Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic inflammation of the airways, primarily due to exposure to noxious particles or gases (1). It remains a major cause of morbidity and mortality worldwide, with an increasing global burden, particularly in low- and middle-income countries (2). Early diagnosis of COPD is critical for effective disease management, as interventions at an early stage can slow disease progression and improve quality of life (3). However, conventional diagnostic methods, such as spirometry, often fail to detect the disease in its initial stages, necessitating the identification of reliable biomarkers for early diagnosis (4).

Airway inflammation plays a central role in COPD pathogenesis, contributing to structural damage, airway remodelling, and progressive decline in lung function (5). Various inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been implicated in COPD, showing elevated levels even in the early stages of the disease (6). These biomarkers not only reflect systemic inflammation but also correlate with disease severity and exacerbation frequency (7). Studies suggest that increased levels of inflammatory biomarkers may precede airflow limitation, highlighting their potential role in early COPD detection (8).

Despite the growing evidence on inflammatory biomarkers in COPD, their utility in early diagnosis remains underexplored. This study aims to assess the levels of CRP, IL-6, and TNF-α in patients with early-stage COPD compared to healthy individuals, thereby evaluating their diagnostic significance. Identifying reliable biomarkers for early COPD detection could facilitate prompt intervention, reducing disease burden and improving patient outcomes (9).

Study Design and Participants

This cross-sectional study was conducted at a tertiary care hospital over six months. A total of 120 participants were enrolled, comprising 60 patients diagnosed with early-stage COPD and 60 age- and gender-matched healthy controls. The inclusion criteria for the COPD group included patients with a smoking history of at least 10 pack-years and a spirometric diagnosis of COPD based on a post-bronchodilator forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) ratio of less than 0.7. Healthy individuals with normal pulmonary function tests and no history of smoking or chronic respiratory conditions were included as controls. Participants with acute respiratory infections, malignancies, autoimmune diseases, or a history of recent corticosteroid use were excluded from the study. For this study written informed consent was obtained from all participants before enrolment and confidentiality of participant data was maintained throughout the study.

Sample Collection and Biomarker Analysis

Venous blood and induced sputum samples were collected from all participants under sterile conditions. Blood samples were centrifuged at 3000 rpm for 10 minutes, and serum was separated for biomarker analysis. Levels of inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were measured using enzyme-linked immunosorbent assay (ELISA) kits following the manufacturer’s instructions. Sputum samples were processed using the dithiothreitol method, and inflammatory marker levels were quantified using the same ELISA technique.

Pulmonary Function Tests (PFTs)

Spirometry was performed using a calibrated spirometer to assess lung function. The test was conducted according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. FEV₁, FVC, and the FEV₁/FVC ratio were recorded before and after bronchodilator administration. COPD severity was classified based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

Statistical Analysis

Data were analyzed using SPSS software version 26.0. Descriptive statistics, including mean and standard deviation, were calculated for continuous variables. The Shapiro-Wilk test was used to assess data normality. Comparisons between groups were performed using the independent t-test for normally distributed data and the Mann-Whitney U test for non-parametric variables. Pearson’s correlation coefficient was used to evaluate the relationship between biomarker levels and lung function parameters. A p-value of less than 0.05 was considered statistically significant.

Baseline Characteristics

The study included 120 participants, with 60 patients diagnosed with early-stage COPD and 60 healthy controls. The mean age of the COPD group was 58.2 ± 6.5 years, while the control group had a mean age of 56.9 ± 5.8 years (p = 0.384). The gender distribution was similar between groups (COPD: 42 males, 18 females; Control: 40 males, 20 females; p = 0.712). The mean BMI was slightly lower in the COPD group (24.3 ± 3.2 kg/m²) than in the control group (25.1 ± 2.9 kg/m²), though this difference was not statistically significant (p = 0.276). However, smoking history (pack-years) was significantly higher in the COPD group (18.7 ± 4.1) compared to the control group (0), with a p-value < 0.001. Pulmonary function tests (PFTs) revealed that the COPD group had significantly lower FEV₁ (% predicted) and FEV₁/FVC ratio compared to the control group (p < 0.001 for both) (Table 1).

