ECMO support may be associated with improved survival in tuberculosis associated severe ARDS

ECMO support may be associated with improved survival in tuberculosis associated severe ARDS | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article ECMO support may be associated with improved survival in tuberculosis associated severe ARDS Bahar Nalbant, Alix Buhlmann, Lennart Wild, Christian Bode, Sascha David, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4925917/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Oct, 2024 Read the published version in BMC Pulmonary Medicine → Version 1 posted 15 You are reading this latest preprint version Abstract Background Data describing outcome of extracorporeal membrane oxygenation (ECMO) support in Tuberculosis (Tbc)-associated acute respiratory distress syndrome (ARDS) remain sparce and are mostly confined to singular case reports. The aim of this case series was to analyze intensive care unit (ICU) survival in patients with Tbc-associated ARDS receiving ECMO support and to compare those to patients not receiving ECMO. Case presentation ICU survival was analyzed retrospectively in 14 patients treated for Tbc-associated ARDS at three ECMO-referral university hospitals (Hannover Medical School, University Hospital Bonn (both Germany) and University Hospital Zurich (Switzerland)) during the last 14 years, of which eight patients received additional veno-venous (vv) ECMO support and six standard care only. ICU survival was significantly higher in patients receiving additional ECMO support (62.5%, n=5/8) compared to those that did not (16.7%, n=1/6) (p=0.021). ECMO support was associated with reduced ICU mortality (Hazard ratio adjusted for baseline SOFA score [adj. HR] 0.125 (95% confidence interval (CI): 0.023-0.689), p=0.017). Median (IQR) time on ECMO and invasive ventilation in the ECMO group were 20 (11-26) and 37 (27-53) days, respectively. Major bleeding defined as transfusion requirement of 4 units of blood or more or surgical and/or radiologic intervention occurred only in one patient, in whom pulmonary bleeding was fatal. Thromboembolic events occurred in none of the ECMO patients. Discussion and Conclusions: This retrospective analysis from three large ECMO centers with similar SOPs suggests ECMO support as a feasible approach in patients with severe Tbc-associated ARDS. Although affiliated with extended runtimes, ECMO might be associated with improved survival in those patients. ECMO support should thus be considered in Tbc-associated ARDS to enable lung protective strategies during prolonged lung recovery. Figures Figure 1 Background Recently Idris et al. described in the Journal outcome of patients with tuberculosis (Tbc) associated critical illness, including those with severe acute respiratory distress syndrome (ARDS), supported by extracorporeal membrane oxygenation (ECMO) (1). In this systematic review and metanalysis of 43 patients receiving diverse modes of ECMO support, the authors reported encouraging clinical outcomes with an overall intensive care unit (ICU) survival of 81.4%. Data describing outcome of ECMO support in Tbc-associated ARDS in general remain sparce and are mostly confined to only singular case reports (2). However, the analysis by Idris et al. has some important limitations. First, patients were included based on singular case reports extracted over a wide time-period of 47 years, given rise to both reporting bias and significant heterogeneity in selection and provision of treatment as well as technology. Second, both patients with primarily respiratory as well as circulatory failure, consequentially receiving diverse modes of ECMO cannulation (vv-, va- and vav-ECMO), were included and analyzed together, thus further increasing clinical heterogeneity despite completely different primary clinical disorders. Case presentation Our study-group has therefore analyzed ICU survival in a more homogenous cohort of patients treated for Tbc-associated ARDS at three ECMO-referral university hospitals (Hannover Medical School, University Hospital Bonn (both Germany) and University Hospital Zurich (Switzerland)) during the last 14 years. A total of 14 patients with Tbc-associated ARDS were included in this present case series, of whom eight received additional veno-venous (vv) ECMO support and six received standard care only. Baseline demographic and clinical characteristics at implementation of invasive ventilation were comparable between the two groups (Table 1 ). Three patients had HIV infection, two patients received medical immunosuppression, one had a congenital immune defect and five patients had chronic alcohol abuse. Patients later receiving ECMO support had significantly lower