Wei-Jie Guan, Charles S Haworth, Harm A W M Tiddens, Michael R Loebinger, Adam T Hill, Oriol Sibila, Felix C Ringshausen, Bridget D Stuart, Yingying Wang, J Stuart Elborn, Nan-Shan Zhong, James D Chalmers
{"title":"The CFTR potentiator Icenticaftor for treatment of bronchiectasis: An international phase 2, double-blind, randomized placebo-controlled trial.","authors":"Wei-Jie Guan, Charles S Haworth, Harm A W M Tiddens, Michael R Loebinger, Adam T Hill, Oriol Sibila, Felix C Ringshausen, Bridget D Stuart, Yingying Wang, J Stuart Elborn, Nan-Shan Zhong, James D Chalmers","doi":"10.1093/ajrccm/aamag032","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag032","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282053","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":"Same Drug, Same Protocol, Different Results: Is Geography the Hidden Variable in ORBIT Trials?","authors":"Bin Deng, Wenhua Liu","doi":"10.1093/ajrccm/aamag020","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag020","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282099","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}
Shivani Singh, Fares Darawshy, Kirby Erlandson, Jayanth Kumar Narayana, Qingsheng Li, Yonghua Li, Isabella Atandi, Kelsey Krolikowski, Shrey Patel, Destiny Collazo, Micheál Mac Aogáin, Amy Gilmour, Merete Long, Miao Chang, Afshana Hoque, Rosemary Schluger, Sanjan Kumar, Cecilia J Chung, Kendrew Wong, Gabriella Porter, Yicheng Feng, Anna Czachor, Colin McCormick, Emily Clementi, Yaa Kyeremateng, Alena Lukovnikova, Danielle Harris, Sebastian Gomez, Taylor Kain, Ibrahim Kocak, Rajbir Singh, Claudia Rodriguez, Benjamin Kwok, Clea Barnett, Matthias Kugler, Michael D Weiden, Nathaniel Nelson, Jake G Natalini, David Luglio, Ludovic Desvignes, Samir Gautam, Erin McGuire, Terry Gordon, Imran Sulaiman, Jun-Chieh J Tsay, Ashwin Basavaraj, Benjamin G Wu, David Kamelhar, Doreen Addrizzo-Harris, James D Chalmers, Sanjay H Chotirmall, Leopoldo N Segal
Rationale: The discoveries of neutrophilic inflammation and Pseudomonas-dominant pulmonary dysbiosis have helped pave the way for host-directed therapy in bronchiectasis. Substantial knowledge gaps still remain about the interplay between neutrophilic signatures and microbes in non-tuberculous mycobacterial lung disease (NTM-LD), a phenotypically diverse lung infection that is increasingly prevalent in the United States and other parts of the world.
Objectives: Evaluate the lower airway microbiota and neutrophilic traits in NTM- and NTM+ bronchiectasis.
Methods: 16S rRNA gene sequencing, cell counts, and neutrophil extracellular trap (NET) immunoassays were performed on bronchoscopic lower airway samples in 200 bronchiectasis subjects (108 NTM-, 92 NTM+). A preclinical model of oral commensal micro-aspiration and NTM infection was used to profile the murine lower airways with flow cytometry and a NET assay.
Measurements and main results: Lower airways of NTM+ bronchiectasis patients were enriched with Mycobacterium and oral commensals (e.g., Veillonella, Prevotella and Streptococcus). NET levels were higher in NTM+ BAL. Mycobacterium and oral commensals co-occurred with NET and neutrophils in network studies. Distinct oral commensal taxa were associated with severe disease phenotypes such as cavitary disease and exacerbators. In a murine micro-aspiration model, the combination of oral commensals and Mycobacterium led to a sustained pro-inflammatory immune response marked by an increase in Th17, γδT cells, PD-1+ T lymphocytes as well as higher NET levels.
Conclusions: Our analyses showed that distinct microbiome features beyond the primary pathogen can contribute to neutrophilic inflammation and severe disease phenotypes in bronchiectasis/ NTM-LD.
