Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial
Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed. In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university ho...
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| Veröffentlicht in: | Pulmonary pharmacology & therapeutics 2024-12, Vol.87, p.102330, Article 102330 |
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| creator | Kjellberg, Anders Zhao, Allan Lussier, Anna Hassler, Adrian Al-Ezerjawi, Sarah Boström, Emil Catrina, Sergiu-Bogdan Bergman, Peter Rodriguez-Wallberg, Kenny Alexandra Lindholm, Peter |
| description | Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.
In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed.
Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p |
| doi_str_mv | 10.1016/j.pupt.2024.102330 |
| format | Article |
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In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed.
Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p < 0.001) and PaO2/FiO2 was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01).
We showed a unique transcriptomic signature related to viral-induced ERS in critically ill COVID-19 patients treated with HBOT. The finding was associated with a positive clinical outcome; the HBOT patients recovered faster and had a reduced HLoS compared with controls.
NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).
[Display omitted]
•Transcriptomic changes associated with HBOT in severe and critical COVID-19 patients are investigated in a randomised controlled trial.•Critically ill COVID-19 patients treated with HBOT recovered faster and had a reduced HLoS compared to controls.•The clinical outcome was associated with a unique transcriptomic signature related to viral-induced endoplasmic reticulum stress.•The link between disease progression and transcriptomic signature enhances our understanding of virus-host interactions and immune response.•Our results are hypothesis-generating for future pharmacological interventions.</description><identifier>ISSN: 1094-5539</identifier><identifier>ISSN: 1522-9629</identifier><identifier>EISSN: 1522-9629</identifier><identifier>DOI: 10.1016/j.pupt.2024.102330</identifier><identifier>PMID: 39393522</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; ARDS ; COVID-19 - complications ; COVID-19 - therapy ; Endoplasmic Reticulum Stress ; Female ; Humans ; Hyperbaric medicine ; Hyperbaric Oxygenation - methods ; Immune modulators ; Length of Stay ; Male ; Middle Aged ; Randomised controlled trial ; Respiratory Distress Syndrome - therapy ; RNA expression ; SARS-CoV-2 ; Sweden ; Transcriptome ; Treatment Outcome</subject><ispartof>Pulmonary pharmacology & therapeutics, 2024-12, Vol.87, p.102330, Article 102330</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c275t-2f0e9637f0f3448720c6034c2c3a6fc25ab2c18ca0bdb7c11825fa1fa6596a653</cites><orcidid>0000-0002-5940-6182 ; 0000-0003-3306-3713 ; 0000-0003-4378-6181 ; 0000-0002-2492-0923 ; 0000-0002-5796-1801 ; 0009-0004-7464-4252 ; 0000-0002-4819-1024 ; 0000-0001-6922-7631 ; 0000-0002-6914-3902 ; 0000-0002-0840-9244</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1094553924000464$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39393522$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:159894819$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Kjellberg, Anders</creatorcontrib><creatorcontrib>Zhao, Allan</creatorcontrib><creatorcontrib>Lussier, Anna</creatorcontrib><creatorcontrib>Hassler, Adrian</creatorcontrib><creatorcontrib>Al-Ezerjawi, Sarah</creatorcontrib><creatorcontrib>Boström, Emil</creatorcontrib><creatorcontrib>Catrina, Sergiu-Bogdan</creatorcontrib><creatorcontrib>Bergman, Peter</creatorcontrib><creatorcontrib>Rodriguez-Wallberg, Kenny Alexandra</creatorcontrib><creatorcontrib>Lindholm, Peter</creatorcontrib><title>Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial</title><title>Pulmonary pharmacology & therapeutics</title><addtitle>Pulm Pharmacol Ther</addtitle><description>Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.
In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed.
Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p < 0.001) and PaO2/FiO2 was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01).
We showed a unique transcriptomic signature related to viral-induced ERS in critically ill COVID-19 patients treated with HBOT. The finding was associated with a positive clinical outcome; the HBOT patients recovered faster and had a reduced HLoS compared with controls.
NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).
