Acute Lung Injury Patients Research Articles

A genetic variant of cortactin linked to acute lung injury impairs lamellipodia dynamics and endothelial wound healing.

Inflammatory mediators released in acute lung injury (ALI) trigger the disruption of interendothelial junctions, leading to loss of vascular barrier function, protein-rich pulmonary edema, and severe hypoxemia. Genetic signatures that predict patient recovery or disease progression are poorly defined, but recent genetic screening of ALI patients has identified an association between lung inflammatory disease and a single nucleotide polymorphism (SNP) in the gene for the actin-binding and barrier-regulatory protein cortactin. This study investigated the impact of this disease-linked cortactin variant on wound healing processes that may contribute to endothelial barrier restoration. A microfabricated platform was used to quantify wound healing in terms of gap closure speed, lamellipodia dynamics, and cell velocity. Overexpression of wild-type cortactin in endothelial cells (ECs) improved directional cell motility and enhanced lamellipodial protrusion length, resulting in enhanced gap closure rates. By contrast, the cortactin SNP impaired wound closure and cell locomotion, consistent with the observed reduction in lamellipodial protrusion length and persistence. Overexpression of the cortactin SNP in lung ECs mitigated the barrier-enhancing activity of sphingosine 1-phosphate. These findings suggest that this common cortactin variant may functionally contribute to ALI predisposition by impeding endothelial wound healing.

Lung protective ventilation in patients undergoing major surgery: a systematic review incorporating a Bayesian approach

ObjectiveProtective ventilation (PV) has been validated in patients with acute respiratory distress syndrome. However, the effect of PV in patients undergoing major surgery is controversial. The study aimed to explore...

Pro-inflammatory and Pro-apoptotic Role of IL-33 in the Human Acute Lung Injury (ALI) Development

The development of acute lung injury (ALI) is always accompanied by remarkably increased production of cytokines in plasma. However, the pathogenesis of this inflammatory response is unclear. In this study, the hypothesis whether Interleukin 33 (IL-33) is induced in the ALI patients and the possible mechanism was tested. The levels of IL-33 were found to be significantly induced in plasma of the ALI patients. Addition of IL-33, enhanced mRNA expression of NLRP-3, Caspase-3, BAX and p53 of peripheral mononuclear blood cells (PBMCs), but inhibited mRNA expression of Caspase-1 found in ALI patients. By stimulating the PBMCs with recombinant Human Interleukin (rhIL)-33, we demonstrated that the chemokines Interleukin 1β (IL-1β), Interleukin 6 (IL-6), Interleukin 18 (IL-18) and Tumor Necrosis Factor (TNF-α) were significantly increased with IL-33 administration in a dose dependent way. Concomitantly, the increase of phosphorylated p38 and enhancement of cell apoptosis were also found in the PBMCs. However, by blocking the IL-33 signaling with p38 inhibitor (SB 203580), the cytokine production and apoptosis were apparently blocked in PBMCs. The present study provided evidences for the IL-33 molecular mechanism in ALI patients. It promots cell apoptosis and cytokines production via the MAPK/p38 signaling in PBMCs. Keywords: Acute lung injury (ALI), inflammation, IL-33, PBMCs, p38.

CAP death: what goes wrong when everything is right?

Community-acquired pneumonia is the leading cause of infectious death in USA 1 Kochanek KD Murphy SL Xu J Arias E Mortality in the United States, 2013. NCHS Data Brief. 2014; 178: 1-8 PubMed Google Scholar and throughout the world. 2 World Health OrganizationThe top 10 causes of death. http://www.who.int/mediacentre/factsheets/fs310/en/index.html Google Scholar Delay in appropriate antibiotic therapy is associated with increased mortality in community-acquired pneumonia, 3 Houck PM Bratzler DW Nsa W Ma A Bartlett JG Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med. 2004; 164: 637-644 Crossref PubMed Scopus (620) Google Scholar and complications of community-acquired pneumonia such as septic shock, 4 Kumar A Haery C Paladugu B et al. The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels. J Infect Dis. 2006; 193: 251-258 Crossref PubMed Scopus (156) Google Scholar acute respiratory distress syndrome, 5 Kojicic M Li G Hanson AC et al. Risk factors for the development of acute lung injury in patients with infectious pneumonia. Crit Care. 2012; 16: R46 Crossref PubMed Scopus (36) Google Scholar , 6 Iscimen R Cartin-Ceba R Yilmaz M et al. Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study. Crit Care Med. 2008; 36: 1518-1522 Crossref PubMed Scopus (176) Google Scholar and acute kidney injury. 7 Plataki M Kashani K Cabello-Garza J et al. Predictors of acute kidney injury in septic shock patients: an observational cohort study. Clin J Am Soc Nephrol. 2011; 6: 1744-1751 Crossref PubMed Scopus (131) Google Scholar The improvements in mortality rates reported over the past decade for each of these infection-related organ failure syndromes might be substantially related to increasing emphasis on rapid provision of appropriate antibiotics. Risk factors for 30-day mortality in patients with pneumonia who receive appropriate initial antibiotics: an observational cohort studyPatients with two or more risk factors were at a higher risk of death during the 30 days assessed than were individuals with no or one risk factor, despite appropriate initial antibiotic treatment. Therefore, adjunctive therapy might be important for improving outcomes in patients with two or more risk factors. Full-Text PDF

