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REVIEW

Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 3501-3546 | Published online: 15 Jun 2022

References

  • Barré-Sinoussi FMX. Animal models are essential to biological research: issues and perspectives. Future Sci OA. 2015;1(4):FSO63. doi:10.4155/fso.15.63
  • Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383(23):2255–2273. doi:10.1056/NEJMra2026131
  • Delclaux C, Azoulay E. Inflammatory response to infectious pulmonary injury. Eur Respir J. 2003;22(42 suppl):10s. doi:10.1183/09031936.03.00420203
  • Kumar V. Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury. Front Immunol. 2020;11:1722. doi:10.3389/fimmu.2020.01722
  • Moldoveanu B, Otmishi P, Jani P, et al. Inflammatory mechanisms in the lung. J Inflamm Res. 2009;2:1–11.
  • Goodman RB, Pugin J, Lee JS, Matthay MA. Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev. 2003;14(6):523–535. doi:10.1016/S1359-6101(03)00059-5
  • Matute-Bello GFC, Martin TR. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2008;295(3):L379–399. doi:10.1152/ajplung.00010.2008
  • Villar JBJ, Zhang H, Slutsky AS. Ventilator-induced lung injury and sepsis: two sides of the same coin? Minerva Anestesiol. 2011;77(6):647–653.
  • Rocco PRM, Marini JJ. What have we learned from animal models of ventilator-induced lung injury? Intensive care Medicine. Dec. 2020;46(12):2377–2380.
  • Wilson MRPB, Takata M. Ventilation with “clinically relevant” high tidal volumes does not promote stretch-induced injury in the lungs of healthy mice. Crit Care Med. 2012;40(10):2850–2857. doi:10.1097/CCM.0b013e31825b91ef
  • Caironi P, Langer T, Carlesso E, Protti A, Gattinoni L. Time to generate ventilator-induced lung injury among mammals with healthy lungs: a unifying hypothesis. Intensive Care Med. 2011;37(12):1913–1920. doi:10.1007/s00134-011-2388-9
  • Webb HH, Tierney DF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis. 1974;110(5):556–565. doi:10.1164/arrd.1974.110.5.556
  • Laffey JG, Kavanagh BP. Fifty years of research in ARDS. Insight into acute respiratory distress syndrome. from models to patients. Am J Respir Crit Care Med. 2017;196(1):18–28. doi:10.1164/rccm.201612-2415CI
  • Tejero J, Shiva S, Gladwin MT. Sources of vascular nitric oxide and reactive oxygen species and their regulation. Physiol Rev. 2019;99(1):311–379. doi:10.1152/physrev.00036.2017
  • Lenaz G. Mitochondria and reactive oxygen species. Which Role in Physiology and Pathology? Adv Exp Med Biol. 2012;942:93–136. doi:10.1007/978-94-007-2869-1_5
  • Sies H. Oxidative stress: from basic research to clinical application. Am J Med. 1991;91:31S–38S. doi:10.1016/0002-9343(91)90281-2
  • Chow CW, Herrera Abreu MT, Suzuki T, Downey GP. Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol. 2003;29(4):427–431. doi:10.1165/rcmb.F278
  • Ottolenghi S, Sabbatini G, Brizzolari A, Samaja M, Chiumello D. Hyperoxia and oxidative stress in anesthesia and critical care medicine. Minerva Anestesiol. 2020;86(1):64–75. doi:10.23736/S0375-9393.19.13906-5
  • Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem. 2015;30(1):11–26. doi:10.1007/s12291-014-0446-0
  • Garcia-Gimenez J-L, Garces C, Roma-Mateo C, Pallardo FV. Oxidative stress-mediated alterations in histone post-translational modifications. Free Radic Biol Med. 2021;170:6–18. doi:10.1016/j.freeradbiomed.2021.02.027
  • Bedard KKK. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245–313. doi:10.1152/physrev.00044.2005
  • Brandes RP, Schroder K. Differential vascular functions of Nox family NADPH oxidases. Curr Opin Lipidol. 2008;19(5):513–518. doi:10.1097/MOL.0b013e32830c91e3
  • Itoh K, Chiba T, Takahashi S, et al. An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements. Biochem Biophys Res Commun. 1997;236(2):313–322. doi:10.1006/bbrc.1997.6943
  • Itoh KWN, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999;13(1):76–86. doi:10.1101/gad.13.1.76
  • Mizumura K, Maruoka S, Shimizu T, Gon Y. Role of Nrf2 in the pathogenesis of respiratory diseases. Respir Investig. 2020;58(1):28–35. doi:10.1016/j.resinv.2019.10.003
  • Chapman KESS, Zhuang D, Hassid A, Desai LP, Waters CM. Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2005;289(5):L834–841. doi:10.1152/ajplung.00069.2005
  • Zeng Q, Ye L, Ling M, et al. TLR4/TRAF6/NOX2 signaling pathway is involved in ventilation-induced lung injury via endoplasmic reticulum stress in murine model. Int Immunopharmacol. 2021;96:107774. doi:10.1016/j.intimp.2021.107774
  • Fisher AB, Dodia C, Chatterjee S, Peptide A. Inhibitor of Peroxiredoxin 6 Phospholipase A2 Activity Significantly Protects against Lung Injury in a Mouse Model of Ventilator Induced Lung Injury (VILI). Antioxidants. 2021;10(6):3466. doi:10.3390/antiox10060925
  • Papaiahgari S, Yerrapureddy A, Reddy SR, et al. Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice. Am J Respir Crit Care Med. 2007;176(12):1222–1235. doi:10.1164/rccm.200701-060OC
  • Ruan H, Li W, Wang J, et al. Propofol alleviates ventilator-induced lung injury through regulating the Nrf2/NLRP3 signaling pathway. Exp Mol Pathol. 2020;114:104427. doi:10.1016/j.yexmp.2020.104427
  • Shan Y, Akram A, Amatullah H, et al. ATF3 protects pulmonary resident cells from acute and ventilator-induced lung injury by preventing Nrf2 degradation. Antioxid Redox Signal. 2015;22(8):651–668. doi:10.1089/ars.2014.5987
  • Sun Z, Wang F, Yang Y, et al. Resolvin D1 attenuates ventilator-induced lung injury by reducing HMGB1 release in a HO-1-dependent pathway. Int Immunopharmacol. 2019;75:105825. doi:10.1016/j.intimp.2019.105825
  • Tao S, Rojo de la Vega M, Quijada H, et al. Bixin protects mice against ventilation-induced lung injury in an NRF2-dependent manner. Sci Rep. 2016;6:18760. doi:10.1038/srep18760
  • Veskemaa LGJ, Pickerodt PA, Taher M, Boemke W, González-López A, Francis RCE. Tert-butylhydroquinone augments Nrf2-dependent resilience against oxidative stress and improves survival of ventilator-induced lung injury in mice. Am J Physiol Lung Cell Mol Physiol. 2021;320(1):L17–L28. doi:10.1152/ajplung.00131.2020
  • Xu J, Li HB, Chen L, et al. BML-111 accelerates the resolution of inflammation by modulating the Nrf2/HO-1 and NF-kappaB pathways in rats with ventilator-induced lung injury. Int Immunopharmacol. 2019;69:289–298. doi:10.1016/j.intimp.2019.02.005
  • Nathan CF. Secretory products of macrophages. J Clin Invest. 1987;79(2):319–326. doi:10.1172/JCI112815
  • Brinkmann VGC, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532–1535. doi:10.1126/science.1092385
  • Porto BN, Stein RT. Neutrophil Extracellular Traps in Pulmonary Diseases: too Much of a Good Thing? Front Immunol. 2016;7:311. doi:10.3389/fimmu.2016.00311
  • Saffarzadeh M, Juenemann C, Queisser MA, et al. Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: a Predominant Role of Histones. PLoS One. 2012;7(2):e32366. doi:10.1371/journal.pone.0032366
  • Abrams ST, Zhang N, Manson J, et al. Circulating Histones Are Mediators of Trauma-associated Lung Injury. Am J Respir Crit Care Med. 2013;187(2):160–169. doi:10.1164/rccm.201206-1037OC
  • Dreyfuss DSG. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med. 1998;157(1):294–323. doi:10.1164/ajrccm.157.1.9604014
  • Imanaka HSM, Shimaoka M, Matsuura N, Nishimura M, Ohta H, Kiyono H. Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs. Anesth Analg. 2001;92(2):428–436. doi:10.1097/00000539-200102000-00029
  • Belperio JA, Keane MP, Burdick MD, et al. Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury. J Clin Invest. 2002;110(11):1703–1716. doi:10.1172/JCI0215849
  • Rossaint JHJ, Herter JM, Van Aken H, et al. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap–mediated sterile inflammation. Blood. 2014;123(16):2573–2584. doi:10.1182/blood-2013-07-516484
  • Li H, Pan P, Su X, et al. Neutrophil Extracellular Traps Are Pathogenic in Ventilator-Induced Lung Injury and Partially Dependent on TLR4. Biomed Res Int. 2017;2017:8272504. doi:10.1155/2017/8272504
  • Yildiz CPN, Otulakowski G, Khan MA, et al. Mechanical ventilation induces neutrophil extracellular trap formation. Anesthesiology. 2015;122(4):864–875. doi:10.1097/ALN.0000000000000605
  • Nailwal NP, Doshi GM. Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation. Inflammopharmacology. 2021;29(3):617–640. doi:10.1007/s10787-021-00813-y
  • Widmann CGS, Jarpe MB, Johnson GL. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev. 1999;79(1):143–180. doi:10.1152/physrev.1999.79.1.143
  • Zhang WLH. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2002;12(1):9–18. doi:10.1038/sj.cr.7290105
  • Ip YTDR. Signal transduction by the c-Jun N-terminal kinase (JNK)-from inflammation to development. Curr Opin Cell Biol. 1998;10(2):205–219. doi:10.1016/S0955-0674(98)80143-9
  • Iwaki M, Ito S, Morioka M, et al. Mechanical stretch enhances IL-8 production in pulmonary microvascular endothelial cells. Biochem Biophys Res Commun. 2009;389(3):531–536. doi:10.1016/j.bbrc.2009.09.020
  • Oudin SPJ. Role of MAP kinase activation in interleukin-8 production by human BEAS-2B bronchial epithelial cells submitted to cyclic stretch. Am J Respir Cell Mol Biol. 2002;27(1):107–114. doi:10.1165/ajrcmb.27.1.4766
  • Dolinay T, Wu W, Kaminski N, et al. Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury. PLoS One. 2008;3(2):e1601. doi:10.1371/journal.pone.0001601
  • Li LF, Yu L, Quinn DA. Ventilation-induced neutrophil infiltration depends on c-Jun N-terminal kinase. Am J Respir Crit Care Med. 2004;169(4):518–524. doi:10.1164/rccm.200305-660OC
  • Uhlig U, Haitsma JJ, Goldmann T, Poelma DL, Lachmann B, Uhlig S. Ventilation-induced activation of the mitogen-activated protein kinase pathway. Eur Respir J. 2002;20(4):946–956. doi:10.1183/09031936.02.01612001
  • Woods SJWA, O’Dea KP, Halford P, Takata M, Wilson MR. Kinetic profiling of in vivo lung cellular inflammatory responses to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol. 2015;308(9):L912–921. doi:10.1152/ajplung.00048.2015
  • Wright JRCJ. Metabolism and turnover of lung surfactant. Am Rev Respir Dis. 1987;136(2):426–444. doi:10.1164/ajrccm/136.2.426
  • Han S, Mallampalli RK. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections. Ann Am Thorac Soc. 2015;12(5):765–774. doi:10.1513/AnnalsATS.201411-507FR
  • Wright J. Immunomodulatory functions of surfactant. Physiol Rev. 1997;77(4):931–962. doi:10.1152/physrev.1997.77.4.931
  • Raghavendran K, Willson D, Notter RH. Surfactant therapy for acute lung injury and acute respiratory distress syndrome. Crit Care Clin. 2011;27(3):525–559. doi:10.1016/j.ccc.2011.04.005
  • Parker JCHL, Peevy KJ. Mechanisms of ventilator-induced lung injury. Crit Care Med. 1993;21(1):131–143. doi:10.1097/00003246-199301000-00024
  • Verbrugge SJ, Bohm SH, Gommers D, Zimmerman LJ, Lachmann B. Surfactant impairment after mechanical ventilation with large alveolar surface area changes and effects of positive end-expiratory pressure. Br J Anaesth. 1998;80(3):360–364. doi:10.1093/bja/80.3.360
  • Taskar V, John J, Robertson B, Jonson B. Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion. Am J Respir Crit Care Med. 1997;1:313–320. doi:10.1164/ajrccm.155.1.9001330
  • Vazquez de Anda GF, Gommers D, Verbrugge SJ, Haitsma J, Lachmann B. Treatment of ventilation-induced lung injury with exogenous surfactant. Intensive Care Med. 2001;27(3):559–565. doi:10.1007/s001340000838
  • Haitsma JJ, Uhlig S, Lachmann U, Verbrugge SJ, Poelma DL, Lachmann B. Exogenous surfactant reduces ventilator-induced decompartmentalization of tumor necrosis factor alpha in absence of positive end-expiratory pressure. Intensive Care Med. 2002;28(8):1131–1137. doi:10.1007/s00134-002-1377-4
  • Krause MFHT. Timing of surfactant administration determines its physiologic response in a rabbit model of airway lavage. Biol Neonate. 2000;77(3):196–202. doi:10.1159/000014216
  • Vassiliou AG, Kotanidou A, Dimopoulou I, Orfanos SE. Endothelial Damage in Acute Respiratory Distress Syndrome. Int J Mol Sci. 2020;21(22). doi:10.3390/ijms21228793
  • Bartoszewski RMS, Collawn JF. Ion channels of the lung and their role in disease pathogenesis. Am J Physiol Lung Cell Mol Physiol. 2017;313(5):L859–L872. doi:10.1152/ajplung.00285.2017
  • Zea Borok ASV. Lung Edema Clearance: 20 Years of Progress Invited Review: role of aquaporin water channels in fluid transport in lung and airways. J Appl Physiol. 2002;93(6):2199–2206. doi:10.1152/japplphysiol.01171.2001
  • Folkesson HG, Matthay MA, Hasegawa H, Kheradmand F, Verkman AS. Transcellular water transport in lung alveolar epithelium through mercury-sensitive water channels. Proc Natl Acad Sci U S A. 1994;91(11):4970–4974. doi:10.1073/pnas.91.11.4970
  • Nielsen S, King LS, Christensen BM, Agre P. Aquaporins in complex tissues. II. Subcellular distribution in respiratory and glandular tissues of rat. Am J Physiol. 1997;273(5):C1549–1561. doi:10.1152/ajpcell.1997.273.5.C1549
  • Vassiliou AG, Manitsopoulos N, Kardara M, Maniatis NA, Orfanos SE, Kotanidou A. Differential Expression of Aquaporins in Experimental Models of Acute Lung Injury. vivo. 2017;31(5):885–894.
