Pub Date : 2024-11-01DOI: 10.1164/rccm.202405-1029ED
Mark Toshner
{"title":"Searching for an Elusive Phantom - Targeting Estrogen in Pulmonary Hypertension.","authors":"Mark Toshner","doi":"10.1164/rccm.202405-1029ED","DOIUrl":"10.1164/rccm.202405-1029ED","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1077-1078"},"PeriodicalIF":19.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454666","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}
Pub Date : 2024-11-01DOI: 10.1164/rccm.202402-0371OC
Steven M Kawut, Rui Feng, Susan S Ellenberg, Roham Zamanian, Todd Bull, Murali Chakinala, Stephen C Mathai, Anna Hemnes, Grace Lin, Margaret Doyle, Ruth Andrew, Margaret MacLean, Ioannis Stasinopoulos, Eric Austin, Angela DeMichele, Haochang Shou, Jasleen Minhas, Nianfu Song, Jude Moutchia, Corey E Ventetuolo
Rationale: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. Objectives: We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). Methods: We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four postmenopausal women with PAH and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at 6 months. By intention-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. Measurements and Main Results: Forty-one subjects were randomized to placebo and 43 to anastrozole, and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued the study drug. There was no significant difference in the change in 6MWD at 6 months (placebo-corrected treatment effect, -7.9 m; 95% confidence interval, -32.7 to 16.9; P = 0.53). There was no difference in adverse events between the groups. Conclusions: Anastrozole did not show a significant effect on 6MWD compared with placebo in postmenopausal women with PAH and in men with PAH. Anastrozole was safe and did not have adverse effects. Clinical trial registered with www.clincialtrials.gov (NCT03229499).
{"title":"Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.","authors":"Steven M Kawut, Rui Feng, Susan S Ellenberg, Roham Zamanian, Todd Bull, Murali Chakinala, Stephen C Mathai, Anna Hemnes, Grace Lin, Margaret Doyle, Ruth Andrew, Margaret MacLean, Ioannis Stasinopoulos, Eric Austin, Angela DeMichele, Haochang Shou, Jasleen Minhas, Nianfu Song, Jude Moutchia, Corey E Ventetuolo","doi":"10.1164/rccm.202402-0371OC","DOIUrl":"10.1164/rccm.202402-0371OC","url":null,"abstract":"<p><p><b>Rationale:</b> Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. <b>Objectives:</b> We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). <b>Methods:</b> We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four postmenopausal women with PAH and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at 6 months. By intention-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. <b>Measurements and Main Results:</b> Forty-one subjects were randomized to placebo and 43 to anastrozole, and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued the study drug. There was no significant difference in the change in 6MWD at 6 months (placebo-corrected treatment effect, -7.9 m; 95% confidence interval, -32.7 to 16.9; <i>P</i> = 0.53). There was no difference in adverse events between the groups. <b>Conclusions:</b> Anastrozole did not show a significant effect on 6MWD compared with placebo in postmenopausal women with PAH and in men with PAH. Anastrozole was safe and did not have adverse effects. Clinical trial registered with www.clincialtrials.gov (NCT03229499).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1143-1151"},"PeriodicalIF":19.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920247","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}
Pub Date : 2024-11-01DOI: 10.1164/rccm.202406-1104LE
Shodai Yoshihiro, Shunsuke Taito
{"title":"True Effect of Fludrocortisone for Septic Shock: Baseline Risk and Transitivity Concerns.","authors":"Shodai Yoshihiro, Shunsuke Taito","doi":"10.1164/rccm.202406-1104LE","DOIUrl":"10.1164/rccm.202406-1104LE","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1161-1162"},"PeriodicalIF":19.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103568","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}
Pub Date : 2024-11-01DOI: 10.1164/rccm.202406-1128RL
Sarah J Morgan, David P Nichols, Windy Ni, Gina Hong, Stephen J Salipante, George M Solomon, Steven M Rowe, John P Clancy, Robert A Cramer, Pradeep K Singh
{"title":"Elexacaftor/Tezacaftor/Ivacaftor Markedly Reduces <i>Aspergillus fumigatus</i> in Cystic Fibrosis.","authors":"Sarah J Morgan, David P Nichols, Windy Ni, Gina Hong, Stephen J Salipante, George M Solomon, Steven M Rowe, John P Clancy, Robert A Cramer, Pradeep K Singh","doi":"10.1164/rccm.202406-1128RL","DOIUrl":"10.1164/rccm.202406-1128RL","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1155-1158"},"PeriodicalIF":19.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071823","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 : 2024-11-01DOI: 10.1164/rccm.202402-0458RL
