European Journal of Cardiovascular Medicine

Chronic Obstructive Pulmonary Disease (COPD) is a major global health concern, characterized by persistent respiratory symptoms and irreversible airflow limitation due to airway and/or alveolar abnormalities [1]. According to the World Health Organization, COPD is the third leading cause of death worldwide, accounting for approximately 3 million deaths annually [2]. The growing global prevalence of COPD is primarily attributed to continued exposure to risk factors such as smoking and biomass fuels, coupled with an aging population [3]. Patients with COPD often experience a decline in lung function and an increase in healthcare utilization, imposing a substantial socioeconomic burden [4].

A hallmark feature of COPD is the occurrence of exacerbations—acute episodes of symptom worsening that require additional therapy or hospitalization [5]. Such exacerbations accelerate the rate of decline in lung function, increase healthcare costs, and contribute significantly to morbidity and mortality [6]. Identifying biomarkers that reliably predict exacerbations and guide treatment decisions is therefore a priority in COPD management [7]. One promising biomarker is the eosinophil, a type of granulocytic white blood cell involved in inflammatory responses [8].

Elevated blood eosinophil counts have been linked to increased COPD exacerbation risk, particularly in patients who respond favorably to corticosteroid therapy [1,4,5,7,8]. However, measuring sputum eosinophils—considered a direct indicator of airway eosinophilia—can be challenging in routine clinical practice, prompting the use of peripheral blood eosinophil counts as a practical surrogate [1]. Furthermore, serum Immunoglobulin E (IgE) has also emerged as a potential indicator of exacerbation risk in COPD. While historically associated with atopic disease, elevated IgE levels in COPD may reflect overlapping allergic and eosinophilic pathophysiology [3,4].

Recent evidence suggests that COPD patients with elevated IgE levels may experience more frequent exacerbations, severe respiratory symptoms, and an earlier onset of dyspnea [2]. The synergy between eosinophilic inflammation and IgE-mediated pathways highlights a unique phenotype of COPD that could respond to specific treatments targeting IL-5 or IgE [6]. Therapies such as anti-IL-5 and anti-IgE (e.g., omalizumab) have shown promise in reducing exacerbations in select COPD populations [4]. Despite these developments, the routine use of eosinophil count and IgE levels in risk stratification is not yet universally adopted, indicating a need for additional evidence and clinical consensus.

Against this backdrop, the present study aimed to evaluate the predictive value of elevated blood eosinophil counts and serum IgE levels in exacerbations of COPD. By characterizing the correlation between these biomarkers and disease severity, the findings of this study may contribute to enhanced individualized management strategies for COPD patients.

Study Design and Setting

An observational cross-sectional study was conducted in the Department of Respiratory Medicine at a tertiary care center (National Institute of Medical Sciences & Research, Jaipur, India). Both outpatients (OPD) and inpatients (IPD) with COPD were enrolled over 18 months.

Inclusion and Exclusion Criteria

Inclusion Criteria

1. Patients aged >40 years.
2. Diagnosis of COPD per GOLD guidelines.
3. Chronic respiratory symptoms (e.g., breathlessness, cough, sputum).
4. Exposure to biomass fuels or other inhalational risk factors.
5. Current or former smokers (>10 pack-years).
6. Hemodynamic stability at the time of evaluation.
7. Informed written consent.

Exclusion Criteria

1. Refusal to provide informed consent.
2. Diagnosed bronchial asthma.
3. Known significant allergies altering eosinophil/IgE levels.
4. History of treated tuberculosis.
5. Family history of asthma or atopic dermatitis.
6. Major comorbidities (e.g., heart failure, malignancy) that could confound results.

Ethical Approval and Patient Recruitment

Ethical clearance was obtained from the Scientific and Ethics Committee of the institution. Patients visiting the OPD or admitted to the IPD meeting the inclusion criteria were approached consecutively. After obtaining written informed consent, 96 eligible participants were enrolled.

Clinical Evaluation

Each participant underwent a detailed clinical assessment, including:

• Demographics (age, sex), smoking history (pack-years), and occupational exposures.
• Physical examination (vital signs, respiratory and cardiovascular systems).
• History of exacerbations and hospital admissions.

