Blood eosinophil count tied to pseudomonas aeruginosa infection but not efficacy of inhaled tobramycin: Study

Bronchiectasis is a chronic airway suppurative disease in which recurrent airway infections, inflammation and remodeling have been implicated. Apart from neutrophils which dominate within the bronchiectatic airways, eosinophils play a role in the pathogenesis and progression of bronchiectasis. A published study has demonstrated that blood eosinophil counts (BECs) correlated with the disease severity, lung function, exacerbations in bronchiectasis. Multinational observational studies have demonstrated that ~20% of bronchiectasis patients had elevated BECs and sputum eosinophil count, who had a shorter time to the next exacerbation. For patients with blood eosinophilia, inhaled corticosteroids (ICS) reportedly reduced the risk of exacerbation, and monoclonal antibodies targeting at interleukin-5 or interleukin-5 receptor ɑ subunit significantly reduced the symptom burden and the frequency of exacerbations.

BECs are a valuable biomarker for assessing type 2 airway inflammation in clinical practice and may guide the clinical management of patients with asthma and COPD. However, BECs vary among different diseases and fluctuate over time in bronchiectasis. Few studies have delineated the factors affecting BECs in bronchiectasis, particularly the impact of airway infection and pharmacologic interventions. Airway infections have been implicated in type 2 inflammation. Although elevated BECs reportedly correlated with the enrichment of genus Pseudomonas within airways, the association between P. aeruginosa and BECs are not entirely clear, and the implications for indicating disease progression and treatment strategies have yet to be elucidated.

This study combined a cohort study and a post hoc analysis of clinical trials. The cohort study was conducted from 2012 to 2023 and included bronchiectasis patients diagnosed by chest HRCT, excluding those with asthma or the receipt of systemic corticosteroids within 4 weeks prior to enrolment. The study prospectively collected clinical symptoms and sputum samples during both clinically stable and exacerbation states and conducted bacterial culture and 16S rRNA sequencing to clarify the link between P. aeruginosa infection and BECs. The post hoc analysis, based on a multicenter randomized controlled trial focusing on P. eruginosa infected patients, aimed to evaluate the effect of inhaled tobramycin (TIS) versus normal saline on BECs. The treatment comprised two 28-day “on-off" cycles over 16 weeks.

The study enrolled 262 patients with stable-state bronchiectasis, revealing that those with P. aeruginosa infection exhibited significantly higher BECs compared with those without (mean: 166 vs. 128 cells/μl, P=0.01). Similar findings were observed during acute exacerbations, where the P. aeruginosa-infected patients also showed elevated BECs (mean: 204 vs. 107 cells/μl, P=0.03). Further analysis using 16S rRNA sequencing on 268 sputum samples, which included 53 stable-exacerbation paired samples, demonstrated a significant positive correlation between the relative abundance of Pseudomonas and BECs (r=0.20, P=0.004). Consistent with sputum culture results, patients with Pseudomonas detection during stable state had higher BECs (mean: 191 vs. 136 cells/μl, P=0.005).

The post hoc analysis showed that during TIS treatment, BECs exhibited a fluctuating pattern - an initial increase followed by a subsequent decrease. In the first treatment cycle, BECs increased (mean: 188 vs. 119 cells/μl, P<0.001), and remained elevated in the second cycle (mean: 164 vs. 121 cells/μl, P<0.001). However, one month after treatment cessation, BECs returned to baseline levels (mean: 135 vs. 122 cells/μl, P=0.11). Notably, despite the temporary increase in BECs during treatment, patients in the TIS group exhibited a reduction in bacterial load and a significant improvement in quality-of-life scores (QoL-B-RSS). Moreover, the therapeutic effects did not differ significantly between patients with high BECs (≥150 cells/μl) and those with low BECs (<150 cells/μl) (P=0.58).

This is the first study which has demonstrated a bidirectional relationship between P. aeruginosa infection and elevated BECs in bronchiectasis patients. Inhaled tobramycin, despite eliciting a temporary increase in BECs, significantly reduced the P. aeruginosa bacterial load and decreased symptom burdens, with its therapeutic effects being independent of baseline BEC levels.

These findings challenge the conventional concept that eosinophilic inflammation counteracts infection. Alterntively, these results indicate that P. aeruginosa infection and eosinophilic inflammation represent two distinct treatable traits in the treatment of bronchiectasis. This implies a need for developing more targeted combination therapies that address both infection and inflammation to optimize treatment outcomes.

Reference:

Ming-xin Shi Shu-jun Guo Jun-qing Yue, Blood eosinophil counts, airway infections and inhaled antibiotic treatment in bronchiectasis, European Respiratory Journal, https://doi.org/10.1183/13993003.00518-2025.