Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory condition characterised by persistent respiratory symptoms and airflow limitation, commonly associated with prolonged exposure to tobacco smoke and environmental pollutants. It remains a major cause of morbidity, mortality and healthcare utilisation worldwide [1]. Acute exacerbation of COPD (AECOPD), characterised by an acute worsening of respiratory symptoms, represents an important event in disease progression[2]. These episodes are associated with increased airway inflammation, respiratory deterioration, hospitalisation, accelerated decline in lung function and impaired quality of life. Recurrent exacerbations further contribute to disease progression and healthcare burden [3,4].The pathophysiology of AECOPD involves complex interactions between airway inflammation, systemic inflammatory responses, oxidative stress and altered immune mechanisms [5,6]. Respiratory infections, including bacterial and viral pathogens, are common precipitating factors, although environmental and non-infectious triggers may also contribute [7,8]. During exacerbations, increased neutrophil activation promotes the release of proteolytic enzymes, reactive oxygen species and inflammatory mediators, while alterations in lymphocyte distribution may reflect physiological stress and immune dysregulation. The magnitude of this inflammatory response may influence exacerbation severity, treatment requirements and subsequent clinical outcomes [5,6].In recent years, considerable attention has been directed towards identifying simple, inexpensive biomarkers for assessing systemic inflammation and predicting disease severity in AECOPD. The neutrophil-to-lymphocyte ratio (NLR), calculated by dividing the absolute neutrophil count by the absolute lymphocyte count obtained from a routine complete blood count, has emerged as a potentially useful inflammatory marker [9,10]. Elevated NLR reflects the combined effects of neutrophilia and relative lymphopenia and has been associated with increased inflammatory burden, exacerbation severity, hospitalisation and adverse clinical outcomes, including mortality [11,12]. Its accessibility and low cost make it particularly relevant in resource-limited healthcare settings.Systemic corticosteroids constitute an important component of pharmacological management in moderate-to-severe AECOPD. Through their anti-inflammatory and immunomodulatory effects, corticosteroids improve lung function and oxygenation, accelerate symptomatic recovery, shorten hospital stay and reduce treatment failure [13,14]. However, their administration may also produce adverse effects, including hyperglycaemia and increased susceptibility to infection. Treatment response may vary according to inflammatory phenotype, exacerbation severity, comorbidities and baseline immune status [13,15]. Identifying readily available biomarkers that complement clinical assessment may therefore improve understanding of treatment-related outcomes.Importantly, corticosteroids can independently alter circulating leukocyte populations by inducing peripheral neutrophilia through demargination and reducing lymphocyte counts, thereby increasing NLR irrespective of underlying disease-related inflammation . Consequently, the timing of NLR measurement in relation to corticosteroid initiation is essential for accurate interpretation. Assessing baseline NLR alongside corticosteroid exposure and subsequent clinical outcomes may provide valuable insight into the relationship between systemic inflammation, therapeutic intervention and recovery.Although NLR has demonstrated prognostic potential in AECOPD, its association with corticosteroid therapy and clinical outcomes requires further evaluation [11,12]. Accordingly, the present study aims to assess the association between neutrophil-to-lymphocyte ratio, corticosteroid therapy and clinical outcomes in patients with acute exacerbation of COPD.

