Occurrence Of Acute Lung Injury Research Articles

Alleviating Acute Lung Injury Induced by Lipopolysaccharide: Dayuan Yin Suppresses Inflammation and Oxidative Stress in Elderly Male Rats.

The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are vital factors in the progression of ALI in this population. Dayuan Yin (DYY) is a classic Chinese herbal formula used for treating pulmonary diseases. Therefore，this situation can be well simulated by selecting suitable aged rats and induced by LPS, which is helpful to evaluate the role of DYY. The objective of this study is to assess the therapeutic efficacy of DYY in reducing pulmonary inflammation and oxidative stress injury in aged rats induced by LPS. In elderly male Sprague Dawley (SD) rats, the ALI model was induced by injecting LPS into the peritoneal cavity. The therapeutic effect of the DYY group was evaluated after 3 days of oral administration. Lung tissue damage was assessed using hematoxylin-eosin staining and the lung wet/dry (W/D) ratio. Inflammatory reaction in lung tissue was analyzed by counting inflammatory agents, measuring total protein (TP), and examining the concentration of inflammatory components in bronchoalveolar lavage fluid (BALF). Lung oxidative stress was assessed by measuring malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) levels in BALF. The impact of DYY on the phosphorylation of PI3K, AKT, and NF-κBp65 protein was analyzed using Western Blot (WB). The administration of DYY exhibited a dose-dependent reduction in the severity of lung injury caused by LPS, leading to a reversal of the LPS-induced lung W/D ratio. Furthermore, DYY treatment resulted in decreased levels of leukocytes, eosinophils, neutrophils, macrophages, lymphocytes, and total protein in BALF. Additionally, DYY significantly inhibited the upregulation of Interleukin -6, Interleukin -10, and Interleukin -1β (IL-6, IL-10, IL-1β) as well as Tumor necrosis factor-α(TNF-α) induced by LPS (P<0.01). The lungs experienced oxidative stress due to LPS, leading to the production of MDA and iNOS, as well as a decrease in SOD activity. DYY reduced oxidative stress in the lungs and inhibited the activation of p-PI3K, p-Akt, and p-NF-κBp65, with a greater effect at higher doses. In a dose-dependent manner, DYY suppresses the inflammatory response and oxidative stress in the lung tissue of elderly rats, thereby reducing ALI caused by LPS. This effect may be attributed to the inhibition of the PI3K/AKT/NF-κB pathway activation.

Sivelestat in Patients at a High Risk of Postoperative Acute Lung Injury After Scheduled Cardiac Surgery: A Prospective Cohort Study.

Sivelestat, a neutrophil elastase inhibitor, is specifically developed to mitigate the occurrence of acute lung injury (ALI) in individuals who are undergoing cardiovascular surgery. However, its impact on patients who are at a heightened risk of developing ALI after scheduled cardiac surgery has yet to be determined. In order to address this knowledge gap, we undertook a study to assess the efficacy of sivelestat in protecting the lungs of these patients. We conducted a prospective cohort study involving 718 patients who were at high risk of developing postoperative acute lung injury (ALI) and underwent scheduled cardiac surgery between April 25th, 2022, and September 7th, 2023. Among them, 52 patients received sivelestat (administered at a dosage of 0.2mg/kg/h for 3 days), while 666 patients served as controls, not receiving sivelestat. The control conditions were the same for all patients, including ventilation strategy, extubating time, and fluid management. Subsequently, a propensity-score matched cohort was established, consisting of 40 patients in both the sivelestat and control groups. The primary outcome measure encompassed a composite of adverse outcomes, including 30-day mortality, ALI, acute respiratory distress syndrome (ARDS), and others. Secondary outcomes assessed included pneumonia, ventricular arrhythmias, mechanical ventilation (MV) time, and more. After conducting propensity matching in our study, we observed that there were no significant differences in 30-day mortality between the sivelestat and control groups (0% vs 2.5%, P=0.32). However, the use of sivelestat exhibited a significant reduction in the incidence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) compared to the control group (0% vs 55%, P<0.01), pneumonia (0 vs 37.5%, P<0.01), MV time (median:8 hours, IQR:4-14.8 hours vs median: 15.2 hours, IQR:14-16.3 hours, P<0.01). Compared to the control group, the sivelestat could significantly decrease white cell count (P<0.01), neutrophile percentage (P<0.01) and C-reactive protein (P<0.01) in the period of postoperative 5 days. The prophylactic administration of sivelestat has shown promising results in reducing the occurrence of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with a heightened risk of developing these conditions after elective cardiac surgery. Our study findings indicate that sivelestat may provide protective effects by suppressing inflammation triggered by neutrophil activation, thereby safeguarding pulmonary function. ChiCTR2200059102, https://www.chictr.org.cn/showproj.html?proj=166643.