  • Wittekindt OH, Dietl P. Aquaporins in the lung. Pflugers Archiv. 2019;471(4):519–532. doi:10.1007/s00424-018-2232-y
  • Verkman AS. More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci. 2005;118(15):3225–3232. doi:10.1242/jcs.02519
  • Vadász IRS, Sznajder JI. Alveolar epithelium and Na,K-ATPase in acute lung injury. Intensive Care Med. 2007;33(7):1243–1251. doi:10.1007/s00134-007-0661-8
  • Morty REEO, Seeger W. Alveolar fluid clearance in acute lung injury: what have we learned from animal models and clinical studies? Intensive Care Med. 2007;33(7):1229–1240. doi:10.1007/s00134-007-0662-7
  • Hales C, Du H, Volokhov A, Mourfarrej R, Quinn DA. Aquaporin channels may modulate ventilator-induced lung injury. Respir Physiol Neurobiol. 2001;124(2):159–166. doi:10.1016/S0034-5687(00)00193-6
  • Fabregat G, Garcia-de-la-asuncion J, Sarria B, et al. Increased expression of AQP 1 and AQP 5 in rat lungs ventilated with low tidal volume is time dependent. PLoS One. 2014;9(12):e114247. doi:10.1371/journal.pone.0114247
  • Fabregat G, Garcia-de-la-asuncion J, Sarria B, et al. Expression of aquaporins 1 and 5 in a model of ventilator-induced lung injury and its relation to tidal volume. Exp Physiol. 2016;101(11):1418–1431. doi:10.1113/EP085729
  • Jin L-D, Wang L-R, Wu L-Q, et al. Effects of COX-2 inhibitor on ventilator-induced lung injury in rats. Int Immunopharmacol. 2013;16(2):288–295. doi:10.1016/j.intimp.2013.03.031
  • Liu Y, Wang Y, Song X, Dong L, Wang W, Wu H. P38 mitogen-activated protein kinase inhibition attenuates mechanical stress induced lung injury via up-regulating AQP5 expression in rats. Biotechnol Biotechnol Equip. 2019;33(1):472–480. doi:10.1080/13102818.2019.1590159
  • Adir Y, Factor P, Dumasius V, Ridge KM, Sznajder JI. Na,K-ATPase gene transfer increases liquid clearance during ventilation-induced lung injury. Am J Respir Crit Care Med. 2003;168(12):1445–1448. doi:10.1164/rccm.200207-702OC
  • Liang ZD, Yin XR, Cai DS, Zhou H, Pei L. Autologous transplantation of adipose-derived stromal cells ameliorates ventilator-induced lung injury in rats. J Transl Med. 2013;11:179. doi:10.1186/1479-5876-11-179
  • Chamorro-Marín V, García-Delgado M, Touma-Fernández A, Aguilar-Alonso E, Fernández-Mondejar E. Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats. Crit Care. 2008;12(2):R39. doi:10.1186/cc6829
  • Vassiliou AG, Orfanos SE, Kotanidou A. Clinical Assays in Sepsis: prognosis, Diagnosis, Outcomes, and the Genetic Basis of Sepsis. Sepsis. 2017;1:54.
  • Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13(3):159–175. doi:10.1038/nri3399
  • Guillon A, Preau S, Aboab J, et al. Preclinical septic shock research: why we need an animal ICU. Ann Intensive Care. 2019;9(1):66. doi:10.1186/s13613-019-0543-6
  • Raetz CR, Ulevitch RJ, Wright SD, Sibley CH, Ding A, Nathan CF. Gram-negative endotoxin: an extraordinary lipid with profound effects on eukaryotic signal transduction. FASEB J. 1991;5(12):2652–2660. doi:10.1096/fasebj.5.12.1916089
  • Remick DG, Ward PA. Evaluation of endotoxin models for the study of sepsis. Shock. 2005;Suppl 1:7–11. doi:10.1097/01.shk.0000191384.34066.85
  • Walley KRLN, Standiford TJ, Strieter RM, Kunkel SL. Balance of inflammatory cytokines related to severity and mortality of murine sepsis. Infect Immun. 1996;64:4733–4738. doi:10.1128/iai.64.11.4733-4738.1996
  • Gnidec AG, Sibbald WJ, Cheung H, Metz CA. Ibuprofen reduces the progression of permeability edema in an animal model of hyperdynamic sepsis. J Appl Physiol. 1988;65(3):1024–1032. doi:10.1152/jappl.1988.65.3.1024
  • Lomas-Neira JL, Chung CS, Wesche DE, Perl M, Ayala A. In vivo gene silencing (with siRNA) of pulmonary expression of MIP-2 versus KC results in divergent effects on hemorrhage-induced, neutrophil-mediated septic acute lung injury. J Leukoc Biol. 2005;77(6):846–853. doi:10.1189/jlb.1004617
  • Chimenti L, Morales-Quinteros L, Puig F, et al. Comparison of direct and indirect models of early induced acute lung injury. Intensive Care Med Exp. 2020;8(Suppl 1):62. doi:10.1186/s40635-020-00350-y
  • Jiang J, Huang K, Xu S, Garcia JGN, Wang C, Targeting CH. NOX4 alleviates sepsis-induced acute lung injury via attenuation of redox-sensitive activation of CaMKII/ERK1/2/MLCK and endothelial cell barrier dysfunction. Redox Biol. 2020;36:101638. doi:10.1016/j.redox.2020.101638
  • Palumbo SSY, Ahmad K, Desai AA, et al. Dysregulated Nox4 ubiquitination contributes to redox imbalance and age-related severity of acute lung injury. Am J Physiol. 2017;312(3):L297–L308. doi:10.1152/ajplung.00305.2016
  • Li D, Cong Z, Yang C, Zhu X. Inhibition of LPS-induced Nox2 activation by VAS2870 protects alveolar epithelial cells through eliminating ROS and restoring tight junctions. Biochem Biophys Res Commun. 2020;524(3):575–581. doi:10.1016/j.bbrc.2020.01.134
  • Thimmulappa RK, Lee H, Rangasamy T, et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J Clin Invest. 2006;116(4):984–995. doi:10.1172/JCI25790
  • Kong X, Thimmulappa R, Craciun F, et al. Enhancing Nrf2 pathway by disruption of Keap1 in myeloid leukocytes protects against sepsis. Am J Respir Crit Care Med. 2011;184(8):928–938. doi:10.1164/rccm.201102-0271OC
  • Cen M, Ouyang W, Zhang W, et al. MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism. Redox Biol. 2021;41:101936. doi:10.1016/j.redox.2021.101936
  • Liu Q, Ci X, Wen Z, Peng L. Diosmetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury through Activating the Nrf2 Pathway and Inhibiting the NLRP3 Inflammasome. Biomol Ther (Seoul). 2018;26(2):157–166. doi:10.4062/biomolther.2016.234
  • Yu Y, Yang Y, Yang M, Wang C, Xie K, Yu Y. Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway. Int Immunopharmacol. 2019;69:11–18. doi:10.1016/j.intimp.2019.01.022
  • Czaikoski PG, Mota JM, Nascimento DC, et al. Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis. PLoS One. 2016;11(2):e0148142. doi:10.1371/journal.pone.0148142
  • Lefrançais E, Mallavia B, Zhuo H, Calfee CS, Looney MR. Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury. JCI Insight. 2018;3(3):e98178. doi:10.1172/jci.insight.98178
  • Clark SR, Ma AC, Tavener SA, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13(4):463–469. doi:10.1038/nm1565
  • Zhang H, Zhou Y, Qu M, et al. Tissue Factor-Enriched Neutrophil Extracellular Traps Promote Immunothrombosis and Disease Progression in Sepsis-Induced Lung Injury. Front Cell Infect Microbiol. 2021;11:677902. doi:10.3389/fcimb.2021.677902
  • Asaduzzaman M, Wang Y, Thorlacius H. Critical role of p38 mitogen-activated protein kinase signaling in septic lung injury. Crit Care Med. 2008;36(2):482–488. doi:10.1097/01.CCM.0B013E31816204FA
  • Fang W, Cai SX, Wang CL, et al. Modulation of mitogen-activated protein kinase attenuates sepsis-induced acute lung injury in acute respiratory distress syndrome rats. Mol Med Rep. 2017;16(6):9652–9658. doi:10.3892/mmr.2017.7811
  • Mannam P, Zhang X, Shan P, et al. Endothelial MKK3 is a critical mediator of lethal murine endotoxemia and acute lung injury. J Immunol. 2013;190(3):1264–1275. doi:10.4049/jimmunol.1202012
  • Qian FDJ, Gantner BN, Flavell RA, Dong C, Christman JW, Ye RD. Map kinase phosphatase 5 protects against sepsis-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2012;302(9):L866–874. doi:10.1152/ajplung.00277.2011
  • Kolomaznik MNZ, Nova Z, Calkovska A. Pulmonary surfactant and bacterial lipopolysaccharide: the interaction and its functional consequences. Physiol Res. 2017;66(Suppl 2):S147–S157. doi:10.33549/physiolres.933672
  • Lewis JFVR, Possmayer F. Altered alveolar surfactant is an early marker of acute lung injury in septic adult sheep. Am J Respir Crit Care Med. 1994;150(1):123–130. doi:10.1164/ajrccm.150.1.8025737
  • Huang W, McCaig LA, Veldhuizen RA, Yao LJ, Lewis JF. Mechanisms responsible for surfactant changes in sepsis-induced lung injury. Eur Respir J. 2005;26(6):1074–1079. doi:10.1183/09031936.05.00085805
  • Nieman G. Surfactant replacement in the treatment of sepsis-induced adult respiratory distress syndrome in pigs. Crit Care Med. 1996;24(6):1025–1033. doi:10.1097/00003246-199606000-00024
  • Guo R, Li Y, Han M, Liu J, Sun Y. Emodin attenuates acute lung injury in Cecal-ligation and puncture rats. Int Immunopharmacol. 2020;85:106626. doi:10.1016/j.intimp.2020.106626
  • Hu X, Liu S, Zhu J, Ni H. Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF-κB signaling pathway in vivo and in vitro. J Cell Biochem. 2019;120(6):8956–8964. doi:10.1002/jcb.27615
  • Liang W, Guo L, Liu T, Qin S. MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1. Allergolog et Immunopathol. 2021;49(5):117–124. doi:10.15586/aei.v49i5.477
  • Liu LDWX, Tao BD, Wang N, Zhang J. Protective effect and mechanism of hydrogen treatment on lung epithelial barrier dysfunction in rats with sepsis. Genet Mol Res. 2016;15(1):65.
  • Hasan B, Li F, Siyit A, et al. Expression of aquaporins in the lungs of mice with acute injury caused by LPS treatment. Respir Physiol Neurobiol. 2014;200:40–45. doi:10.1016/j.resp.2014.05.008
  • Jiao G, Li E, Yu R. Decreased expression of AQP1 and AQP5 in acute injured lungs in rats. Chin Med J. 2002;115(7):963–967.
