{"title":"Progress in Progressive Pulmonary Fibrosis.","authors":"Jesse Roman","doi":"10.1164/rccm.202505-1152ED","DOIUrl":"https://doi.org/10.1164/rccm.202505-1152ED","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537780","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}
Erik H A Michels,Hessel Peters-Sengers,Justin de Brabander,Alex R Schuurman,Tom D Y Reijnders,Bastiaan W Haak,Xanthe Brands,Sebastiaan C M Joosten,Daniël R Faber,Olaf L Cremer,Renée A Douma,Alex F de Vos,W Joost Wiersinga,Joe M Butler,Tom van der Poll
{"title":"The Plasma Proteome in Community-acquired Pneumonia: Pathophysiology, Outcome and 10-Year Risk.","authors":"Erik H A Michels,Hessel Peters-Sengers,Justin de Brabander,Alex R Schuurman,Tom D Y Reijnders,Bastiaan W Haak,Xanthe Brands,Sebastiaan C M Joosten,Daniël R Faber,Olaf L Cremer,Renée A Douma,Alex F de Vos,W Joost Wiersinga,Joe M Butler,Tom van der Poll","doi":"10.1164/rccm.202502-0325oc","DOIUrl":"https://doi.org/10.1164/rccm.202502-0325oc","url":null,"abstract":"RATIONALECommunity-acquired pneumonia (CAP) represents a significant health burden.OBJECTIVESWe aimed to map the plasma proteome in patients with CAP and associate protein abundance with pathophysiology, tissue source, and outcome.METHODSWe measured the plasma proteome of CAP patients upon admission to a general ward using Olink technology (derivation cohort). Additional Olink measurements were performed in CAP patients admitted to the intensive care unit (ICU) and SARS-CoV-2 pneumonia patients across care settings (validation cohorts).MEASUREMENTS AND MAIN RESULTSOf 2676 proteins analysed in 93 ward-CAP patients and 21 healthy controls, 904 (33.8%) were higher in CAP, 396 (14.8%) lower, and 1376 (51.4%) not different. More abundant proteins were associated with innate immune and mitosis pathways, and mainly originated from lung and cardiac tissue. 131 proteins associated with time to clinical stability (TCS), of which 124 (primarily related to monocyte/macrophage and RNA processing) were connected with a long TCS. Most TCS-associated proteins were differentially abundant in non-survivors versus survivors amongst 88 ICU-CAP (1.4- to 3.5-fold higher) and 305 SARS-CoV-2 pneumonia patients (1.16- to 1.35-fold lower or 1.14- to 2.65-fold higher; all p<0.05). In the general population (UK Biobank), 115 of 124 (92.7%) proteins correlated with long TCS were associated with an increased risk of pneumonia during a 10-year follow-up, while 6 of 7 (85.7%) proteins correlated with shorter TCS were associated with a lower risk of pneumonia.CONCLUSIONSThis now publicly available CAP plasma proteome provides information on pathophysiological mechanisms and tissue involvement, and may support development of personalised therapies.","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"13 1","pages":""},"PeriodicalIF":24.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533584","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}
Yuderleys Masias-Leon, Carlos E Ruiz-Gonzalez, Oscar J Nino-Meza, Medha Singh, Mona O Sarhan, Xueyi Chen, Kelly Flavahan, Amy Kronenberg, Elizabeth W Tucker, Joel S Freundlich, Martin A Lodge, Laurence S Carroll, Nicole Parrish, Noah Lechtzin, Sanjay K Jain