Downregulation of ROR2 attenuates LPS-induced A549 cell injury through JNK and ERK signaling pathways.

We aimed to determine whether receptor tyrosine kinase-like orphan receptor 2 (ROR2) is involved in the occurrence of acute lung injury(ALI) by an animal study and explore the effect of ROR2 downregulation on lipopolysaccharide (LPS)-treated human lung carcinoma A549 cells by a cytological study. Murine models of ALI were successfully constructed by intratracheal instillation of LPS. Meanwhile, A549 cell line stimulated with LPS was used for a cytological study. The expression of ROR2 and its effect on proliferation, cell cycle, apoptosis, and inflammation were detected. It was found that LPS administration markedly inhibited the cell proliferation, resulted in cell cycle arrest at G1 phage, elevated levels of pro-inflammatory cytokines and apoptosis rate of A549 cells. However, LPS-mediated adverse effects mentioned above were significantly ameliorated by downregulation of ROR2 in comparison with LPS treatment. In addition, administration of ROR2 siRNA notably decreased the phosphorylation level of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in LPS-challenged A549 cells. Thus, the present data indicate that downregulation of ROR2 may decrease LPS-induced inflammatory responses and cell apoptosis through inhibiting JNK and ERK signaling pathway, which attenuates ALI.

HEMIN ATTENUATED LPS-INDUCED ACUTE LUNG INJURY IN MICE VIA PROTECTING PULMONARY EPITHELIAL BARRIER AND REGULATING HO-1/NLRP3-MEDIATED PYROPTOSIS.

Pulmonary epithelial barrier injury contributes to acute lung injury, accelerating exudate formation, and resulting alveolar edema. Heme oxygenase-1 (HO-1) plays an important role in ameliorating the pathological symptoms of acute lung injury (ALI). Using an ALI mouse model induced by LPS inhalation, the present study explored the potential molecular regulatory effect of hemin (a potent HO-1 inducer) against ALI epithelial damage. Lipopolysaccharide challenge triggered dysfunction of the alveolar epithelial barrier, impaired tight junctions, and disrupted alveoli fluid clearance, while these pathological changes were effectively reversed by hemin treatment. Furthermore, HO-1 elevation inhibited the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome and oxidative stress in alveolar epithelia, leading to the suppression of inflammatory responses and epithelial pyroptosis, as indicated by the decreased levels of NLRP3 and apoptosis-associated speck-like protein containing a CARD domain (ASC), repressed cleavage of caspase-1 and gasdermin D, and reduced expression levels of inflammatory cytokine IL-1β. In contrast, protoporphyrin IX zinc (II) (ZnPP, an HO-1 inhibitor) treatment had no protective effect on LPS inhalation-induced ALI in mice. In summary, HO-1 induction serves a critical role in maintaining airway epithelium homeostasis through the inhibition of NLRP3/ASC/caspase-1-mediated pyroptosis and inflammation in the occurrence of ALI.