The present prospective observational study was conducted in the Department of Medicine at a tertiary care hospital to evaluate the association between neutrophil-to-lymphocyte ratio (NLR), corticosteroid therapy and clinical outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).A total of 160 patients diagnosed with AECOPD and fulfilling the eligibility criteria were enrolled. Inclusion Criteria 1. Patients aged ≥40 years. 2. Established diagnosis of COPD based on clinical history and previous spirometric evidence (post-bronchodilator FEV₁/FVC less than 0.70). 3. Patients presenting with AECOPD requiring hospital-based management. 4. Patients willing to provide informed consent. Exclusion Criteria 1. Patients with bronchial asthma, active pulmonary tuberculosis or other significant respiratory disorders. 2. Patients with haematological malignancies, autoimmune disorders or conditions affecting leukocyte counts. 3. Patients receiving systemic corticosteroids before baseline blood sampling during the current exacerbation. 4. Patients receiving immunosuppressive therapy or chemotherapy. 5. Patients with incomplete essential clinical or laboratory data. Patients were categorised into two groups according to their baseline NLR using a predefined cut-off value:Group A: Patients with low baseline NLR ,Group B: Patients with high baseline NLR Corticosteroid exposure and clinical outcomes were compared between the two groups. Data Collection and Study Procedure Demographic characteristics, smoking history, duration of COPD, previous exacerbations, comorbidities and presenting symptoms were recorded using a structured proforma. Baseline assessment included vital parameters, oxygen saturation (SpO₂) and severity of respiratory distress. Venous blood samples were collected at admission before corticosteroid administration. Complete blood count, absolute neutrophil count and absolute lymphocyte count were measured using an automated haematology analyser. Other relevant investigations, including C-reactive protein, arterial blood gas analysis and chest radiography, were recorded as clinically indicated. NLR was calculated using the following formula: Corticosteroid Therapy and Outcome Assessment Details of systemic corticosteroid therapy, including drug type, route, daily dose, duration and cumulative exposure, were documented. Treatment was administered according to the treating physician's clinical judgement and prevailing COPD management guidelines. Patients were monitored throughout hospitalisation to assess clinical improvement, duration of hospital stay, oxygen requirements, need for non-invasive or invasive mechanical ventilation, ICU admission, complications and in-hospital mortality. Statistical Analysis Data were analysed using SPSS.26 software. Continuous variables were expressed as mean ± standard deviation or median (interquartile range), while categorical variables were presented as frequencies and percentages. Normality was assessed using the Shapiro–Wilk test. Student's t-test or Mann–Whitney U test was used for continuous variables, whereas the Chi-square test or Fisher's exact test was applied to categorical variables. Pearson's or Spearman's correlation analysis was performed to assess relevant associations. ROC curve analysis was used to evaluate the discriminatory ability of baseline NLR for adverse clinical outcomes. Multivariable logistic regression was performed to identify independent associations after adjustment for corticosteroid exposure, baseline exacerbation severity and other relevant confounders. Results were expressed as odds ratios (OR) with 95% confidence intervals (CI). A p-value less than 0.05 was considered statistically significant.