Christine M Bojanowski, Stella E Lee, Giraldina Trevejo-Nunez, Jennifer M Bomberger, Robert P Schleimer, Milene T Saavedra, Jay K Kolls
{"title":"IL-22Ra2 Levels Remain Elevated in People with Cystic Fibrosis despite Modulator Therapy.","authors":"Christine M Bojanowski, Stella E Lee, Giraldina Trevejo-Nunez, Jennifer M Bomberger, Robert P Schleimer, Milene T Saavedra, Jay K Kolls","doi":"10.1164/rccm.202402-0458RL","DOIUrl":"10.1164/rccm.202402-0458RL","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1158-1161"},"PeriodicalIF":19.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085917","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 : 2024-11-01DOI: 10.1164/rccm.202305-0868TR
Paul Brinkman, Michael Wilde, Waqar Ahmed, Ran Wang, Marc van der Schee, Shahd Abuhelal, Chad Schaber, Danen Cunoosamy, Graham W Clarke, Anke-Hilse Maitland-van der Zee, Sven-Erik Dahlén, Salman Siddiqui, Stephen J Fowler
The exhaled breath represents an ideal matrix for noninvasive biomarker discovery, and exhaled metabolomics have the potential to be clinically useful in the era of precision medicine. In this concise translational review, we specifically address volatile organic compounds in the breath, with a view toward fulfilling the promise of these as actionable biomarkers, in particular, for lung diseases. We review the literature paying attention to seminal work linked to key milestones in breath research; discuss potential applications for breath biomarkers across disease areas and healthcare systems, including the perspectives of industry; and outline critical aspects of study design that will need to be considered for any pivotal research going forward if breath analysis is to provide robust validated biomarkers that meet the requirements for future clinical implementation.
{"title":"Fulfilling the Promise of Breathomics: Considerations for the Discovery and Validation of Exhaled Volatile Biomarkers.","authors":"Paul Brinkman, Michael Wilde, Waqar Ahmed, Ran Wang, Marc van der Schee, Shahd Abuhelal, Chad Schaber, Danen Cunoosamy, Graham W Clarke, Anke-Hilse Maitland-van der Zee, Sven-Erik Dahlén, Salman Siddiqui, Stephen J Fowler","doi":"10.1164/rccm.202305-0868TR","DOIUrl":"10.1164/rccm.202305-0868TR","url":null,"abstract":"<p><p>The exhaled breath represents an ideal matrix for noninvasive biomarker discovery, and exhaled metabolomics have the potential to be clinically useful in the era of precision medicine. In this concise translational review, we specifically address volatile organic compounds in the breath, with a view toward fulfilling the promise of these as actionable biomarkers, in particular, for lung diseases. We review the literature paying attention to seminal work linked to key milestones in breath research; discuss potential applications for breath biomarkers across disease areas and healthcare systems, including the perspectives of industry; and outline critical aspects of study design that will need to be considered for any pivotal research going forward if breath analysis is to provide robust validated biomarkers that meet the requirements for future clinical implementation.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1079-1090"},"PeriodicalIF":19.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417227","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}
Pub Date : 2024-11-01DOI: 10.1164/rccm.210i9xxviii
{"title":"November 1 Highlight.","authors":"","doi":"10.1164/rccm.210i9xxviii","DOIUrl":"https://doi.org/10.1164/rccm.210i9xxviii","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"210 9","pages":"xxviii-xxx"},"PeriodicalIF":19.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556953","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 : 2024-10-29DOI: 10.1164/rccm.202403-0568OC
Jamie L Todd, S Sam Weigt, Megan L Neely, Maria V Grau-Sepulveda, Kristen Mason, Michelle L Sever, Karen Kesler, Jerry Kirchner, Courtney W Frankel, Tereza Martinu, Michael Y Shino, Annette M Jackson, Elizabeth N Pavlisko, Nikki Williams, Mark A Robien, Lianne G Singer, Marie Budev, Wayne Tsuang, Pali D Shah, John M Reynolds, Laurie D Snyder, John A Belperio, Scott M Palmer
Rationale: Chronic lung allograft dysfunction (CLAD) hinders lung transplant success. A 2019 consensus refined CLAD diagnosis, introducing probable or definite CLAD based on persistence of lung function decline. Outcomes and risks for probable CLAD remain uncertain.
