Pub Date : 2024-07-08DOI: 10.1016/S2213-2600(24)00148-6
Sjanna B Besteman, Debby Bogaert, Louis Bont, Asuncion Mejias, Octavio Ramilo, Daniel M Weinberger, Ron Dagan
Lower respiratory tract infections, commonly caused by respiratory syncytial virus (RSV) or Streptococcus pneumoniae (pneumococcus), pose a substantial global health burden, especially in children younger than 5 years of age. A deeper understanding of the relationship between RSV and pneumococcus would aid the development of health-care approaches to disease prevention and management. We completed a systematic review to identify and assess evidence pertaining to the relationship between RSV and pneumococcus in the pathogenesis of childhood respiratory infections. We found mechanistic evidence for direct pathogen-pathogen interactions and for indirect interactions involving host modulation. We found a strong seasonal epidemiological association between these two pathogens, which was recently confirmed by a parallel decrease and a subsequent resurgence of both RSV and pneumococcus-associated disease during the COVID-19 pandemic. Importantly, we found that pneumococcal vaccination was associated with reduced RSV hospitalisations in infants, further supporting the relevance of their interaction in modulating severe disease. Overall evidence supports a broad biological and clinical interaction between pneumococcus and RSV in the pathogenesis of childhood respiratory infections. We hypothesise that the implementation of next-generation pneumococcal and RSV vaccines and monoclonal antibodies targeting RSV will act synergistically to reduce global morbidity and mortality related to childhood respiratory infections.
{"title":"Interactions between respiratory syncytial virus and Streptococcus pneumoniae in the pathogenesis of childhood respiratory infections: a systematic review.","authors":"Sjanna B Besteman, Debby Bogaert, Louis Bont, Asuncion Mejias, Octavio Ramilo, Daniel M Weinberger, Ron Dagan","doi":"10.1016/S2213-2600(24)00148-6","DOIUrl":"https://doi.org/10.1016/S2213-2600(24)00148-6","url":null,"abstract":"<p><p>Lower respiratory tract infections, commonly caused by respiratory syncytial virus (RSV) or Streptococcus pneumoniae (pneumococcus), pose a substantial global health burden, especially in children younger than 5 years of age. A deeper understanding of the relationship between RSV and pneumococcus would aid the development of health-care approaches to disease prevention and management. We completed a systematic review to identify and assess evidence pertaining to the relationship between RSV and pneumococcus in the pathogenesis of childhood respiratory infections. We found mechanistic evidence for direct pathogen-pathogen interactions and for indirect interactions involving host modulation. We found a strong seasonal epidemiological association between these two pathogens, which was recently confirmed by a parallel decrease and a subsequent resurgence of both RSV and pneumococcus-associated disease during the COVID-19 pandemic. Importantly, we found that pneumococcal vaccination was associated with reduced RSV hospitalisations in infants, further supporting the relevance of their interaction in modulating severe disease. Overall evidence supports a broad biological and clinical interaction between pneumococcus and RSV in the pathogenesis of childhood respiratory infections. We hypothesise that the implementation of next-generation pneumococcal and RSV vaccines and monoclonal antibodies targeting RSV will act synergistically to reduce global morbidity and mortality related to childhood respiratory infections.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1016/S2213-2600(24)00176-0
Merete B Long, Sanjay H Chotirmall, Michal Shteinberg, James D Chalmers
Bronchiectasis is understood to be the result of a complex interaction between infection, impaired mucociliary clearance, inflammation, and lung damage. Current therapeutic approaches to bronchiectasis are heavily focused on management of infection along with enhancing mucus clearance. Long-term antibiotics have had limited success in clinical trials, suggesting a need to re-evaluate the concept of bronchiectasis as an infective disorder. We invoke the example of asthma, for which treatment paradigms shifted away from targeting smooth muscle constriction, towards permanently suppressing airway inflammation, reducing risk and ultimately inducing remission with precision anti-inflammatory treatments. In this Review, we argue that bronchiectasis is primarily a chronic inflammatory disease, requiring early identification of at-risk individuals, and we introduce a novel concept of disease activity with important implications for clinical practice and future research. A new generation of novel anti-inflammatory treatments are under development and repurposing of anti-inflammatory agents from other diseases could revolutionise patient care.