oxygenation index (Median (Interquartile range (IQR)) 71 (54–92) vs. 188 (146–236) mmHg, p < 0.001). Median (IQR) time to ECMO implantation was 2 (1–4) days. Table 1 Demographic and clinical characteristics at start of invasive ventilation Category Median (interquartile range) / No (%) ECMO (n = 8) no ECMO (n = 6) p Age - y 39 (27–48) 44 (35–68) 0.218 Sex - no (%) 0.733 male 6 (75) 4 (66.7) female 2 (25) 2 (33.3) BMI - kg/m 2 19.9 (17.6–24.6) 22.2 (20-25.4) 0.61 Immunosuppression - no (%) 3 (37.5) 4 (66.7) 0.28 MDR-Tbc - no (%) 1 (12.5) 1 (16.7) 0.825 pO 2 /FiO 2 - mmHg 71 (54–92) 188 (146–236) < 0.001 pCO 2 - mmHg 49 (44–70) 56 (40–61) 0.707 Vasopressor therapy - no (%) 7 (87.5) 5 (83.3) 0.825 Vasopressor dose - ug/kg/min 0.38 (0.2-1.0) 0.33 (0.245–1.455) 0.613 Renal replacement therapy - no (%) 1 (12.5) 2 (33.3) 0.347 SOFA score - points 9 (7–10) 9 (8–11) 0.799 Lactate - mmol/l 1.4 (1.3–4.5) 4 (2.1–6.7) 0.228 Categorical variables are represented by number (n) and percentage (%), while continuous variables are expressed as median (25% to 75% Interquartile Range [IQR]). The normal distribution was checked using the D'Agostino-Pearson omnibus normality test and the Shapiro-Wilk normality test. Two-tailed p values of less than 0.05 were considered to indicate statistical significance. Comparisons of population characteristics between the ECMO and the no-ECMO group were performed using unpaired t-tests, Mann-Whitney tests and χ 2 tests, as appropriate. All reported p-values are two-sided unless indicated otherwise; p-values < 0.05 were considered statistically significant. ARDS – Acute respiratory distress syndrome, ECMO – Extracorporeal membrane oxygenation, MDR – Multi drug resistant, SOFA – Sequential Organ Failure Assessment score, Tbc – Tuberculosis ICU survival was significantly higher in patients receiving additional ECMO support (62.5%, n = 5/8) compared to those that did not (16.7%, n = 1/6) (FIGURE 1 , p = 0.021). ECMO support was associated with reduced ICU mortality (Hazard ratio adjusted for baseline SOFA score [adj. HR] 0.125 (95% confidence interval (CI): 0.023–0.689), p = 0.017). Median (IQR) time on ECMO and invasive ventilation in the ECMO group were 20 (11–26) and 37 (27–53) days, respectively. Major bleeding defined as transfusion requirement of 4 units of blood or more or surgical and/or radiologic intervention occurred only in one patient, in whom pulmonary bleeding was fatal. Thromboembolic events occurred in none of the ECMO patients. Discussion and Conclusions In the meta-analysis by Idris et al. 30 patients had ARDS, 27 were supported by vv-ECMO, of which 23 (85.1%) survived. However, outcomes were reported from a multitude of different centers dating back to 1975, making a reporting bias likely. Our outcome results with a survival of about 60% generated from three centers in a recent time period and similar standard operating procedures in the ECMO cohort are better in line with the more recent ECMO trials such as the CESAR (3) and EOLIA (4) study with regards to mortality. Idris et al. did not report on patients with Tbc-associated ARDS, treated at the same institutions but without ECMO support. The finding of an exceedingly high mortality in patients without ECMO support from this present cohort is provocative, but certainly needs confirmation in prospective studies. Of note, both ECMO runtime and ventilator-days were excessively long in either Idris et al. and our group, underlining the slow recovery from Tbc-associated ARDS (5) and the consequential need to optimize lung-protective strategies in this cohort. In summary, this retrospective analysis from three large ECMO centers with similar SOPs suggests ECMO support as a feasible approach in patients with severe Tbc-associated ARDS. Although affiliated with extended runtimes, ECMO might be associated with improved survival in those patients. ECMO support should thus be considered in Tbc-associated ARDS to enable lung protective strategies during prolonged lung recovery. List of abbreviations ARDS = Acute respiratory distress syndrome CI = Confidence Interval ECMO = Extracorporeal membrane oxygenation HR = Hazard Ratio ICU = Intensive care unit MDR = Multi drug resistant SOFA = Sequential Organ Failure Assessment score SOP = Standard operating procedure Tbc = Tuberculosis Va = Veno-arterial Vav = Veno-arterial-venous Vv = Veno-venous Declarations Ethics approval and consent to participate Due to a retrospective analysis ethics approval was waived. