Firoozeh V Gerayeli, Hye Yun Park, Stephen Milne, Xuan Li, Chen Xi Yang, Josie Tuong, Rachel L Eddy, Seyed Milad Vahedi, Elizabeth Guinto, Chung Y Cheung, Julia Sw Yang, Cassie Gilchrist, Dina Yehia, Tara Stach, Hong Dang, Clarus Leung, Tawimas Shaipanich, Jonathon Leipsic, Graeme J Koelwyn, Janice M Leung, Don D Sin
{"title":"Single cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID.","authors":"Firoozeh V Gerayeli, Hye Yun Park, Stephen Milne, Xuan Li, Chen Xi Yang, Josie Tuong, Rachel L Eddy, Seyed Milad Vahedi, Elizabeth Guinto, Chung Y Cheung, Julia Sw Yang, Cassie Gilchrist, Dina Yehia, Tara Stach, Hong Dang, Clarus Leung, Tawimas Shaipanich, Jonathon Leipsic, Graeme J Koelwyn, Janice M Leung, Don D Sin","doi":"10.1183/13993003.01947-2023","DOIUrl":"https://doi.org/10.1183/13993003.01947-2023","url":null,"abstract":"<p><p>To elucidate the important cellular and molecular drivers of pulmonary long COVID, we generated a single-cell transcriptomic map of the airway mucosa using bronchial brushings from patients with long COVID who reported persistent pulmonary symptoms.Adults with and without long COVID were recruited from the general community in Greater Vancouver, Canada. The cohort was divided into those with pulmonary long COVID (PLC), which was defined as persons with new or worsening respiratory symptoms following at least one year from their initial acute SARS-CoV-2 infection (N=9); and control subjects defined as SARS-CoV-2 infected persons whose acute respiratory symptoms had fully resolved or individuals who had no history of acute COVID-19 (N=9). These participants underwent bronchoscopy from which a single cell suspension was created from bronchial brush samples and then sequenced.A total of 56 906 cells were recovered for the downstream analysis, with 34 840 cells belonging to the PLC group, which strikingly showed a unique cluster of neutrophils in the PLC group (p<0.05). Ingenuity Pathway Analysis revealed that the neutrophil degranulation pathway was enriched across epithelial cell clusters. Differential gene expression analysis between the PLC and control groups demonstrated upregulation of inflammatory chemokines and epithelial barrier dysfunction across epithelial cell clusters, as well as over-expression of mucin genes across secretory cell clusters.In conclusion, a single-cell transcriptomic landscape of the small airways suggest that neutrophils may play a significant role in mediating the chronic small airway inflammation driving pulmonary symptoms of long COVID.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344446","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}
Tasha Tsao, Longhui Qiu, Reena Bharti, Avishai Shemesh, Alberto M Hernandez, Simon J Cleary, Nancy Y Greenland, Jesse Santos, Ruoshi Shi, Lu Bai, Jennifer Richardson, Kimberley Dilley, Matthias Will, Nenad Tomasevic, Tereza Sputova, Adam Salles, Jeffrey Kang, Dongliang Zhang, Steven R Hays, Jasleen Kukreja, Jonathan P Singer, Lewis L Lanier, Mark R Looney, John R Greenland, Daniel R Calabrese
{"title":"CD94<sup>+</sup> natural killer cells potentiate pulmonary ischaemia-reperfusion injury.","authors":"Tasha Tsao, Longhui Qiu, Reena Bharti, Avishai Shemesh, Alberto M Hernandez, Simon J Cleary, Nancy Y Greenland, Jesse Santos, Ruoshi Shi, Lu Bai, Jennifer Richardson, Kimberley Dilley, Matthias Will, Nenad Tomasevic, Tereza Sputova, Adam Salles, Jeffrey Kang, Dongliang Zhang, Steven R Hays, Jasleen Kukreja, Jonathan P Singer, Lewis L Lanier, Mark R Looney, John R Greenland, Daniel R Calabrese","doi":"10.1183/13993003.02171-2023","DOIUrl":"10.1183/13993003.02171-2023","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary ischaemia-reperfusion injury (IRI) is a major contributor to poor lung transplant outcomes. We recently demonstrated a central role of airway-centred natural killer (NK) cells in mediating IRI; however, there are no existing effective therapies for directly targeting NK cells in humans.</p><p><strong>Methods: </strong>We hypothesised that a depleting anti-CD94 monoclonal antibody (mAb) would provide therapeutic benefit in mouse and human models of IRI based on high levels of <i>KLRD1</i> (CD94) transcripts in bronchoalveolar lavage samples from lung transplant patients.