Pulmonary hypertension (elevated pressure within the blood vessels of the lungs) is organized into five groups:
Group 1: Pulmonary arterial hypertension (PAH)
Group 2: Pulmonary venous hypertension (due to problems on the left side of the heart)
Group 3: Pulmonary hypertension due to lung disease
Group 4: Pulmonary hypertension due to blood clots in the lungs
Group 5: Pulmonary hypertension due to blood problems and various other causes
Within group 3, there are three main sub-categories. Chronic obstructive pulmonary disease (emphysema) is the most common. Patients with emphysema tend to have quite mild pulmonary hypertension. Another subcategory of lung disease is interstitial lung disease which includes various types of scarring or inflammatory lung diseases. The best known scarring lung disease is idiopathic pulmonary fibrosis. Other examples include connective tissue related interstitial lung disease and hypersensitivity pneumonitis. As the scarring related lung diseases progress, patients often develop substantial pulmonary hypertension.
Until recently, drug development to treat pulmonary hypertension has focused on PAH. Until now, no PAH medications were shown to be effective in treating pulmonary hypertension in patients whose PH was caused by lung disease. The INCREASE Trial, recently reported top line data that were very exciting. The study involved patients with pulmonary fibrosis (scarring in their lungs) who also had pulmonary hypertension. These patients were randomized to receive inhaled Tyvaso or Placebo. After 16 weeks, patients in the Tyvaso group walked further and had fewer clinical worsening events.
This is a landmark trial and will change the way that we treat pulmonary hypertension in patients with scarring related lung disease such as pulmonary fibrosis. Until now, insurance companies would often refuse to pay for expensive medications arguing that there was not any data to support their use. We now have data that unequivocally supports the use of Tyvaso. Other PAH medications have been studied in interstitial lung disease. The endothelin receptor antagonists (ambrisentan/Letairis, macitentan/Opsumit, bosentan/Tracleer) were all studied extensively in pulmonary fibrosis and shown to be at best not helpful and in some cases harmful. Sildenafil has been evaluated in several studies of patients with pulmonary fibrosis and pulmonary hypertension. The results have not convincingly shown benefit though the studies have not been well designed.
Who will be a candidate for Tyvaso? Patients with interstitial lung disease should have an echocardiogram and blood tests done to look for signs of pulmonary hypertension. Patients will then require a right heart catheterization to accurately measure the pressures on the right and left side of their heart. Patients with elevated pulmonary artery pressure, normal left sided pressures and increased pulmonary vascular resistance are candidates to try Tyvaso.
Tyvaso is an inhaled medication that is taken four times daily using a sophisticated nebulizer device (different from the nebulizer used to deliver albuterol). The Dose of the medication is gradually increased over time. Common side effects include cough, headache, sore throat and nausea and occasionally jaw discomfort. In general these side effects are mild and well tolerated.
We are excited about this new therapy for patients with pulmonary hypertension due to interstitial lung disease.