Transfusion-Related Acute Lung Injury (TRALI) Following Intravenous Immunoglobulin (IVIG) in a Liver Transplant Recipient: A Case Report

Transfusion-Related Acute Lung Injury (TRALI) Following Intravenous Immunoglobulin (IVIG) in a Liver Transplant Recipient: A Case Report | 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 Case Report Transfusion-Related Acute Lung Injury (TRALI) Following Intravenous Immunoglobulin (IVIG) in a Liver Transplant Recipient: A Case Report Roya Alsadat Hosseini Hematabadi, Mohamad Reza Mirjalili This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7921121/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background: Transfusion-related acute lung injury (TRALI) is a severe, life-threatening reaction to blood product transfusion. While it is most often linked to plasma, platelets, or red blood cells, cases following intravenous immunoglobulin (IVIG) are exceedingly rare and under-recognized. Reporting such occurrences is vital to raise awareness among clinicians, especially when managing high-risk patients such as transplant recipients. Case Presentation: A 35-year-old man, two months after liver transplantation, was admitted with abdominal pain and diarrhea. He was receiving immunosuppressive therapy and was diagnosed with cytomegalovirus (CMV) colitis. After transfusions of packed red blood cells and fresh frozen plasma for anemia, he was started on IVIG as adjunctive therapy. Within minutes of the first IVIG infusion, he developed severe respiratory distress, hypoxemia, and bilateral pulmonary edema requiring mechanical ventilation. Despite initial stabilization, a subsequent IVIG rechallenge (20 mL; Kedrion 5 g/100 mL) triggered bradycardia and recurrent respiratory failure. With other causes excluded, IVIG-related TRALI was diagnosed according to the 2019 Delphi criteria. Despite intensive supportive care, the patient died. Conclusions: This case highlights that TRALI can occur as a rare but fatal complication of IVIG therapy. Clinicians should maintain a high index of suspicion, particularly in immunocompromised or critically ill patients. Prompt recognition and immediate discontinuation of IVIG are essential. Further research is needed to better understand the underlying mechanisms and risk factors of IVIG-associated TRALI. Transfusion-Related Acute Lung Injury Intravenous Immunoglobulin Adverse Drug Reaction Liver Transplantation Cytomegalovirus Infection Case Report Background Transfusion-related acute lung injury (TRALI) is a rare but serious transfusion complication characterized by non-cardiogenic pulmonary edema that develops during or within six hours of transfusion.(1,2) It remains one of the leading causes of transfusion-associated mortality.(2) The condition is thought to follow a “two-hit” model: pre-existing patient factors such as systemic inflammation act as the first hit, while transfused biological response modifiers serve as the second.(1,3) Intravenous immunoglobulin (IVIG) is a pooled plasma product derived from thousands of donors, widely used in immune deficiencies, autoimmune diseases, and selected infections.(4) Although TRALI is classically linked to cellular blood products, several reports have implicated IVIG as a trigger.(5–8) As IVIG use continues to expand, awareness of this rare but serious adverse reaction is critical. We present a fatal case of TRALI following IVIG administration in a liver transplant recipient, emphasizing diagnostic challenges and the importance of clinical vigilance. Case Presentation A 35-year-old man, two months after orthotopic liver transplantation, presented with a 10-day history of abdominal pain and diarrhea. His maintenance immunosuppressive regimen included prednisolone (5 mg/day), tacrolimus (3 mg/day), mycophenolate mofetil (2 g/day), and trimethoprim-sulfamethoxazole prophylaxis. Laboratory testing revealed a high CMV viral load, and colonoscopy showed deep ulcerations in the terminal ileum; biopsy confirmed CMV colitis. Intravenous ganciclovir therapy was initiated. Due to melena and anemia, the patient received packed red blood cells and fresh frozen plasma. IVIG was then started as adjunctive therapy per infectious-disease consultation. Minutes into the first IVIG infusion, he developed acute dyspnea, desaturation, and hypotension. Chest imaging revealed bilateral pulmonary edema and pleural effusions. Initially, a transfusion reaction or fluid overload was suspected. He received