Chronic obstructive pulmonary disease (COPD) is a major global health burden, characterized by persistent airflow limitation due to airway and/or alveolar abnormalities, often triggered by exposure to noxious particles or gases [1]. The Global Burden of Disease Study projects COPD to become the third leading cause of death by 2030, with an estimated 380 million people affected worldwide [2]. In India, COPD prevalence ranges from 6.5% to 17.8% in adults, driven by smoking, biomass fuel exposure, and environmental pollutants [3].

Pulmonary hypertension (PH) is a critical complication of COPD, defined as a mean pulmonary artery pressure (mPAP) >20 mmHg at rest, as measured by right heart catheterization (RHC) [4]. PH in COPD, classified under Group 3 (PH due to lung diseases and/or hypoxia) by the European Respiratory Society, increases right ventricular afterload, potentially leading to cor pulmonale and reduced survival [5]. Prevalence of PH in COPD varies widely, from 10% in mild cases to 90% in severe (GOLD Stage 4) disease, though most cases exhibit mild to moderate PH (mPAP 20–35 mmHg) [6]. Severe PH

(mPAP >40 mmHg) is rare, affecting 3–5% of COPD patients, and its mechanisms remain poorly understood [7].

The pathophysiology of COPD-related PH involves chronic hypoxia, inflammation, and vascular remodeling. Cigarette smoke and oxidative stress induce endothelial dysfunction, intimal thickening, and increased pulmonary vascular resistance (PVR) [8]. Small airway dysfunction, reflected by reduced FEF25–75, may exacerbate hypoxia and contribute to PH development [9]. Hypoxemia and hypercapnia further aggravate pulmonary vasoconstriction, increasing mPAP [10]. Clinically, PH in COPD manifests as worsened dyspnea, reduced exercise capacity, and frequent exacerbations, significantly impacting quality of life [11].

Despite its clinical significance, data on PH phenotypes in Indian COPD populations are scarce. Previous studies, such as one by Ramesh et al., reported a 32% PH prevalence in a South Indian COPD cohort, but lacked detailed phenotypic analysis [12]. Understanding PH phenotypes—mild, moderate, and severe—is crucial for tailoring therapeutic strategies, such as supplemental oxygen or targeted PH therapies, which remain understudied in COPD [13]. Echocardiography, a non-invasive alternative to RHC, is widely used for PH screening, though its accuracy depends on operator expertise and patient factors [14]. The BODE index, incorporating body mass index, obstruction, dyspnea, and exercise capacity, is a validated tool for assessing COPD severity and may correlate with PH risk [15].

This study addresses the gap in Indian literature by estimating PH prevalence and characterizing its phenotypes in COPD patients. By evaluating clinical profiles, including spirometric parameters, gas exchange, and BODE index, we aim to identify predictors of PH and inform screening practices. Given the rising COPD burden in India, understanding PH phenotypes is essential for improving patient outcomes and guiding future research.

Aims and Objectives

Primary Objective: To estimate the prevalence of pulmonary hypertension phenotypes in patients with chronic obstructive pulmonary disease.

Secondary Objective: To evaluate the clinical profile of different COPD-PH phenotypes, including associations with spirometric parameters, gas exchange, and BODE index.

This cross-sectional study was conducted at a tertiary care hospital in Dharwad, Karnataka, India, from April 2023 to March 2025. The study was approved by the Institutional Ethics Committee (Ref: SDMIEC/2023/447, dated 12 April 2023), and written informed consent was obtained from all participants.

Study Population

A total of 336 adult patients diagnosed with COPD per GOLD 2024 criteria (post- bronchodilator               FEV1/FVC           <0.7)      were       enrolled consecutively.

Inclusion Criteria:

• Age ≥40 years.
• Confirmed COPD diagnosis via spirometry.
• Stable disease (no exacerbations in the past 4 weeks).

Exclusion Criteria:

• Other lung diseases (e.g., interstitial lung disease, pulmonary tuberculosis).
• Left heart disease (e.g., heart failure with reduced ejection fraction, valvular disease).
• Chronic thromboembolic PH or other Group 1, 4, or 5 PH causes.
• Inability to perform spirometry or echocardiography.

Data Collection

Patients underwent comprehensive assessments at enrollment:

Spirometry: Performed using a calibrated spirometer (MIR Spirolab) per American Thoracic Society guidelines. Parameters included FEV1, forced vital capacity (FVC), and FEF25–75. Severity of obstruction was classified per GOLD stages (1–4).

Echocardiography: Conducted by a trained cardiologist using a Philips Epiq 7 system. PH was defined as mPAP >20 mmHg, estimated via tricuspid regurgitation velocity. Patients were categorized as: no PH (mPAP ≤20 mmHg), mild PH (mPAP 21–30 mmHg), moderate PH (mPAP 31–40 mmHg), or severe PH (mPAP >40 mmHg).