  • Su X, Song Y, Jiang J, Bai C. The role of aquaporin-1 (AQP1) expression in a murine model of lipopolysaccharide-induced acute lung injury. Respir Physiol Neurobiol. 2004;142(1):1–11. doi:10.1016/j.resp.2004.05.001
  • Rump K, Brendt P, Frey UH, et al. Aquaporin 1 and 5 expression evoked by the β2 adrenoreceptor agonist terbutaline and lipopolysaccharide in mice and in the human monocytic cell line THP-1 is differentially regulated. Shock. 2013;40(5):430–436. doi:10.1097/SHK.0000000000000035
  • Guo C, Wu T, Zhu H, Gao L. Aquaporin 4 Blockade Attenuates Acute Lung Injury Through Inhibition of Th17 Cell Proliferation in Mice. Inflammation. 2019;42(4):1401–1412. doi:10.1007/s10753-019-01002-4
  • Berger G, Guetta J, Klorin G, et al. Sepsis impairs alveolar epithelial function by downregulating Na-K-ATPase pump. Am J Physiol Lung Cell Mol Physiol. 2011;301(1):L23–30. doi:10.1016/S2213-2600(20)30404-5
  • Fisher BJ, Kraskauskas D, Martin EJ, et al. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am J Physiol Lung Cell Mol Physiol. 2012;303(1):L20–32. doi:10.1152/ajplung.00300.2011
  • Emr BM, Roy S, Kollisch-Singule M, et al. Electroporation-mediated gene delivery of Na+,K+ -ATPase, and ENaC subunits to the lung attenuates acute respiratory distress syndrome in a two-hit porcine model. Shock. 2015;43(1):16–23. doi:10.1097/SHK.0000000000000228
  • de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med. 2003;167(4):490–511. doi:10.1164/rccm.200207-670SO
  • Fard N, Saffari A, Emami G, Hofer S, Kauczor HU, Mehrabi A. Acute respiratory distress syndrome induction by pulmonary ischemia-reperfusion injury in large animal models. J Surg Res. 2014;189(2):274–284. doi:10.1016/j.jss.2014.02.034
  • Koike KME, Moore FA, Read RA, Carl VS, Banerjee A. Gut ischemia/reperfusion produces lung injury independent of endotoxin. Crit Care Med. 1994;22(9):1438–1444. doi:10.1097/00003246-199409000-00014
  • Sakao YKO, Martin TR, Nakahara Y, Hadden WA. Association of IL-8 and MCP-1 with the development of reexpansion pulmonary edema in rabbits. Ann Thorac Surg. 2001;71(6):1825–1832. doi:10.1016/S0003-4975(01)02489-4
  • Chatterjee SNG, Christie JD, Fisher AB. Shear stress-related mechanosignaling with lung ischemia: lessons from basic research can inform lung transplantation. Am J Physiol Lung Cell Mol Physiol. 2014;307(9):L668–680. doi:10.1152/ajplung.00198.2014
  • Sharma AKLD, Stone ML, Zhao Y, Mehta CK, Kron IL, Laubach VE. NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A2A Receptor to Inhibit Lung Ischemia-Reperfusion Injury. Am J Respir Crit Care Med. 2016;193(9):988–999. doi:10.1164/rccm.201506-1253OC
  • Sharma AK, Mulloy DP, Le LT, Laubach VE. NADPH oxidase mediates synergistic effects of IL-17 and TNF-α on CXCL1 expression by epithelial cells after lung ischemia-reperfusion. Am J Physiol. 2014;306(1):L69–L79. doi:10.1152/ajplung.00205.2013
  • Cui Y, Wang Y, Li G, et al. The Nox1/Nox4 inhibitor attenuates acute lung injury induced by ischemia-reperfusion in mice. PLoS One. 2018;13(12):e0209444. doi:10.1371/journal.pone.0209444
  • Pak O, Sydykov A, Kosanovic D, et al. Lung Ischaemia-Reperfusion Injury: the Role of Reactive Oxygen Species. Adv Exp Med Biol. 2017;967:195–225. doi:10.1007/978-3-319-63245-2_12
  • Chai D, Zhang L, Xi S, Cheng Y, Jiang H, Hu R. Nrf2 Activation Induced by Sirt1 Ameliorates Acute Lung Injury After Intestinal Ischemia/Reperfusion Through NOX4-Mediated Gene Regulation. Cell Physiol Biochem. 2018;46(2):781–792. doi:10.1159/000488736
  • Dong HQZ, Chai D, Peng J, Xia Y, Hu R, Jiang H. Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1. Aging. 2020;12(13):12943–12959. doi:10.18632/aging.103378
  • Fan J, Lv H, Li J, et al. Roles of Nrf2/HO-1 and HIF-1alpha/VEGF in lung tissue injury and repair following cerebral ischemia/reperfusion injury. J Cell Physiol. 2019;234(6):7695–7707. doi:10.1002/jcp.27767
  • Meng Q-T, Cao C, Wu Y, et al. Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia–reperfusion in mice: role of Nrf2. Labor Investig. 2016;96(10):1087–1104. doi:10.1038/labinvest.2016.87
  • Yan J, Li J, Zhang L, et al. Nrf2 protects against acute lung injury and inflammation by modulating TLR4 and Akt signaling. Free Radic Biol Med. 2018;121:78–85. doi:10.1016/j.freeradbiomed.2018.04.557
  • Sayah DM, Mallavia B, Liu F, et al. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2015;191(4):455–463. doi:10.1164/rccm.201406-1086OC
  • Scozzi D, Wang X, Liao F, et al. Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance. Am J Transplant. 2019;19(4):1011–1023. doi:10.1111/ajt.15163
  • Wolf PS, Merry HE, Farivar AS, McCourtie AS, Mulligan MS. Stress-activated protein kinase inhibition to ameliorate lung ischemia reperfusion injury. J Thorac Cardiovasc Surg. 2008;135(3):656–665. doi:10.1016/j.jtcvs.2007.11.026
  • Wang T, Liu C, Pan LH, et al. Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood-Air Barrier Hyperpermeability. Front Pharmacol. 2020;11:569251. doi:10.3389/fphar.2020.569251
  • Xiong -L-L, Tan Y, Ma H-Y, et al. Administration of SB239063, a potent p38 MAPK inhibitor, alleviates acute lung injury induced by intestinal ischemia reperfusion in rats associated with AQP4 downregulation. Int Immunopharmacol. 2016;38:54–60. doi:10.1016/j.intimp.2016.03.036
  • Zheng D-Y, Zhou M, Jin J, et al. Inhibition of P38 MAPK Downregulates the Expression of IL-1βto Protect Lung from Acute Injury in Intestinal Ischemia Reperfusion Rats. Mediators Inflamm. 2016;2016:1–8.
  • Tan J, Liu D, Lv X, et al. MAPK mediates inflammatory response and cell death in rat pulmonary microvascular endothelial cells in an ischemia-reperfusion model of lung transplantation. J Heart Lung Transplant. 2013;32(8):823–831. doi:10.1016/j.healun.2013.05.005
  • Wang J, Tan J, Liu Y, Song L, Li D, Cui X. Amelioration of lung ischemia reperfusion injury by JNK and p38 small interfering RNAs in rat pulmonary microvascular endothelial cells in an ischemia-reperfusion injury lung transplantation model. Mol Med Rep. 2018;17(1):1228–1234. doi:10.3892/mmr.2017.7985
  • Ochs M, Nenadic I, Fehrenbach A, et al. Ultrastructural alterations in intraalveolar surfactant subtypes after experimental ischemia and reperfusion. Am J Respir Crit Care Med. 1999;160(2):718–724. doi:10.1164/ajrccm.160.2.9809060
  • Novick RJ, MacDonald J, Veldhuizen RA, et al. Evaluation of surfactant treatment strategies after prolonged graft storage in lung transplantation. Am J Respir Crit Care Med. 1996;154(1):98–104. doi:10.1164/ajrccm.154.1.8680706
  • van der Kaaij NP, Haitsma JJ, Kluin J, et al. Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung. Eur J Cardio. 2005;27(5):774–782. doi:10.1016/j.ejcts.2004.12.034
  • Dreyer N, Muhlfeld C, Fehrenbach A, et al. Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells. Respir Res. 2008;9:5. doi:10.1186/1465-9921-9-5
  • Mühlfeld C, Becker L, Bussinger C, et al. Exogenous surfactant in ischemia/reperfusion: effects on endogenous surfactant pools. J Heart Lung Transplant. 2010;29(3):327–334. doi:10.1016/j.healun.2009.07.019
  • Mühlfeld C, Schaefer IM, Becker L, et al. Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion. Eur Respir J. 2009;33(3):625–633. doi:10.1183/09031936.00024108
  • van Putte BP, Cobelens PM, van der Kaaij N, et al. Exogenous surfactant attenuation of ischemia-reperfusion injury in the lung through alteration of inflammatory and apoptotic factors. J Thorac Cardiovasc Surg. 2009;137(4):824–828. doi:10.1016/j.jtcvs.2008.08.046
  • Ge H, Zhu H, Xu N, et al. Increased Lung Ischemia-Reperfusion Injury in Aquaporin 1-Null Mice Is Mediated via Decreased Hypoxia-Inducible Factor 2alpha Stability. Am J Respir Cell Mol Biol. 2016;54(6):882–891. doi:10.1165/rcmb.2014-0363OC
  • Qi YC, Chen W, Li XL, Wang YW, Xie XH. H2S Protecting against Lung Injury following Limb Ischemia-reperfusion by Alleviating Inflammation and Water Transport Abnormality in Rats. Biomed Environ Sci. 2014;27(6):410–418. doi:10.3967/bes2014.070
  • Calikoglu M, Tamer L, Sucu N, et al. The effects of caffeic acid phenethyl ester on tissue damage in lung after hindlimb ischemia-reperfusion. Pharmacol Res. 2003;48(4):397–403. doi:10.1016/S1043-6618(03)00156-7
  • Koksel O, Ozdulger A, Aytacoglu B, et al. The influence of iloprost on acute lung injury induced by hind limb ischemia-reperfusion in rats. Pulm Pharmacol Ther. 2005;18(4):235–241. doi:10.1016/j.pupt.2004.12.005
  • Lan CC, Peng CK, Tang SE, Huang KL, Wu CP. Carbonic anhydrase inhibitor attenuates ischemia-reperfusion induced acute lung injury. PLoS One. 2017;12(6):e0179822. doi:10.1371/journal.pone.0179822
  • David PDD, Lu J, Moochhala S. Animal models of smoke inhalation induced injuries. Front Biosci. 2009;1(14):4618–4630.
  • Guo B, Bai Y, Ma Y, et al. Preclinical and clinical studies of smoke-inhalation-induced acute lung injury: update on both pathogenesis and innovative therapy. Ther Adv Respir Dis. 2019;13:1753466619847901. doi:10.1177/1753466619847901
  • Rabinowitz PMSM. Acute inhalation injury. Clin Chest Med. 2002;23(4):707–715. doi:10.1016/S0272-5231(02)00025-4
  • de Carvalho FO, Felipe FA, de Melo Costa ACS, et al. Inflammatory Mediators and Oxidative Stress in Animals Subjected to Smoke Inhalation: a Systematic Review. Lung. 2016;194(4):487–499. doi:10.1007/s00408-016-9879-y
  • Hikichi M, Mizumura K, Maruoka S, Gon Y. Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke. J Thorac Dis. 2019;11(Suppl 17):S2129–S2140. doi:10.21037/jtd.2019.10.43
  • Bhalla DK, Hirata F, Rishi AK, Gairola CG. Cigarette smoke, inflammation, and lung injury: a mechanistic perspective. J Toxicol Environ Health B Crit Rev. 2009;12(1):45–64. doi:10.1080/10937400802545094
  • Lu Q, Gottlieb E, Rounds S. Effects of cigarette smoke on pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2018;314(5):L743–L756. doi:10.1152/ajplung.00373.2017
  • Lee TS, Liu YJ, Tang GJ, Yien HW, Wu YL, Kou YR. Wood smoke extract promotes both apoptosis and proliferation in rat alveolar epithelial type II cells: the role of oxidative stress and heme oxygenase-1. Crit Care Med. 2008;36(9):2597–2606. doi:10.1097/CCM.0b013e318184979c
  • Perng DW, Chang TM, Wang JY, et al. Inflammatory role of AMP-activated protein kinase signaling in an experimental model of toxic smoke inhalation injury. Crit Care Med. 2013;41(1):120–132. doi:10.1097/CCM.0b013e318265f653
  • Liu PLCY, Chen YH, Lin SJ, Kou YR. Wood smoke extract induces oxidative stress-mediated caspase-independent apoptosis in human lung endothelial cells: role of AIF and EndoG. Am J Physiol Lung Cell Mol Physiol. 2005;289(5):L739–749. doi:10.1152/ajplung.00099.2005
  • Müller T, Hengstermann A. Nrf2: friend and foe in preventing cigarette smoking-dependent lung disease. Chem Res Toxicol. 2012;25(9):1805–1824. doi:10.1021/tx300145n
  • Boutten A, Goven D, Artaud-Macari E, Boczkowski J, Bonay M. NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease. Trends Mol Med. 2011;17(7):363–371. doi:10.1016/j.molmed.2011.02.006
  • Kim M, Han CH, Lee MY. NADPH oxidase and the cardiovascular toxicity associated with smoking. Toxicol Res. 2014;30(3):149–157. doi:10.5487/TR.2014.30.3.149
  • Zou Y, Chen X, He B, et al. Neutrophil extracellular traps induced by cigarette smoke contribute to airway inflammation in mice. Exp Cell Res. 2020;389(1):111888. doi:10.1016/j.yexcr.2020.111888
  • Qiu SL, Zhang H, Tang QY, et al. Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells. Thorax. 2017;72(12):1084–1093. doi:10.1136/thoraxjnl-2016-209887
  • Choi WISO, Kwon KY, Quinn DA, Hales CA. JNK activation is responsible for mucus overproduction in smoke inhalation injury. Respir Res. 2010;11(1):172. doi:10.1186/1465-9921-11-172
  • Syrkina OLQD, Jung W, Ouyang B, Hales CA. Inhibition of JNK activation prolongs survival after smoke inhalation from fires. Am J Physiol Lung Cell Mol Physiol. 2007;292(4):L984–991. doi:10.1152/ajplung.00248.2006
  • Banerjee A, Koziol-White C, Panettieri R. p38 MAPK inhibitors, IKK2 inhibitors, and TNFα inhibitors in COPD. Curr Opin Pharmacol. 2012;12(3):287–292. doi:10.1016/j.coph.2012.01.016
  • Mercer BA, D’Armiento JM. Emerging role of MAP kinase pathways as therapeutic targets in COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(2):137–150. doi:10.2147/copd.2006.1.2.137
  • Crotty Alexander LE, Shin S, Hwang JH. Inflammatory Diseases of the Lung Induced by Conventional Cigarette Smoke: a Review. Chest. 2015;148(5):1307–1322. doi:10.1378/chest.15-0409
  • Oulton MRJD, MacDonald JM, Faulkner GT, Scott JE. Effects of smoke inhalation on alveolar surfactant subtypes in mice. Am J Pathol. 1994;145(4):941–950.
