Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition that causes poorly reversible airflow obstruction and an abnormal inflammatory response in the lung. It affects the airways, lung parenchyma, and pulmonary vasculature as well as having extra-pulmonary effects. COPD mechanisms include mucus hypersecretion (chronic bronchitis), tissue destruction (emphysema), and small airway inflammation with fibrosis. The 5-year mortality rate for COPD is estimated at 25%. COPD is considered a preventable and manageable disease, and it is possible to prevent or reduce its burden by avoiding cigarette smoke, indoor and outdoor (e.g biomass smoke) pollution and occupational exposures, among others. COPD is the third leading cause of death worldwide.¹ The World Health Organization reports that COPD affects 210 million people worldwide. The global prevalence ranges between 8% - 20%.²  Pakistan has fourth highest mortality rate in the world due to COPD with 71 deaths per 100,000.³  

 Biological fuels that produce heat are called biomass. Approximately 3 billion people worldwide are exposed to smoke from biomass fuel compared with 1.01 billion people who smoke tobacco, suggesting that exposure to biomass smoke (BS) might be the most important global risk factor for COPD. A study that compared the COPD cases, caused by biomass smoke (BS) exposure and tobacco smoking (TS), reported that vascular changes were more severe in the biomass smoke exposed group which could explain why PH and Corpulmonale in women exposed to biomass smoke is common and high.^4.  Biomass fuels when burnt result in high levels of air pollutants including carbon monoxide (CO) and particulate matter (PM). The people most exposed are women who are routinely responsible for cooking.⁵

Pulmonary hypertension (PH) is a significant and under recognized complication in COPD. PH is defined in hemodynamic terms by an abnormal increase in mean pulmonary arterial pressure (mPAP)  >20 mmHg (at rest), estimated non-invasively using echocardiography  or by Right heart catheterization (RHC). Lung disease, especially COPD, is the second most common cause of PH. PH-COPD may be associated with a worse clinical course, frequent exacerbations, shorter survival, and higher healthcare resource utilization.⁶ PH-COPD when present, defined as group 3 PH, is usually of moderate severity; the mean pulmonary artery pressure (mPAP) level at rest ranges from 25 to 34 mm Hg, with preserved cardiac output. However, a subset of COPD patients present a much higher mPAP. In the most characteristic cases, the level of mPAP is disproportionate to the degree of bronchopulmonary involvement. For these patients who seem to have a particular involvement of pulmonary circulation and who could be potential candidates for vasoactive therapy, the term “out-of-proportion” PH has been replaced with “severe PH-COPD” defined by mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index (<2l/min/m²). However, little is known about the characteristics of COPD patients with severe PH. This pulmonary vascular phxenotype is associated with very poor prognosis, with mortality far higher than expected.⁷  PH has a great role in prognosis of the patients with COPD.  Patients with COPD and mean PAP more than 30 mmHg have a high mortality rate and those with mean PAP of 50 mmHg have 100% mortality rate.⁸ Three important causes contribute to a rise in mean PAP levels. The first factor is lung hyperinflation, which increases thoracic pressure and decreases blood volume in cardiac chambers, reducing stroke volume and increasing sympathetic drive. Another factor is rising filling pressure of the left ventricle due to systolic, diastolic, or combined heart failure, which increases PAP while maintaining normal pulmonary vascular resistance (PVR). The third reason is an increase in PVR, which leads to an increased trans-pulmonary arterio-venous pressure gradient & a decrease in cardiac output.⁹  The rate of progression of PH in COPD patients is about 1 mm Hg per year. PH-COPD, with pulmonary artery pressure (PAP) of above 40 mm Hg may have less severe bronchial obstruction with an average FEV₁ of 50%  but these patients have a poor prognosis. Following prolonged and chronic hypoxia, polycythemia occurs and can further increase pulmonary vascular resistance.¹⁰

In our resource poor setting, where the use of biomass fuel is common during cooking, especially by women, and there is poverty related delay in seeking treatment, this study aimed to assess the frequency and specific features of severe PH in COPD patients presenting to a tertiary care hospital. 

