European Journal of Cardiovascular Medicine

Chronic Obstructive Pulmonary Disease (COPD) is a progressive, inflammatory lung disease characterized by airflow limitation that is not fully reversible. It represents a major global health concern, contributing significantly to morbidity, mortality, and healthcare burden worldwide (1). Acute exacerbations of COPD (AECOPD) are defined as episodes of worsening respiratory symptoms, particularly dyspnea, cough, and sputum production, beyond normal day-to-day variations and often necessitate a change in treatment (2). These exacerbations can accelerate the progression of the disease, reduce quality of life, and are a leading cause of hospitalization and death among COPD patients (3).

Several risk factors have been identified in association with the occurrence of AECOPD. These include advanced age, prior history of exacerbations, poor baseline lung function, ongoing tobacco use, and comorbidities such as cardiovascular diseases and diabetes mellitus (4). Moreover, recent studies have highlighted the role of inflammatory biomarkers such as C-reactive protein (CRP), procalcitonin, neutrophil-to-lymphocyte ratio (NLR) and Eosinophil count in predicting the likelihood and severity of exacerbations (5). Identifying such predictors is essential for stratifying patient risk and implementing targeted preventive strategies.

Despite advancements in the management of COPD, a substantial number of patients continue to experience frequent and severe exacerbations. The ability to predict these episodes early can improve clinical outcomes by allowing for timely intervention. Therefore, this study aims to evaluate the clinical and laboratory predictors of AECOPD among hospitalized patients and to identify those at highest risk for adverse outcomes.

A total of 120 patients admitted with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were enrolled consecutively. Inclusion criteria included adults aged ≥40 years with a confirmed diagnosis of COPD based on spirometric criteria (post-bronchodilator FEV₁/FVC < 0.70), presenting with acute worsening of respiratory symptoms requiring hospitalization. Patients with alternative diagnoses such as bronchial asthma, active tuberculosis, interstitial lung disease, or malignancy were excluded.

Data Collection:
Demographic details such as age, sex, and smoking history were recorded. Clinical information included comorbid conditions, history of previous exacerbations in the past year, medication usage, and baseline oxygen saturation on room air at the time of admission. A detailed physical examination was carried out for each patient.

Laboratory Investigations:
Venous blood samples were collected upon admission for evaluation of routine hematological parameters, including complete blood count (CBC), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and eosinophil count. Arterial blood gas (ABG) analysis was performed to assess respiratory acidosis or hypoxemia. Chest radiographs were evaluated to rule out pneumonia, pulmonary edema, or other acute pathologies.

Outcome Measures:
The primary outcome was the identification of clinical and biochemical predictors associated with acute exacerbations requiring hospitalization. Secondary outcomes included length of hospital stay and need for non-invasive or invasive ventilation.

Statistical Analysis:
Data were entered into Microsoft Excel and analyzed using SPSS version 26.0. Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as frequencies and percentages. Univariate analysis was performed using Chi-square or t-tests as appropriate. Variables with p < 0.05 in univariate analysis were included in a multivariate logistic regression model to determine independent predictors of AECOPD. A p-value < 0.05 was considered statistically significant

A total of 120 patients diagnosed with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were included in the study. The demographic and clinical characteristics of the participants are summarized in Table 1. The mean age of the cohort was 66.5 ± 9.3 years, with a male predominance (68.3%). Most patients (75%) had a history of smoking, and 45% reported two or more exacerbations in the previous year.

Among the comorbidities observed, hypertension (42.5%) and diabetes mellitus (30%) were the most common. Oxygen saturation at admission was below 90% in 58.3% of the cases. Elevated C-reactive protein (CRP > 30 mg/L) was detected in 72 patients (60%),  high neutrophil-to-lymphocyte ratio (NLR > 3.5) was seen in 64 patients (53.3%) and increased eosinophil count>300 cells/µL was seen in 84 patients (70%) as shown in Table 2.