Pathobiological bases of asthma-COVID-19 interaction: A theoretical viewpoint

Patients with asthma are susceptible to viral respiratory infections, due to weakened cellular immunity, chronic airway inflammation, and some other reasons. In fact, asthma was found to be a comorbidity to the Middle East respiratory syndrome coronavirus infection. Moreover, some asthma therapies like systemic corticosteroids used to manage severe asthma were found to be associated with severe acute respiratory syndrome coronavirus (SARS-CoV) viremia in the previous pandemic. However, from the epidemiological studies conducted so far across the globe, asthma patients are not exceptionally susceptible to COVID-19 compared to the general public; as opposed to the association seen with chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and other known comorbidities of COVID-19. The bases for this interaction are not adequately understood. However, the heterogeneity of asthma disease as it relates to its various endotypes, altered angiotensin-converting enzyme (ACE2) expression in the airways, effect of rhinoviral infections, and effect of inhaled corticosteroids and biological response modifiers (BRMs), are the proposed mechanisms behind this interaction. Increased activity of ADAM 17 as induced by interleukin-13 at apical portion of pneumocytes may be responsible for the shedding of ACE2 on asthmatic airways. Furthermore, inhaled corticosteroids may prevent the occurrence of acute lung injury and, hence, acute respiratory distress by transrepression of pro-inflammatory pathways and transactivation of anti-inflammatory pathways. The antiviral effects of some inhaled corticosteroids whose molecular targets are not known may involve downregulation and competitive binding to the chaperone proteins heat shock proteins 90 and 70 between glucocorticoid receptor and nucleoprotein of SARS-CoV-2. MEDLINE was searched for terms such as asthma and COVID-19, antiviral effects of inhaled corticosteroids, BRM, and mechanisms of asthma-COVID-19 interaction. The reference lists of the obtained articles were also searched for additional literature.

XGBoost model predicts acute lung injury after acute pancreatitis

To develop an XGBoost model to predict the occurrence of acute lung injury (ALI) in patients with acute pancreatitis (AP). Using the case database of Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, 1231 cases suffering from AP were screened, and after 137 variables were identified, the clinical characteristics of the samples were statistically analyzed, and the data were randomly divided into a training set (75%) to build the XGBoost model and a test set (25%) for validation. Finally, the performance of the model was evaluated based on accuracy, specificity, sensitivity, and subject characteristics working characteristic curves. The model performance is also compared with that of three other commonly used machine learning algorithms (support vector machine (SVM), logistic regression, and random forest). The age and laboratory tests of patients with AP combined with ALI differed from those of patients without combined acute lung injury. The area under the receiver operating characteristic (ROC) curve of the test set after model evaluation was 0.9534, the specificity was 0.7333, and the sensitivity was 0.7857, with arterial partial pressure of oxygen, bile acid, aspartate transaminase, urea nitrogen, and arterial blood pH as its most important influencing factors. In this study, the XGBoost model has advantages compared with other three machine learning algorithms. The XGBoost model has potential in the application of predicting acute lung injury after acute pancreatitis.

Associations of high-mobility group box 1 and receptor for advanced glycation end products with acute lung injury in patient with acute aortic dissection.

To investigate the associations of high-mobility group box 1 and its specific receptor, receptor for advanced glycation end products with acute lung injury in patients with acute aortic dissection. A total of 96 acute aortic dissection patients were divided into acute aortic dissection with acute lung injury group (38 cases) and acute aortic dissection without acute lung injury group (58 cases), according to partial pressure of oxygen/fraction of inspired oxygen. In addition, 44 healthy individuals were selected for the control group. The blood samples were taken. The serum high-mobility group box 1 and receptor for advanced glycation end products levels were detected by enzyme-linked immunosorbent assay, and the partial pressure of oxygen/fraction of inspired oxygen was measured. 24 h after admission, the high-mobility group box 1 and receptor for advanced glycation end products levels in acute aortic dissection with acute lung injury and acute aortic dissection without acute lung injury groups were significantly higher than those in the control group, respectively (p<0.05), and each index in acute aortic dissection with acute lung injury group was significantly higher than that in acute aortic dissection without acute lung injury group (p<0.05). At each time point within 96 h after admission, compared with acute aortic dissection without acute lung injury group, in acute aortic dissection with acute lung injury group, the high-mobility group box 1 and receptor for advanced glycation end products levels were increased, respectively, and the partial pressure of oxygen/fraction of inspired oxygen was decreased. The correlation analysis showed that, in acute aortic dissection patients, the high-mobility group box 1 and receptor for advanced glycation end products levels were negatively correlated with partial pressure of oxygen/fraction of inspired oxygen, respectively (p<0.05). The serum high-mobility group box 1 and receptor for advanced glycation end products levels may be associated with the occurrence of acute lung injury in acute aortic dissection patients. Monitoring the high-mobility group box 1 and receptor for advanced glycation end products levels can evaluate the risk of acute aortic dissection with acute lung injury.

