Lancet Respiratory Medicine最新文献

{"title":"Morphine for chronic breathlessness (MABEL) in the UK: a multi-site, parallel-group, dose titration, double-blind, randomised, placebo-controlled trial","authors":"Miriam J Johnson, Bronwen Williams, Catriona Keerie, Sharon Tuck, Simon Hart, Sabrina Bajwah, Nazia Chaudhuri, Mark Pearson, Judith Cohen, Rachael A Evans, David C Currow, Irene J Higginson, Peter Hall, Marek Atter, John Norrie, Marie T Fallon","doi":"10.1016/s2213-2600(25)00205-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00205-x","url":null,"abstract":"<h3>Background</h3>The effectiveness of opioids for breathlessness seen in laboratory-based studies has not been replicated in clinical trials. We aimed to assess the effectiveness of oral morphine for breathlessness in long-term conditions.<h3>Methods</h3>This phase 3, parallel-group, double-blind, placebo-controlled trial across 11 centres randomly assigned consenting adults (1:1, stratified by site and causal disease) with a modified Medical Research Council breathlessness score of 3 or more due to cardiorespiratory conditions to receive 5–10 mg twice daily oral long-acting morphine or placebo (as well as a blinded laxative) for 56 days. The primary outcome was worst breathlessness score in the past 24 h at day 28, measured using a numerical rating scale (NRS; 0=not breathless at all; 10=worst imaginable breathlessness). Secondary outcomes included physical activity levels, worst cough NRS, quality of life, and morphine-related toxicities. Patients who received at least one dose of study drug were eligible for inclusion in efficacy and safety analyses. The trial was registered with ISRCTN (ISRCTN87329095) and the EU Clinical Trials Register (EudraCT 2019-002479-33).<h3>Findings</h3>Between March 18, 2021, and Oct 26, 2023, 143 participants were randomly assigned to receive either morphine (73 participants) or placebo (67 participants) and were included in the analyses; three participants did not receive the allocated treatment. Participants had a mean age of 70·5 (SD 9·4) years, were mostly male (93 [66%]), and were mostly White (132 [94%]). By day 28, 64 (88%) participants in the morphine group versus 66 (99%) in the placebo group had 90% adherence or greater. We found no evidence of difference in worst breathlessness at day 28 (morphine 6·19 [95% CI 5·57 to 6·81] <em>vs</em> placebo 6·10 [5·44 to 6·76]; adjusted mean difference 0·09 [95% CI –0·57 to 0·75], p=0·78) or any secondary measure, except for improved cough seen at day 56 (adjusted mean difference –1·41 [–2·18 to –0·64]). Increased moderate to vigorous physical activity was seen at day 28 (adjusted mean difference 9·51 min/day [0·54–18·48]) but this was not significant after multiple-measures correction. The morphine group had more adverse events (251 <em>vs</em> 162), serious adverse events (15 <em>vs</em> three, of which three in the morphine group and zero in the placebo group were deemed to be related to the study), and study drug withdrawals (13 <em>vs</em> two). There were no treatment-related deaths.<h3>Interpretation</h3>We found no evidence that morphine improves worst breathlessness intensity. Further research is needed to understand whether there is any role for morphine in chronic breathlessness, but our findings do not support its use in this setting.<h3>Funding</h3>NIHR Health Technology Assessment programme (HTA Project 17/34/01)","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"141 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183104","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":"Morphine for chronic breathlessness: time to say goodbye","authors":"Marlies van Dijk, Huib A M Kerstjens","doi":"10.1016/s2213-2600(25)00237-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00237-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"97 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183103","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":"Dupilumab versus omalizumab in patients with chronic rhinosinusitis with nasal polyps and coexisting asthma (EVEREST): a multicentre, randomised, double-blind, head-to-head phase 4 trial","authors":"Eugenio De Corso, G Walter Canonica, Enrico Heffler, Michal Springer, Tomasz Grzegorzek, Miguel Viana, Zsuzsanna Horváth, Joaquim Mullol, Philippe Gevaert, Justin Michel, Anju T Peters, Martin Wagenmann, Sherif Zaghloul, Mei Zhang, Mark Corbett, Scott Nash, James T Angello, Amr Radwan, Yamo Deniz, Antonio Martin, Peter W Hellings","doi":"10.1016/s2213-2600(25)00287-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00287-5","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly driven by type 2 inflammation. The biologics dupilumab and omalizumab, which target drivers and mediators of type 2 inflammation (interleukin [IL]-4/IL-13 signaling and immunoglobulin E [IgE], respectively), are efficacious in treating CRSwNP but direct comparisons are few. In EVEREST (EValuating trEatment RESponses of dupilumab versus omalizumab), the first head-to-head trial in respiratory biologics, we aimed to compare the efficacy and safety of dupilumab and omalizumab in patients with severe CRSwNP who had mild, moderate, or severe asthma.