Mucus Plugs and Small Airway Dysfunction in Asthma, COPD, and Asthma-COPD Overlap

Abstract

Purpose There are reports concerning mucus plugs detected on high-resolution computed tomography images and airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). However, little is known about the associations between mucus plugs and small airway dysfunction (SAD). We evaluated the relationship between mucus plugs and pulmonary function in patients with asthma, COPD, and asthma-COPD overlap (ACO), and investigated the relevance to SAD and type 2 inflammation in a retrospective study. Methods Subjects included 49 asthmatic, 40 ACO, and 41 COPD patients. ACO was diagnosed based on the Japanese Respiratory Society ACO guidelines. Clinical and laboratory parameters, including blood eosinophil count, serum total IgE levels, fractional exhaled nitric oxide (FeNO), spirometry, and forced oscillation technique (FOT), were compared between patients with and without mucus plugs. Results Mucus plugs were found in 29 (59%) asthmatic, 25 (65%) ACO, 17 (41%) COPD patients. Patients with mucus plugs had reduced spirometry and larger FOT parameters, especially in COPD patients. Mucus scores correlated positively with IgE in ACO and FeNO in asthmatic patients, but not in COPD patients. Multivariate logistic regression analysis revealed that SAD parameters, including forced vital capacity and resonant frequency, a respiratory reactance parameter, were significantly associated with the presence of mucus plugs in the whole studied population. Conclusions SAD, rather than large airway dysfunction, was associated with mucus plugs in asthma, ACO, and COPD patients.

Clinical Associations of Mucus Plugging in Moderate to Severe Asthma

“…12 It was previously demonstrated that asthma patients with higher MPS have significantly elevated sputum eosinophils, gene expression of IL13 and IL5, and MUC5AC/MUC5B ratios. 4 This explains our findings in this study that asthma patients with MPs exhibit higher levels of routinely measured T2 biomarkers in real-life clinical practice, including blood eosinophils, FeNO, 5 and total IgE, 10 in which median values in the MP group all exceeded traditionally accepted cut points of 300 cells/ mL or greater, 25 parts per billion or greater, and 100 kU/L or greater, respectively. Furthermore, despite the suppressive effect of ICS on FeNO, 13 patients with MPs were receiving a significantly higher ICS dose but still had higher FeNO levels.…”

“…The mean (95% CI) difference of 0.80 L/s (0.44-1.17 L/s) aligns with a recent study. 10 Mucus plugging is thought to be driven by IL4/IL13mediated inflammation. 3 Thus, we postulate that this is a potential mechanism by which the anti-IL4ra dupilumab may improve FEV 1 and FEF 25-75 in severe asthma by reducing mucin and tissue eosinophils in addition to having a direct effect on airway smooth muscle.…”

Clinical Indicators for Asthma-COPD Overlap: A Systematic Review and Meta-Analysis

“…of Studies Reference No. Lower Upper I 2 p-value p-value PB-FEV1% pred ACO vs asthma −1.09 −1.3 −0.87 <0.001 91% 0.357 0.295 28 7 , 9 , 10 , 18–20 , 22 , 24 , 26 , 27 , 29–33 , 36 , 37 , 39 , 41 , 44–47 , 50 , 51 , 53 , 58 , 61 ACO vs COPD 0.15 0.05 0.26 0.004 80% 0.157 0.6 40 7–10 , 18 , 20–29 , 31–36 , 38–43 , 47 , 49–57 , 59–61 DLCO% pred ACO vs asthma −0.83 −1.24 −0.42 <0.001 89% 0.166 0.536 …”

Mucus Plugs and Small Airway Dysfunction: An Important Concept in Airway Disease Pathophysiology

“…In this issue, Tamura et al . 4 investigated the prevalence of mucus plugs using HRCT in patients with asthma, COPD, and asthma-COPD overlap (ACO). In addition, authors assessed the relationship between mucus plugs and the parameters of conventional spirometry or small airway dysfunction (SAD) in patients with airway diseases mentioned above.…”

“…Tamura et al . 4 also assessed SAD using FVC and Fres and reported that SAD rather than large airway dysfunction was associated with mucus plugging in all the 3 obstructive airway diseases. Among several physiological measurements of SAD, FVC depends on patients’ efforts and thus shows a lack of reproducibility.…”