Differential associations between type 2 inflammation and airway mucus plugs in asthma, asthma-COPD overlap, and COPD

The mechanisms by which type 2 (T2) inflammation affects airway mucus plugging in asthma, asthma‒chronic obstructive pulmonary disease (COPD) overlap (ACO), and COPD remain unclear despite their clinical relevance. This study examined whether increased fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophil count (BEC) are differentially associated with mucus plugging among patients with asthma, ACO, and COPD.

The presence and scores of mucus plugs were cross-sectionally visually assessed on ultra-high-resolution computed tomography. The T2 inflammation level was categorized into three groups: low (FeNO <25 ppb and BEC <300/μL), middle (FeNO ≥25 ppb or BEC ≥300/μL), and high (FeNO ≥25 ppb and BEC ≥300/μL).

A total of 245 patients who did not receive biologics or oral corticosteroids, including 81, 45, and 119 patients with asthma, ACO, and COPD, respectively, were classified into low, middle, and high T2 inflammation groups. In patients with asthma, increased T2 inflammation was associated with increased mucus plugging. In patients with ACO, the high T2 inflammation group had the highest prevalence of mucus plugs and the highest mucus plug scores, whereas no difference was found between the middle and low T2 inflammation groups. In patients with COPD, the prevalence and scoring of mucus plugs did not differ among the groups.

The combination of high FeNO and BEC was associated with mucus plugs in patients with asthma or ACO but not in patients with COPD, suggesting the need for a disease-based approach to mucus plug removal.