</p><p><strong>Results: </strong>We found that CD94 is highly expressed on mouse and human NK cells, with increased expression during IRI. Anti-mouse and anti-human mAbs against CD94 showed effective NK cell depletion in mouse and human models and blunted lung damage and airway epithelial killing, respectively. In two different allogeneic orthotopic lung transplant mouse models, anti-CD94 treatment during induction reduced early lung injury and chronic inflammation relative to control therapies. Anti-CD94 did not increase donor antigen-presenting cells that could alter long-term graft acceptance.</p><p><strong>Conclusions: </strong>Lung transplant induction regimens incorporating anti-CD94 treatment may safely improve early clinical outcomes.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079833","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}
Elizabeth V Arkema,Michael C Sachs,Annica Dominicus,Anders Eklund,Anna Smed-Sörensen,Johan Grunewald,Anders Blomberg
{"title":"Inflammatory plasma protein levels are elevated years before sarcoidosis diagnosis: a nested case-control study in Sweden.","authors":"Elizabeth V Arkema,Michael C Sachs,Annica Dominicus,Anders Eklund,Anna Smed-Sörensen,Johan Grunewald,Anders Blomberg","doi":"10.1183/13993003.00277-2024","DOIUrl":"https://doi.org/10.1183/13993003.00277-2024","url":null,"abstract":"Sarcoidosis is an immune-mediated inflammatory disease whose natural development is not well understood. We aimed to determine if inflammatory plasma protein levels are elevated before sarcoidosis diagnosis compared to controls. Furthermore, we investigated which proteins are increased and how long before diagnosis they are increased. Cases with sarcoidosis and controls matched 2:1 on sex, birthdate, subcohort and sample date were identified in the Northern Sweden Health and Disease Study to perform a nested case-control study. Cases were validated and included if they provided ≥1 plasma sample ≥2 years before sarcoidosis diagnosis. Plasma protein levels were measured using the Olink Inflammation panel and expressed in Normalized Protein eXpression values. Unconditional logistic regression models adjusted for age, sex, subcohort and time since sampling were used to estimate log odds ratios with 95% confidence intervals for each protein overall and by time to diagnosis. p-values were adjusted for multiple comparisons using the Benjamini-Hochberg method. We included 152 cases and 341 controls. Mean time between sample and sarcoidosis diagnosis was 13.4 years. Forty-four proteins were significantly elevated prior to sarcoidosis compared to controls in multivariable-adjusted analyses. The ten proteins with the lowest p-values were CCL3, CCL19, CDCP1, CXCL9, CXCL10, IFNγ, IL-12B, MCP-3, TNF, and TNFRSF9. Fewer proteins were associated with sarcoidosis in samples taken longer before diagnosis. Restricting to samples taken ≥10 years prior to sarcoidosis diagnosis, 27 proteins remained statistically significant. Several inflammatory proteins were elevated in plasma many years before sarcoidosis onset compared to controls, revealing a preclinical phase characterised by inflammation.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"29 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328901","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":"ERJ Podcast September 2024: ERS Congress","authors":"European Respiratory Society","doi":"10.1183/13993003.e6403-2024","DOIUrl":"https://doi.org/10.1183/13993003.e6403-2024","url":null,"abstract":"<p>As part of the September issue, the <I>European Respiratory Journal</I> presents the latest in its series of podcasts. Chief Editor James Chalmers and Deputy Chief Editor Don Sin interview section editor Marc Humbert and Pamela McShane (University of Texas, Tyler, TX, USA) about articles presented at the ERS Congress.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"51 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321559","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}
