2)/inspired O(2) fraction 316 +/- 16 vs. 151 +/- 14 Torr; P < 0.05). This was associated with a significantly lower percentage of the functional large aggregates (59 +/- 3 vs. 72 +/- 4%) along with a significantly reduced function (minimum surface tension 17.7 +/- 1.8 vs. 11.8 +/- 3.8 mN/m) compared with nonventilated septic animals (P < 0.05). Sham animals similarly ventilated without PEEP maintained oxygenation, percent large aggregates and surfactant function. With the addition of PEEP, the deterioration in oxygenation was not observed in the septic animals and was associated with no alterations in the surfactant system. We conclude that animals with sepsis-induced lung injury are more susceptible to the harmful effects of mechanical ventilation, specifically lung collapse and reopening, and that alterations in alveolar surfactant may contribute to the development of lung dysfunction.

Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury.

Two exogenous surfactant preparations [Survanta and bovine lipid extract surfactant (BLES)] were evaluated in saline lavage-injured adult sheep with two different delivery methods (instillation vs. aerosolization). Instilled BLES resulted in the greatest improvement in lung function, followed by aerosolized Survanta and then instilled Survanta. Aerosolized BLES was ineffective. Total surfactant recovery and distribution patterns were similar for Survanta and BLES for each delivery method tested. There were significant differences, however, in the proportion of surfactant recovered in the alveolar wash relative to the lung tissue between the groups at killing. Moreover, the ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates isolated from alveolar wash samples correlated with the physiological responses. The calculated contribution of secreted endogenous surfactant to the total alveolar phospholipid pool at killing was significantly greater for the aerosolized Survanta group compared with the aerosolized BLES group. This finding suggested that there were differences in the interaction of the exogenous surfactants and their alveolar environments. We conclude that the response to exogenous surfactant in acute lung injury depends not only on the preparation used but also on how the surfactants are delivered to the injured lung.