Quantification of Dynamic [18F]FDG Pet Studies in Acute Lung Injury.

This work aims to investigate lung glucose metabolism using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography (PET) imaging in acute lung injury (ALI) patients. Eleven ALI patients and five healthy controls underwent a dynamic [(18)F]FDG PET/X-ray computed tomography (CT) scan. The standardized uptake values (SUV) and three different methods for the quantification of glucose metabolism (i.e., ratio, Patlak, and spectral analysis iterative filter, SAIF) were applied both at the region and the voxel levels. SUV reported a lower correlation than the ratio with the net tracer uptake. Patlak and SAIF analyses did not show any significant spatial or quantitative (R(2) > 0.80) difference. The additional information provided by SAIF showed that in lung inflammation, elevated tracer uptake is coupled with abnormal tracer exchanges within and between lung tissue compartments. Full kinetic modeling provides a multi-parametric description of glucose metabolism in the lungs. This allows characterizing the spatial distribution of lung inflammation as well as returning the functional state of the tissues.

Retraction note: Gene expression profiles analysis identifies key genes for acute lung injury in patients with sepsis.

To identify critical genes and biological pathways in acute lung injury (ALI), a comparative analysis of gene expression profiles of patients with ALI + sepsis compared with patients with sepsis alone were performed with bioinformatic tools. GSE10474 was downloaded from Gene Expression Omnibus, including a collective of 13 whole blood samples with ALI + sepsis and 21 whole blood samples with sepsis alone. After pre-treatment with robust multichip averaging (RMA) method, differential analysis was conducted using simpleaffy package based upon t-test and fold change. Hierarchical clustering was also performed using function hclust from package stats. Beisides, functional enrichment analysis was conducted using iGepros. Moreover, the gene regulatory network was constructed with information from Kyoto Encyclopedia of Genes and Genomes (KEGG) and then visualized by Cytoscape. A total of 128 differentially expressed genes (DEGs) were identified, including 47 up- and 81 down-regulated genes. The significantly enriched functions included negative regulation of cell proliferation, regulation of response to stimulus and cellular component morphogenesis. A total of 27 DEGs were significantly enriched in 16 KEGG pathways, such as protein digestion and absorption, fatty acid metabolism, amoebiasis, etc. Furthermore, the regulatory network of these 27 DEGs was constructed, which involved several key genes, including protein tyrosine kinase 2 (PTK2), v-src avian sarcoma (SRC) and Caveolin 2 (CAV2). PTK2, SRC and CAV2 may be potential markers for diagnosis and treatment of ALI. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5865162912987143

Using Post-Outcome Measurement Information in Censoring-by-Death Problems

Summary Many clinical studies on non-mortality outcomes such as quality of life suffer from the problem that the non-mortality outcome can be censored by death, i.e. the non-mortality outcome cannot be measured if the subject dies before the time of measurement. To address the problem that this censoring by death is informative, it is of interest to consider the average effect of the treatment on the non-mortality outcome among subjects whose measurement would not be censored under either treatment or control, which is called the survivor average causal effect (SACE). The SACE is not point identified under usual assumptions but bounds can be constructed. The previous literature on bounding the SACE uses only the survival information before the measurement of the non-mortality outcome. However, survival information after the measurement of the non-mortality outcome could also be informative. For randomized trials, we propose a set of ranked average score assumptions that make use of survival information before and after the measurement of the non-mortality outcome which are plausibly satisfied in many studies and we develop a two-step linear programming approach to obtain the closed form for bounds on the SACE under our assumptions. We also extend our method to randomized trials with non-compliance or observational studies with a valid instrumental variable to obtain bounds on the complier SACE which is presented in on-line supplementary material. We apply our method to a randomized trial of the effect of mechanical ventilation with lower tidal volume versus traditional tidal volume for acute lung injury patients. Our bounds on the SACE are much shorter than the bounds that are obtained by using only the survival information before the measurement of the non-mortality outcome.