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The medical committee of Hannover Medical School (No. 11141_BO_K_2023), University Hospital Bonn (No 437/23-EP) and University Hospital Zurich (BASEC-No: 2024-00034) approved the study. All personal patient data were pseudonymized before data collection. Consent of publication Not applicable Competing interests None declared. Clinical trial number Not applicable Funding Not applicable Author Contribution KS and BN conceived the presented idea. BN, AB and LW obtained the retrospective data and performed the analysis. NB, AB, LW and KS discussed the data and generated figures. CB, SD, BS and KS wrote the manuscript; all authors discussed the results and contributed to the final manuscript. The BonHanZA study group is a three-center research consortium, that all authors are part of. Acknowledgement Further members of the BonHanZA (Bonn-Hannover-Zurich ARDS) study group, not directly contributing to the manuscript, are: Thorben Pape1,2,7, Jannik Ruwisch1,2,7, Marius M. Hoeper1,2,7, Pedro David Wendel-Garcia3,7, Daniel A. Hofmaenner3,7, Rolf Erlebach3,7, Mattia Mueller3,7, Rea Andermatt3,7, Konrad Peukert4,7, Andrea Sauer4,7We are grateful to the late Prof. Tobias Welte, who inspired this analysis and so many more. He and his influence on this study group will never be forgotten. Data Availability The datasets used and analyzed are during the current study are available from the corresponding author on reasonable request. References Idris R, Zielbauer AS, Koepsell J, Kloka J, Wetzstein N. Extracorporeal membrane oxygenation (ECMO) in patients with tuberculosis: systematic review and meta-analysis of 43 cases. BMC Pulm Med. 2024;24(1):47. Besa S, Morales Á J, Salas P, Bravo MS, Garrido-Olivares L. Extracorporeal membrane oxygenation for tuberculosis pneumonia with empyema. Respir Med Case Rep. 2021;34:101481. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009;374(9698):1351-63. Combes A, Hajage D, Capellier G, Demoule A, Lavoué S, Guervilly C, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018;378(21):1965-75. Agarwal R, Gupta D, Aggarwal AN, Behera D, Jindal SK. Experience with ARDS caused by tuberculosis in a respiratory intensive care unit. Intensive Care Med. 2005;31(9):1284-7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 24 Oct, 2024 Read the published version in BMC Pulmonary Medicine → Version 1 posted Editorial decision: Revision requested 30 Sep, 2024 Reviews received at journal 24 Sep, 2024 Reviews received at journal 19 Sep, 2024 Reviews received at journal 16 Sep, 2024 Reviewers agreed at journal 14 Sep, 2024 Reviewers agreed at journal 13 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviewers agreed at journal 03 Sep, 2024 Reviewers invited by journal 03 Sep, 2024 Editor invited by journal 30 Aug, 2024 Editor assigned by journal 30 Aug, 2024 Submission checks completed at journal 30 Aug, 2024 First submitted to journal 16 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4925917","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":360153967,"identity":"34bf3bd9-89ec-4a5d-a594-0e56f83520e8","order_by":0,"name":"Bahar Nalbant","email":"","orcid":"","institution":"Hannover Medical School","correspondingAuthor":false,"prefix":"","firstName":"Bahar","middleName":"","lastName":"Nalbant","suffix":""},{"id":360153968,"identity":"056204b3-bda2-4e76-985c-64f0e08c1251","order_by":1,"name":"Alix Buhlmann","email":"","orcid":"","institution":"University Hospital Zurich","correspondingAuthor":false,"prefix":"","firstName":"Alix","middleName":"","lastName":"Buhlmann","suffix":""},{"id":360153969,"identity":"b58277ef-8cd9-49c0-9a9f-7d9bbc17a9ee","order_by":2,"name":"Lennart Wild","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Lennart","middleName":"","lastName":"Wild","suffix":""},{"id":360153970,"identity":"64ce8221-4997-49d9-aba4-d508ad104e58","order_by":3,"name":"Christian Bode","email":"","orcid":"","institution":"University Hospital Bonn","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"","lastName":"Bode","suffix":""},{"id":360153971,"identity":"7347f88c-0c8d-4ffb-8ec8-40d070ef4649","order_by":4,"name":"Sascha David","email":"","orcid":"","institution":"University Hospital Zurich","correspondingAuthor":false,"prefix":"","firstName":"Sascha","middleName":"","lastName":"David","suffix":""},{"id":360153972,"identity":"46216d98-3554-46f0-8699-4c695ece76a3","order_by":5,"name":"Benjamin Seeliger","email":"","orcid":"","institution":"Hannover Medical School","correspondingAuthor":false,"prefix":"","firstName":"Benjamin","middleName":"","lastName":"Seeliger","suffix":""},{"id":360153973,"identity":"5e9d6aa8-6c30-48a0-80da-bee90d6565bd","order_by":6,"name":"Klaus Stahl","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIie2Pv0rEQBCH5zhYm+Gu3aAkr7BHIL7OHAeXZmMTkCAWgYN09orgvYI2YqlN0gTrlRNdEVJZnAiW6u4h2Oz5p7PYrxpm55vfDoDH8z9hoIG2TNHTvRLo6+FyrcDMGKEp++LPCuO/UqL5rNMEUxwept3ezQXsDI8Prh6xuINBUzoVUbNtQSCRK5ksshZyfns9ibHNIWjdMYJBwgkKBCXZIqvex6Vxg6OKQChyKlG18bpSIpV2eVbBeL5S3oxyr93H1GhTJJqdSd8qp0bhz6VNcRuilrucxBRH7VO8aZUzJWOxrAmDds3HZs05XxaTMGzShxernCg50rRP4aBxn/+Z5ejhN/Mej8fj+YEPMftfLZtVHUoAAAAASUVORK5CYII=","orcid":"","institution":"Hannover