  • Oulton MMH, Scott JE, Janigan DT, Hajela R. Effects of smoke inhalation on surfactant phospholipids and phospholipase A2 activity in the mouse lung. Am J Pathol. 1991;138(1):195–202.
  • Sun YQX, Wu G. The effects of porcine pulmonary surfactant on smoke inhalation injury. J Surg Res. 2015;198(1):200–207. doi:10.1016/j.jss.2015.05.019
  • Scott JE. The pulmonary surfactant: impact of tobacco smoke and related compounds on surfactant and lung development. Tob Induc Dis. 2004;2(1):3–25. doi:10.1186/1617-9625-2-1-3
  • Sorensen GL. Surfactant Protein D in Respiratory and Non-Respiratory Diseases. Front Med. 2018;5:18. doi:10.3389/fmed.2018.00018
  • Chang J, Chen Z, Zhao R, Nie HG, Ji HL. Ion transport mechanisms for smoke inhalation-injured airway epithelial barrier. Cell Biol Toxicol. 2020;36(6):571–589. doi:10.1007/s10565-020-09545-1
  • Raghavendran K, Nemzek J, Napolitano LM, Knight PR. Aspiration-induced lung injury. Crit Care Med. 2011;39(4):818–826. doi:10.1097/CCM.0b013e31820a856b
  • Effros RMJE, Schapira RM, Biller J. Response of the lungs to aspiration. Am J Med. 2000;108(Suppl4a):15S–19S. doi:10.1016/S0002-9343(99)00290-9
  • Marik P. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344(9):665–671. doi:10.1056/NEJM200103013440908
  • Davidson BA, Vethanayagam RR, Grimm MJ, et al. NADPH oxidase and Nrf2 regulate gastric aspiration-induced inflammation and acute lung injury. J Immunol. 2013;190(4):1714–1724. doi:10.4049/jimmunol.1202410
  • Segal BHDB, Hutson AD, Russo TA, et al. Acid aspiration-induced lung inflammation and injury are exacerbated in NADPH oxidase-deficient mice. Am J Physiol. 2007;292(3):L760–768. doi:10.1152/ajplung.00281.2006
  • Puri G, Naura AS. Critical role of mitochondrial oxidative stress in acid aspiration induced ALI in mice. Toxicol Mech Methods. 2020;30(4):266–274. doi:10.1080/15376516.2019.1710888
  • Li HZX, Tan H, Hu Y, et al. Neutrophil extracellular traps contribute to the pathogenesis of acid-aspiration-induced ALI/ARDS. Oncotarget. 2017;9(2):1772–1784. doi:10.18632/oncotarget.22744
  • Chen Q, Huang Y, Yang Y, Qiu H. Acid‑induced cell injury and death in lung epithelial cells is associated with the activation of mitogen‑activated protein kinases. Mol Med Rep. 2013;8(2):565–570. doi:10.3892/mmr.2013.1537
  • Wang M, Cao X, Luan C, Li Z. Hydrogen Sulfide Attenuates Hydrogen Peroxide-Induced Injury in Human Lung Epithelial A549 Cells. Int J Mol Sci. 2019;20:16.
  • Davidson BA, Knight PR, Wang Z, et al. Surfactant alterations in acute inflammatory lung injury from aspiration of acid and gastric particulates. Am J Physiol Lung Cell Mol Physiol. 2005;288(4):L699–708. doi:10.1152/ajplung.00229.2004
  • Brackenbury AM, McCaig LA. Evaluation of exogenous surfactant in HCL-induced lung injury. Am J Respir Crit Care Med. 2001;163(5):1135–1142. doi:10.1164/ajrccm.163.5.2004049
  • Khalife-Hocquemiller T, Sage E, Dorfmuller P, et al. Exogenous surfactant attenuates lung injury from gastric-acid aspiration during ex vivo reconditioning in pigs. Transplantation. 2014;97(4):413–418. doi:10.1097/01.TP.0000441320.10787.c5
  • Nakajima D, Liu M, Ohsumi A, et al. Lung Lavage and Surfactant Replacement During Ex Vivo Lung Perfusion for Treatment of Gastric Acid Aspiration-Induced Donor Lung Injury. J Heart Lung Transplant. 2017;36(5):577–585. doi:10.1016/j.healun.2016.11.010
  • Chen CL, Li TP, Zhu LH. [Effect of MAPK signal transduction pathway inhibitor U0126 on aquaporin 4 expression in alveolar type II cells in rats with oleic acid-induced acute lung injury]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29(8):1525–1528. Chinese.
  • Song Y, Fukuda N, Bai C, Ma T, Matthay MA, Verkman AS. Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice. J Physiol. 2000;525 Pt 3(Pt3):771–779. doi:10.1111/j.1469-7793.2000.00771.x
  • Gonçalves-de-albuquerque CF, Burth P, Silva AR, et al. Oleic acid inhibits lung Na/K-ATPase in mice and induces injury with lipid body formation in leukocytes and eicosanoid production. J Inflamm. 2013;10(1):34. doi:10.1186/1476-9255-10-34
  • Chen HI, Hsieh NK, Kao SJ, Su CF. Protective effects of propofol on acute lung injury induced by oleic acid in conscious rats. Crit Care Med. 2008;36(4):1214–1221. doi:10.1097/CCM.0b013e31816a0607
  • Giuranno L, Ient J, De Ruysscher D, Vooijs MA. Radiation-Induced Lung Injury (RILI). Front Oncol. 2019;9:877. doi:10.3389/fonc.2019.00877
  • Maniatis NA, Kotanidou A, Catravas JD, Orfanos SE. Endothelial pathomechanisms in acute lung injury. Vascul Pharmacol. 2008;49(4–6):119–133. doi:10.1016/j.vph.2008.06.009
  • Beach TA, Groves AM, Williams JP, Finkelstein JN. Modeling radiation-induced lung injury: lessons learned from whole thorax irradiation. Int J Radiat Biol. 2020;96(1):129–144. doi:10.1080/09553002.2018.1532619
  • Azzam EI, Jay-Gerin JP, Pain D. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett. 2012;327(1–2):48–60. doi:10.1016/j.canlet.2011.12.012
  • Spitz DRAE, Li JJ, Gius D. Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metastasis Rev. 2004;23(3–4):311–322. doi:10.1023/B:CANC.0000031769.14728.bc
  • Park S, Ahn JY, Lim MJ, et al. Sustained expression of NADPH oxidase 4 by p38 MAPK-Akt signaling potentiates radiation-induced differentiation of lung fibroblasts. J Mol Med. 2010;88(8):807–816. doi:10.1007/s00109-010-0622-5
  • Sakai Y, Yamamori T, Yoshikawa Y, et al. NADPH oxidase 4 mediates ROS production in radiation-induced senescent cells and promotes migration of inflammatory cells. Free Radic Res. 2018;52(1):92–102. doi:10.1080/10715762.2017.1416112
  • Zhang Y, Zhang X, Rabbani ZN, Jackson IL, Vujaskovic Z. Oxidative stress mediates radiation lung injury by inducing apoptosis. Int J Radiat Oncol Biol Phys. 2012;83(2):740–748. doi:10.1016/j.ijrobp.2011.08.005
  • Hong ZY, Li S, Liu X, et al. Blocking C-Raf alleviated high-dose small-volume radiation-induced epithelial mesenchymal transition in mice lung. Sci Rep. 2020;10(1):11158. doi:10.1038/s41598-020-68175-z
  • Liang X, Gu J, Yu D, et al. Low-Dose Radiation Induces Cell Proliferation in Human Embryonic Lung Fibroblasts but not in Lung Cancer Cells. Dose-Response. 2016;14(1):155932581562217. doi:10.1177/1559325815622174
  • Jung JW, Hwang SY, Hwang JS, Oh ES, Park S, Han IO. Ionising radiation induces changes associated with epithelial-mesenchymal transdifferentiation and increased cell motility of A549 lung epithelial cells. Eur J Cancer. 2007;43(7):1214–1224. doi:10.1016/j.ejca.2007.01.034
  • Malaviya R, Gow AJ, Francis M, Abramova EV, Laskin JD, Laskin DL. Radiation-induced lung injury and inflammation in mice: role of inducible nitric oxide synthase and surfactant protein D. Toxicol Sci. 2015;144(1):27–38. doi:10.1093/toxsci/kfu255
  • Rubin P, Siemann DW, Shapiro DL, Finkelstein JN, Penney DP. Surfactant release as an early measure of radiation pneumonitis. Int J Radiat Oncol Biol Phys. 1983;9(11):1669–1673. doi:10.1016/0360-3016(83)90420-0
  • Christofidou-Solomidou M, Pietrofesa RA, Arguiri E, Koumenis C, Segal R. Radiation Mitigating Properties of Intranasally Administered KL4 Surfactant in a Murine Model of Radiation-Induced Lung Damage. Radiat Res. 2017;188(5):491–504. doi:10.1667/RR14686.1
  • Sun CY, Zhao YX, Zhong W, et al. The expression of aquaporins 1 and 5 in rat lung after thoracic irradiation. J Radiat Res. 2014;55(4):683–689. doi:10.1093/jrr/rru008
  • Li Y, Lu H, Lv X, et al. Blockade of Aquaporin 4 Inhibits Irradiation-Induced Pulmonary Inflammation and Modulates Macrophage Polarization in Mice. Inflammation. 2018;41(6):2196–2205. doi:10.1007/s10753-018-0862-z
  • Verheye-Dua FA, Böhm L. Influence of ouabain on cell inactivation by irradiation. Strahlentherapie und Onkologie. 1996;172(3):156–161.
