Longitudinal Changes in Airway Mucus Plugs and FEV1 in COPD

doi:10.1056/NEJMc2502456

. 2025 May 15;392(19):1973-1975.

doi: 10.1056/NEJMc2502456.

Longitudinal Changes in Airway Mucus Plugs and FEV₁ in COPD

Sofia K Mettler¹, Pietro Nardelli¹, Monica Iturrioz Campo¹, Rubén San José Estépar¹, Padma P Manapragada², Mostafa Abozeed², Muhammad Usman Aziz², Mohd Zahid², Scott Grumley², Hrudaya P Nath², Andrew Yen³, Sushilkumar Sonavane⁴, Christian F Clarenbach⁵, Wei Wang¹, Carrie L Pistenmaa¹, George R Washko¹, Raúl San José Estépar¹, Michael H Cho¹, Alejandro A Diaz¹; COPDGene Investigators; COPDGene site investigators

Collaborators, Affiliations

Collaborators

COPDGene site investigators:
James D Crapo, Edwin K Silverman, Barry J Make, Elizabeth A Regan, Terri Beaty, Ferdouse Begum, Peter J Castaldi, Michael Cho, Dawn L DeMeo, Adel R Boueiz, Marilyn G Foreman, Eitan Halper-Stromberg, Lystra P Hayden, Craig P Hersh, Jacqueline Hetmanski, Brian D Hobbs, John E Hokanson, Nan Laird, Christoph Lange, Sharon M Lutz, Merry-Lynn McDonald, Margaret M Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O Coxson, Craig J Galban, MeiLan K Han, Eric A Hoffman, Stephen Humphries, Francine L Jacobson, Philip F Judy, Ella A Kazerooni, Alex Kluiber, David A Lynch, Pietro Nardelli, John D Newell Jr, Aleena Notary, Andrea Oh, James C Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R Washko, Carla G Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A Young, Surya P Bhatt, Jessica Bon, Alejandro A Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L Curtis, Perry G Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R Graham Barr, John Austin, Belinda D'Souza, Byron Thomashow, Neil MacIntyre Jr, H Page McAdams, Lacey Washington, Eric Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhane, Christine Wendt, Brian Bell, Ken M Kunisaki, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P Comellas, Karin F Hoth, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E Ruiz, Harjinder Singh

Affiliations

¹ Brigham and Women's Hospital, Boston.
² University of Alabama at Birmingham, Birmingham.
³ University of California, San Diego, La Jolla.
⁴ Mayo Clinic, Jacksonville, FL.
⁵ University Hospital Zurich, Zurich, Switzerland.

PMID: 40367384
PMCID: PMC12356501
DOI: 10.1056/NEJMc2502456

Longitudinal Changes in Airway Mucus Plugs and FEV₁ in COPD

Sofia K Mettler et al. N Engl J Med. 2025.

. 2025 May 15;392(19):1973-1975.

doi: 10.1056/NEJMc2502456.

Authors

Collaborators

COPDGene site investigators:
James D Crapo, Edwin K Silverman, Barry J Make, Elizabeth A Regan, Terri Beaty, Ferdouse Begum, Peter J Castaldi, Michael Cho, Dawn L DeMeo, Adel R Boueiz, Marilyn G Foreman, Eitan Halper-Stromberg, Lystra P Hayden, Craig P Hersh, Jacqueline Hetmanski, Brian D Hobbs, John E Hokanson, Nan Laird, Christoph Lange, Sharon M Lutz, Merry-Lynn McDonald, Margaret M Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O Coxson, Craig J Galban, MeiLan K Han, Eric A Hoffman, Stephen Humphries, Francine L Jacobson, Philip F Judy, Ella A Kazerooni, Alex Kluiber, David A Lynch, Pietro Nardelli, John D Newell Jr, Aleena Notary, Andrea Oh, James C Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R Washko, Carla G Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A Young, Surya P Bhatt, Jessica Bon, Alejandro A Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L Curtis, Perry G Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R Graham Barr, John Austin, Belinda D'Souza, Byron Thomashow, Neil MacIntyre Jr, H Page McAdams, Lacey Washington, Eric Flenaugh, Silanth Terpenning, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhane, Christine Wendt, Brian Bell, Ken M Kunisaki, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P Comellas, Karin F Hoth, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E Ruiz, Harjinder Singh

Affiliations

¹ Brigham and Women's Hospital, Boston.
² University of Alabama at Birmingham, Birmingham.
³ University of California, San Diego, La Jolla.
⁴ Mayo Clinic, Jacksonville, FL.
⁵ University Hospital Zurich, Zurich, Switzerland.