{"title":"Dynamic <sup>11</sup>C-<i>Para</i>-Aminobenzoic Acid Positron Emission Tomography/Computed Tomography for Visualizing Pulmonary <i>Mycobacteroides abscessus</i> Infections.","authors":"Yuderleys Masias-Leon, Carlos E Ruiz-Gonzalez, Oscar J Nino-Meza, Medha Singh, Mona O Sarhan, Xueyi Chen, Kelly Flavahan, Amy Kronenberg, Elizabeth W Tucker, Joel S Freundlich, Martin A Lodge, Laurence S Carroll, Nicole Parrish, Noah Lechtzin, Sanjay K Jain","doi":"10.1164/rccm.202409-1792OC","DOIUrl":"10.1164/rccm.202409-1792OC","url":null,"abstract":"<p><p><b>Rationale:</b> <i>Mycobacteroides abscessus</i> infections affect immunocompromised patients and those with underlying pulmonary disease. Conventional imaging cannot distinguish <i>M. abscessus</i> infections from underlying pulmonary disease or sterile inflammation, requiring invasive procedures for definitive diagnosis. <b>Objectives:</b> We evaluated <sup>11</sup>C-<i>para</i>-aminobenzoic acid (<sup>11</sup>C-PABA), a chemically identical radioanalog of PABA, to detect and localize infections due to <i>M. abscessus</i>. <b>Methods:</b> <i>In vitro</i> uptake assays were performed to test the metabolism and accumulation of PABA into <i>M. abscessus</i> reference and clinical isolates. Dynamic <sup>11</sup>C-PABA positron emission tomography (PET) was performed in a mouse model of <i>M. abscessus</i> pulmonary infection and in a patient with microbiologically confirmed <i>M. abscessus</i> pulmonary infection (NCT05611905). <b>Measurements and Main Results:</b> <sup>11</sup>C-PABA was intracellularly metabolized by <i>M. abscessus</i> to <sup>11</sup>C-7,8-dihydropteroate. In addition, the reference strain and all 13 randomly chosen clinical isolates, including 3 resistant to trimethoprim-sulfamethoxazole, rapidly accumulated PABA. No PABA accumulation was noted by heat-inactivated bacteria or mammalian cells. Dynamic <sup>11</sup>C-PABA PET in a mouse model of <i>M. abscessus</i> pulmonary infection rapidly distinguished infection from sterile inflammation and also accurately monitored response to antibiotic treatment. Finally, dynamic <sup>11</sup>C-PABA PET in a 33-year-old woman with cystic fibrosis and microbiologically confirmed <i>M. abscessus</i> pulmonary infection was safe and demonstrated significantly higher and sustained PET uptake in the affected lesions. <b>Conclusions:</b> <sup>11</sup>C-PABA PET is an innovative, clinically translatable, noninvasive, bacteria-specific diagnostic to differentiate <i>M. abscessus</i> infections from underlying pulmonary disease in patients. This tool could also help in monitoring treatment responses and enable precision medicine approaches for patients with complicated infections.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1253-1263"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735565","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}
{"title":"Publication Bias: For How Much Longer?","authors":"Fernando M de Benedictis","doi":"10.1164/rccm.202502-0482LE","DOIUrl":"10.1164/rccm.202502-0482LE","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1316-1317"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966394","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}
Maeve Georgia MacMurdo, Hasan Bayram, Emily Brigham, Daniel P Croft, Gillian C Goobie, Alison G Lee, Laura C Myers, Nicholas Nassikas, Jared Radbel
{"title":"Letting Cooler Heads Prevail: The Necessity of Occupational Regulation of Heat and Smoke Exposure.","authors":"Maeve Georgia MacMurdo, Hasan Bayram, Emily Brigham, Daniel P Croft, Gillian C Goobie, Alison G Lee, Laura C Myers, Nicholas Nassikas, Jared Radbel","doi":"10.1164/rccm.202502-0466VP","DOIUrl":"10.1164/rccm.202502-0466VP","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1130-1131"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970259","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}
Ary Serpa Neto, Lisa Higgins, Elizabeth Lorenzi, Lindsay Berry, Elizabeth Ryan, Stephane Heritier, Shannah Anderson, Judit Orosz, Aidan Burrell, Zoe McQuilten, Priya Nair, Carol L Hodgson
