Chronic Obstructive Pulmonary Disease (COPD) is a prevalent, debilitating lung condition characterized by persistent airflow limitation that is not fully reversible. This progressive disease is primarily caused by exposure to noxious particles or gases, with cigarette smoking being the most prominent risk factor¹. The global burden of COPD is substantial, affecting millions of individuals worldwide and leading to significant morbidity and mortality. In 2019 alone, COPD was responsible for an estimated 3.23 million deaths, making it the third leading cause of mortality globally². The impact of COPD extends beyond physical health, significantly impairing patients' quality of life due to breathlessness, fatigue, and limitations in daily activities³. Moreover, COPD imposes a substantial economic burden on healthcare systems due to the high costs associated with hospitalizations, medications, and long-term care^1,4. 

Despite advances in understanding the pathophysiology of COPD, managing this complex disease remains a challenge. One of the most significant hurdles is the prevention and treatment of acute exacerbations, which are episodes of acute worsening of respiratory symptoms that often necessitate hospitalization and accelerate disease progression. These exacerbations are frequently triggered by respiratory infections or exposure to environmental pollutants, but their underlying mechanisms remain incompletely understood⁵. The ability to predict and prevent exacerbations is crucial for improving the quality of life and survival of COPD patients. 

The pathophysiology of COPD involves a complex interplay of factors, including airflow limitation, chronic inflammation, and systemic effects. Airflow limitation, the hallmark of COPD, is primarily caused by a combination of small airway disease (bronchiolitis) and parenchymal destruction (emphysema)¹. Chronic inflammation plays a pivotal role in the development and progression of COPD, involving the infiltration of inflammatory cells, such as neutrophils, macrophages, and lymphocytes, into the airways and lung parenchyma. These inflammatory cells release a variety of mediators, including cytokines, chemokines, and reactive oxygen species, which contribute to tissue damage and airway remodelling⁶. Furthermore, COPD is increasingly recognized as a systemic disease, with inflammation extending beyond the lungs and affecting various organ systems, leading to comorbidities such as cardiovascular disease, osteoporosis, and skeletal muscle dysfunction⁷. Understanding the complex interplay between local and systemic inflammation is essential for developing effective therapeutic strategies for COPD.

The study was conducted at the Department of Respiratory Medicine, Amaltas Institute of Medical Sciences, Dewas. This prospective observational study was conducted on patients attending the Amaltas Institute of Medical Sciences between 2023 and 2025. The study focused on individuals admitted to the inpatient department of pulmonary medicine who met the inclusion and exclusion criteria. After obtaining informed consent, a total of 70 patients with Chronic Obstructive Pulmonary Disease (COPD) were enrolled. The study duration was 18 months.

Inclusion Criteria

• Both outpatients and inpatients were eligible.
• Individuals with a confirmed diagnosis of COPD patients.
• Patients who provided informed consent.

Exclusion Criteria

• Patients with bronchial asthma.
• Individuals with active tuberculosis or any history of pulmonary fibrosis.
• Presence of any tumour, hepatitis, thyroid disease, or autoimmune disease.
• Patients receiving systemic corticosteroids, antibiotics, or immunosuppressive treatment.
• Those who had not been exacerbation-free for at least the preceding 8 weeks.

Withdrawal of consent.

Table 1 – Distribution of patients according to the age group

The distribution of patients by age group. The majority of patients (35 out of 102, 34.3%) were in the 51-60 years age group, followed closely by the 61-70 years group (32 patients, 31.4%). The youngest (≤50 years) and oldest (≥81 years) age groups represented the smallest proportions of the study population, with 6.9% (7 patients) and 7.8% (8 patients), respectively. Approximately 19.6% (20 patients) were aged between 71 and 80 years. The mean age of the patients was noted as 64.82 years with a SD of 10.32 years.

Table 2 - Distribution of patients according to the Body Mass Index in kg/m²

The distribution of patients based on their Body Mass Index (BMI). The largest proportion of patients (56 out of 102, 54.9%) fell within the BMI range of 18.5-22.9 kg/m². A substantial number of patients (35 out of 102, 34.3%) had a BMI <18.5 kg/m². Only a small percentage of patients had a BMI in the overweight (23.0-24.9 kg/m²) and obese (≥25.0 kg/m²) categories, accounting for 2.9% (3 patients) and 7.8% (8 patients), respectively.

Table 3– Distribution of patients based on the 6-minute walk distance results

Table 3 shows the distribution of patients (n = 70) according to their 6-minute walk distance. The most frequent result was a distance of 250-349 meters, observed in 50.0% of the patients (35 patients). 27.1% of the patients (19 patients) achieved a distance of ≥350 meters. Distances of 150-249 meters and ≤149 meters were less common, accounting for 15.7% (11 patients) and 7.1% (5 patients), respectively. The mean 6MWD was noted as 293.8 with a SD of 82.1 m.

