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Zhang J, Guo Y, Mak M, Tao Z. Translational medicine for acute lung injury. J Transl Med 2024; 22:25. [PMID: 38183140 PMCID: PMC10768317 DOI: 10.1186/s12967-023-04828-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 12/24/2023] [Indexed: 01/07/2024] Open
Abstract
Acute lung injury (ALI) is a complex disease with numerous causes. This review begins with a discussion of disease development from direct or indirect pulmonary insults, as well as varied pathogenesis. The heterogeneous nature of ALI is then elaborated upon, including its epidemiology, clinical manifestations, potential biomarkers, and genetic contributions. Although no medication is currently approved for this devastating illness, supportive care and pharmacological intervention for ALI treatment are summarized, followed by an assessment of the pathophysiological gap between human ALI and animal models. Lastly, current research progress on advanced nanomedicines for ALI therapeutics in preclinical and clinical settings is reviewed, demonstrating new opportunities towards developing an effective treatment for ALI.
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Affiliation(s)
- Jianguo Zhang
- Department of Emergency Medicine, The Affiliated Hospital, Jiangsu University, Zhenjiang, 212001, Jiangsu, China
| | - Yumeng Guo
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
| | - Michael Mak
- Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University, New Haven, 06520, USA
| | - Zhimin Tao
- Department of Emergency Medicine, The Affiliated Hospital, Jiangsu University, Zhenjiang, 212001, Jiangsu, China.
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
- Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University, New Haven, 06520, USA.
- Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China.
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Yu X, Xu J, Liu W, Zhang Z, He C, Xu W. Protective effects of pulmonary surfactant on decompression sickness in rats. J Appl Physiol (1985) 2020; 130:400-407. [PMID: 33270509 DOI: 10.1152/japplphysiol.00807.2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Decompression sickness (DCS) is a systemic pathophysiological process featured by bubble load. Lung dysfunction plays a harmful effect on off-gassing, which contributes to bubble load and subsequent DCS occurrence. This study aimed to investigate the effects of pulmonary surfactant on DCS as it possesses multiple advantages on the lung. Rats were divided into three groups: the normal (n = 10), the surfactant (n = 36), and the saline (n = 36) group. Animals in surfactant or saline group were administered aerosol surfactant or saline 12 h before a stimulated diving, respectively. Signs of DCS were recorded and bubble load was detected. The contents of phospholipid and surfactant protein A (SPA), protein, IL-1 and IL-6 in bronchoalveolar lavage fluid (BALF), and lung wet/dry (W/D) ratio were determined. Serum levels of IL-6, ICAM-1, E-selectin, GSH, and GSSG were detected. In surfactant-treated rats, the morbidity and mortality of DCS markedly decreased (P < 0.01 and P < 0.05, respectively). Survival time prolonged and the latency to DCS dramatically delayed (P < 0.01). More importantly, bubble load markedly decreased (P < 0.01). The increases of protein, IL-1 and IL-6 in BALF, and lung W/D ratio were alleviated. Restoration of total phospholipid and SPA in BALF and ICAM-1 and E-selectin in serum was observed. The inflammation and oxidation were attenuated (P < 0.01). In conclusion, prediving administrating exogenous surfactant by aerosolization is an efficient, simple, and safe method for DCS prevention in rats.NEW & NOTEWORTHY This is the first study exploring the effects of aerosol surfactant on DCS prevention and it was proven to be an efficient and simple method. The role of surfactant in facilitating off-gassing was thought to be the critical mechanism in bubble degrading and subsequent DCS prevention.
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Affiliation(s)
- Xuhua Yu
- Department of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, China
| | - Jiajun Xu
- Department of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, China
| | - Wenwu Liu
- Department of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, China
| | - Ze Zhang
- The 17th detachment of the frigate, Jiangmen, China
| | - Chunyang He
- Department of Hyperbaric Oxygen, General Hospital in Western Theater of Operations, Chengdu, China
| | - Weigang Xu
- Department of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, China
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Hagan R, Gillan CJ, Spence I, McAuley D, Shyamsundar M. Comparing regression and neural network techniques for personalized predictive analytics to promote lung protective ventilation in Intensive Care Units. Comput Biol Med 2020; 126:104030. [PMID: 33068808 PMCID: PMC7543875 DOI: 10.1016/j.compbiomed.2020.104030] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 09/29/2020] [Accepted: 09/29/2020] [Indexed: 12/11/2022]
Abstract
Mechanical ventilation is a lifesaving tool and provides organ support for patients with respiratory failure. However, injurious ventilation due to inappropriate delivery of high tidal volume can initiate or potentiate lung injury. This could lead to acute respiratory distress syndrome, longer duration of mechanical ventilation, ventilator associated conditions and finally increased mortality. In this study, we explore the viability and compare machine learning methods to generate personalized predictive alerts indicating violation of the safe tidal volume per ideal body weight (IBW) threshold that is accepted as the upper limit for lung protective ventilation (LPV), prior to application to patients. We process streams of patient respiratory data recorded per minute from ventilators in an intensive care unit and apply several state-of-the-art time series prediction methods to forecast the behavior of the tidal volume metric per patient, 1 hour ahead. Our results show that boosted regression delivers better predictive accuracy than other methods that we investigated and requires relatively short execution times. Long short-term memory neural networks can deliver similar levels of accuracy but only after much longer periods of data acquisition, further extended by several hours computing time to train the algorithm. Utilizing Artificial Intelligence, we have developed a personalized clinical decision support tool that can predict tidal volume behavior within 10% accuracy and compare alerts recorded from a real world system to highlight that our models would have predicted violations 1 hour ahead and can therefore conclude that the algorithms can provide clinical decision support.
