Introduction
Asthma is a chronic respiratory condition marked by airway inflammation and increased reactivity. It’s increasingly recognized as a heterogeneous disease with various subtypes, among which eosinophilic asthma stands out for its less-defined diagnostic criteria. Current guidelines suggest that diagnosing eosinophilic asthma requires at least two blood samples showing 300 eosinophil granulocytes per microliter outside of asthma exacerbations. However, another leading report recommends considering type 2 inflammation when blood eosinophils reach or exceed 150 cells per microliter.
Study Design and Methods
Participants and Setup
This cross-sectional study was carried out at the Outpatient Department of Pneumology and Angiology at the University Hospital of Bonn from June 2022 to February 2023. It included 112 consecutive adult patients with pre-existing asthma. The exclusion criteria were lack of consent or a blood eosinophil count (BEC) of 1,500 cells per microliter or higher to eliminate eosinophilia caused by comorbidities like hypereosinophilic syndrome. All participants provided written informed consent, and no one had an acute asthma exacerbation during the study. The ethics committee of the Medical Faculty of the University of Bonn approved the research, ensuring it adhered to the principles of the Declaration of Helsinki.
The key measurements in the study were the aortic diameter and radial strain. Additional blood parameters such as eosinophil count and IgE levels were also evaluated from the latest medical records. Researchers included patients with at least two documented elevated blood eosinophil levels in the past year, ensuring records were unaffected by treatments like systemic corticosteroids or targeted therapies like anti-IL-5(R).
Asthma Control and FeNO
Asthma control was gauged using the Asthma Control Test (ACT), a five-question scale ranging from five to 25 points, where higher scores indicate better control. The minimum clinically important difference in ACT score is three points. Fractional exhaled nitric oxide (FeNO) values were recorded as they reflect disease activity and align with the GINA guidelines. Elevated NO levels contribute to bronchial hyperreactivity, airway inflammation, and tissue damage, and they have been associated with aneurysm formation in mouse models.
Statistical Approach
Data analysis was performed using IBM® SPSS® Statistics, Version 29.0. Continuous data is presented as mean ± standard deviation (SD), while categorical data is expressed as n (%). Linear regression analysis was used to examine correlations between variables, adjusting for sex. P-values less than 0.05 were considered statistically significant.
Findings and Analysis
Patient Characteristics
Out of the 112 patients, 42 (37.5%) were male. The patients were grouped based on their BEC: one with BEC of 300 cells per microliter or more (66 patients), and another with BEC below this threshold (46 patients).
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Table 1 Baseline Characteristics
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Patients in the high BEC group had poorer asthma control (ACT score: 16.1 ± 5.3 vs 13.4 ± 5.7, p=0.014). These patients were also more frequently male (23.1% vs 45.5%, p=0.037), and more often received biologic therapy (32.6% vs 69.7%, p).
Aortic Diameter and Eosinophil Count
The study found that patients with BEC of 300 cells per microliter or higher had a significantly wider aortic diameter than those with lower BECs. Three patients diagnosed with abdominal aortic aneurysm (AAA) were selected for further clinical examination, all with BEC of 300 cells per microliter or higher.
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Figure 2 The abdominal aortic diameter was compared between asthma patients with blood eosinophil count (BEC).
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Given that gender is an independent risk factor for AAA, the analysis adjusted for sex. The findings revealed a small but significant positive correlation between BEC and the abdominal aortic diameter (R²=0.131, b=0.000, p).
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Figure 3 Linear regression analysis of the blood eosinophil count (BEC) and the abdominal aortic diameter, adjusted for sex category.
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Vascular Strain Analysis
Strain analysis indicated that arterial elasticity was reduced in patients with BEC of 300 cells per microliter or more. Patients in this group displayed lower circumferential strain (2.15 ± 1.79% vs 3.35 ± 2.68%, p=0.01) and radial strain rate (0.24 ± 0.10 1/s vs 0.38 ± 0.23 1/s, p).
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Figure 4 Analysis of the mean strain parameters between two patient groups stratified by blood eosinophil counts (BEC) a) radial strain, b) circumferential strain, c) radial strain rate, d) circumferential strain rate. No statistically significant differences were observed for radial velocity or radial displacement. Outliers are denoted by asterisks (*).