Objectives: Determine the prognosis and clinical risks for probable CLAD in a prospective multicenter cohort.
Methods: Clinical Trials in Organ Transplantation-20 included 745 CLAD-eligible adult lung recipients at 5 centers and applied rigorous methods to prospectively adjudicate probable CLAD. The impact of probable CLAD on graft loss was determined using a Cox model that considered CLAD as a time-dependent covariate. Regularized Cox modeling with LASSO penalty was used to evaluate donor or recipient characteristics and the occurrence and timing of posttransplant events as probable CLAD risks. Similar analyses were performed for definite CLAD.
Measurements and main results: Probable CLAD occurred in 29.7% of patients at 3 years posttransplant and conferred a marked increase in risk for graft loss (unadjusted HR 4.38, p<0.001). Most patients (80%) with probable CLAD progressed to definite CLAD. Cytomegalovirus infection and specifically late presence (>90 days posttransplant) of donor-specific alloantibodies, acute rejection, acute lung injury, or organizing pneumonia contributed the greatest independent information about probable CLAD risk. Definite CLAD risks were similar.
Conclusions: Probable CLAD identifies patients at high risk for graft loss, supporting prospective identification of this condition for early initiation of CLAD-directed interventions. More effective strategies to prevent posttransplant cytomegalovirus, inhibit allospecific immunity, and reduce tissue injury are needed to reduce probable CLAD and improve lung recipient survival.
{"title":"Prognosis and Risks for Probable Chronic Lung Allograft Dysfunction: A Prospective Multicenter Study.","authors":"Jamie L Todd, S Sam Weigt, Megan L Neely, Maria V Grau-Sepulveda, Kristen Mason, Michelle L Sever, Karen Kesler, Jerry Kirchner, Courtney W Frankel, Tereza Martinu, Michael Y Shino, Annette M Jackson, Elizabeth N Pavlisko, Nikki Williams, Mark A Robien, Lianne G Singer, Marie Budev, Wayne Tsuang, Pali D Shah, John M Reynolds, Laurie D Snyder, John A Belperio, Scott M Palmer","doi":"10.1164/rccm.202403-0568OC","DOIUrl":"10.1164/rccm.202403-0568OC","url":null,"abstract":"<p><strong>Rationale: </strong>Chronic lung allograft dysfunction (CLAD) hinders lung transplant success. A 2019 consensus refined CLAD diagnosis, introducing probable or definite CLAD based on persistence of lung function decline. Outcomes and risks for probable CLAD remain uncertain.</p><p><strong>Objectives: </strong>Determine the prognosis and clinical risks for probable CLAD in a prospective multicenter cohort.</p><p><strong>Methods: </strong>Clinical Trials in Organ Transplantation-20 included 745 CLAD-eligible adult lung recipients at 5 centers and applied rigorous methods to prospectively adjudicate probable CLAD. The impact of probable CLAD on graft loss was determined using a Cox model that considered CLAD as a time-dependent covariate. Regularized Cox modeling with LASSO penalty was used to evaluate donor or recipient characteristics and the occurrence and timing of posttransplant events as probable CLAD risks. Similar analyses were performed for definite CLAD.</p><p><strong>Measurements and main results: </strong>Probable CLAD occurred in 29.7% of patients at 3 years posttransplant and conferred a marked increase in risk for graft loss (unadjusted HR 4.38, p<0.001). Most patients (80%) with probable CLAD progressed to definite CLAD. Cytomegalovirus infection and specifically late presence (>90 days posttransplant) of donor-specific alloantibodies, acute rejection, acute lung injury, or organizing pneumonia contributed the greatest independent information about probable CLAD risk. Definite CLAD risks were similar.</p><p><strong>Conclusions: </strong>Probable CLAD identifies patients at high risk for graft loss, supporting prospective identification of this condition for early initiation of CLAD-directed interventions. More effective strategies to prevent posttransplant cytomegalovirus, inhibit allospecific immunity, and reduce tissue injury are needed to reduce probable CLAD and improve lung recipient survival.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520730","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 : 2024-10-29DOI: 10.1164/rccm.202403-0632OC
Emily Wan, Andrew Yen, Rim Elalami, Scott Grumley, Hrudaya P Nath, Wei Wang, Sharon Brouha, Padma P Manapragada, Mostafa Abozeed, Muhammad Usman Aziz, Mohd Zahid, Asmaa N Ahmed, Nina L Terry, Pietro Nardelli, James C Ross, Victor Kim, Sushilkumar Sonavane, Seth J Kligerman, Jørgen Vestbo, Alvar Agusti, Kangjin Kim, Raul San José Estépar, Edwin K Silverman, Michael H Cho, Alejandro A Diaz
Rationale/Objective: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively.