Arterial Blood Gas (ABG): Measured using a Radiometer ABL800 analyzer to assess partial pressure of oxygen (PO2) and PCO2.

Chest X-ray: Evaluated for signs of hyperinflation, bullae, or cardiomegaly.

BODE Index: Calculated based on BMI, FEV1, modified Medical Research Council (mMRC)dyspnea score, and 6-minute walk test (6MWT) distance.

Other Investigations: Complete blood count (CBC), brain natriuretic peptide (BNP), renal function tests (RFT), and liver function tests (LFT) were performed to rule out comorbidities.

Statistical Analysis

Data were analyzed using SPSS version 25.0. Descriptive statistics (means, standard deviations, percentages) summarized patient characteristics. Comparisons between PH and no-PH groups used independent t-tests for continuous variables (e.g., FEV1, PCO2) and chi-square tests for categorical variables (e.g., gender, GOLD stage). ANOVA assessed differences across PH severity groups. Spearman’s rank correlation evaluated associations between BODE index and FEV1. A p-value <0.05 was considered statistically significant.

Of the 336 COPD patients (mean age 62.4 ± 8.7 years, 68% male), 65 (19.35%) had PH. Mild PH was most common (40/336, 11.90%), followed by moderate PH (13/336, 3.87%) and severe PH (12/336, 3.57%). Tables 1–5 summarize key findings.

Table 1: Prevalence of Pulmonary Hypertension

Table 2: Association of PH with Gender

No significant gender difference was observed in PH prevalence (p=0.84).

Table 3: Association of PH with BMI

BMI was not significantly associated with PH (p=0.73).

Table 4: Spirometric Parameters by PH Status

Patients with PH had significantly lower FEV1, FVC, and FEF25–75 compared to those without PH (p<0.05).

Table 5: Gas Exchange and BODE Index by PH Status

PH patients exhibited lower PO2, higher PCO2, and higher BODE scores (p<0.05). Spearman’s correlation showed a moderate negative correlation between BODE index and FEV1 (r = -0.62, p<0.001).

This study found a 19.35% prevalence of PH in COPD patients, consistent with global estimates ranging from 10–30% in stable COPD cohorts [6]. Mild PH predominated (11.90%), aligning with Kovacs et al., who reported mild PH in 15–20% of COPD patients with moderate-to-severe disease [7]. The low prevalence of severe PH (3.57%) corroborates its rarity, as noted by Brewis et al., who found severe PH in only 4% of COPD patients [13].

Unlike Ramesh et al.’s study in South India (32% PH prevalence, n=100), our larger sample size and use of echocardiography rather than RHC may explain the lower prevalence [12]. Echocardiography, while less precise than RHC, is practical for screening large cohorts, though it may underestimate mPAP in early PH [14]. Our finding of no association between PH and age, gender, or BMI contrasts with Katiyar et al., who reported higher PH prevalence in males (p=0.04) [15]. This discrepancy may reflect regional differences in smoking patterns or sample characteristics.

Small airway dysfunction (FEF25–75 <50% predicted) was a significant predictor of PH (p=0.02), supporting Barbera` et al.’s hypothesis that small airway obstruction drives hypoxia and vascular remodeling [8]. PH patients had lower FEV1 (42.3% vs. 58.7% predicted, p<0.001) and higher PCO2 (48.2 vs. 41.5 mmHg, p=0.01), indicating more severe respiratory impairment. These findings align with Vizza et al., who noted worse spirometry and gas exchange in COPD-PH patients (FEV1 38% predicted, p<0.01) [9].

The higher BODE index in PH patients (5.8 vs. 3.2, p<0.001) suggests greater disease burden, consistent with Friedlander et al.’s observation that BODE scores predict PH risk (p<0.05) [10]. The negative correlation between BODE index and FEV1 (r = -0.62, p<0.001) underscores the interplay between airflow limitation and functional impairment in PH.

Limitations include the single-center design and reliance on echocardiography, which may miss subtle PH cases. Future studies should incorporate RHC for precise phenotyping and explore longitudinal outcomes. Our findings highlight the need for routine PH screening in COPD, particularly in patients with small airway dysfunction, to optimize management and reduce morbidity.

Pulmonary hypertension affects nearly one in five COPD patients, with mild PH being the most common phenotype. Small airway dysfunction, lower FEV1, and higher PCO2 are key predictors of PH, contributing to increased disease severity and functional impairment. The BODE index is a valuable tool for identifying high-risk patients. Routine echocardiographic screening is recommended to detect PH early and guide therapeutic interventions, such as supplemental oxygen or pulmonary rehabilitation, to improve outcomes in Indian COPD populations. Further research is needed to validate these findings and explore targeted PH therapies in COPD.

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