{"title":"Rethinking bronchiectasis as an inflammatory disease.","authors":"Merete B Long, Sanjay H Chotirmall, Michal Shteinberg, James D Chalmers","doi":"10.1016/S2213-2600(24)00176-0","DOIUrl":"https://doi.org/10.1016/S2213-2600(24)00176-0","url":null,"abstract":"<p><p>Bronchiectasis is understood to be the result of a complex interaction between infection, impaired mucociliary clearance, inflammation, and lung damage. Current therapeutic approaches to bronchiectasis are heavily focused on management of infection along with enhancing mucus clearance. Long-term antibiotics have had limited success in clinical trials, suggesting a need to re-evaluate the concept of bronchiectasis as an infective disorder. We invoke the example of asthma, for which treatment paradigms shifted away from targeting smooth muscle constriction, towards permanently suppressing airway inflammation, reducing risk and ultimately inducing remission with precision anti-inflammatory treatments. In this Review, we argue that bronchiectasis is primarily a chronic inflammatory disease, requiring early identification of at-risk individuals, and we introduce a novel concept of disease activity with important implications for clinical practice and future research. A new generation of novel anti-inflammatory treatments are under development and repurposing of anti-inflammatory agents from other diseases could revolutionise patient care.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-05-21DOI: 10.1016/S2213-2600(24)00145-0
Thomas Engelhardt, Nicola Disma
{"title":"Paediatric anaesthesia: it is not only what you do, but how you do it.","authors":"Thomas Engelhardt, Nicola Disma","doi":"10.1016/S2213-2600(24)00145-0","DOIUrl":"10.1016/S2213-2600(24)00145-0","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-05-02DOI: 10.1016/S2213-2600(24)00072-9
Robert P Frantz, Vallerie V McLaughlin, Sandeep Sahay, Pilar Escribano Subías, Ronald L Zolty, Raymond L Benza, Richard N Channick, Kelly M Chin, Anna R Hemnes, Luke S Howard, Olivier Sitbon, Jean-Luc Vachiéry, Roham T Zamanian, Matt Cravets, Robert F Roscigno, David Mottola, Robin Osterhout, Jean-Marie Bruey, Erin Elman, Cindy-Ann Tompkins, Ed Parsley, Richard Aranda, Lawrence S Zisman, Hossein-Ardeschir Ghofrani
Background: Morbidity and mortality in pulmonary arterial hypertension (PAH) remain high. Activation of platelet-derived growth factor receptor, colony stimulating factor 1 receptor, and mast or stem cell growth factor receptor kinases stimulates inflammatory, proliferative, and fibrotic pathways driving pulmonary vascular remodelling in PAH. Seralutinib, an inhaled kinase inhibitor, targets these pathways. We aimed to evaluate the efficacy and safety of seralutinib in patients with PAH receiving standard background therapy.
Methods: The TORREY trial was a phase 2, randomised, multicentre, multinational, double-blind, placebo-controlled study. Patients with PAH from 40 hospital and community sites were randomly assigned 1:1 via interactive response technologies to receive seralutinib (60 mg twice daily for 2 weeks, then increased to 90 mg twice daily as tolerated) or placebo by dry powder inhaler twice daily for 24 weeks. Randomisation was stratified by baseline pulmonary vascular resistance (PVR; <800 dyne·s/cm5 and ≥800 dyne·s/cm5). Patients were eligible if classified as WHO Group 1 PH (PAH), WHO Functional Class II or III, with a PVR of 400 dyne·s/cm5 or more, and a 6 min walk distance of between 150 m and 550 m. The primary endpoint was change in PVR from baseline to 24 weeks. Analyses for efficacy endpoints were conducted in randomly assigned patients (intention-to-treat population). Safety analyses included all patients who received the study drug. TORREY was registered with ClinicalTrials.gov (NCT04456998) and EudraCT (2019-002669-37) and is completed.
Findings: From Nov 12, 2020, to April 20, 2022, 151 patients were screened for eligibility, and following exclusions, 86 adults receiving PAH background therapy were randomly assigned to seralutinib (n=44; four male, 40 female) or placebo (n=42; four male, 38 female), and comprised the intention-to-treat population. At baseline, treatment groups were balanced except for a higher representation of WHO Functional Class II patients in the seralutinib group. The least squares mean change from baseline to week 24 in PVR was 21·2 dyne·s/cm5 (95% CI -37·4 to 79·8) for the placebo group and -74·9 dyne·s/cm5 (-139·7 to -10·2) for the seralutinib group. The least squares mean difference between the seralutinib and placebo groups for change in PVR was -96·1 dyne·s/cm5 (95% CI -183·5 to -8·8; p=0·03). The most common treatment-emergent adverse event in both treatment groups was cough: 16 (38%) of 42 patients in the placebo group; 19 (43%) of 44 patients in the seralutinib group.