Paraquat promotes acute lung injury in rats by regulating alveolar macrophage polarization through glycolysis

The present study investigates whether paraquat (PQ) regulates polarization of alveolar macrophages through glycolysis and promotes the occurrence of acute lung injury in rats. In vivo, the PQ intraperitoneal injection was used to construct a model of acute lung injury in rats. In vitro, the study measured the effect of different concentrations of PQ on the viability of the alveolar macrophages, and explored the polarization and glycolysis metabolism of alveolar macrophages at different time points after PQ intervention. Compared with the normal control (NC) group, the lung pathological damage in rats increased gradually after PQ poisoning, reaching a significant degree at 48 h after poisoning. The PQ-poisoned rat serum showed increased expressions of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), and M1 macrophage marker, iNOS, while the expression of interleukin-10 (IL-10) and M2 macrophage marker, Arg1, decreased. The toxic effect of PQ on alveolar macrophages was dose- and time-dependent. Compared with the NC group, IL-6 and TNF-α in the cell supernatant gradually increased after PQ intervention, while the IL-10 content gradually decreased. The PQ intervention in alveolar macrophages increased the expression of intracellular glycolysis rate-limiting enzyme pyruvate kinase isozymes M1/M2 (PKM1/M2), lactate, lactate/pyruvate ratio, and the polarization of alveolar macrophage towards M1. Inhibition of cellular glycolysis significantly reduced the PQ-induced alveolar macrophage polarization to M1 type. Thus, PQ induced increased polarization of lung macrophages toward M1 and decreased polarization toward M2, promoting acute lung injury. Therefore, it can be concluded that PQ regulates the polarization of alveolar macrophages through glycolysis.

Selective inhibition of JNK mitochondrial location is protective against seawater inhalation‑induced ALI/ARDS.

Localization of phosphorylated (p)-JNK to the mitochondria can lead to functional mitochondrial disorder, resulting in a decrease in energy supply and membrane potential, as well as an increase in reactive oxygen species production and apoptosis. JNK is involved in the occurrence of acute lung injury (ALI), and activation of the JNK pathway is one of the crucial factors resulting in injury. The aim of the present study was to investigate whether the JNK-mitochondria (mitoJNK) location participated in the occurrence of ALI and acute respiratory distress syndrome (ALI/ARDS). The present study examined the activation of the JNK pathway, the content of JNK located on the mitochondria and the treatment effects of a cell-permeable peptide Tat-SabKIM1, which can selectively inhibit the location of JNK on mitochondria. The expression levels of proteins were detected by western blot analysis. Lung injuries were evaluated by histological examination, wet-to-dry weight ratios, and H2O2 and malondialdehyde concentrations in the lung tissues. Lung cells apoptosis was evaluated using TUNEL assay. The results demonstrated that JNK was phosphorylated and activated during seawater inhalation-induced ALI/ARDS, not only in the routine JNK pathway but also in the mitoJNK pathway. It was also found that Tat-SabKIM1 could specifically inhibit JNK localization to mitochondria and the activation of mitoJNK signaling. Furthermore, Tat-SabKIM1 could inhibit Bcl-2-regulated autophagy and mitochondria-mediated apoptosis. In conclusion, mitoJNK localization disrupted the normal physiological functions of the mitochondria during ALI/ARDS, and selective inhibition of JNK and mitochondrial SH3BP5 (also known as Sab) binding with Tat-SabKIM1 can block deterioration from ALI/ARDS.