CRRT at early stageon in patients with severe acute pancreatitis applied to preventing acute lung injury in patients with severe acute pancreatitis

Objective To investigate the effects of early continuous renal replacement thempy(CRRT) on acute lung injury and prognosis in severe acute pancreatitis(SAP) patients. Methods 46 SAP patients were divided into the two groups randomly:the control group and CRRT treatment group. The levels of IL- 1β,IL-6,TNF-α,the APACHE Ⅱ score, oxygenation index, the incidence of acute lung injury(ALI)/acute respiratory distress syndrome(ARDS), ICU stay were compared between the two groups. Results The level of interleukin - 6(IL- 6)in the control group was significantly higher than that in CRRT group in day 1(t= 2.265,P 0.05). Conclusion Early CRRT therapy can eliminate the IL- 1β,IL- 6 and TNF-αin SAP patients, which can improve the oxygenation index and reduce the incidences of ALI/ARDS, may provide more clinical benefits in the early phase of SAP. Key words: Pancreatitis; Interleukin; Tumor necrosis factor-α; Continuous renal replacement therapy; Oxygenation index; Acute lung injury/acute respiratory distress syndrome

Effects of neutrophil elastase inhibitor in patients undergoing esophagectomy: a systematic review and meta-analysis.

To evaluate the benefit and safety of sivelestat (a neutrophil elastase inhibitor) administration in patients undergoing esophagectomy. Online databases including PubMed, EMBASE, the Cochrane Library, Web of Knowledge, and Chinese databases (Wanfang database, VIP and CNKI) were searched systematically up to November 2013. Randomized controlled trials and high-quality comparative studies were considered eligible for inclusion. Three reviewers evaluated the methodological quality of the included studies, and Stata 12.0 software was used to analyze the extracted data. The risk ratio (RR) was used to express the effect size of dichotomous outcomes, and mean difference (MD) or standardized mean difference was used to express the effect size of continuous outcomes. Thirteen studies were included in this systematic review and nine studies were included in the meta-analysis. The duration of mechanical ventilation was significantly decreased in the sivelestat group on postoperative day 5 [I (2) = 76.3%, SMD = -1.41, 95%CI: -2.63-(-0.19)]. Sivelestat greatly lowered the incidence of acute lung injury in patients after surgery (I (2) = 0%, RR = 0.27, 95%CI: 0.08-0.93). However, it did not decrease the incidence of pneumonia, intensive care unit stay or postoperative hospital stay, and did not increase the incidence of complications such as anastomotic leakage, recurrent nerve palsy, wound infection, sepsis and catheter-related fever. A neutrophil elastase inhibitor is beneficial in patients undergoing esophagectomy. More high quality, large sample, multi-center and randomized controlled trials are needed to validate this effect.

Extravascular lung water index as an indicator of lung injury in septic patients

Introduction. Transpulmonary thermodilution using PiCCO (Pulse-induced Contour Cardiac Output) is a standard minimally invasive method used for haemodynamic monitoring. Objectives. The goal of this paper is to examine the correlation and dynamics of the ExtraVascular Lung Water Index (EVLWI) as an indicator of acute lung injury in septic patients who underwent major abdominal surgery. Two groups of patients were selected: the ones with ALI (Acute Lung Injury): ALI patient group, and the ones without ALI: non-ALI patient group. A correlation between EVLWI and other haemodynamic and respiratory data in both groups were analyzed.Materials and methods. The study included 48 patients. Throughout the seven-day period EVLWI, GEDVI (Global End-Diastolic Volume Index), ITBVI (IntraThoracic Blood Volume Index), CI (Cardiac Index), SVRI (Systemic Vascular Resistance Index) were measured in both groups using PiCCO monitoring over 8-hour intervals as well as heart rate, mean arterial pressure, serum albumin concentration, PaCO2 (arterial partial pressure of carbon dioxide), PaO2 (arterial partial pressure of oxygen), PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio, lung compliance, lung resistance and ScvO2 (central venous oxygen saturation). All patients were analgosedated, intubated, mechanically ventilated, in sinus cardiac rhythm. Circulatory unstable patients had vasoactive support and Sequential Organ Failure Assessment (SOFA) scores calculated. Ventilator settings and dosage of vasoactive drugs were kept constant during the study.Results. EVLWI was significantly higher in ALI patients group compared to non-ALI patients group. In patients with ALI group 11/22 patients died (50%), in the non-ALI patients group 6/26 patients died (23%). EVLWI was significantly higher in patients that died compared to ones who survived.Conclusion. EVLWI is a good indicator of early acute lung injury in surgical patients with sepsis.

