Neutrophilic Asthma Is Associated with Increased Airway Bacterial Burden and Disordered Community Composition

Abstract

Neutrophilic asthma (NA) is an important asthma inflammatory phenotype associated with disease severity, airflow limitation, and steroid resistance, and its mechanism is still uncertain. Evidences suggest a potential role for bacteria in its pathogenesis, but, so far, this remains poorly understood. We sought to investigate airway bacterial burden, community composition, and inflammatory response in NA. Fifty-four stable asthmatics without infection were enrolled and separated into either NA group (n = 20) or non-NA group (n = 34). Subject demographics, Asthma Control Test (ACT) scores, medications, and pulmonary functions were documented. Sputum cytology, airway bacterial burden, microbial community composition, and inflammatory cytokines were assessed. The total airway bacterial burden was significantly increased in subjects with NA versus non-NA and was positively correlated with the sputum neutrophil percentage. Airway neutrophilia was associated with less airway bacterial community richness and diversity, along with a distinct community composition. In patients with NA, bacteria in phylum Proteobacteria, especially Haemophilus spp. and Moraxella spp., showed significant increases in both actual loads and relative abundances, while bacteria in phyla Firmicutes, Actinobacteria, and Saccharibacteria showed decreased relative abundances compared with non-NA. Patients with NA demonstrated higher levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-12, IL-17A, and tumor necrosis factor-α (TNF-α) in sputum samples compared with non-NA. Increased bacterial burden and distinct microbiota composition were the key characters of neutrophilic phenotype in asthma, accompanied by excessive airway inflammation. Understanding the relationship between airway microbiota and neutrophilic inflammation may help in treatment and management of asthma, such as targeting airway microbiota.