MicroRNA-486-5p Promotes Acute Lung Injury via Inducing Inflammation and Apoptosis by Targeting OTUD7B.

The aim of this article is to study the effect of miR-486-5p in acute lung injury (ALI). MiR-486-5p expression in peripheral blood was determined in ALI patients and healthy volunteers by qRT-PCR. ALI mouse model were reproduced by LPS treatment, and miR-486-5p NC and miRNA-486 inhibitors were injected through trachea. ALI patients' peripheral blood and LPS-induced acute lung injury in mice had significantly higher miR-486-5p levels than control subjects. Inhibition of miR-486-5p by injection with antagomiR-486-5p markedly reduced LPS-induced lung inflammation. Moreover, knockdown of miR-486-5p can reduce protects A549 cell against LPS-induced injury and its corresponding inflammatory response. In addition, Mechanistic analysis indicated that miR-486-5p on the occurrence of ALI is related to the inhibition of OTUD7B activity, which induces the downregulation of inflammatory in ALI. Our results identified miR-486-5p independently associated with ALI. miR-486-5p can mediate the formation of ALI by promoting inflammation.

Which Anesthesia Regimen Should Be Used for Lung Surgery?

The aim of this review is to assess the particularities of general anesthesia for patients undergoing lung surgery and one-lung ventilation (OLV), and to suggest the ideal anesthesia regimen based on the current literature. Pulmonary surgery is often performed using OLV. This is accompanied by specific physiological challenges and risks, principally hypoxemia and acute lung injury (ALI). Anesthetic strategies to prevent ALI include close adjustment of mechanical ventilation settings using low tidal volumes (< 6 ml/kg for OLV), positive end-expiratory pressure between 5 and 10 cmH2O, and the minimum FiO2 required, as well as the use of volatile anesthetics, which have anti-inflammatory properties. For thoracotomies, combined general and neuraxial anesthesia are recommended. So far, there is still no evidence if certain anesthetics have a beneficial effect on tumor outcome in lung cancer surgery. Protective ventilation and the use of volatile anesthetics are recommended to diminish the occurrence of ALI in lung surgery patients, for thoracotomies in combination with neuraxial anesthesia. Both general and local anesthetics can have an effect on growth and recurrence of some cancer types, and their specific effect on lung cancer must be further clarified.

Effects of electroacupuncture on postoperative acute lung injury in patients with acute abdomen complicated with abdominal infection

Objective To evaluate the effects of electroacupuncture(EA) on postoperative acute lung injury(ALI) in patients with acute abdomen complicated with abdominal infection. Methods Ninety patients of both sexes with acute abdomen complicated with abdominal infection, with body mass index of 18-30 kg/m2, aged 35-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, scheduled for elective abdominal surgery with general anesthesia, were divided into 3 groups(n=30 each) using a random number table method: control group(group C), EA at acupoint group(group E) and EA at non-acupoint group(group N). Anesthesia was induced with midazolam, propofol, cis-atracurium and sufentanil.The patients were mechanically ventilated after tracheal intubation.Anesthesia was maintained with inhalation of sevoflurane, IV infusion of propofol and cis-atracurium and intermittent IV boluses of sufentanil.At 15 min of anesthesia induction, 2 h after skin incision and 2, 12 and 24 h after tracheal intubation, Hegu, Zusanli and Neiguan acupoints were stimulated for 15 min every time in group E, and the points 1 cm lateral to the acupoints of Hegu, Zusanli and Neiguan were stimulated for 15 min every time in group N, with disperse-dense waves, frequency 2/15 Hz, wave length 0.2-0.6 ms, at a voltage of 1-2 mA.Arterial blood samples were collected at 15 min before induction(T1) and 24 and 48 h after operation(T2 and T3) for blood gas analysis, oxygenation index was calculated, and the development of ALI(oxygenation index<300 mmHg) was recorded at T2 and T3.The concentrations of club cell protein 16(CC16), surfactant protein D(SP-D), soluble receptor for advanced glycation end products(sRAGE), interleukin-1(IL-1), IL-10, and tumor necrosis factor-alpha(TNF-α) in serum were detected by enzyme-linked immunosorbent assay. Results Compared with the baseline at T1, the serum concentrations of CC16, SP-D, sRAGE, IL-1 and TNF-α were significantly increased, and the serum IL-10 concentrations were decreased at T2 in C, E and N groups(P 0.05). Conclusion Although EA does not decrease the occurrence of ALI, it mitigates the degree of ALI to some extent in the patients with acute abdomen complicated with abdominal infection. Key words: Elactroacupuncture; Abdomen, acute; Intraabdominal infections; Respiratory distress syndrome, adult

