{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:30:24Z","timestamp":1760059824008,"version":"build-2065373602"},"reference-count":85,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T00:00:00Z","timestamp":1752278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["16\/23933-0","13\/21623-6","22\/02821-0","23\/10186-6"],"award-info":[{"award-number":["16\/23933-0","13\/21623-6","22\/02821-0","23\/10186-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Infectious Disease Reports"],"abstract":"<jats:p>Background\/Objective: Pulmonary fungal infections are a significant diagnostic challenge, primarily affecting immunocompromised individuals, such as those with HIV, cancer, or organ transplants, and they often lead to substantial morbidity and mortality if untreated. These infections trigger acute inflammatory and immune responses, which may progress to chronic inflammation. This process involves myofibroblast recruitment, the deposition of extracellular matrix, and vascular remodeling, ultimately contributing to pulmonary hypertension. Despite its clinical relevance, pulmonary hypertension secondary to fungal infections remains under-recognized in practice and poorly studied in research. Results\/Conclusion: This narrative mini-review explores three key mechanisms underlying vascular remodeling in this context: (1) endothelial injury caused by fungal emboli or autoimmune reactions, (2) direct vascular remodeling during chronic infection driven by inflammation and fibrosis, and (3) distant vascular remodeling post-infection, as seen in granulomatous diseases like paracoccidioidomycosis. Further research and clinical screening for pulmonary hypertension in fungal infections are crucial to improving patient outcomes.<\/jats:p>","DOI":"10.3390\/idr17040084","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T10:46:05Z","timestamp":1752662765000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pulmonary Hypertension Secondary to Fungal Infections: Underexplored Pathological Links"],"prefix":"10.3390","volume":"17","author":[{"given":"Andrea Jazel","family":"Rodr\u00edguez-Herrera","sequence":"first","affiliation":[{"name":"Department of Pathology and Forensic Medicine, Ribeir\u00e3o Preto Medical School (FMRP), University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Setembre Batah","sequence":"additional","affiliation":[{"name":"Department of Pathology and Forensic Medicine, Ribeir\u00e3o Preto Medical School (FMRP), University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J\u00falia","family":"Faci do Marco","sequence":"additional","affiliation":[{"name":"Department of Pathology and Forensic Medicine, Ribeir\u00e3o Preto Medical School (FMRP), University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6840-0460","authenticated-orcid":false,"given":"Carlos Mario","family":"Gonz\u00e1lez-Zambrano","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology and Infectious Agents (LIAI), Experimental Research Unity (UNIPEX), Sector 5, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9254-2074","authenticated-orcid":false,"given":"Luciane Alarc\u00e3o","family":"Dias-Melicio","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology and Infectious Agents (LIAI), Experimental Research Unity (UNIPEX), Sector 5, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"},{"name":"Department of Pathology, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre Todorovic","family":"Fabro","sequence":"additional","affiliation":[{"name":"Department of Pathology and Forensic Medicine, Ribeir\u00e3o Preto Medical School (FMRP), University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1080\/14787210.2024.2403017","article-title":"Diagnosing fungal infections in clinical practice: A narrative review","volume":"22","author":"Sedik","year":"2024","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1371\/journal.pntd.0007964","article-title":"Fungal diseases as neglected pathogens: A wake-up call to public health officials","volume":"14","author":"Rodrigues","year":"2020","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e70003","DOI":"10.1002\/pul2.70003","article-title":"Infection and pulmonary vascular diseases consortium: United against a global health challenge","volume":"14","author":"Oliveira","year":"2024","journal-title":"Pulm. Circ."