Lancet Respiratory Medicine最新文献

{"title":"Anti-CTLA-4 in non-small-cell lung cancer: insights from the NIPPON study.","authors":"Molly S C Li, Stephanie P L Saw, Alfredo Addeo","doi":"10.1016/S2213-2600(24)00218-2","DOIUrl":"10.1016/S2213-2600(24)00218-2","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"840-842"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005806","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":"Easing the stress of chronic cough.","authors":"Marta Dąbrowska, Lorcan McGarvey","doi":"10.1016/S2213-2600(24)00254-6","DOIUrl":"10.1016/S2213-2600(24)00254-6","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"838-839"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121127","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":"Efficacy and safety of gefapixant in women with chronic cough and cough-induced stress urinary incontinence: a phase 3b, randomised, multicentre, double-blind, placebo-controlled trial.","authors":"Surinder S Birring, Linda Cardozo, Roger Dmochowski, Peter Dicpinigaitis, Amna Afzal, Carmen La Rosa, Susan Lu, Allison Martin Nguyen, Ruji Yao, Paul A Reyfman","doi":"10.1016/S2213-2600(24)00222-4","DOIUrl":"10.1016/S2213-2600(24)00222-4","url":null,"abstract":"<p><strong>Background: </strong>Approximately two-thirds of women with chronic cough have cough-induced stress urinary incontinence (CSUI). We aimed to evaluate the efficacy and safety of gefapixant in reducing CSUI episodes in women with refractory or unexplained chronic cough.</p><p><strong>Methods: </strong>This phase 3b, double-blind, randomised, placebo-controlled trial done at 90 sites in 12 countries enrolled women aged 18 years or older who had chronic cough for at least 1 year, a diagnosis of refractory or unexplained chronic cough, a cough severity visual analogue scale score of 40 mm or more (100 mm maximum), and CSUI for 3 months or more. Participants were randomised 1:1 to oral gefapixant or placebo for 12 weeks. The primary outcome was percentage change from baseline in daily CSUI episodes (7-day average) at week 12. This study is registered with ClinicalTrials.gov (NCT04193176).</p><p><strong>Findings: </strong>From May 10, 2020, to Sept 2, 2022, 375 participants were randomised to and treated with gefapixant 45 mg twice daily (n=185) or placebo (n=190). Mean age was 56·4 years (SD 11·4), with mean chronic cough duration of 5·2 years (SD 6·6) and SUI duration of 4·0 years (SD 5·9). Least-squares mean percentage change from baseline in daily CSUI episodes was -52·8% (95% CI -58·4 to -47·1%) for gefapixant and -41·1% (-46·7 to -35·4%) for placebo (estimated treatment difference: -11·7% [95% CI -19·7 to -3·7]; p=0·004). 129 (70%) of 185 participants who received gefapixant and 71 (37%) of 190 participants who received placebo had at least one adverse event. Safety and tolerability were consistent with previous trials of gefapixant; the most frequent adverse events were taste related.</p><p><strong>Interpretation: </strong>Gefapixant 45 mg twice daily is the first treatment to show efficacy versus placebo in reducing CSUI episodes in participants with refractory or unexplained chronic cough.</p><p><strong>Funding: </strong>Merck Sharp & Dohme, a subsidiary of Merck & Co.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"855-864"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121128","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":"Fatal dyspnoea at the Palace of Versailles.","authors":"Emmanuel Drouin, Serge Wasersztrum, Arnaud Chambellan","doi":"10.1016/S2213-2600(24)00270-4","DOIUrl":"10.1016/S2213-2600(24)00270-4","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"852-854"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005820","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":"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":"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":" ","pages":"901-914"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","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}