Interpretation: Treatment with inhaled seralutinib significantly decreased PVR, meeting the primary endpoint of the study among patients receiving background therapy for PAH.
Funding: Gossamer Bio.
背景:肺动脉高压(PAH)的发病率和死亡率居高不下。血小板衍生生长因子受体、集落刺激因子 1 受体和肥大细胞或干细胞生长因子受体激酶的激活刺激了炎症、增殖和纤维化途径,推动了 PAH 的肺血管重塑。塞拉鲁替尼是一种吸入性激酶抑制剂,可靶向这些通路。我们旨在评估塞拉鲁替尼对接受标准背景疗法的 PAH 患者的疗效和安全性:TORREY试验是一项2期、随机、多中心、跨国、双盲、安慰剂对照研究。来自40家医院和社区的PAH患者通过交互响应技术以1:1的比例随机分配到接受塞拉鲁替尼(60毫克,每天两次,连续2周,然后在耐受的情况下增加到90毫克,每天两次)或安慰剂治疗,干粉吸入剂每天两次,连续24周。根据基线肺血管阻力(PVR;5 和≥800 dyne-s/cm5)进行分层随机化。如果患者被归类为WHO第1组PH(PAH)、WHO功能分级II级或III级、PVR大于或等于400 dyne-s/cm5、6分钟步行距离在150米至550米之间,则符合条件。疗效终点分析在随机分配的患者(意向治疗人群)中进行。安全性分析包括所有接受研究药物的患者。TORREY已在ClinicalTrials.gov(NCT04456998)和EudraCT(2019-002669-37)注册,研究结果已完成:从2020年11月12日至2022年4月20日,共筛选出151名符合条件的患者,经排除后,86名接受PAH背景治疗的成人被随机分配到seralutinib(n=44;4名男性,40名女性)或安慰剂(n=42;4名男性,38名女性)治疗组,并构成意向治疗人群。基线时,各治疗组之间的比例均衡,只是Seralutinib组中WHO功能II级患者的比例较高。从基线到第24周,安慰剂组PVR的最小平方均值变化为21-2 dyne-s/cm5(95% CI -37-4至79-8),而塞拉鲁替尼组PVR的最小平方均值变化为-74-9 dyne-s/cm5(-139-7至-10-2)。在PVR变化方面,塞拉鲁替尼组与安慰剂组之间的最小二乘均值差为-96-1 dyne-s/cm5(95% CI -183-5 to -8-8;P=0-03)。两个治疗组中最常见的治疗突发不良事件是咳嗽:安慰剂组42名患者中有16名(38%)咳嗽;塞拉鲁替尼组44名患者中有19名(43%)咳嗽:在接受背景治疗的PAH患者中,吸入塞拉鲁替尼治疗可显著降低PVR,达到了研究的主要终点:Gossamer Bio.
{"title":"Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial.","authors":"Robert P Frantz, Vallerie V McLaughlin, Sandeep Sahay, Pilar Escribano Subías, Ronald L Zolty, Raymond L Benza, Richard N Channick, Kelly M Chin, Anna R Hemnes, Luke S Howard, Olivier Sitbon, Jean-Luc Vachiéry, Roham T Zamanian, Matt Cravets, Robert F Roscigno, David Mottola, Robin Osterhout, Jean-Marie Bruey, Erin Elman, Cindy-Ann Tompkins, Ed Parsley, Richard Aranda, Lawrence S Zisman, Hossein-Ardeschir Ghofrani","doi":"10.1016/S2213-2600(24)00072-9","DOIUrl":"10.1016/S2213-2600(24)00072-9","url":null,"abstract":"<p><strong>Background: </strong>Morbidity and mortality in pulmonary arterial hypertension (PAH) remain high. Activation of platelet-derived growth factor receptor, colony stimulating factor 1 receptor, and mast or stem cell growth factor receptor kinases stimulates inflammatory, proliferative, and fibrotic pathways driving pulmonary vascular remodelling in PAH. Seralutinib, an inhaled kinase inhibitor, targets these pathways. We aimed to evaluate the efficacy and safety of seralutinib in patients with PAH receiving standard background therapy.</p><p><strong>Methods: </strong>The TORREY trial was a phase 2, randomised, multicentre, multinational, double-blind, placebo-controlled study. Patients with PAH from 40 hospital and community sites were randomly assigned 1:1 via interactive response technologies to receive seralutinib (60 mg twice daily for 2 weeks, then increased to 90 mg twice daily as tolerated) or placebo by dry powder inhaler twice daily for 24 weeks. Randomisation was stratified by baseline pulmonary vascular resistance (PVR; <800 dyne·s/cm<sup>5</sup> and ≥800 dyne·s/cm<sup>5</sup>). Patients were eligible if classified as WHO Group 1 PH (PAH), WHO Functional Class II or III, with a PVR of 400 dyne·s/cm<sup>5</sup> or more, and a 6 min walk distance of between 150 m and 550 m. The primary endpoint was change in PVR from baseline to 24 weeks. Analyses for efficacy endpoints were conducted in randomly assigned patients (intention-to-treat population). Safety analyses included all patients who received the study drug. TORREY was registered with ClinicalTrials.gov (NCT04456998) and EudraCT (2019-002669-37) and is completed.