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. 2024 Nov;166(5):1010-1019.
doi: 10.1016/j.chest.2023.11.033. Epub 2023 Nov 25.

Silent Airway Mucus Plugs in COPD and Clinical Implications

Sofia K Mettler  1 , Hrudaya P Nath  2 , Scott Grumley  2 , José L Orejas  3 , Wojciech R Dolliver  4 , Pietro Nardelli  5 , Andrew C Yen  6 , Seth J Kligerman  7 , Kathleen Jacobs  6 , Padma P Manapragada  2 , Mostafa Abozeed  2 , Muhammad Usman Aziz  2 , Mohd Zahid  2 , Asmaa N Ahmed  2 , Nina L Terry  2 , Rim Elalami  4 , Ruben San José Estépar  5 , Sushilkumar Sonavane  8 , Ehab Billatos  9 , Wei Wang  10 , Raúl San José Estépar  5 , Jeremy B Richards  11 , Michael H Cho  12 , Alejandro A Diaz  3
Affiliations

Silent Airway Mucus Plugs in COPD and Clinical Implications

Sofia K Mettler et al. Chest. 2024 Nov.

Abstract

Background: Airway mucus plugs are frequently identified on CT scans of patients with COPD with a smoking history without mucus-related symptoms (ie, cough, phlegm [silent mucus plugs]).

Research question: In patients with COPD, what are the risk and protective factors associated with silent airway mucus plugs? Are silent mucus plugs associated with functional, structural, and clinical measures of disease?

Study design and methods: We identified mucus plugs on chest CT scans of participants with COPD from the COPDGene study. The mucus plug score was defined as the number of pulmonary segments with mucus plugs, ranging from 0 to 18, and categorized into three groups (0, 1-2, and ≥ 3). We determined risk and protective factors for silent mucus plugs and the associations of silent mucus plugs with measures of disease severity using multivariable linear and logistic regression models.

Results: Of 4,363 participants with COPD, 1,739 had no cough or phlegm. Among the 1,739 participants, 627 (36%) had airway mucus plugs identified on CT scan. Risk factors of silent mucus plugs (compared with symptomatic mucus plugs) were older age (OR, 1.02), female sex (OR, 1.40), and Black race (OR, 1.93) (all P values < .01). Among those without cough or phlegm, silent mucus plugs (vs absence of mucus plugs) were associated with worse 6-min walk distance, worse resting arterial oxygen saturation, worse FEV1 % predicted, greater emphysema, thicker airway walls, and higher odds of severe exacerbation in the past year in adjusted models.

Interpretation: Mucus plugs are common in patients with COPD without mucus-related symptoms. Silent mucus plugs are associated with worse functional, structural, and clinical measures of disease. CT scan-identified mucus plugs can complement the evaluation of patients with COPD.

Keywords: COPD; COPDGene; CT scan; airway; chronic bronchitis; chronic mucus hypersecretion; cough; emphysema; mucus plug; phlegm; silent mucus plug.

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Conflict of interest statement

Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. H. C. reported receiving grants from Bayer. A. A. D. reported receiving personal fees from Boehringer-Ingelheim and having a patent for Methods and Compositions Relating to Airway Dysfunction pending (701586-190200USPT). N. L. T. reported that she and/or her husband are general stockholders with no controlling interest in the following: Johnson & Johnson, Kimberly-Clark Corp, Microsoft Corp, Amgen Inc, Bristol Myers Squibb, Cisco Systems Inc, Medtronic, Merck & Co Inc, Procter & Gamble, Crisper Therapeutics, Nvidia, Texas Instruments, Hewlett-Packard, United Health, Abbott Labs, Eli Lilly and Co, AbbVie Inc, and LyondellBasell Industries. Ruben S. J. Estépar reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Raúl S. J. Estépar reported being a founder and equity holder of Quantitative Imaging Solutions; receiving grants from Boehringer-Ingelheim; contracts to serve as image core from Insmed and Lung Biotechnology; and personal fees from LeukoLab and Chiesi. A. C. Y. is supported by the NIH [Grants R01HL149861, R01HL164824, U01HL089897]. None declared (S. K. M., H. P. N., S. G., J. L. O., W. R. D., P. N., S. J. K., K. J., P. P. M., M. A., M. U. A., M. Z., A. N. A., R. E., S. S., E. B., W. W., J. B. R.).

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