Pub Date : 2025-02-20DOI: 10.1016/s2213-2600(24)00425-9
Franck F Rahaghi, Marc Humbert, Marius M Hoeper, R James White, Robert P Frantz, Paul M Hassoun, Anna R Hemnes, Steven M Kawut, Vallerie V McLaughlin, Gergely Meszaros, Peter G M Mol, Steven D Nathan, Mitchel A Psotka, Farbod N Rahaghi, Olivier Sitbon, Norman Stockbridge, Jason Weatherald, Faiez Zannad, Sandeep Sahay
Novel treatments in pulmonary arterial hypertension (PAH) with significant pathophysiological and clinical responses have generated renewed interest in changing the course of the disease and achieving long-term disease control. Historically, the term disease modification was coined in rheumatological conditions with therapies that managed to treat the underlying condition as opposed to just alleviating symptoms. With the advent of novel therapies, the term disease modification was introduced in our discussions. Last year, a group of experts discussed this concept in PAH and proposed clinical trial designs to show disease modification in PAH. Taking a step further we convened a group of international experts at the 20th Global CardioVascular Clinical Trialists Forum, patients' representatives, and members of global regulatory agencies to discuss future treatment objectives and trial designs in PAH. The deliberations revealed the difficulty with securely defining disease modification, in that there are no pathophysiological biomarkers that reflect disease activity and studies are not designed or performed in a way that would support such designation. Regulatory agencies indicated they are going away from making this designation a priority in PAH. They declared interest in encouraging trials that advance interventions with significant pathophysiological effect, in particular showing reverse pulmonary vascular remodelling, which is likely to bring about more potent clinical response, partial or complete remission, and perhaps cure. In this Personal View, we provide a review of our understanding of defining disease modification in PAH along with providing definitions of what might constitute a partial or full remission in PAH.
{"title":"Future treatment paradigms in pulmonary arterial hypertension: a personal view from physicians, health authorities, and patients","authors":"Franck F Rahaghi, Marc Humbert, Marius M Hoeper, R James White, Robert P Frantz, Paul M Hassoun, Anna R Hemnes, Steven M Kawut, Vallerie V McLaughlin, Gergely Meszaros, Peter G M Mol, Steven D Nathan, Mitchel A Psotka, Farbod N Rahaghi, Olivier Sitbon, Norman Stockbridge, Jason Weatherald, Faiez Zannad, Sandeep Sahay","doi":"10.1016/s2213-2600(24)00425-9","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00425-9","url":null,"abstract":"Novel treatments in pulmonary arterial hypertension (PAH) with significant pathophysiological and clinical responses have generated renewed interest in changing the course of the disease and achieving long-term disease control. Historically, the term disease modification was coined in rheumatological conditions with therapies that managed to treat the underlying condition as opposed to just alleviating symptoms. With the advent of novel therapies, the term disease modification was introduced in our discussions. Last year, a group of experts discussed this concept in PAH and proposed clinical trial designs to show disease modification in PAH. Taking a step further we convened a group of international experts at the 20th Global CardioVascular Clinical Trialists Forum, patients' representatives, and members of global regulatory agencies to discuss future treatment objectives and trial designs in PAH. The deliberations revealed the difficulty with securely defining disease modification, in that there are no pathophysiological biomarkers that reflect disease activity and studies are not designed or performed in a way that would support such designation. Regulatory agencies indicated they are going away from making this designation a priority in PAH. They declared interest in encouraging trials that advance interventions with significant pathophysiological effect, in particular showing reverse pulmonary vascular remodelling, which is likely to bring about more potent clinical response, partial or complete remission, and perhaps cure. In this Personal View, we provide a review of our understanding of defining disease modification in PAH along with providing definitions of what might constitute a partial or full remission in PAH.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"22 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462473","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 : 2025-02-14DOI: 10.1016/s2213-2600(25)00042-6