[Display omitted]
•Transcriptomic changes associated with HBOT in severe and critical COVID-19 patients are investigated in a randomised controlled trial.•Critically ill COVID-19 patients treated with HBOT recovered faster and had a reduced HLoS compared to controls.•The clinical outcome was associated with a unique transcriptomic signature related to viral-induced endoplasmic reticulum stress.•The link between disease progression and transcriptomic signature enhances our understanding of virus-host interactions and immune response.•Our results are hypothesis-generating for future pharmacological interventions.</description><subject>Adult</subject><subject>Aged</subject><subject>ARDS</subject><subject>COVID-19 - complications</subject><subject>COVID-19 - therapy</subject><subject>Endoplasmic Reticulum Stress</subject><subject>Female</subject><subject>Humans</subject><subject>Hyperbaric medicine</subject><subject>Hyperbaric Oxygenation - methods</subject><subject>Immune modulators</subject><subject>Length of Stay</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Randomised controlled trial</subject><subject>Respiratory Distress Syndrome - therapy</subject><subject>RNA expression</subject><subject>SARS-CoV-2</subject><subject>Sweden</subject><subject>Transcriptome</subject><subject>Treatment Outcome</subject><issn>1094-5539</issn><issn>1522-9629</issn><issn>1522-9629</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhiMEoqXwAiyQl2wy9SVxEsSmmhZaqVIlblvLcU4GD44dfCmd1-IJcZRpl8iSfXT-_3y2_BfFW4I3BBN-vt_MaY4bimmVG5Qx_Kw4JTWlZcdp9zzXuKvKumbdSfEqhD3GuKlY_bI4YV1e2Xha_L0-zOB76bVC7uGwA4viT_ByPiAZkLRIT1OybnJDMjI6f0DaRvD3YKN2WbVoe_fj5rIkXantkBQM6OLL5dcP6OphNs5ru0PKaKuVNMilqNwEC3ZA0UsblNdzdFO-O-idlTH5rGamRFkdshAyTzkbvTMGliEtzevixShNgDfH86z4_unq2_a6vL37fLO9uC0VbepY0hFDx1kz4pFVVdtQrDhmlaKKST4qWsueKtIqifuhbxQhLa1HSUbJ647njZ0V5coNf2BOvZi9nqQ_CCe1OLZ-5QpE23JOePa_X_2zd78ThCjy-xUYIy24FAQjpG4a3BGarXS1Ku9C8DA-wQkWS7ZiL5ZsxZKtWLPNQ--O_NRPMDyNPIaZDR9XA-RfudfgRVAabM5Ee1BRDE7_j_8PbSu6MQ</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Kjellberg, Anders</creator><creator>Zhao, Allan</creator><creator>Lussier, Anna</creator><creator>Hassler, Adrian</creator><creator>Al-Ezerjawi, Sarah</creator><creator>Boström, Emil</creator><creator>Catrina, Sergiu-Bogdan</creator><creator>Bergman, Peter</creator><creator>Rodriguez-Wallberg, Kenny Alexandra</creator><creator>Lindholm, Peter</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><orcidid>https://orcid.org/0000-0002-5940-6182</orcidid><orcidid>https://orcid.org/0000-0003-3306-3713</orcidid><orcidid>https://orcid.org/0000-0003-4378-6181</orcidid><orcidid>https://orcid.org/0000-0002-2492-0923</orcidid><orcidid>https://orcid.org/0000-0002-5796-1801</orcidid><orcidid>https://orcid.org/0009-0004-7464-4252</orcidid><orcidid>https://orcid.org/0000-0002-4819-1024</orcidid><orcidid>https://orcid.org/0000-0001-6922-7631</orcidid><orcidid>https://orcid.org/0000-0002-6914-3902</orcidid><orcidid>https://orcid.org/0000-0002-0840-9244</orcidid></search><sort><creationdate>20241201</creationdate><title>Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial</title><author>Kjellberg, Anders ; Zhao, Allan ; Lussier, Anna ; Hassler, Adrian ; Al-Ezerjawi, Sarah ; Boström, Emil ; Catrina, Sergiu-Bogdan ; Bergman, Peter ; Rodriguez-Wallberg, Kenny Alexandra ; Lindholm, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c275t-2f0e9637f0f3448720c6034c2c3a6fc25ab2c18ca0bdb7c11825fa1fa6596a653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>ARDS</topic><topic>COVID-19 - complications</topic><topic>COVID-19 - therapy</topic><topic>Endoplasmic Reticulum Stress</topic><topic>Female</topic><topic>Humans</topic><topic>Hyperbaric medicine</topic><topic>Hyperbaric Oxygenation - methods</topic><topic>Immune modulators</topic><topic>Length of Stay</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Randomised controlled trial</topic><topic>Respiratory Distress Syndrome - therapy</topic><topic>RNA expression</topic><topic>SARS-CoV-2</topic><topic>Sweden</topic><topic>Transcriptome</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kjellberg, Anders</creatorcontrib><creatorcontrib>Zhao, Allan</creatorcontrib><creatorcontrib>Lussier, Anna</creatorcontrib><creatorcontrib>Hassler, Adrian</creatorcontrib><creatorcontrib>Al-Ezerjawi, Sarah</creatorcontrib><creatorcontrib>Boström, Emil</creatorcontrib><creatorcontrib>Catrina, Sergiu-Bogdan</creatorcontrib><creatorcontrib>Bergman, Peter</creatorcontrib><creatorcontrib>Rodriguez-Wallberg, Kenny Alexandra</creatorcontrib><creatorcontrib>Lindholm, Peter</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Pulmonary pharmacology & therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kjellberg, Anders</au><au>Zhao, Allan</au><au>Lussier, Anna</au><au>Hassler, Adrian</au><au>Al-Ezerjawi, Sarah</au><au>Boström, Emil</au><au>Catrina, Sergiu-Bogdan</au><au>Bergman, Peter</au><au>Rodriguez-Wallberg, Kenny Alexandra</au><au>Lindholm, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial</atitle><jtitle>Pulmonary pharmacology & therapeutics</jtitle><addtitle>Pulm Pharmacol Ther</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>87</volume><spage>102330</spage><pages>102330-</pages><artnum>102330</artnum><issn>1094-5539</issn><issn>1522-9629</issn><eissn>1522-9629</eissn><abstract>Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.
In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed.
Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p < 0.001) and PaO2/FiO2 was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01).
We showed a unique transcriptomic signature related to viral-induced ERS in critically ill COVID-19 patients treated with HBOT. The finding was associated with a positive clinical outcome; the HBOT patients recovered faster and had a reduced HLoS compared with controls.
NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).
[Display omitted]
•Transcriptomic changes associated with HBOT in severe and critical COVID-19 patients are investigated in a randomised controlled trial.•Critically ill COVID-19 patients treated with HBOT recovered faster and had a reduced HLoS compared to controls.•The clinical outcome was associated with a unique transcriptomic signature related to viral-induced endoplasmic reticulum stress.•The link between disease progression and transcriptomic signature enhances our understanding of virus-host interactions and immune response.•Our results are hypothesis-generating for future pharmacological interventions.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>39393522</pmid><doi>10.1016/j.pupt.2024.102330</doi><orcidid>https://orcid.org/0000-0002-5940-6182</orcidid><orcidid>https://orcid.org/0000-0003-3306-3713</orcidid><orcidid>https://orcid.org/0000-0003-4378-6181</orcidid><orcidid>https://orcid.org/0000-0002-2492-0923</orcidid><orcidid>https://orcid.org/0000-0002-5796-1801</orcidid><orcidid>https://orcid.org/0009-0004-7464-4252</orcidid><orcidid>https://orcid.org/0000-0002-4819-1024</orcidid><orcidid>https://orcid.org/0000-0001-6922-7631</orcidid><orcidid>https://orcid.org/0000-0002-6914-3902</orcidid><orcidid>https://orcid.org/0000-0002-0840-9244</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1094-5539 |
| ispartof | Pulmonary pharmacology & therapeutics, 2024-12, Vol.87, p.102330, Article 102330 |
| issn | 1094-5539 1522-9629 1522-9629 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Aged ARDS COVID-19 - complications COVID-19 - therapy Endoplasmic Reticulum Stress Female Humans Hyperbaric medicine Hyperbaric Oxygenation - methods Immune modulators Length of Stay Male Middle Aged Randomised controlled trial Respiratory Distress Syndrome - therapy RNA expression SARS-CoV-2 Sweden Transcriptome Treatment Outcome |
| title | Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial |
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