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Affiliation(s)
- Rachael Hagan
- School of Electrical and Electronic Engineering and Computer Science, Queen's University Belfast, Queen's Road, Queen's Island, Belfast, Northern Ireland, BT9 3DT, United Kingdom.
| | - Charles J Gillan
- School of Electrical and Electronic Engineering and Computer Science, Queen's University Belfast, Queen's Road, Queen's Island, Belfast, Northern Ireland, BT9 3DT, United Kingdom
| | - Ivor Spence
- School of Electrical and Electronic Engineering and Computer Science, Queen's University Belfast, Queen's Road, Queen's Island, Belfast, Northern Ireland, BT9 3DT, United Kingdom
| | - Danny McAuley
- The Centre for Experimental Medicine, School of Medicine, Dentistry and Biological Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, United Kingdom
| | - Murali Shyamsundar
- The Centre for Experimental Medicine, School of Medicine, Dentistry and Biological Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, United Kingdom
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Yeh JJ. Predictors of Initial Smear-Negative Active Pulmonary Tuberculosis with Acute Early Stage Lung Injury by High-Resolution Computed Tomography and Clinical Manifestations: An Auxiliary Model in Critical Patients. Sci Rep 2019; 9:4527. [PMID: 30872774 PMCID: PMC6418143 DOI: 10.1038/s41598-019-40799-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 02/21/2019] [Indexed: 12/13/2022] Open
Abstract
This study evaluated the diagnostic use of high-resolution computed tomography (HRCT), chest X-ray (CXR), and clinical manifestations (CM) to identify initial smear-negative (iSN) active pulmonary tuberculosis (aPTB) [iSN-aPTB] in patients with iSN-pulmonary diseases (PD) and acute lung injury (ALI). In the derivation cohort, the [iSN-PD] with ALI patients were divided into the [iSN-aPTB] (G1, n = 26) and [non-aPTB-PD] (G2, n = 233) groups. Lung morphology, number, and lobar (segmental) distribution were evaluated using CXR and HRCT. A multivariate analysis was performed to identify independent variables associated with G1, which were used to generate predictive score models for G1. The predictive model was validated in a separate population of patients (n = 372) with [iSN-PD] and (ALI). The validated model for [HRCT (CXR + Hypoalbuminemia)] had 93.5% (25.8%) sensitivity, 99.5% (89.4%) specificity, and a negative predictive value of 99.5% (93.0%). For [iSN-aPTB], the post-test probability in the derivation cohort (prevalence = 10%), validation cohort (prevalence = 8.3%), and the given prevalence (prevalence = 1%) was 88.7%, 94.4%, and 41.5%, respectively. The HRCT model effectively identified the [iSN-aPTB] subjects among the [iSN-PD] with ALI, regardless of CM. The [non-aPTB-PD] were also correctly classified by the HRCT and [CXR + Hypoalbuminemia] models.
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Affiliation(s)
- Jun-Jun Yeh
- Department of Pulmonary Medicine, Section of Thoracic Imaging, and Family Medicine, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chiayi, Taiwan.
- Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
- China Medical University, Taichung, Taiwan.
- Pingtung Christian Hospital, Pingtung, Taiwan.
- Heng Chun Christian Hospital, Pingtung, Taiwan.
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Tian YG, Zhang J. Protective effect of SIRT3 on acute lung injury by increasing manganese superoxide dismutase-mediated antioxidation. Mol Med Rep 2018; 17:5557-5565. [PMID: 29363727 DOI: 10.3892/mmr.2018.8469] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 12/19/2016] [Indexed: 11/06/2022] Open
Abstract
Prolonged exposure to hyperoxia results in acute lung injury (ALI). Pulmonary damage caused by oxygen toxicity occurs due to the generation of reactive oxygen species and subsequent formation of more potent oxidants. The present study demonstrated that sirtuin 3 (SIRT3) may attenuate hyperoxia‑induced ALI due to its potential antioxidative effect. In the present study, a hyperoxia‑induced acute lung injury mouse model, reverse transcription‑quantitative polymerase chain reaction, western blotting, retroviral mediated gene over‑expression and knockdown assays revealed that the expression of SIRT3 in the lung tissue of mice with hyperoxia‑induced ALI was decreased and overexpression of SIRT3 may significantly reduce hyperoxia‑induced ALI, as reflected by decreases in protein concentration, infiltrated neutrophils in bronchoalveolar lavage (BAL) fluid and wet/dry ratio of lung tissues. Furthermore, overexpression of SIRT3 increased the protein levels and enzymatic activity of manganese superoxide dismutase (MnSOD), and inhibited oxidative stress in the lungs of ALI mice. Additionally, the current study demonstrated that SIRT3 promoted the expression of MnSOD, and this regulation was crucial for the protective effect of SIRT3 on hyperoxia‑induced ALI. In summary, the results of the current study indicated that SIRT3 overexpression may effectively ameliorate hyperoxia‑induced ALI in mice, which indicates a potential application for SIRT3‑based gene therapy to treat clinical adult respiratory distress syndrome.
