WHO Category of Pulmonary Hypertension Grade 3
The WHO category of pulmonary hypertension grade 3 is pulmonary hypertension due to lung diseases and/or hypoxia. 1, 2
Classification Details
The World Health Organization (WHO) classifies pulmonary hypertension into 5 distinct groups based on etiology, pathophysiology, and therapeutic approach:
Group 1: Pulmonary arterial hypertension (PAH)
- Includes idiopathic PAH, heritable PAH, drug-induced PAH, and PAH associated with connective tissue disease, HIV, portal hypertension, or congenital heart disease
Group 2: PH due to left heart disease
- Includes PH associated with left ventricular systolic/diastolic dysfunction, valvular disease, and congenital/acquired left heart obstructions
Group 3: PH due to lung diseases and/or hypoxia
- Includes PH associated with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, alveolar hypoventilation disorders, chronic high-altitude exposure, and developmental lung diseases
Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH)
- Includes PH due to organized thrombi in pulmonary arteries and other pulmonary artery obstructions
Group 5: PH with unclear and/or multifactorial mechanisms
- Includes PH associated with hematological disorders, systemic disorders, metabolic disorders, and other conditions
Pathophysiology of Group 3 PH
Group 3 PH is characterized by specific pathological changes that distinguish it from other forms of PH:
- Medial hypertrophy and intimal obstructive proliferation of distal pulmonary arteries 1
- Variable destruction of the vascular bed in emphysematous or fibrotic areas 1
- Hypoxic pulmonary vasoconstriction as a key initiating mechanism 3
- Pulmonary vascular remodeling in response to chronic hypoxia 3
- Endothelial dysfunction and inflammation contributing to disease progression 3
Clinical Significance
Group 3 PH represents a significant proportion of PH cases:
- Up to one-third of affected children have Group 3 PH 1
- Bronchopulmonary dysplasia is the most common underlying diagnosis in children 1
- In adults, COPD and ILD are the most common causes 4, 5
- The presence of PH in patients with lung disease is associated with worse outcomes and increased mortality 4, 6
Management Approach
The foundation for managing Group 3 PH is to treat the underlying lung disease:
- Optimize treatment of the primary lung condition (COPD, ILD, etc.) 1, 5
- Minimize further insults to the lungs and avoid atelectasis 1
- Normalize oxygenation and ventilation when possible 1
- Sildenafil is sometimes used in specific cases, such as infants with bronchopulmonary dysplasia 1
- Caution is needed with pulmonary vasodilators as they may worsen ventilation-perfusion mismatch 5, 7
- Lung transplantation may be considered for progressive disease despite optimal therapy 1
Diagnostic Considerations
Diagnosis requires:
- Right heart catheterization showing mean pulmonary arterial pressure >20 mmHg 2
- Pre-capillary pattern (pulmonary arterial wedge pressure ≤15 mmHg, PVR ≥3 Wood units) 2
- Evidence of underlying lung disease through appropriate testing (pulmonary function tests, imaging) 2
It's important to distinguish Group 3 PH from other forms, particularly Group 1 PAH, as treatment approaches differ significantly and PAH-specific therapies may be harmful in Group 3 PH due to worsening ventilation-perfusion matching 5, 7.