{"title":"Serotonin pathway blockade in pulmonary arterial hypertension.","authors":"Marcin Kurzyna","doi":"10.1016/S2213-2600(24)00291-1","DOIUrl":"10.1016/S2213-2600(24)00291-1","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"839-840"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300408","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":"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":"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":" ","pages":"915-932"},"PeriodicalIF":2.2,"publicationDate":"2024-11-01","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}

{"title":"New thinking and a new direction in bronchiectasis.","authors":"Ian D Pavord","doi":"10.1016/S2213-2600(24)00244-3","DOIUrl":"10.1016/S2213-2600(24)00244-3","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"844-845"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047489","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":"Comparison of platinum combination chemotherapy plus pembrolizumab versus platinum combination chemotherapy plus nivolumab-ipilimumab for treatment-naive advanced non-small-cell lung cancer in Japan (JCOG2007): an open-label, multicentre, randomised, phase 3 trial.","authors":"Yoshimasa Shiraishi, Shogo Nomura, Shunichi Sugawara, Hidehito Horinouchi, Yasuto Yoneshima, Hidetoshi Hayashi, Koichi Azuma, Satoshi Hara, Seiji Niho, Ryo Morita, Masafumi Yamaguchi, Toshihide Yokoyama, Kiyotaka Yoh, Takayasu Kurata, Hiroaki Okamoto, Masaki Okamoto, Takashi Kijima, Kazuo Kasahara, Yutaka Fujiwara, Shuji Murakami, Shintaro Kanda, Hiroaki Akamatsu, Shinnosuke Takemoto, Hiroyasu Kaneda, Toshiyuki Kozuki, Masahiko Ando, Yuta Sekino, Haruhiko Fukuda, Yuichiro Ohe, Isamu Okamoto","doi":"10.1016/S2213-2600(24)00185-1","DOIUrl":"10.1016/S2213-2600(24)00185-1","url":null,"abstract":"<p><strong>Background: </strong>The combination of platinum-based chemotherapy and an antibody to PD-1 or to its ligand PD-L1, with or without an antibody to CTLA-4, has improved the survival of individuals with metastatic non-small-cell lung cancer (NSCLC). However, no randomised controlled trial has evaluated the survival benefit of adding a CTLA-4 inhibitor to platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.</p><p><strong>Methods: </strong>This open-label, randomised, phase 3 trial was conducted at 48 hospitals in Japan. Eligible patients were aged 20 years or older with previously untreated advanced NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with known driver oncogenes were excluded. Participants were randomly assigned (1:1) to receive platinum-based chemotherapy (four cycles) plus pembrolizumab (pembrolizumab group) or platinum-based chemotherapy (two cycles) plus nivolumab-ipilimumab (nivolumab-ipilimumab group). The primary endpoint was overall survival and assessed in all randomly assigned patients on an intention-to-treat basis. The trial is registered in the Japan Registry for Clinical Trials, jRCTs031210013, and is now closed to new enrolment and is ongoing.</p><p><strong>Findings: </strong>Between patient accrual initiation on April 6, 2021, and discontinuation of the trial on March 30, 2023, 11 (7%) of 148 patients in the nivolumab-ipilimumab group had a treatment-related death. Because of the high number of treatment-related deaths, patient accrual was terminated early, resulting in 295 patients (236 [80%] male and 59 [20%] female) enrolled; the primary analysis was done on the basis of 117 deaths (fewer than the required 329 deaths). By May 25, 2023 (data cutoff), overall survival did not differ significantly between the nivolumab-ipilimumab group and the pembrolizumab group (median 23·7 months [95% CI 17·6-not estimable] vs 20·5 months [17·6-not estimable], respectively; hazard ratio 0·98 [90% CI 0·72-1·34]; p=0·46). Non-haematological adverse events of grade 3 or worse occurred in 87 (60%) of 146 patients in the nivolumab-ipilimumab group and 59 (41%) of 144 patients in the pembrolizumab group. The pembrolizumab group tended to have a better quality of life compared with the nivolumab-ipilimumab group.</p><p><strong>Interpretation: </strong>The safety and efficacy data suggest an unfavourable benefit-risk profile for nivolumab-ipilimumab combined with platinum-based chemotherapy relative to pembrolizumab combined with platinum-based chemotherapy as a first-line treatment for patients with advanced NSCLC, although a definitive conclusion awaits an updated analysis of overall survival.