Pneumonia Injury Research Articles

A meta-analysis of risk factors for acute kidney injury in pneumonia: Effectiveness of nursing interventions.

The spread of coronavirus disease 2019 (COVID-19) worldwide since November 2019 is of interest to understand its impact on various organs. COVID-19 patients experience a higher incidence of acute kidney injury (AKI) compared with non-COVID-19 patients. A systematic literature search was conducted that covered the period from November 1, 2019 to February 28, 2021. The analysis incorporated a comprehensive review of 19 studies of 21 362 patients. The older age (mean difference [MDs] = 5.11), cardiovascular disease (CVD) (odds ratio [OR] = 1.94), male sex (OR = 1.55), chronic kidney disease (CKD) (OR = 3.82), hypertension (OR = 2.15), diabetes (OR = 1.71), cancer (OR = 1.16), and chronic obstructive pulmonary disease (COPD) (OR = 1.40), mechanical ventilation (OR = 8.66), and vasopressor (OR = 6.30), were significantly associated with risk factor for AKI (P < 0.05). The analysis revealed independent risk factors for AKI.

LncRNA UCA1 remits LPS-engendered inflammatory damage through deactivation of miR-499b-5p/TLR4 axis.

Neonatal pneumonia is a high neonatal mortality disease. The current research was designed to elucidate the modulatory function and feasible molecular mechanism of UCA1 in LPS-induced injury in pneumonia. Herein, LPS was applied to induce WI-38 cell inflammatory damage. We displayed that UCA1 was elevated in LPS-injured WI-38 cells. In the functional aspect, intervention of UCA1 evidently aggrandized cell viability in LPS-triggered WI-38 cells. In the meanwhile, elimination of UCA1 distinctly assuaged cell apoptosis concomitant with declined levels of proapoptotic proteins Bax and C-caspase-3, and ascended the expression of antiapoptotic protein Bcl-2. Subsequently, disruption of UCA1 manifestly restrained inflammatory damage as characterized by declination of multiple pro-inflammatory factors IL-1β, IL-6, and TNF-α in WI-38 cells under LPS circumstance. More importantly, we predicted and verified that UCA1 functioned as a ceRNA by efficaciously binding to miR-499b-5p thereby inversely adjusting miR-499b-5p expression. Interesting, TLR4 was identified as direct target of miR-499b-5p, and positively regulated by UCA1 through sponging miR-499b-5p. Mechanistically, absence of miR-499b-5p or restoration of TLR4 impeded the beneficial effects of UCA1 ablation on LPS-stimulated apoptosis and inflammatory response. Collectively, these observations illuminated that UCA1 inhibition protected WI-38 cells against LPS-managed inflammatory injury and apoptosis process via miR-499b-5p/TLR4 crosstalk, which ultimately influencing the development of pneumonia.

Knockdown XIST alleviates LPS-induced WI-38 cell apoptosis and inflammation injury via targeting miR-370-3p/TLR4 in acute pneumonia.

Pneumonia is an inflammatory disease that occurs in the lungs associated with pathogens or other factors. It has been well established that long noncoding RNA X inactivate‐specific transcript (XIST) is involved in several cancers. The present study focused on the effect and detailed mechanism of XIST in lipopolysaccharide (LPS)‐induced injury in pneumonia. Here, XIST was silenced by transfection with XIST‐targeted siRNA, and then, mRNA expression, cell viability, apoptosis, and protein expression were, respectively, assessed by qRT‐PCR, CCK‐8, flow cytometry, and Western blotting. Luciferase reporter, RIP, and RNA pull‐down assays were used to detect the combination of miR‐370‐3p and XIST. Besides, the tested proinflammatory factors were analysed by qRT‐PCR and Western blot, and their productions were quantified by ELISA. The results showed that XIST expression was robustly increased in serum of patients with acute‐stage pneumonia and LPS‐induced WI‐38 human lung fibroblasts cells. Functional analyses demonstrated that knockdown of XIST remarkably alleviated LPS‐induced cell injury through increasing cell viability and inhibiting apoptosis and inflammatory cytokine levels. Mechanistically, XIST functioned as a competitive endogenous RNA (ceRNA) by effectively binding to miR‐370‐3p and then restoring TLR4 expression. More importantly, miR‐370‐3p inhibitor abolished the function of XIST knockdown on cell injury and JAK/STAT and NF‐κB pathways. Taken together, XIST may be involved in progression of cell inflammatory response, and XIST/miR‐370‐3p/TLR4 axis thus may shed light on the development of novel therapeutics to the treatment of acute stage of pneumonia.Significance of the studyOur study demonstrated that XIST was highly expressed in patients with acute stage of pneumonia. Knockdown of XIST remarkably alleviated LPS‐induced cell injury through increasing cell viability and inhibiting apoptosis and inflammatory cytokine levels through regulating JAK/STAT and NF‐κB pathways.