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Affiliation(s)
- Yong Gang Tian
- Department of Critical Care Medicine, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
| | - Jian Zhang
- Department of Critical Care Medicine, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China
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Mizock BA, DeMichele SJ. The Acute Respiratory Distress Syndrome: Role of Nutritional Modulation of Inflammation Through Dietary Lipids. Nutr Clin Pract 2017; 19:563-74. [PMID: 16215155 DOI: 10.1177/0115426504019006563] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The acute respiratory distress syndrome (ARDS) is the most serious form of acute hypoxic respiratory failure. ARDS represents the expression of an acute, diffuse, inflammatory process in the lungs consequent to a variety of infectious and noninfectious conditions. It is characterized pathologically by damage to pulmonary epithelial and endothelial cells, with subsequent alveolar-capillary leak and exudative pulmonary edema. The main clinical features of ARDS include rapid onset of dyspnea, severe defects in gas exchange, and imaging studies demonstrating diffuse pulmonary infiltrates. The role of nutrition in the management of ARDS has traditionally been supportive. Recent research has demonstrated the potential of certain dietary oils (eg, fish oil, borage oil) to modulate pulmonary inflammation, thereby improving lung compliance and oxygenation, and reducing time on mechanical ventilation. This article reviews the alterations in the immune response that underlie ARDS, discusses the physiology of dietary oils as immunonutrients, summarizes animal and human studies that explore the therapeutic effects of dietary oils, and provides clinical recommendations for their use.
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Affiliation(s)
- Barry A Mizock
- Department of Medicine, Cook County Hospital, 1900 West Polk Street, Chicago, Illinois 60612, USA.
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Abstract
Lung involvement in malaria has been recognized for more than 200 hundred years, yet our knowledge of its pathogenesis and management is limited. Pulmonary edema is the most severe form of lung involvement. Increased alveolar capillary permeability leading to intravascular fluid loss into the lungs is the main pathophysiologic mechanism. This defines malaria as another cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).Pulmonary edema has been described most often in non-immune individuals with Plasmodium falciparum infections as part of a severe systemic illness or as the main feature of acute malaria. P.vivax and P.ovale have also rarely caused pulmonary edema.Clinically, patients usually present with acute breathlessness that can rapidly progress to respiratory failure either at disease presentation or, interestingly, after treatment when clinical improvement is taking place and the parasitemia is falling. Pregnant women are particularly prone to developing pulmonary edema. Optimal management of malaria-induced ALI/ARDS includes early recognition and diagnosis. Malaria must always be suspected in a returning traveler or a visitor from a malaria-endemic country with an acute febrile illness. Slide microscopy and/or the use of rapid antigen tests are standard diagnostic tools. Malaria must be treated with effective drugs, but current choices are few: e.g. parenteral artemisinins, intravenous quinine or quinidine (in the US only). A recent trial in adults has shown that intravenous artesunate reduces severe malaria mortality by a third compared with adults treated with intravenous quinine. Respiratory compromise should be managed on its merits and may require mechanical ventilation.Patients should be managed in an intensive care unit and particular attention should be paid to the energetic management of other severe malaria complications, notably coma and acute renal failure. ALI/ARDS may also be related to a coincidental bacterial sepsis that may not be clinically obvious. Clinicians should employ a low threshold for starting broad spectrum antibacterials in such patients, after taking pertinent microbiologic specimens. Despite optimal management, the prognosis of severe malaria with ARDS is poor.ALI/ARDS in pediatric malaria appears to be rare. However, falciparum malaria with severe metabolic acidosis or acute pulmonary edema may present with a clinical picture of pneumonia, i.e. with tachypnea, intercostal recession, wheeze or inspiratory crepitations. This results in diagnostic confusion and suboptimal treatment. Whilst this is increasingly being recognized in malaria-endemic countries, clinicians in temperate zones should be aware that malaria may be a possible cause of 'pneumonia' in a visiting or returning child.
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Affiliation(s)
- Walter R J Taylor
- Travel and Migration Medicine Unit, Department of Community Medicine, Geneva University Hospital, Geneva, Switzerland
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Mehta D, Ravindran K, Kuebler WM. Novel regulators of endothelial barrier function. Am J Physiol Lung Cell Mol Physiol 2014; 307:L924-35. [PMID: 25381026 PMCID: PMC4269690 DOI: 10.1152/ajplung.00318.2014] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Accepted: 11/05/2014] [Indexed: 12/15/2022] Open
Abstract
Endothelial barrier function is an essential and tightly regulated process that ensures proper compartmentalization of the vascular and interstitial space, while allowing for the diffusive exchange of small molecules and the controlled trafficking of macromolecules and immune cells. Failure to control endothelial barrier integrity results in excessive leakage of fluid and proteins from the vasculature that can rapidly become fatal in scenarios such as sepsis or the acute respiratory distress syndrome. Here, we highlight recent advances in our understanding on the regulation of endothelial permeability, with a specific focus on the endothelial glycocalyx and endothelial scaffolds, regulatory intracellular signaling cascades, as well as triggers and mediators that either disrupt or enhance endothelial barrier integrity, and provide our perspective as to areas of seeming controversy and knowledge gaps, respectively.