</p><p><strong>Findings: </strong>From Nov 12, 2020, to April 20, 2022, 151 patients were screened for eligibility, and following exclusions, 86 adults receiving PAH background therapy were randomly assigned to seralutinib (n=44; four male, 40 female) or placebo (n=42; four male, 38 female), and comprised the intention-to-treat population. At baseline, treatment groups were balanced except for a higher representation of WHO Functional Class II patients in the seralutinib group. The least squares mean change from baseline to week 24 in PVR was 21·2 dyne·s/cm<sup>5</sup> (95% CI -37·4 to 79·8) for the placebo group and -74·9 dyne·s/cm<sup>5</sup> (-139·7 to -10·2) for the seralutinib group. The least squares mean difference between the seralutinib and placebo groups for change in PVR was -96·1 dyne·s/cm<sup>5</sup> (95% CI -183·5 to -8·8; p=0·03). The most common treatment-emergent adverse event in both treatment groups was cough: 16 (38%) of 42 patients in the placebo group; 19 (43%) of 44 patients in the seralutinib group.</p><p><strong>Interpretation: </strong>Treatment with inhaled seralutinib significantly decreased PVR, meeting the primary endpoint of the study among patients receiving background therapy for PAH.</p><p><strong>Funding: </strong>Gossamer Bio.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-06-05DOI: 10.1016/S2213-2600(24)00175-9
Linsey Wehner, Atul Malhotra, Jeremy Orr
{"title":"Living with spinal muscular atrophy while working in critical care.","authors":"Linsey Wehner, Atul Malhotra, Jeremy Orr","doi":"10.1016/S2213-2600(24)00175-9","DOIUrl":"10.1016/S2213-2600(24)00175-9","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-05-21DOI: 10.1016/S2213-2600(24)00115-2
Susan Humphreys, Britta S von Ungern-Sternberg, Fiona Taverner, Andrew Davidson, Justin Skowno, Ben Hallett, David Sommerfield, Neil Hauser, Tara Williams, Susan Spall, Trang Pham, Tiffany Atkins, Mark Jones, Emma King, Laura Burgoyne, Philip Stephens, Shyan Vijayasekaran, Nicola Slee, Hannah Burns, Donna Franklin, Judith Hough, Andreas Schibler
Background: Tubeless upper airway surgery in children is a complex procedure in which surgeons and anaesthetists share the same operating field. These procedures are often interrupted for rescue oxygen therapy. The efficacy of nasal high-flow oxygen to decrease the frequency of rescue interruptions in children undergoing upper airway surgery is unknown.
Methods: In this multicentre randomised trial conducted in five tertiary hospitals in Australia, children aged 0-16 years who required tubeless upper airway surgery were randomised (1:1) by a web-based randomisation tool to either nasal high-flow oxygen delivery or standard oxygen therapy (oxygen flows of up to 6 L/min). Randomisation was stratified by site and age (<1 year, 1-4 years, and 5-16 years). Subsequent tubeless upper airway surgery procedures in the same child could be included if there were more than 2 weeks between the procedures, and repeat surgical procedures meeting this condition were considered to be independent events. The oxygen therapy could not be masked, but the investigators remained blinded until outcome data were locked. The primary outcome was successful anaesthesia without interruption of the surgical procedure for rescue oxygenation. A rescue oxygenation event was defined as an interruption of the surgical procedure to deliver positive pressure ventilation using either bag mask technique, insertion of an endotracheal tube, or laryngeal mask to improve oxygenation. There were ten secondary outcomes, including the proportion of procedures with a hypoxaemic event (SpO2 <90%). Analyses were done on an intention-to-treat (ITT) basis. Safety was assessed in all enrolled participants. This trial is registered in the Australian New Zealand Clinical Trials Registry, ACTRN12618000949280, and is completed.