The aquaporin 5 -1364A/C promoter polymorphism impacts on resolution of acute kidney injury in pneumonia evoked ARDS.

BackgroundAquaporin 5 (AQP5) expression impacts on cellular water transport, renal function but also on key mechanisms of inflammation and immune cell migration that prevail in sepsis and ARDS. Thus, the functionally relevant AQP5 -1364A/C promoter single nucleotide polymorphism could impact on the development and resolution of acute kidney injury (AKI). Accordingly, we tested the hypothesis that the AQP5 promoter -1364A/C polymorphism is associated with AKI in patients suffering from pneumonia evoked ARDS.MethodsThis prospective study included 136 adult patients of Caucasian ethnicity with bacterially evoked pneumonia resulting in ARDS. Blood sampling was performed within 24 hours of ICU admission and patients were genotyped for the AQP5 promoter -1364A/C single nucleotide polymorphism. The development of an AKI and the cumulative net fluid balance was described over a 30-day observation period and compared between the AA and AC/CC genotypes, and between survivors and non-survivors.ResultsIncidence of an AKI upon admission did not differ in AA (58%) and AC/CC genotype carriers (60%; p = 0.791). However, on day 30, homozygous AA genotypes (57%) showed an increased prevalence of AKI compared to AC/CC genotypes (24%; p = 0.001). Furthermore, the AA genotype proved to be a strong, independent risk factor for predicting AKI persistence (odds-ratio: 3.35; 95%-CI: 1.2–9.0; p = 0.017). While a negative cumulative fluid balance was associated with increased survival (p = 0.001) the AQP5 promoter polymorphism had no impact on net fluid balance (p = 0.96).ConclusionsIn pneumonia evoked ARDS, the AA genotype of the AQP5 promoter polymorphism is associated with a decreased recovery rate from AKI and this is independent of fluid balance. Consequently, the role of AQP5 in influencing AKI likely rests in factors other than fluid balance.

Long noncoding RNA HAGLROS regulates cell apoptosis and autophagy in lipopolysaccharides-induced WI-38 cells via modulating miR-100/NF-κB axis

Pneumonia is a lower respiratory disease caused by pathogens or other factors. This study aimed to explore the roles and mechanism of long noncoding RNA HAGLROS in lipopolysaccharides (LPS)-induced inflammatory injury in pneumonia. The HAGLROS expression in serum of patients with acute stage pneumonia was detected. To induce pulmonary injury, WI-38 human lung fibroblasts were stimulated with lipopolysaccharides (LPS). The HAGLROS expressions in LPS-treated WI-38 cells and the effects of HAGLROS knockdown on the viability, apoptosis, and autophagy of LPS-induced cells were detected. Moreover, the regulatory relationship between HAGLROS and miR-100 was explored as well as the functional targets of miR-100 were identified. Furthermore, the regulatory relationship between miR-100 and PI3K/AKT/NF-κB pathway was elucidated. LncRNA HAGLROS was higher expressed in serum of patients with acute stage pneumonia compared with that in serum of healthy control. LPS caused WI-38 cell injury and increased HAGLROS levels. Downregulation of HAGLROS alleviated LPS-induced cell injury via increasing cell viability, and inhibiting apoptosis and autophagy. Moreover, there was a negative correlation between HAGLROS and miR-100, and the effects of HAGLROS downregulation on LPS-induced apoptosis and autophagy in WI-38 cells were by regulation of miR-100. Furthermore, NFΚB3 was verified as a functional target of miR-100 and effects of miR-100 inhibition on LPS-induced WI-38 cell injury were alleviated by knockdown of NFΚB3. Besides, Knockdown of HAGLROS inhibited the activation of PI3K/AKT/NF-κB pathway. Our findings reveal that downregulation of HAGLROS may alleviate LPS-induced inflammatory injury in WI-38 cells via modulating miR-100/NF-κB axis. HAGLROS/miR-100/NF-κB axis may provide a new strategy for treating acute stage of pneumonia.

Epithelial Sodium Channel-α Mediates the Protective Effect of the TNF-Derived TIP Peptide in Pneumolysin-Induced Endothelial Barrier Dysfunction.

