Association between Blood Eosinophil Count and Bacterial Infection and Clinical Outcomes in Patients with Severe Exacerbations of Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD) is a significant global health burden, and acute exacerbations of COPD (AECOPD) are critical events that negatively impact patients’ health status, disease progression, and mortality. These exacerbations are often triggered by viral and bacterial infections, with studies indicating that bacterial infections are present in approximately 55% of hospitalized AECOPD patients. While antibiotic therapy has been shown to reduce short-term mortality and improve prognosis in some cases, not all patients benefit from such treatment. This highlights the need for biomarkers that can guide appropriate management strategies. One such biomarker is the blood eosinophil count, which has been associated with eosinophil-related airway inflammation and sepsis. However, the relationship between peripheral blood eosinophil count and bacterial pathogens in AECOPD has not been thoroughly explored. This study aimed to analyze the associations among eosinophil count, bacterial pathogens, clinical treatments, and outcomes in patients with severe AECOPD, providing valuable insights for optimizing management strategies.
The study included patients aged over 40 years who were admitted to the Department of Respiratory and Critical Care Medicine of Peking University Third Hospital between January 2013 and June 2018. The diagnosis of COPD and AECOPD was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Patients with conditions such as bronchial asthma, allergic rhinitis, eczema, urticaria, other allergic diseases, bronchiectasis, interstitial lung disease, tuberculosis, or those who had received pre-admission oral corticosteroid treatment were excluded. The eosinophil count from the first blood cell count obtained during hospitalization was used to categorize patients into two groups: a low eosinophil group (eosinopenia, defined as <2%) and a high eosinophil group (eosinophilia, defined as ≥2%). Demographic data, comorbidities, lung function, and laboratory results, including blood cell counts, C-reactive protein (CRP), procalcitonin (PCT), and D-dimers, were recorded. Clinical outcomes, such as duration of hospitalization, intensive care unit (ICU) stay, mechanical ventilation, mortality, readmission rates, and use of systemic corticosteroids and antibiotics, were compared between the two groups.
The study identified 630 patients with AECOPD from an initial review of 1282 cases. After exclusions, 596 patients were included in the analysis, with 34.9% (n=208) in the eosinophilia group and 65.1% (n=388) in the eosinopenia group. There were no significant differences in age or sex between the two groups. However, the eosinopenia group had fewer smokers (78.6% vs. 87.0%), more patients with diabetes (26.3% vs. 15.4%) and hypertension (54.6% vs. 42.8%), and worse lung function, as indicated by a lower percentage of predicted forced expiratory volume in one second (FEV1% pred: 49.9% vs. 60.7%). Patients in the eosinopenia group were also more likely to present with cough (88.9% vs. 82.2%).
Bacterial infection was assessed using a CRP concentration of ≥20 mg/L as a surrogate marker, combined with clinical symptoms such as purulent sputum, increased dyspnea, and increased sputum volume. Bacterial infection was detected in 36.1% of patients in the eosinophilia group and 47.7% in the eosinopenia group. The eosinophil percentage was significantly lower in patients with bacterial infection (1.3% vs. 2.4%). Additionally, white blood cell (WBC) count, neutrophil count, CRP, and PCT concentrations were significantly higher in the eosinopenia group compared to the eosinophilia group, indicating more severe infection and systemic inflammation.
Sputum cultures were analyzed to identify bacterial pathogens. Of the 233 sputum isolates with identified pathogens, 57 were from the eosinophilia group and 176 from the eosinopenia group. The overall bacterial isolation rate was higher in the eosinopenia group (45.4% vs. 27.4%). Gram-negative bacilli were the dominant pathogens in both groups, but the eosinopenia group had significantly higher percentages of Coagulase Negative Staphylococcus (11.9% vs. 5.3%) and Enterococcus (2.6% vs. 0%). Staphylococcus aureus and Enterococcus were also more prevalent in the eosinopenia group. These findings suggest that the presence of Gram-positive cocci, particularly Staphylococcus, may contribute to the poor clinical prognosis observed in patients with eosinopenia.
Clinical outcomes differed significantly between the two groups. Patients in the eosinopenia group had longer hospital stays (15 vs. 14 days), longer ICU stays, and a greater need for invasive mechanical ventilation (3.4% vs. 1.0%). Kaplan-Meier analyses confirmed that the hospital stay was longer in the eosinopenia group. However, there were no significant differences in mortality during hospitalization, readmission rates at 7 and 14 days after discharge, or systemic corticosteroid use between the two groups.
The study highlights the importance of determining whether AECOPD is caused by bacterial infection to guide the rational use of antibiotics. The peripheral blood eosinophil count was found to be a useful biomarker for this purpose. Patients with a low eosinophil count were more likely to have bacterial infections, as indicated by higher CRP, PCT, and WBC levels, and they exhibited more severe systemic inflammation. These findings suggest that empirical antibiotic use may be beneficial in patients with AECOPD who have a low eosinophil count. In contrast, patients with high eosinophil counts may have exacerbations triggered by other factors, such as eosinophilic airway inflammation, viral infections, or environmental factors.
The analysis of bacterial pathogens provides further insights into the relationship between eosinophil count and specific infection subtypes. The higher prevalence of Gram-positive cocci, particularly Staphylococcus, in the eosinopenia group may explain the poorer clinical outcomes in these patients. The presence of Staphylococcus in sputum samples has been associated with prolonged hospital stays and increased mortality in AECOPD patients. Although the positive sputum culture rate was reduced due to prehospital antibiotic use, the comparison between the two groups remains valid, as both groups received antibiotic treatment.
These findings have practical implications for the management of AECOPD. In patients with a low eosinophil count, clinicians should consider the increased likelihood of bacterial infection and the potential presence of Gram-positive cocci when selecting empirical antibiotics. For patients with high eosinophil counts, a short course of narrow-spectrum antibiotics may be sufficient, as bacterial infections are less likely to be the primary cause of exacerbation.
In conclusion, this study demonstrates that peripheral blood eosinophil count can serve as an effective biomarker to guide antibiotic use in hospitalized patients with AECOPD. Patients with low eosinophil counts are more likely to have bacterial infections and may benefit from empirical antibiotic therapy. The integration of eosinophil count with other inflammatory markers, such as CRP and clinical symptoms, can help achieve personalized and precise treatment for AECOPD. However, the study’s findings should be further validated in large-scale prospective clinical trials to confirm their applicability in broader clinical settings.
doi.org/10.1097/CM9.0000000000001690
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