&lt;h3&gt;Methods&lt;/h3&gt;EVEREST was an international, randomised, double-blind, phase 4 trial, conducted at 100 hospitals or clinical centres in 17 countries. Sites were selected with otolaryngology, pneumologist, allergist, and immunologist practices; needed to have previously conducted double-blind studies; and were required have nasal endoscopy and electrocardiogram machines. Eligible patients aged 18 years or older with severe uncontrolled CRSwNP (with a nasal polyp score of 5 or more [and ≥2 for each nostril]), symptoms of nasal congestion and loss of smell for at least 8 weeks before screening, and physician-diagnosed asthma. Patients were randomly assigned (1:1) to subcutaneous dupilumab 300 mg every 2 weeks or omalizumab weight-tiered and IgE-tiered dosing every 2 weeks or 4 weeks for 24 weeks, with background mometasone furoate nasal spray. Patients and investigators were masked to the study drugs. Primary endpoints were change from baseline in endoscopic nasal polyp score and University of Pennsylvania Smell Identification Test (UPSIT) at 24 weeks. Efficacy was assessed in the intention-to-treat population and safety was assessed in patients who received at least one dose of study medication. The trial was registered at ClinicalTrials.gov, &lt;span&gt;&lt;span&gt;NCT04998604&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;.&lt;h3&gt;Findings&lt;/h3&gt;Between Sept 27, 2021, and Dec 27, 2024, 819 individuals were screened for study inclusion, 459 were excluded (most common screen failures were: 167 did not meet nasal polyp score ≥5 or did not have ongoing symptoms of nasal congestion and loss of smell, 114 did not meet pre-bronchodilator FEV&lt;sub&gt;1&lt;/sub&gt; ≤85% predicted normal, and 99 did not meet eligibility as per omalizumab drug-dosing), and 360 participants were randomly assigned (181 assigned to the dupilumab group and 179 assigned to the omalizumab group). Of the 360 participants, 198 (55%) participants were male, 162 (45%) were female, and the mean age of the total population sample was 52 years (SD 13·1). Improvements were significantly greater with dupilumab than omalizumab for all primary and secondary efficacy endpoints at week 24. Least squares mean differences in change from","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"104 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183148","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":"Durvalumab, carboplatin, and etoposide in patients who are treatment-naive with extensive-stage small-cell lung cancer and poor performance status (NEJ045A): a single-arm phase 2 trial","authors":"Tetsuhiko Asao, Yu Saida, Satoshi Watanabe, Akira Kisohara, Kazuma Kishi, Ryo Morita, Taku Nakagawa, Yoko Tsukita, Naoki Furuya, Taichi Miyawaki, Nobuhisa Ishikawa, Tadaaki Yamada, Takahiro Tanaka, Satoshi Morita, Toshiaki Kikuchi, Makoto Maemondo, Kunihiko Kobayashi","doi":"10.1016/s2213-2600(25)00240-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00240-1","url":null,"abstract":"<h3>Background</h3>Treating patients with extensive-stage small-cell lung cancer (SCLC) with poor performance status poses considerable challenges. We aimed to evaluate the combination of an immune checkpoint inhibitor with platinum-based therapy in this population.<h3>Methods</h3>This open-label, single-arm phase 2 NEJ045A trial enrolled untreated patients with extensive-stage SCLC with performance status 2 or 3. Participants received four cycles of durvalumab, carboplatin, and etoposide, followed by durvalumab maintenance. A dose adjustment strategy was used, with initial reductions in carboplatin–etoposide dosages, subsequently adjusted based on adverse events, allowing for potential escalation. The primary endpoint was tolerability, assessed by the proportion of patients completing induction therapy. A key secondary endpoint was 1-year survival rate. This trial is registered at the Japan Registry of Clinical Trials (jRCTs031200319) and has been completed.<h3>Findings</h3>Between April 8, 2021, and Oct 3, 2023, 57 patients (performance status 2 n=43 and performance status 3 n=14) were enrolled with a median age of 73·5 years (IQR 69·0–77·5), 44 (79%) of 56 were male. 26 (67%; 80% CI 55·2–76·7; p&lt;0·0001) of 39 patients with performance status 2 and five (50%; 26·7–73·3; p=0·0088) of ten with performance status 3 completed induction therapy, exceeding the pre-specified threshold. Grade 3 or higher adverse events occurred in 52 (93%) of 56 patients, and 12 (21%) of 56 discontinued due to adverse events. The 1-year survival rates were 43·4% (80% CI 34·1–53·1) overall (p&lt;0·0001), 50·0% (39·1–60·9) in performance status 2 (p&lt;0·0001), and 18·2% (5·0–41·5) in performance status 3.<h3>Interpretation</h3>Durvalumab, carboplatin, and etoposide showed tolerability and promising efficacy as a first-line treatment for patients with untreated extensive-stage SCLC with poor performance status, supporting the integration of immune checkpoint inhibitors in this therapeutically challenging population.<h3>Funding</h3>AstraZeneca KK.