Findings: From Sept 4, 2018, to April 12, 2021, 581 procedures in 487 children were randomly assigned to high-flow oxygen (297 procedures) or standard care (284 procedures); after exclusions, 528 procedures (267 assigned to high-flow oxygen and 261 assigned to standard care) in 483 children (293 male and 190 female) were included in the ITT analysis. The primary outcome of successful anaesthesia without interruption for tubeless airway surgery was achieved in 236 (88%) of 267 procedures on high-flow oxygen and in 229 (88%) of 261 procedures on standard care (adjusted risk ratio [RR] 1·02, 95% CI 0·96-1·08, p=0·82). There were 51 (19%) procedures with a hypoxaemic event in the high-flow oxygen group and 57 (22%) in the standard care group (RR 0·86, 95% CI 0·58-1·24). Of the other prespecified secondary outcomes, none showed a significant difference between groups. Adverse events of epistaxis, laryngospasm, bronchospasm, hypoxaemia, bradycardia, cardiac arrest, hypotension, or death were similar in both study groups.
Interpretation: Nasal high-flow oxygen during tubeless upper airw
{"title":"High-flow nasal oxygen for children's airway surgery to reduce hypoxaemic events: a randomised controlled trial.","authors":"Susan Humphreys, Britta S von Ungern-Sternberg, Fiona Taverner, Andrew Davidson, Justin Skowno, Ben Hallett, David Sommerfield, Neil Hauser, Tara Williams, Susan Spall, Trang Pham, Tiffany Atkins, Mark Jones, Emma King, Laura Burgoyne, Philip Stephens, Shyan Vijayasekaran, Nicola Slee, Hannah Burns, Donna Franklin, Judith Hough, Andreas Schibler","doi":"10.1016/S2213-2600(24)00115-2","DOIUrl":"10.1016/S2213-2600(24)00115-2","url":null,"abstract":"<p><strong>Background: </strong>Tubeless upper airway surgery in children is a complex procedure in which surgeons and anaesthetists share the same operating field. These procedures are often interrupted for rescue oxygen therapy. The efficacy of nasal high-flow oxygen to decrease the frequency of rescue interruptions in children undergoing upper airway surgery is unknown.</p><p><strong>Methods: </strong>In this multicentre randomised trial conducted in five tertiary hospitals in Australia, children aged 0-16 years who required tubeless upper airway surgery were randomised (1:1) by a web-based randomisation tool to either nasal high-flow oxygen delivery or standard oxygen therapy (oxygen flows of up to 6 L/min). Randomisation was stratified by site and age (<1 year, 1-4 years, and 5-16 years). Subsequent tubeless upper airway surgery procedures in the same child could be included if there were more than 2 weeks between the procedures, and repeat surgical procedures meeting this condition were considered to be independent events. The oxygen therapy could not be masked, but the investigators remained blinded until outcome data were locked. The primary outcome was successful anaesthesia without interruption of the surgical procedure for rescue oxygenation. A rescue oxygenation event was defined as an interruption of the surgical procedure to deliver positive pressure ventilation using either bag mask technique, insertion of an endotracheal tube, or laryngeal mask to improve oxygenation. There were ten secondary outcomes, including the proportion of procedures with a hypoxaemic event (SpO<sub>2</sub> <90%). Analyses were done on an intention-to-treat (ITT) basis. Safety was assessed in all enrolled participants. This trial is registered in the Australian New Zealand Clinical Trials Registry, ACTRN12618000949280, and is completed.</p><p><strong>Findings: </strong>From Sept 4, 2018, to April 12, 2021, 581 procedures in 487 children were randomly assigned to high-flow oxygen (297 procedures) or standard care (284 procedures); after exclusions, 528 procedures (267 assigned to high-flow oxygen and 261 assigned to standard care) in 483 children (293 male and 190 female) were included in the ITT analysis. The primary outcome of successful anaesthesia without interruption for tubeless airway surgery was achieved in 236 (88%) of 267 procedures on high-flow oxygen and in 229 (88%) of 261 procedures on standard care (adjusted risk ratio [RR] 1·02, 95% CI 0·96-1·08, p=0·82). There were 51 (19%) procedures with a hypoxaemic event in the high-flow oxygen group and 57 (22%) in the standard care group (RR 0·86, 95% CI 0·58-1·24). Of the other prespecified secondary outcomes, none showed a significant difference between groups. Adverse events of epistaxis, laryngospasm, bronchospasm, hypoxaemia, bradycardia, cardiac arrest, hypotension, or death were similar in both study groups.</p><p><strong>Interpretation: </strong>Nasal high-flow oxygen during tubeless upper airw","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}