hydrocortisone and diuretics but required mechanical ventilation for persistent respiratory acidosis. Infectious workup, including PCR for SARS-CoV-2 and influenza, was negative. During his ICU stay, he developed ventilator-associated pneumonia (Klebsiella and Acinetobacter), which was treated successfully, and he was eventually weaned off the ventilator. Although CMV viremia resolved, he developed acute liver graft rejection. To control rejection, prophylactic ganciclovir and another IVIG course were recommended. Shortly after starting a 20 mL infusion of IVIG (Kedrion 5 g/100 mL), he developed bradycardia and severe respiratory distress, necessitating re-intubation. Echocardiography showed normal cardiac function, and right atrial pressure was normal. Pulmonary embolism and infection were excluded. Given the temporal relationship, hypoxemia, bilateral infiltrates, and exclusion of cardiogenic or infectious causes, IVIG-related TRALI was diagnosed using the 2019 Delphi criteria. Despite full supportive measures, the patient’s condition deteriorated, and he died. Discussion and Conclusions TRALI is defined as acute hypoxemic respiratory failure occurring within six hours of transfusion, unrelated to cardiac failure or fluid overload. Diagnosis requires careful exclusion of mimics such as transfusion-associated circulatory overload (TACO), anaphylaxis, or cardiogenic pulmonary edema.(1,2) This case offers several important lessons. First, TRALI can occur after IVIG administration, even though this association is often overlooked. The initial episode was attributed to the preceding blood transfusions, delaying recognition of IVIG as the culprit. The clear rechallenge response strongly supports causality. Second, our patient’s condition fits the two-hit model: his post-transplant status, immunosuppression, and CMV infection created a primed inflammatory environment (first hit), while IVIG infusion provided the second hit, possibly through donor antibodies or neutrophil-activating factors. Although IVIG-related TRALI is rare, reported cases show high morbidity and mortality.(2) Differentiation from TACO is crucial since diuretics beneficial in TACO are ineffective in TRALI, where management relies on immediate cessation of the transfusion and supportive respiratory care.(1) In summary, clinicians should recognize TRALI as a potential adverse reaction to IVIG, particularly in vulnerable populations such as transplant recipients. Any acute respiratory distress during or soon after IVIG infusion warrants immediate cessation and evaluation for TRALI. Increased awareness, prompt diagnosis, and supportive management are key to improving outcomes. Further studies are needed to clarify the pathophysiology and identify predictive risk factors to prevent future occurrences. Abbreviations ARDS: Acute Respiratory Distress Syndrome CMV: Cytomegalovirus FFP: Fresh Frozen Plasma HLA: Human Leukocyte Antigen HNA: Human Neutrophil Antigen IVIG: Intravenous Immunoglobulin PCR: Polymerase Chain Reaction TACO: Transfusion-Associated Circulatory Overload TRALI: Transfusion-Related Acute Lung Injury VAP: Ventilator-Associated Pneumonia Declarations Ethics approval and consent to participate This case report was approved by the Institutional Review Board (IRB) of Shahid Sadoughi University of Medical Sciences under the ethical approval code IR.SSU.REC.1404.091 . Informed consent was obtained from the patient for participation and the use of clinical data presented in this report. Consent for publication Written informed consent for publication of their clinical details was obtained from the patient. Availability of data and materials All data generated during this study are included in this published article Competing interests The authors declare no competing interests Funding This case report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors Authors' contributions Roya Alsadat Hosseini Hematabadi designed the study, collected clinical data and wrote the manuscript. Mohamad Reza Mirjalili revised the manuscript. Authors' information Dr. Roya Alsadat Hosseini Hematabadi is Assistant Professor of Gastroenterology and Hepatology in Shahid Sadoughi University of Medical Sciences, Yazd, Iran Dr. Mohamad Reza Mirjalili is Professor of Internal Medicine in Shahid Sadoughi University of Medical Sciences, Yazd, Iran References Kuriri FA. Transfusion-related acute lung injury (TRALI): Current understanding, challenges, and future directions. Saudi Medical Journal. 