  • Looney MR, Gropper MA, Matthay MA. Transfusion-related acute lung injury: a review. Chest. 2004;126(1):249–258. doi:10.1378/chest.126.1.249
  • Popovsky MA, Moore SB. Diagnostic and pathogenetic considerations in transfusion-related acute lung injury. Transfusion. 1985;25(6):573–577. doi:10.1046/j.1537-2995.1985.25686071434.x
  • Fung YL, Tung JP. How different animal models help us understand TRALI. ISBT Sci Series. 2018;13(3):197–205. doi:10.1111/voxs.12423
  • Silliman CC, Ambruso DR, Boshkov LK. Transfusion-related acute lung injury. Blood. 2005;105(6):2266–2273. doi:10.1182/blood-2004-07-2929
  • Thomas GM, Carbo C, Curtis BR, et al. Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice. Blood. 2012;119(26):6335–6343. doi:10.1182/blood-2012-01-405183
  • Lögdberg LE, Vikulina T, Zimring JC, Hillyer CD. Animal Models of Transfusion-Related Acute Lung Injury. Transfus Med Rev. 2009;23(1):13–24. doi:10.1016/j.tmrv.2008.09.002
  • Looney MR, Matthay MA. Animal models of transfusion-related acute lung injury. Crit Care Med. 2006;34(5):548. doi:10.1097/01.CCM.0000214287.58444.2D
  • Silliman CC, Thurman GW, Ambruso DR. Stored blood components contain agents that prime the neutrophil NADPH oxidase through the platelet-activating-factor receptor. Vox Sang. 1992;63(2):133–136. doi:10.1111/j.1423-0410.1992.tb02500.x
  • Bayat B, Tjahjono Y, Sydykov A, et al. Anti–Human Neutrophil Antigen-3a Induced Transfusion-Related Acute Lung Injury in Mice by Direct Disturbance of Lung Endothelial Cells. Arterioscler Thromb Vasc Biol. 2013;33(11):2538–2548. doi:10.1161/ATVBAHA.113.301206
  • McQuinn ER, Smith SA, Viall AK, Wang C, LeVine DN. Neutrophil extracellular traps in stored canine red blood cell units. J Vet Intern Med. 2020;34(5):1894–1902. doi:10.1111/jvim.15876
  • Rebetz J, Semple JW, Kapur R. The Pathogenic Involvement of Neutrophils in Acute Respiratory Distress Syndrome and Transfusion-Related Acute Lung Injury. Transfus Med Hemother. 2018;45(5):290–298. doi:10.1159/000492950
  • Caudrillier A, Kessenbrock K, Gilliss BM, et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest. 2012;122(7):2661–2671. doi:10.1172/JCI61303
  • Curtis BR, McFarland JG. Mechanisms of transfusion-related acute lung injury (TRALI): anti-leukocyte antibodies. Crit Care Med. 2006;34(5):548. doi:10.1097/01.CCM.0000214293.72918.D8
  • Álvarez P, Carrasco R, Romero-Dapueto C, Castillo RL. Transfusion-Related Acute Lung Injured (TRALI): current Concepts. Open Respir Med J. 2015;9:92–96. doi:10.2174/1874306401509010092
  • Looney MR, Su X, Van Ziffle JA, Lowell CA, Matthay MA. Neutrophils and their Fcγ receptors are essential in a mouse model of transfusion-related acute lung injury. J Clin Invest. 2006;116(6):1615–1623. doi:10.1172/JCI27238
  • Krammer F, Smith GJD, Fouchier RAM, et al. Influenza. Nat Rev Dis Primers. 2018;4(1):3. doi:10.1038/s41572-018-0002-y
  • Barnard DL. Animal models for the study of influenza pathogenesis and therapy. Antiviral Res. 2009;82(2):A110–A122. doi:10.1016/j.antiviral.2008.12.014
  • van Vught LA, Klein klouwenberg PMC, Spitoni C, et al. Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis. JAMA. 2016;315(14):1469–1479. doi:10.1001/jama.2016.2691
  • Bouvier NM, Lowen AC. Animal Models for Influenza Virus Pathogenesis and Transmission. Viruses. 2010;2(8):798. doi:10.3390/v20801530
  • Yageta Y, Ishii Y, Morishima Y, et al. Role of Nrf2 in Host Defense against Influenza Virus in Cigarette Smoke-Exposed Mice. J Virol. 2011;85(10):4679–4690. doi:10.1128/JVI.02456-10
  • Simon PF, McCorrister S, Hu P, et al. Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce More Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains. J Proteome Res. 2015;14(11):4511–4523. doi:10.1021/acs.jproteome.5b00196
  • Shoji M, Arakaki Y, Esumi T, et al. Bakuchiol Is a Phenolic Isoprenoid with Novel Enantiomer-selective Anti-influenza A Virus Activity Involving Nrf2 Activation *. J Biol Chem. 2015;290(46):28001–28017. doi:10.1074/jbc.M115.669465
  • Ma -L-L, Wang H-Q, Wu P, et al. Rupestonic acid derivative YZH-106 suppresses influenza virus replication by activation of heme oxygenase-1-mediated interferon response. Free Radical Biol Med. 2016;96:347–361. doi:10.1016/j.freeradbiomed.2016.04.021
  • Dai J, Gu L, Su Y, et al. Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways. Int Immunopharmacol. 2018;54:177–187. doi:10.1016/j.intimp.2017.11.009
  • Dai J-P, Wang Q-W, Su Y, et al. Emodin Inhibition of Influenza A Virus Replication and Influenza Viral Pneumonia via the Nrf2, TLR4, p38/JNK and NF-kappaB Pathways. Molecules. 2017;22:10. doi:10.3390/molecules22101754
  • Guo Y, Tu YH, Wu X, et al. ResolvinD1 Protects the Airway Barrier Against Injury Induced by Influenza A Virus Through the Nrf2 Pathway. Front Cell Infect Microbiol. 2020;10:616475. doi:10.3389/fcimb.2020.616475
  • Snelgrove RJ, Edwards L, Rae AJ, Hussell T. An absence of reactive oxygen species improves the resolution of lung influenza infection. Eur J Immunol. 2006;36(6):1364–1373. doi:10.1002/eji.200635977
  • Vlahos R, Stambas J, Bozinovski S, Broughton BR, Drummond GR, Selemidis S. Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation. PLoS Pathog. 2011;7(2):e1001271. doi:10.1371/journal.ppat.1001271
  • Imai Y, Kuba K, Neely GG, et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008;133(2):235–249. doi:10.1016/j.cell.2008.02.043
  • Amatore D, Sgarbanti R, Aquilano K, et al. Influenza virus replication in lung epithelial cells depends on redox-sensitive pathways activated by NOX4-derived ROS. Cell Microbiol. 2015;17(1):131–145. doi:10.1111/cmi.12343
  • Selemidis S, Seow HJ, Broughton BR, et al. Nox1 oxidase suppresses influenza a virus-induced lung inflammation and oxidative stress. PLoS One. 2013;8(4):e60792. doi:10.1371/journal.pone.0060792
  • Narasaraju T, Yang E, Samy RP, et al. Excessive Neutrophils and Neutrophil Extracellular Traps Contribute to Acute Lung Injury of Influenza Pneumonitis. Am J Pathol. 2011;179(1):199–210. doi:10.1016/j.ajpath.2011.03.013
  • Ashar HK, Mueller NC, Rudd JM, et al. The Role of Extracellular Histones in Influenza Virus Pathogenesis. Am J Pathol. 2018;188(1):135–148. doi:10.1016/j.ajpath.2017.09.014
  • Garcia CC, Weston-Davies W, Russo RC, et al. Complement C5 activation during influenza A infection in mice contributes to neutrophil recruitment and lung injury. PLoS One. 2013;8(5):e64443. doi:10.1371/journal.pone.0064443
  • Chan LLY, Nicholls JM, Peiris JSM, Lau YL, Chan MCW, Chan RWY. Host DNA released by NETosis in neutrophils exposed to seasonal H1N1 and highly pathogenic H5N1 influenza viruses. Respir Res. 2020;21(1):160. doi:10.1186/s12931-020-01425-w
  • Yu J, Sun X, Goie JY, Zhang Y. Regulation of Host Immune Responses against Influenza A Virus Infection by Mitogen-Activated Protein Kinases (MAPKs). Microorganisms. 2020;8:7. doi:10.3390/microorganisms8071067
  • Zhang R, Ai X, Duan Y, et al. Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways. Biomed Pharmacother. 2017;89:660–672. doi:10.1016/j.biopha.2017.02.081
  • Xing Z, Cardona CJ, Anunciacion J, Adams S, Dao N. Roles of the ERK MAPK in the regulation of proinflammatory and apoptotic responses in chicken macrophages infected with H9N2 avian influenza virus. J Gen Virol. 2010;91(Pt 2):343–351. doi:10.1099/vir.0.015578-0
  • Lee DC, Cheung CY, Law AH, Mok CK, Peiris M, Lau AS. p38 mitogen-activated protein kinase-dependent hyperinduction of tumor necrosis factor alpha expression in response to avian influenza virus H5N1. J Virol. 2005;79(16):10147–10154. doi:10.1128/JVI.79.16.10147-10154.2005
  • Gao W, Sun W, Qu B, et al. Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus. PLoS One. 2012;7(1):e30328. doi:10.1371/journal.pone.0030328
  • Li Y, Xu J, Shi W, et al. Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice. Stem Cell Res Ther. 2016;7(1):159. doi:10.1186/s13287-016-0395-z
  • Yu C-H, Yu W-Y, Fang J, et al. Mosla scabra flavonoids ameliorate the influenza A virus-induced lung injury and water transport abnormality via the inhibition of PRR and AQP signaling pathways in mice. J Ethnopharmacol. 2016;179:146–155. doi:10.1016/j.jep.2015.12.034
  • Geiler J, Michaelis M, Naczk P, et al. N-acetyl-l-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochem Pharmacol. 2010;79(3):413–420. doi:10.1016/j.bcp.2009.08.025
  • Ding Z, Sun G, Zhu Z. Hesperidin Attenuates Influenza a virus (H1N1) Induced Lung Injury in Rats through its Anti-Inflammatory Effect. Antivir Ther. 2017;23(7):611–615. doi:10.3851/IMP3235
  • Growcott EJ, Bamba D, Galarneau JR, et al. The effect of P38 MAP kinase inhibition in a mouse model of influenza. J Med Microbiol. 2018;67(3):452–462. doi:10.1099/jmm.0.000684
  • Wang W, Yang P, Zhong Y, et al. Monoclonal antibody against CXCL-10/IP-10 ameliorates influenza A (H1N1) virus induced acute lung injury. Cell Res. 2013;23(4):577–580. doi:10.1038/cr.2013.25
  • Huang F, Zhang C, Liu Q, et al. Identification of amitriptyline HCl, flavin adenine dinucleotide, azacitidine and calcitriol as repurposing drugs for influenza A H5N1 virus-induced lung injury. PLoS Pathog. 2020;16(3):e1008341. doi:10.1371/journal.ppat.1008341
  • Li J, Jie X, Liang X, et al. Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings. BMC Complement Med Therap. 2020;20(1):135. doi:10.1186/s12906-020-02918-3
  • Wang Q-W, Su Y, Sheng J-T, et al. Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways. PLoS One. 2018;13(1):e0191793. doi:10.1371/journal.pone.0191793
  • Dai J-P, Wang Q-W, Su Y, et al. Oxymatrine Inhibits Influenza A Virus Replication and Inflammation via TLR4, p38 MAPK and NF-κB Pathways. Int J Mol Sci. 2018;19(4):548. doi:10.3390/ijms19040965
  • Cui L, Zheng D, Lee YH, et al. Metabolomics Investigation Reveals Metabolite Mediators Associated with Acute Lung Injury and Repair in a Murine Model of Influenza Pneumonia. Sci Rep. 2016;6:26076. doi:10.1038/srep26076
  • Woods PS, Doolittle LM, Rosas LE, Joseph LM, Calomeni EP, Davis IC. Lethal H1N1 influenza A virus infection alters the murine alveolar type II cell surfactant lipidome. Am J Physiol Lung Cell Mol Physiol. 2016;311(6):L1160–L1169. doi:10.1152/ajplung.00339.2016
  • Numata M, Mitchell JR, Tipper JL, et al. Pulmonary surfactant lipids inhibit infections with the pandemic H1N1 influenza virus in several animal models. J Biol Chem. 2020;295(6):1704–1715. doi:10.1074/jbc.RA119.012053
  • Donovan BW, Reuter JD, Cao Z, Myc A, Johnson KJ, Baker JR. Prevention of Murine Influenza a Virus Pneumonitis by Surfactant Nano-Emulsions. Antivir Chem Chemother. 2000;11(1):41–49. doi:10.1177/095632020001100104
  • Fukushi M, Yamashita M, Miyoshi-Akiyama T, Kubo S, Yamamoto K, Kudo K. Laninamivir Octanoate and Artificial Surfactant Combination Therapy Significantly Increases Survival of Mice Infected with Lethal Influenza H1N1 Virus. PLoS One. 2012;7(8):e42419. doi:10.1371/journal.pone.0042419
  • Chen X-J, Seth S, Yue G, et al. Influenza virus inhibits ENaC and lung fluid clearance. Am J Physiol. 2004;287(2):L366–L373. doi:10.1152/ajplung.00011.2004
  • Peteranderl C, Morales-Nebreda L, Selvakumar B, et al. Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection. J Clin Invest. 2016;126(4):1566–1580. doi:10.1172/JCI83931
  • Chan MCW, Kuok DIT, Leung CYH, et al. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo. Proc Natl Acad Sci. 2016;113(13):3621. doi:10.1073/pnas.1601911113
  • Dockrell DH, Whyte MKB, Mitchell TJ. Pneumococcal pneumonia: mechanisms of infection and resolution. Chest. 2012;142(2):482–491. doi:10.1378/chest.12-0210
  • Kadioglu A, Weiser JN, Paton JC, Andrew PW. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat Rev Microbiol. 2008;6(4):288–301. doi:10.1038/nrmicro1871
  • Brooks LRK, Mias GI. Streptococcus pneumoniae’s Virulence and Host Immunity: aging, Diagnostics, and Prevention. Front Immunol. 2018;1:9.