Thaliporphine derivative improves acute lung injury after traumatic brain injury.

Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI.

Effect of Chest Physiotherapy and Recruitment Maneuvers on Hemodynamics and ICU Stay of Mechanically Ventilated Patients with Acute Lung Injury.

AbstractBackground Acute lung injury Patients may require mechanical ventilation to survive Chest physiotherapy & Recruitment maneuvers are two methods that improve respiratory efficiency and promote Hemodynamic stability Aim To investigate effect of chest Physiotherapy & recruitment maneuvers on hemodynamic parameters and length of ICU stay of mechanically ventilated Patients with Acute lung Injury Design Quasi-experimental designSetting The study was carried out in trauma intensive care unit at Assiut university hospital. Subjects: A convenience sample of 60 matched patients and randomly assigned into two equal groups diagnosed as having an acute lung injury, coma scale ≥ 13, on mechanical ventilation Tools Tool: acute lung injury mechanically ventilated patient assessment sheet were utilized to collect data Methods study group was exposed to two sessions/day of chest physiotherapy& recruitment maneuvers until disconnection from mechanical ventilator in addition to the routine hospital care. Results Significant statistical was put into evidence between the two studied groups in the hemodynamic parameters HR was (96.71±11.39) in study group (110.64±11.14) control group after 30 min (p=0.001) after 12 (93.16±22.79) in study group (91.07±7.0) in control group (p=0.05) Temperature in control group (38.9 to 38.6) (37.3 to 37.7) in study group (p=0.001) control group stayed longer in ICU than study group (p=0.001)Conclusion Combining Chest physiotherapy Recruitment maneuvers are of great values for improvement of respiratory efficiency and promote Hemodynamic parameters Replication of the study on larger propriety sample is recommended.

Abstract 13333: Imatinib Attenuates LPS-induced Inflammation and Vascular Leakage in Clinically Relevant Murine Models of Acute Lung Injury

Introduction: Acute lung injury (ALI) is characterized by inflammation-induced disruption of the endothelial cell (EC) barrier lining the pulmonary vasculature, which causes leakage of fluid and inflammatory cells into the airspaces. The mechanisms underlying ALI are critically dependent on EC cytoskeletal regulation of vascular permeability. The Abl family kinases Abl and Abl Related Gene (Arg) are key mediators of the endothelial cytoskeleton. The pharmaceutical agent imatinib inhibits these kinases and is used clinically for the treatment of multiple different malignancies. Hypothesis: Imatinib attenuates LPS-induced inflammation and vascular leakage in murine ALI and retains its protective properties when combined with high tidal volume (Tv) mechanical ventilation (MV). Methods: As a clinically relevant combination model of ALI stimuli, animals were given intratracheal (i.t) LPS (0.5mg/kg) (vs. PBS), allowed to recover for 20 hours, and then intubated for MV (Tv 30ml/kg, RR 75/min, PEEP 0 cm H2O, 4hrs). Imatinib (75mg/kg) (vs. vehicle) was given i.p. 30 min before LPS and 30 min before MV. For post-injury experiments, imatinib (75mg/kg) (vs. vehicle) was given 4 hours after LPS (1mg/kg) and animals were harvested after 18 hrs. Bronchoalveolar lavage fluid (BAL) was analyzed for total cell counts, neutrophil number, total protein, albumin content, and cytokine levels. Lung tissues were used for MPO activity, albumin content, histology, and Evans Blue dye extravasation. Results: Imatinib attenuated inflammation in both combination model studies and post-LPS treatment studies as measured by BAL cell count, PMN number, MPO activity, TNFα levels, and H&E staining. Additionally, in both models, imatinib decreased vascular leakage as measured by total protein, BAL and lung tissue albumin, and Evans Blue dye extravasation. Conclusions: Imatinib attenuates LPS-induced inflammation and vascular leak in mice. Additionally, imatinib is protective in a clinically relevant murine model of combined LPS and mechanical ventilation injury. Imatinib may have potential for translational use in ALI patients.

