An alternative method of acute lung injury classification for use in observational studies.
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ABSTRACT:
SUBMITTER: Shah CV
PROVIDER: S-EPMC2972624 | biostudies-literature | 2010 Nov
REPOSITORIES: biostudies-literature
Publications
An alternative method of acute lung injury classification for use in observational studies.
Shah Chirag V CV Lanken Paul N PN Localio A Russell AR Gallop Robert R Bellamy Scarlett S Ma Shwu-Fan SF Flores Carlos C Kahn Jeremy M JM Finkel Barbara B Fuchs Barry D BD Garcia Joe G N JG Christie Jason D JD
Chest 20100624 5
<h4>Background</h4>In observational studies using acute lung injury (ALI) as an outcome, a spectrum of lung injury and difficult-to-interpret chest radiographs (CXRs) may hamper efforts to uncover risk factor associations. We assessed the impact of excluding patients with difficult-to-classify or equivocal ALI diagnosis on clinical and genetic risk factor associations for ALI after trauma.<h4>Methods</h4>This study was of a prospective cohort of 280 critically ill trauma patients. The primary ou ...[more]
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Project description:BackgroundRecent studies have suggested a potential increased risk of acute kidney injury (AKI) among proton-pump inhibitor (PPI) users. However, the present results are conflicting. Thus, we performed a meta-analysis to investigate the association between PPI therapy and the risk of AKI.MethodsEMBASE, PubMed, Web of Science, and Cochrane Library databases (up to September 23, 2016) were systematically searched for any studies assessing the relationship between PPI use and risk of AKI. Studies that reported relevant risk ratios (RRs), odds ratios, or hazard ratios were included. We calculated the pooled RRs with 95% confidence intervals (CI) using a random-effects model of the meta-analysis. Subgroup analysis was conducted to explore the source of heterogeneity.ResultsSeven observational studies (five cohort studies and two case-control studies) were identified and included, and a total of 513,696 cases of PPI use among 2,404,236 participants were included in the meta-analysis. The pooled adjusted RR of AKI in patients with PPIs use was 1.61 (95% CI: 1.16-2.22; I2=98.1%). Furthermore, higher risks of AKI were found in the subgroups of cohort studies, participant's average age <60 years, participants with and without baseline PPI excluded, sample size <300,000, and number of adjustments ?11. Subgroup analyses revealed that participants with or without baseline PPI excluded might be a source of heterogeneity.ConclusionPPI use could be a risk factor for AKI and should be administered carefully. Nevertheless, some confounding factors might impact the outcomes. More well-designed prospective studies are needed to clarify the association.
| S-EPMC5411168 | biostudies-literature
Project description:It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality.Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative vs. liberal fluid management and of management guided by a central venous vs. pulmonary artery catheter.Acute Respiratory Distress Syndrome Network hospitals.One thousand patients.None.The incidence of acute kidney injury, defined as an absolute rise in creatinine of ?0.3 mg/dL or a relative change of >50% over 48 hrs, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of acute kidney injury before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57% vs. 51%, p = .04). After adjustment for fluid balance, the incidence of acute kidney injury was greater in those managed with the liberal fluid protocol (66% vs. 58%, p = .007). Patients who met acute kidney injury criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet acute kidney injury criteria both before and after adjustment for fluid balance (31% vs. 12%, p < .001) and those who had acute kidney injury before but not after adjustment for fluid balance (31% vs. 11%, p = .005). The mortality of those patients meeting acute kidney injury criteria after but not before adjustment for fluid balance was similar to patients with acute kidney injury both before and after adjustment for fluid balance (31% vs. 38%, p = .18).Fluid management influences serum creatinine and therefore the diagnosis of acute kidney injury using creatinine-based definitions. Patients with "unrecognized" acute kidney injury that is identified after adjusting for positive fluid balance have higher mortality rates, and patients who have acute kidney injury before but not after adjusting for fluid balance have lower mortality rates. Future studies of acute kidney injury should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis.