Downregulation of miR-199a-3p mediated by the CtBP2-HDAC1-FOXP3 transcriptional complex contributes to acute lung injury by targeting NLRP1.

Emerging evidence indicates that microRNAs (miRNAs) play fundamental roles in the pathogenesis of multiple diseases, including acute lung injury (ALI). Here, we discovered that miR-199a-3p was significantly downregulated in ALI lung tissues using a microarray analysis. In vitro lipopolysaccharide (LPS) treatment of the human epithelial cell line A549 and the human macrophage cell line U937 caused a decrease of miR-199a-3p. Mechanically, miR-199a-3p specifically bound to the 3'-untranslated region (3'-UTR) of NLRP1 (nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 1), a critical member of inflammasomes. Ectopic overexpression or downregulation of miR-199a-3p resulted in the repression or induction of NLRP1, respectively, thereby downregulating or activating its downstream events. Moreover, transcription factor FOXP3 (forkhead box P3) was able to specifically bind to the promoter of miR-199a-3p. Knockdown or overexpression of FOXP3 resulted in a decrease or induction miR-199a-3p expression, respectively. Using immunoprecipitation (IP), mass spectrometry and co-IP assays, we found that FOXP3 formed a transcriptional complex with HDAC1 (histone deacetylase 1) and CtBP2 (C-terminal-binding protein 2). Collectively, our results suggested that the CtBP2-HDAC1-FOXP3 transcriptional complex (CHFTC) could specifically bind to the promoter of miR-199a-3p and repress its expression. Downregulation of miR-199a-3p eliminated its inhibition of NLRP1, causing activation of NLRP1 and cleavage of pro-IL-1β and pro-IL-18 mediated by Caspase-1. The secretion of IL-1β and IL-18 further aggravated the inflammatory response and resulted in the occurrence of ALI.

Emphysema induced by elastase enhances acute inflammatory pulmonary response to intraperitoneal LPS in rats.

Abnormalities in lungs caused by emphysema might alter their response to sepsis and the occurrence of acute lung injury (ALI). This study compared the extension of ALI in response to intraperitoneal lipopolysaccharide (LPS) injection in Wistar rats with and without emphysema induced by elastase. Adult male Wistar rats were randomized into four groups: control, emphysema without sepsis, normal lung with sepsis and emphysema with sepsis. Sepsis was induced, and 24 h later the rats were euthanised. The following analysis was performed: blood gas measurements, bronchoalveolar lavage (BAL), lung permeability and histology. Animals that received LPS showed significant increase in a lung injury scoring system, inflammatory cells in bronchoalveolar lavage (BAL) and IL-6, TNF-α and CXCL2 mRNA expression in lung tissue. Animals with emphysema and sepsis showed increased alveolocapillary membrane permeability, demonstrated by higher BAL/serum albumin ratio. In conclusion, the presence of emphysema induced by elastase increases the inflammatory response in the lungs to a systemic stimulus, represented in this model by the intraperitoneal injection of LPS.