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Affiliation(s)
- Dolly Mehta
- Department of Pharmacology and Center for Lung and Vascular Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois;
| | - Krishnan Ravindran
- Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada
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Davies J, Karmouty-Quintana H, Le TT, Chen NY, Weng T, Luo F, Molina J, Moorthy B, Blackburn MR. Adenosine promotes vascular barrier function in hyperoxic lung injury. Physiol Rep 2014; 2:2/9/e12155. [PMID: 25263205 PMCID: PMC4270235 DOI: 10.14814/phy2.12155] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Hyperoxic lung injury is characterized by cellular damage from high oxygen concentrations that lead to an inflammatory response in the lung with cellular infiltration and pulmonary edema. Adenosine is a signaling molecule that is generated extracellularly by CD73 in response to injury. Extracellular adenosine signals through cell surface receptors and has been found to be elevated and plays a protective role in acute injury situations. In particular, ADORA2B activation is protective in acute lung injury. However, little is known about the role of adenosine signaling in hyperoxic lung injury. We hypothesized that hyperoxia-induced lung injury leads to CD73-mediated increases in extracellular adenosine, which is protective through ADORA2B signaling pathways. To test this hypothesis, we exposed C57BL6, CD73(-/-), and Adora2B(-/-) mice to 95% oxygen or room air and examined markers of pulmonary inflammation, edema, and monitored lung histology. Hyperoxic exposure caused pulmonary inflammation and edema in association with elevations in lung adenosine levels. Loss of CD73-mediated extracellular adenosine production exacerbated pulmonary edema without affecting inflammatory cell counts. Furthermore, loss of the ADORA2B had similar results with worsening of pulmonary edema following hyperoxia exposure without affecting inflammatory cell infiltration. This loss of barrier function correlated with a decrease in occludin in pulmonary vasculature in CD73(-/-) and Adora2B(-/-) mice following hyperoxia exposure. These results demonstrate that exposure to a hyperoxic environment causes lung injury associated with an increase in adenosine concentration, and elevated adenosine levels protect vascular barrier function in hyperoxic lung injury through the ADORA2B-dependent regulation of occludin.
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Affiliation(s)
- Jonathan Davies
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
| | - Harry Karmouty-Quintana
- Department of Biochemistry and Molecular Biology, The University of Texas - Houston Medical School, Houston, Texas
| | - Thuy T Le
- Department of Biochemistry and Molecular Biology, The University of Texas - Houston Medical School, Houston, Texas
| | - Ning-Yuan Chen
- Department of Biochemistry and Molecular Biology, The University of Texas - Houston Medical School, Houston, Texas
| | - Tingting Weng
- Department of Biochemistry and Molecular Biology, The University of Texas - Houston Medical School, Houston, Texas
| | - Fayong Luo
- Department of Biochemistry and Molecular Biology, The University of Texas - Houston Medical School, Houston, Texas
| | - Jose Molina
- Department of Biochemistry and Molecular Biology, The University of Texas - Houston Medical School, Houston, Texas
| | - Bhagavatula Moorthy
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
| | - Michael R Blackburn
- Department of Biochemistry and Molecular Biology, The University of Texas - Houston Medical School, Houston, Texas
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Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury. Redox Biol 2014; 2:314-22. [PMID: 24563849 PMCID: PMC3926109 DOI: 10.1016/j.redox.2014.01.013] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Revised: 01/14/2014] [Accepted: 01/14/2014] [Indexed: 01/07/2023] Open
Abstract
Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to ≥99% O2 (hyperoxia) significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF) prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1) caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP), inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation.
Exposure to hyperoxia results in accumulation of high levels of airway HMGB1 that precede inflammatory acute lung injury (ALI). Airway HMGB1 is critical in mediating hyperoxia-induced inflammatory ALI via recruiting leukocytes including neutrophils. Extracellular HMGB1-accumulated upon prolonged exposure to hyperoxia is hyperacetylated, existing in different redox states. Small molecule EP, administrated even after the onset of hyperoxic exposure, can mitigate hyperoxia-induced inflammatory ALI by inhibiting HMGB1 release into the extracellular milieu.
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Key Words
- ALI, acute lung injury
- BALF, bronchoalveolar lavage fluids
- EP, ethyl pyruvate
- GST, gluthatione-s-transferase
- HMGB1
- HMGB1, high mobility group box protein 1
- Hyperacetylation
- Hyperoxia
- MV, mechanical ventilation
- Macrophage
- NLS, nuclear localization signal
- PMNs, polymorphonuclear neutrophils
- RA, room air
- ROS, reactive oxygen species
- Redox state
- rHMGB1, recombinant HMGB1
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McCartney R, Saha S, Rees J, Lawy T, Mosaheb R. Inhaled Nitric Oxide: A Review of the Action, Current Literature, and An Analysis of its Use in the NHS Today. J Intensive Care Soc 2013. [DOI: 10.1177/175114371301400311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Nitric oxide is a potent vasodilator which when inhaled causes dilatation in the pulmonary vasculature. It is this action that has been studied in intensive care medicine, especially in relation to hypoxic vasoconstriction associated with acute respiratory distress syndrome (ARDS). The use of inhaled nitric oxide has been shown to improve ventilation:perfusion matching, and thus to improve oxygenation. This article reviews the chemistry and clinical properties of nitric oxide as well as its potential uses, clinical effectiveness and side effects. The authors also surveyed UK intensive care units to review the current prevalence of the use of inhaled nitric oxide. It was found that while the majority do not currently use inhaled nitric oxide in ARDS patients, it had still been used in 27% (n=61) of the departments surveyed.