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"1 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183253","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":"Country in Focus: Nigeria's push to clear the air at home","authors":"Paul Adepoju","doi":"10.1016/s2213-2600(25)00333-9","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00333-9","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"51 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140549","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":"Beyond the ventilator: rethinking daily evaluation of respiratory drive and effort","authors":"Denise Battaglini, Patricia R M Rocco","doi":"10.1016/s2213-2600(25)00326-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00326-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"69 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140552","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":"Pooled testing for TB: revisiting a cost-saving innovation","authors":"Vibol Iem, Rachel L Byrne, Tushar Garg, Victor Santos, Mohammed A Yassin, Immaculate Kathure, Valerie Flore Donkeng Donfack, Comfort Vuchas, Christopher R Bilder, Jacob Creswell, Stephen B Squire, Tom Wingfield","doi":"10.1016/s2213-2600(25)00328-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00328-5","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"11 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140551","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":"Chronic respiratory diseases and inhalers in Africa","authors":"Esther Nakkazi","doi":"10.1016/s2213-2600(25)00360-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00360-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"86 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127315","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":"Association of respiratory drive and effort with mortality and time to discharge in patients on mechanical ventilation in Canada: a longitudinal, prospective, registry-based cohort study","authors":"Jose Dianti, Leif Erik Lovblom, Mohammed A Iftikhar, Sarina Sahetya, Irene Telias, Martin Urner, Lorenzo Del Sorbo, Marcelo B P Amato, Arthur S Slutsky, Laurent Brochard, Niall D Ferguson, Eddy Fan, Ewan C Goligher","doi":"10.1016/s2213-2600(25)00297-8","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00297-8","url":null,"abstract":"<h3>Background</h3>Physiological data suggest that insufficient and excessive respiratory drive and effort during mechanical ventilation might injure the lung and diaphragm, but their clinical relevance is unknown.<h3>Methods</h3>In this prospective, registry-based cohort study from the Toronto Intensive Care Observational Registry, we included all adults on mechanical ventilation admitted to the medical-surgical intensive care unit (ICU) at Toronto General Hospital from June 25, 2019, to April 1, 2022. There were no exclusion criteria. We obtained daily measurements of drive (airway occlusion pressure, P_0·1), effort (expiratory occlusion pressure, P_occ), lung stress during spontaneous breathing (dynamic transpulmonary driving pressure, ΔP_L,dyn), and ventilator-delivered dynamic driving pressure (ΔP_aw,dyn) for the first 10 days of mechanical ventilation. Daily hazards of death in ICU or discharge alive from ICU were quantified using Cox proportional hazards models adjusted for changing severity of illness over time.<h3>Findings</h3>We included 1186 patients. 298 (25%) patients died during follow-up. P_0·1 and P_<em>occ</em> showed a non-linear association with the hazards of death and discharge alive (p≤0·024). In patients with a ratio of arterial partial pressure of oxygen to inspired fraction of oxygen (PaO₂:FiO₂) of 150 mm Hg or less, both low and high levels of P_0·1 and P_<em>occ</em> were associated with lower rate of ICU discharge; when PaO₂:FiO₂ was greater than 150 mm Hg, higher P_0·1 and P_<em>occ</em> were associated with accelerated ICU discharge (interaction p&lt;0·0001). High ΔP_{<em>L,dyn</em>} was associated with lower rate of ICU discharge (p&lt;0·0001), especially when PaO₂:FiO₂ was less than 150 mm Hg. Higher effort magnified the association between ΔP_{<em>aw,dyn</em>} and rate of discharge alive (interaction p=0·0052).<h3>Interpretation</h3>In patients on mechanical ventilation, insufficient or excessive respiratory drive and effort were associated with higher ICU mortality and lower rate of ICU discharge, particularly when oxygenation was more severely impaired. Elevated respiratory effort exacerbated the effect of ventilator-delivered driving pressure on outcome.<h3>Funding</h3>National Sanitarium Association, Canada.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"22 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089026","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":"Can the positive findings from POD1UM-304 improve patient care worldwide?","authors":"Francesca R Ogliari, Jessica Menis, Lizza E L Hendriks","doi":"10.1016/s2213-2600(25)00260-7","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00260-7","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"129 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089027","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}