Preserving Heart-Lung Function in Pulmonary Hypertension (PH)

Pulmonary hypertension (PH) is an increase in pressure in the blood vessels leading from the heart to the lungs due to the stiffening and narrowing of these blood vessels. This can cause excessive stress on the heart. Patients can have shortness of breath, fatigue, chest pain, heart failure and in its most severe forms, inability to perform usual daily activities, and even death.


According to the American Thoracic Society there are approximately 200,000 hospitalizations and 15,000 deaths each year directly or indirectly attributed to PH.  PH can affect people of all ages, genders, and races. While the symptoms of PH can be treated, there is currently no definitive cure.

Credit: Centers for Disease Control (2014)

Certain forms of PH are caused by increased inflammation in the blood vessels serving the lungs and/or in the lung tissue itself.  There is increasing evidence that this lung inflammation is driven by immune system cells called macrophages. This immune response, when excessive and unchecked, can harm the lung blood vessels and tissue causing increased stress on the heart and decreased oxygen supply to the body.

The World Health Organization (WHO) has classified subsets of PH based on  understanding of the various factors causing PH. Of particular interest are WHO Group 1 – pulmonary arterial hypertension (PAH) and WHO Group 3 – PH resulting from lung disease and/or hypoxia.

PH WHO Group 1 - Pulmonary Arterial Hypertension (PAH)

PAH is a rare, incurable disease that causes the walls of the pulmonary arteries to tighten and stiffen. As a result, the right side of the heart must work harder to pump blood through these narrowed arteries to and through the lungs (right ventricle strain). The extra stress eventually causes heart enlargement, reduced heart and lung function, and eventually death due to heart failure.

There is increasing evidence that inflammation driven by excessive leukotriene B4 (LTB4), a chemical that controls immune response, plays a large role in PAH, especially PAH associated with connective tissue disease (CTD-PAH). Dysregulated levels of LTB4 can cause excessive burden of macrophages in the lungs leading to inflammation resulting in narrowing and stiffening of the lung arteries. It is believed that treating underlying inflammation may help decrease the associated PAH and improve clinical outcomes.

Patients with CTD-PAH (or APAH-CTD) have a significantly higher risk of death compared with those with idiopathic PAH (IPAH).

Adapted from Andersen et al. Respir Med (2012) 106:875-882

PH WHO Group 3 - Pulmonary Hypertension derived from Lung Disease and/or Hypoxia

PH can result from various lung diseases or hypoxic conditions including interstitial lung disease (ILD), chronic obstructive pulmonary disease (COPD),  sleep-disordered breathing, chronic exposure to high altitudes, and other similar conditions. Collectively, PH associated with these conditions are classified under WHO Group 3.

ILD in particular is characterized by excessive inflammation, fibrosis, and stiffening and thickening of the lung vasculature, leading to markedly reduced lung function. PH often manifests itself alongside ILD, and patients exhibiting PH-ILD show markedly reduced survival rates compared to those without PH. Excessive LTB4 levels and dysregulated macrophages are believed to be major contributors to the underlying inflammation in PH-ILD and decline in lung function in these patients.

There is currently no effective treatment for PH-ILD patients.

Adapted from Benza et al. Chest (2012) 142(2):448-456.