Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers.

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Abstract

Rationale: The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain.Objectives: To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD.Methods: We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images, and imaging software automatically quantified emphysema percentage. Unadjusted and adjusted relationships between mucus plug score, emphysema percentage, and lung function were determined using regression.Measurements and Main Results: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema, and subgroups could be identified with mucus-dominant and emphysema-dominant disease. Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and emphysema percentage were independently associated with lower values for FEV1 and peripheral oxygen saturation (P < 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema (P < 0.001). Compared with smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 ± 7.7 vs. 14.4 ± 13.3), more frequent annual exacerbations (0.75 ± 1.1 vs. 0.43 ± 0.85), and shorter 6-minute-walk distance (329 ± 115 vs. 392 ± 117 m) (P < 0.001).Conclusions: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting patients with mucus-high/emphysema-low COPD in clinical trials of mucoactive treatments.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

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Author and article information

Journal

Journal ID (iso-abbrev): Am J Respir Crit Care Med

Title: American journal of respiratory and critical care medicine

Publisher: American Thoracic Society

ISSN (Electronic): 1535-4970

ISSN (Print): 1073-449X

Publication date (Electronic): Apr 15 2021

Volume: 203

Issue: 8

Affiliations

[1 ] Education and Research Centre, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland.

[2 ] Department of Radiology and Biomedical Imaging.

[3 ] Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.

[4 ] Department of Medical Physics and.

[5 ] Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

[6 ] Division of Pulmonary and Critical Care Medicine, Department of Medicine.

[7 ] Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California Los Angeles, Los Angeles, California.

[8 ] Division of General Medicine, Department of Medicine, Columbia University, New York City, New York.

[9 ] Division of Genetics, Genomics, and Precision Medicine, Department of Medicine, University of Arizona, Tucson, Arizona.

[10 ] Marsico Lung Institute/UNC Cystic Fibrosis Center, and.

[11 ] Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, Colorado.

[12 ] Cardiovascular Research Institute, and.

[13 ] Division of Pulmonary, Critical Care, and Occupational Medicine, Department of Internal Medicine.

[14 ] Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

[15 ] Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, Pennsylvania.

[16 ] Division of Pulmonary, Allergy, & Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

[17 ] Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.

[18 ] Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan at Ann Arbor, Ann Arbor, Michigan.

[19 ] Pulmonary, Critical Care, Allergy, and Immunologic Medicine, Department of Internal Medicine, Wake Forest University, Winston-Salem, North Carolina.

[20 ] Department of Radiology.

[21 ] Department of Medicine, and.

[22 ] Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa.

[23 ] Division of Pulmonary, Critical Care, Sleep, and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.

[24 ] Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine and New York-Presbyterian Weill Cornell Medical Center, New York, New York.

[25 ] Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, California.

[26 ] Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Utah Hospitals and Clinics, Salt Lake City, Utah.

[27 ] Department of Veterans Affairs Medical Center, Salt Lake City, Utah; and.

[28 ] Department of Radiology, University of Utah School of Medicine, Salt Lake City, Utah.

Article

DOI: 10.1164/rccm.202006-2248OC

PMC ID: 8048745

PubMed ID: 33180550

SO-VID: 4f2ffbc9-4d13-43d6-87b9-798f35a3d4c6

History

Keywords: mucus plugs,FEV1,emphysema,COPD,computed tomography

Data availability:

Keywords: mucus plugs, FEV1, emphysema, COPD, computed tomography

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