From the Guidelines
The primary treatment for pulmonary arterial hypertension (PAH) associated with chronic lung disease, specifically type 3 pulmonary hypertension, is optimizing the underlying lung condition and addressing the pulmonary vascular disease, with a focus on long-term oxygen therapy and avoiding the use of targeted PAH drugs unless in cases of 'out of proportion' PH due to lung diseases. The cornerstone of therapy is managing the underlying lung disease, such as COPD, interstitial lung disease, or sleep-disordered breathing, with treatments including bronchodilators, inhaled corticosteroids, antibiotics for infections, and oxygen therapy to maintain oxygen saturation above 90% 1. Long-term oxygen therapy is particularly important for patients with chronic hypoxemia, typically prescribed for at least 15 hours daily. Pulmonary vasodilators used in other forms of pulmonary hypertension should be used cautiously in type III, as medications like prostacyclins, endothelin receptor antagonists (bosentan, ambrisentan), and phosphodiesterase-5 inhibitors (sildenafil, tadalafil) may worsen ventilation-perfusion matching and oxygenation 2. Some key points to consider in the treatment of type III pulmonary hypertension include:
- Optimizing treatment of the underlying lung disease
- Using long-term oxygen therapy for patients with chronic hypoxemia
- Avoiding the use of targeted PAH drugs unless in specific cases
- Considering non-pharmacological approaches such as pulmonary rehabilitation, smoking cessation, and maintaining ideal body weight
- Referring patients with 'out of proportion' PH due to lung diseases to expert centers for potential enrollment in clinical trials targeting PAH-specific drug therapy 3. In severe cases with right heart failure, diuretics like furosemide (20-80 mg daily) or spironolactone (25-100 mg daily) may help reduce fluid overload. For end-stage disease, lung transplantation may be considered. The rationale for this approach is that improving the underlying lung condition and oxygenation can reduce hypoxic pulmonary vasoconstriction, which contributes significantly to the development and progression of pulmonary hypertension in these patients.
From the FDA Drug Label
Sildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in adults to improve exercise ability and delay clinical worsening. The treatment for pulmonary arterial hypertension (PAH) associated with chronic lung disease, specifically type 3 pulmonary hypertension, is not directly addressed in the provided drug labels. Sildenafil is indicated for the treatment of pulmonary arterial hypertension (WHO Group I), but the labels do not specify its use for type 3 pulmonary hypertension or provide information on its efficacy in this specific population [4] [5].
From the Research
Treatment for Pulmonary Arterial Hypertension (PAH) Associated with Chronic Lung Disease
- The treatment for PAH associated with chronic lung disease, specifically type 3 pulmonary hypertension, is not well established 6, 7, 8.
- There are no specific therapies available for group 3 pulmonary hypertension, and the focus of management remains optimisation of the underlying lung therapy, along with treating hypoventilation syndromes as indicated 8.
- Pulmonary vasodilators have yielded equivocal results in this patient population, although recent evidence shows modestly improved outcomes with inhaled treprostinil in interstitial lung disease-associated pulmonary hypertension 7.
- The use of PAH-specific therapy in WHO Group III PH patients has not been proven to be beneficial, with inconsistent results in terms of symptomatic burden, pulmonary artery pressures, and pulmonary vascular resistance 9.
- Lung transplantation remains the only cure for this deadly disease, and the right ventricle may provide a novel intervention target 7.
- Management of PH patients with chronic lung diseases requires careful evaluation and understanding of pathophysiological mechanisms, and referral to specialist PH centres for further investigation and definitive management is mandated in certain cases 6, 8.