Medical School","correspondingAuthor":true,"prefix":"","firstName":"Klaus","middleName":"","lastName":"Stahl","suffix":""}],"badges":[],"createdAt":"2024-08-16 15:21:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4925917/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4925917/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12890-024-03356-4","type":"published","date":"2024-10-24T15:57:49+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66871153,"identity":"ba57b9de-5cfb-4184-b863-989cebc5e9cd","added_by":"auto","created_at":"2024-10-17 09:42:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50140,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIntensive Care Unit\u003c/strong\u003e\u003cem\u003e \u003c/em\u003e\u003cstrong\u003eSurvival in patients with and without ECMO support for Tbc-associated ARDS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eICU survival following ECMO decannulation was analyzed for the whole cohort and for the subgroups ECMO vs. no-ECMO, respectively. Survival was visualized using Kaplan-Meier plots and analysed using the log-rank test. Influence of ECMO support on ICU survival- was analyzed by means of uni- and multivariate Cox-proportional hazard regression models. All reported p-values are two-sided unless indicated otherwise; p-values \u0026lt; 0.05 were considered statistically significant.\u003c/p\u003e\n\u003cp\u003eGraphPad Prism (Version 10.0, GraphPad Software, La Jolla, CA) and IBM SPSS Statistics (Version 25.0, IBM Corp., Armonk, NY) were used for data analysis and graph generation.\u003c/p\u003e\n\u003cp\u003eARDS – Acute respiratory distress syndrome, ECMO – Extracorporeal membrane oxygenation, CI – Confidence Interval, HR – Hazard ratio\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4925917/v1/0a0dfbc0903dd4730e4303e2.png"},{"id":67683931,"identity":"9057f2a2-94db-494c-a0a0-89b6c13271e4","added_by":"auto","created_at":"2024-10-28 16:21:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":421057,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4925917/v1/f3ec30c2-2b14-4e72-b01a-7ceeb1984b40.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eECMO support may be associated with improved survival in tuberculosis associated severe ARDS\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eRecently Idris et al. described in \u003cem\u003ethe Journal\u003c/em\u003e outcome of patients with tuberculosis (Tbc) associated critical illness, including those with severe acute respiratory distress syndrome (ARDS), supported by extracorporeal membrane oxygenation (ECMO) (1). In this systematic review and metanalysis of 43 patients receiving diverse modes of ECMO support, the authors reported encouraging clinical outcomes with an overall intensive care unit (ICU) survival of 81.4%. Data describing outcome of ECMO support in Tbc-associated ARDS in general remain sparce and are mostly confined to only singular case reports (2). However, the analysis by Idris et al. has some important limitations. First, patients were included based on singular case reports extracted over a wide time-period of 47 years, given rise to both reporting bias and significant heterogeneity in selection and provision of treatment as well as technology. Second, both patients with primarily respiratory as well as circulatory failure, consequentially receiving diverse modes of ECMO cannulation (vv-, va- and vav-ECMO), were included and analyzed together, thus further increasing clinical heterogeneity despite completely different primary clinical disorders.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eOur study-group has therefore analyzed ICU survival in a more homogenous cohort of patients treated for Tbc-associated ARDS at three ECMO-referral university hospitals (Hannover Medical School, University Hospital Bonn (both Germany) and University Hospital Zurich (Switzerland)) during the last 14 years. A total of 14 patients with Tbc-associated ARDS were included in this present case series, of whom eight received additional veno-venous (vv) ECMO support and six received standard care only.\u003c/p\u003e \u003cp\u003eBaseline demographic and clinical characteristics at implementation of invasive ventilation were comparable between the two groups (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Three patients had HIV infection, two patients received medical immunosuppression, one had a congenital immune defect and five patients had chronic alcohol abuse. Patients later receiving ECMO support had significantly lower oxygenation index (Median (Interquartile range (IQR)) 71 (54\u0026ndash;92) vs. 188 (146\u0026ndash;236) mmHg, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Median (IQR) time to ECMO implantation was 2 (1\u0026ndash;4) days.