Bronchiectasis is a complex and heterogeneous disease with various clinical phenotypes and endotypes. The aim of this study was to examine the clinical phenotype of EB and compare it with NEB. The study design employed a retrospective case-control approach, analyzing data from 169 patients hospitalized for acute exacerbations of non-cystic fibrosis bronchiectasis. Patients were categorized into EB and NEB groups based on blood eosinophil levels, with a threshold of ≥ 300 cells/µl for EB and  < 300 cells/µl for NEB. Our findings demonstrate that EB represents a distinct phenotype within the spectrum of bronchiectasis, characterized by elevated blood eosinophil counts and unique clinical characteristics.

In bronchiectasis, studies have shown varying prevalence of eosinophilia, with approximately 20.4% of non-asthmatic or allergic bronchopulmonary aspergillosis-related bronchiectasis patients exhibiting peripheral blood eosinophilia [6]. In this study, the prevalence of EB in bronchiectasis patients is 22.5%, which is consistent with findings from previous limited studies. High blood eosinophil count in adults is independently associated with male sex, current smoking, positive skin prick test, COPD, and asthma [11]. Consistent with the aforementioned studies, the EB patients in this study exhibited similar characteristics, including male smokers, elevated levels of total IgE, and reduced lung function.

The association between peripheral eosinophil count and exacerbations in bronchiectasis, along with the optimal cut-off point that accurately reflects this relationship, remains a topic of debate [12]. In a study conducted by Kwok et al. [13], focusing on Chinese patients, the role of blood eosinophil counts in hospitalizations due to bronchiectasis exacerbations was investigated. The study findings suggest that an eosinophil count of 250 cells/µl is the threshold that identifies a higher risk of hospitalization for bronchiectasis. In the current study, we employed pre-established cut-offs that are widely acknowledged in the literature on COPD and asthma [9, 14], and these cutoffs are also consistent with those reported in a European Multicohort Study [6]. However, future research should explore different cut-off values to validate and refine the definition of EB.

One of the key findings of this study is the association between blood eosinophil count and the severity of bronchiectasis. Patients with EB exhibited greater overall disease severity, as evidenced by lower lung function, higher glucocorticoid medication usage, worse scores on bronchiectasis severity indices (BSI and E-FACED), and increased hospitalization cost. This observation suggests that blood eosinophil count could serve as a potential biomarker for disease severity in bronchiectasis, aiding in risk stratification and treatment decision-making.

Several studies have demonstrated a correlation between severe eosinophilic inflammation and disease progression in respiratory conditions like asthma and COPD [15,16,17,18]. This association could be attributed to the involvement of eosinophils in airway remodeling. Eosinophils can secrete matrix metalloproteinases, promoting fibroblast activation and differentiation into myofibroblasts, both of which contribute to airway remodeling [19]. Additionally, eosinophils are stimulated by pathogens to release eosinophil extracellular traps (EET), accompanied by the release of exosomes and elastase, which further impact airway remodeling and extracellular matrix changes [20]. However, various studies have demonstrated the bactericidal and antiviral properties of eosinophils, both during stable phases and exacerbations [21]. This finding may provide an explanation for the lower incidence of NTM infection observed in the EB group.

It is important to note that our results did not reveal an association between EB and the Pseudomonas aeruginosa infection rate. Firstly, the size and specific characteristics of our study cohort may differ from those in other studies, contributing to variations in observed associations [22, 23]. Additionally, inhaled corticosteroids (ICS) use is associated with an increased risk of Pseudomonas aeruginosa (PA) infection [24, 25]. Furthermore, in this study, the diagnosis of Pseudomonas aeruginosa infection relied on positive sputum bacterial culture results. Unlike the high-throughput sequencing method, the positive rate of sputum culture was markedly lower. Consequently, the Pseudomonas aeruginosa infection rate in this study was also significantly reduced. This discrepancy constitutes one of the reasons why our findings do not suggest an association between eosinophilic disease and the Pseudomonas aeruginosa infection rate.

The infiltration of eosinophils significantly influences airway remodeling and, consequently, lung function levels, resulting in eosinophilic bronchiectasis displaying notably lower lung function compared to other bronchiectasis subtypes. The correlation between blood eosinophil counts and sputum eosinophil counts, as well as serum total IgE levels, further supports the role of eosinophilic inflammation in EB. The positive correlation between these parameters indicates a close relationship between blood and airway eosinophilia, emphasizing the involvement of eosinophils in the pathogenesis of EB. The identification of EB as a distinct phenotype within bronchiectasis has important implications for personalized treatment strategies. Current therapies targeting neutrophils, such as inhaled antibiotics and liposomal ciprofloxacin, may not be effective for EB patients [26, 27]. Instead, therapies that specifically target eosinophilic inflammation, such as corticosteroids or monoclonal antibodies against interleukin-5, could be explored as potential treatment options for EB [28, 29]. A single-center observational cross-sectional study, including 249 patients, reported bronchiectasis predominantly characterized by type 2 immune response (peripheral blood eosinophil count ≥ 300/µl or FeNO ≥ 25 ppb) [30]. In the case series of severe bronchiectasis, treatment with mepolizumab or benralizumab significantly reduced exacerbation rates for up to 2 years. These findings suggest the importance of T2-high endotype-targeted biological treatments in bronchiectasis patients.

We acknowledge several limitations in our study. Firstly, it was a retrospective study conducted at a single center, and the sample size was small, which may introduce selection bias. Secondly, we did not assess blood or sputum inflammatory markers to evaluate the impact of type 2 inflammation on bronchodilation. Third, this study did not investigate the potential relationship between the phenotype of eosinophilic bronchiectasis and the microbiota. Despite these limitations, our study provides valuable insights into the topic, and future research should aim to address these shortcomings.