Group 3 Pulmonary Hypertension: Causes
Group 3 pulmonary hypertension is caused by chronic lung diseases and/or hypoxia, with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) being the most common etiologies. 1
Primary Causes
According to the 2015 ESC/ERS Guidelines, Group 3 PH encompasses seven distinct categories of lung diseases and hypoxic conditions 1:
Parenchymal Lung Diseases
- Chronic obstructive pulmonary disease (COPD) - the most frequently encountered cause, though severe PH (mean PAP ≥35 mmHg) occurs in only 1-4% of COPD patients 1, 2
- Interstitial lung disease - commonly develops mild PH, with severe PH being uncommon 1
- Combined emphysema/fibrosis syndrome - demonstrates particularly high prevalence of PH compared to isolated COPD or ILD 1, 2
- Other pulmonary diseases with mixed restrictive and obstructive patterns 1
Hypoventilation and Sleep Disorders
- Sleep-disordered breathing - nocturnal hypoxemia drives pulmonary vascular changes 1, 2
- Alveolar hypoventilation disorders - cause PH through chronic hypoxemia and hypercapnia 1
Environmental and Developmental Causes
- Chronic exposure to high altitude - sustained hypoxic pulmonary vasoconstriction leads to PH 1
- Developmental lung diseases - congenital abnormalities predispose to PH from early life 1
Pathophysiological Mechanism
The underlying mechanism across all Group 3 causes involves chronic hypoxemia and/or destruction of the pulmonary vascular bed 1. The pathological changes characteristically include:
- Medial hypertrophy of distal pulmonary arteries 1
- Intimal obstructive proliferation 1
- Variable degrees of vascular bed destruction in emphysematous or fibrotic areas 1
Clinical Distinction
Group 3 PH is distinguished from Group 1 (pulmonary arterial hypertension) by the presence of significant underlying lung disease and/or hypoxia as the primary driver. 1 The hemodynamic profile shows pre-capillary PH (mean PAP ≥25 mmHg, pulmonary arterial wedge pressure ≤15 mmHg) in the context of documented parenchymal lung disease or chronic hypoxia 1, 2.
Important Clinical Caveat
In COPD patients with severe PH (mean PAP >40 mmHg), approximately 60% have another potential cause of PH beyond COPD alone, such as anorexigen exposure, connective tissue disease, thromboembolic disease, or left ventricular disease 1. When severe PH is present in the setting of only mild-to-moderate airflow obstruction, alternative diagnoses must be actively excluded.