Effect of alpha-lipoic acid on acute lung injury and acute kidney injury in major postpartum hemorrhage

Introduction Postpartum hemorrhage (PPH) is a major cause of maternal morbidity and mortality. Resuscitated hemorrhagic shock patients are susceptible to the development of a systemic inflammatory response and organ dysfunction. This study aimed to investigate the effects of alpha-lipoic acid (ALA) as an adjunctive therapy that protects against the occurrence of acute lung injury (ALI) and acute kidney injury (AKI) in patients with major PPH. Patients and methods Forty patients admitted to Ain Shams Obstetric ICU with major PPH were randomly allocated into two equal groups: the ALA group received intravenous 1200 mg ALA once daily for 3 days and the placebo group received 500 ml of 0.9% isotone saline solution over 60 min once daily for 3 days. The primary study outcome was the serum levels of thiobarbituric acid reactive species as a marker of oxidative damage and interleukin-6 as a marker of inflammatory response. The secondary outcomes were the incidence of ALI and AKI. Results ALA attenuated the oxidative damage and the inflammatory response as evidenced by the reduction in both thiobarbituric acid reactive species and interleukin-6 levels, respectively ( P 2 /FiO 2 ) reached less than 300 in 10% of patients in the ALA group and in 30% of patients in the placebo group. Conclusion ALA decreases markers of oxidative stress and inflammatory response and also has a preventive effect on the progression of ALI and AKI in patients with major PPH.

Role of Sulfur Dioxide in Acute Lung Injury Following Limb Ischemia/Reperfusion in Rats

Sulfur dioxide (SO2) is naturally synthesized by glutamate-oxaloacetate transaminase (GOT) from L-cysteine in mammalian cells. We aim to investigate the role of SO2 in inflammation in acute lung injury (ALI) following limb ischemia/reperfusion (I/R). Male Wistar rats were subjected to limb I/R and were injected with saline, GOT inhibitor hydroxamate (HDX, 0.47 mmol/kg), or the SO2 donor Na2 SO3 /NaHSO3 (0.54 mmol/kg/0.18 mmol/kg). Compared with the sham operation, the plasma SO2 levels were significantly decreased by limb I/R treatment. In addition, SO2 concentration and GOT activity in the lung tissue were also reduced in ALI. The occurrence of ALI following limb I/R can be prevented by Na2 SO3 /NaHSO3 treatment, whereas it can be significantly aggravated by HDX. The plasma IL-1β, IL-6, and IL-10 levels were consistent with myeloperoxidase activity and inflammation in lung tissue. In conclusion, our data suggest that downregulation of endogenous SO2 production might be involved in pathogenesis of ALI following limb I/R in rats.

Risk factors for the development of acute lung injury in patients with infectious pneumonia.

IntroductionAlthough pneumonia has been identified as the single most common risk factor for acute lung injury (ALI), we have a limited knowledge as to why ALI develops in some patients with pneumonia and not in others. The objective of this study was to determine frequency, risk factors, and outcome of ALI in patients with infectious pneumonia.MethodsA retrospective cohort study of adult patients with microbiologically positive pneumonia, hospitalized at two Mayo Clinic Rochester hospitals between January 1, 2005, and December 31, 2007. In a subsequent nested case-control analysis, we evaluated the differences in prehospital and intrahospital exposures between patients with and without ALI/acute respiratory distress syndrome (ARDS) matched by specific pathogen, isolation site, gender, and closest age in a 1:1 manner.ResultsThe study included 596 patients; 365 (61.2%) were men. The median age was 65 (IQR, 53 to 75) years. In total, 171 patients (28.7%) were diagnosed with ALI. The occurrence of ALI was less frequent in bacterial (n = 99 of 412, 24%) compared with viral (n = 19 of 55, 35%), fungal (n = 39 of 95, 41%), and mixed isolates pneumonias (n = 14 of 34, 41%; P = 0.002). After adjusting for baseline severity of illness and comorbidities, patients in whom ALI developed had a markedly increased risk of hospital death (ORadj 9.7; 95% CI, 6.0 to 15.9). In a nested case-control study, presence of shock (OR, 8.9; 95% CI, 2.8 to 45.9), inappropriate initial antimicrobial treatment (OR, 3.2; 95% CI, 1.3 to 8.5), and transfusions (OR, 4.8; 95% CI, 1.5 to 19.6) independently predicted ALI development.ConclusionsThe development of ALI among patients hospitalized with infectious pneumonia varied among pulmonary pathogens and was associated with increased mortality. Inappropriate initial antimicrobial treatment and transfusion predict the development of ALI independent of pathogen.