{"title":"Development of a New Longitudinal Ordinal Outcome for Clinical Trials in Extracorporeal Membrane Oxygenation Patients.","authors":"Ary Serpa Neto, Lisa Higgins, Elizabeth Lorenzi, Lindsay Berry, Elizabeth Ryan, Stephane Heritier, Shannah Anderson, Judit Orosz, Aidan Burrell, Zoe McQuilten, Priya Nair, Carol L Hodgson","doi":"10.1164/rccm.202408-1582OC","DOIUrl":"10.1164/rccm.202408-1582OC","url":null,"abstract":"<p><p><b>Rationale:</b> Randomized clinical trials in intensive care often prioritize disease-focused outcomes rather than patient-centered outcomes. <b>Objectives:</b> To report and evaluate the DOSE (daily organ support for patients on extracorporeal membrane oxygenation [ECMO]) outcome. This is a new longitudinal ordinal outcome for clinical trials in patients receiving ECMO. <b>Methods:</b> A prospective, multicenter study was conducted at 28 hospitals in Australia and New Zealand. Adult patients admitted to participating ICUs between February 2019 and September 2023 who received any type of ECMO were included. The DOSE outcome was created considering <i>1</i>) death, <i>2</i>) receiving ECMO, <i>3</i>) ventilated but not receiving ECMO, <i>4</i>) in an ICU but not ventilated, <i>5</i>) in a hospital ward, and <i>6</i>) discharged from the hospital. DOSE was developed in collaboration with consumers and other stakeholders and validated against death and new disability at 6 months. Simulations were performed to compare the power obtained against 28-day mortality alone. <b>Measurements and Main Results:</b> Among 1,375 patients who received ECMO (median age, 52 yr; 34% women), at Day 90, 42%, 29%, and 66% of those receiving venoarterial, venovenous ECMO, or extracorporeal cardiopulmonary resuscitation were deceased, respectively. DOSE accurately predicted death and new disability at 6 months (area under the curve > 0.800). With a sample size of 400 patients per arm and an odds ratio of 1.20, DOSE provided 56% more power than an analysis considering 28-day mortality alone (36% vs. 91%) in simulations of a two-arm clinical trial. <b>Conclusions:</b> The DOSE outcome performed well compared with a patient-centered outcome. Compared with 28-day mortality, DOSE provided more statistical power in a simulated two-arm clinical trial.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1220-1228"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735547","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}
Georgios D Kitsios, Menaal Haque, William G Bain, Charles Dela Cruz, Bryan J McVerry, Faraaz A Shah
{"title":"Clinician Prediction of Hyperinflammatory Acute Respiratory Distress Syndrome Subphenotypes: Overestimated but Prognostic.","authors":"Georgios D Kitsios, Menaal Haque, William G Bain, Charles Dela Cruz, Bryan J McVerry, Faraaz A Shah","doi":"10.1164/rccm.202409-1816RL","DOIUrl":"10.1164/rccm.202409-1816RL","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1294-1297"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770932","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}
Chung-Chu Tung, Wen-Bin Yeh, Renin Chang, Wei-Kai Lee
{"title":"Methodological Considerations in the Study of Preserved-Ratio Impaired Spirometry and Dementia Risk.","authors":"Chung-Chu Tung, Wen-Bin Yeh, Renin Chang, Wei-Kai Lee","doi":"10.1164/rccm.202411-2115LE","DOIUrl":"10.1164/rccm.202411-2115LE","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1306"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956442","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}