  • Henriques-Normark B, Tuomanen EI. The pneumococcus: epidemiology, microbiology, and pathogenesis. Cold Spring Harb Perspect Med. 2013;3(7):432. doi:10.1101/cshperspect.a010215
  • Chiavolini D, Pozzi G, Ricci S. Animal Models of Streptococcus pneumoniae Disease. Clin Microbiol Rev. 2008;21(4):666–685. doi:10.1128/CMR.00012-08
  • Borsa N, Di Pasquale M, Restrepo MI. Animal Models of Pneumococcal pneumonia. Int J Mol Sci. 2019;20:17. doi:10.3390/ijms20174220
  • Zahlten J, Kim Y-J, Doehn J-M, et al. Streptococcus pneumoniae–Induced Oxidative Stress in Lung Epithelial Cells Depends on Pneumococcal Autolysis and Is Reversible by Resveratrol. J Infect Dis. 2015;211(11):1822–1830. doi:10.1093/infdis/jiu806
  • Gomez JC, Dang H, Martin JR, Doerschuk CM. Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice. J Immunol. 2016;197(7):2864–2879. doi:10.4049/jimmunol.1600043
  • Marriott HM, Jackson LE, Wilkinson TS, et al. Reactive oxygen species regulate neutrophil recruitment and survival in pneumococcal pneumonia. Am J Respir Crit Care Med. 2008;177(8):887–895. doi:10.1164/rccm.200707-990OC
  • Moorthy AN, Rai P, Jiao H, et al. Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia. Oncotarget. 2016;7(15):19327–19340. doi:10.18632/oncotarget.8451
  • Mori Y, Yamaguchi M, Terao Y, Hamada S, Ooshima T, Kawabata S. α-Enolase of Streptococcus pneumoniae induces formation of neutrophil extracellular traps. J Biol Chem. 2012;287(13):10472–10481. doi:10.1074/jbc.M111.280321
  • Narayana Moorthy A, Narasaraju T, Rai P, et al. In vivo and in vitro studies on the roles of neutrophil extracellular traps during secondary pneumococcal pneumonia after primary pulmonary influenza infection. Front Immunol. 2013;4:654. doi:10.3389/fimmu.2013.00056
  • Wartha F, Beiter K, Albiger B, et al. Capsule and d-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps. Cell Microbiol. 2007;9(5):1162–1171. doi:10.1111/j.1462-5822.2006.00857.x
  • Beiter K, Wartha F, Albiger B, Normark S, Zychlinsky A, Henriques-Normark B. An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps. Curr Biol. 2006;16(4):401–407. doi:10.1016/j.cub.2006.01.056
  • N’Guessan PD, Schmeck B, Ayim A, et al. Streptococcus pneumoniae R6x induced p38 MAPK JNK-mediated Caspase-dependent apoptosis in human endothelial cells. Thromb Haemost. 2005;94(08):295–303. doi:10.1160/TH04-12-0822
  • Xu F, Droemann D, Rupp J, et al. Modulation of the inflammatory response to Streptococcus pneumoniae in a model of acute lung tissue infection. Am J Respir Cell Mol Biol. 2008;39(5):522–529. doi:10.1165/rcmb.2007-0328OC
  • Schmeck B, Zahlten J, Moog K, et al. Streptococcus pneumoniae-induced p38 MAPK-dependent phosphorylation of RelA at the interleukin-8 promotor. J Biol Chem. 2004;279(51):53241–53247. doi:10.1074/jbc.M313702200
  • N’Guessan PD, Hippenstiel S, Etouem MO, et al. Streptococcus pneumoniae induced p38 MAPK- and NF-κB-dependent COX-2 expression in human lung epithelium. Am J Physiol. 2006;290(6):L1131–L1138. doi:10.1152/ajplung.00383.2005
  • Szymanski KV, Toennies M, Becher A, et al. Streptococcus pneumoniae-induced regulation of cyclooxygenase-2 in human lung tissue. Eur Respir J. 2012;40(6):1458–1467. doi:10.1183/09031936.00186911
  • Boyd AR, Shivshankar P, Jiang S, Berton MT, Orihuela CJ. Age-related defects in TLR2 signaling diminish the cytokine response by alveolar macrophages during murine pneumococcal pneumonia. Exp Gerontol. 2012;47(7):507–518. doi:10.1016/j.exger.2012.04.004
  • Jounblat R, Kadioglu A, Iannelli F, Pozzi G, Eggleton P, Andrew PW. Binding and agglutination of Streptococcus pneumoniae by human surfactant protein D (SP-D) vary between strains, but SP-D fails to enhance killing by neutrophils. Infect Immun. 2004;72(2):709–716. doi:10.1128/IAI.72.2.709-716.2004
  • Jounblat R, Clark H, Eggleton P, Hawgood S, Andrew PW, Kadioglu A. The role of surfactant protein D in the colonisation of the respiratory tract and onset of bacteraemia during pneumococcal pneumonia. Respir Res. 2005;6(1):126. doi:10.1186/1465-9921-6-126
  • Tyrrell C, McKechnie SR, Beers MF, Mitchell TJ, McElroy MC. Differential alveolar epithelial injury and protein expression in pneumococcal pneumonia. Exp Lung Res. 2012;38(5):266–276. doi:10.3109/01902148.2012.683321
  • LaCanna R, Liccardo D, Zhang P, et al. Yap/Taz regulate alveolar regeneration and resolution of lung inflammation. J Clin Invest. 2019;129(5):2107–2122. doi:10.1172/JCI125014
  • Witzenrath M, Gutbier B, Hocke AC, et al. Role of pneumolysin for the development of acute lung injury in pneumococcal pneumonia. Crit Care Med. 2006;34(7):87. doi:10.1097/01.CCM.0000220496.48295.A9
  • Ross JT, Nesseler N, Leligdowicz A, et al. The ex vivo perfused human lung is resistant to injury by high-dose S. pneumoniae bacteremia. Am J Physiol Lung Cell Mol Physiol. 2020;319(2):L218–L227. doi:10.1152/ajplung.00053.2020
  • Czikora I, Alli AA, Sridhar S, et al. Epithelial Sodium Channel-α Mediates the Protective Effect of the TNF-Derived TIP Peptide in Pneumolysin-Induced Endothelial Barrier Dysfunction. Front Immunol. 2017;8:842. doi:10.3389/fimmu.2017.00842
  • Rabaan AA, Al-Ahmed SH, Haque S, et al. SARS-CoV-2, SARS-CoV, and MERS-COV: a comparative overview. Le infezioni in medicina. Ahead Print. 2020;28(2):174–184.
  • Abdool Karim SS, de Oliveira T. New SARS-CoV-2 Variants — clinical, Public Health, and Vaccine Implications. N Engl J Med. 2021;384(19):1866–1868. doi:10.1056/NEJMc2100362
  • Gong S, Bao L. The battle against SARS and MERS coronaviruses: reservoirs and Animal Models. Anim Models Exp Med. 2018;1(2):125–133. doi:10.1002/ame2.12017
  • Pandey K, Acharya A, Mohan M, Ng CL, Reid SP, Byrareddy SN. Animal models for SARS-CoV-2 research: a comprehensive literature review. Transbound Emerg Dis. 2021;68(4):1868–1885. doi:10.1111/tbed.13907
  • Becker K, Beythien G, de Buhr N, et al. Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2. Front Immunol. 2021;12:640842. doi:10.3389/fimmu.2021.640842
  • Adrover JM, Carrau L, Daßler-Plenker J, et al. Disulfiram inhibits neutrophil extracellular trap formation and protects rodents from acute lung injury and SARS-CoV-2 infection. JCI Insight. 2022;7(5):53. doi:10.1172/jci.insight.157342
  • Jimenez-Guardeño JM, Nieto-Torres JL, DeDiego ML, et al. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. PLoS Pathog. 2014;10(8):e1004320. doi:10.1371/journal.ppat.1004320
  • Chang YJ, Liu CY, Chiang BL, Chao YC, Chen CC. Induction of IL-8 release in lung cells via activator protein-1 by recombinant baculovirus displaying severe acute respiratory syndrome-coronavirus spike proteins: identification of two functional regions. J Immunol. 2004;173(12):7602–7614. doi:10.4049/jimmunol.173.12.7602
  • Kopecky-Bromberg SA, Martinez-Sobrido L, Palese P. 7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase. J Virol. 2006;80(2):785–793. doi:10.1128/JVI.80.2.785-793.2006
  • Li SW, Wang CY, Jou YJ, et al. SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway. Sci Rep. 2016;6:25754. doi:10.1038/srep25754
  • Gu T, Zhao S, Jin G, et al. Cytokine Signature Induced by SARS-CoV-2 Spike Protein in a Mouse Model. Front Immunol. 2020;11:621441. doi:10.3389/fimmu.2020.621441
  • Gralinski LE, Bankhead A, Jeng S, et al. Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury. mBio. 2013;4(4):515. doi:10.1128/mBio.00271-13
  • Suresh V, Mohanty V, Avula K, et al. Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host factors having implication in the disease pathogenesis and severity. FASEB J. 2021;35(7):e21713. doi:10.1096/fj.202100431R
  • Hsieh M-H, Beirag N, Murugaiah V, et al. Human Surfactant Protein D Binds Spike Protein and Acts as an Entry Inhibitor of SARS-CoV-2 Pseudotyped Viral Particles. Front Immunol. 2021;12:641360. doi:10.3389/fimmu.2021.641360
  • Nagata N, Iwata N, Hasegawa H, et al. Mouse-passaged severe acute respiratory syndrome-associated coronavirus leads to lethal pulmonary edema and diffuse alveolar damage in adult but not young mice. Am J Pathol. 2008;172(6):1625–1637. doi:10.2353/ajpath.2008.071060
  • Yu P, Xu Y, Deng W, et al. Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus. PLoS One. 2017;12(2):e0172093. doi:10.1371/journal.pone.0172093
  • Allnoch L, Beythien G, Leitzen E, et al. Vascular Inflammation Is Associated with Loss of Aquaporin 1 Expression on Endothelial Cells and Increased Fluid Leakage in SARS-CoV-2 Infected Golden Syrian Hamsters. Viruses. 2021;13(4):548. doi:10.3390/v13040639
  • Gattinoni L, Marini JJ, Collino F, et al. The future of mechanical ventilation: lessons from the present and the past. Crit Care. 2017;21(1):183. doi:10.1186/s13054-017-1750-x
  • Hubmayr RD, Kallet RH. Understanding Pulmonary Stress-Strain Relationships in Severe ARDS and Its Implications for Designing a Safer Approach to Setting the Ventilator. Respir Care. 2018;63(2):219–226. doi:10.4187/respcare.05900
  • InterNational consensus conferences in intensive care medicine: Ventilator-associated Lung Injury in ARDS. This official conference report was cosponsored by the American Thoracic Society, The European Society of Intensive Care Medicine, and The Societé de Réanimation de Langue Française, and was approved by the ATS Board of Directors 1999. Am J Respir Crit Care Med. 1999;160(6):2118–2124. doi:10.1164/ajrccm.160.6.ats16060.
  • Force* TADT. Acute Respiratory Distress Syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–2533. doi:10.1001/jama.2012.5669.
  • Bernard GRAA, Brigham KL, Carlet J, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3Pt 1):818–824. doi:10.1164/ajrccm.149.3.7509706
  • Hoidal JR, Xu P, Huecksteadt T, Sanders KA, Pfeffer K, Sturrock AB. Lung injury and oxidoreductases. Environ Health Perspect. 1998;106(suppl 5):1235–1239. doi:10.1289/ehp.98106s51235
  • Carnesecchi S, Dunand-Sauthier I, Zanetti F, et al. NOX1 is responsible for cell death through STAT3 activation in hyperoxia and is associated with the pathogenesis of acute respiratory distress syndrome. Int J Clin Exp Pathol. 2014;7(2):537–551.
  • O’Mahony DS, Glavan BJ, Holden TD, et al. Inflammation and immune-related candidate gene associations with acute lung injury susceptibility and severity: a validation study. PLoS One. 2012;7(12):e51104. doi:10.1371/journal.pone.0051104
  • Williams AECR. The mercurial nature of neutrophils: still an enigma in ARDS? Am J Physiol Lung Cell Mol Physiol. 2014;306(3):L217–230. doi:10.1152/ajplung.00311.2013
  • Ebrahimi F, Giaglis S, Hahn S, et al. Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia: secondary analysis of a randomised controlled trial. Eur Respir J. 2018;51(4):45. doi:10.1183/13993003.01389-2017
  • Park SY, Shrestha S, Youn Y-J, et al. Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis. Am J Respir Crit Care Med. 2017;196(5):577–589. doi:10.1164/rccm.201603-0596OC
  • Hu L, Zhao T, Sun Y, Chen Y, Bai K, Xu F. Bioinformatic identification of hub genes and key pathways in neutrophils of patients with acute respiratory distress syndrome. Medicine. 2020;99(15):e19820. doi:10.1097/MD.0000000000019820
  • Juss JK, House D, Amour A, et al. Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition. Am J Respir Crit Care Med. 2016;194(8):961–973. doi:10.1164/rccm.201509-1818OC
  • 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. Crit Care. 2006;10(2):R41. doi:10.1186/cc4851
  • Hintz SR, Poole WK, Wright LL, et al. Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era. Arch Dis Child Fetal Neonatal Ed. 2005;90(2):F128–133. doi:10.1136/adc.2003.046268
  • Meng SS, Chang W, Lu ZH, et al. Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome: a meta-analysis of randomized controlled trials. BMC Pulm Med. 2019;19(1):9. doi:10.1186/s12890-018-0761-y
  • Spragg RG, Lewis JF, Wurst W, et al. Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant. Am J Respir Crit Care Med. 2003;167(11):1562–1566. doi:10.1164/rccm.200207-782OC
  • Willson DF, Notter RH. The future of exogenous surfactant therapy. Respir Care. 2011;56(9):1369–1388. doi:10.4187/respcare.01306
  • Taut FJH, Rippin G, Schenk P, et al. A Search for Subgroups of Patients With ARDS Who May Benefit From Surfactant Replacement Therapy: a Pooled Analysis of Five Studies With Recombinant Surfactant Protein-C Surfactant (Venticute). Chest. 2008;134(4):724–732. doi:10.1378/chest.08-0362
  • Matthay MA, Folkesson HG, Clerici C. Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev. 2002;82(3):569–600. doi:10.1152/physrev.00003.2002
  • Rahmel T, Rump K, Peters J, Adamzik M. Aquaporin 5-1364A/C Promoter Polymorphism Is Associated with Pulmonary Inflammation and Survival in Acute Respiratory Distress Syndrome. Anesthesiology. 2019;130(3):404–413. doi:10.1097/ALN.0000000000002560
  • Matthay MA. Alveolar fluid clearance in patients with ARDS: does it make a difference? Chest. 2002;122(6Suppl):340S–343S. doi:10.1378/chest.122.6_suppl.340S
  • Krenn K, Lucas R, Croizé A, et al. Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated patients with acute respiratory distress syndrome: a phase IIa randomized placebo-controlled trial. Crit Care. 2017;21(1):194. doi:10.1186/s13054-017-1795-x
  • Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017;45(3):486–552. doi:10.1097/CCM.0000000000002255
  • Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810. doi:10.1001/jama.2016.0287
  • Kangelaris KN, Prakash A, Liu KD, et al. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS. Am J Physiol. 2015;308(11):L1102–L1113. doi:10.1152/ajplung.00380.2014
  • Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and Outcomes of Acute Lung Injury. N Engl J Med. 2005;353(16):1685–1693. doi:10.1056/NEJMoa050333
  • Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ. 2016;353:i1585. doi:10.1136/bmj.i1585
  • Leligdowicz A, Matthay MA. Heterogeneity in sepsis: new biological evidence with clinical applications. Crit Care. 2019;23(1):80. doi:10.1186/s13054-019-2372-2
  • Acosta-Herrera M, Pino-Yanes M, Blanco J, et al. Common variants of NFE2L2 gene predisposes to acute respiratory distress syndrome in patients with severe sepsis. Crit Care. 2015;19(1):256. doi:10.1186/s13054-015-0981-y
  • Lefrancais E, Mallavia B, Zhuo H, Calfee CS, Looney MR. Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury. JCI Insight. 2018;3(3):5485.