},{"unstructured":"Drummond, R.A. (2023). Microcomputed tomography to visualize and quantify fungal infection burden and inflammation in the mouse lung over time. Antifungal Immunity: Methods and Protocols, Springer.","key":"ref_4"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.berh.2008.09.009","article-title":"The role of infectious agents in the pathogenesis of vasculitis","volume":"22","author":"Pipitone","year":"2008","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"doi-asserted-by":"crossref","unstructured":"Revercomb, L., Hanmandlu, A., Wareing, N., Akkanti, B., and Karmouty-Quintana, H. (2021). Mechanisms of pulmonary hypertension in acute respiratory distress syndrome (ARDS). Front. Mol. Biosci., 7.","key":"ref_6","DOI":"10.3389\/fmolb.2020.624093"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1164\/rccm.202410-2045ST","article-title":"Treatment of invasive pulmonary aspergillosis and preventive and empirical therapy for invasive candidiasis in adult pulmonary and critical care patients: An official American Thoracic Society clinical practice guideline","volume":"211","author":"Epelbaum","year":"2025","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/S1010-7940(98)00217-6","article-title":"Aspergillus endocarditis: Rare but serious Aspergillus ball obstructing the pulmonary artery","volume":"14","author":"Navabi","year":"1998","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1017\/S1047951114000432","article-title":"Aspergillus endocarditis in a paediatric patient after a cardiac surgery, associated with septic pulmonary embolism and pulmonary hypertension","volume":"25","author":"Miranda","year":"2015","journal-title":"Cardiol. Young"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/nm.2514","article-title":"The neutrophil in vascular inflammation","volume":"17","author":"Phillipson","year":"2011","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2172264","DOI":"10.1080\/21505594.2023.2172264","article-title":"Pathogenicity and virulence of Aspergillus fumigatus","volume":"14","author":"Earle","year":"2023","journal-title":"Virulence"},{"doi-asserted-by":"crossref","unstructured":"Puerta-Arias, J.D., Mej\u00eda, S.P., and Gonz\u00e1lez, A. (2020). The role of the interleukin-17 axis and neutrophils in the pathogenesis of endemic and systemic mycoses. Front. Cell. Infect. Microbiol., 10.","key":"ref_12","DOI":"10.3389\/fcimb.2020.595301"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s00109-022-02197-0","article-title":"NETs, pulmonary arterial hypertension, and thrombo-inflammation","volume":"100","author":"Santos","year":"2022","journal-title":"J. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1161\/ATVBAHA.116.307634","article-title":"Neutrophil extracellular traps promote angiogenesis: Evidence from vascular pathology in pulmonary hypertension","volume":"36","author":"Aldabbous","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/nm.2053","article-title":"Extracellular histones are major mediators of death in sepsis","volume":"15","author":"Xu","year":"2009","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nm.2184","article-title":"Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases","volume":"16","author":"Massberg","year":"2010","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1538-7836.2011.04544.x","article-title":"Neutrophil extracellular traps promote deep vein thrombosis in mice","volume":"10","author":"Brill","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15880","DOI":"10.1073\/pnas.1005743107","article-title":"Extracellular DNA traps promote thrombosis","volume":"107","author":"Fuchs","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1084\/jem.20112322","article-title":"Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo","volume":"209","author":"Stark","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1182\/blood-2011-03-343061","article-title":"Extracellular histones promote thrombin generation through platelet-dependent mechanisms: Involvement of platelet TLR2 and TLR4","volume":"118","author":"Semeraro","year":"2011","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.25259\/VJIM_38_2022","article-title":"Post-COVID Pulmonary Aspergillosis with Pulmonary Thromboembolism and Pulmonary Artery Hypertension Unmasking Prediabetes: A Case Report","volume":"33","author":"Kamath","year":"2023","journal-title":"Vidarbha J. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.7754\/Clin.Lab.2023.230407","article-title":"Acute heart failure due to pulmonary Aspergillus fumigatus and Cryptococcus neoformans infection associated with COVID-19","volume":"69","author":"Ren","year":"2023","journal-title":"Clin. Lab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.mmcr.2019.07.001","article-title":"Cor pulmonale complicating chronic pulmonary aspergillosis with fatal consequences: Experience from Uganda","volume":"25","author":"Bongomin","year":"2019","journal-title":"Med. Mycol. Case Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1128\/IAI.05530-11","article-title":"Repeated exposure to Aspergillus fumigatus conidia results in CD4+ T cell-dependent and -independent pulmonary arterial remodeling in a mixed Th1\/Th2\/Th17 microenvironment that requires interleukin-4 (IL-4) and IL-10","volume":"80","author":"Shreiner","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1080\/03079459008418720","article-title":"Pulmonary aspergillosis causing right ventricular failure and ascites in meat-type chickens","volume":"19","author":"Julian","year":"1990","journal-title":"Avian Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ajpath.2013.10.027","article-title":"CD4+ T cells and IFN-\u03b3 are required for the development of pneumocystis-associated pulmonary hypertension","volume":"184","author":"Swain","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"790","DOI":"10.2353\/ajpath.2007.070178","article-title":"Pulmonary hypertension can be a sequela of prior pneumocystis pneumonia","volume":"171","author":"Swain","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.4049\/jimmunol.1200185","article-title":"Differential interaction of the two related fungal species Candida albicans and Candida dubliniensis with human neutrophils","volume":"189","author":"Staib","year":"2012","journal-title":"J. Immunol."},{"doi-asserted-by":"crossref","unstructured":"Campos-Garcia, L., Jimenez-Valdes, R.J., Hernandez-Bello, R., Palma-Nicolas, J., Gonzalez, G.M., and Sanchez-Gonzalez, A. (2019). Candida albicans and non-albicans isolates from bloodstream have different capacities to induce neutrophil extracellular traps. J. Fungi, 5.","key":"ref_29","DOI":"10.3390\/jof5020028"},{"doi-asserted-by":"crossref","unstructured":"Bruns, S., Kniemeyer, O., Hasenberg, M., Aimanianda, V., Nietzsche, S., Thywien, A., Jeron, A., Latg\u00e9, J.P., Brakhage, A.A., and Gunzer, M. (2010). Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA. PLoS Pathog., 6.","key":"ref_30","DOI":"10.1371\/journal.ppat.1000873"},{"doi-asserted-by":"crossref","unstructured":"Thompson-Souza, G.A., Santos, G.M.P., Silva, J.C., Muniz, V.S., Braga, Y.A.V., Figueiredo, R.T., Melo, R.C.N., Santos, A.L.S., Pinto, M.R., and Neves, J.S. (2020). Histoplasma capsulatum-induced extracellular DNA trap release in human neutrophils. Cell. Microbiol., 22.","key":"ref_31","DOI":"10.1111\/cmi.13195"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s11046-021-00554-0","article-title":"Neutrophil extracellular traps serve as key effector molecules in the protection against Phialophora verrucosa","volume":"186","author":"Liu","year":"2021","journal-title":"Mycopathologia"},{"doi-asserted-by":"crossref","unstructured":"Rocha, J.D.B., Nascimento, M.T.C., Decote-Ricardo, D., C\u00f4rte-Real, S., Morrot, A., Heise, N., Nunes, M.P., Previato, J.O., Mendon\u00e7a-Previato, L., and DosReis, G.A. (2015). Capsular polysaccharides from Cryptococcus neoformans modulate production of neutrophil extracellular traps (NETs) by human neutrophils. Sci. Rep., 5.","key":"ref_33","DOI":"10.1038\/srep08008"},{"doi-asserted-by":"crossref","unstructured":"Reis, A.P.C., Celestrino, G.A., Igoa, M.V.B., Jesus, T.M., Fran\u00e7a, T.T., Moreira, D.V.S., Rigato, P.O., Sato, P.K., Condino-Neto, A., and Noronha, I.L. (2022). The dermatophyte Trichophyton rubrum induces neutrophil extracellular traps release by human neutrophils. J. Fungi, 8.","key":"ref_34","DOI":"10.3390\/jof8020147"},{"doi-asserted-by":"crossref","unstructured":"Zonta, Y.R., Dezen, A.L.O., Della Coletta, A.M., Yu, K.S.T., Carvalho, L., Santos, L.A., Depr\u00e1, I.C., Kratofil, R.M., Willson, M.E., and Zbytnuik, L. (2021). Paracoccidioides brasiliensis releases a DNase-like protein that degrades NETs and allows for fungal escape. Front. Cell. Infect. Microbiol., 10.","key":"ref_35","DOI":"10.3389\/fcimb.2020.592022"},{"key":"ref_36","first-page":"104472","article-title":"Production of neutrophil extracellular traps (NETs) in response to Scedosporium apiospermum in a murine model of pulmonary infection","volume":"149","author":"Montoya","year":"2020","journal-title":"Microb. Pathog."