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Affiliation(s)
- Robert McCartney
- Year One Core Medical Trainee, Respiratory Medicine Department, Whipps Cross Hospital, Leytonstone, London
| | - Shibaji Saha
- Consultant Anaesthetist, Queen's Hospital, Romford, Essex
| | - James Rees
- Year One Anaesthetic Trainee, Queen's Hospital, Romford, Essex
| | - Tom Lawy
- Senior House Officer, Critical Care Department, Queen's Hospital, Romford, Essex
| | - Rishi Mosaheb
- Senior House Officer, Critical Care Department, Queen's Hospital, Romford, Essex
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Li HD, Zhang ZR, Zhang QX, Qin ZC, He DM, Chen JS. Treatment with exogenous hydrogen sulfide attenuates hyperoxia-induced acute lung injury in mice. Eur J Appl Physiol 2013; 113:1555-1563. [PMID: 23307012 DOI: 10.1007/s00421-012-2584-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2012] [Accepted: 12/29/2012] [Indexed: 01/15/2023]
Abstract
The aim of this work was to test the effect of treatment with hydrogen sulfide (H2S) on hyperoxia-induced acute lung injury in mice. Mice were exposed to room air or 95 % O2, and treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.56 mol/l NaHS). Treatment with H2S partly restored the reduced H2S levels in plasma and lungs of mice exposed to hyperoxia. Treatment with H2S attenuated hyperoxia-induced acute lung injury marked by reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, and cell numbers and protein content in bronchoalveolar lavage (BAL) and decreased apoptosis. Treatment with H2S markedly prolonged the survival of mice under oxygen exposure. Treatment with H2S abated hyperoxia-induced oxidative stress marked by reduced malondialdehyde and peroxynitrite formation, reduced NADPH oxidase activity, enhanced translocation of nuclear factor E2-related factor (Nrf2) into nucleus and increased activity of HO-1. Treatment with H2S decreased IL-1β, MCP-1, and MIP-2, and increased IL-10 expression in lungs of mice exposed to hyperoxia. Treatment with H2S decreased NFκB activity and iNOS expression in lungs, and reduced NOx content in BAL of mice exposed to hyperoxia. Treatment with H2S reduced lung permeability and suppressed VEGF release and VEGFR2 expression in lungs of mice under oxygen exposure. Treatment with exogenous H2S attenuated hyperoxia-induced acute lung injury through abating oxidative stress, suppressing inflammation, and reducing lung permeability in mice.
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Affiliation(s)
- Huai-Dong Li
- Department of Respiratory Disease, The Chinese PLA General Hospital, Beijing 100853, China.
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Soepandi PZ, Burhan E, Mangunnegoro H, Nawas A, Aditama TY, Partakusuma L, Isbaniah F, Ikhsan M, Swidarmoko B, Sutiyoso A, Malik S, Benamore R, Baird JK, Taylor WRJ. Clinical course of avian influenza A(H5N1) in patients at the Persahabatan Hospital, Jakarta, Indonesia, 2005-2008. Chest 2010; 138:665-73. [PMID: 20507944 PMCID: PMC7094603 DOI: 10.1378/chest.09-2644] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Background Limited understanding of the presentation and course of influenza A(H5N1) infection in humans hinders evidence-based management. Methods We reviewed the case records of patients admitted to the Persahabatan Hospital (RSP), Jakarta, Indonesia, with influenza A(H5N1) confirmed by real-time polymerase chain reaction. Results Twenty-two previously well patients, aged 3 to 47 years (median 24.5 years), were identified. All attended a clinic or hospital after a median of 2 days of illness (range 0–7). Times to first dose of oseltamivir (three died before receiving oseltamivir) were 2 to 12 days (median 7 days), administered mostly (n = 15) at RSP. Nineteen patients required mechanical ventilation. Deaths numbered 18 (case fatality = 82%) occurring within hours to 6 days of RSP admission, corresponding to 6 to 16 days of illness. Admission hyperglycemia (≥ 140 mg/dL), unrelated to steroids or known underlying diabetes mellitus, and elevated D-dimer levels (0.81–5.2 mg/L, upper limit of normal < 0.5 mg/L) were present in 14/21 (67%) and 20/21 (95%) patients, respectively. Fibrinogen concentrations were mostly low/normal at 129.9 to 517.9 mg/dL (median 241.1, normal 200–400 mg/dL), whereas C-reactive protein (9/11) and ferritin (6/8) levels were increased. Risk factors for death (univariate analysis) included: (1) increased D-dimers, (2) hyperglycema, (3) increased urea, (4) more extensive chest radiograph shadowing, and (5) lower admission oxygen saturation. Conclusions Early diagnosis and effective treatment of human influenza A(H5N1) infection remains challenging. Most patients were referred late with advanced disease. Oseltamivir had limited clinical impact. Elevated D-dimer levels, consistent with fibrinolysis, and hyperglycemia warrant more research to determine their underlying mechanisms and optimal treatment.
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Sun Y, Yang R, Zhong JG, Fang F, Jiang JJ, Liu MY, Lu J. Aerosolised surfactant generated by a novel noninvasive apparatus reduced acute lung injury in rats. Crit Care 2009; 13:R31. [PMID: 19257907 PMCID: PMC2689462 DOI: 10.1186/cc7737] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2008] [Revised: 02/23/2009] [Accepted: 03/04/2009] [Indexed: 11/18/2022] Open
Abstract
Introduction Exogenous surfactant has been explored as a potential therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, a nebuliser driven by oxygen lines found in the hospital was developed to deliver aerosolised porcine pulmonary surfactant (PPS). We hypothesised that aerosolised surfactant inhaled through spontaneous breathing may effectively reduce severe lung injury. Methods Rats were intravenously injected with oleic acid (OA) to induce ALI and 30 minutes later they were divided into five groups: model (injury only), PPS aerosol (PPS-aer), saline aerosol (saline-aer), PPS instillation (PPS-inst), and saline instillation (Saline-Inst). Blood gases, lung histology, and protein and TNF-α concentrations in the bronchoalveolar lavage fluid (BALF) were examined. Results The PPS aerosol particles were less than 2.0 μm in size as determined by a laser aerosol particle counter. Treatment of animals with a PPS aerosol significantly increased the phospholipid content in the BALF, improved lung function, reduced pulmonary oedema, decreased total protein and TNF-α concentrations in BALF, ameliorated lung injury and improved animal survival. These therapeutic effects are similar to those seen in the PPS-inst group. Conclusions This new method of PPS aerosolisation combines the therapeutic effects of a surfactant with partial oxygen inhalation under spontaneous breathing. It is an effective, simple and safe method of administering an exogenous surfactant.