  • Wang D, Li Y, Gu C, Liu M, Wang Y. Identification of Key Pathways and Genes of Acute Respiratory Distress Syndrome Specific Neutrophil Phenotype. Biomed Res Int. 2019;2019:9528584. doi:10.1155/2019/9528584
  • Anzueto A, Baughman RP, Guntupalli KK, et al. Aerosolized Surfactant in Adults with Sepsis-Induced Acute Respiratory Distress Syndrome. N Engl J Med. 1996;334(22):1417–1422. doi:10.1056/NEJM199605303342201
  • Walmrath D, Grimminger F, Pappert D, et al. Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics. Eur Respir J. 2002;19(5):805–810. doi:10.1183/09031936.02.00243402
  • Weg JG, Balk RA, Tharratt RS, et al. Safety and Potential Efficacy of an Aerosolized Surfactant in Human Sepsis-Induced Adult Respiratory Distress Syndrome. JAMA. 1994;272(18):1433–1438. doi:10.1001/jama.1994.03520180057035
  • Zeyed YF, Bastarache JA, Matthay MA, Ware LB. The severity of shock is associated with impaired rates of net alveolar fluid clearance in clinical acute lung injury. Am J Physiol. 2012;303(6):L550–L555. doi:10.1152/ajplung.00190.2012
  • Vassiliou AG, Maniatis NA, Orfanos SE, et al. Induced expression and functional effects of aquaporin-1 in human leukocytes in sepsis. Crit Care. 2013;17(5):R199. doi:10.1186/cc12893
  • Adamzik M, Frey UH, Möhlenkamp S, et al. Aquaporin 5 Gene Promoter −1364A/C Polymorphism Associated with 30-day Survival in Severe Sepsis. Anesthesiology. 2011;114(4):912–917. doi:10.1097/ALN.0b013e31820ca911
  • Rump K, Unterberg M, Dahlke A, et al. DNA methylation of a NF-κB binding site in the aquaporin 5 promoter impacts on mortality in sepsis. Sci Rep. 2019;9(1):18511. doi:10.1038/s41598-019-55051-8
  • Li G, Zhang Y, Fan Z. Cellular Signal Transduction Pathways Involved in Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion. Oxid Med Cell Longev. 2021;2021:9985701.
  • Weyker PD, Webb CA, Kiamanesh D, Flynn BC. Lung ischemia reperfusion injury: a bench-to-bedside review. Semin Cardiothorac Vasc Anesth. 2013;17(1):28–43. doi:10.1177/1089253212458329
  • Christie JD, Carby M, Bag R, et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005;24(10):1454–1459. doi:10.1016/j.healun.2004.11.049
  • Hohlfeld JM, Tiryaki E, Hamm H, et al. Pulmonary surfactant activity is impaired in lung transplant recipients. Am J Respir Crit Care Med. 1998;158(3):706–712. doi:10.1164/ajrccm.158.3.9708063
  • Amital A, Shitrit D, Raviv Y, et al. The Use of Surfactant in Lung Transplantation. Transplantation. 2008;86:11. doi:10.1097/TP.0b013e31818a8418
  • Kermeen FD, McNeil KD, Fraser JF, et al. Resolution of Severe Ischemia–Reperfusion Injury Post–Lung Transplantation After Administration of Endobronchial Surfactant. J Heart Lung Transplant. 2007;26(8):850–856. doi:10.1016/j.healun.2007.05.016
  • Strüber M, Fischer S, Niedermeyer J, et al. Effects of exogenous surfactant instillation in clinical lung transplantation: a prospective, randomized trial. J Thorac Cardiovasc Surg. 2007;133(6):1620–1625. doi:10.1016/j.jtcvs.2006.12.057
  • Strüber M, Hirt SW, Cremer J, Harringer W, Haverich A. Surfactant replacement in reperfusion injury after clinical lung transplantation. Intensive Care Med. 1999;25(8):862–864. doi:10.1007/s001340050967
  • Ware LB, Golden JA, Finkbeiner WE, Matthay MA. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation. Am J Respir Crit Care Med. 1999;159(3):980–988. doi:10.1164/ajrccm.159.3.9802105
  • Dries DJEFS. Inhalation injury: epidemiology, pathology, treatment strategies. J Trauma Resusc Emerg Med. 2013;21:31. doi:10.1186/1757-7241-21-31
  • Cho HY, Kleeberger SR. Nrf2 protects against airway disorders. Toxicol Appl Pharmacol. 2010;244(1):43–56. doi:10.1016/j.taap.2009.07.024
  • Barnes PJ. Oxidative stress-based therapeutics in COPD. Redox Biol. 2020;33:101544. doi:10.1016/j.redox.2020.101544
  • Tamimi A, Serdarevic D, Hanania NA. The effects of cigarette smoke on airway inflammation in asthma and COPD: therapeutic implications. Respir Med. 2012;106(3):319–328. doi:10.1016/j.rmed.2011.11.003
  • Zhao CZ, Fang XC, Wang D, Tang FD, Wang XD. Involvement of type II pneumocytes in the pathogenesis of chronic obstructive pulmonary disease. Respir Med. 2010;104(10):1391–1395. doi:10.1016/j.rmed.2010.06.018
  • Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogué S, Ferrer M. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet. 1999;354(9193):1851–1858. doi:10.1016/S0140-6736(98)12251-1
  • Potts RG, Zaroukian MH, Guerrero PA, Baker CD. Comparison of blue dye visualization and glucose oxidase test strip methods for detecting pulmonary aspiration of enteral feedings in intubated adults. Chest. 1993;103(1):117–121. doi:10.1378/chest.103.1.117
  • Morgan GWBS. Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat Oncol Biol Phys. 1995;31(2):361–369. doi:10.1016/0360-3016(94)00477-3
  • Byhardt RWAR, Almagro U. The association of adult respiratory distress syndrome (ARDS) with thoracic irradiation (RT). Int J Radiat Oncol Biol Phys. 1988;15(6):1441–1446. doi:10.1016/0360-3016(88)90241-6
  • Chen S, Zhou S, Zhang J, Yin FF, Marks LB, Das SK. A neural network model to predict lung radiation-induced pneumonitis. Med Phys. 2007;34(9):3420–3427. doi:10.1118/1.2759601
  • Jarzebska N, Karetnikova ES, Markov AG, Kasper M, Rodionov RN, Spieth PM. Scarred Lung. An Update on Radiation-Induced Pulmonary Fibrosis. Front Med. 2020;7:585756. doi:10.3389/fmed.2020.585756
  • Tung J-P, Chiaretti S, Dean MM, Sultana AJ, Reade MC, Fung YL. Transfusion-related acute lung injury (TRALI): potential pathways of development, strategies for prevention and treatment, and future research directions. Blood Rev. 2022;53:100926. doi:10.1016/j.blre.2021.100926
  • Toy P, Lowell C. TRALI–definition, mechanisms, incidence and clinical relevance. Best Pract Res Clin Anaesthesiol. 2007;21(2):183–193. doi:10.1016/j.bpa.2007.01.003
  • Lenahan SE, Domen RE, Silliman CC, Kingsley CP, Romano PJ. Transfusion-Related Acute Lung Injury Secondary to Biologically Active Mediators. Arch Pathol Lab Med. 2001;125(4):523–526. doi:10.5858/2001-125-0523-TRALIS
  • Wu T-J, Teng R-J, Yau K-IT. Transfusion-related acute lung injury treated with surfactant in a neonate. Eur J Pediatr. 1996;155(7):589–591. doi:10.1007/BF01957910
  • Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J. 2015;45(5):1463–1478. doi:10.1183/09031936.00186214
  • Kosmider B, Messier EM, Janssen WJ, et al. Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus. Respir Res. 2012;13(1):43. doi:10.1186/1465-9921-13-43
  • Zhu L, Liu L, Zhang Y, et al. High Level of Neutrophil Extracellular Traps Correlates With Poor Prognosis of Severe Influenza A Infection. J Infect Dis. 2018;217(3):428–437. doi:10.1093/infdis/jix475
  • Zhang N, Zhu L, Zhang Y, et al. Circulating Rather Than Alveolar Extracellular Deoxyribonucleic Acid Levels Predict Outcomes in Influenza. J Infect Dis. 2020;222(7):1145–1154. doi:10.1093/infdis/jiaa241
  • Herrera-Ramos E, López-Rodríguez M, Ruíz-Hernández JJ, et al. Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection. Crit Care. 2014;18(3):R127. doi:10.1186/cc13934
  • To KKW, Zhou J, Song Y-Q, et al. Surfactant Protein B Gene Polymorphism Is Associated With Severe Influenza. Chest. 2014;145(6):1237–1243. doi:10.1378/chest.13-1651
  • Kongchanagul A, Suptawiwat O, Boonarkart C, et al. Decreased expression of surfactant protein D mRNA in human lungs in fatal cases of H5N1 avian influenza. J Med Virol. 2011;83(8):1410–1417. doi:10.1002/jmv.22105
  • Choreño-Parra JA, Jiménez-álvarez LA, Ramírez-Martínez G, et al. Expression of Surfactant Protein D Distinguishes Severe Pandemic Influenza A(H1N1) from Coronavirus Disease 2019. J Infect Dis. 2021;224(1):21–30. doi:10.1093/infdis/jiab113
  • Burgos J, Falcó V, Borrego A, et al. Impact of the emergence of non-vaccine pneumococcal serotypes on the clinical presentation and outcome of adults with invasive pneumococcal pneumonia. Clin Microbiol Infect. 2013;19(4):385–391. doi:10.1111/j.1469-0691.2012.03895.x
  • Lanks CW, Musani AI, Hsia DW. Community-acquired Pneumonia and Hospital-acquired Pneumonia. Med Clin North Am. 2019;103(3):487–501. doi:10.1016/j.mcna.2018.12.008
  • Suaya JA, Fletcher MA, Georgalis L, et al. Identification of Streptococcus pneumoniae in hospital-acquired pneumonia in adults. J Hosp Infect. 2021;108:146–157. doi:10.1016/j.jhin.2020.09.036
  • Sender V, Hentrich K, Henriques-Normark B. Virus-Induced Changes of the Respiratory Tract Environment Promote Secondary Infections With Streptococcus pneumoniae. Front Cell Infect Microbiol. 2021;11:643326. doi:10.3389/fcimb.2021.643326
  • Nucci LA, Santos SS, Brunialti MK, et al. Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients. PLoS One. 2017;12(2):e0172024. doi:10.1371/journal.pone.0172024
  • García-Laorden M. Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study. Crit Care. 2011;15(1):R57. doi:10.1186/cc10030
  • Saleh NY, Ibrahem RAL, Saleh AAH, Soliman SES, Mahmoud AAS. Surfactant protein D: a predictor for severity of community-acquired pneumonia in children. Pediatr Res. 2022;91(3):665–671. doi:10.1038/s41390-021-01492-9
  • Liu J, Zheng X, Tong Q, et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol. 2020;92(5):491–494. doi:10.1002/jmv.25709
  • Vassiliou AG, Keskinidou C, Jahaj E, et al. ICU Admission Levels of Endothelial Biomarkers as Predictors of Mortality in Critically Ill COVID-19 Patients. Cells. 2021;10(1):87. doi:10.3390/cells10010186
  • Vassiliou AG, Zacharis A, Keskinidou C, et al. Soluble Angiotensin Converting Enzyme 2 (ACE2) Is Upregulated and Soluble Endothelial Nitric Oxide Synthase (eNOS) Is Downregulated in COVID-19-induced Acute Respiratory Distress Syndrome (ARDS). Pharmaceuticals. 2021;14(7):25. doi:10.3390/ph14070695
  • Keskinidou C, Vassiliou AG, Zacharis A, et al. Endothelial, Immunothrombotic, and Inflammatory Biomarkers in the Risk of Mortality in Critically Ill COVID-19 Patients: the Role of Dexamethasone. Diagnostics. 2021;11(7):53. doi:10.3390/diagnostics11010053
  • Leisman DE, Ronner L, Pinotti R, et al. Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Lancet Respir Med. 2020;8(12):1233–1244.
  • Vassiliou AG, Dimopoulou I, Jahaj E, et al. Selection of the Appropriate Control Group Is Essential in Evaluating the Cytokine Storm in COVID-19. In vivo. 2021;35(2):1295–1298. doi:10.21873/invivo.12381
  • Deshmukh V, Motwani R, Kumar A, Kumari C, Raza K. Histopathological observations in COVID-19: a systematic review. J Clin Pathol. 2021;74(2):76. doi:10.1136/jclinpath-2020-206995
  • Martines RB, Ritter JM, Matkovic E, et al. Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States. Emerg Infect Dis. 2020;26(9):2005–2015. doi:10.3201/eid2609.202095
  • Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust. 2020;213(2):54–56 e51. doi:10.5694/mja2.50674
  • Violi F, Oliva A, Cangemi R, et al. Nox2 activation in Covid-19. Redox Biol. 2020;36:101655. doi:10.1016/j.redox.2020.101655
  • Damiano S, Sozio C, La Rosa G, Santillo M. NOX-Dependent Signaling Dysregulation in Severe COVID-19: clues to Effective Treatments. Front Cell Infect Microbiol. 2020;10:608435. doi:10.3389/fcimb.2020.608435
  • Cuadrado A, Pajares M, Benito C, et al. Can Activation of NRF2 Be a Strategy against COVID-19? Trends in pharmacological sciences. Sep. 2020;41(9):598–610.