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In contrast, no statistically significant differences were found in radial displacement (0.17 ± 0.21 mm vs 0.23 ± 0.18 mm, p=0.097) and radial velocity (0.13 ± 0.14 cm/s vs 0.16 ± 0.13 cm/s, p=0.208) between the groups. Further linear regression, with adjustments for sex, pointed to a weak but significant negative correlation between BEC and both radial strain (R²=0.131, b=−0.002, p=0.001) and radial strain rate (R²=0.327, b=−0.000, p=0.003).
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Figure 5 Linear regression analysis of blood eosinophil count (BEC) and abdominal aortic strain (rate), adjusted for sex category. The analysis reveals a small but significant negative correlation between BEC and a) the radial strain, and b) the strain rate.
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FeNO and ACT in Relation to Vascular Changes
In this study, FeNO and ACT scores did not correlate with a wider aortic diameter or reduced radial strain, as seen in the linear regression analysis. This suggests that while eosinophil levels may be linked to vascular changes, the current measures of disease activity do not directly reflect these results.
Implications and Discussion
This research highlights an association between eosinophil levels and cardiovascular risk factors in asthma, specifically aortic diameter and arterial stiffness. It contributes to the growing body of evidence linking allergic asthma to atherosclerotic changes. These findings were consistent with previous studies that connected asthma severity with vascular alterations, indicating systemic inflammation as a critical factor.
Additionally, the patient group with high eosinophils had more exacerbations and a higher utilization of biologic therapy, typical characteristics of eosinophilic asthma. These patients displayed more pronounced disease, reflecting a higher burden of eosinophil-mediated inflammation over time. However, the study did not find a direct correlation between disease activity or severity and AAA formation.
While there is substantial literature on inflammation markers, such as IL-6 and CRP, their role in linking asthma to cardiovascular events remains complex. Some experimental evidence suggests eosinophils in thrombotic processes, relevant mainly in later stages like aneurysms, while others propose that these cells may affect arterial stiffness without infiltrating the vascular walls.
The study acknowledges that further research is necessary to understand the specific mechanisms underlying this relationship. As AAA typically develops in individuals over 65, the relatively younger age of the study cohort might explain why pre-atherosclerotic changes were more evident.
The role of eosinophils in AAA formation is controversial. While some studies propose that allergic inflammation can exacerbate vascular conditions, others suggest that the absence of eosinophils or their substitute, type 2 innate cells, may provide a protective effect. The relationship between eosinophils and cardiovascular disease appears to be multifaceted, and the full scope remains to be clarified.
Limitations of the Research
This study’s exploratory nature limits its ability to establish causality between eosinophils and vascular changes. Selection bias might exist, as it was conducted at a single center in a university hospital, potentially including patients with more severe conditions. Variability in eosinophil counts further complicates accurate phenotyping.
The age of the cohort is a significant limitation, as AAA typically occurs later in life. Nonetheless, the study provides valuable insight into pre-atherosclerotic vascular changes in asthma patients, potentially indicating a higher risk for developing AAA in the future.
Conclusion
The study indicates a correlation between high blood eosinophil counts and increased abdominal aortic diameter and vascular stiffness in asthma patients. This finding aligns with the notion that eosinophils play a role in systemic inflammation, a known risk factor for cardiovascular diseases. Further research should aim to confirm these findings and elucidate the underlying mechanisms to better understand the connection between eosinophilic asthma and cardiovascular risk.
Exploring these links could pave the way for improved risk assessment and management strategies in asthma patients, potentially preventing serious cardiovascular complications.
As this study takes a step forward in understanding the association between eosinophilic asthma and cardiovascular health, it emphasizes the importance of considering systemic markers like blood eosinophils in the clinical evaluation of asthma patients.
Call to Action
We invite asthma patients, healthcare professionals, and researchers to share your thoughts on this study. Your insights could contribute valuable perspectives to our ongoing efforts to understand the complexities of eosinophilic asthma and its associated risks. Please feel free to comment or share your experiences below, or subscribe to our newsletter for the latest updates in medical research.