2025 Aug;46(8):865. Vlaar APJ, Toy P, Fung M, et al. A consensus redefinition of transfusion-related acute lung injury. Transfusion. 2019;59(7):2465–2476. Looney MR, Gropper MA, Matthay MA. Transfusion-related acute lung injury: a review. Chest. 2004;126(1):249-258. Orange JS, Hossny EM, Weiler CR, et al. Use of intravenous immunoglobulin in human disease. J Allergy Clin Immunol. 2006;117(4 Suppl):S525-S553. Rizk A, Gorson KC, Kenney K, et al. Transfusion-related lung injury after administration of IVIG. Muscle Nerve. 2001;24(5):733-738. Reddy YN, Vaidya PN, Greene JN. Acute lung injury after IVIG for myasthenia gravis. Am J Med Sci. 2006;331(4):220–222. Degtiarova G, Vitaliti G, Pavone P, et al. TRALI following IVIG in a child with MS. Pediatr Pulmonol. 2014;49(5):E90-E92. Braudel S, Rabian C, Deschamps T, et al. TRALI after IVIG: a potentially severe and underestimated adverse effect. Transfus Clin Biol. 2016;23(1):e9-e13. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 02 Dec, 2025 Reviews received at journal 30 Nov, 2025 Reviews received at journal 23 Nov, 2025 Reviewers agreed at journal 23 Nov, 2025 Reviewers agreed at journal 20 Nov, 2025 Reviewers invited by journal 20 Nov, 2025 Editor invited by journal 28 Oct, 2025 Editor assigned by journal 27 Oct, 2025 Submission checks completed at journal 27 Oct, 2025 First submitted to journal 22 Oct, 2025 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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act as the first hit, while transfused biological response modifiers serve as the second.(1,3)\u003c/p\u003e\u003cp\u003eIntravenous immunoglobulin (IVIG) is a pooled plasma product derived from thousands of donors, widely used in immune deficiencies, autoimmune diseases, and selected infections.(4) Although TRALI is classically linked to cellular blood products, several reports have implicated IVIG as a trigger.(5\u0026ndash;8) As IVIG use continues to expand, awareness of this rare but serious adverse reaction is critical. We present a fatal case of TRALI following IVIG administration in a liver transplant recipient, emphasizing diagnostic challenges and the importance of clinical vigilance.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 35-year-old man, two months after orthotopic liver transplantation, presented with a 10-day history of abdominal pain and diarrhea. His maintenance immunosuppressive regimen included prednisolone (5 mg/day), tacrolimus (3 mg/day), mycophenolate mofetil (2 g/day), and trimethoprim-sulfamethoxazole prophylaxis. Laboratory testing revealed a high CMV viral load, and colonoscopy showed deep ulcerations in the terminal ileum; biopsy confirmed CMV colitis. Intravenous ganciclovir therapy was initiated.\u003c/p\u003e\u003cp\u003eDue to melena and anemia, the patient received packed red blood cells and fresh frozen plasma. IVIG was then started as adjunctive therapy per infectious-disease consultation. Minutes into the first IVIG infusion, he developed acute dyspnea, desaturation, and hypotension. Chest imaging revealed bilateral pulmonary edema and pleural effusions. Initially, a transfusion reaction or fluid overload was suspected. He received hydrocortisone and diuretics but required mechanical ventilation for persistent respiratory acidosis.\u003c/p\u003e\u003cp\u003eInfectious workup, including PCR for SARS-CoV-2 and influenza, was negative. During his ICU stay, he developed ventilator-associated pneumonia (Klebsiella and Acinetobacter), which was treated successfully, and he was eventually weaned off the ventilator. Although CMV viremia resolved, he developed acute liver graft rejection.\u003c/p\u003e\u003cp\u003eTo control rejection, prophylactic ganciclovir and another IVIG course were recommended. Shortly after starting a 20 mL infusion of IVIG (Kedrion 5 g/100 mL), he developed bradycardia and severe respiratory distress, necessitating re-intubation. Echocardiography showed normal cardiac function, and right atrial pressure was normal. Pulmonary embolism and infection were excluded. Given the temporal relationship, hypoxemia, bilateral infiltrates, and exclusion of cardiogenic or infectious causes, IVIG-related TRALI was diagnosed using the 2019 Delphi criteria. Despite full supportive measures, the patient’s condition deteriorated, and he died.