},{"doi-asserted-by":"crossref","unstructured":"Zhong, H., Lu, R.Y., and Wang, Y. (2022). Neutrophil extracellular traps in fungal infections: A seesaw battle in hosts. Front. Immunol., 13.","key":"ref_37","DOI":"10.3389\/fimmu.2022.977493"},{"doi-asserted-by":"crossref","unstructured":"Della Coletta, A.M., Bachiega, T.F., de Quaglia e Silva, J.C., Soares, \u00c2.M.V.d.C., De Faveri, J., Marques, S.A., Marques, M.E., Ximenes, V.F., and Dias-Melicio, L.A. (2015). Neutrophil Extracellular Traps Identification in Tegumentary Lesions of Patients with Paracoccidioidomycosis and Different Patterns of NETs Generation In Vitro. PLoS Negl. Trop. Dis., 9.","key":"ref_38","DOI":"10.1371\/journal.pntd.0004037"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7505","DOI":"10.18632\/aging.205770","article-title":"Erratum: Correction for: Neutrophil extracellular traps amplify neutrophil recruitment and inflammation in neutrophilic asthma by stimulating the airway epithelial cells to activate the TLR4\/NF-\u03baB pathway and secrete chemokines","volume":"16","author":"Wan","year":"2024","journal-title":"Aging"},{"doi-asserted-by":"crossref","unstructured":"King, P.T., and Dousha, L. (2024). Neutrophil Extracellular Traps and Respiratory Disease. J. Clin. Med., 13.","key":"ref_40","DOI":"10.3390\/jcm13082390"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1159\/000295791","article-title":"In cystic fibrosis homozygotes and heterozygotes, neutrophil apoptosis is delayed and modulated by diamide or roscovitine: Evidence for an innate neutrophil disturbance","volume":"2","author":"Moriceau","year":"2010","journal-title":"J. Innate Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1164\/rccm.201311-1932OC","article-title":"Lack of neutrophil elastase reduces inflammation, mucus hypersecretion, and emphysema, but not mucus obstruction, in mice with cystic fibrosislike lung disease","volume":"189","author":"Gehrig","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jaci.2017.04.022","article-title":"Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease","volume":"141","author":"Dicker","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12931-015-0221-7","article-title":"Neutrophil extracellular trap (NET) formation characterises stable and exacerbated COPD and correlates with airflow limitation","volume":"16","author":"Obermayer","year":"2015","journal-title":"Respir. Res."},{"doi-asserted-by":"crossref","unstructured":"King, P.T. (2018). The role of the immune response in the pathogenesis of bronchiectasis. BioMed Res. Int., 2018.","key":"ref_45","DOI":"10.1155\/2018\/6802637"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1164\/ajrccm.164.9.2105083","article-title":"Bronchial Inflammation and Colonization in Patients with Clinically Stable Bronchiectasis","volume":"164","author":"Angrill","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1164\/rccm.201605-1027OC","article-title":"Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis","volume":"195","author":"Chalmers","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S2213-2600(20)30504-X","article-title":"Neutrophil extracellular traps, disease severity, and antibiotic response in bronchiectasis: An international, observational, multicohort study","volume":"9","author":"Keir","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1164\/rccm.201810-1869OC","article-title":"Extracellular DNA, neutrophil extracellular traps, and inflammasome activation in severe asthma","volume":"199","author":"Dunican","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1182\/blood-2009-05-221606","article-title":"Restoration of NET formation by gene therapy in CGD controls aspergillosis","volume":"114","author":"Bianchi","year":"2009","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1701389","DOI":"10.1183\/13993003.01389-2017","article-title":"Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia: Secondary analysis of a randomised controlled trial","volume":"51","author":"Ebrahimi","year":"2018","journal-title":"Eur. Respir. J."