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Affiliation(s)
- Yu Sun
- Department of Pathophysiology, College of Basic Medical Sciences, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433, China
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Murray LA, Knight DA, McAlonan L, Argentieri R, Joshi A, Shaheen F, Cunningham M, Alexopolou L, Flavell RA, Sarisky RT, Hogaboam CM. Deleterious role of TLR3 during hyperoxia-induced acute lung injury. Am J Respir Crit Care Med 2008; 178:1227-37. [PMID: 18849495 DOI: 10.1164/rccm.200807-1020oc] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
RATIONALE Acute respiratory distress syndrome (ARDS) manifests clinically as a consequence of septic and/or traumatic injury in the lung. Oxygen therapy remains a major therapeutic intervention in ARDS, but this can contribute further to lung damage. Patients with ARDS are highly susceptible to viral infection and it may be due to altered Toll-like receptor (TLR) expression. OBJECTIVES To evaluate the role of TLR3 in ARDS. METHODS TLR3 expression and signaling was determined in airway epithelial cells after in vitro hyperoxia challenge. Using a murine model of hyperoxia-induced lung injury, the role of TLR3 was determined using either TLR3-gene deficient mice or a specific neutralizing antibody directed to TLR3. MEASUREMENTS AND MAIN RESULTS Increased TLR3 expression was observed in airway epithelial cells from patients with ARDS. Further, hyperoxic conditions alone were a major stimulus for increased TLR3 expression and activation in cultured human epithelial cells. Interestingly, TLR3(-/-) mice exhibited less acute lung injury, activation of apoptotic cascades, and extracellular matrix deposition after 5 days of 80% oxygen compared with wild-type (TLR3(+/+)) mice under the same conditions. Administration of a monoclonal anti-TLR3 antibody to TLR3(+/+) mice exposed to hyperoxic conditions likewise protected these mice from lung injury and inflammation. CONCLUSIONS The potential for redundancy in function as well as cross-talk between distinct TLRs may indeed contribute to whether the inflammatory cascade can be effectively disrupted once signaling has been initiated. Together, these data show that TLR3 has a major role in the development of ARDS-like pathology in the absence of a viral pathogen.
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Abstract
PURPOSE OF REVIEW Until recently the right ventricle's role in myocardial dynamics has not been fully appreciated. This article provides an overview of the pathophysiology, imaging and management of right ventricular dysfunction. RECENT FINDINGS That levosimendan may promote right ventricular function opens new avenues for treatment. In addition there are existing therapies such as phosphodiesterase inhibitors and nitric oxide, which offer yet further modalities to improve outcome in right ventricular failure. How these drugs are used, in combination or alone, in conjunction with ventilatory and cardiovascular strategies has not been evaluated in multicentred randomized controlled trials. SUMMARY Acute right ventricular dysfunction is relatively common. There is a lack of convincing evidence in favour of any single treatment modality. Imaging methods now permit a more accurate evaluation of the right ventricle and its function. Combining treatments may offer significant advantages and the imaging and monitoring available allows real-time assessment of the response to intervention. This article illustrates how incomplete our knowledge of this condition and its management within the critical care setting is and reinforces previous calls for suitably designed trials to evaluate and develop guidelines for existing strategies and therapeutic agents.
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Affiliation(s)
- Justin Woods
- Department of Anaesthesia and Intensive Care Medicine, St George's Hospital, London, UK
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18
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Thammanomai A, Majumdar A, Bartolák-Suki E, Suki B. Effects of reduced tidal volume ventilation on pulmonary function in mice before and after acute lung injury. J Appl Physiol (1985) 2007; 103:1551-9. [PMID: 17690203 DOI: 10.1152/japplphysiol.00006.2007] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
We investigated the influence of load impedance on ventilator performance and the resulting effects of reduced tidal volume (Vt) on lung physiology during a 30-min ventilation of normal mice and 10 min of additional ventilation following lavage-induced injury at two positive end-expiratory pressure (PEEP) levels. Respiratory mechanics were regularly monitored, and the lavage fluid was tested for the soluble E-cadherin, an epithelial cell adhesion molecule, and surfactant protein (SP) B. The results showed that, due to the load dependence of the delivered Vt from the small-animal ventilator: 1) uncontrolled ventilation in normal mice resulted in a lower delivered Vt (6 ml/kg at 3-cmH2O PEEP and 7 ml/kg at 6-cmH2O PEEP) than the prescribed Vt (8 ml/kg); 2) at 3-cmH2O PEEP, uncontrolled ventilation in normal mice led to an increase in lung parenchymal functional heterogeneity, a reduction of SP-B, and an increase in E-cadherin; 3) at 6-cmH2O PEEP, ventilation mode had less influence on these parameters; and 4) in a lavage model of acute respiratory distress syndrome, delivered Vt decreased to 4 ml/kg from the prescribed 8 ml/kg, which resulted in severely compromised lung function characterized by increases in lung elastance, airway resistance, and alveolar tissue heterogeneity. Furthermore, the low Vt ventilation also resulted in poor survival rate independent of PEEP. These results highlight the importance of delivering appropriate Vt to both the normal and injured lungs. By leaving the Vt uncompensated, it can significantly alter physiological and biological responses in mice.