Erythropoietin promotes the protective properties of transplanted endothelial progenitor cells against acute lung injury via PI3K/Akt pathway.

Accumulating evidences have indicted the participation and repairing effects of endothelial progenitor cells (EPCs) on acute lung injury (ALI). Researchers have also revealed that erythropoietin (EPO) may exert multiple effects on EPCs including proliferative and adhesive properties. The present study was designed to investigate whether EPO can promote the healing efficiency of transplanted EPCs against ALI and the potential mechanism. Endothelial progenitor cells were derived from bone marrow mononuclear cells of BALB/c mice. In our in vitro studies, we tested the proproliferative and antiapoptotic effects of EPO on cultured EPCs. In our in vivo studies, we induced BALB/c mice ALI model by intratracheal instillation of lipopolysaccharide and treated with/without intravenous injection of enhanced green fluorescent protein-EPCs harvested from enhanced green fluorescent protein-BALB/c mice. Mice that received EPC transplantation either underwent EPO administration or not. The effects of EPO and EPC treatment on promoting pulmonary endothelial repair, decreasing pulmonary capillary permeability, alleviating pulmonary inflammation, improving gas exchange, and promoting pulmonary vessel angiogenesis were tested. The potential mechanisms that mediate EPO functions on EPC were also investigated. Our studies revealed a significant antiapoptotic property of EPO on cultured EPCs as well as its promotion on EPC proliferation. We also found the severity of ALI was reduced by EPC therapy, and the protective effects of EPCs were highly enhanced when combined with EPO administration. However, all these stimulating effects of EPO on EPCs were consisted with the expression of phospho-Akt and were abrogated by PI3K inhibitors. Transplanted EPCs directly incorporated into the injured pulmonary vessels and maintain the integrity of pulmonary endothelium. Erythropoietin improved the survival and proliferation of transplanted EPCs and recruited them to the injured sites to exert their repairing functions. PI3K/Akt pathway mediated EPO's functions on EPCs. The combination of EPO and EPC treatment may be a promising cell-based therapy for ALI patients.

Gene expression profiles analysis identifies key genes for acute lung injury in patients with sepsis.

BackgroundTo identify critical genes and biological pathways in acute lung injury (ALI), a comparative analysis of gene expression profiles of patients with ALI + sepsis compared with patients with sepsis alone were performed with bioinformatic tools.MethodsGSE10474 was downloaded from Gene Expression Omnibus, including a collective of 13 whole blood samples with ALI + sepsis and 21 whole blood samples with sepsis alone. After pre-treatment with robust multichip averaging (RMA) method, differential analysis was conducted using simpleaffy package based upon t-test and fold change. Hierarchical clustering was also performed using function hclust from package stats. Beisides, functional enrichment analysis was conducted using iGepros. Moreover, the gene regulatory network was constructed with information from Kyoto Encyclopedia of Genes and Genomes (KEGG) and then visualized by Cytoscape.ResultsA total of 128 differentially expressed genes (DEGs) were identified, including 47 up- and 81 down-regulated genes. The significantly enriched functions included negative regulation of cell proliferation, regulation of response to stimulus and cellular component morphogenesis. A total of 27 DEGs were significantly enriched in 16 KEGG pathways, such as protein digestion and absorption, fatty acid metabolism, amoebiasis, etc. Furthermore, the regulatory network of these 27 DEGs was constructed, which involved several key genes, including protein tyrosine kinase 2 (PTK2), v-src avian sarcoma (SRC) and Caveolin 2 (CAV2).ConclusionPTK2, SRC and CAV2 may be potential markers for diagnosis and treatment of ALI.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5865162912987143

0991. Nebulized heparin reduces pulmonary inflammatory responses in a rat model of acute lung injury

Sepsis is a mayor cause of acute lung injury (ALI). Pulmonary coagulopathy is intrinsic to ALI and in sepsis, anticoagulant system is impaired, due to consumption and downregulation by inflammatory mediators. Several studies, in ALI patients and in ALI experimental models, inconsistently suggest beneficial effects of systemic anticoagulants which affect systemic coagulation. Nebulization of anticoagulants might allow for higher pulmonary concentration and reduce the risk of systemic bleeding.