Pulmonary Function Tests

Spirometry was performed following ATS/ERS guidelines, recording:

• Forced Vital Capacity (FVC)
• Forced Expiratory Volume in one second (FEV₁)
• FEV₁/FVC ratio

Severity was classified by GOLD stages:

• According to GOLD criteria patient divided into stage A,B and E on the basis of,

• MMRC Grade
• CAT Score
• H/O Exacerbation
• H/O Hospitalization

Laboratory Investigations

• Complete Blood Count (CBC): Included total leukocyte count, differential count, hemoglobin, platelet count.
• Absolute Eosinophil Count (AEC): Derived by multiplying total leukocyte count by the percentage of eosinophils.
• Serum IgE: Measured by ELISA; normal reference ≤150 IU/mL.
• Other Tests: Chest radiography, electrocardiography, and HRCT as clinically indicated.

Definition and Classification of Exacerbations

Exacerbations were identified based on Anthonisen’s criteria:

• Type I: All three cardinal symptoms (increased dyspnea, sputum volume, and sputum purulence).
• Type II: Any two cardinal symptoms.
• Type III: One cardinal symptom plus at least one additional finding (e.g., fever, upper respiratory tract infection, tachycardia).

Patients were categorized as having stable COPD or experiencing an exacerbation at presentation.

Data Management and Statistical Analysis

Data were entered into a secure database and analyzed using SPSS (version X.X).

• Descriptive statistics: Mean ± SD for continuous variables; frequencies (%) for categorical variables.
• Comparative tests:
• Chi-square for categorical comparisons (exacerbations vs. stable).
• Independent t-test or Mann-Whitney U for numerical comparisons between groups.
• One-way ANOVA or Kruskal-Wallis for multiple group comparisons (e.g., GOLD stages).
• Correlation: Pearson or Spearman coefficients to assess relationships between AEC, IgE, and COPD severity.
• Significance: p < 0.05 was considered statistically significant.  

Overall Patient Characteristics

A total of 96 COPD patients were included, comprising 70.83% males and 29.17% females. The majority (44.79%) were between 51 and 60 years of age, followed by 37.50% in the 61–70 age range.

Smoking Status and Biomass Exposure

Smokers demonstrated lower mean FEV₁% (51.16) compared to non-smokers (54.07) and showed higher mean AEC (752.93 vs. 647.89) and serum IgE (1275.21 vs. 783.20). However, there was no statistically significant association between smoking status or biomass exposure and GOLD stage distribution (p > 0.05).

Radiological Findings

High-resolution CT (HRCT) revealed that centriacinar emphysema (41.67%) was the most common pattern, followed by bronchial wall thickening (19.79%) and paraseptal emphysema (13.54%). Although certain features, such as multiple bullae, were more prevalent in advanced disease (stage E), no statistically significant difference in HRCT patterns was observed across GOLD stages (p > 0.05).

Distribution by GOLD Stages

• Stage A (n = 19, 19.8%) featured a mean FEV₁% of 78.37 ± 4.95, mean AEC of 468 ± 102.26, and mean serum IgE of 271.15 ± 86.44.
• Stage B (n = 26, 27.1%) had a mean FEV₁% of 63.23 ± 7.31, mean AEC of 696.50 ± 234.59, and mean serum IgE of 778.86 ± 468.30.
• Stage E (n = 51, 53.1%) showed the lowest mean FEV₁% (36.41 ± 7.56) yet the highest mean AEC (832.24 ± 115.05) and serum IgE (1641.84 ± 580.50).

Figure 1 illustrates the progressive increase in AEC across GOLD stages, and Figure 2 shows the corresponding rise in serum IgE levels. (Hypothetical figures described.)

Relationship Between Symptoms and Disease Severity

Symptom burden, as measured by the Modified Medical Research Council (MMRC) grade and COPD Assessment Test (CAT) score, increased from Stage A to B and peaked in Stage E (p < 0.0001). Fever and sputum purulence were more frequent in stage E, aligning with higher rates of exacerbations.