| S-EPMC3220741 | biostudies-literature
Project description:BackgroundAcute lung injury (ALI) is characterized by suppressed fibrinolytic activity in bronchoalveolar lavage fluid (BALF) attributed to elevated plasminogen activator inhibitor-1 (PAI-1). Restoring pulmonary fibrinolysis by delivering tissue-type plasminogen activator (tPA), urokinase plasminogen activator (uPA), and plasmin could be a promising approach.ObjectivesTo systematically analyze the overall benefit of fibrinolytic therapy for ALI reported in preclinical studies.MethodsWe searched PubMed, Embase, Web of Science, and CNKI Chinese databases, and analyzed data retrieved from 22 studies for the beneficial effects of fibrinolytics on animal models of ALI.ResultsBoth large and small animals were used with five routes for delivering tPA, uPA, and plasmin. Fibrinolytics significantly increased the fibrinolytic activity both in the plasma and BALF. Fibrin degradation products in BALF had a net increase of 408.41 ng/ml vs controls (P < 0.00001). In addition, plasma thrombin-antithrombin complexes increased 1.59 ng/ml over controls (P = 0.0001). In sharp contrast, PAI-1 level in BALF decreased 21.44 ng/ml compared with controls (P < 0.00001). Arterial oxygen tension was improved by a net increase of 15.16 mmHg, while carbon dioxide pressure was significantly reduced (11.66 mmHg, P = 0.0001 vs controls). Additionally, fibrinolytics improved lung function and alleviated inflammation response: the lung wet/dry ratio was decreased 1.49 (P < 0.0001 vs controls), lung injury score was reduced 1.83 (P < 0.00001 vs controls), and BALF neutrophils were lesser (3 × 104/ml, P < 0.00001 vs controls). The mortality decreased significantly within defined study periods (6 h to 30 days for mortality), as the risk ratio of death was 0.2-fold of controls (P = 0.0008).ConclusionWe conclude that fibrinolytic therapy may be effective pharmaceutic strategy for ALI in animal models.
| S-EPMC6110197 | biostudies-literature
Project description:Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical animal studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury (ALI) holds great promise, and Phase I and II clinical trials are currently under way internationally. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, as well as the prohibitive cost of production, storage, and distribution of cells in bone marrow transplant facilities, may limit access to this lifesaving therapy. Accumulating evidence now suggest that novel stem cell-derived therapies, including MSC-conditioned medium and extracellular vesicles (EVs) released from MSCs, might constitute compelling alternatives. The current review summarizes the preclinical studies testing MSC EVs as treatment for ALI and other inflammatory lung diseases. While certain logistic obstacles limit the clinical applications of MSC-conditioned medium such as the volume required for treatment and lack of standardization of what constitutes the components of conditioned medium, the therapeutic application of MSC EVs remains promising, primarily due to ability of EVs to maintain the functional phenotype of the parent cell. However, utilization of MSC EVs will require large-scale production and standardization concerning identification, characterization, and quantification.
| S-EPMC6368889 | biostudies-literature
Project description:Background and objectivesPatients undergoing lung resection surgery are at risk of developing postoperative acute kidney injury. Determination of cytokine levels allows the detection of an early inflammatory response. We investigated any temporal relationship among perioperative inflammatory status and development of acute kidney injury after lung resection surgery. Furthermore, we evaluated the impact of acute kidney injury on outcome and analyzed the feasibility of cytokines to predict acute kidney injury.MethodsWe prospectively analyzed 174 patients scheduled for elective lung resection surgery with intra-operative periods of one-lung ventilation. Fiberoptic broncho-alveolar lavage was performed in each lung before and after one-lung ventilation periods for cytokine analysis. As well, cytokine levels were measured from arterial blood samples at five time points. Acute kidney injury was diagnosed within 48h of surgery based estabilished criteria for its diagnosis. We analyzed the association between acute kidney injury and cardiopulmonary complications, length of intensive care unit and hospital stays, intensive care unit re-admission, and short-term and long-term mortality.ResultsThe incidence of acute kidney injury in our study was 6.9% (12/174). Acute kidney injury patients showed higher plasma cytokine levels after surgery, but differences in alveolar cytokines were not detected. Although no patient required renal replacement therapy, acute kidney injury patients had higher incidence of cardiopulmonary complications and increased overall mortality. Plasma interleukin-6 at 6h was the most predictive cytokine of acute kidney injury (cut-off point at 4.89pg.mL-1).ConclusionsIncreased postoperative plasma cytokine levels are associated with acute kidney injury after lung resection surgery in our study, which worsens the prognosis. Plasma interleukin-6 may be used as an early indicator for patients at risk of developing acute kidney injury after lung resection surgery.
