Pub Date : 2024-09-13DOI: 10.1164/rccm.202408-1594le
Adam J Byrne,Vipin Kumar,Albert Agro,Marc Hertz
{"title":"Reply to Yasuma et al.: Inhibiting iNKT Cell Activation: A Promising Strategy Against Pulmonary Fibrosis.","authors":"Adam J Byrne,Vipin Kumar,Albert Agro,Marc Hertz","doi":"10.1164/rccm.202408-1594le","DOIUrl":"https://doi.org/10.1164/rccm.202408-1594le","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":24.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233524","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 : 2024-09-13DOI: 10.1164/rccm.202408-1513le
Taro Yasuma,Hajime Fujimoto,Corina N D'Alessandro-Gabazza,Esteban C Gabazza,Osamu Hataji,Tetsu Kobayashi
{"title":"Inhibiting iNKT Cell Activation: A Promising Strategy Against Pulmonary Fibrosis.","authors":"Taro Yasuma,Hajime Fujimoto,Corina N D'Alessandro-Gabazza,Esteban C Gabazza,Osamu Hataji,Tetsu Kobayashi","doi":"10.1164/rccm.202408-1513le","DOIUrl":"https://doi.org/10.1164/rccm.202408-1513le","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":24.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233523","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 : 2024-09-13DOI: 10.1164/rccm.202401-0127oc
Alexander J Bell,Sundaresh Ram,Wassim W Labaki,Susan Murray,Ella A Kazerooni,Stefanie Galban,Fernando J Martinez,Charles R Hatt,Jennifer M Wang,Vladimir Ivanov,Paul McGettigan,Edward Khokhlovich,Enrico Maiorino,Rahul Suryadevara,Adel Boueiz,Peter Castaldi,Evgeny M Mirkes,Andrei Zinovyev,Alexander N Gorban,Craig J Galban,MeiLan K Han
BACKGROUNDChronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships.METHODSCross-sectional data from 8,972 tobacco-exposed COPDGene participants, with and without COPD, were used to train a model with EPGA, using thirty clinical, physiologic and CT features. Principal component analysis (PCA) was used to reduce data dimensionality to six principal components. An elastic principal tree was fitted to the reduced space. 4,585 participants from COPDGene Phase 2 were used to test longitudinal trajectories. 2,652 participants from SPIROMICS tested external reproducibility.RESULTSOur analysis used cross-sectional data to create an elastic principal tree, where the concept of time is represented by distance on the tree. Six clinically distinct tree segments were identified that differed by lung function, symptoms, and CT features: 1) Subclinical (SC); 2) Parenchymal Abnormality (PA); 3) Chronic Bronchitis (CB); 4) Emphysema Male (EM); 5) Emphysema Female (EF); and 6) Severe Airways (SA) disease. Cross-sectional SPIROMICS data confirmed similar groupings. 5-year data from COPDGene mapped longitudinal changes onto the tree. 29% of patients changed segment during follow-up; longitudinal trajectories confirmed a net flow of patients along the tree, from SC towards Emphysema, although alternative trajectories were noted, through airway disease predominant phenotypes, CB and SA.CONCLUSIONThis novel analytic methodology provides an approach to defining longitudinal phenotypic trajectories using cross sectional data. These insights are clinically relevant and could facilitate precision therapy and future trials to modify disease progression.
{"title":"Temporal Exploration of COPD Phenotypes: Insights from the COPDGene and SPIROMICS Cohorts.","authors":"Alexander J Bell,Sundaresh Ram,Wassim W Labaki,Susan Murray,Ella A Kazerooni,Stefanie Galban,Fernando J Martinez,Charles R Hatt,Jennifer M Wang,Vladimir Ivanov,Paul McGettigan,Edward Khokhlovich,Enrico Maiorino,Rahul Suryadevara,Adel Boueiz,Peter Castaldi,Evgeny M Mirkes,Andrei Zinovyev,Alexander N Gorban,Craig J Galban,MeiLan K Han","doi":"10.1164/rccm.202401-0127oc","DOIUrl":"https://doi.org/10.1164/rccm.202401-0127oc","url":null,"abstract":"BACKGROUNDChronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships.METHODSCross-sectional data from 8,972 tobacco-exposed COPDGene participants, with and without COPD, were used to train a model with EPGA, using thirty clinical, physiologic and CT features. Principal component analysis (PCA) was used to reduce data dimensionality to six principal components. An elastic principal tree was fitted to the reduced space. 4,585 participants from COPDGene Phase 2 were used to test longitudinal trajectories. 2,652 participants from SPIROMICS tested external reproducibility.RESULTSOur analysis used cross-sectional data to create an elastic principal tree, where the concept of time is represented by distance on the tree. Six clinically distinct tree segments were identified that differed by lung function, symptoms, and CT features: 1) Subclinical (SC); 2) Parenchymal Abnormality (PA); 3) Chronic Bronchitis (CB); 4) Emphysema Male (EM); 5) Emphysema Female (EF); and 6) Severe Airways (SA) disease. Cross-sectional SPIROMICS data confirmed similar groupings. 5-year data from COPDGene mapped longitudinal changes onto the tree. 29% of patients changed segment during follow-up; longitudinal trajectories confirmed a net flow of patients along the tree, from SC towards Emphysema, although alternative trajectories were noted, through airway disease predominant phenotypes, CB and SA.CONCLUSIONThis novel analytic methodology provides an approach to defining longitudinal phenotypic trajectories using cross sectional data. These insights are clinically relevant and could facilitate precision therapy and future trials to modify disease progression.","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":24.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233525","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 : 2024-09-12DOI: 10.1164/rccm.202407-1480ed