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics at start of invasive ventilation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eMedian (interquartile range) / No (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eECMO\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eno ECMO\u003c/b\u003e (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge - y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (27\u0026ndash;48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (35\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex - no (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI - kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.9 (17.6\u0026ndash;24.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.2 (20-25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppression - no (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMDR-Tbc - no (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.825\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e - mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (54\u0026ndash;92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e188 (146\u0026ndash;236)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epCO\u003csub\u003e2\u003c/sub\u003e - mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (44\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (40\u0026ndash;61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.707\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasopressor therapy - no (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (83.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.825\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasopressor dose - ug/kg/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.38 (0.2-1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.33 (0.245\u0026ndash;1.455)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.613\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal replacement therapy - no (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.347\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA score - points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (7\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.799\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate - mmol/l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.4 (1.3\u0026ndash;4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2.1\u0026ndash;6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCategorical variables are represented by number (n) and percentage (%), while continuous variables are expressed as median (25% to 75% Interquartile Range [IQR]). The normal distribution was checked using the D\u0026apos;Agostino-Pearson omnibus normality test and the Shapiro-Wilk normality test. Two-tailed p values of less than 0.05 were considered to indicate statistical significance.\u0026nbsp;Comparisons of population characteristics between the ECMO and the no-ECMO group were performed using unpaired t-tests, Mann-Whitney tests and\u0026nbsp;\u0026chi;\u003csup\u003e2\u003c/sup\u003e tests, as appropriate.\u0026nbsp;All reported p-values are two-sided unless indicated otherwise; p-values \u0026lt; 0.05 were considered statistically significant.\u003c/p\u003e\n\u003cp\u003eARDS \u0026ndash; Acute respiratory distress syndrome, ECMO \u0026ndash; Extracorporeal membrane oxygenation, MDR \u0026ndash; Multi drug resistant, SOFA \u0026ndash; Sequential Organ Failure Assessment score, Tbc \u0026ndash; Tuberculosis\u003c/p\u003e\u003cp\u003eICU survival was significantly higher in patients receiving additional ECMO support (62.5%, n\u0026thinsp;=\u0026thinsp;5/8) compared to those that did not (16.7%, n\u0026thinsp;=\u0026thinsp;1/6) (FIGURE \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, p\u0026thinsp;=\u0026thinsp;0.021). ECMO support was associated with reduced ICU mortality (Hazard ratio adjusted for baseline SOFA score [adj. HR] 0.125 (95% confidence interval (CI): 0.023\u0026ndash;0.689), p\u0026thinsp;=\u0026thinsp;0.017). Median (IQR) time on ECMO and invasive ventilation in the ECMO group were 20 (11\u0026ndash;26) and 37 (27\u0026ndash;53) days, respectively. Major bleeding defined as transfusion requirement of 4 units of blood or more or surgical and/or radiologic intervention occurred only in one patient, in whom pulmonary bleeding was fatal. Thromboembolic events occurred in none of the ECMO patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eIn the meta-analysis by