Anders Kjellberg , Allan Zhao , Anna Lussier , Adrian Hassler , Sarah Al-Ezerjawi , Emil Boström , Sergiu-Bogdan Catrina , Peter Bergman , Kenny Alexandra Rodriguez-Wallberg , Peter Lindholm
{"title":"高压氧疗法作为 COVID-19 诱导的 ARDS 的免疫调节干预措施：在随机对照试验中探索临床结果和转录组特征。","authors":"Anders Kjellberg , Allan Zhao , Anna Lussier , Adrian Hassler , Sarah Al-Ezerjawi , Emil Boström , Sergiu-Bogdan Catrina , Peter Bergman , Kenny Alexandra Rodriguez-Wallberg , Peter Lindholm","doi":"10.1016/j.pupt.2024.102330","DOIUrl":null,"url":null,"abstract":"<div><div>Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.</div><div>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.</div><div>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 PaO<sub>2</sub>/FiO<sub>2</sub> was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01).</div><div>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.</div></div><div><h3>Trial registration</h3><div>NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial\",\"authors\":\"Anders Kjellberg , Allan Zhao , Anna Lussier , Adrian Hassler , Sarah Al-Ezerjawi , Emil Boström , Sergiu-Bogdan Catrina , Peter Bergman , Kenny Alexandra Rodriguez-Wallberg , Peter Lindholm\",\"doi\":\"10.1016/j.pupt.2024.102330\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.</div><div>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.</div><div>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 PaO<sub>2</sub>/FiO<sub>2</sub> was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01).</div><div>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.</div></div><div><h3>Trial registration</h3><div>NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).</div></div>\",\"PeriodicalId\":20799,\"journal\":{\"name\":\"Pulmonary pharmacology & therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pulmonary pharmacology & therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1094553924000464\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pulmonary pharmacology & therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1094553924000464","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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 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.
Trial registration
NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).
期刊介绍：
Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews.
Research Areas Include:
• All major diseases of the lung
• Physiology
• Pathology
• Drug delivery
• Metabolism
• Pulmonary Toxicology.
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