},{"doi-asserted-by":"crossref","unstructured":"Scozzi, D., Liao, F., Krupnick, A.S., Kreisel, D., and Gelman, A.E. (2022). The role of neutrophil extracellular traps in acute lung injury. Front. Immunol., 13.","key":"ref_52","DOI":"10.3389\/fimmu.2022.953195"},{"doi-asserted-by":"crossref","unstructured":"Zhou, X., Jin, J., Lv, T., and Song, Y. (2024). A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome\/Acute Lung Injury. Int. J. Mol. Sci., 25.","key":"ref_53","DOI":"10.3390\/ijms25031464"},{"doi-asserted-by":"crossref","unstructured":"Czaikoski, P.G., Mota, J.M.S.C., Nascimento, D.C., S\u00f4nego, F., Castanheira, F.V.E.S., Melo, P.H., Scortegagna, G.T., Silva, R.L., Barroso-Sousa, R., and Souto, F.O. (2016). Neutrophil extracellular traps induce organ damage during experimental and clinical sepsis. PLoS ONE, 11.","key":"ref_54","DOI":"10.1371\/journal.pone.0148142"},{"doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhou, Y., Qu, M., Yu, Y., Chen, Z., Zhu, S., Guo, K., Chen, W., and Miao, C. (2021). Tissue Factor-Enriched Neutrophil Extracellular Traps Promote Immunothrombosis and Disease Progression in Sepsis-Induced Lung Injury. Front. Cell Infect. Microbiol., 13.","key":"ref_55","DOI":"10.3389\/fcimb.2021.677902"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e98178","DOI":"10.1172\/jci.insight.98178","article-title":"Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury","volume":"3","author":"Mallavia","year":"2018","journal-title":"JCI Insight"},{"doi-asserted-by":"crossref","unstructured":"Pu, S., Wang, D., Liu, D., Zhao, Y., Qi, D., He, J., and Zhou, G. (2017). Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: A meta-analysis of randomized controlled trials. BMC Pulm. Med., 17.","key":"ref_57","DOI":"10.1186\/s12890-017-0498-z"},{"key":"ref_58","first-page":"e138999","article-title":"Neutrophil extracellular traps in COVID-19","volume":"5","author":"Zuo","year":"2020","journal-title":"JCI Insight"},{"doi-asserted-by":"crossref","unstructured":"Reusch, N., De Domenico, E., Bonaguro, L., Schulte-Schrepping, J., Ba\u00dfler, K., Schultze, J.L., and Aschenbrenner, A.C. (2021). Neutrophils in COVID-19. Front. Immunol., 12.","key":"ref_59","DOI":"10.3389\/fimmu.2021.652470"},{"doi-asserted-by":"crossref","unstructured":"Arcanjo, A., Logullo, J., Menezes, C.C.B., de Souza Carvalho Giangiarulo, T.C., dos Reis, M.C., de Castro, G.M.M., da Silva Fontes, Y., Todeschini, A.R., Freire-de-Lima, L., and Decot\u00e9-Ricardo, D. (2020). The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19). Sci. Rep., 10.","key":"ref_60","DOI":"10.1038\/s41598-020-76781-0"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e20200652","DOI":"10.1084\/jem.20200652","article-title":"Targeting potential drivers of COVID-19: Neutrophil extracellular traps","volume":"217","author":"Barnes","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1182\/blood.2020007008","article-title":"Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome","volume":"136","author":"Middleton","year":"2020","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"108516","DOI":"10.1016\/j.intimp.2021.108516","article-title":"Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality","volume":"104","author":"Alexiou","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/CIRCULATIONAHA.120.048488","article-title":"Immunothrombotic Dysregulation in COVID-19 Pneumonia Is Associated With Respiratory Failure and Coagulopathy","volume":"42","author":"Nicolai","year":"2020","journal-title":"Circulation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"20201129","DOI":"10.1084\/jem.20201129","article-title":"SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology","volume":"217","author":"Veras","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s10020-020-00215-w","article-title":"Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: A case series","volume":"26","author":"Weber","year":"2020","journal-title":"Mol. Med."},{"key":"ref_67","first-page":"8881115","article-title":"The Use of Dornase Alfa in the Management of COVID-19-Associated Adult Respiratory Distress Syndrome","volume":"2021","author":"Toma","year":"2021","journal-title":"Crit. Care Res. Pract."