A total of 160 patients were divided into Group A (low NLR, n=68) and Group B (high NLR, n=92). Group B patients were significantly older (65.8 ± 10.1 vs. 61.4 ± 9.2 years; p=0.005), with greater smoking exposure (29.8 ± 12.4 vs. 24.6 ± 10.2 pack-years; p=0.005), longer COPD duration (p=0.003), and more frequent previous exacerbations (p<0.001). Baseline SpO₂ was significantly lower (87.8 ± 4.2% vs. 91.2 ± 3.4%), while respiratory rate was higher (28.6 ± 4.1 vs. 24.8 ± 3.2 breaths/min) in Group B (both p<0.001). Sex distribution, smoking status, diabetes, and hypertension were comparable between groups (Table 1).Group B demonstrated significantly higher total leukocyte and absolute neutrophil counts, with lower absolute lymphocyte counts (all p<0.001). Median NLR was 6.4 (IQR: 4.8–8.6) in Group B versus 2.8 (IQR: 2.2–3.2) in Group A. CRP was significantly elevated (58 vs. 24 mg/L), accompanied by lower PaO₂ (61.8 vs. 69.4 mmHg) and higher PaCO₂ (51.6 vs. 44.2 mmHg) in Group B (all p<0.001) (Table 2).All patients received systemic corticosteroids. Intravenous administration was more frequent in Group B (53.3% vs. 29.4%; p=0.003), with significantly longer treatment duration (6.8 ± 1.7 vs. 5.2 ± 1.1 days) and higher cumulative prednisolone-equivalent dose (286 ± 74 vs. 208 ± 48 mg; both p<0.001). Additional corticosteroid courses (18.5% vs. 7.4%; p=0.044) and steroid-associated hyperglycaemia (26.1% vs. 13.2%; p=0.047) were also more frequent in Group B (Table 3).Patients with high NLR had significantly longer hospital stays (8.2 ± 2.6 vs. 5.4 ± 1.8 days; p<0.001), greater requirements for supplemental oxygen (84.8% vs. 63.2%; p=0.002), non-invasive ventilation (39.1% vs. 17.6%; p=0.003), and invasive ventilation (14.1% vs. 4.4%; p=0.043). ICU admission (32.6% vs. 13.2%; p=0.005) and in-hospital complications (31.5% vs. 14.7%; p=0.014) were significantly higher, whereas clinical improvement within 72 hours was lower (53.3% vs. 79.4%; p<0.001). Mortality was numerically higher in Group B (9.8% vs. 2.9%) but was not statistically significant (p=0.120) (Table 4, Figure 1).Baseline NLR showed significant positive correlations with CRP (ρ=0.52), respiratory rate (r=0.46), PaCO₂ (r=0.39), corticosteroid duration (ρ=0.36), cumulative dose (ρ=0.33), and hospital stay (ρ=0.48). A significant negative correlation was observed with baseline SpO₂ (r=−0.43). Age and previous exacerbation frequency also demonstrated positive associations with NLR (all p≤0.002) (Table 5, Figure 2).Following multivariable adjustment, high baseline NLR (≥3.5) remained independently associated with ICU admission (AOR=2.86; 95% CI: 1.19–6.88; p=0.019), along with baseline SpO₂ below 90% (AOR=3.24; 95% CI: 1.38–7.61; p=0.007). Age ≥65 years, previous exacerbation frequency, and cumulative corticosteroid dose did not retain statistical significance after adjustment (Table 6, Figure 3). Table 1. Comparison of Baseline Demographic and Clinical Characteristics Between the Study Groups (N=160) Parameter Group A: Low NLR (n=68) Group B: High NLR (n=92) p-value Statistical test Age (years), mean ± SD 61.4 ± 9.2 65.8 ± 10.1 0.005 Independent t-test Male, n (%) 49 (72.1) 69 (75.0) 0.678 Chi-square Female, n (%) 19 (27.9) 23 (25.0) Current/ex-smoker, n (%) 54 (79.4) 78 (84.8) 0.375 Chi-square Smoking exposure (pack-years) 24.6 ± 10.2 29.8 ± 12.4 0.005 Independent t-test COPD duration (years) 6.2 ± 3.1 7.8 ± 3.6 0.003 Independent t-test Previous exacerbations/year 1.4 ± 0.8 2.1 ± 1.0 <0.001 Mann–Whitney U Diabetes mellitus, n (%) 16 (23.5) 28 (30.4) 0.334 Chi-square Hypertension, n (%) 22 (32.4) 35 (38.0) 0.459 Chi-square Baseline SpO₂ (%) 91.2 ± 3.4 87.8 ± 4.2 <0.001 Independent t-test Respiratory rate (breaths/min) 24.8 ± 3.2 28.6 ± 4.1 <0.001 Independent t-test Table 2. Comparison of Baseline Haematological and Inflammatory Parameters Between the Study Groups Parameter Group A (n=68) Group B (n=92) p-value Statistical test Total leukocyte count (×10³/µL) 9.8 ± 2.4 13.2 ± 3.6 <0.001 Independent t-test Absolute neutrophil count (×10³/µL) 6.4 ± 1.8 10.6 ± 2.9 <0.001 Independent t-test Absolute lymphocyte count (×10³/µL) 2.3 ± 0.6 1.5 ± 0.5 <0.001 Independent t-test NLR, median (IQR) 