Influence of different modes of mechanical ventilation on the development of acute lung injury in patients with severe combined traumatic brain injury

Sabirov, D.1; Rosstalnaya, A.1; Krasnenkova, M.1; Atahanov, S.1; Akalaev, R.2 Author Information

Automated Alerting and Recommendations for the Management of Patients With Preexisting Hypoxia and Potential Acute Lung Injury

Blum, James M.*; Stentz, Michael J.*; Maile, Michael D.*; Jewell, Elizabeth*; Raghavendran, Krishnan†; Engoren, Milo*; Ehrenfeld, Jesse M.‡ Author Information

Haplotype analysis of ApoAI gene and sepsis-associated acute lung injury.

BackgroundApolipoprotein A1 (ApoA1) is the major apoprotein constituent of high density lipoprotein (HDL) which exerts innate protective effects in systemic inflammation. However, its role in the acute lung injury (ALI) has not been well studied. In the present study we investigated the association between polymorphisms of ApoA1 gene and ALI in a Chinese population.MethodsThree polymorphisms of the ApoA1 gene (rs11216153, rs2070665, and rs632153) were genotyped by TaqMan method in 290 patients with sepsis-associated ALI, 285 patients sepsis alone and 330 age- and sex-matched healthy controls.ResultsWe found rs11216153 polymorphism of ApoA1 was associated with ALI, the GG genotype and G allele was common in the ALI patients (76.9%, 88.1%, respectively) than both in the control subjects (55.8%, 75.8%, respectively) and in the sepsis alone patients (58.2%, 78.4%, respectively). Haplotype consisting of these three SNPs strengthened the association with ALI susceptibility. The frequency of haplotype GTG in the ALI samples was significantly higher than that in the healthy control group (OR = 2.261, 95% CI: 1.735 ~ 2.946, P <0.001) and the sepsis alone group (OR = 1.789, 95% CI: 1.373 ~ 2.331.P < 0.001). Carriers of the haplotype TTG had a lower risk for ALI compared with healthy control group (OR = 0.422, 95% CI: 0.310 ~ 0.574, P < 0.001) and sepsis alone group (OR = 0.491, 95% CI: 0.356 ~ 0.676, P <0.001).ConclusionsThese results indicated that genetic variants in the ApoA1 gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population.

(292) - Acute Fibrinous and Organizing Pneumonia is a Common Histological Pattern of Acute Lung Injury in Patients Developing Restrictive Allograft Syndrome

identify the histologic features of AMR in allograft biopsies and correlate them with the presence of serologic alloantibodies in lung transplant patients. Methods: We reviewed a consecutive series of lung allograft biopsies stained with hematoxylin-eosin, anti-CD68, and anti-C4d, blinded to serologic data. Findings of ACR were classified by ISHLT criteria. Complement deposition was considered positive if there was capillary endothelial positivity, excluding stromal and larger vessel staining. Macrophages were considered increased if there was linear granular staining in capillary septa. Results: There were 628 biopsies from 111 patients. Panel reactive alloantibodies (PRA) and donor specific antibodies (DSA) were available in 103 and 100 patients, respectively. There were 73 men (64 ± 13 years) and 38 women (60 ± 12 years). PRA was positive in 38% of patients, and DSA in 30%. 24 patients had ≥ 1 biopsy with positive complement staining and 26 patients had increased macrophage density. 65 patients had ≥ 1 episode of ACR (31 A only, 25 AB, and 6 B; all were grade 1 or 2). There was a positive correlation between ACR and PRA to type II HLA antigens (p= .02), any DSA (p= .0016), the number of DSA (p= .0008) as well as the presence of DSA to type II HLA antigens (p= .003). Additionally, there was a positive correlation between increased macrophages and PRA to type II HLA antigens (p= .04), presence of DSA (p= .009) and the number of DSA type II HLA antibodies (p= .02). There was a positive correlation between complement staining and the presence of any DSA (p= .05). Other correlations were not significant. Conclusion: There is a correlation between multiple histologic findings suggestive of rejection and the serologic presence of donor specific alloantibodies, specifically against type II HLA antigens. The correlation is strongest for ACR, followed by the presence of increased capillary septal macrophages, and weakest for complement staining for C4d.