Soluble CD40 ligand, a mediator of sepsis or of transfusion-related adverse effects?

Dr Lorente and colleagues [1] report on the interesting association between serum soluble CD40 ligand (sCD40L) levels and mortality in patients with sepsis. Some variables that can influence outcome in sepsis were accounted for in their analysis. However, the amount of transfused blood products, which may influence levels of sCD40L, was not reported. sCD40L accumulates to biologically relevant levels during storage of blood products [2,3], in particular of platelet products. Following transfusion, blood products can induce an inflammatory reaction - by activating CD40-positive cells - associated with the occurrence of acute lung injury and other potential serious complications [3]. Levels of sCD40L were also found to be elevated in patients with lung injury following transfusion [2]. Even more, transfusion itself contributes to mortality in the critically ill [4], as well as to adverse outcome of sepsis [5]. Taken together, we suggest that blood transfusion could have potentially influenced both serum sCD40L levels and outcome in the study performed by Lorente and colleagues. The authors state that modulation of sCD40L levels could represent a therapeutic target. Would it not be more appropriate to question whether sCD40L from (stored) blood products contributed to elevated serum levels in their trial, before embarking on therapeutic interventions?

BPI A645G SNP but Not NOD2 Genotype Predicts for Acute Lung Injury After Allogeneic Stem Cell Transplantation

AbstractAbstract 2324 Introduction:Infectious as well as non-infectious pulmonary complications are key determinants of non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Single nucleotide polymorphisms (SNP) in two genes coding for nucleotide-binding oligomerization domain containing 2 (NOD2) and bactericidal/permeability-increasing protein (BPI) have been shown to predict for the occurrence of GvHD and chronic pulmonary complications after allo-HSCT. We aimed at determining the effect of SNPs in these genes on the occurrence of acute lung injury (ALI) after allo-HSCT. Patients and Methods:We retrospectively analyzed a cohort of 272 patients undergoing allo-HSCT and their respective related and unrelated donors. ALI was functionally defined as a drop of the oxygenation index (OI = partial pressure of oxygen in arterialized capillary blood/inhaled oxygen concentration) below 300. Genotyping for NOD2 SNP 8, 12 and 13 and BPI SNP A645G was done using Real Time-PCR. The incidence of ALI was assessed by univariate competing events statistics and by a multivariate model according to Fine and Gray. Results:Overall, 115 of 272 (42.3%) patients suffered from ALI at least once during the first 100 days post allo-HSCT. Median time to onset was 11 days. Neither NOD2 polymorphisms in the donor nor in the recipient correlated with the occurrence of ALI. Further, BPI recipient genotype was not associated with an increased incidence of this complication. On the other hand, ALI was more frequent in patients receiving a transplant from a donor homozygous for the G allele of the BPI A645G SNP (Figure 1). This association was confirmed in multivariate analysis (OR 1.46, p = 0.048). Other independent risk factors for the occurrence of ALI were age (as continuous variable, OR 1.03, p = 0.002) and transplantation from an unrelated vs. related donor (OR 1.66, p = 0.018) whereas the use of intensive conditioning was a risk factor of borderline significance (OR 1.59, p = 0.077). In spite of its association with ALI, BPI donor genotype did not correlate with cumulative incidence of NRM at 100 days (G/G: 6.7%, 95% CI: 1.0 – 12.4% vs. A/A or A/G: 10.2%, 95% CI: 6.0 – 14.4%; p = 0.380) or overall survival. Conclusion:In contrast to other investigators we found no correlation between NOD2 genotype and the occurrence of acute pulmonary complications after allo-HSCT. On the other hand, BPI A645G SNP in the donor was identified as an independent risk factor for ALI in these patients. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Acute lung injury in TBI patients with SIRS: role of vascular endothelial damage

The pathological organ dysfunction that occurs in patients with SIRS or sepsis is believed to be related to vascular endothelial damage. We investigated the role of vascular endothelial damage in the occurrence of acute lung injury in severe TBI patients with SIRS.