</p><p><strong>Funding: </strong>The National Cancer Center Research and Development Fund and Japan Agency for Medical Research and Development.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"877-887"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005807","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":"The expanded French compassionate programme for elexacaftor-tezacaftor-ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study.","authors":"Pierre-Régis Burgel, Isabelle Sermet-Gaudelus, Emmanuelle Girodon, Isabelle Durieu, Véronique Houdouin, Camille Audousset, Julie Macey, Dominique Grenet, Michele Porzio, Marlène Murris-Espin, Philippe Reix, Mélisande Baravalle, Chantal Belleguic, Laurent Mely, Juliette Verhille, Laurence Weiss, Martine Reynaud-Gaubert, Marie Mittaine, Rebecca Hamidfar, Sophie Ramel, Laure Cosson, Benoit Douvry, Isabelle Danner-Boucher, Pierre Foucaud, Charlotte Roy, Espérie Burnet, Caroline Raynal, Marie-Pierre Audrezet, Jennifer Da Silva, Clémence Martin","doi":"10.1016/S2213-2600(24)00208-X","DOIUrl":"10.1016/S2213-2600(24)00208-X","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Elexacaftor-tezacaftor-ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTR variant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor-tezacaftor-ivacaftor for people with cystic fibrosis without a F508del CFTR variant in France and to determine CFTR variant responsiveness to elexacaftor-tezacaftor-ivacaftor based on the observed clinical response.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The French compassionate programme expanded access to elexacaftor-tezacaftor-ivacaftor to people with cystic fibrosis, aged 6 years and older, without a F508del variant, excluding those with two variants previously characterised as non-responsive. Participants at France's 47 cystic fibrosis centres were given a 4-6 week trial of elexacaftor-tezacaftor-ivacaftor and response was determined by a centralised committee based on evolution of clinical data, lung function, and sweat chloride concentration. Responsiveness of individual CFTR variants was derived from observed clinical responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;The first compassionnate programme was launched on May 19, 2022; by March 8, 2024, 516 people with cystic fibrosis had been identified for inclusion in this real-word study: 37 were not included due to the presence of two variants previously characterised as non-responsive to elexacaftor-tezacaftor-ivacaftor, and 479 (229 females [48%] and 250 males [52%]) received elexacaftor-tezacaftor-ivacaftor for 4-6 weeks. Among 443 participants who received no CFTR modulator before elexacaftor-tezacaftor-ivacaftor, 83 had at least one FDA-approved variant, of whom 81 (98%) were responders and continued elexacaftor-tezacaftor-ivacaftor; in responders, mean absolute change in sweat chloride was -44·5 mmol/L (95% CI -39·1 to -49·8) and percentage of predicted FEV&lt;sub&gt;1&lt;/sub&gt; (ppFEV&lt;sub&gt;1&lt;/sub&gt;) was 11·1 percentage points (95% CI 8·4 to 13·7; both comparisons p&lt;0·0001). Among 360 participants with no FDA-approved variant and no previous CFTR modulator, 177 (49%) were responders; in responders, mean absolute change in sweat chloride was -20·5 mmol/L (-17·2 to -23·8) and ppFEV&lt;sub&gt;1&lt;/sub&gt; was 13·2 percentage points (11·4 to 15·0; both comparisons p&lt;0·0001). Among 36 participants who were receiving ivacaftor before elexacaftor-tezacaftor-ivacaftor, 32 (89%) continued elexacaftor-tezacaftor-ivacaftor. Of 251 individual CFTR variants, 64 (28 FDA-approved) were classified as responsive or possibly responsive to elexacaftor-tezacaftor-ivacaftor, and 123 (two FDA-approved) as non-responsive or possibly non-responsive to elexacaftor-tezacaftor-ivacaftor.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In France, over half of the population with cystic fibrosis without a F508del variant responded to elexacaftor-tezacaftor-ivacaftor, with mo","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"888-900"},"PeriodicalIF":38.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996918","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}