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eTRALI is defined as acute hypoxemic respiratory failure occurring within six hours of transfusion, unrelated to cardiac failure or fluid overload. Diagnosis requires careful exclusion of mimics such as transfusion-associated circulatory overload (TACO), anaphylaxis, or cardiogenic pulmonary edema.(1,2)\u003c/p\u003e\u003cp\u003eThis case offers several important lessons. First, TRALI can occur after IVIG administration, even though this association is often overlooked. The initial episode was attributed to the preceding blood transfusions, delaying recognition of IVIG as the culprit. The clear rechallenge response strongly supports causality.\u003c/p\u003e\u003cp\u003eSecond, our patient’s condition fits the two-hit model: his post-transplant status, immunosuppression, and CMV infection created a primed inflammatory environment (first hit), while IVIG infusion provided the second hit, possibly through donor antibodies or neutrophil-activating factors.\u003c/p\u003e\u003cp\u003eAlthough IVIG-related TRALI is rare, reported cases show high morbidity and mortality.(2) Differentiation from TACO is crucial since diuretics beneficial in TACO are ineffective in TRALI, where management relies on immediate cessation of the transfusion and supportive respiratory care.(1)\u003c/p\u003e\u003cp\u003eIn summary, clinicians should recognize TRALI as a potential adverse reaction to IVIG, particularly in vulnerable populations such as transplant recipients. Any acute respiratory distress during or soon after IVIG infusion warrants immediate cessation and evaluation for TRALI. Increased awareness, prompt diagnosis, and supportive management are key to improving outcomes. Further studies are needed to clarify the pathophysiology and identify predictive risk factors to prevent future occurrences.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eARDS:\u003c/strong\u003e Acute Respiratory Distress Syndrome\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCMV:\u003c/strong\u003e Cytomegalovirus\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eFFP:\u003c/strong\u003e Fresh Frozen Plasma\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eHLA:\u003c/strong\u003e Human Leukocyte Antigen\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eHNA:\u003c/strong\u003e Human Neutrophil Antigen\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIVIG:\u003c/strong\u003e Intravenous Immunoglobulin\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePCR:\u003c/strong\u003e Polymerase Chain Reaction\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTACO:\u003c/strong\u003e Transfusion-Associated Circulatory Overload\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTRALI:\u003c/strong\u003e Transfusion-Related Acute Lung Injury\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eVAP:\u003c/strong\u003e Ventilator-Associated Pneumonia\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report was approved by the Institutional Review Board (IRB) of Shahid Sadoughi University of Medical Sciences under the ethical approval code IR.SSU.REC.1404.091 . Informed consent was obtained from the patient for participation and the use of clinical data presented in this report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of their clinical details was obtained from the patient.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated during this study are included in this published article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRoya Alsadat \u0026nbsp;Hosseini Hematabadi designed the study, collected clinical data and wrote the manuscript. Mohamad Reza Mirjalili revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Roya Alsadat \u0026nbsp;Hosseini Hematabadi is Assistant Professor of Gastroenterology and Hepatology in Shahid Sadoughi University of Medical Sciences, Yazd, Iran\u003c/p\u003e\n\u003cp\u003eDr. Mohamad Reza Mirjalili is Professor of Internal Medicine in Shahid Sadoughi University of Medical Sciences, Yazd, Iran\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKuriri FA. Transfusion-related acute lung injury (TRALI): Current understanding, challenges, and future directions. Saudi Medical Journal. 2025 Aug;46(8):865. \u003c/li\u003e\n\u003cli\u003eVlaar APJ, Toy P, Fung M, et al. A consensus redefinition of transfusion-related acute lung injury. Transfusion. 2019;59(7):2465\u0026ndash;2476. \u003c/li\u003e\n\u003cli\u003eLooney MR, Gropper MA, Matthay MA. Transfusion-related acute lung injury: a review. Chest. 2004;126(1):249-258.