| S-EPMC9391883 | biostudies-literature
Project description:BackgroundThe association between preoperative aspirin use and postoperative acute kidney injury (AKI) in cardiovascular surgery is unclear. We sought to evaluate the effect of preoperative aspirin use on postoperative AKI in cardiac surgery.MethodsA total of 770 patients who underwent cardiovascular surgery under cardiopulmonary bypass were reviewed. Perioperative clinical parameters including preoperative aspirin administration were retrieved. We matched 108 patients who took preoperative aspirin continuously with patients who stopped aspirin more than 7 days or did not take aspirin for the month before surgery. The parameters used in the matching included variables related to surgery type, patient's demographics, underlying medical conditions and preoperative medications.ResultsIn the first seven postoperative days, 399 patients (51.8%) developed AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and 128 patients (16.6%) required hemodialysis. Most patients took aspirin 100 mg once daily (n = 195, 96.5%) and the remaining 75 mg once daily. Multivariable analysis showed that preoperative maintenance of aspirin was independently associated with decreased incidence of postoperative AKI (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.21-0.98, P = 0.048; after propensity score matching: OR 0.39, 95% CI 0.22-0.67, P = 0.001). Preoperative maintenance of aspirin was associated with less incidence of AKI defined by KDIGO both in the entire and matched cohort (n = 44 [40.7%] vs. 69 [63.9%] in aspirin and non-aspirin group, respectively in matched sample, relative risk [RR] 0.64, 95% CI 0.49, 0.83, P = 0.001). Preoperative aspirin was associated with decreased postoperative hospital stay after matching (12 [9-18] days vs. 16 [10-25] in aspirin and non-aspirin group, respectively, P = 0.038). Intraoperative estimated or calculated blood loss using hematocrit difference and estimated total blood volume showed no difference according to aspirin administration in both entire and matched cohort.ConclusionsPreoperative low dose aspirin administration without discontinuation was protective against postoperative AKI defined by KDIGO criteria independently in both entire and matched cohort. Preoperative aspirin was also associated with decreased hemodialysis requirements and decreased postoperative hospital stay without increasing bleeding. However, differences in AKI and hospital stay were not associated with in-hospital mortality.
| S-EPMC5417712 | biostudies-literature
Project description:With advances in supportive therapy in the last two decades, mortality rates from ALI/ARDS have improved somewhat, but remain around 30 to 40% with significant morbidity in survivors. Several promising treatments are in various stages of evaluation, but many have failed to prove beneficial in large randomized clinical trials (RCT). The first definitive step forward in ALI therapeutics occurred recently as a result of a large RCT demonstrating a mortality decrease from 40 to 31% with the use of low-volume ventilation strategies. From this, it is clear that the opportunity for successful intervention in ALI exists. However, therapeutic advances remain frustrated by the lack of complete understanding of ALI pathophysiology. This stresses the importance of integrating basic and clinical research of the molecular pathogenesis of this disease. The conclusions of a recent National Heart, Lung, and Blood Institute (NHLBI) Working Group on ALI support this type of research as a priority for future investigations of ALI. One of the areas of research given priority by this ALI Working Group is the issue of ALI severity progression and the role of cells of innate immunity in this process. Currently, the processes that determine which ALI patients progress to ARDS and which do not are unclear. As with many phenotype differences, there is most likely a genetic component involved. The basis for this has been demonstrated. For example, a surfactant protein B (SP-B) polymorphism appears to increase a patient’s risk of developing ALI from pneumonia. Additionally, a polymorphism in the promoter region of the gene for interleukin-6 (IL-6) has been associated with a poor prognosis in patients with ARDS. Understanding the intracellular processes of these genes and the cells expressing them in ALI progression could lead to the identification of molecular markers of ALI severity and eventually to the development of targeted therapies. An examination of genetically uniform animals will provide a clearer insight into the interaction between immune cells in ALI progression as well as guide future human experiments. Keywords: Time Series Design, ALI - acute lung injury, ARDS - acute respiratory distress syndrome, CLP - cecal ligation and puncture
2008-02-02 | GSE10343 | GEO
Project description:Multiple single biomarkers have been associated with poor outcomes in acute lung injury; however, no single biomarker has sufficient discriminating power to clearly indicate prognosis. Using both derivation and replication cohorts, we tested novel risk reclassification methods to determine whether measurement of multiple plasma biomarkers at the time of acute lung injury diagnosis would improve mortality prediction in acute lung injury.Analysis of plasma biomarker levels and prospectively collected clinical data from patients enrolled in two randomized controlled trials of ventilator therapy for acute lung injury.Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network.Subjects enrolled in a trial of lower tidal volume ventilation (derivation cohort) and subjects enrolled in a trial of higher vs. lower positive end-expiratory pressure (replication cohort).None.The plasma biomarkers were intercellular adhesion molecule-1, von Willebrand factor, interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D. In the derivation cohort (n = 547), adding data on these biomarkers to clinical predictors (Acute Physiology and Chronic Health Evaluation III score) at the time of study enrollment improved the accuracy of risk prediction, as reflected by a net reclassification improvement of 22% (95% confidence interval 13% to 32%; p < .001). In the replication cohort (n = 500), the net reclassification improvement was 17% (95% confidence interval 7% to 26%; p < .001). A reduced set of three biomarkers (interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D) had nearly equivalent prognostic value in both cohorts.When combined with clinical data, plasma biomarkers measured at the onset of acute lung injury can improve the accuracy of risk prediction. Combining three or more biomarkers may be useful for selecting a high-risk acute lung injury population for enrollment in clinical trials of novel therapies.