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Davidson WJ, Dorscheid D, Spragg R, Schulzer M, Mak E, Ayas NT. Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2006; 10:R41. [PMID: 16542488 PMCID: PMC1550886 DOI: 10.1186/cc4851] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2005] [Revised: 02/09/2006] [Accepted: 02/13/2006] [Indexed: 01/11/2023]
Abstract
INTRODUCTION The purpose of this study was to perform a systematic review and meta-analysis of exogenous surfactant administration to assess whether this therapy may be useful in adult patients with acute respiratory distress syndrome. METHODS We performed a computerized literature search from 1966 to December 2005 to identify randomized clinical trials. The primary outcome measure was mortality 28-30 days after randomization. Secondary outcome measures included a change in oxygenation (PaO2:FiO2 ratio), the number of ventilation-free days, and the mean duration of ventilation. Meta-analysis was performed using the inverse variance method. RESULTS Two hundred and fifty-one articles were identified. Five studies met our inclusion criteria. Treatment with pulmonary surfactant was not associated with reduced mortality compared with the control group (odds ratio 0.97; 95% confidence interval (CI) 0.73, 1.30). Subgroup analysis revealed no difference between surfactant containing surface protein or not - the pooled odds ratio for mortality was 0.87 (95% CI 0.48, 1.58) for trials using surface protein and the odds ratio was 1.08 (95% CI 0.72, 1.64) for trials without surface protein. The mean difference in change in the PaO2:FiO2 ratio was not significant (P = 0.11). There was a trend for improved oxygenation in the surfactant group (pooled mean change 13.18 mmHg, standard error 8.23 mmHg; 95% CI -2.95, 29.32). The number of ventilation-free days and the mean duration of ventilation could not undergo pooled analysis due to a lack of sufficient data. CONCLUSION Exogenous surfactant may improve oxygenation but has not been shown to improve mortality. Currently, exogenous surfactant cannot be considered an effective adjunctive therapy in acute respiratory distress syndrome.
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Affiliation(s)
- Warren J Davidson
- Department of Medicine University of British Columbia, Vancouver, British Columbia, Canada.
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20
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Silva PSLD, Monteiro Neto H, Andrade MMT, Neves CVDM. Negative-pressure pulmonary edema: a rare complication of upper airway obstruction in children. Pediatr Emerg Care 2005; 21:751-4. [PMID: 16280950 DOI: 10.1097/01.pec.0000186430.92388.a6] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
UNLABELLED Negative-pressure pulmonary edema is a rare but life-threatening complication of upper airway obstruction. Because negative-pressure pulmonary edema may occur in a large spectrum of pathologies associated with upper airway obstruction, awareness of this condition is crucial during daily clinical practice. We report a case of negative-pressure pulmonary edema during anesthetic recovery to highlight this condition. CASE A 2-year-old boy was scheduled for orchidopexy under general anesthesia. Shortly after an uneventful operation, the patient presented airway obstruction. Serious oxygen desaturation and bradycardia ensued, during inefficient attempts at positive-pressure ventilation. After emergency intubation, copious pink secretions emerged from the airway. Pulmonary edema was confirmed by clinical examination, pulse oximetry, and chest radiography. The finding of pulmonary edema was resolved within 24 hours after mechanical ventilation and positive end-expiratory pressure. The child suffered no sequelae. This report highlights the clinical features of negative-pressure pulmonary edema and serves as a reminder to the pediatrician who must be able to recognize and initiate treatment for conditions that are uncommon but life-threatening.
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Affiliation(s)
- Paulo Sérgio Lucas da Silva
- Department of Pediatric Intensive Care Unit, Hospital Estadual de Diadema, Universidade Federal de São Paulo, São Paulo, Brazil.
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21
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Crimi E, Slutsky AS. Inflammation and the acute respiratory distress syndrome. Best Pract Res Clin Anaesthesiol 2004; 18:477-92. [PMID: 15212340 DOI: 10.1016/j.bpa.2003.12.007] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Acute respiratory distress syndrome (ARDS) is a clinical syndrome of non-cardiogenic pulmonary oedema associated with bilateral pulmonary infiltrates, stiff lungs and refractory hypoxaemia. ARDS is characterized by an explosive acute inflammatory response in the lung parenchyma, leading to alveolar oedema, decreased lung compliance and, ultimately, hypoxaemia. Although our understanding of the causes and pathophysiology of ARDS has increased, the mortality rate remains in the range of 30-50%. No major advances in pharmacological therapy have been achieved. Mechanical ventilation is the main therapeutic intervention in the management of ARDS. The only approach that has been shown to reduce the inflammatory response and mortality is the use of lung-protective ventilatory strategy with a low tidal volume and high positive-end expiratory pressure. This chapter will review the current state of the literature on the pathogenesis of ARDS and ventilatory and pharmacotherapy approaches to its management.