{"title":"Lower Airway Dysbiosis in NTM+ Bronchiectasis is Associated with NET-Predominant Severe Phenotypes.","authors":"Shivani Singh, Fares Darawshy, Kirby Erlandson, Jayanth Kumar Narayana, Qingsheng Li, Yonghua Li, Isabella Atandi, Kelsey Krolikowski, Shrey Patel, Destiny Collazo, Micheál Mac Aogáin, Amy Gilmour, Merete Long, Miao Chang, Afshana Hoque, Rosemary Schluger, Sanjan Kumar, Cecilia J Chung, Kendrew Wong, Gabriella Porter, Yicheng Feng, Anna Czachor, Colin McCormick, Emily Clementi, Yaa Kyeremateng, Alena Lukovnikova, Danielle Harris, Sebastian Gomez, Taylor Kain, Ibrahim Kocak, Rajbir Singh, Claudia Rodriguez, Benjamin Kwok, Clea Barnett, Matthias Kugler, Michael D Weiden, Nathaniel Nelson, Jake G Natalini, David Luglio, Ludovic Desvignes, Samir Gautam, Erin McGuire, Terry Gordon, Imran Sulaiman, Jun-Chieh J Tsay, Ashwin Basavaraj, Benjamin G Wu, David Kamelhar, Doreen Addrizzo-Harris, James D Chalmers, Sanjay H Chotirmall, Leopoldo N Segal","doi":"10.1093/ajrccm/aamag015","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag015","url":null,"abstract":"<p><strong>Rationale: </strong>The discoveries of neutrophilic inflammation and Pseudomonas-dominant pulmonary dysbiosis have helped pave the way for host-directed therapy in bronchiectasis. Substantial knowledge gaps still remain about the interplay between neutrophilic signatures and microbes in non-tuberculous mycobacterial lung disease (NTM-LD), a phenotypically diverse lung infection that is increasingly prevalent in the United States and other parts of the world.</p><p><strong>Objectives: </strong>Evaluate the lower airway microbiota and neutrophilic traits in NTM- and NTM+ bronchiectasis.</p><p><strong>Methods: </strong>16S rRNA gene sequencing, cell counts, and neutrophil extracellular trap (NET) immunoassays were performed on bronchoscopic lower airway samples in 200 bronchiectasis subjects (108 NTM-, 92 NTM+). A preclinical model of oral commensal micro-aspiration and NTM infection was used to profile the murine lower airways with flow cytometry and a NET assay.</p><p><strong>Measurements and main results: </strong>Lower airways of NTM+ bronchiectasis patients were enriched with Mycobacterium and oral commensals (e.g., Veillonella, Prevotella and Streptococcus). NET levels were higher in NTM+ BAL. Mycobacterium and oral commensals co-occurred with NET and neutrophils in network studies. Distinct oral commensal taxa were associated with severe disease phenotypes such as cavitary disease and exacerbators. In a murine micro-aspiration model, the combination of oral commensals and Mycobacterium led to a sustained pro-inflammatory immune response marked by an increase in Th17, γδT cells, PD-1+ T lymphocytes as well as higher NET levels.</p><p><strong>Conclusions: </strong>Our analyses showed that distinct microbiome features beyond the primary pathogen can contribute to neutrophilic inflammation and severe disease phenotypes in bronchiectasis/ NTM-LD.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281845","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":"Reply to Tang and Sun, and to Deng and Liu.","authors":"Jamie Stobo, Rebecca C Hull, James D Chalmers","doi":"10.1093/ajrccm/aamag021","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag021","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282036","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":"Bronchiolocentric interstitial pneumonia: words matter.","authors":"Vincent Cottin","doi":"10.1093/ajrccm/aamag010","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag010","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281869","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":"Oxygenation and Organ Function: The Timeless Quest to Preserve Function and Avoid Toxicity.","authors":"Mark E Mikkelsen, Chiara Robba","doi":"10.1093/ajrccm/aamag005","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag005","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282047","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 EIT-Guided PEEP in ARDS: How Much Titration Is Too Much?","authors":"Tobias Becher, Eduardo Costa","doi":"10.1093/ajrccm/aamag012","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag012","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282106","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":"Predicting response to immunosuppression in non-IPF ILDs: Can molecular endotyping lead the way?","authors":"Jeffrey A Sparks, Barry S Shea","doi":"10.1093/ajrccm/aamag009","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag009","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282013","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}
Vincent D Gaertner, Leandra Ramin-Wright, Andreas D Waldmann, Carina Belting, Kaylen Gähwiler, Vanessa L Büchler, Christian Haslinger, Dirk Bassler, Christoph M Rüegger
Background: It remains unclear how the lung is aerated after birth in human infants. We aimed to describe volume changes over the first breaths of life.