| S-EPMC3260884 | biostudies-literature
Project description:Although respiratory distress is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria; however, no model of malaria-induced lung injury has been definitively established. This work used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of acute lung injury (ALI) in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of cerebral malaria (CM), indicating disruption of the alveolar-capillary membrane barrier â the physiological hallmark of acute lung injury (ALI). In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis comparing malaria-induced ALI with sepsis-induced ALI identified several common gene ontology groups characterizing ALI in these models, including defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. CD36-/- mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM indicate that distinct genetic determinants likely regulate susceptibility to these two important causes of malaria-associated morbidity and mortality. Keywords: Time course Lungs were excised immediately following euthanasia, snap-frozen in liquid nitrogen and stored at â80°C until use. Total RNA was extracted using Trizol reagent (Invitrogen) according to the manufacturerâs instructions, and mRNA was purified using an Oligo-dT cellulose column (NEB, Mississauga, ON) as described previously [54]. cDNA with incorporated 5-(3-aminoallyl)-2âdeoxyuridine-5â-triphosphate (AAdUTP; Sigma, Oakville ON) was reverse-transcribed from 1-2 µg mRNA. Purified cDNA was coupled with N-hydroxysuccinimide esters of Cy3 or Cy5 (GE Lifesciences, Baie d'Urfe QC). Cy3 and Cy5-labeled cDNA pairs and Agilent control spots were added to a final volume of 0.5ml hybridization buffer (1 M NaCl, 0.5% sodium sarcosine, 50 mM methyl ethane sulfonate (MES), pH 6.5, 33% formamide and 40µg salmon sperm DNA (Invitrogen)). Hybridizations were performed in Agilent hybridization (Agilent, Palo Alto CA) chambers at 42°C with rotation for 18-24 hours. Slides were washed in 6X SSPE, 0.005% sarcosine, followed by 0.06X SSPE, allowed to dry and scanned with a 4000A microarray scanner (Axon Instruments, Union City CA). TIFF images were quantified with GenePix (Axon Instruments). Variance stabilizing normalization [55] and loess smoothing were applied in Bioconductor [56] and the data were transformed to log2 scale. Each array was hybridized with cDNA transcribed from an RNA pool of 5 C57BL/6 mice per timepoint (Day 0 and 6) and technical replicates (dye-swap) experiments were performed for both time points.
2010-05-26 | E-GEOD-9497 | biostudies-arrayexpress
Project description:Clinical studies have shown that statin use may alter the risk of lung cancer. However, these studies yielded different results. To quantify the association between statin use and risk of lung cancer, we performed a detailed meta-analysis. A literature search was carried out using MEDLINE, EMBASE and COCHRANE database between January 1966 and November 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to calculate the pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. A total of 20 (five randomized controlled trials, eight cohorts, and seven case-control) studies contributed to the analysis. Pooled results indicated a non-significant decrease of total lung cancer risk among all statin users (RR = 0.89, 95% CI [0.78, 1.02]). Further, long-term statin use did not significantly decrease the risk of total lung cancer (RR = 0.80, 95% CI [0.39 , 1.64]). In our subgroup analyses, the results were not substantially affected by study design, participant ethnicity, or confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of results. The findings of this meta-analysis suggested that there was no significant association between statin use and risk of lung cancer. More studies, especially randomized controlled trials and high quality cohort studies are warranted to confirm this association.
| S-EPMC3808274 | biostudies-literature