This was an cross-sectional study of patients presenting to (medical unit III) a tertiary care hospital (Bolan Medical Complex Hospital, Quetta), between 01.07.2025 and 31.12.2025. The required sample size required for the study was 100 patients. Included were individuals of different age groups (ranged 35-76), both genders, current or former smokers, patients having history of chronic domestic wood smoke inhalation/ biomass fire use, occupational exposure etc. Other inclusion criteria were, being diagnosed with COPD with a post-bronchodilator FEV1 (forced expiratory volume in 1 second) /FVC (forced vital capacity) <0.7 (< 70%), FEV1 < 80 % predicted) and without asthma as assessed by clinical history and response to bronchodilators (change 12% in FEV1 following inhaled salbutamol). Exclusion criteria were other significant lung diseases, bronchiectasis, allergy, asthma, ischemic heart disease, systemic inflammatory diseases, or non-compliance with study procedures. Severe pulmonary hypertension (PH), was defined by mean Pulmonary Artery Pressure (mPAP) ≥35 mm Hg, at rest. SPSS version 25.0 was used for data analysis. A P-value less than 0.05 was considered statistically significant. Demographic data, such as age, gender, residency, socioeconomic status, and address, were recorded using a predefined pro-forma. FEV1, FVC, and the FEV1/FVC ratio were measured using spirometry testing. The severity of COPD was categorized using GOLD criteria. Mean pulmonary arterial pressure (mPAP) was measured using doppler echocardiography to identify PH, if any, and classify its severity. The Doppler echocardiography was performed by a prominent cardiologist from the hospital's cardiology department. If a person's calculated mean pulmonary arterial pressure using transthoracic echocardiography (Doppler) was more than 20 mm Hg at rest, they were classified as having pulmonary hypertension. SPSS version 25.0 was used for data analysis. Quantitative variables such as age were presented as Mean ± standard deviation. Similarly, for quantitative data that was not normally distributed, the median (IQR) was calculated by applying Shappiro-Wilk test. Age, gender, socioeconomic position, a smoking history, biomass smoke exposure history, severity of breathlessness (NYHA class), length of COPD, and severity of COPD were used to stratify PH. A P-value less than 0.05 was considered statistically significant. Tables were used to display the data analysis results.

Out of the total 100 participants, female were n=80 (80%) and male were n=20 (20%). The mean age of the study participants was 61±9.4 years. Females had history of chronic domestic biomass smoke inhalation n=80 (80%), while men had history of smoking n=20 (20%). The most prevalent age group was 56-76 years which was n=64 (64%). Baselines characteristics of the study participants are given in table 1.  

Although COPD associated pulmonary hypertension (mPAP ≥20 mmHg) was seen in 52 (52%), but out of these, severe PAH (mPAP ≥35 mm Hg) in found in 8 (8%) of patients, all of which  were females. COPD severity were shown to be significantly associated with presence and severity of pulmonary hypertension (P < 0.005). Age  was shown to be significantly associated with presence and severity of pulmonary hypertension (P < 0.005). Patients having severe PH were more functionally impaired and had severe  breathlessness (NYHA class IV) despite mostly having moderate airway obstruction FeV₁ % (predicted) 50-80 %.         PH stratification on the basis of gender, socioeconomic status, age, smoking history, biomass/ wood smoke exposure history and COPD severity is detailed in table 2.

Table 2. PH stratification on the basis of gender, socioeconomic status, age, smoking history, biomass smoke exposure and COPD severity