2.8 (2.2–3.2) 6.4 (4.8–8.6) — Grouping variable CRP (mg/L), median (IQR) 24 (16–38) 58 (36–84) <0.001 Mann–Whitney U PaO₂ (mmHg) 69.4 ± 8.2 61.8 ± 9.4 <0.001 Independent t-test PaCO₂ (mmHg) 44.2 ± 7.6 51.6 ± 9.2 <0.001 Independent t-test Table 3. Comparison of Corticosteroid Therapy and Treatment-Related Characteristics Parameter Group A (n=68) Group B (n=92) p-value Statistical test Systemic corticosteroid therapy, n (%) 68 (100.0) 92 (100.0) — — Oral corticosteroids, n (%) 48 (70.6) 43 (46.7) 0.003 Chi-square Intravenous corticosteroids, n (%) 20 (29.4) 49 (53.3) Duration of therapy (days) 5.2 ± 1.1 6.8 ± 1.7 <0.001 Independent t-test Cumulative prednisolone-equivalent dose (mg) 208 ± 48 286 ± 74 <0.001 Independent t-test Additional corticosteroid course, n (%) 5 (7.4) 17 (18.5) 0.044 Chi-square Steroid-associated hyperglycaemia, n (%) 9 (13.2) 24 (26.1) 0.047 Chi-square Table 4. Comparison of Clinical Outcomes Between Low and High NLR Groups Clinical outcome Group A (n=68) Group B (n=92) p-value Statistical test Duration of hospital stay (days) 5.4 ± 1.8 8.2 ± 2.6 <0.001 Independent t-test Supplemental oxygen, n (%) 43 (63.2) 78 (84.8) 0.002 Chi-square Non-invasive ventilation, n (%) 12 (17.6) 36 (39.1) 0.003 Chi-square Invasive mechanical ventilation, n (%) 3 (4.4) 13 (14.1) 0.043 Fisher's exact ICU admission, n (%) 9 (13.2) 30 (32.6) 0.005 Chi-square Clinical improvement within 72 hours, n (%) 54 (79.4) 49 (53.3) <0.001 Chi-square In-hospital complications, n (%) 10 (14.7) 29 (31.5) 0.014 Chi-square In-hospital mortality, n (%) 2 (2.9) 9 (9.8) 0.120 Fisher's exact Table 5. Correlation of Baseline Neutrophil-to-Lymphocyte Ratio With Corticosteroid Exposure and Clinical Parameters (N=160) Parameter Correlation coefficient (r/ρ) p-value Statistical test Age 0.24 0.002 Spearman correlation CRP level 0.52 <0.001 Spearman correlation Baseline SpO₂ −0.43 <0.001 Pearson correlation Respiratory rate 0.46 <0.001 Pearson correlation PaCO₂ 0.39 <0.001 Pearson correlation Corticosteroid duration 0.36 <0.001 Spearman correlation Cumulative corticosteroid dose 0.33 <0.001 Spearman correlation Duration of hospital stay 0.48 <0.001 Spearman correlation Previous exacerbations/year 0.35 <0.001 Spearman correlation Table 6. Multivariable Logistic Regression Analysis of Factors Associated With ICU Admission (N=160) Predictor variable Crude OR (95% CI) p-value Adjusted OR (95% CI) p-value Age ≥65 years 1.92 (0.94–3.91) 0.073 1.64 (0.72–3.74) 0.238 High baseline NLR (≥3.5) 3.17 (1.40–7.18) 0.006 2.86 (1.19–6.88) 0.019 Baseline SpO₂ less than 90% 3.82 (1.82–8.02) <0.001 3.24 (1.38–7.61) 0.007 ≥2 previous exacerbations/year 2.48 (1.17–5.26) 0.018 2.12 (0.94–4.78) 0.070 Cumulative corticosteroid dose (per 100 mg) 1.32 (1.03–1.69) 0.028 1.18 (0.87–1.60) 0.287

The present prospective observational study evaluated the association between baseline neutrophil-to-lymphocyte ratio (NLR), corticosteroid therapy and clinical outcomes among 160 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients were categorised into Group A (NLR less than 3.5; n=68) and Group B (NLR ≥3.5; n=92). The findings demonstrated that elevated NLR was associated with greater inflammatory burden, increased corticosteroid exposure and unfavourable clinical outcomes.In our study, patients with elevated NLR were comparatively older (65.8 ± 10.1 vs. 61.4 ± 9.2 years; p=0.005), had longer COPD duration (7.8 ± 3.6 vs. 6.2 ± 3.1 years; p=0.003) and experienced more previous exacerbations (2.1 ± 1.0 vs. 1.4 ± 0.8/year; p<0.001). Baseline SpO₂ was significantly lower in Group B (87.8 ± 4.2% vs. 91.2 ± 3.4%; p<0.001). Vestbo et al. (2013) [16], in the SUMMIT study protocol involving approximately 16,000 planned participants, emphasised the importance of evaluating morbidity and mortality among COPD patients with increased cardiovascular risk. Although NLR was not specifically assessed, their study supports evaluating baseline clinical characteristics alongside