Inflammatory Biomarker Levels

Serum levels of inflammatory biomarkers were significantly elevated in the COPD group compared to healthy controls (Table 2). The mean CRP level in COPD patients was 5.2 ± 1.1 mg/L, significantly higher than in the control group (1.8 ± 0.6 mg/L, p < 0.001). Similarly, IL-6 levels were elevated in the COPD group (12.4 ± 2.3 pg/mL) compared to controls (4.9 ± 1.2 pg/mL, p < 0.001). TNF-α levels were also significantly increased in COPD patients (8.6 ± 1.5 pg/mL) relative to the control group (3.2 ± 0.8 pg/mL, p < 0.001).

Correlation Analysis

A negative correlation was observed between inflammatory biomarker levels and lung function parameters. CRP levels showed a significant inverse correlation with FEV₁ (% predicted) (r = -0.72, p < 0.001). Similar trends were found for IL-6 (r = -0.68, p < 0.001) and TNF-α (r = -0.65, p < 0.001), indicating that higher inflammation marker levels were associated with greater impairment in lung function. ​​

Table 1: Baseline Characteristics of Study Participants

Table 2: Comparison of Inflammatory Biomarker Levels

The present study assessed the role of airway inflammation biomarkers in the early detection of Chronic Obstructive Pulmonary Disease (COPD). Our findings revealed significantly elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in COPD patients compared to healthy controls. These biomarkers demonstrated a strong negative correlation with pulmonary function, indicating their potential as early diagnostic indicators.

Inflammation plays a critical role in COPD pathogenesis, contributing to airway remodelling, mucus hypersecretion, and progressive decline in lung function (1). Systemic and local inflammatory responses in COPD are driven by elevated cytokine levels, which perpetuate airway damage and exacerbate disease progression (2). CRP, an acute-phase protein, is widely recognized as a marker of systemic inflammation and has been linked to disease severity in COPD (3). Previous studies have shown that CRP levels increase during acute exacerbations and correlate with airflow limitation, consistent with our findings (4,5).

IL-6, a pro-inflammatory cytokine, plays a key role in immune response regulation and has been implicated in the progression of COPD (6). Elevated IL-6 levels are associated with increased airway inflammation, systemic effects such as muscle wasting, and worsening pulmonary function (7). Our study confirmed significantly higher IL-6 levels in COPD patients, supporting its role as a biomarker for early detection. This aligns with reports suggesting that IL-6 is a predictor of COPD-related hospitalizations and mortality (8).

Similarly, TNF-α, a potent inflammatory mediator, has been linked to chronic airway inflammation in COPD (9). TNF-α contributes to the recruitment of inflammatory cells, destruction of lung parenchyma, and induction of oxidative stress, exacerbating disease progression (10). In our study, TNF-α levels were markedly elevated in COPD patients compared to controls, corroborating previous research that demonstrated a strong association between TNF-α and declining lung function (11,12).

The negative correlation observed between biomarker levels and pulmonary function parameters highlights their potential utility in early COPD detection. Studies have reported that systemic inflammation precedes structural lung changes, emphasizing the need for biomarkers to identify individuals at risk before irreversible damage occurs (13). Although spirometry remains the gold standard for COPD diagnosis, its limited sensitivity in early disease stages underscores the importance of complementary diagnostic tools, such as biomarker analysis (14,15).

Despite the promising results, this study has certain limitations. The cross-sectional design precludes the establishment of causality between biomarker elevation and COPD progression. Additionally, factors such as comorbidities, environmental exposures, and genetic predisposition may influence inflammatory biomarker levels, necessitating further research with larger, more diverse cohorts. Future longitudinal studies should explore whether biomarker monitoring can predict disease progression and guide therapeutic interventions.

In conclusion, our findings suggest that CRP, IL-6, and TNF-α serve as valuable biomarkers for early COPD detection. Their significant association with pulmonary function decline reinforces their potential role in disease screening and risk stratification. Integrating biomarker assessment with conventional diagnostic tools may enhance early COPD detection, enabling timely intervention and improved patient outcomes.

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