Methods: Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene. Associations between ordinal mucus plug score categories (0/1-2/≥3) and prospectively-ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate-to-severe) and/or ER/hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment.
Results: Among 3,250 participants in COPDGene (mean±SD age 63.7±8.4 years, FEV1 50.6%±17.8% predicted, 45.1% female) and 1,716 participants in ECLIPSE (age 63.3±7.1 years, FEV1 48.3%±15.8% predicted, 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1-2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio, aRR [95%CI]=1.07[1.05-1.09] and 1.15[1.1-1.2] in COPDGene; aRR=1.06[1.02-1.09] and 1.12[1.04-1.2] in ECLIPSE, respectively) for prospective moderate-to-severe AEs. The presence of 1-2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR=1.05[1.01-1.08] and 1.09[1.02-1.18] in COPDGene; aRR=1.17[1.07-1.27] and 1.37[1.15-1.62] in ECLIPSE, respectively).
Conclusion: CT-based mucus plugs are associated with an increased risk for future COPD AEs.
{"title":"Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in COPD.","authors":"Emily Wan, Andrew Yen, Rim Elalami, Scott Grumley, Hrudaya P Nath, Wei Wang, Sharon Brouha, Padma P Manapragada, Mostafa Abozeed, Muhammad Usman Aziz, Mohd Zahid, Asmaa N Ahmed, Nina L Terry, Pietro Nardelli, James C Ross, Victor Kim, Sushilkumar Sonavane, Seth J Kligerman, Jørgen Vestbo, Alvar Agusti, Kangjin Kim, Raul San José Estépar, Edwin K Silverman, Michael H Cho, Alejandro A Diaz","doi":"10.1164/rccm.202403-0632OC","DOIUrl":"10.1164/rccm.202403-0632OC","url":null,"abstract":"<p><p>Rationale/Objective: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively.</p><p><strong>Methods: </strong>Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene. Associations between ordinal mucus plug score categories (0/1-2/≥3) and prospectively-ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate-to-severe) and/or ER/hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment.</p><p><strong>Results: </strong>Among 3,250 participants in COPDGene (mean±SD age 63.7±8.4 years, FEV1 50.6%±17.8% predicted, 45.1% female) and 1,716 participants in ECLIPSE (age 63.3±7.1 years, FEV1 48.3%±15.8% predicted, 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1-2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio, aRR [95%CI]=1.07[1.05-1.09] and 1.15[1.1-1.2] in COPDGene; aRR=1.06[1.02-1.09] and 1.12[1.04-1.2] in ECLIPSE, respectively) for prospective moderate-to-severe AEs. The presence of 1-2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR=1.05[1.01-1.08] and 1.09[1.02-1.18] in COPDGene; aRR=1.17[1.07-1.27] and 1.37[1.15-1.62] in ECLIPSE, respectively).</p><p><strong>Conclusion: </strong>CT-based mucus plugs are associated with an increased risk for future COPD AEs.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520728","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}