David M Mannino,Jean Wright
{"title":"Are We Getting Closer to the \"Cholesterol\" for Chronic Respiratory Disease?","authors":"David M Mannino,Jean Wright","doi":"10.1164/rccm.202407-1480ed","DOIUrl":"https://doi.org/10.1164/rccm.202407-1480ed","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":24.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231382","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 : 2024-09-12DOI: 10.1164/rccm.202408-1516ed
Terence R Flotte
{"title":"The Road Less Traveled: Slow but Steady Progress Toward Cystic Fibrosis Gene Therapy by UK Respiratory Gene Therapy Consortium.","authors":"Terence R Flotte","doi":"10.1164/rccm.202408-1516ed","DOIUrl":"https://doi.org/10.1164/rccm.202408-1516ed","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":24.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231381","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 : 2024-09-10DOI: 10.1164/rccm.202403-0613oc
Gabrielle Y Liu,Andrew S Perry,George R Washko,Eric Farber-Eger,Laura A Colangelo,Quanhu Sheng,Quinn Wells,Xiaoning Huang,Bharat Thyagarajan,Weihua Guan,Shaina J Alexandria,Raúl San José Estépar,Russell P Bowler,Anthony J Esposito,Sadiya S Khan,Ravi V Shah,Bina Choi,Ravi Kalhan
RATIONALEAccelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice.OBJECTIVETo determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality.METHODSIn CARDIA, a population-based cohort starting in young adulthood, longitudinal measurements of FEV1 percent predicted (up to six timepoints over 30 years) were used to identify accelerated and normal decline trajectories. Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression. The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality.MEASUREMENTS AND RESULTSHigher susceptibility score was independently associated with all-cause mortality (UKBB: HR 1.56, 95%CI 1.50-1.61; COPDGene: HR 1.75, 95%CI 1.63-1.88), respiratory mortality (UKBB: HR 2.39, 95% CI 2.16-2.64; COPDGene: HR 1.83, 95%CI 1.33-2.51), incident COPD (UKBB: HR 1.84, 95%CI 1.71-1.98), incident respiratory exacerbation (COPDGene: OR 1.11, 95%CI 1.03-1.20), and incident exacerbation requiring hospitalization (COPDGene: OR 1.18, 95%CI 1.08-1.28).CONCLUSIONSA proteomic signature of increased respiratory susceptibility identifies people at risk of respiratory death, incident COPD, and respiratory exacerbations. This susceptibility score is comprised of proteins with well-known and novel associations with lung health and holds promise for the early detection of lung disease without requiring years of spirometry measurements.
{"title":"Proteomic Risk Score of Increased Respiratory Susceptibility: A Multi-Cohort Study.","authors":"Gabrielle Y Liu,Andrew S Perry,George R Washko,Eric Farber-Eger,Laura A Colangelo,Quanhu Sheng,Quinn Wells,Xiaoning Huang,Bharat Thyagarajan,Weihua Guan,Shaina J Alexandria,Raúl San José Estépar,Russell P Bowler,Anthony J Esposito,Sadiya S Khan,Ravi V Shah,Bina Choi,Ravi Kalhan","doi":"10.1164/rccm.202403-0613oc","DOIUrl":"https://doi.org/10.1164/rccm.202403-0613oc","url":null,"abstract":"RATIONALEAccelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice.OBJECTIVETo determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality.METHODSIn CARDIA, a population-based cohort starting in young adulthood, longitudinal measurements of FEV1 percent predicted (up to six timepoints over 30 years) were used to identify accelerated and normal decline trajectories. Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression. The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality.MEASUREMENTS AND RESULTSHigher susceptibility score was independently associated with all-cause mortality (UKBB: HR 1.56, 95%CI 1.50-1.61; COPDGene: HR 1.75, 95%CI 1.63-1.88), respiratory mortality (UKBB: HR 2.39, 95% CI 2.16-2.64; COPDGene: HR 1.83, 95%CI 1.33-2.51), incident COPD (UKBB: HR 1.84, 95%CI 1.71-1.98), incident respiratory exacerbation (COPDGene: OR 1.11, 95%CI 1.03-1.20), and incident exacerbation requiring hospitalization (COPDGene: OR 1.18, 95%CI 1.08-1.28).CONCLUSIONSA proteomic signature of increased respiratory susceptibility identifies people at risk of respiratory death, incident COPD, and respiratory exacerbations. This susceptibility score is comprised of proteins with well-known and novel associations with lung health and holds promise for the early detection of lung disease without requiring years of spirometry measurements.","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":24.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165949","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 : 2024-09-10DOI: 10.1164/rccm.202407-1494ed