Table 4– Descriptive statistics of patient’s NLR values

The descriptive statistics for the neutrophil-to-lymphocyte ratio (NLR) in the study population (n = 102). The NLR values ranged from a minimum of 1.07 to a maximum of 10.26, with a median of 4.05 and a mean of 4.35 (standard deviation = 2.37).

Table 5 – Distribution of patients without exacerbation on the basis of FEV₁% of predicted according to BODE index.

Table 6 – Distribution of patients without exacerbation on the basis of MMRC grading

The distribution of patients without exacerbation (n = 70) according to their FEV1% of predicted. The most frequent category was 50-64% predicted FEV1, representing 37.1% of these patients (26 patients). Patients with FEV1% of predicted ≥65% constituted 25.7% (18 patients), while 27.1% (19 patients) had FEV1% of predicted between 36-49%. The smallest proportion (10.0%, 7 patients) had the lowest FEV1% of predicted (≤35%). The mean FEV₁% was noted as 54.1 with a SD of 15.7%.

Table 7– Distribution of patients on the basis of BODE Index values

The distribution of patients (n = 70) according to their BODE Index values. The most common category was a BODE Index of <5, accounting for 61.4% of the patients (43 patients). 22.9% (16 patients) had a BODE Index of 5-6, and 15.7% (11 patients) had a BODE Index of ≥7. The mean BODE index was noted as 4.2 with a SD of 2.29.

Table 8– NLR Values Across BODE Index Categories

The relationship between neutrophil-to-lymphocyte ratio (NLR) and BODE Index categories was investigated, and the results are presented. A statistically significant difference in NLR across BODE Index categories was observed (Kruskal-Wallis H = 16.555, p < 0.001). The mean NLR increased with increasing BODE Index category, ranging from 3.07 (SD = 2.00) in the <5 category to 6.05 (SD = 2.21) in the ≥7 category. The mean ranks also showed a corresponding increase, from 28.91 in the <5 category to 54.86 in the ≥7 category, indicating that higher disease severity (as reflected by a higher BODE Index) is associated with higher NLR.

Table 9 – Comparison of NLR between Patients with and Without Exacerbation

A comparison of neutrophil-to-lymphocyte ratio (NLR) between patients with and without exacerbation revealed a statistically significant difference (Mann-Whitney U statistic = 613.00, p < 0.001). Patients experiencing exacerbation (n = 32) had a significantly higher mean NLR (5.56, SD = 2.06) compared to those without exacerbation (n = 70), who had a mean NLR of 3.79 (SD = 2.30). This difference is further supported by the mean rank values, with the exacerbation group exhibiting a mean rank of 67.34 and the non-exacerbation group a mean rank of 44.26, and sum of ranks of 2155.00 and 3098.00 respectively, indicating a clear elevation of NLR during exacerbation events.

The specific aims were to assess the correlation between NLR and the multidimensional BODE index, to compare mean NLR values between stable COPD patients and those experiencing acute exacerbations, and to evaluate the potential role of NLR in predicting exacerbation events. This study yielded pertinent findings regarding these objectives, demonstrating clear associations between NLR and comprehensive indices of disease severity, including functional status and symptom scores⁸. Furthermore, the study confirmed distinctly elevated NLR level in stable COPD patients, underscoring the marker's sensitivity to the heightened inflammatory activity characteristic of these events. These results provide context for discussing NLR's role in the assessment of COPD within this specific patient population.

A key objective of this study was to evaluate the relationship between NLR and a multidimensional assessment of COPD severity. The results demonstrated a statistically significant moderate positive correlation between NLR and the BODE index score (r = 0.570, p < 0.01) among the participants (Table 14). This finding is in accordance with several previous investigations that have explored this association.

For instance, Furutate et al. (2016)⁹ reported a significant positive correlation (p<0.001) between NLR and the BODE index in their cohort of stable COPD patients. Similarly, Lee et al. (2016)¹⁰ observed a significant correlation between NLR and the BODE index. The systematic review by Pascual-González et al. (2018)¹¹ also highlighted a significant correlation between NLR and the BODE index based on pooled data, and comparable positive correlations have been noted in other studies, such as those by Sharma et al. (2023)¹². The consistency of this finding across studies suggests that NLR, as a marker of systemic inflammation, parallels the integrated measure of disease severity provided by the BODE index.

This correlation likely reflects the contribution of systemic inflammation to various components encompassed within the BODE score, including airflow limitation, dyspnea perception, exercise capacity, and potentially nutritional status (BMI).

This study demonstrated a significant positive correlation between the Neutrophil-to-Lymphocyte Ratio (NLR) and the BODE index in the studied COPD patient cohort, indicating an association between NLR and overall disease severity. A significant difference in mean NLR was observed between patient groups, with markedly higher values found in individuals experiencing acute exacerbations compared to those in a stable state. These findings support the potential role of NLR in reflecting the heightened inflammatory state associated with acute exacerbations of COPD. Within this specific study population, NLR serves as an accessible marker associated with both multidimensional disease severity and the presence of acute exacerbations in COPD.

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