Mucus plugging on computed tomography and the sputum microbiome in patients with asthma, chronic obstructive pulmonary disease, and asthma-COPD overlap

Background: Despite clinical implications, the pathogenesis of mucus plugging in asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) remains unclear. We hypothesized that distinct airway microbiomes might affect mucus plugging differently between ACO, asthma, and COPD and between different extents of airway eosinophilic inflammation.Methods: The sputum microbiome, sputum cell differential count, and mucus plug score on computed tomography were cross-sectionally evaluated in patients with chronic airflow limitation.Results: Patients with ACO, asthma, or COPD were enrolled (n=56, 10, and 25). Higher mucus plug scores were associated with a greater relative abundance of the phylum Proteobacteria (rho = 0.29) only in patients with ACO, and a greater relative abundance of the phylum Actinobacteria (rho = 0.46) only in patients with COPD. In multivariable models including only patients with ACO, the mucus plugs presence was associated with a greater relative abundance of the phylum Proteobacteria and the genus Haemophilus, independent of smoking status, airflow limitation, and emphysema severity. Moreover, the mucus score was associated with a greater relative abundance of the genus Streptococcus (rho = 0.46) in patients with a high sputum eosinophil count (n=22) and with that of the genus Haemophilus (rho = 0.46) in those with a moderate sputum eosinophil count (n=26).Conclusions: The associations between mucus plugging and the microbiome in ACO differed from those in COPD and asthma. A greater relative abundance of the phylum Proteobacteria and genus Haemophilus may be involved in mucus plugging in patients with ACO and moderate airway eosinophilic inflammation.