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Affiliation(s)
- Ettore Crimi
- Division of Respiratory Medicine, Department of Critical Care Medicine, St Michael's Hospital, University of Toronto, Toronto, Ont., Canada
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22
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Sue RD, Belperio JA, Burdick MD, Murray LA, Xue YY, Dy MC, Kwon JJ, Keane MP, Strieter RM. CXCR2 is critical to hyperoxia-induced lung injury. THE JOURNAL OF IMMUNOLOGY 2004; 172:3860-8. [PMID: 15004193 DOI: 10.4049/jimmunol.172.6.3860] [Citation(s) in RCA: 118] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Hyperoxia-induced lung injury is characterized by infiltration of activated neutrophils in conjunction with endothelial and epithelial cell injury, followed by fibrogenesis. Specific mechanisms recruiting neutrophils to the lung during hyperoxia-induced lung injury have not been fully elucidated. Because CXCL1 and CXCL2/3, acting through CXCR2, are potent neutrophil chemoattractants, we investigated their role in mediating hyperoxia-induced lung injury. Under variable concentrations of oxygen, murine survival during hyperoxia-induced lung injury was dose dependent. Eighty percent oxygen was associated with 50% mortality at 6 days, while greater oxygen concentrations were more lethal. Using 80% oxygen, we found that lungs harvested at day 6 demonstrated markedly increased neutrophil sequestration and lung injury. Expression of CXCR2 ligands paralleled neutrophil recruitment to the lung and CXCR2 mRNA expression. Inhibition of CXC chemokine ligands/CXCR2 interaction using CXCR2(-/-) mice exposed to hyperoxia significantly reduced neutrophil sequestration and lung injury, and led to a significant survival advantage as compared with CXCR2(+/+) mice. These findings demonstrate that CXC chemokine ligand/CXCR2 biological axis is critical during the pathogenesis of hyperoxia-induced lung injury.
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MESH Headings
- Animals
- Cell Movement/genetics
- Cell Movement/immunology
- Chemokine CXCL1
- Chemokines, CXC/biosynthesis
- Chemokines, CXC/genetics
- Dose-Response Relationship, Drug
- Hyperoxia/immunology
- Hyperoxia/metabolism
- Hyperoxia/mortality
- Hyperoxia/pathology
- I-kappa B Proteins/metabolism
- Intercellular Signaling Peptides and Proteins/biosynthesis
- Intercellular Signaling Peptides and Proteins/genetics
- Ligands
- Lung/immunology
- Lung/metabolism
- Lung/pathology
- Lung/physiopathology
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- NF-KappaB Inhibitor alpha
- NF-kappa B/antagonists & inhibitors
- Neutrophils/pathology
- Oxygen/toxicity
- Phosphorylation
- RNA, Messenger/biosynthesis
- Receptors, CXCR3
- Receptors, Chemokine/biosynthesis
- Receptors, Chemokine/genetics
- Receptors, Interleukin-8B/biosynthesis
- Receptors, Interleukin-8B/deficiency
- Receptors, Interleukin-8B/genetics
- Receptors, Interleukin-8B/physiology
- Signal Transduction/genetics
- Signal Transduction/immunology
- Up-Regulation/immunology
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Affiliation(s)
- Richard D Sue
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Abstract
Approximately 20% of patients with severe acute respiratory syndrome (SARS) develop respiratory failure that requires admission to an intensive care unit (ICU). Old age, comorbidity, and elevated lactate dehydrogenase on hospital admission are associated with increased risk for ICU admission. ICU admission usually is late and occurs 8 to 10 days after symptom onset. Acute respiratory distress syndrome occurs in almost all admitted patients and most require mechanical ventilation. ICU admission is associated with significant morbidity, particularly an apparent increase in the incidence of barotrauma and nosocomial sepsis. Long-term mortality for patients admitted to the ICU ranges from 30% to 50%. Many procedures in ICUs pose a high risk for transmission of SARS coronavirus to health care workers. Contact and airborne infection isolation precautions, in addition to standard precautions, should be applied when caring for patients with SARS. Ensuring staff safety is important to maintain staff morale and delivery of adequate services.
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Affiliation(s)
- Gavin M. Joynt
- Department of Anesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region, China.
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Nie QH, Luo XD, Hui WL. Advances in clinical diagnosis and treatment of severe acute respiratory syndrome. World J Gastroenterol 2003; 9:1139-43. [PMID: 12800213 PMCID: PMC4611773 DOI: 10.3748/wjg.v9.i6.1139] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2003] [Revised: 06/02/2003] [Accepted: 06/04/2003] [Indexed: 02/06/2023] Open
Abstract
It has been proved that severe acute respiratory syndrome (SARS) is caused by SARS-associated coronavirus, a novel coronavirus. SARS originated in Guangdong Province, the People's Republic of China at the end of 2002. At present, it has spread to more than 33 countries or regions all over the world and affected 8 360 people and killed 764 by May 31,2003. Identification of the SARS causative agent and development of a diagnostic test are important. Detecting disease in its early stage, understanding its pathways of transmission and implementing specific prevention measures for the disease are dependent upon swift progress. Due to the efforts of the WHO-led network of laboratories testing for SARS, tests for the novel coronavirus have been developed with unprecedented speed. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses. WHO established the definitions of suspected and confirmed and probable cases. But the laboratory tests and definitions are limited. Until now, the primary measures included isolation, ribavirin and corticosteroid therapy, mechanical ventilation, etc. Other therapies such as convalescent plasma are being explored. It is necessary to find more effective therapy. There still are many problems to be solved in the course of conquering SARS.
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Affiliation(s)
- Qing-He Nie
- The Chinese PLA Center of Diagnosis and Treatment for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
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