Sandeep Bodduluri,Arie Nakhmani,Abhilash S Kizhakke Puliyakote,Joseph M Reinhardt,Mark T Dransfield,Surya P Bhatt
{"title":"Airway Tapering in Chronic Obstructive Pulmonary Disease.","authors":"Sandeep Bodduluri,Arie Nakhmani,Abhilash S Kizhakke Puliyakote,Joseph M Reinhardt,Mark T Dransfield,Surya P Bhatt","doi":"10.1183/13993003.00191-2024","DOIUrl":"https://doi.org/10.1183/13993003.00191-2024","url":null,"abstract":"BACKGROUNDLuminal narrowing is a hallmark feature of airway remodeling in COPD, but current measures focus on airway wall remodeling. Quantification of the natural increase in cumulative cross-sectional area along the length of the human airway tree can facilitate assessment of airway narrowing.METHODSWe analysed the airway trees of 7641 subjects enrolled in the multicenter COPDGene cohort. Airway luminal tapering was assessed by estimating the slope of the change in cumulative cross-sectional area along the length of the airway tree over successive generations (T-Slope). We performed multivariable regression analyses to test the associations between T-Slope and lung function, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea score, 6-minute walk distance (6 MWD), FEV1 change, exacerbations, and all-cause mortality after adjusting for demographics, %CT emphysema, and total airway count.RESULTSThe T-Slope decreased with increasing COPD severity: 2.69 (0.70) in nonsmokers and 2.33 (0.70), 2.11 (0.65), 1.78 (0.58), 1.60 (0.53), and 1.57 (0.52) in GOLD stages 0 through 4 respectively (Jonckheere-Terpstra p=0.04). On multivariable analyses, the T-Slope was independently associated with FEV1 (β=0.13 L, 95% CI 0.10 to 0.15, p<0.001), 6MWD (β=15.0 m, 95%CI 10.8 to 19.2, p<0.001), change in FEV1 (β=-4.50 ml·year-1, 95% CI -7.32 to -1.67; p=0.001), exacerbations (IRR=0.78, 95% CI 0.73 to 0.83, p<0.001), and mortality (HR=0.79, 95% CI 0.72 to 0.86, p<0.001).CONCLUSIONT-Slope is a measure of airway luminal remodeling and is associated with respiratory morbidity and mortality.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"29 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328890","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}
Ali Önder Yildirim, Thomas M. Conlon, Ian M. Adcock, Reinoud Gosens, Mareike Lehmann, Theodore S. Kapellos, Yohannes Tesfaigzi, Francesca Polverino, Maor Sauler, Roxana Wasnick, Enid Rose Neptune
{"title":"COPD-iNET: a call to the lung community for action to combat the global epidemic of COPD","authors":"Ali Önder Yildirim, Thomas M. Conlon, Ian M. Adcock, Reinoud Gosens, Mareike Lehmann, Theodore S. Kapellos, Yohannes Tesfaigzi, Francesca Polverino, Maor Sauler, Roxana Wasnick, Enid Rose Neptune","doi":"10.1183/13993003.00921-2024","DOIUrl":"https://doi.org/10.1183/13993003.00921-2024","url":null,"abstract":"<sec><st>Extract</st>\u0000<p>COPD is an increasingly prevalent, progressive and often debilitating lung disease, currently the third leading cause of death globally. While commonly considered a disease of smokers, common causes of COPD also include environmental pollution, infection, pre- and peri-natal life insults, and genetic predisposition [1, 2]. Current therapies are limited to reducing the burden of symptoms or exacerbations, but do not fundamentally alter the trajectory of the disease.</p>\u0000</sec>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"8 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321558","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}
Kathryn A Ramsey,Sanja Stanojevic,Luis Chavez,Noah Johnson,Cole Bowerman,Graham L Hall,Philipp Latzin,Katherine O'Neill,Paul D Robinson,Mirjam Stahl,Daniel J Weiner,Annelies M Zwitserloot,Alex Horsley,