Jennifer K Quint
{"title":"The Role of ICS in Reducing Cardiovascular Risk - Seeing Is Not Always Believing.","authors":"Jennifer K Quint","doi":"10.1164/rccm.202407-1494ed","DOIUrl":"https://doi.org/10.1164/rccm.202407-1494ed","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":24.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170492","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":"Paradigm Shift in ICU Candidacy for Allogeneic Hematopoietic Stem-Cell Transplantation: Who, When, and How Long?","authors":"Marina García-de-Acilu, Laveena Munshi, Oriol Roca","doi":"10.1164/rccm.202407-1496ED","DOIUrl":"https://doi.org/10.1164/rccm.202407-1496ED","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139035","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 : 2024-09-05DOI: 10.1164/rccm.202402-0389CI
Jane C Davies, Deepika Polineni, A Christopher Boyd, Scott Donaldson, Deborah R Gill, Uta Griesenbach, Stephen C Hyde, Raksha Jain, Gerry McLachlan, Marcus A Mall, Eric Wfw Alton
Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. While cystic fibrosis is a multi-organ disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of CFTR mutations on CFTR function has allowed for the development of CFTR modulator therapies. Despite the remarkable impact that these therapies have had, there remains a significant proportion of people with cystic fibrosis (estimated at 10-15% of the global cystic fibrosis population) who are genetically ineligible for, or intolerant to, current CFTR-targeting therapies and whose therapeutic needs remain unmet. Inhaled genetic therapies offer the prospect of addressing the unmet pulmonary treatment need in people with cystic fibrosis, with several approaches, including gene addition therapy (the focus of this review), RNA-based therapies, antisense oligonucleotides and gene editing, being explored. Various non-viral and viral vectors have been investigated for cystic fibrosis gene addition therapy for mutation-agnostic restoration of CFTR function in the lungs. Lentiviral vectors offer the prospect of highly efficient and long-lasting gene expression, and the potential to be safely and, in contrast to other commonly used viral vectors, effectively re-dosed. A third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV.F/HN) has been developed for the treatment of cystic fibrosis. Promising preclinical results support the progression of this vector carrying a full-length CFTR transgene (BI 3720931) into a first-in-human clinical trial expected to begin in 2024.
{"title":"Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-In-Human Trial.","authors":"Jane C Davies, Deepika Polineni, A Christopher Boyd, Scott Donaldson, Deborah R Gill, Uta Griesenbach, Stephen C Hyde, Raksha Jain, Gerry McLachlan, Marcus A Mall, Eric Wfw Alton","doi":"10.1164/rccm.202402-0389CI","DOIUrl":"https://doi.org/10.1164/rccm.202402-0389CI","url":null,"abstract":"<p><p>Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (<i>CFTR</i>) gene. While cystic fibrosis is a multi-organ disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of <i>CFTR</i> mutations on CFTR function has allowed for the development of CFTR modulator therapies. Despite the remarkable impact that these therapies have had, there remains a significant proportion of people with cystic fibrosis (estimated at 10-15% of the global cystic fibrosis population) who are genetically ineligible for, or intolerant to, current CFTR-targeting therapies and whose therapeutic needs remain unmet. Inhaled genetic therapies offer the prospect of addressing the unmet pulmonary treatment need in people with cystic fibrosis, with several approaches, including gene addition therapy (the focus of this review), RNA-based therapies, antisense oligonucleotides and gene editing, being explored. Various non-viral and viral vectors have been investigated for cystic fibrosis gene addition therapy for mutation-agnostic restoration of CFTR function in the lungs. Lentiviral vectors offer the prospect of highly efficient and long-lasting gene expression, and the potential to be safely and, in contrast to other commonly used viral vectors, effectively re-dosed. A third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV.F/HN) has been developed for the treatment of cystic fibrosis. Promising preclinical results support the progression of this vector carrying a full-length <i>CFTR</i> transgene (BI 3720931) into a first-in-human clinical trial expected to begin in 2024.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139034","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 : 2024-09-03DOI: 10.1164/rccm.202407-1428ED
Don D Sin, William W Busse
{"title":"What Harm Are We Doing to Our Patients with Asthma by Using High-Dose Inhaled Corticosteroids?","authors":"Don D Sin, William W Busse","doi":"10.1164/rccm.202407-1428ED","DOIUrl":"https://doi.org/10.1164/rccm.202407-1428ED","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124578","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：