European Journal of Cardiovascular Medicine

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating chronic inflammatory condition characterized by persistent respiratory symptoms and progressive airflow limitation.¹ The pathophysiology of COPD involves complex interactions between environmental exposures, genetic susceptibility, and inflammatory processes.² Systemic inflammation has been increasingly recognized as a key contributor to the development and progression of COPD, as well as its associated comorbidities and disease severity.3

Fibrinogen, a plasma glycoprotein synthesized primarily by hepatocytes, plays a critical role in the coagulation cascade and inflammatory response.⁴ Elevated fibrinogen levels have been associated with an increased risk of cardiovascular events, metabolic disorders, and various chronic inflammatory conditions.^5,6 In the context of COPD, fibrinogen has emerged as a potential biomarker of systemic inflammation and disease severity.⁷

Several observational studies have reported higher circulating fibrinogen levels in COPD patients compared to healthy individuals.^8,9 Furthermore, elevated fibrinogen levels have been associated with an increased risk of acute exacerbations, lung function decline, and mortality in COPD patients.^10,11 These findings suggest that fibrinogen may serve as a valuable marker for assessing the systemic inflammatory burden and predicting disease outcomes in COPD.¹²

However, the relationship between fibrinogen levels and COPD severity remains incompletely understood, with conflicting evidence from different studies.¹³ Some researchers have proposed that fibrinogen may be a useful biomarker for identifying COPD patients at higher risk of adverse outcomes, guiding therapeutic decisions, and monitoring disease progression.¹⁴ Others have questioned the specificity and clinical utility of fibrinogen as a standalone marker, advocating for a more comprehensive evaluation of inflammatory biomarkers in COPD.¹⁵

Additionally, the potential factors influencing fibrinogen levels in COPD patients, such as smoking status, comorbidities, and treatment regimens, require further investigation.¹⁶ Understanding these associations may provide insights into the pathophysiological mechanisms underlying systemic inflammation in COPD and contribute to the development of personalized treatment strategies.¹⁷

In this study, we aim to explore the relationship between serum fibrinogen levels and clinical severity in COPD patients. By evaluating fibrinogen levels in conjunction with lung function, symptom burden, and other clinical parameters, we seek to elucidate the potential role of fibrinogen as a marker of disease severity and progression in COPD.

This was a cross-sectional observational study conducted at the Department of General Medicine of The Oxford Medical College Hospital and Research Centre, Bangalore between April 2023 to September 2024. The study protocol was approved by the Institutional Ethics Committee before commencement.

Patients aged 20 years and above, diagnosed with COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, were included in the study. Patients with a history of other chronic inflammatory diseases, active malignancy, recent acute exacerbation (within 4 weeks), or acute infections were excluded to minimize potential confounding factors.

Eligible 60 patients were identified from the outpatient and inpatient departments of General Medicine. After obtaining written informed consent, participants underwent a detailed clinical evaluation, including a medical history, physical examination, and assessment of COPD severity based on the GOLD criteria (spirometry, symptom assessment, and exacerbation history).

Venous blood samples were collected from participants after an overnight fast. Serum fibrinogen levels were measured using immunoturbidimetry at the hospital's central laboratory. The laboratory personnel were blinded to the clinical details of the participants.

In addition to serum fibrinogen levels, Demographic information like age, gender, smoking history, clinical parameters like body mass index (BMI), vital signs, comorbidities and  COPD severity including post-bronchodilator forced expiratory volume in 1 second (FEV1), FEV1% predicted, GOLD stage, COPD Assessment Test (CAT) score, exacerbation history and Treatment details were collected.

Descriptive statistics (mean, standard deviation, frequencies, and percentages) were used to summarize the demographic and clinical characteristics of the study population. Participants were stratified based on COPD severity (GOLD stages) and serum fibrinogen levels. The primary analysis involved comparing serum fibrinogen levels across different COPD severity groups using analysis of variance (ANOVA), as appropriate. Post-hoc pairwise comparisons were performed to identify significant differences between specific groups. Correlation analyses (Pearson's or Spearman's rank correlation) were conducted to assess the relationship between serum fibrinogen levels and continuous variables such as FEV1, FEV1% predicted, CAT score, and BMI.

Table 1 describes the demographic and clinical characteristics of the study population. The mean age was 67.15 years, with a majority (56.7%) being males. 40% of the participants were former smokers, while 40% were current smokers and 20% never smoked. The distribution of COPD severity showed that 18.3% had mild COPD, 36.7% had moderate COPD, 30% had severe COPD, and 15% had very severe COPD according to the GOLD staging system.