  • Emanuele S, Celesia A, D’Anneo A, et al. The Good and Bad of Nrf2: an Update in Cancer and New Perspectives in COVID-19. Int J Mol Sci. 2021;22:15. doi:10.3390/ijms22157963
  • McCord JM, Hybertson BM, Cota-Gomez A, Gao B. Nrf2 activator PB125® as a carnosic acid-based therapeutic agent against respiratory viral diseases, including COVID-19. Free Radic Biol Med. 2021;175:56–64. doi:10.1016/j.freeradbiomed.2021.05.033
  • Singh E, Matada GSP, Abbas N, Dhiwar PS, Ghara A, Das A. Management of COVID-19-induced -cytokine -storm by Keap1-Nrf2 system: a review. Inflammopharmacology. 2021;29(5):1347–1355. doi:10.1007/s10787-021-00860-5
  • Olagnier D, Farahani E, Thyrsted J, et al. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat Commun. 2020;11(1):4938. doi:10.1038/s41467-020-18764-3
  • Arcanjo A, Logullo J, Menezes CCB, et al. The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19). Sci Rep. 2020;10(1):19630. doi:10.1038/s41598-020-76781-0
  • Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med. 2020;217(6):54. doi:10.1084/jem.20200652
  • Jing H, Chen X, Zhang S, et al. Neutrophil extracellular traps (NETs): the role of inflammation and coagulation in COVID-19. Am J Transl Res. 2021;13(8):8575–8588.
  • Masso-Silva JA, Moshensky A, Lam MTY, et al. Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients: a case series and review of the literature. Clin Infect Dis. 2021;2:532.
  • Ouwendijk WJD, Raadsen MP, van Kampen JJA, et al. High Levels of Neutrophil Extracellular Traps Persist in the Lower Respiratory Tract of Critically Ill Patients With Coronavirus Disease 2019. J Infect Dis. 2021;223(9):1512–1521. doi:10.1093/infdis/jiab050
  • Teluguakula N. Neutrophils Set Extracellular Traps to Injure Lungs in Coronavirus Disease 2019. J Infect Dis. 2021;223(9):1503–1505. doi:10.1093/infdis/jiab053
  • Middleton EA, He XY, Denorme F, et al. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020;136(10):1169–1179. doi:10.1182/blood.2020007008
  • Skendros P, Mitsios A, Chrysanthopoulou A, et al. Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis. J Clin Invest. 2020;130(11):6151–6157. doi:10.1172/JCI141374
  • Tomar B, Anders HJ, Desai J, Mulay SR. Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19. Cells. 2020;9(6):58. doi:10.3390/cells9061383
  • Yaqinuddin A, Kashir J. Novel therapeutic targets for SARS-CoV-2-induced acute lung injury: targeting a potential IL-1β/neutrophil extracellular traps feedback loop. Med Hypotheses. 2020;143:109906. doi:10.1016/j.mehy.2020.109906
  • Zuo Y, Yalavarthi S, Shi H, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11):87.
  • Zuo Y, Yalavarthi S, Navaz SA, et al. Autoantibodies stabilize neutrophil extracellular traps in COVID-19. JCI Insight. 2021;6(15):87.
  • Fisher J, Mohanty T, Karlsson CAQ, et al. Proteome Profiling of Recombinant DNase Therapy in Reducing NETs and Aiding Recovery in COVID-19 Patients. Mol Cell Proteom. 2021;20:100113. doi:10.1016/j.mcpro.2021.100113
  • Hazeldine J, Lord JM. Neutrophils and COVID-19: active Participants and Rational Therapeutic Targets. Front Immunol. 2021;12:680134. doi:10.3389/fimmu.2021.680134
  • Holliday ZM, Earhart AP, Alnijoumi MM, Krvavac A, Allen LH, Schrum AG. Non-Randomized Trial of Dornase Alfa for Acute Respiratory Distress Syndrome Secondary to Covid-19. Front Immunol. 2021;12:714833. doi:10.3389/fimmu.2021.714833
  • Weber AG, Chau AS, Egeblad M, Barnes BJ, Janowitz T. Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series. Mol Med. 2020;26(1):91. doi:10.1186/s10020-020-00215-w
  • Goel S, Saheb Sharif-Askari F, Saheb Sharif Askari N, et al. SARS-CoV-2 Switches ‘on’ MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression. Frontiers in Pharmacology. 2021;12. doi:10.3389/fphar.2021.631879
  • Grimes JM, Grimes KV. p38 MAPK inhibition: a promising therapeutic approach for COVID-19. J Mol Cell Cardiol. 2020;144:63–65. doi:10.1016/j.yjmcc.2020.05.007
  • Roy RK, Sharma U, Wasson MK, Jain A, Hassan MI, Prakash H. Macrophage Activation Syndrome and COVID 19: impact of MAPK Driven Immune-Epigenetic Programming by SARS-Cov-2. Front Immunol. 2021;12:763313. doi:10.3389/fimmu.2021.763313
  • Shahgolzari M, Yavari A, Arjeini Y, et al. Immunopathology and Immunopathogenesis of COVID-19, what we know and what we should learn. Gene Reports. 2021;25:101417. doi:10.1016/j.genrep.2021.101417
  • Horie S, McNicholas B, Rezoagli E, et al. Emerging pharmacological therapies for ARDS: COVID-19 and beyond. Intensive Care Med. 2020;46(12):2265–2283. doi:10.1007/s00134-020-06141-z
  • Wu YP, Liu ZH, Wei R, et al. Elevated plasma surfactant protein D (SP-D) levels and a direct correlation with anti-severe acute respiratory syndrome coronavirus-specific IgG antibody in SARS patients. Scand J Immunol. 2009;69(6):508–515. doi:10.1111/j.1365-3083.2009.02245.x
  • Islam ABMMK, Khan M-A-A-K. Lung transcriptome of a COVID-19 patient and systems biology predictions suggest impaired surfactant production which may be druggable by surfactant therapy. Sci Rep. 2020;10(1):19395. doi:10.1038/s41598-020-76404-8
  • Avdeev SN, Trushenko NV, Chikina SY, et al. Beneficial effects of inhaled surfactant in patients with COVID-19-associated acute respiratory distress syndrome. Respir Med. 2021;185:106489. doi:10.1016/j.rmed.2021.106489
  • Heching M, Lev S, Shitenberg D, Dicker D, Kramer MR. Surfactant for the Treatment of ARDS in a Patient With COVID-19. Chest. 2021;160(1):e9–e12. doi:10.1016/j.chest.2021.01.028
  • Piva S, DiBlasi RM, Slee AE, et al. Surfactant therapy for COVID-19 related ARDS: a retrospective case–control pilot study. Respir Res. 2021;22(1):20. doi:10.1186/s12931-020-01603-w
  • Bhatt RM, Clark HW, Girardis M, Busani S. Exogenous pulmonary surfactant in COVID-19 ARDS. The similarities to neonatal RDS suggest a new scenario for an ‘old’ strategy. BMJ Open Respir Res. 2021;8(1):87. doi:10.1136/bmjresp-2020-000867
  • Kryvenko V, Vadász I. Molecular mechanisms of Na,K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19. Am J Physiol Lung Cell Mol Physiol. 2021;320(6):L1186–L1193. doi:10.1152/ajplung.00056.2021
  • Mariajoseph-Antony LF, Kannan A, Panneerselvam A, Loganathan C, Anbarasu K, Prahalathan C. Could aquaporin modulators be employed as prospective drugs for COVID-19 related pulmonary comorbidity? Med Hypotheses. 2020;143:110201. doi:10.1016/j.mehy.2020.110201
  • Hernández-Beeftink T, Guillen-Guio B, Villar J, Flores C. Genomics and the Acute Respiratory Distress Syndrome: current and Future Directions. Int J Mol Sci. 2019;20:16. doi:10.3390/ijms20164004
  • Bime C, Pouladi N, Sammani S, et al. Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor. Am J Respir Crit Care Med. 2018;197(11):1421–1432. doi:10.1164/rccm.201705-0961OC
  • Christie JD, Wurfel MM, Feng R, et al. Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma. PLoS One. 2012;7(1):e28268. doi:10.1371/journal.pone.0028268
  • Du M, Garcia JGN, Christie JD, et al. Integrative omics provide biological and clinical insights into acute respiratory distress syndrome. Intensive Care Med. 2021;47(7):761–771. doi:10.1007/s00134-021-06410-5
  • Guillen-Guio B, Lorenzo-Salazar JM, Ma SF, et al. Sepsis-associated acute respiratory distress syndrome in individuals of European ancestry: a genome-wide association study. Lancet Respir Med. 2020;8(3):258–266. doi:10.1016/S2213-2600(19)30368-6
  • Lee S, Emond MJ, Bamshad MJ, et al. Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies. Am J Hum Genet. 2012;91(2):224–237. doi:10.1016/j.ajhg.2012.06.007
  • Shortt K, Chaudhary S, Grigoryev D, et al. Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq. PLoS One. 2014;9(11):e111953. doi:10.1371/journal.pone.0111953
  • Lynn H, Sun X, Casanova N, Gonzales-Garay M, Bime C, Garcia JGN. Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality. Antioxid Redox Signal. 2019;31(14):1027–1052. doi:10.1089/ars.2018.7701
  • Kovach MA, Stringer KA, Bunting R, et al. Microarray analysis identifies IL-1 receptor type 2 as a novel candidate biomarker in patients with acute respiratory distress syndrome. Respir Res. 2015;16(1):29. doi:10.1186/s12931-015-0190-x
  • Meyer NJ. Beyond single-nucleotide polymorphisms: genetics, genomics, and other ‘omic approaches to acute respiratory distress syndrome. Clin Chest Med. 2014;35(4):673–684. doi:10.1016/j.ccm.2014.08.006
  • Giannini HM, Meyer NJ. Genetics of Acute Respiratory Distress Syndrome: pathways to Precision. Crit Care Clin. 2021;37(4):817–834. doi:10.1016/j.ccc.2021.05.006
  • Lv X, Zhang Y, Lu W, et al. Digital gene expression analysis of transcriptomes in lipopolysaccharide-induced acute respiratory distress syndrome. Clin Chim Acta. 2016;453:182–189. doi:10.1016/j.cca.2015.07.018
  • Wang M, Yan J, He X, Zhong Q, Zhan C, Li S. Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile. Biol Res. 2016;49:25. doi:10.1186/s40659-016-0085-4
  • Cao Y, Lyu YI, Tang J, MicroRNAs: LY. Novel regulatory molecules in acute lung injury/acute respiratory distress syndrome. Biomed Rep. 2016;4(5):523–527. doi:10.3892/br.2016.620
  • Guo W, Wang Z, Wang S, Liao X, Qin T. Transcriptome sequencing reveals differential expression of circRNAs in sepsis induced acute respiratory distress syndrome. Life Sci. 2021;278:119566. doi:10.1016/j.lfs.2021.119566
  • Hurskainen M, Mižíková I, Cook DP, et al. Single cell transcriptomic analysis of murine lung development on hyperoxia-induced damage. Nat Commun. 2021;12(1):1565. doi:10.1038/s41467-021-21865-2
  • Jiang Y, Rosborough BR, Chen J, et al. Single cell RNA sequencing identifies an early monocyte gene signature in acute respiratory distress syndrome. JCI Insight. 2020;5(13):87. doi:10.1172/jci.insight.135678
  • Riemondy KA, Jansing NL, Jiang P, et al. Single cell RNA sequencing identifies TGFβ as a key regenerative cue following LPS-induced lung injury. JCI Insight. 2019;5(8):287.
  • Grigoryev DN, Cheranova DI, Chaudhary S, Heruth DP, Zhang LQ, Ye SQ. Identification of new biomarkers for Acute Respiratory Distress Syndrome by expression-based genome-wide association study. BMC Pulm Med. 2015;15:95. doi:10.1186/s12890-015-0088-x
  • Zhang S, Wu Z, Xie J, Yang Y, Wang L, Qiu H. DNA methylation exploration for ARDS: a multi-omics and multi-microarray interrelated analysis. J Transl Med. 2019;17(1):345. doi:10.1186/s12967-019-2090-1
  • Wen XP, Zhang YZ, Wan QQ. Non-targeted proteomics of acute respiratory distress syndrome: clinical and research applications. Proteome Sci. 2021;19(1):5. doi:10.1186/s12953-021-00174-y
  • Gao Y, Li X, Gao J, et al. Metabolomic Analysis of Radiation-Induced Lung Injury in Rats: the Potential Radioprotective Role of Taurine. Dose Response. 2019;17(4):1559325819883479. doi:10.1177/1559325819883479
  • Stringer KA, McKay RT, Karnovsky A, Quémerais B, Lacy P. Metabolomics and Its Application to Acute Lung Diseases. Front Immunol. 2016;7:44. doi:10.3389/fimmu.2016.00044
  • Long Y, Zhang Y, Gong Y, et al. Diagnosis of Sepsis with Cell-free DNA by Next-Generation Sequencing Technology in ICU Patients. Arch Med Res. 2016;47(5):365–371. doi:10.1016/j.arcmed.2016.08.004
  • Zhang XJ, Zheng JY, Li X, Liang YJ, Zhang ZD. Usefulness of metagenomic next-generation sequencing in adenovirus 7-induced acute respiratory distress syndrome: A case report. World journal of clinical cases. 2021;9(21):6067–6072.
  • Fischer N, Rohde H, Indenbirken D, et al. Rapid metagenomic diagnostics for suspected outbreak of severe pneumonia. Emerging infectious diseases. 2014;20(6):1072-1075.
  • Zhang P, Chen Y, Li S, et al. Metagenomic next-generation sequencing for the clinical diagnosis and prognosis of acute respiratory distress syndrome caused by severe pneumonia: a retrospective study. PeerJ. 2020;8:e9623.
  • Liao SY, Casanova NG, Bime C, Camp SM, Lynn H, Garcia JGN. Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches. Scientific reports. 2021;11(1):18874.