Matthieu Legrand, Edouard Jullien, Antoine Kimmoun, Guillaume Geri, Hafid Ait-Oufella, Stanislas Abrard, Samuel Gaugain, Fanny Bounes, Philippe Guerci, Julien Pottecher, Matthieu Jamme, Yves Poncelin de Raucourt, Damien Barraud, Jean-Michel Constantin, William Juguet, Sigismond Lasocki, Romain Sonneville, Juliette Audibert, Gaëtan Plantefève, Olivier Ellrodt, Anne-Laure Fedou, Marc Leone, Laurent Lefebvre, Adrien Auvet, David Chen, Eric Vicaut, François Dépret
{"title":"Iloprost for the Treatment of Severe Septic Shock with Persistent Hypoperfusion: A Double-Blind, Randomized Controlled Trial.","authors":"Matthieu Legrand, Edouard Jullien, Antoine Kimmoun, Guillaume Geri, Hafid Ait-Oufella, Stanislas Abrard, Samuel Gaugain, Fanny Bounes, Philippe Guerci, Julien Pottecher, Matthieu Jamme, Yves Poncelin de Raucourt, Damien Barraud, Jean-Michel Constantin, William Juguet, Sigismond Lasocki, Romain Sonneville, Juliette Audibert, Gaëtan Plantefève, Olivier Ellrodt, Anne-Laure Fedou, Marc Leone, Laurent Lefebvre, Adrien Auvet, David Chen, Eric Vicaut, François Dépret","doi":"10.1164/rccm.202410-1924OC","DOIUrl":"10.1164/rccm.202410-1924OC","url":null,"abstract":"<p><p><b>Rationale:</b> Preclinical and preliminary clinical data suggest that iloprost may improve tissue perfusion in septic shock. However, its effect on organ failure remains unclear. <b>Objectives:</b> To investigate whether iloprost provides organ protection in septic shock with hypoperfusion. <b>Methods:</b> In this multicenter, double-blind, randomized controlled trial, adults with septic shock and persistent hypoperfusion (i.e., increased capillary refill time and/or skin mottling) were randomized to receive a 48-hour intravenous infusion of iloprost or placebo. The primary outcome was the change in the Sequential Organ Failure Assessment (SOFA) score from randomization to Day 7. Secondary outcomes included mortality at Day 28, organ support-free days by Day 28, and mean daily SOFA score. <b>Measurements and Main Results:</b> A total of 240 patients were randomized, and 236 were included in the analysis. Median (IQR) changes in SOFA score were -4 (-7 to 7) in the iloprost group and -5 (-8 to 5) in the placebo group (median difference, 1; 95% CI, 0-3; <i>P</i> = 0.12). At 28 days, 48 patients (42%) had died in the iloprost group and 47 (39%) had died in the placebo group (relative risk, 1.08; 95% CI, 0.80-1.5). The median average SOFA score was 11.2 (7.4-15.9) in the iloprost group, compared with 10.5 (6.8-16.5) in the placebo group (median difference, 0.25; 95% CI, -1.1 to 1.8). Median (95% confidence interval) between-group differences in 28-day ventilation-, vasopressor-, and renal replacement therapy-free survival days were 0 (0-0), 0 (-1 to 1), and 0 (0-0), respectively. Severe adverse events occurred in 15% of patients in the iloprost group and 7% of patients in the placebo group (<i>P</i> = 0.06). <b>Conclusions:</b> Among patients with septic shock and persistent hypoperfusion, iloprost did not reduce the severity of organ failure. Clinical trial registered with www.clinicaltrials.gov (NCT03788837) and EudraCT (2018-001709-10).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1211-1219"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092574","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}
