Lancet Respiratory Medicine最新文献

{"title":"Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial.","authors":"Olivier Sitbon, Andris Skride, Jeremy Feldman, Sandeep Sahay, Oksana A Shlobin, Vallerie McLaughlin, Hossein-Ardeschir Ghofrani, David Langleben, Ed Parsley, Gwyn D'Souza, Tonya Marmon, Watiri Kamau-Kelley, Renee Jones, Ravi Grewal, Steve Wring, Michelle Palacios, Himanshu Naik, Jill Denning, Howard M Lazarus, Marc Humbert","doi":"10.1016/S2213-2600(24)00226-1","DOIUrl":"10.1016/S2213-2600(24)00226-1","url":null,"abstract":"<p><strong>Background: </strong>The role of serotonin in pulmonary arterial hypertension has been extensively studied in recent decades, with preclinical data strongly indicating involvement in disease pathogenesis; however, clinical studies have yielded mixed results.</p><p><strong>Methods: </strong>ELEVATE-2 was a phase 2b dose-ranging, randomised, double-blind, placebo-controlled, multicentre trial investigating rodatristat ethyl as a treatment for patients with pulmonary arterial hypertension. The study was conducted at 64 sites across 16 countries in Europe and North America. Eligible participants were aged 18 years or older, had pulmonary arterial hypertension with WHO functional class II or III symptom severity, and had received a stable dose and regimen of one or more pulmonary arterial hypertension treatments for at least 12 weeks. Participants were randomly assigned 1:1:1 to receive two placebo tablets, one placebo and one rodatristat ethyl 300 mg tablet, or two rodatristat ethyl 300 mg tablets twice daily using an interactive response system. Participants, investigators, site personnel, and sponsors were masked to treatment allocation. Participants who completed the 24 week treatment period were invited to continue in an open-label extension. The primary endpoint was percent change in pulmonary vascular resistance (PVR) from baseline to week 24. Primary efficacy analyses were conducted on the intention-to-treat population and analyses of harms were conducted in the safety population, which included all patients who received any amount of the study drug. This trial is registered with ClinicalTrials.gov, NCT04712669, and is now complete.</p><p><strong>Findings: </strong>Between March 18, 2021 and Dec 13, 2022, 108 participants were enrolled and randomly assigned. 36 participants received placebo, 36 received rodatristat ethyl 300 mg, and 36 received rodatristat ethyl 600 mg twice daily. Overall, 85 (79%) of participants were female and 23 (21%) were male. The mean age was 52·8 years (SD 14·7) in the full analysis set. In the open-label extension phase, 62 (82%) of participants were female and 14 (18%) were male, and the mean age was 52·8 years (SD 14·7); this phase was terminated following sponsor review of unmasked main study results. Least-squares mean percent change in PVR from baseline to week 24 favoured placebo and was 5·8% (SE 18·1) for the placebo group, 63·1% (18·5) for the rodatristat ethyl 300 mg group, and 64·2% (18·0) for the rodatristat ethyl 600 mg group. Treatment-emergent adverse events (TEAE) were reported for 29 (81%) patients in the placebo group, 33 (92%) patients in the rodatristat ethyl 300 mg group, and all 36 (100%) patients in the rodatristat ethyl 600 mg group. TEAE leading to study discontinuation were reported for three (8%) patients in the placebo group, four (11%) patients in the rodatristat ethyl 300 mg group, and four (11%) in the rodatristat ethyl 600 mg group. There was one (3%) TEAE leading to death in","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"865-876"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300405","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":"Strengthening intensive care: addressing challenges and embracing opportunities.","authors":"Elie Azoulay, Maurizio Cecconi, Jan J De Waele","doi":"10.1016/S2213-2600(24)00294-7","DOIUrl":"10.1016/S2213-2600(24)00294-7","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"845-847"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332039","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":"Health promotion in the management of respiratory diseases: an Indian perspective","authors":"Arundhati Garud, Debabani Biswas, Saibal Moitra, Subhabrata Moitra","doi":"10.1016/s2213-2600(24)00332-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00332-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"60 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542070","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":"Nivolumab plus ipilimumab versus carboplatin-based doublet as first-line treatment for patients with advanced non-small-cell lung cancer aged ≥70 years or with an ECOG performance status of 2 (GFPC 08–2015 ENERGY): a randomised, open-label, phase 3 study","authors":"Hervé Léna, Laurent Greillier, Claire Cropet, Olivier Bylicki, Isabelle Monnet, Clarisse Audigier-Valette, Lionel Falchero, Alain Vergnenègre, Pierre Demontrond, Margaux Geier, Florian Guisier, Stéphane Hominal, Chrystèle Locher, Romain Corre, Christos Chouaid, Charles Ricordel","doi":"10.1016/s2213-2600(24)00264-9","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00264-9","url":null,"abstract":"<h3>Background</h3>Combined treatment with anti-PD-1 and anti-CTLA-4 antibodies has shown superiority over chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC), but data for older patients (aged ≥70 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 or those with an ECOG performance status of 2 are scarce. We aimed to test the superiority of the PD-1 antibody nivolumab and the CTLA-4 antibody ipilimumab over platinum-based doublet chemotherapy as first-line treatment in patients with NSCLC aged 70 years or older or with an ECOG performance status of 2.