Eunji Choi, Julie A Barta
No Abstract
{"title":"Use of lung-cancer trends for global and public health priorities","authors":"Eunji Choi, Julie A Barta","doi":"10.1016/s2213-2600(25)00042-6","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00042-6","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"270 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417390","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 : 2025-02-14DOI: 10.1016/s2213-2600(25)00038-4
Tony Kirby
No Abstract
{"title":"Patient in her 70s with COPD and asthma improving significantly since using monoclonal antibody dupilumab","authors":"Tony Kirby","doi":"10.1016/s2213-2600(25)00038-4","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00038-4","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"184 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417389","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 : 2025-02-12DOI: 10.1016/s2213-2600(25)00017-7
Tony Kirby
No Abstract
{"title":"Patient with cystic fibrosis not diagnosed until age 23 years now treated with the new triple therapy Trikafta","authors":"Tony Kirby","doi":"10.1016/s2213-2600(25)00017-7","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00017-7","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"63 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401654","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 : 2025-02-10DOI: 10.1016/s2213-2600(24)00362-x
Mario Castro, Alberto Papi, Celeste Porsbjerg, Njira L Lugogo, Christopher E Brightling, Francisco-Javier González-Barcala, Arnaud Bourdin, Mykola Ostrovskyy, Maria Staevska, Pai-Chien Chou, Liliana Duca, Ana Margarida Pereira, Charles Fogarty, Rufai Nadama, Mei Zhang, Amelie Rodrigues, Xavier Soler, Harry J Sacks, Yamo Deniz, Paul J Rowe, Juby A Jacob-Nara
<h3>Background</h3>Asthma is a respiratory disease characterised by chronic airway inflammation and mucus hypersecretion. VESTIGE used functional respiratory imaging to assess changes in airway structure and function, including mucus plugging, in response to dupilumab.<h3>Methods</h3>VESTIGE was a randomised, double-blind, placebo-controlled, phase 4 trial done at 72 research sites or academic centres in 14 countries. We recruited adult patients (aged 18–70 years) with physician-diagnosed, uncontrolled, moderate-to-severe type 2 asthma (blood eosinophil count ≥300 cells/μL and fractional exhaled nitric oxide [FeNO] ≥25 parts per billion [ppb]) being treated with medium-dose to high-dose inhaled corticosteroids combined with other controller medications. Patients were randomly assigned (2:1; block size of 6) via interactive voice–web response technology to receive add-on dupilumab 300 mg subcutaneously once every 2 weeks or volume-matched placebo up to week 24. Randomisation was stratified by inhaled corticosteroids dose level and region (USA <em>vs</em> non-USA). Participants and investigators, including those assessing outcomes, were masked to group assignment. The primary endpoints were the proportion of patients with a FeNO concentration below 25 ppb at week 24, and percentage change from baseline to week 24 in airway volumes (specific regional airway volumes corrected for lung volume, [s]iV<sub><em>aw</em></sub>) at total lung capacity (TLC), both assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug or placebo. 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>NCT04400318</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>, and is completed.<h3>Findings</h3>Patient recruitment occurred from July 18, 2020, to Jan 6, 2023. Patients (mean age 50·4 years [SD 12·6]; 68 [62%] female and 41 [38%] male) were randomly assigned to receive dupilumab 300 mg (n<em>=</em>72) or placebo (n<em>=</em>37). At week 24, patients in the dupilumab group were significantly more likely than those in the placebo group to have a FeNO concentration below 25 ppb (41 [57%] of 72 patients <em>vs</em> four [11%] of 37; odds ratio: 9·8 [95% CI 3·1 to 30·8]; p<0·001). Treatment with dupilumab versus placebo led to a numerical increase in (s)iV<sub><em>aw</em></sub> at TLC from baseline to week 24, although the difference was not significant (least squares [LS] mean percentage change from baseline to week 24: 19·7% [SE 8·1] for dupilumab and −2·0% [11·5] for placebo; LS mean difference <em>vs</em> placebo: 21·8%