Idris et al. 30 patients had ARDS, 27 were supported by vv-ECMO, of which 23 (85.1%) survived. However, outcomes were reported from a multitude of different centers dating back to 1975, making a reporting bias likely. Our outcome results with a survival of about 60% generated from three centers in a recent time period and similar standard operating procedures in the ECMO cohort are better in line with the more recent ECMO trials such as the CESAR (3) and EOLIA (4) study with regards to mortality. Idris et al. did not report on patients with Tbc-associated ARDS, treated at the same institutions but without ECMO support. The finding of an exceedingly high mortality in patients without ECMO support from this present cohort is provocative, but certainly needs confirmation in prospective studies. Of note, both ECMO runtime and ventilator-days were excessively long in either Idris et al. and our group, underlining the slow recovery from Tbc-associated ARDS (5) and the consequential need to optimize lung-protective strategies in this cohort.\u003c/p\u003e \u003cp\u003eIn summary, this retrospective analysis from three large ECMO centers with similar SOPs suggests ECMO support as a feasible approach in patients with severe Tbc-associated ARDS. Although affiliated with extended runtimes, ECMO might be associated with improved survival in those patients. ECMO support should thus be considered in Tbc-associated ARDS to enable lung protective strategies during prolonged lung recovery.\u003c/p\u003e "},{"header":"List of abbreviations","content":"\u003cp\u003eARDS = Acute respiratory distress syndrome\u003c/p\u003e\u003cp\u003eCI = Confidence Interval\u003c/p\u003e\u003cp\u003eECMO = Extracorporeal membrane oxygenation\u003c/p\u003e\u003cp\u003eHR = Hazard Ratio\u003c/p\u003e\u003cp\u003eICU = Intensive care unit\u003c/p\u003e\u003cp\u003eMDR = Multi drug resistant\u003c/p\u003e\u003cp\u003eSOFA = Sequential Organ Failure Assessment score\u003c/p\u003e\u003cp\u003eSOP = Standard operating procedure\u003c/p\u003e\u003cp\u003eTbc = Tuberculosis\u003c/p\u003e\u003cp\u003eVa = Veno-arterial\u003c/p\u003e\u003cp\u003eVav = Veno-arterial-venous\u003c/p\u003e\u003cp\u003eVv = Veno-venous\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003e Due to a retrospective analysis ethics approval was waived. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The medical committee of Hannover Medical School (No. 11141_BO_K_2023), University Hospital Bonn (No 437/23-EP) and University Hospital Zurich (BASEC-No: 2024-00034) approved the study. All personal patient data were pseudonymized before data collection.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent of publication\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eNone declared.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eClinical trial number\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eKS and BN conceived the presented idea. BN, AB and LW obtained the retrospective data and performed the analysis. NB, AB, LW and KS discussed the data and generated figures. CB, SD, BS and KS wrote the manuscript; all authors discussed the results and contributed to the final manuscript. The BonHanZA study group is a three-center research consortium, that all authors are part of.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eFurther members of the BonHanZA (Bonn-Hannover-Zurich ARDS) study group, not directly contributing to the manuscript, are: Thorben Pape1,2,7, Jannik Ruwisch1,2,7, Marius M. Hoeper1,2,7, Pedro David Wendel-Garcia3,7, Daniel A. Hofmaenner3,7, Rolf Erlebach3,7, Mattia Mueller3,7, Rea Andermatt3,7, Konrad Peukert4,7, Andrea Sauer4,7We are grateful to the late Prof. Tobias Welte, who inspired this analysis and so many more. He and his influence on this study group will never be forgotten.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and analyzed are during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eIdris R, Zielbauer AS, Koepsell J, Kloka J, Wetzstein N. Extracorporeal membrane oxygenation (ECMO) in patients with tuberculosis: systematic review and meta-analysis of 43 cases. BMC Pulm Med. 2024;24(1):47.\u003c/li\u003e\n\u003cli\u003eBesa S, Morales \u0026Aacute; J, Salas P, Bravo MS, Garrido-Olivares L. Extracorporeal membrane oxygenation for tuberculosis pneumonia with empyema. Respir Med Case Rep. 2021;34:101481.\u003c/li\u003e\n\u003cli\u003ePeek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009;374(9698):1351-63.\u003c/li\u003e\n\u003cli\u003eCombes A, Hajage D, Capellier G, Demoule A, Lavou\u0026eacute; S, Guervilly C, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018;378(21):1965-75.