},{"doi-asserted-by":"crossref","unstructured":"Shao, B.Z., Yao, Y., Li, J.P., Chai, N.L., and Linghu, E.Q. (2021). The Role of Neutrophil Extracellular Traps in Cancer. Front. Oncol., 11.","key":"ref_68","DOI":"10.3389\/fonc.2021.714357"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13076","DOI":"10.1073\/pnas.1200419109","article-title":"Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis","volume":"109","author":"Demers","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.immuni.2020.03.001","article-title":"CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity","volume":"19","author":"Teijeira","year":"2020","journal-title":"Immunity"},{"doi-asserted-by":"crossref","unstructured":"Stoiber, D., and Assinger, A. (2020). Platelet-Leukocyte Interplay in Cancer Development and Progression. Cells, 9.","key":"ref_71","DOI":"10.3390\/cells9040855"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12967-019-1838-y","article-title":"Emodin regulates neutrophil phenotypes to prevent hypercoagulation and lung carcinogenesis","volume":"17","author":"Li","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12950-023-00329-y","article-title":"Neutrophil extracellular traps and pulmonary fibrosis: An update","volume":"20","author":"Yan","year":"2023","journal-title":"J. Inflamm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1111\/jcmm.14858","article-title":"Neutrophil extracellular traps activate lung fibroblast to induce polymyositis-related interstitial lung diseases via TLR9-miR-7-Smad2 pathway","volume":"24","author":"Zhang","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/path.4359","article-title":"Neutrophil extracellular traps promote differentiation and function of fibroblasts","volume":"233","author":"Chrysanthopoulou","year":"2014","journal-title":"J. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1165\/rcmb.2019-0433OC","article-title":"PAD4 Deficiency improves bleomycin-induced neutrophil extracellular traps and fibrosis in mouse lung","volume":"63","author":"Suzuki","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ajpath.2011.03.013","article-title":"Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis","volume":"179","author":"Narasaraju","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/0002-9149(62)90263-1","article-title":"Chronic Cor Pulmonale Due to Paracoccidioidomycosis Clinical, Functional and Anatomical Study","volume":"10","author":"Yepez","year":"1962","journal-title":"Am. J. Cardiol."},{"key":"ref_79","first-page":"241","article-title":"Considerations on South American blastomycosis. The cardiovascular repercussions of the pulmonary lesions. Hemodynamic, oximetric and angiopneumographical data","volume":"60","author":"Lisboa","year":"1961","journal-title":"Hospital"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1590\/S0036-46651991000400005","article-title":"Paracoccidioidomycosis: Radiologic and pulmonary study in 58 cases","volume":"33","author":"Campos","year":"1991","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1590\/s1678-9946202062089","article-title":"Paracoccidioidomycosis due to Paracoccidioides lutzii complicated with adrenal injury and pulmonary arterial hypertension","volume":"62","author":"Gaspar","year":"2020","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1002\/ctm2.213","article-title":"Pulmonary paracoccidioidomycosis-induced pulmonary hypertension","volume":"10","author":"Batah","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/annrheumdis-2018-213181","article-title":"REDD1\/autophagy pathway promotes thromboinflammation and fibrosis in human systemic lupus erythematosus (SLE) through NETs decorated with tissue factor (TF) and interleukin-17A (IL-17A)","volume":"78","author":"Frangou","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1164\/rccm.201411-2030ED","article-title":"Live and Let Die: Targeting Alveolar Epithelial Cell Proliferation in Pulmonary Fibrosis","volume":"190","author":"Bonniaud","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1189\/jlb.3HI1014-493R","article-title":"Neutrophil elastase promotes myofibroblast differentiation in lung fibrosis","volume":"98","author":"Gregory","year":"2015","journal-title":"J. Leukoc. 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