{"title":"ERS technical standard: Global Lung Function Initiative reference values for multiple breath washout indices.","authors":"Kathryn A Ramsey,Sanja Stanojevic,Luis Chavez,Noah Johnson,Cole Bowerman,Graham L Hall,Philipp Latzin,Katherine O'Neill,Paul D Robinson,Mirjam Stahl,Daniel J Weiner,Annelies M Zwitserloot,Alex Horsley,","doi":"10.1183/13993003.00524-2024","DOIUrl":"https://doi.org/10.1183/13993003.00524-2024","url":null,"abstract":"BACKGROUNDMultiple breath washout is a lung function test based on tidal breathing that assesses lung volume and ventilation distribution. The aim of this analysis was to use the Global Lung Function Initiative methodology to develop all-age reference equations for the multiple breath washout indices lung clearance index (LCI) and functional residual capacity (FRC).METHODSMultiple breath washout data from healthy individuals were collated from sites. Data were re-analysed using the latest software versions. Reference equations were derived using the lambda-mu-sigma (LMS) method using the generalised additive models of location shape and scale programme in R. The impact of equipment type, inert tracer gas, and equipment dead space volume on the derived reference ranges were investigated.RESULTSData from 23 sites (n=3647 test occasions) were submitted. Reference equations were derived from 1581 unique observations from participants between the ages of 2 and 81 years. Equipment type, inert tracer gas, and equipment dead space volume did not significantly affect the prediction equations for either LCI or FRC. Reference equations for LCI include age as the only predictor, whereas sex-specific reference equations for FRC included height and age.CONCLUSIONSGlobal Lung Function Initiative reference equations for multiple breath washout variables provide a standard for reporting and interpretation of LCI and FRC.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"7 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328860","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}
Nidhy P Varghese, Eric D Austin, Csaba Galambos, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman
{"title":"An interdisciplinary consensus approach to pulmonary hypertension in developmental lung disease.","authors":"Nidhy P Varghese, Eric D Austin, Csaba Galambos, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman","doi":"10.1183/13993003.00639-2024","DOIUrl":"10.1183/13993003.00639-2024","url":null,"abstract":"<p><p>It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximise long-term outcomes. To better define the nature of PH in the setting of developmental lung disease (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise clinical features of infants with DEVLD/DEVLD-PH and identify decision-making challenges including genetic evaluations, the role of lung biopsies, the use of imaging modalities and treatment approaches. The importance of working with team members from multiple disciplines, enhancing communication and providing sufficient counselling services for families is emphasised to create an interdisciplinary consensus.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nick H Kim,Richard Channick,Marion Delcroix,Michael Madani,Joanna Pepke-Zaba,Julian I Borissoff,Valerie Easton,Sophie Gesang,Dominik Richard,Hossein-Ardeschir Ghofrani
{"title":"Efficacy and safety of selexipag in patients with inoperable or persistent/recurrent CTEPH (SELECT randomised trial).","authors":"Nick H Kim,Richard Channick,Marion Delcroix,Michael Madani,Joanna Pepke-Zaba,Julian I Borissoff,Valerie Easton,Sophie Gesang,Dominik Richard,Hossein-Ardeschir Ghofrani","doi":"10.1183/13993003.00193-2024","DOIUrl":"https://doi.org/10.1183/13993003.00193-2024","url":null,"abstract":"BACKGROUNDSELECT was the first global randomised controlled trial of selexipag with standard of care in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension.METHODSSELECT was a multicentre, randomised, double-blind, placebo-controlled, parallel-group, group-sequential, phase 3 study (NCT03689244). Adults aged ≤85 years in WHO functional class I-IV, with a 6-minute walk distance (6 MWD) of 100-450 m, were randomised (1:1) to receive selexipag (200-1600 µg b.i.d. titration until individual maximum tolerated dose)+standard of care or placebo+standard of care. Patients were recruited into the haemodynamic set (first 91 randomised patients to undergo right heart catheterisation [RHC]; Week 20) or non-haemodynamic cohort (remaining patients, no RHC required). Primary endpoint was percent of baseline pulmonary vascular resistance (PVR; Week 20). Safety was also assessed.RESULTSOf 