Mohsen Sadatsafavi, Trung N Tran, Ghislaine Scelo, Ming-Ju Tsai, John Busby, Benjamin Emmanuel, Liam G Heaney, Christine Jenkins, Flavia Hoyte, Giorgio Walter Canonica, Rohit Katial, Enrico Heffler, Eileen Wang, Francesca Puggioni, Michael E Wechsler, Ledit R F Ardusso, Jorge Máspero, Martin Sivori, Cathy Emmas, Andrew N Menzies-Gow, Neda Stjepanovic, Sinthia Z Bosnic-Anticevich, Belinda Cochrane, Eve Denton, Peter G Gibson, Mark Hew, Peter G Middleton, Matthew J Peters, Guy G Brusselle, Renaud Louis, Florence Schleich, George C Christoff, Todor A Popov, Celine Bergeron, Mohit Bhutani, Kenneth R Chapman, Andréanne Côté, Simon Couillard, Delbert R Dorscheid, Libardo Jiménez-Maldonado, Ivan Solarte, Carlos A Torres-Duque, Susanne Hansen, Celeste M Porsbjerg, Charlotte Suppli Ulrik, Alan Altraja, Arnaud Bourdin, Konstantinos P Exarchos, Athena Gogali, Konstantinos Kostikas, Michael P Makris, Andriana I Papaioannou, Patrick D Mitchell, Takashi Iwanaga, Tatsuya Nagano, Yuji Tohda, Mona S Al-Ahmad, Désirée Larenas-Linnemann, Bernt Bøgvald Aarli, Piotr Kuna, Cláudia Chaves Loureiro, Riyad Al-Lehebi, Adeeb A Bulkhi, Wenjia Chen, Yah Ru Juang, Mariko Siyue Koh, Anqi Liu, Chin Kook Rhee, Borja G Cosio, Luis Perez-de-Llano, Diahn-Warng Perng, Chau-Chyun Sheu, Hao-Chien Wang, Bassam Mahboub, Laila Salameh, David J Jackson, Pujan H Patel, Paul E Pfeffer, Njira Lugogo, Roy Alton Pleasants, Aaron Beastall, Lakmini Bulathsinhala, Victoria Carter, Nevaashni Eleangovan, Kirsty Fletton, John Townend, Ruth B Murray, David B Price
{"title":"Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics.","authors":"Mohsen Sadatsafavi, Trung N Tran, Ghislaine Scelo, Ming-Ju Tsai, John Busby, Benjamin Emmanuel, Liam G Heaney, Christine Jenkins, Flavia Hoyte, Giorgio Walter Canonica, Rohit Katial, Enrico Heffler, Eileen Wang, Francesca Puggioni, Michael E Wechsler, Ledit R F Ardusso, Jorge Máspero, Martin Sivori, Cathy Emmas, Andrew N Menzies-Gow, Neda Stjepanovic, Sinthia Z Bosnic-Anticevich, Belinda Cochrane, Eve Denton, Peter G Gibson, Mark Hew, Peter G Middleton, Matthew J Peters, Guy G Brusselle, Renaud Louis, Florence Schleich, George C Christoff, Todor A Popov, Celine Bergeron, Mohit Bhutani, Kenneth R Chapman, Andréanne Côté, Simon Couillard, Delbert R Dorscheid, Libardo Jiménez-Maldonado, Ivan Solarte, Carlos A Torres-Duque, Susanne Hansen, Celeste M Porsbjerg, Charlotte Suppli Ulrik, Alan Altraja, Arnaud Bourdin, Konstantinos P Exarchos, Athena Gogali, Konstantinos Kostikas, Michael P Makris, Andriana I Papaioannou, Patrick D Mitchell, Takashi Iwanaga, Tatsuya Nagano, Yuji Tohda, Mona S Al-Ahmad, Désirée Larenas-Linnemann, Bernt Bøgvald Aarli, Piotr Kuna, Cláudia Chaves Loureiro, Riyad Al-Lehebi, Adeeb A Bulkhi, Wenjia Chen, Yah Ru Juang, Mariko Siyue Koh, Anqi Liu, Chin Kook Rhee, Borja G Cosio, Luis Perez-de-Llano, Diahn-Warng Perng, Chau-Chyun Sheu, Hao-Chien Wang, Bassam Mahboub, Laila Salameh, David J Jackson, Pujan H Patel, Paul E Pfeffer, Njira Lugogo, Roy Alton Pleasants, Aaron Beastall, Lakmini Bulathsinhala, Victoria Carter, Nevaashni Eleangovan, Kirsty Fletton, John Townend, Ruth B Murray, David B Price","doi":"10.1164/rccm.202501-0246OC","DOIUrl":"10.1164/rccm.202501-0246OC","url":null,"abstract":"<p><p><b>Rationale:</b> Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. <b>Objective:</b> To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. <b>Methods:</b> This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. <b>Measurements and Main Results:</b> A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; <i>P</i> = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; <i>P</i> = 0.006), major cardiovascular events (0.65 [0.44-0.97]; <i>P</i> = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; <i>P</i> = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. <b>Conclusions:</b> Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1165-1174"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092575","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}