Table 1: Baseline Characteristics of Study Participants (N=60)

Table 2 presents the mean serum fibrinogen levels stratified by COPD severity. There was a significant increasing trend in serum fibrinogen levels with worsening COPD severity (p<0.001, ANOVA). Patients with mild COPD had a mean fibrinogen level of 3.4 g/L, while those with very severe COPD had a mean level of 4.9 g/L. This suggests that serum fibrinogen levels are elevated in COPD patients and are associated with the severity of the disease.

Table 2: Serum Fibrinogen Levels by COPD Severity

Table 3 shows the results of correlation analyses between serum fibrinogen levels and various clinical parameters. Serum fibrinogen levels were inversely correlated with FEV1% predicted (r = -0.62, p<0.001), indicating that higher fibrinogen levels were associated with lower lung function. Additionally, there was a positive correlation between serum fibrinogen and the COPD Assessment Test (CAT) score (r = 0.48, p<0.001), suggesting that higher fibrinogen levels were associated with increased symptom burden. No significant correlation was found between serum fibrinogen and body mass index (BMI).

Table 3: Correlation Analysis

Table 4 presents the results of a multivariable linear regression analysis, which examined the independent association between serum fibrinogen levels and COPD severity, adjusting for potential confounders such as age, gender, smoking status, and comorbidities. After adjustment, serum fibrinogen levels remained independently associated with COPD severity (β = 0.37, p = 0.002). Furthermore, each 1 g/L increase in serum fibrinogen levels was associated with a 6.8% decrease in FEV1% predicted (95% CI: -10.2% to -3.4%, p<0.001), indicating a significant impact on lung function.

Table 4: Multivariable Linear Regression Analysis

The present cross-sectional study sought to investigate the relationship between serum fibrinogen levels and clinical severity in COPD patients. Our findings demonstrate a significant association between elevated serum fibrinogen and more severe COPD, characterized by lower lung function, increased symptom burden, and a higher degree of airflow limitation.

The observed trend of increasing serum fibrinogen levels with worsening COPD severity is consistent with previous reports in the literature. Groenewegen et al. ¹¹ found that higher fibrinogen levels were associated with an increased risk of exacerbations and lung function decline in COPD patients. Similarly, Dahl et al.¹⁰ reported that elevated fibrinogen was a predictor of poor prognosis and mortality in COPD. Our results further corroborate these findings and highlight the potential utility of serum fibrinogen as a marker of disease severity in COPD patients.

The inverse correlation between serum fibrinogen and FEV1% predicted in our study aligns with the findings of Duvoix et al.⁷, who demonstrated a significant negative correlation between fibrinogen levels and lung function parameters, including FEV1, in a large cohort of COPD patients. This association supports the notion that systemic inflammation, as reflected by elevated fibrinogen levels, contributes to the pathophysiological processes underlying airflow limitation and lung function impairment in COPD.³

Furthermore, our observation of a positive correlation between serum fibrinogen and the COPD Assessment Test (CAT) score is consistent with the study by Thomsen et al.¹², which reported an association between elevated inflammatory biomarkers, including fibrinogen, and increased symptom burden in COPD patients.¹⁸ This relationship suggests that systemic inflammation may play a role in exacerbating respiratory symptoms and impacting the overall quality of life in COPD patients.

Interestingly, we did not find a significant correlation between serum fibrinogen levels and body mass index (BMI) in our study population. This contrasts with some previous reports that have suggested an association between elevated fibrinogen and higher BMI in COPD patients. However, other studies have failed to demonstrate a consistent relationship between these variables¹⁹, indicating that the influence of BMI on fibrinogen levels in COPD may be complex and potentially influenced by other factors, such as disease severity and comorbidities.

The multivariable linear regression analysis in our study revealed that serum fibrinogen levels remained independently associated with COPD severity, even after adjusting for potential confounders like age, gender, smoking status, and comorbidities. This finding is in line with the results of Dickens et al.¹⁴, who reported that fibrinogen was one of the most stable and reproducible biomarkers associated with COPD severity and progression, independent of other clinical variables.

While our study provides further evidence supporting the role of serum fibrinogen as a marker of clinical severity in COPD, it is important to note that fibrinogen is a non-specific marker of systemic inflammation and may be influenced by various factors, including cardiovascular comorbidities, metabolic disorders, and acute inflammatory processes.^{7, 20} Therefore, the interpretation of fibrinogen levels in COPD should be contextualized within the broader clinical picture and combined with other relevant biomarkers and assessments.

In conclusion, our study adds to the growing body of evidence suggesting that serum fibrinogen levels are associated with COPD severity, lung function impairment, and respiratory symptom burden. While further prospective studies are warranted to establish causality and elucidate the underlying mechanisms, our findings support the potential utility of serum fibrinogen as a complementary biomarker for assessing disease severity and guiding management strategies in COPD patients.

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