PMID: 40367384
PMCID: PMC12356501
DOI: 10.1056/NEJMc2502456

No abstract available

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Figures

**Figure 1**
**(A)** Unadjusted post-bronchodilator FEV₁ in mL at the baseline and 5-year follow-up visits by mucus plug change category. **(B)** Estimated marginal means of post-bronchodilator FEV₁ (mL/year) changes by mucus plug change category (negative numbers indicate decline). Marginal means are estimated by a multivariable linear regression model adjusting for age, sex, race, BMI, height, pack-years, change in smoking status, baseline FEV₁, history of asthma, history of congestive heart failure, CT measures of wall thickness and emphysema and baseline mucus plug score. **(C)** Estimated marginal means with the same multivariable model, including interaction between mucus plug change and smoking status change. Error bars represent 95% confidence intervals. See Table S5 for complete results.

See this image and copyright information in PMC

References

1. Okajima Y, Come CE, Nardelli P, et al. Luminal Plugging on Chest CT Scan: Association With Lung Function, Quality of Life, and COPD Clinical Phenotypes. Chest 2020;158:121–30. - PMC - PubMed
1. Dunican EM, Elicker BM, Henry T, et al. Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers. Am J Respir Crit Care Med 2021;203:957–68. - PMC - PubMed
1. Diaz AA, Orejas JL, Grumley S, et al. Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease. Jama 2023;329:1832–9. - PMC - PubMed
1. Regan EA, Hokanson JE, Murphy JR, et al. Genetic epidemiology of COPD (COPDGene) study design. COPD 2010;7:32–43. - PMC - PubMed
1. Nordenmark LH, Hellqvist A, Emson C, et al. Tezepelumab and Mucus Plugs in Patients with Moderate-to-Severe Asthma. NEJM Evid 2023;2:EVIDoa2300135. - PubMed

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[1] Okajima Y, Come CE, Nardelli P, et al. Luminal Plugging on Chest CT Scan: Association With Lung Function, Quality of Life, and COPD Clinical Phenotypes. Chest 2020;158:121–30. - PMC - PubMed

[2] Okajima Y, Come CE, Nardelli P, et al. Luminal Plugging on Chest CT Scan: Association With Lung Function, Quality of Life, and COPD Clinical Phenotypes. Chest 2020;158:121–30. - PMC - PubMed

[3] Dunican EM, Elicker BM, Henry T, et al. Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers. Am J Respir Crit Care Med 2021;203:957–68. - PMC - PubMed

[4] Dunican EM, Elicker BM, Henry T, et al. Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers. Am J Respir Crit Care Med 2021;203:957–68. - PMC - PubMed

[5] Diaz AA, Orejas JL, Grumley S, et al. Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease. Jama 2023;329:1832–9. - PMC - PubMed

[6] Diaz AA, Orejas JL, Grumley S, et al. Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease. Jama 2023;329:1832–9. - PMC - PubMed

[7] Regan EA, Hokanson JE, Murphy JR, et al. Genetic epidemiology of COPD (COPDGene) study design. COPD 2010;7:32–43. - PMC - PubMed

[8] Regan EA, Hokanson JE, Murphy JR, et al. Genetic epidemiology of COPD (COPDGene) study design. COPD 2010;7:32–43. - PMC - PubMed

[9] Nordenmark LH, Hellqvist A, Emson C, et al. Tezepelumab and Mucus Plugs in Patients with Moderate-to-Severe Asthma. NEJM Evid 2023;2:EVIDoa2300135. - PubMed

[10] Nordenmark LH, Hellqvist A, Emson C, et al. Tezepelumab and Mucus Plugs in Patients with Moderate-to-Severe Asthma. NEJM Evid 2023;2:EVIDoa2300135. - PubMed

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Longitudinal Changes in Airway Mucus Plugs and FEV₁ in COPD

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Longitudinal Changes in Airway Mucus Plugs and FEV₁ in COPD

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Figures

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References

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Grants and funding

LinkOut - more resources

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