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}
Pub Date : 2024-09-01DOI: 10.1164/rccm.202310-1871LE
Lida P Hariri, Amita Sharma, Sreyankar Nandy, Sarita R Berigei, Satomi Yamamoto, Rebecca A Raphaely, Bess M Flashner, Ashok Muniappan, Hugh G Auchincloss, Michael Lanuti, Robert W Hallowell, Barry S Shea, Colleen M Keyes
{"title":"Endobronchial Optical Coherence Tomography as a Novel Method for <i>In Vivo</i> Microscopic Assessment of Interstitial Lung Abnormalities.","authors":"Lida P Hariri, Amita Sharma, Sreyankar Nandy, Sarita R Berigei, Satomi Yamamoto, Rebecca A Raphaely, Bess M Flashner, Ashok Muniappan, Hugh G Auchincloss, Michael Lanuti, Robert W Hallowell, Barry S Shea, Colleen M Keyes","doi":"10.1164/rccm.202310-1871LE","DOIUrl":"10.1164/rccm.202310-1871LE","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139428851","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":"September 1 Highlight.","authors":"","doi":"10.1164/rccm.210i5xiv","DOIUrl":"https://doi.org/10.1164/rccm.210i5xiv","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103572","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 : 2024-09-01DOI: 10.1164/rccm.202405-0914SO
Sandeep Sahay, Murali M Chakinala, Nick H Kim, Ioana R Preston, Thenappan Thenappan, Vallerie V Mclaughlin
Pulmonary arterial hypertension (PAH) is a complex fatal condition that requires aggressive treatment with close monitoring. Significant progress has been made over the last three decades in the treatment of PAH, but, despite this progress, survival has remained unacceptably low. In the quest to improve survival, therapeutic interventions play a central role. In the last few years, there have been remarkable attempts to identify novel treatments. Finally, we have had a breakthrough with the discovery of the fourth treatment pathway in PAH. Activin signaling inhibition distinguishes itself as a potential antiproliferative intervention as opposed to the traditional therapies, which mediate their effect primarily by vasodilatation. With this novel treatment pathway, we stand at an important milestone with an exciting future ahead and the natural question of when to use an activin signaling inhibitor for the treatment of PAH. In this state-of-the-art review, we focus on the placement of this novel agent in the PAH treatment paradigm, based on the available evidence, with special focus on the U.S. patient population. This review also provides an expert opinion of the current treatment algorithm in important subgroups of patients with comorbidities from the U.S. perspective.
{"title":"Contemporary Treatment of Pulmonary Arterial Hypertension: A U.S. Perspective.","authors":"Sandeep Sahay, Murali M Chakinala, Nick H Kim, Ioana R Preston, Thenappan Thenappan, Vallerie V Mclaughlin","doi":"10.1164/rccm.202405-0914SO","DOIUrl":"10.1164/rccm.202405-0914SO","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a complex fatal condition that requires aggressive treatment with close monitoring. Significant progress has been made over the last three decades in the treatment of PAH, but, despite this progress, survival has remained unacceptably low. In the quest to improve survival, therapeutic interventions play a central role. In the last few years, there have been remarkable attempts to identify novel treatments. Finally, we have had a breakthrough with the discovery of the fourth treatment pathway in PAH. Activin signaling inhibition distinguishes itself as a potential antiproliferative intervention as opposed to the traditional therapies, which mediate their effect primarily by vasodilatation. With this novel treatment pathway, we stand at an important milestone with an exciting future ahead and the natural question of when to use an activin signaling inhibitor for the treatment of PAH. In this state-of-the-art review, we focus on the placement of this novel agent in the PAH treatment paradigm, based on the available evidence, with special focus on the U.S. patient population. This review also provides an expert opinion of the current treatment algorithm in important subgroups of patients with comorbidities from the U.S. perspective.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562436","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 : 2024-09-01DOI: 10.1164/rccm.v210erratum5
{"title":"Erratum: Shift-Level Team Familiarity Is Associated with Improved Outcomes in Mechanically Ventilated Adults.","authors":"","doi":"10.1164/rccm.v210erratum5","DOIUrl":"https://doi.org/10.1164/rccm.v210erratum5","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103571","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 : 2024-09-01DOI: 10.1164/rccm.202403-0492RL
Lisa D Burry, Chaim M Bell, Andrea Hill, Ruxandra Pinto, Damon C Scales, Susan E Bronskill, Louise Rose, David Williamson, Robert Fowler, Hannah Wunsch
{"title":"Trends in Sedative Prescription among Older Adults after Critical Illness: A Population-based Cohort Study.","authors":"Lisa D Burry, Chaim M Bell, Andrea Hill, Ruxandra Pinto, Damon C Scales, Susan E Bronskill, Louise Rose, David Williamson, Robert Fowler, Hannah Wunsch","doi":"10.1164/rccm.202403-0492RL","DOIUrl":"10.1164/rccm.202403-0492RL","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305223","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 : 2024-09-01DOI: 10.1164/rccm.v210erratum2
{"title":"Erratum: Serum Cell-Free DNA-based Detection of <i>Mycobacterium avium</i> Complex Infection.","authors":"","doi":"10.1164/rccm.v210erratum2","DOIUrl":"https://doi.org/10.1164/rccm.v210erratum2","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103570","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 : 2024-09-01DOI: 10.1164/rccm.202311-2161LE
Lei Ni, Ye Sun, Jian Ping Zhou, Qing Yun Li
{"title":"Comprehensive Strategies for the Follow-Up of Interstitial Lung Abnormality.","authors":"Lei Ni, Ye Sun, Jian Ping Zhou, Qing Yun Li","doi":"10.1164/rccm.202311-2161LE","DOIUrl":"10.1164/rccm.202311-2161LE","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309349","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 : 2024-09-01DOI: 10.1164/rccm.202404-0777LE
Yong Huang, Shwu-Fan Ma, Imre Noth
{"title":"Reply to van der Sar <i>et al.</i>: Classifying Interstitial Lung Disease: Omics Are in the Air.","authors":"Yong Huang, Shwu-Fan Ma, Imre Noth","doi":"10.1164/rccm.202404-0777LE","DOIUrl":"10.1164/rccm.202404-0777LE","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":null,"pages":null},"PeriodicalIF":19.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850028","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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