Streptococcus pneumoniae is a major etiologic agent of bacterial pneumonia. Autolysis and antibiotic-mediated lysis of pneumococci induce release of the pore-forming toxin, pneumolysin (PLY), their major virulence factor, which is a prominent cause of acute lung injury. PLY inhibits alveolar liquid clearance and severely compromises alveolar-capillary barrier function, leading to permeability edema associated with pneumonia. As a consequence, alveolar flooding occurs, which can precipitate lethal hypoxemia by impairing gas exchange. The α subunit of the epithelial sodium channel (ENaC) is crucial for promoting Na+ reabsorption across Na+-transporting epithelia. However, it is not known if human lung microvascular endothelial cells (HL-MVEC) also express ENaC-α and whether this subunit is involved in the regulation of their barrier function. The presence of α, β, and γ subunits of ENaC and protein phosphorylation status in HL-MVEC were assessed in western blotting. The role of ENaC-α in monolayer resistance of HL-MVEC was examined by depletion of this subunit by specific siRNA and by employing the TNF-derived TIP peptide, a specific activator that directly binds to ENaC-α. HL-MVEC express all three subunits of ENaC, as well as acid-sensing ion channel 1a (ASIC1a), which has the capacity to form hybrid non-selective cation channels with ENaC-α. Both TIP peptide, which specifically binds to ENaC-α, and the specific ASIC1a activator MitTx significantly strengthened barrier function in PLY-treated HL-MVEC. ENaC-α depletion significantly increased sensitivity to PLY-induced hyperpermeability and in addition, blunted the protective effect of both the TIP peptide and MitTx, indicating an important role for ENaC-α and for hybrid NSC channels in barrier function of HL-MVEC. TIP peptide blunted PLY-induced phosphorylation of both calmodulin-dependent kinase II (CaMKII) and of its substrate, the actin-binding protein filamin A (FLN-A), requiring the expression of both ENaC-α and ASIC1a. Since non-phosphorylated FLN-A promotes ENaC channel open probability and blunts stress fiber formation, modulation of this activity represents an attractive target for the protective actions of ENaC-α in both barrier function and liquid clearance. Our results in cultured endothelial cells demonstrate a previously unrecognized role for ENaC-α in strengthening capillary barrier function that may apply to the human lung. Strategies aiming to activate endothelial NSC channels that contain ENaC-α should be further investigated as a novel approach to improve barrier function in the capillary endothelium during pneumonia.

Imaging Findings of Aspiration Pneumonia Injury Caused by Gas From Smoke Bomb

Imaging Findings of Aspiration Pneumonia Injury Caused by Gas From Smoke Bomb

New Pathogenetic Concepts and Pharmacological Studies on Adjuvant Therapy in Severe Pneumonia

Acute lung injury secondary to pneumonia results from inadequate activation of the innate immune system with hyperinflammation and alveolar-capillary barrier dysfunction. To date, effective strategies for prevention or treatment of acute lung injury in pneumonia besides antibiotics are lacking. In preclinical studies, promising therapeutic targets have been identified and novel strategies demonstrated to protect against lung failure in pneumonia. This review highlights some adjuvant therapeutic strategies for modulation of inflammation and stabilization of lung barrier function in pneumonia.

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

IntroductionVentilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia.MethodsWe analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation.ResultsIn pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1–3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut).ConclusionsMV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

Epidermal Growth Factor Improves SurvivaL and Prevents Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

Experimental study on development and lung injury in pneumonia under neutropenic condition

This study was performed to demonstrate the characteristic findings in pneumonia under neutropenic condition. The results were as follows. 1) After nebulizing Klebsiella pneumonia DT-S strains, the survival rate in the neutropenic mouse group rapidly decreased compared with that of the control group. 2) In the neutropenic state, a rapid decline of survival rate was demonstrated during the initial stage of infection. Bacteremia and endotoxemia developed earlier than in the healthy control group. 3) In neutropenic pneumonia, the neutrophil cell count in BALF was significantly lower than that in usual pneumonia. Consequently, a large number of bacteria grew in the alveolar spaces during the early period after inhalation. Neither inflammatory cell infiltration nor thickening of the alveolar wall was present; however, structural destruction of alveolar and vascular walls was found. 4) These pathological changes were also seen following intratracheal inoculation of some extracellular enzymes of Klebsiella pneumoniae DT-S into rabbit lung. However, no destruction of alveolar walls was observed after nebulizing the killed Klebsiella pneumoniae DT-S. It was suggested that the significant amount of enzymes produced by the bacteria growing in the alveoli caused tissue damage, especially in the neutropenic state. 5) Thus the typical inflammatory changes that occurred in the usual state, were not seen in neutropenic pneumonia, and a large number of bacteria grew in the alveoli. Marked tissue damage was caused by extracellular enzymes produced by bacteria. Consequently, bacteria entered the blood stream and bacteremia and endotoxemia developed. These processes observed in neutropenic pneumonia readily progressed to bacteremia of endotoxemia, which are more severe in this state.