\u003c/li\u003e\n\u003cli\u003eAgarwal R, Gupta D, Aggarwal AN, Behera D, Jindal SK. Experience with ARDS caused by tuberculosis in a respiratory intensive care unit. Intensive Care Med. 2005;31(9):1284-7.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4925917/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4925917/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData describing outcome of extracorporeal membrane oxygenation (ECMO) support in Tuberculosis (Tbc)-associated acute respiratory distress syndrome (ARDS) remain sparce and are mostly confined to singular case reports.\u003cstrong\u003e \u003c/strong\u003eThe aim of this case series was to analyze intensive care unit (ICU) survival in patients with Tbc-associated ARDS receiving ECMO support and to compare those to patients not receiving ECMO.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eICU survival was analyzed retrospectively in 14 patients treated for Tbc-associated ARDS at three ECMO-referral university hospitals (Hannover Medical School, University Hospital Bonn (both Germany) and University Hospital Zurich (Switzerland)) during the last 14 years, of which eight patients received additional veno-venous (vv) ECMO support and six standard care only.\u003c/p\u003e\n\u003cp\u003eICU survival was significantly higher in patients receiving additional ECMO support (62.5%, n=5/8) compared to those that did not (16.7%, n=1/6) (p=0.021). ECMO support was associated with reduced ICU mortality (Hazard ratio adjusted for baseline SOFA score [adj. HR] 0.125 (95% confidence interval (CI): 0.023-0.689), p=0.017). Median (IQR) time on ECMO and invasive ventilation in the ECMO group were 20 (11-26) and 37 (27-53) days, respectively. Major bleeding defined as transfusion requirement of 4 units of blood or more or surgical and/or radiologic intervention occurred only in one patient, in whom pulmonary bleeding was fatal. Thromboembolic events occurred in none of the ECMO patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion and Conclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective analysis from three large ECMO centers with similar SOPs suggests ECMO support as a feasible approach in patients with severe Tbc-associated ARDS. Although affiliated with extended runtimes, ECMO might be associated with improved survival in those patients. ECMO support should thus be considered in Tbc-associated ARDS to enable lung protective strategies during prolonged lung recovery.\u003c/p\u003e","manuscriptTitle":"ECMO support may be associated with improved survival in tuberculosis associated severe ARDS","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-17 09:42:30","doi":"10.21203/rs.3.rs-4925917/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-30T10:33:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-24T14:27:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-19T12:51:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-16T23:17:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"291762385041559587228102270745414886471","date":"2024-09-14T11:47:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285714224448681991898404344834941549213","date":"2024-09-13T18:26:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"91820660316294412356325076489111884157","date":"2024-09-11T23:13:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"281306104893443061323498054488133541540","date":"2024-09-11T22:41:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283688640528644010598768379062395572767","date":"2024-09-11T19:04:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66629289878282483346123829231899823770","date":"2024-09-03T15:07:20+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-03T13:46:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-30T13:22:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-30T05:54:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-30T05:52:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2024-08-16T15:20:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8321742f-193a-48b2-ae02-b4394bede85b","owner":[],"postedDate":"October 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-28T16:08:21+00:00","versionOfRecord":{"articleIdentity":"rs-4925917","link":"https://doi.org/10.1186/s12890-024-03356-4","journal":{"identity":"bmc-pulmonary-medicine","isVorOnly":false,"title":"BMC Pulmonary Medicine"},"publishedOn":"2024-10-24 15:57:49","publishedOnDateReadable":"October 24th, 2024"},"versionCreatedAt":"2024-10-17 09:42:30","video":"","vorDoi":"10.1186/s12890-024-03356-4","vorDoiUrl":"https://doi.org/10.1186/s12890-024-03356-4","workflowStages":[]},"version":"v1","identity":"rs-4925917","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4925917","identity":"rs-4925917","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}