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Sofia Mettler, MD, MSc, MPH







Channing Division of Network Medicine


Sofia K. Mettler*, Hrudaya P. Nath, Scott Grumley, José L. Orejas, Wojciech R. Dolliver, Andrew A. 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, Michael H. Cho, Alejandro Diaz

Principal Investigator

Alejandro Diaz, Michael Cho


Persistent airway mucus plugs and changes in lung function in COPD


Background: Airway mucus plugs (MP) are frequently found on CT scans of smokers with COPD and associated with impaired lung function in cross-sectional studies. However, whether changes in MP over time in individuals with COPD are associated with changes in lung function is unknown.

Methods: We evaluated chest CT scans of current and former smokers with COPD from the COPDGene study at the baseline (Phase[P]1) and 5-year follow-up (P2). We defined MP as any completely occluded airway in at least one pulmonary segment. MP changes were classified as persistently negative (no MP in P1 and P2), persistently positive (MP in P1 and P2), resolved (MP only in P1) and newly positive (MP only in P2). We assessed the association between MP changes and changes in FEV1 using multivariable linear and logistic regression models.
Results: Of 1,857 participants with both P1 and P2 CT scans evaluated, 855 (46%) were persistently negative for MP, 302 (16%) were newly positive, 327 (18%) resolved and 373 (20%) were persistently positive. Compared to persistently negative, persistently positive MP status was associated with a greater decline in FEV1 (-65.5mL, p=0.002; -2.66% predicted, p<0.001, FEV1/FVC -0.022, p<0.001) and higher odds of rapid decline in FEV1, i.e., decline in FEV1>40ml per year (odds ratio 1.59 [95% CI: 1.19, 2.12]), after adjusting for age, sex, race, BMI, smoking status/history, FEV1 at baseline, asthma and quantitative emphysema on CT. When compared to persistently positive, resolved MP status was associated with lower decline in FEV1 (97.6ml, p<0.001; 4.07% predicted, p<0.001 and FEV1/FVC 0.029, p<0.001) in adjusted multivariable models.

Conclusion: In individuals with COPD, persistent MP is associated with decline in FEV1 while resolution of MP is associated with lower decline lung function. Our findings support MP as a possible modifiable therapeutic target in COPD.

Clinical Implications

Chronic mucus hypersecretion is a central pathophysiology of COPD and airway mucus plugs are commonly found on chest CT scans of smokers with COPD. Several studies have shown associations between the presence of airway mucus plugs and worse lung functions. However, it is yet unknown whether changes in mucus plugs over time are associated with changes in lung functions. Our study shows that persistent mucus plugs are associated with worsening lung function over time, while resolution of mucus plugs is associated with lower decline in lung function. Our results suggest that mucus plugs could be a potentially modifiable airway pathology in COPD.