subsequent outcomes.Group B demonstrated higher leukocyte counts (13.2 ± 3.6 vs. 9.8 ± 2.4 ×10³/µL), neutrophil counts (10.6 ± 2.9 vs. 6.4 ± 1.8 ×10³/µL) and CRP levels (58 vs. 24 mg/L), with all p<0.001. Median NLR was 6.4 (IQR: 4.8–8.6) in Group B compared with 2.8 (2.2–3.2) in Group A. Zinellu et al. (2022) [12] , in their systematic review and meta-analysis, similarly reported an association between elevated NLR and adverse outcomes in AECOPD, supporting its potential prognostic utility.Taşoğlu et al. (2017) [17] investigated mean platelet volume and platelet-to-lymphocyte ratio as inflammatory markers in hip osteoarthritis, while Tanrikulu et al. (2014) [18] evaluated mean platelet volume and red cell distribution width in acute appendicitis. Although these studies involved different diseases and haematological indices, they illustrate the broader investigation of routine blood-derived parameters as potential inflammatory markers. Their findings are not directly comparable with NLR in AECOPD.All 160 patients received systemic corticosteroids. Intravenous administration was more frequent in Group B (53.3% vs. 29.4%; p=0.003), with longer treatment duration (6.8 ± 1.7 vs. 5.2 ± 1.1 days; p<0.001) and higher cumulative prednisolone-equivalent exposure (286 ± 74 vs. 208 ± 48 mg; p<0.001). Steroid-associated hyperglycaemia was also higher in Group B (26.1% vs. 13.2%; p=0.047).Ernst et al. (2015) [19] reviewed the clinical evidence regarding inhaled corticosteroids in COPD, highlighting the need to balance therapeutic benefits against adverse effects, particularly pneumonia risk. Although their review concerned inhaled rather than systemic corticosteroids, it reinforces the importance of evaluating treatment-related complications. Similarly, Vestbo et al. (2013) [16] described the SUMMIT trial design comparing fluticasone furoate/vilanterol (100/25 µg), fluticasone furoate (100 µg), vilanterol (25 µg) and placebo, with mortality as the primary endpoint.Patients with elevated NLR experienced significantly longer hospitalisation (8.2 ± 2.6 vs. 5.4 ± 1.8 days; p<0.001), greater non-invasive ventilation requirements (39.1% vs. 17.6%; p=0.003) and higher ICU admission rates (32.6% vs. 13.2%; p=0.005). Clinical improvement within 72 hours was lower in Group B (53.3% vs. 79.4%; p<0.001). Mortality was numerically higher (9.8% vs. 2.9%), although statistically insignificant (p=0.120). These observations are consistent in direction with Zinellu et al. [12], who identified elevated NLR as a potential marker of adverse clinical outcomes in AECOPD.Baseline NLR demonstrated positive correlations with CRP (ρ=0.52), corticosteroid duration (ρ=0.36), cumulative corticosteroid dose (ρ=0.33) and hospital stay (ρ=0.48), while showing a negative correlation with SpO₂ (r=−0.43); all p<0.001. ROC analysis demonstrated an AUC of 0.78 (95% CI: 0.70–0.86) for predicting ICU admission. Multivariable logistic regression identified elevated NLR (≥3.5) as independently associated with ICU admission (adjusted OR: 2.86; 95% CI: 1.19–6.88; p=0.019), supporting further investigation of NLR as an adjunctive prognostic marker in AECOPD.

Elevated baseline neutrophil-to-lymphocyte ratio (NLR) was associated with greater inflammatory burden, increased corticosteroid exposure and unfavourable clinical outcomes in patients with AECOPD. Higher NLR was associated with prolonged hospitalisation, increased ventilatory support and greater ICU admission requirements. NLR may serve as a simple, inexpensive and readily available adjunctive prognostic marker for early risk stratification in AECOPD. LIMITATIONS The single-centre observational design and relatively small sample size (N=160) limit the generalisability of the findings and preclude causal interpretation. Variations in baseline disease severity and corticosteroid exposure may have influenced NLR and subsequent clinical outcomes.

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