Correlation Between AEC and Serum IgE

A strong positive correlation (r = 0.793, p < 0.0001) was observed between AEC and serum IgE. Patients with the highest AEC and IgE levels were more likely to experience repeated hospital admissions and severe exacerbations, as defined by Anthonisen’s criteria.

Table 1. Distribution Of Cases According To Sex

Table 2. Distribution Of Cases According To Age

Table 3. Mean AEC And Serum IgE By Gold Stage

TABLE 4. CORRELATION BETWEEN AEC AND SERUM IGE

Figure 1 Shows the Mean Absolute Eosinophil Count (AEC) Across Gold Stages, Highlighting A Progressive Increase from Stages A To E.

Figure 2 Displays the Corresponding Rise in Serum IgE Levels Across the Same Gold Stages, With A Noticeable Increase Especially in Stage E.

COPD exacerbations pose a significant clinical and economic challenge, as they are the primary drivers of morbidity and healthcare utilization [9]. This study confirms previous reports indicating that both blood eosinophil count and serum IgE levels are elevated in patients with more advanced disease and frequent exacerbations [10–12]. The observed stepwise increase in absolute eosinophil count (AEC) from stage A to E closely aligns with previous findings that link eosinophilic inflammation to a heightened risk of exacerbations and favorable corticosteroid responsiveness [13,14]. Blood eosinophil levels, while an indirect measure of eosinophilic airway inflammation, offer a pragmatic alternative to sputum eosinophil assessments that may be logistically challenging [15].

The marked elevation in serum IgE observed in stage E patients is particularly noteworthy, underscoring potential overlapping pathophysiological mechanisms between COPD, atopy, and allergic inflammation [16–18]. Several studies have postulated that smokers with a predisposition to atopy may exhibit heightened IgE production, exacerbating bronchial inflammation [19]. Elevated IgE in COPD has also been linked to earlier onset of respiratory symptoms and a higher frequency of exacerbations [20–22]. The robust correlation (r = 0.793) between AEC and serum IgE reinforces the concept of an “eosinophilic-atopic” COPD phenotype that may benefit from targeted therapies [23–25]. Agents targeting interleukin-5 (IL-5), which regulates eosinophil survival, have demonstrated reductions in exacerbation rates among eosinophilic COPD subgroups [26,27]. Similarly, anti-IgE therapy (omalizumab) has shown promise in selected COPD patients with prominent allergic features [28–30].

Clinically, these findings underscore the importance of routine measurement of both AEC and serum IgE in COPD management. Incorporating these biomarkers into risk stratification models could enable personalized therapeutic approaches, potentially improving outcomes while minimizing unnecessary steroid exposure or other interventions [31]. Although the present cross-sectional design did not track long-term exacerbation patterns, the significant associations observed here suggest that these biomarkers hold prognostic value [32,33]. Larger longitudinal studies would be valuable for quantifying how cut-off thresholds of AEC and IgE might optimize treatment decisions in diverse COPD populations [34,35].

Finally, our data demonstrate that advanced GOLD stage patients (stage E) tend to have significantly lower FEV₁%, lower BMI, and higher frequencies of hospital admission, aligning with previous research linking malnutrition and frequent exacerbations to advanced disease [36–38]. Integrating biomarker assessments with nutritional and functional measures can offer a more holistic view of patient risk profiles [39]. In conclusion, the present study adds to the mounting evidence that elevated eosinophil counts and serum IgE levels may serve as actionable biomarkers in COPD, guiding clinicians toward personalized management strategies aimed at reducing exacerbations and improving overall patient outcomes.

In this cross-sectional study of COPD patients, higher blood eosinophil counts and elevated serum IgE levels were strongly associated with advanced disease and increased exacerbation frequency. These findings support the role of eosinophilic and atopic mechanisms in COPD pathogenesis, highlighting the potential of these biomarkers to refine risk stratification and treatment strategies. Clinicians may consider incorporating routine measurement of AEC and IgE to identify high-risk individuals who could benefit from targeted anti-eosinophil or anti-IgE therapies, thereby improving patient outcomes and reducing the burden of frequent exacerbations.

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