<h3>Methods</h3>This open-label, multicentre, randomised, controlled, phase 3 trial was done at 30 hospitals and cancer centres in France. Eligible patients had stage IV histologically proven NSCLC, with no known oncogenic alterations, and were either aged 70 years or older with ECOG performance status of 0–2 or younger than 70 years with an ECOG performance status of 2. Patients were randomly assigned (1:1) centrally, using a computer-generated algorithm stratified by age (<70 <em>vs</em> ≥70 years), ECOG performance status (0–1 <em>vs</em> 2), and histology (squamous <em>vs</em> non-squamous) to receive nivolumab plus ipilimumab or platinum-based doublet chemotherapy (carboplatin [area under the curve ≤700 mg] plus pemetrexed [500 mg/m<sup>2</sup> intravenous infusion every 3 weeks] or carboplatin [on day 1; area under the curve ≤700 mg] plus paclitaxel [90 mg/m<sup>2</sup> as intravenous infusion on days 1, 5, and 15, every 4 weeks]). The primary endpoint was overall survival; secondary endpoints included progression-free survival and safety. All efficacy analyses were performed in the intention-to-treat population, which included all randomly assigned patients. Safety was analysed in the safety analysis set, which included all randomly assigned patients who received at least one dose of study treatment and who had at least one safety follow-up. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03351361</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>The trial was stopped early for futility on the basis of a pre-planned interim analysis after 33% of the expected events had occurred. Between Feb 12, 2018, and Dec 15, 2020, 217 patients were randomly assigned, of whom 216 patients were included in the final analysis, with 109 patients in the nivolumab plus ipilimumab group and 107 in the chemotherapy group; median age was 74 years (IQR 70–78). Median overall survival was 14·7 months (95% CI 8·0–19·7) in the nivolumab plus ipilimumab","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"62 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541685","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":"Spirometry in female individuals","authors":"Martin R Miller, Brian L Graham, Sanja Stanojevic","doi":"10.1016/s2213-2600(24)00306-0","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00306-0","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"238 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541686","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":"Correction to Lancet Respir Med 2020; 8: 696–708","authors":"","doi":"10.1016/s2213-2600(24)00326-6","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00326-6","url":null,"abstract":"<em>Moll M, Sakornsakolpat P, Shrine N, et al. Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts.</em> Lancet Respir Med <em>2020; <strong>8:</strong> 696–708</em>—In this Article, a subset of participants from the SPIROMICS cohort were included in the study who were later found to have not provided consent for genetics or to have withdrawn consent for genetics. SPIROMICS I enrolled participants from 2010 to 2016 and performed up to three follow-up visits up to 2016. During SPIROMICS I, the consent form included several questions, including one on genetics. At each follow-up visit, the consent form was repeated and blood was drawn. This process yielded a complex set of consent flags and biospecimens across up to four visits. Unfortunately, the consent flags extracted from consent form questions were not properly reviewed before the isolation of DNA from the stored blood. Therefore, in 2016, some participants who did not consent for genetics, or who had withdrawn consent for genetics, had DNA isolated from blood and were included in the genome-wide association study. To correct the use of SPIROMICS data in this Article, the individuals who did not provide or who withdrew consent (11 controls and 15 cases) were removed and all analyses involving SPIROMICS data were repeated. In figure 2, the odds ratio (OR) for the association of combined polygenic risk score with chronic obstructive pulmonary disease (COPD) was corrected to 2·15 (95% CI 1·88–2·46) for the SPIROMICS non-Hispanic white (NHW) cohort, to 1·82 (1·74–1·89) for the overall fixed-effect model for European cohorts, and to 1·84 (1·60–2·11) for the overall random-effects model for European cohorts. In figure 3A, the ORs for COPD in European cohorts were corrected. In figure 4, the areas under the curve for predicting COPD in the SPIROMICS NHW cohort were corrected. The appendix has also been corrected. None of the findings changed significantly, and the conclusions of the study are unaffected. These corrections have been made to the online version as of Oct 29, 2024.