321 patients screened, 128 were randomised (haemodynamic set: n=91 [selexipag: n=47; placebo: n=44]). In the haemodynamic set, 29 (31.9%) patients had previous pulmonary endarterectomy (PEA), 20 (22.0%) balloon pulmonary angioplasty (BPA), and 14 (15.4%) both PEA and BPA; 28 (30.8%) were inoperable. The Independent Data Monitoring Committee recommended to stop the study for futility as no statistically significant difference was observed for the primary endpoint (between-treatment geometric least squares mean ratio of PVR: 0.95 [95% CI 0.84, 1.07; p=0.412]). Adverse events were reported in 63 (98.4%) and 53 (82.8%) patients for selexipag and placebo, respectively.CONCLUSIONSELECT was discontinued for futility, as no treatment effect on the primary endpoint (PVR) was observed. Safety data were consistent with the established safety profile of selexipag, with no new safety signals identified.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"37 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328861","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}
Michael E Wechsler,Guy Brusselle,J Christian Virchow,Arnaud Bourdin,Konstantinos Kostikas,Jean-Pierre Llanos,Stephanie L Roseti,Christopher S Ambrose,Gillian Hunter,David J Jackson,Mario Castro,Njira Lugogo,Ian D Pavord,Neil Martin,Christopher E Brightling
{"title":"Clinical response and on-treatment clinical remission with tezepelumab in a broad population of patients with severe, uncontrolled asthma: results over 2 years from the NAVIGATOR and DESTINATION studies.","authors":"Michael E Wechsler,Guy Brusselle,J Christian Virchow,Arnaud Bourdin,Konstantinos Kostikas,Jean-Pierre Llanos,Stephanie L Roseti,Christopher S Ambrose,Gillian Hunter,David J Jackson,Mario Castro,Njira Lugogo,Ian D Pavord,Neil Martin,Christopher E Brightling","doi":"10.1183/13993003.00316-2024","DOIUrl":"https://doi.org/10.1183/13993003.00316-2024","url":null,"abstract":"BACKGROUNDIn asthma, clinical response is characterized by disease improvement with treatment, whereas clinical remission is characterized by long-term disease stabilization with or without ongoing treatment. The proportion of patients receiving tezepelumab who responded to treatment and those who achieved on-treatment clinical remission was assessed in the NAVIGATOR (NCT03347279) and DESTINATION (NCT03706079) studies of severe, uncontrolled asthma.METHODSNAVIGATOR and DESTINATION were phase 3, randomized, double-blind, placebo-controlled studies; DESTINATION was an extension of NAVIGATOR. Complete clinical response was defined as achieving all of the following: ≥50% reduction in exacerbations versus the previous year, improvements in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) of ≥100 mL or ≥5%, improvements in Asthma Control Questionnaire (ACQ)-6 score of ≥0.5 and physicians' assessment of asthma improvement. On-treatment clinical remission was defined as an ACQ-6 total score ≤1.5, stable lung function (pre-BD FEV1 >95% of baseline) and no exacerbations or use of oral corticosteroids during the time periods assessed.RESULTSHigher proportions of tezepelumab than placebo recipients achieved complete clinical response over weeks 0-52 (46% versus 24%; OR: 2.83 [95% CI: 2.10-3.82]), and on-treatment clinical remission over weeks 0-52 (28.5% versus 21.9%; OR: 1.44 [95% CI: 0.95-2.19]) and weeks >52-104 (33.5% versus 26.7%; OR: 1.44 [95% CI: 0.97-2.14]). Tezepelumab recipients who achieved on-treatment clinical remission versus complete clinical response at week 52 had better preserved lung function and lower inflammatory biomarkers at baseline, and fewer exacerbations in the 12 months before the study.CONCLUSIONSAmong patients with severe, uncontrolled asthma, tezepelumab treatment was associated with an increased likelihood of achieving complete clinical response and on-treatment clinical remission compared with placebo. Both are clinically important outcomes but may be driven by different patient characteristics.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"22 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328888","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}