On multivariate logistic regression analysis (Table 3), three variables were identified as significant independent predictors of hospitalization due to AECOPD: a history of ≥2 exacerbations in the past year (OR: 3.21, 95% CI: 1.78–5.84, p = 0.002), CRP >30 mg/L (OR: 2.89, 95% CI: 1.45–4.73, p = 0.005), and NLR >3.5 (OR: 2.56, 95% CI: 1.39–4.21, p = 0.008), eosinophil count>300 cells/µL (OR: 2.59, 95% CI:1.44-5.27, p=0.002).

Table 1: Baseline Demographic and Clinical Characteristics of the Study Population (N = 120)

Table 2: Laboratory Parameters of Patients with AECOPD

Table 3: Multivariate Logistic Regression Analysis for Predictors of AECOPD

These findings highlight that a combination of prior exacerbation history and elevated inflammatory markers significantly increases the risk of severe AECOPD episodes requiring hospitalization.

The present study aimed to identify clinical and laboratory predictors of acute exacerbation in hospitalized COPD patients. The findings indicate that a history of frequent prior exacerbations, elevated C-reactive protein (CRP) levels, increased neutrophil-to-lymphocyte ratio (NLR) and eosinophil count are significant predictors for in-hospital AECOPD events. These results are consistent with previous literature and support the utility of these markers in routine clinical risk assessment.

Frequent exacerbations in the past have long been recognized as a major risk factor for future episodes and increased hospitalization rates in COPD patients (1,2). Hurst et al. emphasized the concept of an "exacerbator phenotype," where certain patients exhibit a higher propensity for recurrent exacerbations despite optimal therapy (3). This phenotype is often linked with more severe disease, comorbidities, and poor treatment adherence (4).

Inflammatory biomarkers, particularly CRP, have emerged as important tools in predicting and monitoring AECOPD. Elevated CRP reflects systemic inflammation and has been shown to correlate with disease severity, bacterial infections, and treatment response (5,6). Studies have demonstrated that a CRP level above 10 mg/L is associated with poor clinical outcomes and longer hospital stays (7). The current study reinforces this by identifying CRP >30 mg/L as a significant independent predictor of exacerbation.

The neutrophil-to-lymphocyte ratio (NLR) along with eosinphil count  are cost-effective inflammatory markers, has gained prominence in recent years as a prognostic indicator in various respiratory and cardiovascular diseases (8,9). In COPD, elevated NLR and eosinphil count have been linked to disease severity, exacerbation frequency, and mortality (10). Rahimirad et al. found that patients with NLR and esosinphil count above normal range had significantly higher exacerbation rates and worse outcomes (11). The present study supports this observation, demonstrating a strong association between NLR >3.5 and eosinophil count> 300 cells/µL and AECOPD-related hospitalization.

In addition to inflammatory markers, arterial blood gas (ABG) abnormalities such as respiratory acidosis and hypercapnia were also frequently observed in the current study. These findings align with previous research showing that pH <7.35 and PaCO₂ >45 mmHg are common features during acute exacerbations and may signal impending respiratory failure (12,13).

Comorbid conditions, especially cardiovascular diseases, diabetes, and hypertension, contribute to the complexity of COPD management and have been associated with increased exacerbation risk (14). Though the present study did not find a statistically significant association between comorbidities and exacerbation severity, the high prevalence of comorbidities among participants underscores the need for comprehensive care.

The results of this study highlight the importance of using a multidimensional approach in identifying high-risk patients. Incorporating clinical history with biomarkers like CRP, NLR and Eosinophil count may facilitate early interventions, reduce readmissions, and improve overall patient outcomes (15).

This study highlights that a history of frequent exacerbations, elevated CRP levels, high NLR and increased eosinphil count are significant predictors of acute COPD exacerbations requiring hospitalization. Early identification and monitoring of these markers can aid in timely intervention, potentially reducing morbidity and improving patient outcomes.

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