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"130 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541689","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":"Correction to Lancet Respir Med 2024; 12: 888–900","authors":"","doi":"10.1016/s2213-2600(24)00333-3","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00333-3","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"107 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541688","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":"First-line treatment for advanced NSCLC in older patients and those with poor performance status","authors":"Ziming Li, Shun Lu","doi":"10.1016/s2213-2600(24)00365-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00365-5","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"86 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541684","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":"Spirometry in female individuals – Authors' reply","authors":"Philippe Haouzi, Johnathan McCully","doi":"10.1016/s2213-2600(24)00307-2","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00307-2","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"6 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541687","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":"Nintedanib for patients with lymphangioleiomyomatosis: a phase 2, open-label, single-arm study","authors":"Sergio Harari, Davide Elia, Antonella Caminati, Jens Geginat, Francesca Luisi, Giuseppe Pelosi, Claudia Specchia, Olga Torre, Roberta Trevisan, Chiara Vasco, Maurizio Zompatori, Roberto Cassandro","doi":"10.1016/s2213-2600(24)00217-0","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00217-0","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Lymphangioleiomyomatosis is an ultra-rare disease mainly affecting women of childbearing age. The MILES trial showed the efficacy of sirolimus, an mTOR inhibitor, in stabilising lung function in patients with lymphangioleiomyomatosis. Drug toxicity and development of resistance are potential limitations of therapy with sirolimus. Nintedanib is a multikinase inhibitor that inhibits PDGFR, which is active in human and murine lymphangioleiomyomatosis lesions. We aimed to investigate the activity and safety of nintedanib in patients with lymphangioleiomyomatosis.&lt;h3&gt;Methods&lt;/h3&gt;This phase 2, open-label, single-arm study was conducted at MultiMedica IRCCS, a national referral university centre for rare pulmonary diseases in Milan, Italy. Eligible participants were aged 18 years and older and had sporadic or tuberous sclerosis complex-associated lymphangioleiomyomatosis with progressive pulmonary function decline in the past year despite treatment with sirolimus or treatment naive. Patients received nintedanib 150 mg orally twice per day, with a possible reduction to 100 mg twice per day in case of side-effects or hepatoxicity, for 12 months, followed by a period of 12 additional months without study treatment. The primary endpoint was the change in FEV&lt;sub&gt;1&lt;/sub&gt; (FEV&lt;sub&gt;1&lt;/sub&gt; slope in L) over 12 months. This study is registered with &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&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;span&gt;&lt;span&gt;NCT03062943&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;From Oct 14, 2016, to Dec 13, 2019, 35 female patients (mean age 50 years [SD 11]) entered the study, 30 of whom were eligible and received nintedanib. After 12 months, 22 patients completed the treatment, 19 of whom also completed the 12 months of follow-up. FEV&lt;sub&gt;1&lt;/sub&gt; remained stable after one year of treatment (predicted mean difference 0·001 L [95% CI –0·063 to 0·066]; p=0·97). During the 12 months off treatment, a slight decline in FEV&lt;sub&gt;1&lt;/sub&gt; was observed (predicted mean difference –0·076 L [95% CI –0·149 to –0·004]; p=0·040). The most frequent adverse events were nausea (15 [50%] patients), diarrhoea (eight [26%]), and abdominal pain (two [7%]). No serious adverse events were observed during the treatment period.&lt;h3&gt;Interpretation&lt;/h3&gt;Our findings suggest that nintedanib did not improve FEV&lt;sub&gt;1&lt;/sub&gt;, but that the treatment was generally well tolerated. These results might support nintedanib as a second-line therapy in patients not controlled by standard treatment with mTOR inhibitors. Further investigation, such as a non-inferiority trial comparing nintedanib and sirolimus could help to better","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"32 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490068","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}