Design: Prospective observational study in healthy infants after vaginal delivery.
Methods: Electrical impedance tomography (EIT) data were collected continuously after birth. End-expiratory lung volume (EELV), tidal volume (VT) and markers for regional ventilation distribution including center of ventilation (CoV), silent spaces (SS), functional lung size (FLS) and coefficient of variation (CV) for each of the first ten breaths and at each full minute until ten minutes after birth.
Main results: 10'546 breaths from 46 infants were analyzed. During the initial five breaths of life, EELV increased rapidly, and VT were approximately three-fold higher than post-transitional VT (linear mixed-model, both p<0.001). During the initial two breaths, there were unique regional inhomogeneities with preferential ventilation occurring sequentially in the right and left lung (CoVRL first vs second breath: 29.2±12.3 vs 53.5±9.5, post-hoc test, padj=0.003), before resolving quickly to a more even distribution of lung volume (decrease in CV, LMM: p<0.001). Finally, the lung periphery is less ventilated during the initial ten breaths, which improves over the subsequent ten minutes (increase in FLS, LMM: p<0.001).
Conclusions: This study visualizes and characterizes the first breaths of life, describing lung physiology during this crucial moment. Functional residual capacity is largely established within the first five breaths. The first breaths are characterized by large VT and show highly interesting regional inhomogeneities, likely reflecting complex anatomical and positional factors.
{"title":"The first breaths after birth-early lung function in healthy term infants.","authors":"Vincent D Gaertner, Leandra Ramin-Wright, Andreas D Waldmann, Carina Belting, Kaylen Gähwiler, Vanessa L Büchler, Christian Haslinger, Dirk Bassler, Christoph M Rüegger","doi":"10.1093/ajrccm/aamag008","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag008","url":null,"abstract":"<p><strong>Background: </strong>It remains unclear how the lung is aerated after birth in human infants. We aimed to describe volume changes over the first breaths of life.</p><p><strong>Design: </strong>Prospective observational study in healthy infants after vaginal delivery.</p><p><strong>Methods: </strong>Electrical impedance tomography (EIT) data were collected continuously after birth. End-expiratory lung volume (EELV), tidal volume (VT) and markers for regional ventilation distribution including center of ventilation (CoV), silent spaces (SS), functional lung size (FLS) and coefficient of variation (CV) for each of the first ten breaths and at each full minute until ten minutes after birth.</p><p><strong>Main results: </strong>10'546 breaths from 46 infants were analyzed. During the initial five breaths of life, EELV increased rapidly, and VT were approximately three-fold higher than post-transitional VT (linear mixed-model, both p<0.001). During the initial two breaths, there were unique regional inhomogeneities with preferential ventilation occurring sequentially in the right and left lung (CoVRL first vs second breath: 29.2±12.3 vs 53.5±9.5, post-hoc test, padj=0.003), before resolving quickly to a more even distribution of lung volume (decrease in CV, LMM: p<0.001). Finally, the lung periphery is less ventilated during the initial ten breaths, which improves over the subsequent ten minutes (increase in FLS, LMM: p<0.001).</p><p><strong>Conclusions: </strong>This study visualizes and characterizes the first breaths of life, describing lung physiology during this crucial moment. Functional residual capacity is largely established within the first five breaths. The first breaths are characterized by large VT and show highly interesting regional inhomogeneities, likely reflecting complex anatomical and positional factors.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282072","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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