{"title":"Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial","authors":"Mario Castro, Alberto Papi, Celeste Porsbjerg, Njira L Lugogo, Christopher E Brightling, Francisco-Javier González-Barcala, Arnaud Bourdin, Mykola Ostrovskyy, Maria Staevska, Pai-Chien Chou, Liliana Duca, Ana Margarida Pereira, Charles Fogarty, Rufai Nadama, Mei Zhang, Amelie Rodrigues, Xavier Soler, Harry J Sacks, Yamo Deniz, Paul J Rowe, Juby A Jacob-Nara","doi":"10.1016/s2213-2600(24)00362-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00362-x","url":null,"abstract":"<h3>Background</h3>Asthma is a respiratory disease characterised by chronic airway inflammation and mucus hypersecretion. VESTIGE used functional respiratory imaging to assess changes in airway structure and function, including mucus plugging, in response to dupilumab.<h3>Methods</h3>VESTIGE was a randomised, double-blind, placebo-controlled, phase 4 trial done at 72 research sites or academic centres in 14 countries. We recruited adult patients (aged 18–70 years) with physician-diagnosed, uncontrolled, moderate-to-severe type 2 asthma (blood eosinophil count ≥300 cells/μL and fractional exhaled nitric oxide [FeNO] ≥25 parts per billion [ppb]) being treated with medium-dose to high-dose inhaled corticosteroids combined with other controller medications. Patients were randomly assigned (2:1; block size of 6) via interactive voice–web response technology to receive add-on dupilumab 300 mg subcutaneously once every 2 weeks or volume-matched placebo up to week 24. Randomisation was stratified by inhaled corticosteroids dose level and region (USA <em>vs</em> non-USA). Participants and investigators, including those assessing outcomes, were masked to group assignment. The primary endpoints were the proportion of patients with a FeNO concentration below 25 ppb at week 24, and percentage change from baseline to week 24 in airway volumes (specific regional airway volumes corrected for lung volume, [s]iV<sub><em>aw</em></sub>) at total lung capacity (TLC), both assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug or placebo. 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>NCT04400318</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>, and is completed.<h3>Findings</h3>Patient recruitment occurred from July 18, 2020, to Jan 6, 2023. Patients (mean age 50·4 years [SD 12·6]; 68 [62%] female and 41 [38%] male) were randomly assigned to receive dupilumab 300 mg (n<em>=</em>72) or placebo (n<em>=</em>37). At week 24, patients in the dupilumab group were significantly more likely than those in the placebo group to have a FeNO concentration below 25 ppb (41 [57%] of 72 patients <em>vs</em> four [11%] of 37; odds ratio: 9·8 [95% CI 3·1 to 30·8]; p<0·001). Treatment with dupilumab versus placebo led to a numerical increase in (s)iV<sub><em>aw</em></sub> at TLC from baseline to week 24, although the difference was not significant (least squares [LS] mean percentage change from baseline to week 24: 19·7% [SE 8·1] for dupilumab and −2·0% [11·5] for placebo; LS mean difference <em>vs</em> placebo: 21·8%","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"41 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385476","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 : 2025-02-10DOI: 10.1016/s2213-2600(24)00380-1
Richard E K Russell
No Abstract
{"title":"Management and mechanisms of eosinophil action in asthma: mind the gap?","authors":"Richard E K Russell","doi":"10.1016/s2213-2600(24)00380-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00380-1","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"14 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385477","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 : 2025-02-04DOI: 10.1016/s2213-2600(24)00426-0
Rossa Brugha, Kavita Dave, Vicky Gerovasili, Amit Adlakha
No Abstract
{"title":"Expanding CFTR modulator access to benefit all patients who are waiting for a lung transplant","authors":"Rossa Brugha, Kavita Dave, Vicky Gerovasili, Amit Adlakha","doi":"10.1016/s2213-2600(24)00426-0","DOIUrl":"https://doi.org/10.1016/s2213-2600(24)00426-0","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"50 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124446","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}
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