Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of Lung Inflammation

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

Download Full-text

Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration–induced Lung Injury

Anesthesiology ◽

10.1097/aln.0b013e31827542aa ◽

2012 ◽

Vol 117 (6) ◽

pp. 1322-1334 ◽

Cited By ~ 17

Author(s):

Aline M. Ambrosio ◽

Rubin Luo ◽

Denise T. Fantoni ◽

Claudia Gutierres ◽

Qin Lu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Lung Inflammation ◽

Recruitment Maneuver ◽

Alveolar Wall ◽

Arterial Oxygenation ◽

Positive End Expiratory Pressure ◽

Acid Aspiration ◽

Recruitment Maneuvers ◽

Alveolar Area

Background In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Download Full-text

miR-34b-5p inhibition attenuates lung inflammation and apoptosis in an LPS-induced acute lung injury mouse model by targeting progranulin

Journal of Cellular Physiology ◽

10.1002/jcp.26274 ◽

2018 ◽

Vol 233 (9) ◽

pp. 6615-6631 ◽

Cited By ~ 34

Author(s):

Wang Xie ◽

Qingchun Lu ◽

Kailing Wang ◽

Jingjing Lu ◽

Xia Gu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Model ◽

Lung Inflammation

Download Full-text

The differential expression of novel circular RNAs in an acute lung injury rat model caused by smoke inhalation

Journal of Physiology and Biochemistry ◽

10.1007/s13105-017-0598-5 ◽

2017 ◽

Vol 74 (1) ◽

pp. 25-33 ◽

Cited By ~ 7

Author(s):

Zhiqiang Ye ◽

Xuhui Liu ◽

Yuewu Yang ◽

Xianling Zhang ◽

Ting Yu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Differential Expression ◽

Rat Model ◽

Smoke Inhalation ◽

Circular Rnas

Download Full-text

Vanillin protects lipopolysaccharide-induced acute lung injury by inhibiting ERK1/2, p38 and NF-κB pathway

Future Medicinal Chemistry ◽

10.4155/fmc-2018-0432 ◽

2019 ◽

Vol 11 (16) ◽

pp. 2081-2094 ◽

Cited By ~ 1

Author(s):

Tingting Guo ◽

Zhenzhong Su ◽

Qi Wang ◽

Wei Hou ◽

Junyao Li ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Western Blot ◽

Lung Inflammation ◽

Macrophage Activation ◽

Myeloperoxidase Activity ◽

Histopathological Changes ◽

Tnf Α ◽

Anti Inflammatory ◽

Inflammatory Effect

Aim: Thus far, the anti-inflammatory effect of vanillin in acute lung injury (ALI) has not been studied. This study aimed to investigate the effect of vanillin in lipopolysaccharide (LPS)-induced ALI. Results & methodology: Our study detected the anti-inflammatory effects of vanillin by ELISA and western blot, respectively. Pretreatment of mice with vanillin significantly attenuated LPS-stimulated lung histopathological changes, myeloperoxidase activity and expression levels of proinflammatory cytokines by inhibiting the phosphorylation activities of ERK1/2, p38, AKT and NF-κB p65. In addition, vanillin inhibited LPS-induced TNF-α and IL-6 expression in RAW264.7 cells via ERK1/2, p38 and NF-κB signaling. Conclusion: Vanillin can inhibit macrophage activation and lung inflammation, which suggests new insights for clinical treatment of ALI.

Download Full-text

Keratinocyte growth factor therapy in murine oleic acid-induced acute lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00450.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. L1179-L1192 ◽

Cited By ~ 40

Author(s):

K. Ulrich ◽

M. Stern ◽

M. E. Goddard ◽

J. Williams ◽

J. Zhu ◽

...

Keyword(s):

Cell Proliferation ◽

Acute Lung Injury ◽

Gene Delivery ◽

Lung Injury ◽

Time Course ◽

Lung Compliance ◽

Alveolar Type ◽

Protein Therapy ◽

Cell Numbers ◽

Atii Cell

Alveolar type II (ATII) cell proliferation and differentiation are important mechanisms in repair following injury to the alveolar epithelium. KGF is a potent ATII cell mitogen, which has been demonstrated to be protective in a number of animal models of lung injury. We have assessed the effect of recombinant human KGF (rhKGF) and liposome-mediated KGF gene delivery in vivo and evaluated the potential of KGF as a therapy for acute lung injury in mice. rhKGF was administered intratracheally in male BALB/c mice to assess dose response and time course of proliferation. SP-B immunohistochemistry demonstrated significant increases in ATII cell numbers at all rhKGF doses compared with control animals and peaked 2 days following administration of 10 mg/kg rhKGF. Protein therapy in general is very expensive, and gene therapy has been suggested as a cheaper alternative for many protein replacement therapies. We evaluated the effect of topical and systemic liposome-mediated KGF-gene delivery on ATII cell proliferation. SP-B immunohistochemistry showed only modest increases in ATII cell numbers following gene delivery, and these approaches were therefore not believed to be capable of reaching therapeutic levels. The effect of rhKGF was evaluated in a murine model of OA-induced lung injury. This model was found to be associated with significant alveolar damage leading to severe impairment of gas exchange and lung compliance. Pretreatment with rhKGF 2 days before intravenous OA challenge resulted in significant improvements in Po2, Pco2, and lung compliance. This study suggests the feasibility of KGF as a therapy for acute lung injury.

Download Full-text