\u003c/li\u003e\n\u003cli\u003eOrange JS, Hossny EM, Weiler CR, et al. Use of intravenous immunoglobulin in human disease. J Allergy Clin Immunol. 2006;117(4 Suppl):S525-S553. \u003c/li\u003e\n\u003cli\u003eRizk A, Gorson KC, Kenney K, et al. Transfusion-related lung injury after administration of IVIG. Muscle Nerve. 2001;24(5):733-738.\u003c/li\u003e\n\u003cli\u003eReddy YN, Vaidya PN, Greene JN. Acute lung injury after IVIG for myasthenia gravis. Am J Med Sci. 2006;331(4):220\u0026ndash;222.\u003c/li\u003e\n\u003cli\u003eDegtiarova G, Vitaliti G, Pavone P, et al. TRALI following IVIG in a child with MS. Pediatr Pulmonol. 2014;49(5):E90-E92. \u003c/li\u003e\n\u003cli\u003eBraudel S, Rabian C, Deschamps T, et al. TRALI after IVIG: a potentially severe and underestimated adverse effect. Transfus Clin Biol. 2016;23(1):e9-e13.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Transfusion-Related Acute Lung Injury, Intravenous Immunoglobulin, Adverse Drug Reaction, Liver Transplantation, Cytomegalovirus Infection, Case Report","lastPublishedDoi":"10.21203/rs.3.rs-7921121/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7921121/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eTransfusion-related acute lung injury (TRALI) is a severe, life-threatening reaction to blood product transfusion. While it is most often linked to plasma, platelets, or red blood cells, cases following intravenous immunoglobulin (IVIG) are exceedingly rare and under-recognized. Reporting such occurrences is vital to raise awareness among clinicians, especially when managing high-risk patients such as transplant recipients.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e\u003cp\u003eA 35-year-old man, two months after liver transplantation, was admitted with abdominal pain and diarrhea. He was receiving immunosuppressive therapy and was diagnosed with cytomegalovirus (CMV) colitis. After transfusions of packed red blood cells and fresh frozen plasma for anemia, he was started on IVIG as adjunctive therapy. Within minutes of the first IVIG infusion, he developed severe respiratory distress, hypoxemia, and bilateral pulmonary edema requiring mechanical ventilation. Despite initial stabilization, a subsequent IVIG rechallenge (20 mL; Kedrion 5 g/100 mL) triggered bradycardia and recurrent respiratory failure. With other causes excluded, IVIG-related TRALI was diagnosed according to the 2019 Delphi criteria. Despite intensive supportive care, the patient died.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e\u003cp\u003eThis case highlights that TRALI can occur as a rare but fatal complication of IVIG therapy. Clinicians should maintain a high index of suspicion, particularly in immunocompromised or critically ill patients. Prompt recognition and immediate discontinuation of IVIG are essential. Further research is needed to better understand the underlying mechanisms and risk factors of IVIG-associated TRALI.\u003c/p\u003e","manuscriptTitle":"Transfusion-Related Acute Lung Injury (TRALI) Following Intravenous Immunoglobulin (IVIG) in a Liver Transplant Recipient: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-28 09:54:22","doi":"10.21203/rs.3.rs-7921121/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"113353618662519466556251740067317959016","date":"2025-12-02T20:45:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-30T20:21:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-24T00:55:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"65114847746293490443031688239286869841","date":"2025-11-23T22:04:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"173849142632870016695808957057280262725","date":"2025-11-20T20:45:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-20T18:13:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-28T05:45:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-27T12:38:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-27T12:37:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2025-10-22T06:30:33+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":"cde4f033-c3c7-4af1-8976-0172a46e2bd4","owner":[],"postedDate":"November 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-28T09:54:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-28 09:54:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7921121","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7921121","identity":"rs-7921121","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}