Silent Airway Mucus Plugs in COPD and Clinical Implications

Sofia K Mettler; Hrudaya P Nath; Scott Grumley; José L Orejas; Wojciech R Dolliver; Pietro Nardelli; Andrew C Yen; Seth J Kligerman; Kathleen Jacobs; Padma P Manapragada; Mostafa Abozeed; Muhammad Usman Aziz; Mohd Zahid; Asmaa N Ahmed; Nina L Terry; Rim Elalami; Ruben San José Estépar; Sushilkumar Sonavane; Ehab Billatos; Wei Wang; Raúl San José Estépar; Jeremy B Richards; Michael H Cho; Alejandro A Diaz

doi:10.1016/j.chest.2023.11.033

Silent Airway Mucus Plugs in COPD and Clinical Implications

Chest. 2023 Nov 25:S0012-3692(23)05825-7. doi: 10.1016/j.chest.2023.11.033. Online ahead of print.

Authors

Sofia K Mettler¹, Hrudaya P Nath², Scott Grumley², José L Orejas³, Wojciech R Dolliver⁴, Pietro Nardelli⁵, Andrew C Yen⁶, Seth J Kligerman⁷, Kathleen Jacobs⁶, Padma P Manapragada², Mostafa Abozeed², Muhammad Usman Aziz², Mohd Zahid², Asmaa N Ahmed², Nina L Terry², Rim Elalami⁴, Ruben San José Estépar⁵, Sushilkumar Sonavane⁸, Ehab Billatos⁹, Wei Wang¹⁰, Raúl San José Estépar⁵, Jeremy B Richards¹¹, Michael H Cho¹², Alejandro A Diaz³

Affiliations

¹ Department of Medicine, Mount Auburn Hospital, Cambridge, MA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. Electronic address: sofiakyonhi.mettler@uzh.ch.
² Department of Radiology, University of Alabama at Birmingham, Birmingham, AL.
³ Harvard Medical School, Boston, MA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA.
⁴ Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA.
⁵ Harvard Medical School, Boston, MA; Department of Radiology, Brigham and Women's Hospital, Boston, MA.
⁶ Department of Radiology, University of California San Diego, San Diego, CA.
⁷ Department of Radiology, National Jewish Health, Denver, CO.
⁸ Department of Radiology, Mayo Clinic, Jacksonville, FL.
⁹ Department of Medicine, Boston University School of Medicine, Boston, MA.
¹⁰ Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, MA.
¹¹ Department of Medicine, Mount Auburn Hospital, Cambridge, MA; Harvard Medical School, Boston, MA.
¹² Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA.

PMID: 38013161
DOI: 10.1016/j.chest.2023.11.033

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.