PH is a frequent complication of COPD, associated with increased exacerbation frequency, reduced survival, and greater healthcare resource utilization.6 This study finds a 52% prevalence of PH (mPAP of 21 to 34 mm Hg) in COPD patients. Other studies have found similar findings. Mekov et al., in their study found a 52.1% prevalence of PH in COPD.6 Ashraf et al., in their study showed similar findings of 52.5% cases of PH, which supports our study.9 In this study, although COPD associated Pulmonary Hypertension (mPAP of 21 to 34 mm Hg) was seen in 52 (52%), but severe PAH (mPAP ≥35 mm Hg) in found in 8 (8%) of patients, all of which were females. In different studies it has been observed that pulmonary hypertension (PH, in COPD) is usually mild to moderate (in 50%), as defined by a mean pulmonary arterial pressure (mPAP) of 21 to 34 mm Hg, but about 6% to 8% of these patients demonstrate severe PH (mPAP ≥ 35 mm Hg).11 Vizza et al, analyzed the characteristics and outcome of patients, enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), with moderate or severe PH in COPD who received medical therapy for PH. The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307). Patients with severe PH in COPD experienced worse outcomes than patients with moderate PH in COPD, with estimated survival probabilities at 1, 3, and 5 years of 84%, 52%, and 36% compared with 95%, 68%, and 49%, respectively (P = .009).11 The prevalence of severe PH varies slightly among different researches. Mekov et al, found that 1/96, ( 1% ) had severe PH-COPD (PAPm greater than 35-40 mmHg at rest) as seen on (non-invasive) transthoracic echocardiography6. However, in a study by Samarehfekri et al, they revealed that while in their study the prevalence of severe PH-COPD (by noninvasive echocardiographic evaluations), was 13.7%, but in most studies the prevalence of severe PH in COPD patients range from 5 to 13.5%.10 Differences between results of different studies vary depending on whether mPAP was measured invasively (by right heart catheterization) or non-invasively (by transthoracic echocardiography), and also by the included patients and their demographic/ social characteristics. Another study that used non-invasive echocardiography to study Severe Pulmonary Hypertension in COPD, was by Kovacs G. et al, and they stated that severe pulmonary hypertension (PH) was present in 1% to 4% of patients and may represent a pulmonary vascular phenotype of COPD. Given the high prevalence of COPD, probably many thousands of patients with COPD worldwide harbor severe PH, outnumbering patients with pulmonary arterial hypertension (PAH).12 A point of variance in this study was that, although COPD is projected to be most commonly due to smoking and more in men, but in this study 80% were non-smokers and women. This study’s female majority had chronic domestic wood /biomass smoke inhalation history. These findings are common in areas where biomass fuel is commonly used by women especially during cooking. A study done by Ramírez-Venegas et al, on COPD patients who were chronically exposed to wood-derived biomass smoke during cooking, stated that 87% were females.13 Similarly Sertogullarindan B. et al, observed that PH (systolic pulmonary artery pressure >35 mmHg) was more frequent in females than males (63,6%, 37,5% p=0,005). All Females were biomass exposer and males were tobacco smoker. Their study demonstrated that PH frequency is higher in female COPD cases due to biomass smoke than in male COPD cases due to tobacco smoke.4 The reason why women who had chronic domestic biomass smoke exposure more commonly developed severe pulmonary hypertension, could be as explained by Pérez-Padilla R. et al, that autopsies of patients with COPD from biomass smoke exposure show increased pulmonary artery small vessel intimal thickening which may explain pulmonary hypertension, in addition to emphysema and airway disease.14 Another reason why this study found severe PH-COPD more common in females that were exposed to biomass smoke could be that they are responsible for cooking/ heating chores. According to Ortiz-Quintero B. et al, nearly 3 billion people worldwide use solid organic materials as the primary fuel for indoor cooking and heating. Biomass smoke is generated from the incomplete combustion of organic material such as wood, crop residues, twigs, dried animal dung, and charcoal in rudimentary stoves or open fires. This biomass smoke contains high concentrations of hazardous inhalable particulate matter.15 Factors influencing Pulmonary Arterial Pressure (PAP) in smoker and non-smoker COPD patients with Pulmonary Hypertension have been compared, by Halvani A.H. et al, in their study8, and they observed that in smoker patients, significant correlation between PAP and PaO2 was seen (p-value=0.047), but not seen in non-smokers. A significant correlation between PAP and FEV1 (P value=0.025) was seen in non-smoker patients but not in smokers. In non-smoker patients with COPD, degree of pulmonary parenchymal lesions and bronchial obliteration plays a more important role than hypoxia in the pathogenesis of pulmonary hypertension.8 Advanced age is common factor in most COPD- PH patients. In this study the mean age of the study participants was 61±9.4 years. The majority of patients n=64 (64%) were between 56-76 years of age. Age was shown to be significantly associated with presence and severity of pulmonary hypertension (P < 0.005). In the present study, COPD severity was shown to be significantly associated with pulmonary hypertension (P < 0.005). These findings are comparable to those of Iftikhar et al, who found that there was a statistically significant positive association between the severity of COPD and presence of pulmonary arterial hypertension (p=0.038).16 Kovacs G, et al,12 found that found that the severity of both airflow limitation and pulmonary vascular disease contributed to increased mortality significantly, independently, and about equally. Naseer S. et al, found that with exposure to Biomass smoke 48 (58.5%) had Pulmonary Hypertension. Age group analysis showed a higher prevalence in individuals aged 56-80 years (71.5%), these tally with this study’s findings.17

As this study finds 8% frequency of severe PH (mPAP ≥35 mm Hg) in COPD patients, seen in females who had a history of chronic domestic biomass smoke inhalation during cooking and heating chores, therefore there is need to increase awareness by widespread educational programs about the deleterious effects of biomass fuel smoke and means of its prevention. As this mainly affects women from disadvantaged areas and countries and this requires an organized effort for its control, like provision of improved vented biomass stoves or even more efficient stoves. Also, by identifying mPAP cutoffs, this research addresses the need for non-invasive, practical tools to improve risk stratification and guide personalized treatment strategies in COPD-PH management. Finally, there is need to better identify patients at risk of severe PH-COPD and improve PH diagnosis in this population; 2) identify the subset of patients in whom vascular disease predominates and who may benefit from PAH-approved therapies.